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Introduction {#sec1} ============ Liberia and other countries in the WHO African Region continue to be affected by inconsistent data at all levels of the surveillance system, which may affect the implementation of the IDSR in a negative manner. Public health data are used to monitor trends in the health and wellbeing of the community and of health determinants. Also, they are used to assess the risks of adverse health effects associated with certain determinants, and the positive effects associated with protective factors. The data informs the development of public health policy and the establishment of priorities for investment in interventions aimed at modifying health determinants. They are also used to monitor and evaluate the implementation, cost and outcomes of public health interventions, and to implement surveillance of emerging health issues \[[@cit0001]\]. Thus, public health data can help public health agencies to make appropriate decisions, take effective and efficient action, and evaluate the outcomes \[[@cit0001], [@cit0002]\]. For example, health indicators set up the goals for the relevant government-funded public health agencies \[[@cit0003]\]. Data verification was conducted at selected sites by reviewing data sources that include but not limited to, Supportive Supervision Reports, Outbreak Reports, Maternal and Neonatal Death Surveillance and Response Reports, Assessment Report (including family health database), IDSR aggregate and line-list database, Health Management Information System (HMIS)/District Health Informative System two (DHIS2) database, Case investigation forms and eDEWS assessment reports within the period of January-December, 2016. Data quality in public health has different definitions from different perspectives. These include: "fit for use in the context of data users, timely and reliable data essential for public health core functions at all levels of government, accurate, reliable, valid, and trusted data in integrated public health informatics networks" \[[@cit0004]\]. The government of Liberia has been gradually strengthening the national disease surveillance system until the country was hit by the unprecedented outbreak of Ebola virus disease (EVD) in 2014; an epidemic that virtually collapsed the health system. The health system's weakness was revealed as the result of its inability to detect, investigate and respond to the epidemic in a timely manner; during the outbreak, there was increased deaths and fatality rates among health workers that reflects a weakness in the public health system. The post EVD assessment revealed major weaknesses and the need to establish a national public health institute to focus on building a resilient public health system in the country \[[@cit0001]\]; ensure preparedness and response; Source of technical expertise in generating, analysing and interpreting public health data in the health sector for the formation of health policies; catalyst for the implementation of international health regulations (IHR, 2005) that are both; sustainable and suitable for the local context; exclusively devoted to overcoming public health challenges and improving the population consciousness on health threats; surveillance, detection, response, and research and generating information to allocate resources for maximal public health benefits. The IDSR system (guidelines) was revitalized in 2015 and 2016 as per lessons learned from the EVD outbreak to serve as a guide for improving early detection, and preparedness activities, improve timely investigation and response, and foster integration to strengthen national cross-sectoral capacity for collaborative disease surveillance and epidemic preparedness, thereby addressing systemic weaknesses within the animal, human and environmental health sectors that hinder effective disease surveillance and response and ensure efficient use of resources \[[@cit0005]\] The establishment of the national public health institute of Liberia and development of the national investment plan for health resulted in structural reforms-(e.g. the divisions infectious disease and epidemiology (DIDE), division of environmental health were migrated from the MOH and placed under the NPHIL to give examples) in the health sector geared towards a fit for purpose, motivated and productive health work force, re-engineered health infrastructures, and strengthen public health surveillance, epidemic preparedness, diagnostics and response capacity across all levels. The republic of Liberia suffered a devastating civil war which lasted from 1999 - 2003 \[[@cit0006]\]. The 14 years of civil war destroyed the economy, infrastructures and the health care delivery system such as the hospitals, clinics, electricity, and other essential resources \[[@cit0007], [@cit0008]\]. Liberia was known to be one of countries with the poorest health system in the sub region \[[@cit0004]\]. As part of the attempts to restore the public health infrastructure of the country, the WHO integrated disease surveillance and response system (IDSR) was adopted in 2004 \[[@cit0009]\]. The IDSR strategy is an integrated approach for improving public health surveillance and response and promotes the rational use of resources \[[@cit0010]\]. It is aimed at improving the use of information for early detection of outbreaks and timely response. In the African region, IHR (2005) is implemented in the context of IDSR. The implementation of IDSR in Liberia concentrated on case detection, notification, investigation and confirmation, outbreak preparedness and response, data management and analysis, monitoring and evaluation and support functions (laboratory services, supportive supervision and training based on identified gaps) \[[@cit0011]\] -prior to the EVD epidemic, the IDSR implementation was limited to AFP surveillance and was not robust in timely detection, investigation, and reporting -( there was no standard data collection and reporting tool at the sub national levels of the health system). In view of this, the timeliness and completeness of the IDSR reports was low, inadequate case detection, reporting, investigation and response to outbreaks, no or inadequate documentation of IDSR data and counties were not using surveillance data for public health actions. It was also observed that data management, and analysis at the sub-national level was very low \[[@cit0012]\]. The MoH/NPHIL in collaboration with the World Health Organization (WHO) and other partners implemented surveillance activities in all counties and districts, 769 health facilities, and implemented community event-based-surveillance in half of the country to increase for 14 immediately reportable conditions. Over 2,000 health workers were trained in IDSR with at least two officers from each health facility. The early warning and IDSR data is published weekly by the division of infectious disease and epidemiology (DIDE) of the national public health institute of Liberia (NPHIL)/Ministry of Health (MoH). This bulletin highlights numbers of immediately reportable diseases as well as reporting coverage by health facilities, districts and counties during each epidemiologic week. The information is generated from surveillance activities captured by surveillance officers at district and county levels inclusive of laboratory. Over a period of time, the reporting and analysing of IDSR data has improved but the data source remains the county surveillance officers and laboratory only. Efforts are being made in coordination and active involvement of parallel divisions like family health, expanded programme on immunization, and health management evaluation and research at both national and county level to contribute in the collection, correlation and analysing of surveillance data for the priority diseases. In ensuring reliability, quality and credibility of IDSR data generated from the grass root health facilities, the MoH division of infectious disease and epidemiology along with implementing partners commenced the process IDSR data quality audit across the country in selected counties and health facilities. The objective of this paper is to document data quality, identify technical, managerial, and organizational determinants within the Liberian context and inform an operational plan to address data quality needs for IDSR activities. Methods {#sec2} ======= **The data quality audit was conducted in five phases:** phase one focused on the preparatory activities, phase two involved desk review of reported data, phase three activity was field assessment, during phase four, an action plan was developed, and phase five focused on the compilation of data, report writing, and results dissemination to stakeholders. This exercise was carried out from January 2-April 17, 2018 ([Table 1](#t0001){ref-type="table"}). ###### Data quality assessment (DQA) activities implementation schedule, 2017 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Phase 1: preparation January 2-March 14, 2017 ------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Identifying resources, partners, and staff, scheduling activities, venues, and transport, finalizing protocol and data collection tools (printed or electronic). An estimated budget should be developed along with a timeline and agenda of planned activities. **Phase 2: desk Review** **January 16-20, 2017** Review IDSR surveillance information flow by developing a data flow schematic.\ Review IDSR surveillance data disaggregated by sub-national levels Select Field Assessment sites.\ **Timeline: 1 week** **Phase 3: field assessment** **March 13-April 1, 2017** **Includes planning** **Identify Teams**\ A 3-day training on assessment protocol and piloting of questionnaires.\ Conduct assessment and summarize findings.\ **Timeline: 14 days** **Phase 4: develop an action plan** **April 3-4, 2017** Develop an action plan for next steps to address challenges, weaknesses, and improvements.\ Use assessment finding to inform supportive supervision plan.\ **Timeline: 2 days** **Phase 5: Report writing** Analyze data.Develop draft report for inputs from staff and partners.\ **Timeline: 8 (working) days** **April 17, 2017** **Result dissemination** Presentation of results/findings.\ **Timeline: 1 day** -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Sampling Method:** multi-stage cluster sampling that included stage 1: simple random sample (SRS) of five counties, stage 2: SRS of two districts and stage 3: SRS of three health facilities. Pilot assessment was done in Montserrado County with Liberia institute of bio medical research (LIBR) inclusive. A total of thirty (30) facilities was targeted, twenty-nine (29) of the facilities were successfully audited: one hospital, two (2) health centers, twenty-six (26) clinics and respondents included: health facility surveillance focal persons, ownal surveillance officers (ZSOs), district surveillance officers (DSOs) and County surveillance officers (CSOs) ([Figure 1](#f0001){ref-type="fig"}). {#f0001} **Data quality assessment (DQA) tool:** the WHO DQA tool was used for the assessment. The tool was piloted in Montserrado County. Techniques used for data collection were direct observation of data collection and management at all levels. At the health facility, the source of data (patients ledgers and surveillance ledgers) were reviewed, surveillance officers at that level were observed documenting the data or information, interviews and focused group discussions with health facility surveillance focal persons, ZSOs, DSOs and CSOs were conducted by the assessment team form NPHIL/MOH/WHO/ CDC/ John Hopkins University (JHU). Surveillance staff background and training history, competency, specimen collection procedures, case reporting procedures, data analysis, interpretation, and use, support Infrastructure, data Sources, validation of maternal deaths, acute bloody diarrhea, measles, and acute flaccid paralysis, IDSR weekly reporting form, health management information system, health facility registers & charts, identification of key areas for improvement, action items, supervision, mentorship, and feedback and perceptions, knowledge, and attitudes about surveillance. **Key informants:** these were the surveillance focal persons, district surveillance officers and County ourveillance officers. An interviewer-administered questionnaire was used to interview key informants to assess their knowledge on data quality and operations of the surveillance system. The field assessment was carried out by five (5) teams comprising of four (4) persons. One team was assigned to each county. Each team was made up of a NPHIL staff (National level), a surveillance officer (County level) and a staff from supporting agencies such as WHO, CDC and JHU. Permission was sought from the MoH and NPHIL to carry out this study as part of strengthening public health surveillance in Liberia. Verbal or written consent was obtained from all interviewees and confidentiality was guaranteed, and the questionnaire for this data quality assessment was structured according to the levels of Liberia health care delivery system ([Figure 2](#f0002){ref-type="fig"}). {#f0002} **Data quality audit process:** as part of the monitoring and evaluation strategies for continuous improvement in surveillance activities, a data quality audit (DQA) was conducted in five selected counties to assess the quality of data generated and determine factors that influence the quality of surveillance data within the IDSR reporting system. A descriptive cross-sectional study was conducted in 30 health facilities A multi-stage cluster sampling technique was used. Five counties (Montserrado, River Gee, Bong, Grand Bassa, and Gbarpolu), were initially selected using simple random sampling. The districts under each county were classified as urban and rural. In each stratum, one health district was selected giving a total of ten (10) health districts. Within each health district three (3) health facilities were randomly sampled making a total of 30 health facilities ([Figure 3](#f0003){ref-type="fig"}). {#f0003} Results {#sec3} ======= The findings indicated that 23% (7/29) reported a dedicated phone for the health facility, 20% (6/29) reported no cell phone network, 17% (5/29) reported daily access to internet, 56.6% (17/29) reported a consistent supply of electricity, no facility reported access to functional laptop and 70% (21/29) reported access to a motorbike for community visits ([Figure 4](#f0004){ref-type="fig"}). The findings also indicated that all the DSOs correctly recalled the definition of zero reporting, case definition for measles, and case definition for maternal death. Only one DSO did not correctly recall epidemiology week, and AFP case. Recall of diseases under surveillance was \>80% for all conditions ([Figure 5](#f0005){ref-type="fig"}). During the data quality audit, it was observed that 40% of health facilities have experienced a stock out of lab packaging supplies in the past year; Stock outs lasted an average of 2 months; All types of packaging was reported as low stock, including red top tubes, purple top tubes; About half of the surveyed health facilities delivered specimens through Riders, about half were assisted by the DSO while there was a large variety in the reported packaging process, with many staff unable to give clear processes. The findings during the exercise indicated that 91% of health facility staff were mentored on data quality check and data management including the importance of the timeliness and completeness of reporting through supportive supervision and mentorship; 65% of the health facility assessed received supervision on IDSR Core Performance Indicator; and 58% of the health facility Officer In Charge gave feedback to the community level. It also indicated that, 78% of the health facility use Bar chart as methods to detect outbreaks; 56% used trend lines; 33% used summary table and 11% used map to determine outbreaks. The findings further indicated that for routine data harmonization at the peripheral level of the IDSR implementation, 90% of the DSOs routinely check the DHIS2 platform for data consistency with IDSR data reported the same period; it was also observed that 40% of the health facility focal persons lack training in data management; while 85% of the health facility recorded information on cases detected at community level. {#f0004} {#f0005} **For the data analysis and use:** a checklist as per WHO guidelines for data quality audit was used to assess key indicators of quality surveillance data. A vicariate and bivariate analysis was conducted to summarize data collected using Epi Inform™ version Most health facilities reported using data to inform topics during the health talks. 100% of the DSOs assessed, correctly recalled the definition of zero reporting, case definition for measles, and case definition for maternal death and high numbers of disease are used for sensitization, specifically around measles and diarrhea 1 DSO did not correctly recall the epidemiologic week, and AFP case. Recall of diseases under surveillance was \>80% for all conditions. Discussion {#sec4} ========== Sound and reliable data quality assessment is vital to obtain the high data quality which enhances users' confidence in public health and their performance. As Liberia monitors and evaluates the performance and progress of IDSR indicators, the need for data quality assessment in public health information system that store the performance-and-progress-related data needs to be routinely undertaken to ensure generation of credible, reliable and quality data. High quality data and effective data quality assessment are required for accurately evaluating the impact of public health interventions and measuring public health outcomes. Data use, and data collection process as the major dimensions of data quality, all need to be continuously assessed for overall data quality. Data quality audit "DQA" has been routinely conducted by MoH/NPHIL-Liberia as part of the IDSR implementation strategy to improve disease surveillance and the information generated helps to improve training, supervision, and reporting tools of the program across the country. Data are essential to public health. They represent and reflect public health practice. The broad application of data in IDSR for the evaluation of public health accountability and performance has raised the awareness of NPHIL, MoH, WHO and public health agencies of data quality, and of methods and approaches for its assessment \[[@cit0013]\]. We systematically reviewed the current status of quality assessment for each of the three dimensions of data quality: data, data collection process and data use. The results suggest existence of data capture tools at all levels of health care system with most assessed indicators above 80%. Our findings based on the proposed conceptual framework of data quality assessment for public health identified gaps in reporting aggregated IDSR data not harmonised with DHIS2, and limited data use for decision making. Data quality is influenced by technical, organizational, behavioural and environmental factors. It covers large information systems contexts, specific knowledge and multi-disciplinary techniques. Data quality audit is frequently done as a component of the quality or effectiveness or performance of the IDSR. However, data quality assessment hidden within other scopes may lead to ignorance of data management and thereby the unawareness of data quality problems enduring in public health practice. Data quality needs to be positioned at the forefront of IDSR as a distinct area that deserves specific scientific research and management investment. While this review provides a detailed overview of data quality assessment issues, there are some limitations in its coverage, constrained by the access to the databases and the breadth of public health information systems making it challenging to conduct systematic comparison among studies. The importance of systematic, scientific data quality assessment needs to be highlighted. All three dimensions of data quality, data use and data collection process, need to be systematically evaluated. The quality of data use and data collection process has not received adequate attention. This lack of recognition of data use and data collection process might reflect a lack of consensus on the dimensions of data quality. Further development in methods to assess data collection process and data use is required. Effort should also be directed towards clear conceptualisation of the definitions of the relevant terms that are commonly used to describe and measure data quality, such as the dimensions and attributes of data quality. Data quality assessment was mixed methods (qualitative and quantitative assessment methods) to assess data from multiple sources (records, organisational documentation, and data collection process and data users) and used at health facility, district and county levels. The validity of a study would be doubtful if the quality of data could not be verified in the field, especially when the data from data capture tools are varied with data submitted to national level has no errors. This was limited by the coverage to 5 out of 15 counties and to the databases of IDSR, DHIS2 and data capture tools at health facility, district and county levels. Further research could develop consistent data quality definitions, attributes, quality of data use and the quality of data collection process. Data-use and data-process have not been given adequate attention at health facility, district and county levels, although they were equally important factors which determine the quality of data. **Recommendations:** conduct regular data harmonization/audit at subnational level to ensure that health workers are knowledgeable on the importance of quality and reliable data. Capacity building for health workers at sub national level in data management. Ensure the institutionalize data management training in pre-service and academic institutions, on-going in-service refresher trainings in data analysis for public health actions. Establish an effective system to improve data harmonization at the subnational level. Conclusion {#sec5} ========== Public health is a data-intensive field which needs high-quality data and authoritative information to support public health assessment, decision-making and to assure the health of communities. Data quality assessment is important for public health. In this review Completeness, accuracy, and timeliness were the three most-assessed attributes. Quantitative data quality assessment primarily used descriptive surveys and data audits, while qualitative data quality assessment methods include primarily interview, questionnaire administration, documentation review and field observation. We found that data-use and data-process have not been given adequate attention, although they were equally important factors which determine the quality of data. Other limitations of the previous studies were inconsistency in the definition of the attributes of data quality, failure to address data users' concerns and a lack of triangulation of mixed methods for data quality assessment. The reliability and validity of the data quality assessment were rarely reported. These gaps suggest that in the future, data quality assessment for public health needs to consider equally the three dimensions of data quality, data, data use and data process. Measuring the perceptions of end users or consumers towards data quality will enrich our understanding of data quality issues Data use is limited to risk communication and sensitization, no examples of use of data for prioritization or decision making. What is known about this topic {#sec5.1} ------------------------------ - Data quality audits lead to improvement in over reporting and under reporting which compromise informed decisions, integrity of generated data, quality assurance standards and compliance levels; - Public health is a data-intensive field which requires high-quality data to support public health decision-making; - Improving data quality requires good data capturing tools that are capable of analysing the quality of data generated based on data quality audits. What this study adds {#sec5.2} -------------------- - Forty percent (40%) of surveillance officers at health facility level lack training in data management; - Undefined data management strategy and quality level makes data generated overwhelming and less useful in decision making; - Regular data quality audit is necessary to understand the actual status of data quality and integrity issues in the health care delivery system and addresses data quality challenges aimed at improving data consistency, reliability and informed decisions. Competing interests =================== The authors declare no competing interest. The authors wish to gratefully acknowledge the entire team that conducted the data quality audit, all the respondents during the audit, the 15 County Health Officers and 15 County Surveillance Officers, 93 DSOs, 22 ZSOs, HSFPs of the counties assessed, Ministry of Health, National Public Health Institute of Liberia, WHO field coordinators and Johns Hopkins University that spear headed the DQA. Special thanks to WHO country and regional offices for supporting the development of Liberia experiences in IHR core capacities post Ebola outbreak against which we were encouraged and motivated to document this paper. Authors' contributions ====================== Thomas Nagbe, Kwuakuan Yealue, Joseph Asamoah Frimpong, led the development of the conceptual framework of the manuscript, collected the data, performed the data analysis and interpretation, drafted and coordinated manuscript writing and wrote the first draft, all others participated in data collection. Monday Julius Rude, reorganized the first draft critically for key logical content. Roland Tuopileyi, Laura Skrip, Nuha Mouhamoud, Monday Julius Rude, Trokon Yeabah: data collection, data analysis and read critically the manuscript, provided the necessary corrections and approved for submission. Mary Stephen, Okeibunor Joseph Chukwudi, Ambrose Talisuna, Chukwuemeka Agbo, Ali Ahmed Yahaya: data collection, data analysis, read critically reviewed, corrected and approved the manuscript Alex Gasasira, Thomas Nagbe, Ibrahima Socé Fall, Soatiana Rajatonirina, Esther Hamblion, Chukwuemeka Agbo and Bernice Dahn read critically the manuscript and provided corrections, inputs and were involved in data analysis. All authors read and approved the final version of the manuscript and agreed upon submission for publication.

Laryngeal granuloma in experimental rats with gastroesophageal reflux disease and mechanically injured vocal cord mucosa. This study was undertaken to elucidate the mechanisms underlying laryngeal granuloma formation in a rat model of gastroesophageal reflux disease (GERD) with mechanically injured vocal cord mucosa. The rat model of GERD was surgically created by tying the pyloric sphincter and ligating the transitional region between the forestomach and the glandular portion (limiting ridge). The control rats received only a midline incision. In all the animals, a plastic bar was inserted into the trachea, and moved vertically thrice in 3 seconds to cause mechanical injury of the vocal cord mucosa. The rats were sacrificed 2 weeks postsurgically, and their pharynx and larynx were observed histologically. Granulomas were observed in the vocal cord mucosa of the GERD group (3 of 5 animals); they presented a similar pathological structure to that of human laryngeal granulomas. In contrast, only abrasions and blisters were observed on the vocal cord mucosa in the control group (all 5 animals). The development of laryngeal granuloma may involve both mechanical injury and gastric acid reflux.

Genotoxicity of inorganic lead salts and disturbance of microtubule function. Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 microM lead chloride and 0.05 microM lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 microM lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 microM. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 microM and reached half-maximal inhibition of motility at about 50 microM. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels.

Americans are pointing the finger at President Trump Donald John TrumpBarr criticizes DOJ in speech declaring all agency power 'is invested in the attorney general' Military leaders asked about using heat ray on protesters outside White House: report Powell warns failure to reach COVID-19 deal could 'scar and damage' economy MORE more than congressional Democrats as a partial government shutdown heads into its second week. In a new The Hill-HarrisX poll released Monday, only 22 percent of registered voters surveyed blamed Democrats for the shutdown, while 42 percent said President Trump was to blame. One-third of voters said that both parties in Congress and the president were all equally responsible. The government has been shut down since Dec. 22 when President Trump said he would not sign a spending bill that did not provide his requested $5 billion in funding for a border wall. Democrats have offered $1.3 billion for border security. Normally, each party tries to point the finger at the other over budgetary impasses, but the president complicated that strategy for Republicans during an extraordinary Dec. 11 White House meeting with Speaker-designate Nancy Pelosi Nancy PelosiPowell warns failure to reach COVID-19 deal could 'scar and damage' economy Overnight Defense: House to vote on military justice bill spurred by Vanessa Guillén death | Biden courts veterans after Trump's military controversies Intelligence chief says Congress will get some in-person election security briefings MORE (D-Calif.) and Senate Minority Leader Chuck Schumer Chuck SchumerDemocrats scramble on COVID-19 relief amid division, Trump surprise Pelosi, Schumer 'encouraged' by Trump call for bigger coronavirus relief package Schumer, Sanders call for Senate panel to address election security MORE (D-N.Y.). In that meeting, Trump claimed he would be "proud to shut down the government for border security" and that he would not blame Democrats for any government closure that might result from the lack of a spending deal. In the days since, however, Trump has shifted his rhetoric to claim Democrats are responsible for the partial shutdown. On Dec. 21, the day before the shutdown began, the president wrote in a Twitter posting that "The Democrats now own the shutdown!" The shifting GOP messaging appears to have caused some confusion for Republican voters over whom to blame for the situation. While 75 percent of Democratic respondents in The Hill-HarrisX poll pointed the finger at Trump, only 47 percent of Republican voters said congressional Democrats were responsible for the shutdown. Many GOP respondents, 39 percent, said that both parties in Congress and the president are to blame. Just 17 percent of Democratic respondents agreed with that assertion. "The president did say 'I will shut down the government if I don't get this, this will be the Trump shutdown.' The fact that he sort of owned it makes it easier for a lot of these Americans to say, 'Yeah it's his fault,' " Molly Murphy, a Democratic pollster said Monday on "What America's Thinking," Hill.TV's show about polling and public opinion. While Republican partisans have been slow to adjust their opinions to echo Trump's attempts to blame Democrats for the shutdown, a plurality of independent voters, 44 percent, said that both parties are equally at fault. Thirty-seven percent of independents said that Trump is to blame while 16 percent said congressional Democrats were primarily responsible. The latest Hill-HarrisX survey was conducted Dec. 30 through 31 and is part of an ongoing project of The Hill's new online TV division, Hill.TV, and the HarrisX polling company that asks 1,000 registered voters a day about issues of public policy and current events. The latest poll has a sampling margin of error of 3.1 percentage points. — Matthew Sheffield

628 S.E.2d 63 (2006) 48 Va. App. 35 CHESAPEAKE BAY FOUNDATION, INC. v. COMMONWEALTH of Virginia, ex rel. STATE WATER CONTROL BOARD, Department of Environmental Quality, Robert G. Burnley, Director, Department of Environmental Quality and Philip Morris USA Inc. Record No. 1175-05-2. Court of Appeals of Virginia, Richmond. April 4, 2006. *66 Jon A. Mueller, Washington, DC (Brian L. Buniva, Richmond; LeClair Ryan, on briefs), for appellant. John K. Byrum, Jr., Assistant Attorney General (Judith Williams Jagdmann, Attorney General; Roger L. Chaffe, Senior Assistant Attorney General, on brief), for appellee Commonwealth of Virginia, ex rel. State Water Control Board, Department of Environmental Quality, and Robert G. Burnley, Director, Department of Environmental Quality. Brooks M. Smith (Andrea W. Wortzel; Hunton & Williams LLP, on brief), Richmond, for appellee Philip Morris USA Inc. Present: ELDER and HUMPHREYS, JJ., and COLEMAN, S.J. ELDER, Judge. The Chesapeake Bay Foundation, Inc. (CBF) appeals from a decision dismissing its challenge to a permit issued to Philip Morris USA Inc. by the State Water Control Board (SWCB), upon the recommendation of the Department of Environmental Quality (DEQ) and Director Robert Burnley. CBF contends the circuit court erroneously granted the demurrers of SWCB, DEQ, Burnley, and Philip Morris. CBF argues the court erroneously held that Virginia law does not provide for representational standing and that CBF failed to plead sufficient facts to demonstrate standing to sue in its own right. In the alternative, CBF contends the trial court erroneously denied its motion for leave to amend its petition to allege additional facts sufficient to establish standing. Based on this Court's decision in Chesapeake Bay Foundation and Citizens of Stumpy Lake v. Commonwealth, 46 Va.App. 104, 616 S.E.2d 39 (2005) [hereinafter Stumpy Lake], we hold the trial court's conclusion that Virginia law does not permit representational standing was erroneous. We hold further the facts alleged in CBF's petition for appeal, accepted as true, were sufficient to survive the appellees' demurrers. Thus, we reverse the trial court's dismissal of the petition with prejudice without addressing the trial court's ruling on CBF's request for leave to amend, and we remand to the trial court *67 for further proceedings consistent with this opinion. I. BACKGROUND Because this case involves the granting of a demurrer, we accept as true, for purposes of reviewing this motion only, all facts alleged in the petition. See Code § 8.01-273; Runion v. Helvestine, 256 Va. 1, 7, 501 S.E.2d 411, 415 (1998); Stumpy Lake, 46 Va.App. at 107, 616 S.E.2d at 41. CBF is a nonprofit Maryland corporation that is registered to do business in Virginia; maintains offices in Richmond and Norfolk; and has approximately 40,000 members who reside in Virginia. It is the largest conservation organization dedicated solely to protecting the Chesapeake Bay watershed and its tributaries, including the James River. In 2004, the SWCB reissued to Philip Morris a permit under the Virginia Pollution Discharge Elimination System (VPDES), allowing it to discharge into the James River, from its Park 500 Plant in Chester, wastewater containing, inter alia, certain levels of nitrogen and phosphorus. CBF actively participated in the public comment process related to the permit. After the permit's reissuance, CBF filed a petition for appeal in the Circuit Court of Chesterfield County alleging that the levels of certain substances Philip Morris was allowed to discharge under the permit exceeded applicable state and federal standards. In its twenty-five page petition, CBF alleged that it meets the legal standing standards required for obtaining judicial review [of the permit] under Va.Code Ann. § 62.1-44.29. The CBF has suffered and will continue to suffer actual and/or imminent injury and represents members and citizens of the Commonwealth who have suffered and will continue to suffer actual and imminent injury: a. resulting from the unlawful re-issuance of the Permit and authorizing Philip Morris to discharge nitrogen and phosphorus pollution to this water quality limited and "impaired waters" segment of the James River in amounts and concentrations that do not ensure that Virginia [water quality standards] WQS will be maintained; b. the injuries suffered are directly traceable to the unlawful "case decision" rendered by the SWCB and implemented by Burnley by its decision to re-issue the Permit to Philip Morris; and c. the injuries suffered by CBF and its members are capable of effective and meaningful redress by a favorable decision of this Court setting aside the Permit, and remanding the "case decision" to the SWCB with instructions to re-issue the Permit . . . and ordering the Permit to include numeric effluent limitations for nitrogen and phosphorus in concentrations and amounts that will ensure that the Virginia WQS for this segment of the James River will be maintained as is required by law and valid regulations. CBF provided more detailed information regarding the ways in which it alleged it and its members would be harmed by the permit. It also alleged an equal protection violation, contending Philip Morris's permit was more favorable than one issued to the Crooked Run Sewage Treatment Facility on the same day. CBF asked the court to suspend the challenged permit and requested various other forms of relief. Philip Morris and the Commonwealth filed demurrers and motions to dismiss, contending, inter alia, that no relevant statute authorized CBF to sue in a representational capacity; that CBF failed to plead sufficient facts to show standing to sue in its own right; that the equal protection claim failed to state a claim upon which relief could be granted; that DEQ and Director Burnley were improper parties; and that much of the relief sought was beyond that authorized by the Administrative Process Act. On January 4, 2005, after hearing argument on the motions, the circuit court granted the motions, reasoning as follows: [CBF] has not alleged any . . . specific injury-in-fact. While the CBF asserts that the "permitted discharges will cause injury to the CBF and its programs as well as its members," (Pet. P. 5), the CBF fails to state what impact the discharge will have on its educational or restorative programs, *68 the operation of its vessel, the recreational or aesthetic activities of its members or its replenishment of underwater grasses in segments of the James River.5 5 To the contrary, the CBF states that phosphorus, nitrogen, and other effluent contents will foster plant growth. (Pet. 8-9). Consequently, the Court finds that the CBF does not have standing as an individual to sue. The court ruled that no Virginia statute authorized CBF to sue in a representative capacity. The court also refused to grant CBF leave to amend its petition. The court granted the demurrers and noted that it was not necessary to "address the ancillary issues of equal protection, unavailability of relief prayed for, and misjoinder of parties." CBF then filed a motion for reconsideration or, in the alternative, for leave to amend its petition for appeal "to allege in greater detail its Article III `case' or `controversy' standing element required by Va.Code § 62.1-44.29." The trial court denied the motion, again rejecting CBF's representational standing claim and its request for leave to amend. On the latter issue, the court reasoned that CBF "failed to initially plead any [injuries in fact]," that "any allegation of specific injury to the CBF will be new," and that "[s]uch an addition is impermissible." On April 28, 2005, the court entered an order denying the motion to amend and granting appellees' motions to dismiss with prejudice. II. ANALYSIS "A demurrer admits the truth of all material facts properly pleaded. . . . [T]he facts admitted are those expressly alleged, those which fairly can be viewed as impliedly alleged, and those which may be fairly and justly inferred from the facts alleged." Rosillo v. Winters, 235 Va. 268, 270, 367 S.E.2d 717, 717 (1988) (emphases added). A demurrer does not "admit `inferences or conclusions from facts not stated.'" Arlington Yellow Cab v. Transp., Inc., 207 Va. 313, 319, 149 S.E.2d 877, 881 (1966) (quoting 71 C.J.S. Pleading § 261, at 528, 529). A demurrer "does not admit the correctness of the pleader's conclusions of law. [Its] function . . . is to test the legal sufficiency of the facts. Because our review of a circuit court's decision sustaining a demurrer addresses that same legal question, we review the circuit court's judgment de novo." Stumpy Lake, 46 Va.App. at 110-11, 616 S.E.2d at 42 (citations omitted). Our resolution of this appeal turns first on whether CBF pleaded sufficient facts to demonstrate standing to challenge SWCB's issuance of the VPDES permit to Philip Morris. "A plaintiff has standing to institute a . . . proceeding if it has a `justiciable interest' in the subject matter of the proceeding, either in its own right or in a representative capacity. In order to have a `justiciable interest' in a proceeding, the plaintiff must demonstrate an actual controversy between the plaintiff and the defendant, such that his rights will be affected by the outcome of the case." Id. at 119-20, 616 S.E.2d at 47 (quoting W.S. Carnes, Inc. v. Bd. of Supers., 252 Va. 377, 383, 478 S.E.2d 295, 299 (1996) (citations omitted)) (emphasis added). CBF asserts the trial court incorrectly ruled that Virginia does not recognize representational standing and that it has pleaded facts sufficient to prove both standing to sue in its own right and representational standing on behalf of its members. We agree on all counts. A. STANDING OF CBF TO SUE IN ITS OWN RIGHT Code § 62.1-44.29, the State Water Control Law's judicial review provision, provides as follows: Any owner aggrieved by, or any person who has participated, in person or by submittal of written comments, in the public comment process related to, a final decision of the Board under [various provisions of the State Water Control Law], whether such decision is affirmative or negative, is entitled to judicial review thereof in accordance with the provisions of the Administrative Process Act . . . if such person *69 meets the standard for obtaining judicial review of a case or controversy pursuant to Article III of the United States Constitution. A person shall be deemed to meet such standard if (i) such person has suffered an actual or imminent injury which is an invasion of a legally protected interest and which is concrete and particularized; (ii) such injury is fairly traceable to the decision of the Board and not the result of the independent action of some third party not before the court; and (iii) such injury will likely be redressed by a favorable decision by the court. The parties agree that in order for CBF to plead sufficient facts to establish standing to sue in its own right, it must meet this three-part test. "While each of the three prongs of standing should be analyzed distinctly, their proof often overlaps." Friends of the Earth, Inc. [(FOE)] v. Gaston Copper Recycling Corp., 204 F.3d 149, 154 (4th Cir.2000) (reversing dismissal, following six-day bench trial, for lack of standing based on "holding that none of plaintiffs' members had shown injury in fact"). 1. Injury in Fact The injury alleged to support a claim of standing must be both (a) concrete and particularized and (b) actual or imminent, thereby "preclud[ing] those with merely generalized grievances from bringing suit to vindicate an interest common to the entire public." Id. at 156. Such an injury may be to the plaintiff's economic interests, but it may also be to the plaintiff's "aesthetic or recreational interests." Id. at 154. "Aesthetic and environmental well-being, like economic well-being, are important ingredients of the quality of life in our society, and the fact that particular environmental interests are shared by the many rather than the few does not make them less deserving of legal protection through the judicial process" as long as "the party seeking review [is] himself among the injured." Sierra Club v. Morton, 405 U.S. 727, 734-35, 92 S.Ct. 1361, 1366, 31 L.Ed.2d 636, 643 (1972). Thus, "environmental plaintiffs adequately allege injury in fact when they aver that they use the affected area and are persons `for whom the aesthetic and recreational values of the area will be lessened' by the challenged activity." FOE v. Laidlaw Environmental Servs. (TOC), Inc., 528 U.S. 167, 183, 120 S.Ct. 693, 705, 145 L.Ed.2d 610, 628 (2000); see Lujan v. Defenders of Wildlife, 504 U.S. 555, 562-63, 112 S.Ct. 2130, 2137, 119 L.Ed.2d 351, 365 (1992) ("[T]he desire to use or observe an animal species, even for purely aesthetic purposes, is undeniably a cognizable interest for purpose of standing."). Although the injury alleged must be concrete and particularized, it "`need not be large[;] an identifiable trifle will suffice.'" Gaston Copper, 204 F.3d at 156 (quoting Sierra Club v. Cedar Point Oil Co., 73 F.3d 546, 557 (5th Cir.1996) (internal quotation marks omitted)). Further, "[t]he Supreme Court has consistently recognized that threatened rather than actual injury can satisfy Article III standing requirements. `One does not have to await the consummation of threatened injury to obtain preventive relief. If the injury is certainly impending that is enough.'" Id. at 160 (quoting Babbitt v. United Farm Workers Nat'l Union, 442 U.S. 289, 298, 99 S.Ct. 2301, 2308, 60 L.Ed.2d 895, 906 (1979) (internal quotation marks omitted)) (citations omitted). Where the claim of injury is based on allegations that a company is discharging chemicals in quantities that exceed those specified in a permit and the discharge restrictions were "set at the level necessary to protect the designated uses of the receiving waterways, the[] violation [of the discharge restrictions] necessarily means that these [designated] uses may be harmed." Id. at 156-57. Here, CBF has alleged sufficient facts to claim both the existence of an injury in fact and to allege the injury is to itself as an organization. CBF's claim of injury is similar to the claim made in Gaston Copper. Gaston Copper involved an allegation that the company was violating its permit, which contained limits formulated to protect the statutorily designated uses of the receiving waterways. Id. Here, CBF's allegation is that the permit itself fails to comply with federal and state statutory limits formulated to protect the designated uses of the receiving waterways, *70 thereby involving tacit governmental approval of the alleged polluting via issuance of the permit. CBF cites 9 VAC XX-XXX-XX(A), which provides that all state waters, which necessarily include the James River segment into which the subject Philip Morris facility discharges its wastewater, are designated for certain "recreational uses, e.g., swimming and boating; the propagation and growth of a balanced, indigenous population of aquatic life, including game fish, which might reasonably be expected to inhabit them; and the production of edible and marketable natural resources, e.g., fish and shellfish." Further, the SWCB is charged with developing "water quality standards" or "criteria" which, if met, "will generally protect the designated use[s]" of the body of water to which they apply. See 9 VAC 25-260-5; 9 VAC XX-XXX-XX. The SWCB's general criteria provide that [s]tate waters . . . shall be free from substances attributable to sewage, industrial waste, or other waste in concentrations, amounts, or combinations which contravene established standards or interfere directly or indirectly with designated uses of such water or which are inimical or harmful to human, animal, plant, or aquatic life. Specific substances to be controlled include. . . substances that produce . . . turbidity. . . and substances which nourish undesirable or nuisance aquatic plant life. 9 VAC XX-XXX-XX(A). Thus, here, as in Gaston Copper, an allegation of "the[] violation [of the discharge restrictions, if proved,] necessarily means that these [designated] uses may be harmed." Gaston Copper, 204 F.3d at 156-57. Further, CBF alleged with specificity that the unlawful discharges of nitrogen and phosphorus "nourish undesirable or nuisance aquatic plant life" by "assisting in the formation of nuisance algae blooms" and increase chlorophyll-a, turbidity and other things that contribute to the failure of the relevant segment of the James River to meet state and federal water quality standards. These statements allege a concrete and imminent threat of harm to "the propagation and growth of a balanced, indigenous population of aquatic life, including game fish, which might reasonably be expected to inhabit [the subject waters]." See 9 VAC XX-XXX-XX(A). CBF further alleged with particularity that the organization itself is "among [those] injured" by the alleged violation. Morton, 405 U.S. at 735, 92 S.Ct. at 1366, 31 L.Ed.2d at 643. CBF, sometimes using its own vessel, "The Chesapeake," "travels the James River impaired waters around and downstream from the [Philip Morris] facility for its educational, recreational, and Bay restorative efforts, all of which are harmed by the continuing excessive discharge of nutrients. . . as authorized by the challenged permit." CBF detailed one particular program that "[is] and will continue to be adversely affected by the unlawful nutrient discharges" — its "replenishment of underwater aquatic grasses in the vicinity of and downstream from the Philip Morris facility." CBF explained that it has and continues to operate programs designed to reduce the effect of [discharges such as Philip Morris's], including in and downstream from the water quality impaired segment of the James River where Philip Morris discharges its wastewater, including planting underwater aquatic grasses necessary for the healthy maintenance and replenishment of aquatic plant, fish and animal life destroyed in part by [the excessive effluent discharges allowed under the permit]. CBF also alleged that it expended over $100,000 on its James River replanting program during the previous fiscal year and that it sponsored an average of 84 trips each year for that purpose, in which approximately 1,800 volunteers participate. Sufficiently implicit, if not explicit, in these allegations is that the allegedly excessive discharge of effluents allowed by the permit has contributed to the destruction of indigenous aquatic plant, fish and animal life, and that the discharge, if allowed to continue, threatens to do the same to the grasses CBF has planted in an effort to combat the harm caused by the allegedly unlawful ongoing discharges. Thus, CBF has alleged sufficient economic, aesthetic, and recreational injuries to itself, injuries that are both concrete and particularized *71 and actual or imminent, to establish standing to maintain suit. 2. Causal Connection To withstand the appellees' demurrer, the petition must also allege the claimed injury is "fairly traceable to the decision of the Board and not the result of the independent action of some third party not before the court." Code § 62.1-44.29. The "fairly traceable" requirement ensures that there is a genuine nexus between a plaintiff's injury and a defendant's alleged illegal conduct. But traceability "`does not mean that plaintiffs must show to a scientific certainty that defendant's effluent. . . caused the precise harm suffered by the plaintiffs.'" . . . Rather than pinpointing the origins of particular molecules, a plaintiff "must merely [allege] that a defendant discharges a pollutant that causes or contributes to the kinds of injuries alleged" in the specific geographic area of concern. In this way a plaintiff demonstrates that a particular defendant's discharge has affected or has the potential to affect his interests. Gaston Copper, 204 F.3d at 161 (quoting Natural Resources Defense Council, Inc. v. Watkins, 954 F.2d 974, 980 & n. 7 (4th Cir.1992) (quoting Public Interest Group of New Jersey, Inc. v. Powell Duffryn Terms., Inc., 913 F.2d 64, 72 (3d Cir.1990))) (internal quotation marks omitted from and emphasis added in last quoted passage). The same allegations cited above as being sufficient to plead injury in fact also constitute facts sufficient to plead the necessary causal nexus in this case. CBF alleges that SWCB's issuance of the permit allows the discharge of effluents at levels in excess of those permitted by state and federal law and that Philip Morris's discharge of nitrogen and phosphorus in concentrations and amounts authorized by the permit (1) contributes to the growth of "undesirable or nuisance plant life" by "assisting in the formation of nuisance algae blooms" and increasing chlorophyll-a, turbidity and other things that contribute to the failure of the relevant segment of the James River to meet state and federal water quality standards, (2) contributes to the destruction of "aquatic plant, fish and animal life," and (3) contributes to the destruction of aquatic grasses planted by CBF in an effort to foster "the healthy maintenance of replenishment of aquatic plant, fish and animal life." CBF need not allege that Philip Morris's Park 500 Plant is the only facility discharging effluents capable of causing this harm. "It would be strange indeed if polluters were protected from suit simply by virtue of the fact that others are also engaging in the illegal activity." American Canoe Ass'n v. Murphy Farms, Inc., 326 F.3d 505, 520 (4th Cir.2003). 3. Redressability Finally, a plaintiff must allege sufficient facts to support the conclusion that his injury "will likely be redressed by a favorable decision by the court." Code § 62.1-44.29. He also "must demonstrate standing separately for each form of relief sought." Laidlaw, 528 U.S. at 185, 120 S.Ct. at 706, 145 L.Ed.2d at 629. "The redressability requirement ensures that a plaintiff `personally would benefit in a tangible way from the court's intervention.'" Gaston Copper, 204 F.3d at 162 (quoting Warth v. Seldin, 422 U.S. 490, 508, 95 S.Ct. 2197, 2210, 45 L.Ed.2d 343, 360 (1975)). This benefit need not be monetary to be sufficiently tangible. Laidlaw, 528 U.S. at 185-87, 120 S.Ct. at 706-07, 145 L.Ed.2d at 629-31. The Supreme Court has recognized that "citizen plaintiffs facing ongoing violations" have standing to seek civil penalties in appropriate cases. Id. "To the extent [civil penalties] encourage defendants to discontinue current violations and deter them from committing future ones, they afford redress to citizen plaintiffs who are injured or threatened with injury as a consequence of ongoing unlawful conduct." Id. at 186, 120 S.Ct. at 706-07, 145 L.Ed.2d at 630. Appellees contend the harm alleged by CBF is not redressable by a decision vacating the permit because CBF's allegations concede that Philip Morris is not the sole or even the primary contributor of nutrients to the James River. We disagree. As discussed above, the harm or threatened harm may be an "`identifiable trifle.'" Gaston Copper, 204 F.3d at 156 (quoting Cedar Point *72 Oil Co., 73 F.3d at 557). Thus, as long as the relief CBF seeks would redress the part of the harm caused by Philip Morris, that harm is, in fact, redressable to the extent required to demonstrate standing. As quoted above, "[I]t would be strange indeed if polluters were protected from suit simply by virtue of the fact that others are also engaging in the illegal activity." American Canoe Ass'n, 326 F.3d at 520. Thus, we hold the harm alleged is redressable to the extent that CBF seeks to have the permit set aside and re-issued only if it complies with applicable laws necessary to ensure that water quality standards shall be maintained.[1] B. REPRESENTATIONAL STANDING 1. Legal Validity of Doctrine in Virginia By letter opinions of January 4 and April 8, 2005, incorporated into its order of April 28, 2005, the trial court ruled that Code § 62.1-44.29 of the State Water Control law did not confer upon CBF standing to sue in a representational capacity. However, by decision rendered July 19, 2005, a panel of this Court reached the opposite conclusion. See Stumpy Lake, 46 Va.App. at 111-18, 616 S.E.2d at 42-46. Following an extended analysis in Stumpy Lake, we held that "Virginia recognizes representational standing. . . and that Code § 62.1-44.29 confers this representational standing" in cases meeting its requirements. Id. (relying on Concerned Taxpayers of Brunswick County v. DEQ, 31 Va.App. 788, 525 S.E.2d 628 (2000) (holding almost identical judicial review provision in Solid Waste Management Act authorized representational standing in case meeting its requirements), rev'd on other grounds sub nom., Aegis Waste Solutions v. Concerned Taxpayers of Brunswick County, 261 Va. 395, 544 S.E.2d 660 (2001)). Although a petition for appeal of the Stumpy Lake decision was filed, the Supreme Court ultimately refused to consider the appeal on the merits. See Commonwealth v. CBF, No. 051767 (Va. Sup.Ct. Jan. 25, 2006). Thus, our decision in Stumpy Lake remains binding legal precedent. Appellees recognize that stare decisis may bind us to follow the decision in Stumpy Lake. Nevertheless, quoting Commonwealth v. Burns, 240 Va. 171, 174, 395 S.E.2d 456, 457 (1990), they argue we are not so bound if we find that the decision in Stumpy Lake was based on "`flagrant error or mistake.'" Appellees misconstrue the holding in Burns, which permits this Court to correct "`flagrant error or mistake' in a panel decision. . . through the en banc hearing process." Burns, 240 Va. at 174, 395 S.E.2d at 457. Contrary to appellees' assertions, Burns affirms the principle that the decision of one panel is binding on all other panels unless and until reversed by the Court sitting en banc or by a higher court on appeal. Id.; see Johnson v. Commonwealth, 252 Va. 425, 429-30, 478 S.E.2d 539, 541 (1996). Thus, we are not at liberty to revisit the holding of the panel in Stumpy Lake that "Virginia recognizes representational standing . . . and that Code § 62.1-44.29 confers this representational standing" in cases meeting its requirements. 46 Va.App. at 118, 616 S.E.2d at 46. 2. Sufficiency of Facts Pleaded to Establish Representational Standing[2] "[A]n association has Article III standing to sue on behalf of its members when `(a) its members would otherwise have standing to sue in their own right; (b) the interests it seeks to protect are germane to the organization's purpose; and (c) neither the claim asserted nor the relief requested requires the participation of individual members in the lawsuit.'" Stumpy Lake, 46 Va.App. at 114, 616 S.E.2d at 44 (quoting Hunt v. Wash. State Apple Advertising *73 Comm'n, 432 U.S. 333, 343, 97 S.Ct. 2434, 2441, 53 L.Ed.2d 383, 394 (1977)). (a) Standing of Members to Sue in Their Own Right As our holding in Stumpy Lake, 46 Va.App. at 116, 616 S.E.2d at 45, reiterates, the first prong of the representational standing test requires that "at least one member of the association, but not all of its members," satisfy the three-part test for Article III standing set out in Lujan, 504 U.S. at 560-61, 112 S.Ct. at 2136, 119 L.Ed.2d at 364, and adopted in Code § 62.1-44.29: First, there must be an injury in fact that is both "(a) concrete and particularized[] and (b) actual or imminent." Stumpy Lake, 46 Va. App. at 112, 616 S.E.2d at 43. Second, "a causal connection must exist between the injury and the conduct complained of." Id. Third, "it must be likely that the injury would be redressed by a favorable decision." Id. We hold CBF's petition contains sufficient allegations to plead injury in fact, causation and redressability as to at least one of its members. (1) Injury in Fact As discussed above, "environmental plaintiffs adequately allege injury in fact when they aver that they use the affected area and are persons `for whom the aesthetic and recreational values of the area will be lessened' by the challenged activity." Laidlaw, 528 U.S. at 183, 120 S.Ct. at 705, 145 L.Ed.2d at 628. The injury "`need not be large[;] an identifiable trifle will suffice.'" Gaston Copper, 204 F.3d at 156 (quoting Cedar Point Oil Co., 73 F.3d at 557 (internal quotation marks omitted)). Further, "threatened rather than actual injury can satisfy Article III standing requirements. `One does not have to await the consummation of threatened injury to obtain preventive relief. If the injury is certainly impending that is enough.'" Id. at 160 (quoting Babbitt, 442 U.S. at 298, 99 S.Ct. at 2308, 60 L.Ed.2d at 906 (internal quotation marks omitted)) (citations omitted). Where the claim of injury is based on allegations that a company is discharging chemicals in quantities that exceed those specified in a permit and the discharge restrictions were "set at the level necessary to protect the designated uses of the receiving waterways, the[] violation [of the discharge restrictions] necessarily means that these [designated] uses may be harmed." Id. at 156-57. As with the allegation of harm to CBF as an organization, the claim of injury to CBF's members as individuals rests on allegations that the permit allows the discharge of chemicals in amounts greater than those set by applicable law to protect the designated uses of the receiving waterway. As set out above, relevant water quality regulations provide that all state waters, which necessarily include the James River segment into which the subject Philip Morris facility discharges its wastewater, are designated for certain "recreational uses, e.g., swimming and boating; the propagation and growth of a balanced, indigenous population of aquatic life, including game fish, which might reasonably be expected to inhabit them; and the production of edible and marketable natural resources, e.g., fish and shellfish." 9 VAC XX-XXX-XX(A). Thus, here, as in Gaston Copper, an allegation of "the[ ] violation [of the discharge restrictions, if proved,] necessarily means that these [designated] uses may be harmed." Gaston Copper, 204 F.3d at 156-57. CBF further alleged with particularity that its members are "among [those] injured" by this alleged violation. Morton, 405 U.S. at 735, 92 S.Ct. at 1366, 31 L.Ed.2d at 643. It expressly asserted as follows: The discharge of nutrients in amounts and concentrations authorized by the unlawful Permit, which does not ensure that the Virginia WQS [water quality standards] for this stream segment will be maintained, has and will continue to cause injury to . . . [CBF's] members who regularly use and enjoy the James River . . . for swimming, boating, kayaking, canoeing, sport fishing, and other educational and recreational pursuits. CBF need not, at the pleading stage, name those members or further specify how they have been harmed. Laidlaw, 528 U.S. at 183, 120 S.Ct. at 705, 145 L.Ed.2d at 628. *74 (2) Causal Connection These same allegations provide a sufficient causal connection between the act and the harm under the standards set out in Part II.A.2, supra. (3) Redressability For the reasons set out in Part II.A.3, supra, we hold the harm alleged is redressable to the extent that CBF seeks to have the permit set aside and re-issued only if it complies with applicable laws necessary to ensure that water quality standards shall be maintained.[3] (b) and (c) Nature of Interests and Requested Relief Appellees do not expressly challenge parts (b) and (c) of the representational standing test, which require that "`(b) the interests [the organization] seeks to protect are germane to [its] purpose[] and (c) neither the claim asserted nor the relief requested requires the participation of individual members in the lawsuit.'" Stumpy Lake, 46 Va.App. at 114, 616 S.E.2d at 44 (quoting Hunt, 432 U.S. at 343, 97 S.Ct. at 2441, 53 L.Ed.2d at 394). We hold that the facts alleged satisfy all prongs of the test for representational standing. Thus, we conclude that CBF has alleged sufficient facts to establish standing to sue in both an individual and a representative capacity. C. RULING ON MOTION FOR LEAVE TO AMEND TO CORRECT DEFICIENCIES IN PLEADING Because we hold CBF alleged sufficient facts to establish standing to sue in both an individual and a representative capacity, we need not consider the trial court's ruling on CBF's request for leave to amend its petition for appeal. III. For these reasons, we hold the trial court's conclusion that Virginia law does not permit representational standing was erroneous. We hold further the facts alleged in CBF's petition for appeal, accepted as true, were sufficient to survive the appellees' demurrers. Thus, we reverse the trial court's dismissal of the petition with prejudice without addressing the trial court's ruling on CBF's request for leave to amend, and we remand to the trial court for further proceedings consistent with this opinion. Reversed and remanded. NOTES [1] We do not address in this appeal whether the trial court has the authority to render the other forms of relief CBF seeks. [2] The record does not make clear whether the trial court considered the sufficiency of the facts pleaded to establish representational standing. Regardless, because this question involves a demurrer and, thus, does not require the resolution of any disputed factual issues, we may consider it in this appeal. Cf. Stumpy Lake, 46 Va.App. at 111, 616 S.E.2d at 42 (noting review of circuit court ruling on demurrer is de novo). [3] We do not address in this appeal whether the trial court has the authority to render the other forms of relief CBF seeks.

Ale Moreno looks at the highs and lows for Major League Soccer in 2018 ranging from die-hard fans, pitch invaders, Vikings and absolutely bonkers celebrations. (7:27) Veteran Diego Ribas has reached a final agreement with Major League Soccer club Orlando City on a three-year deal worth $2 million per season, sources tell ESPN Brazil. The 33-year-old attacker from Brazil has six months remaining on his contract with Flamengo and both clubs are still negotiating whether his release will be in January or whether he will remain in Brazil until his contract runs out and then join Orlando, according to Jorge Nicola and Gustavo Zupak. The former Brazil national team player began his career with Santos and played for Porto, Werder Bremen, Atletico Madrid, Wolfsburg and Fenerbahce before returning to his home country with Flamengo. Reports out of Brazil say that Flamengo's new manager, Abel Braga, is not interested in Diego's services and the club had informed him that they would not extend his contract beyond the existing one. Diego is seen as having the role that veteran forward Kaka filled for the MLS club, the reports say. Negotations in the United States turned in Diego's favor after Orlando could not reach an agreement with Peruvian left-back Yoshimar Yotun, who ultimately signed a deal with Cruz Azul in Liga MX.

Install Cyanogenmod 13 Nightly on Galaxy S3 Marshmallow 6.0.1 The Samsung Galaxy S3 notonly it isone ofthe most selling Samsung phones but also it’s world’s best selling smartphone. Although, this phone is launched in 2014, May the phone is still having support from developers of the custom ROMs. Fortunately, there are many custom ROMs for Samsung Galaxy S3 that you can find by checking XDA-Developers site, but only some of them are completely stable and comes without issues. Cyanogenmod Team has released many custom firmwares for Galaxy S3 such as CM12, CM12.1 and this time also CM13. For people who do not know, CM13 ROM is based on Marshmallow 6.0.x which means that it comes installed with all Android Marshmallow 6.0 features, applications and capabilities. Before starting the guide how to update Samsung Galaxy S3 to Marshmallow 6.0.1 I recommend you to check some Prerequisites from below Please use this guide only with the Samsung Galaxy S3 GT-I9300 variants. Your phone should have root access. You can easily verify if your phone have root access using Root Checker application. You need to installed a custom recovery image such as TWRP, CWM or even pHilz. Since, we will complete an unofficial operation during the update process you will have to perform a factory reset. All your personal data will be erased so, I highly recommend you to backup your important data. Make sure you have installed Samsung drivers or Samsung Kies software on your computer.

Q: Inkscape - Exclusion/Difference: remove fill but preserve stroke (size) For my background, I'm not entirely comfortable with Inkscape, but I'm not entirely new with it either. Say I have a large object with a smaller object inside of it. I want to remove the smaller object with Path -> Exclusion (or Difference). If I do this, the smaller object's fill will be removed and its stroke will be preserved. However, the stroke size will be reset. Is there a way for me to preserve the stroke size when using Exclusion? Neither stroke to path or object to path do what I'd like. Let me know if I need to explain myself more. EDIT I think I just figured it out. It looks how I want it to look at least. I chose the smaller object and selected Path -> Inset. Then I chose both objects and selected Path -> Exclusion. EDIT Nevermind, I didn't figure it out; it doesn't work for a different set of objects. Here's the image. I'm trying to use Exclusion on the mouth and teeth. A: As per your post I understood this way. I created both the paths. Duplicated the mouth path.Ensure that duplicated mouth path is in the top Z-order. Select mouth & a tooth & apply path-difference. Now your result looks like this image. Similarly repeat step 2 & 3 for another tooth. Now you can move the stroked teeth downward. You can now remove the stroke & fill the mouth area. The final result after these steps. Is this the result what you want ?

Q: spring 3 annotation dependency injection For a new legacy application I have to use Latest Spring framework 3.x with Hibernate 3.x. Earlier I used Spring IoC with xml configuration. Now i would like to go for annotation based IoC. Below link from rose india shows use annotation without xml file. rose india but i have found some other way of implementing in another site: blog I am confused here which way to implement IoC with latest technology. Please refer some good site for sample. Also please share some sample code for IoC with annotation. EDIT: Spring reference document 3.x says use @Configuration or xml configuration i.e. with annotation <context:annotation-config/>. Which one is better to use? Why? A: Your best bet is to start with the Spring 3.0 Documentation. If you already are familiar with Dependency Injection using xml configuration, take a look at Spring's annotation support in Section 3.9 Annotation-based container configuration. There should be plenty of details there to help get you started. If this is not a WebApp, and you need to load the ApplicationContext yourself, you should take a look at Section 3.11 Java-based container configuration. This section details how you can create your ApplicationContext with your xml configuration. I would recommend using the @Autowired annotations for wiring with @Component annotation for defining beans within the ApplicationContext, and use the scan(String) method provided by the AnnotationConfigApplicationContext to find all annotated components: public static void main(String[] args) { AnnotationConfigApplicationContext ctx = new AnnotationConfigApplicationContext(); ctx.scan("your.package.here"); ctx.refresh(); MyService myService = ctx.getBean(MyService.class); //use myService }

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Q: Why is not Monster model displayed by glTFLoader of three.js on iOS? -Spec- three.js version : r84 (NOW) Device : iPad Air2 iOS version : 10.0.2 Browser : Chrome, Safari -glTFLoader- URL : https://threejs.org/examples/#webgl_loader_gltf Monster -> NOT displayed The others -> displayed Why do I ask this question? I have same issue in my self-made model. My model is exported by the following process. Modeling, UV, Skinning and Animation by MODO Exported Collada by MODO Converted glTF from Collada by COLLADA2GLTF tool My model is displayed on Windows and macOS, but not displayed on iOS. So, I'm in the same situation as the example. Is there a rule for displaying it? PS I don't have new Android device. I don't check on Android... A: The cause is max number of bones. If we use number of bones more than that are supported by OS, WebGL renderer outputs "too many uniforms" error. I hear that iOS (10.x?) support 22 bones (Phong shading) or 22 bones (Lambert shading). This issue has already been listed on github. https://github.com/mrdoob/three.js/issues/7807 A simple solution is that we use less than 22 bones. Hmm... It's a small number for human model and so on. Thank you Marco13 and everyone. note: The Monster model has 32 bones. (my self-made model has 52 bones (!).) I was able to learn how to debug with iOS safari + macOS safari. The following is the log of the Monster model.

Twilight Sparkle has been working herself into such a state of fatigue that Celestia has ordered her to take a five month vacation from her studies and has given Spike the assignment to ensure that Twilight relaxes. A lot can happen in five months. A young boy, a little girl, a chance encounter, and a big heart. All of these things will lead to changes in the Sparkle household that no one is prepared for, but will enhance their lives in ways that no one expects. It's been a few months since the Mane Six played their first game of Truth or Dare at their slumber party. Starlight and Spike are here to join the fun, too. Then two unexpected guests come knocking. It'll be total chaos. Telling your older brother how much you care about him is sometimes very difficult. More often than not, the truth is left untold. Twilight does however get around to tell him what she thinks, even if it is ten years too late. Spike and Twilight return from the alternate world to only see that Spike has not changed back to a dragon. Spike must come to terms with his new form and fight to protect those that come to rely on him. Pinkie Pie always loved Freddy Fazbear’s Pizza Place, the restaurant was (almost) as good at throwing parties as she was! It's a place where dreams come true. She never imagined it would also bring her nightmares to life. While investigating a string of crimes in Canterlot, detective Gro'gar stumbles on a conspiracy. Together with a young Shining Armor and a former cultist filly, he'll have to uncover a terrible truth that will test his resolve and integrity Six years after her ascension to princesshood, Twilight and Spike have started to grow apart. Spike starts to fear what age will do to him, and he comes to the realization that he must tell Twilight a shocking truth before it's too late. This is a very beautifully written story, even if in first chapter Twi might seem to be a little OOC, the second one explains clearly why she acts like she acts. I love how you used the confusion in her heart to propel her actions it certainly is befitting her character. Favored, Liked and... Hope for a sequel, to see them struggle with the important gift they realized they have. I think that the best thing I can say about the story is that your prose is pleasant to read. Other than that... well...you turned Spike into a misery sue... which immediately makes me dislike the story. More than that, everything, from the characterization to the wording, to the events seems slightly... off somehow; and italics in speech as well as in thought are simply confusing... In Spike's coma sequence, you mixed up past and present tenses, quite often in fact. You should re-read and rectify that. As for the content... it's quite warm to read, but it feels as though it's missing so much of the story, I can't see this as complete. The scarf, for example, was barely touched upon, while its significance was barely skimmed. Twilight's initial reaction to Spike's admission confuses me, and honestly makes no sense. I cannot fathom why Twilight would tell him to leave--the whole "a princess and a dragon/assistant can never be together" thing seems like a very weak defense, and I don't really find her inner argument against her feelings valid. This was such a beautiful story. Twilight's emotional struggle felt real for her character and the blizzard was just a perfect add on to the drama and turmoil. Probably one of my favorite Spilight story right now. Liked, faved... and a sequel maybe? 4165440 I think they were mad at Twilight for, essentially, killing Spike. It was her fault that he ran away, she didn't go save him. Celestia loves Twilight, but letting her son die would make any mother furious. The same can be said for Luna. As for the others, they were all disappointed in Twilight, they all cared for Spike to some degree and now he was gone because of her.Now with all the negativity and anger felt by three Alicorns and the Element bearers, I guess that made the wendigoes reappear? 4165440After the breaking of harmony, each of the mane six and princesses among themselves blamed for the fate of Spike, undoing the spirit of unity that kept the equestrian realm away from the cold and ice. Which brings the question, in his "almost" death, saw Spike a possible consequence for his death? I got nothing complimentary to say about Celestia in this one. The dragon she's responsible for is suffering a ver unique personal crisis, and she just gives him a children's show platitude? Weak, especially for a being who's lived thousands of years. She tells him to be proud of who and what he is, but if his identity is the very thing that's preventing him from being close to someone, what's there for him to be proud of? Accepting that he'll never receive the love he gives so willingly? She's pretty much telling him to take pride in his lonely, martyr-like existence. Most Spike-suicides fics are just cheap indulgences, but I can easily see him ending it all when he finds out he will never have a significant other with whom to share that life. 4163598I'd love to hear what you have to say on this matter. I did think that Twi was OOC, and to an extend, that was the plan. However, I am starting to realize that her small revelation chapter might not be enough to erase the notion that she's too different. This is why I feel your input would be very welcome on this matter. 4199899 I wouldn't say its jarring, more likely that Twilight's reasons should be portrayed earlier to avoid initial confusion which shows itself in chapter 1. As for the sequel...seeing those like/dislike ratio I guess a lot of people favored. That alone should be feedback big enough to inform you that people enjoyed it and would probably enjoy sequel as well. You have a great idea and potential with this fic that can bloom into beautiful tale... which is exactly why I do hope for sequel. (and because it would be about Twilight and Spike in relationship and there aren't many fics like that, most of them are about this duo falling in love).

Background ========== Mouse models are currently used to research many human cancers including colon cancer. On a genome wide scale, mouse protein sequences share 78.5% sequence identity with human counterparts \[[@B1]\]. With such high levels of sequence identity it may seem reasonable to expect that many orthologs between mouse and human would have conserved functions. However, in the \~180 Million Years (MY) of independent evolution \[[@B2]\], it is possible that certain proteins have functionally diverged. One example of ortholog divergence between human and mouse is the *TDP1* gene, required in Topo1-DNA complex repair, protein sequence similarity of 81%. A point mutation from an adenine to a guanine at position 1478 in human *TDP1* is linked with a disorder known as SCAN1 that results in cerebellar atrophy and peripheral neuropathy. However, this mutation in mouse does not result in the same condition/phenotype \[[@B3]\]. Specific mutations in any of the following genes in human result in disease: BCL10, PKLR and SGCA, but the same mutations in the mouse homologs do not result in phenotypic change to a disease state \[[@B4]\]. BRCA1 is heavily implicated in breast cancer in humans, with BRCA1^+/−^ women having a 50% risk of developing breast cancer, while BRCA^+/−^ mice do not exhibit increased susceptibility to cancer \[[@B5]\]. These observed differences in phenotype could potentially be the result of protein functional shifts in cancer-associated genes between human and mouse. While the analysis of the mouse lineage versus human is important from an evolutionary medicine perspective to determine/predict those specific cases where mouse may not effectively model the human disease phenotype, the analysis of all other lineages frames these results in the context of all mammals. Therefore, in this study we have not only examined the human and mouse lineages but all lineages leading to extant species in our dataset. This allows us to gain a greater understanding of the level of lineage-specific functional shift that has occurred in colon cancer associated genes. Positive selection is the retention and spread of advantageous mutations throughout a population and has long been considered synonymous with protein functional shift. There are a number of driving forces for positive selection including external mechanisms such as adaptation to different ecological niches and response to disease and internal mechanisms such as co-evolution and compensatory mutations \[[@B6]\], all of which are relevant to the data and species we are analyzing. At the molecular level, the ratio of nonsynonymous substitutions per nonsynonymous site (*dN*) to synonymous substitutions per synonymous site (*dS*) is known as ω, and indicates the selective pressure at work in that sequence. If ω \> 1 it signifies positive selective pressure, ω = 1 signifies neutral evolution, while ω \< 1 indicates purifying selective pressure. Previous work assessed the level of positive selection present in mammal genomes and estimated 5%-9% of genes in mammals are under positive selection under a Bayesian framework, and thus provides us with a reference or expected level of positive selection for our analysis \[[@B7],[@B8]\]. Here we have applied a Maximum Likelihood method based on codon models of evolution to assess the selective pressures across our dataset \[[@B9]\]. These methods are far more robust than alternatives such as the sliding window approach \[[@B10]\], nonetheless they do suffer from limitations and have strict criteria in terms of dataset size for statistical robustness \[[@B11],[@B12]\]. Another feature of sequence evolution that can negatively impact on a selective pressure analysis is recombination \[[@B13]\]. To evaluate the robustness of the Likelihood Ratio Tests (LRTs), simulations have been performed that show that type 1 error rates can be up to 90% with relatively high rates of recombination in protein coding sequences resulting in the misinterpretation of recombination as positive selection \[[@B13]\]. We have incorporated a test for recombination for all genes in the dataset prior to the ML selective pressure analysis. Recent studies using these codon models of evoluton in an ML framework have combined evolutionary predictions of positive selection with biochemical verification of functional affects of these substitutions \[[@B14]-[@B16]\], and thus support the link between positive selection and protein functional shift. We have taken colon cancer as an example for our study given the large amount of mutation and epigenetic data available for this form of cancer \[[@B17]\]. Lineage-specific positive selection in genes associated with colon cancer is strongly suggestive of functional shift and could have serious implications in the use of certain lineages for modeling colon cancer. Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and second in females and we have focused on this in our study \[[@B18]\]. CRC arises through the accumulation of multiple genetic and epigenetic changes. Genetic changes consist of both somatic and germline (i.e. heritable) mutations. The genes in which there are germline mutations that are highly associated with the development of colon cancer are analyzed here (22 genes in total) and are referred to throughout this manuscript as "colon cancer associated genes". Colon cancer associated genes work in conjunction with other proteins and pathways and can be thought of as contributing to, rather than being the single cause of colon cancer (note: these genes also have other functions outside of their association that may contribute to selective pressure variation in different lineages). Epigenetic changes such as hypermethylation of certain genes, loss of imprinting and acetylation/phosphorylation/methylation of particular histones are also implicated in cancer. Detailed information on colon cancer epigenetics have been made available to the community through the StatEpigen biomedical resource \[[@B17]\]. Other events such as loss of heterozygosity, microsatellite instability and CpG island methylator phenotype can also play an important role. Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is a hereditary predisposition for the development of colorectal cancer, and accounts for 3% of all colon cancer cases \[[@B19]\]. The 22 genes we have analyzed were selected based on the presence of known germline mutations associated with colon cancer. What follows is a brief description of each gene in the study. The genes linked with HNPCC are: MLH1, PMS2, MSH2, MSH6, and PMS1, all of which are members of the MMR DNA repair pathway \[[@B19]\]. MLH1 (mutL homologue 1) is a mismatch repair gene and is commonly associated with HNPCC. Missense mutations in MLH1 occur in the C-terminal domain, which is responsible for constitutive dimerization with the mismatch repair endonuclease PMS2 \[[@B20]\]. Studies have also shown that microsatellite instability (MSI) is the molecular fingerprint of a deficient mismatch repair system. It is estimated that some 15% of colorectal cancers display MSI owing to the epigenetic silencing of MLH1, and/or germline mutation in any one of the following mismatch repair genes: PMS2, MLH1, MSH2, and MSH6 \[[@B21]\]. The mismatch repair endonuclease PMS2 is known to interact with MLH1 and is a component of the post-replicative DNA mismatch repair system (MMR). PMS2 is recruited to cleave damaged DNA this recruitment is triggered by the binding of MSH2 and MSH6 proteins to dsDNA mismatches followed by the recruitment of MLH1 (Figure [1](#F1){ref-type="fig"}). PMS1 is also involved in the repair of DNA mismatches, and it can form heterodimers with MLH1. Additional genes in our study include the tumor suppressor gene TP53, CDH1, MUTYH, and APC. TP53 is a hub protein in the cellular DNA damage response pathway known as the P53 signaling pathway \[[@B22]\], it is linked with colorectal cancer and many other cancers. The genes CDH1, MUTYH, and APC also interact with one another in addition to their involvement in the MMR pathway described above. For example, CDH1 and APC combine to act as a ubiquitin ligase, which is involved in glycolysis regulation during the cell cycle \[[@B23]\]. In fact, most of the colon cancer associated genes in this study can be grouped into critical pathways, such as apoptosis, DNA damage control, and cell cycle signaling \[[@B24]\]. {#F1} To assess if there is evidence for protein functional shift from the patterns of substitution in colon cancer associated genes we have carried out selective pressure analyses using codon models of lineage-specific rate heterogeneity. Methods ======= Sequence data assembled ----------------------- The colon cancer gene dataset used in this study consists of 22 genes taken from the Cancer Gene Census at the Sanger Institute \[[@B25]\]. All 22 genes have reported cases of germline mutations that are associated with colon cancer (See Table [1](#T1){ref-type="table"} for summary of data, detail on the complete dataset is available in Additional file [1](#S1){ref-type="supplementary-material"} ). Using Compara data from Ensembl \[[@B26],[@B27]\], single gene orthologs were identified for each gene across the vertebrate genomes chosen. The 21 species were selected based on genome coverage. These included representatives from 3 of the 4 main lineages of Eutheria, namely Afrotheria, Euarchontoglires, and Laurasiatheria, as well as outgroup species including platypus, zebrafish, and zebra finch (see Additional file [1](#S1){ref-type="supplementary-material"}). ###### Colon Cancer Gene Set analyzed in this study **Gene (HGNC code)** **Ensembl Identifier** **Taxa Number**^**2**^ **Alignment Length**^**3**^ **Syndrome** **Tumor Types Observed** **Pathway(s)** **References**^**4**^ ---------------------- ------------------------ ------------------------ ----------------------------- --------------------------------------------------- ----------------------------------------------------- -------------------------------------- ------------------------------------- APC ENSG00000134982 20 9177 Familial adenomatous polyposis (FAP) Colon, thyroid, stomach, intestine APC \[[@B19],[@B24]\] ATM ENSG00000149311 18 9189 Ataxia telangiectasia (A-T) Leukemia, lymphoma, colorectal CIN \[[@B24]\], \[[@B24]\] BHD ENSG00000154803 20 1737 Birt-Hogg-Dube syndrome Renal, colon AMPK, mTOR, STAT \[[@B24]\] BMPR1A ENSG00000107779 19 1596 Juvenile polyposis Gastrointestinal SMAD \[[@B24]\] CDH1 ENSG00000039068 15 2649 Familial gastric carcinoma Stomach AP \[ \[[@B24],[@B28]\] (E-cadherin)\] MADH4 ENSG00000141646 16 1656 Juvenile polyposis Gastrointestinal SMAD \[ \[[@B24]\], (SMAD4)\] MET ENSG00000105976 21 4146 Hereditary papillary renal cell carcinoma (HPRCC) Kidney, colorectal RAS, PI3K, STAT, Beta-catenin, Notch \[[@B24]\] MLH1 ENSG00000076242 19 2274 Hereditary non-polyposis colon cancer (HNPCC) Colon, uterus MMR \[[@B24]\] MSH2 ENSG00000095002 18 2802 Hereditary non-polyposis colon cancer (HNPCC) Colon, uterus MMR \[[@B24]\] MSH6 ENSG00000116062 19 4101 Hereditary non-polyposis colon cancer (HNPCC) Colon, uterus MMR \[[@B24]\] MUTYH ENSG00000132781 21 1569 Attenuated Polyposis Colon BER \[[@B24]\] NF1 ENSG00000196712 17 8523 Neurofibromatosis type I Neurofibroma, colon RTK \[[@B24]\] PMS1 ENSG00000064933 20 2799 Hereditary non-polyposis colon cancer (HNPCC) Colon, uterus MMR   PMS2 ENSG00000122512 21 2592 Hereditary non-polyposis colon cancer (HNPCC) Colon, uterus MMR \[[@B24]\] PTEN ENSG00000171862 18 1209 Cowden syndrome Hamartoma, glioma, colorectum PI3K \[[@B24]\], \[[@B24]\] SDHB ENSG00000117118 18 840 Hereditary paraganglioma, Carney--Stratakis Paragangliomas, pheochromocytomas, gastrointestinal HIF1 \[[@B24]\] SDHC ENSG00000143252 16 507 Hereditary paraganglioma, Carney--Stratakis Paragangliomas, pheochromocytomas, gastrointestinal HIF1 \[[@B24]\] STK11 ENSG00000118046 18 1320 Peutz-Jeghers syndrome Intestinal, ovarian, pancreatic, colorectal PI3K \[[@B24],[@B29]\] TP53 ENSG00000141510 16 1185 Li-Fraumeni syndrome/sarcoma Breast, sarcoma, adrenal, brain, colorectal p53 \[[@B24],[@B29]\] TSC1 ENSG00000165699 18 3495 Tuberous sclerosis Hamartoma, kidney, colorectal PI3K \[[@B24],[@B29]\] TSC2 ENSG00000103197 19 5436 Tuberous sclerosis Hamartoma, kidney, colorectal PI3K \[[@B24],[@B29]\] VHL ENSG00000134086 18 639 Von Hippel-Lindau syndrom Kidney, colorectal HIF1 \[[@B24]\] Each of the 22 genes analyzed in this study are detailed, including their HGNC approved gene symbols, and Ensembl gene IDs. The total number of species analyzed for each gene and the overall length of alignment in base pairs are also given. The syndrome, tumor type observed and pathway involved are detailed. References citing alternative gene names are identified using rounded parentheses. Multiple sequence alignment --------------------------- The coding DNA sequences of the single gene orthologs were translated and the resulting amino acid sequences were aligned using the default parameters in ClustalW 2.0.12 \[[@B30],[@B31]\]. We mapped gaps from the amino acid multiple sequence alignment (MSA) to the corresponding nucleotide sequences to produce a nucleotide alignment. All alignments were reviewed for quality and any poorly aligned regions were manually edited using Se-Al \[[@B32]\]. All alignments are available in Additional file [2](#S2){ref-type="supplementary-material"}. Alignment criteria for selective pressure analysis -------------------------------------------------- It has been shown through computer simulations that sequence length has an impact on the power to infer positive selection \[[@B33]\]. Power was also found to increase with greater taxonomic representation and greater divergence, although extreme levels of divergence were found to cause a reduction in power. Simulations have shown that the presence of longer foreground branches also increased the power of the test statistic, but extremely long foreground branches reduced the power \[[@B34]\]. To increase the statistical power of the analyses performed here we have therefore only considered single gene families containing 6 or more taxa, and alignment lengths of greater than 500 amino acids. Recombination analysis ---------------------- Recombination events can result in the incorrect detection of positive selection. To reduce the detection of potential false positives from our analyses, we have implemented GENECONV (version 1.81a) \[[@B35]\]. GENECONV detects gene conversion events between ancestors of sequences in a multiple sequence alignment. Default parameters where employed, and 10,000 randomly permuted datasets were generated for each Single Gene Orthologous family and global inner fragments were listed if P-value \<= 0.05 or smaller. Selective pressure analysis using codon models of evolution ----------------------------------------------------------- Selective pressure analyses were performed using Codeml from PAML version 4.4 \[[@B36],[@B37]\]. Because each gene family analyzed was composed of single gene orthologs, pruned species phylogenies were used as per previous publications \[[@B2],[@B38]\]. Codeml implements a number of codon-based models in a Maximum Likelihood framework that can be used to test alternative and nested evolutionary hypotheses. Three different types of codon model were used in this study: (i) a homogeneous model (Model 0) - a single ω-value is estimated for the entire alignment; (ii) site-heterogeneous models - the sites of the gene sequence are grouped into two or more site classes, each with its own ω-value; and (iii) lineage-specific heterogeneous models - a different ω parameter is estimated for different site classes in combination with different lineages \[[@B9],[@B36],[@B39]\]. Seven site-heterogeneous models were used, we have retained conventional annotations for these models: Model 1a (Nearly Neutral), Model 2a (Selection), Model 3 Discrete (k = 2), Model 3 Discrete (k = 3), Model 7, Model 8 and Model 8a. Two lineage-specific heterogeneous models were used: Model A and Model A Null. These models have been applied similarly elsewhere \[[@B40]\]. The goodness-of-fit of the different models was assessed statistically using a likelihood ratio test (LRT). The LRT compares the log-likelihoods of a null model with the alternative model. For hierarchically nested models, the test statistic of an LRT approximates the *χ*^2^ distribution with degrees of freedom equal to the number of additional free parameters in the alternative model compared to the null model. Because of this, the critical value of the test statistic can be determined from standard statistical tables. If the p-value of the test statistic exceeds that critical value (i.e. if the alternative model fits the data significantly better than the null model), then the null model can be rejected. For example, if the test statistic of an LRT comparing Model 1a (Nearly Neutral) with Model 2a (Selection) is greater than the critical value determined from the *χ*^2^ distribution, Model 1 a can be rejected. If ω~1~ \> 1 under Model 2a, positive selection may be inferred. Additional file [3](#S3){ref-type="supplementary-material"} shows the set of LRTs used for selective pressure analysis. In cases where positive selection is inferred, the posterior probability of a site belonging to the positively selected class is estimated using two calculations: Naïve Empirical Bayes (NEB) or Bayes Empirical Bayes (BEB). If both BEB and NEB are predicted, we will preferentially use the BEB results as these have been shown to be more robust \[[@B37]\]. In-house software was designed to prepare all files for analysis and to process all output. PAML output files were parsed for parameter estimates and log likelihood values, and LRTs were performed (see Additional file [3](#S3){ref-type="supplementary-material"}). Where positively selected sites were inferred under a given model, positively selected sites were mapped to the sequence (or sequences) of interest and included in the summary file (see Additional file [4](#S4){ref-type="supplementary-material"}). This software was used to reduce the scope for human error in setting up and interpreting PAML analyses and is available from the authors on request. Functional annotation of sites under positive selection for each protein was obtained from UniProt \[[@B41]\]. Human population analysis ------------------------- Selective pressures within the present day human population were analyzed for those genes with evidence of lineage-specific positive selection in the human ancestral lineages. The online tool SNP\@Evolution^2^ and HapMap release II source data was used to look at variations within the East Asian (A), Northern and Western European (C), and African Yoruba (Y) populations. The "integrated haplotype score" or iHS, described first in \[[@B42]\], was employed here as a test for directional selection. The iHS is standardized using genome wide empirical distributions, it has an approximate normal distribution allowing for direct comparisons of the score across genes, and it outperforms in comparison to other available approaches \[[@B42]\]. A derived allele that has been segregating in the population receives a large iHS (\> + 2) while a large negative iHS (\<−2) indicates that the derived allele has increased in frequency. Results and discussion ====================== Starting with a dataset of 22 genes, we identified single gene orthologs across 21 complete vertebrate genomes. Ortholog identification resulted in families with between 15 and 21 taxa, and alignment lengths of between 507 and 9,189 base pairs thus satisfying the criteria described in the materials and methods section. The test for recombination on all 22 genes is summarized in Additional file [5](#S5){ref-type="supplementary-material"}. The analysis revealed that only the TP53 protein showed significant levels of recombination, the regions where recombination was present were noted and compared to regions where positive selection was detected. If these regions overlapped - the positive selection result was deemed a false positive. To assess the selective pressure variation, we performed both site- and lineage-specific selective pressure analyses and subsequently assessed the statistical significance of all results via LRT analyses to ascertain the codon evolutionary model of best fit. In those cases where the ω value vastly exceeds 1, we have simply denoted them as ω \> \> 1 throughout the manuscript, as there is no biological significance for these extremely large ω values (the precise numbers are shown in the Tables throughout). The lineage-specific analyses are more pertinent to the main focus of the paper, i.e. - the identification of species-specific patterns of substitution in these colon cancer associated genes. Therefore the lineage-specific results have been described in detail in the following section. Site-specific results are briefly summarized on a gene-by-gene basis. All positively selected sites were assessed using functional information from the Uniprot database \[[@B41]\]. The model of best fit along with associated parameter estimates are described and a summary table for each of the 22 genes is given in Additional file [4](#S4){ref-type="supplementary-material"}. Lineage-specific selective pressure analyses -------------------------------------------- Lineage-specific models of codon evolution were assessed at multiple phylogenetic depths, (i) the extant lineages within the Euarchontoglires clade, and (ii), all ancestral lineages leading from the Euarchontoglires to modern mouse and human were also tested independently as depicted in Figure [1](#F1){ref-type="fig"}. Analysis of the extant human and mouse lineages did not yield evidence of positive selection. Conversely, analysis of the lineages within the Euarchontoglires clade resulted in significant evidence of lineage-specific positive selection, 6 genes in ancestral lineages and 12 in extant lineages, see Figure [1](#F1){ref-type="fig"}. The STK11 gene showed evidence of positive selection in the Euarchontoglires ancestral lineage and again in the Hominidae ancestral lineage. CDH1 showed patterns of substitution conducive with positive selection in the ancestral primate lineage. In the ancestral Muridae lineage there is evidence for positive selection acting on the TSC1 gene. The ancestral Murinae lineage showed evidence of positive selection for both MSH6 and SDHC, see Table [2](#T2){ref-type="table"} for summary. ###### Summary of parameter estimates and likelihood scores for the model of best fit showing evidence of positive selection **Gene** **Model** **lnL** **Parameter Estimates** **Positive Selection** **BEB Positively Selected Sites** --------------------------------------- ----------- -------------- ----------------------------------------------------------------------------------------------------------------- ------------------------ ------------------------------------ **Lineage-Specific Analyses** **Euarchontoglires Ancestral Branch** STK11 modelA −8602.921472 p~0~ = 0.93299, p~1~ = 0.05633, p~2~ = 0.01007, p~3~ = 0.00061 ω~0~ = 0.03346, ω~1~ = 1.00000, ω~2~ = 197.90897 Yes 3 \> 0.50, 1 \> 0.95, 0 \> 0.99 **Primate Ancestral Branch** CDH1 modelA −16658.03484 p~0~ = 0.75454, p~1~ = 0.23453, p~2~ = 0.00834, p~3~ = 0.00259 ω~0~ = 0.05683, ω~1~ = 1.00000, ω~2~ = 10.20516 Yes 9 \> 0.50, 1 \> 0.95, 0 \> 0.99 **Hominidae Ancestral Branch** STK11 modelA −8601.056009 p~0~ = 0.93574, p~1~ = 0.05920, p~2~ = 0.00476, p~3~ = 0.00030 ω~0~ = 0.03323, ω~1~ = 1.00000, ω~2~ = 44.31709 Yes 3 \> 0.50, 2 \> 0.95, 1 \> 0.99 VHL modelA −4263.853291 p~0~ = 0.73748, p~1~ = 0.25109, p~2~ = 0.00853, p~3~ = 0.00290 ω~0~ = 0.05985, ω~1~ = 1.00000, ω~2~ = 220.34533 Yes 1 \> 0.50, 0 \> 0.95, 0 \> 0.99 **Chimpanzee Extant Branch** TSC2 modelA −42659.27711 p~0~ = 0.90352, p~1~ = 0.09434, p~2~ = 0.00194, p~3~ = 0.00020 ω~0~ = 0.04404, ω~1~ = 1.00000, ω~2~ = 190.09480 Yes 6 \> 0.50, 2 \> 0.95, 2 \> 0.99 VHL modelA −4262.098043 p~0~ = 0.73571, p~1~ = 0.25251, p~2~ = 0.00877, p~3~ = 0.00301 ω~0~ = 0.05976, ω~1~ = 1.00000, ω~2~ = 262.72662 Yes 3 \> 0.50, 0 \> 0.95, 0 \> 0.99 **Gorilla Extant Branch** MSH2 modelA −19485.4338 p~0~ = 0.92233, p~1~ = 0.06298, p~2~ = 0.01375, p~3~ = 0.00094 ω~0~ = 0.06427, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 46 \> 0.50, 34 \> 0.95, 18 \> 0.99 TSC2 modelA −42569.22884 p~0~ = 0.89862, p~1~ = 0.08796, p~2~ = 0.01222, p~3~ = 0.00120 ω~0~ = 0.04339, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 27 \> 0.50, 14 \> 0.95, 12 \> 0.99 MSH6 modelA −34009.90221 p~0~ = 0.78382, p~1~ = 0.18418, p~2~ = 0.02591, p~3~ = 0.00609 ω~0~ = 0.06974, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 46 \> 0.50, 34 \> 0.95, 18 \> 0.99 ATM modelA −69374.08393 p~0~ = 0.80673, p~1~ = 0.17971, p~2~ = 0.01109, p~3~ = 0.00247 ω~0~ = 0.09745, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 48 \> 0.50, 23 \> 0.95, 19 \> 0.99 **Orangutan Extant Branch** TSC1 modelA −24068.71106 p~0~ = 0.79963, p~1~ = 0.18828, p~2~ = 0.00978, p~3~ = 0.00230 ω~0~ = 0.08020, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 13 \> 0.50, 6 \> 0.95,5 \> 0.99 TSC2 modelA −42673.92339 p~0~ = 0.90414, p~1~ = 0.09295, p~2~ = 0.00263, p~3~ = 0.00027 ω~0~ = 0.04433, ω~1~ = 1.00000, ω~2~ = 40.47366 Yes 9 \> 0.50, 0 \> 0.95, 0 \> 0.99 **Marmoset Extant Branch** TSC2 modelA −42616.04524 p~0~ = 0.89841, p~1~ = 0.09019, p~2~ = 0.01035, p~3~ = 0.00104 ω~0~ = 0.04325, ω~1~ = 1.00000, ω~2~ = 235.10448 Yes 38 \> 0.50, 9 \> 0.95 MSH6 modelA −34009.90221 p~0~ = 0.78382, p~1~ = 0.18418, p~2~ = 0.02591, p~3~ = 0.00609 ω~0~ = 0.06974, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 45 \> 0.50, 16 \> 0.95, 12 \> 0.99 VHL modelA −4262.443441 p~0~ = 0.72045, p~1~ = 0.22453, p~2~ = 0.04195, p~3~ = 0.01307 ω~0~ = 0.05886, ω~1~ = 1.00000, ω~2~ = 90.26952 Yes 10 \> 0.50, 0 \> 0.95, 0 \> 0.99 ATM modelA −69583.23068 p~0~ = 0.81640, p~1~ = 0.18148, p~2~ = 0.00173, p~3~ = 0.00038 ω~0~ = 0.09939, ω~1~ = 1.00000, ω~2~ = 46.82466 Yes 2 \> 0.50, 0 \> 0.95, 0 \> 0.99 **Muridae Ancestral Branch** TSC1 modelA −24126.17894 p~0~ = 0.80995, p~1~ = 0.18416, p~2~ = 0.00481, p~3~ = 0.00109 ω~0~ = 0.08293, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 1 \> 0.59, 0 \> 0.95, 0 \> 0.99 **Murinae Ancestral Branch** SDHC modelA −3846.690164 p~0~ = 0.87666, p~1~ = 0.08131, p~2~ = 0.03846, p~3~ = 0.00357 ω~0~ = 0.15340, ω~1~ = 1.00000, ω~2~ = 253.61375 Yes 9 \> 0.50, 2 \> 0.95, 1 \> 0.99 MSH6 modelA −34190.13821 p~0~ = 0.79911, p~1~ = 0.19671, p~2~ = 0.00335, p~3~ = 0.00082 ω~0~ = 0.07057, ω~1~ = 1.00000, ω~2~ = 126.22513 Yes 3 \> 0.50, 1 \> 0.95, 0 \> 0.99 **Rat Extant Branch** MADH4 modelA −6092.186945 p~0~ = 0.93360, p~1~ = 0.01536, p~2~ = 0.05021, p~3~ = 0.00083 ω~0~ = 0.01379, ω~1~ = 1.00000, ω~2~ = 102.33013 Yes 24 \> 0.50, 11 \> 0.95, 10 \> 0.99 NF1 modelA −37750.29866 p~0~ = 0.96609, p~1~ = 0.02476, p~2~ = 0.00892, p~3~ = 0.00023 ω~0~ = 0.02265, ω~1~ = 1.00000, ω~2~ = 999.00000 Yes 39 \> 0.50, 10 \> 0.95, 10 \> 0.99 **Guinea pig Extant Branch** TSC1 modelA −24116.58577 p~0~ = 0.80206, p~1~ = 0.18611, p~2~ = 0.00961, p~3~ = 0.00223 ω~0~ = 0.08093, ω~1~ = 1.00000, ω~2~ = 284.22603 Yes 9 \> 0.50, 4 \> 0.95, 0 \> 0.99 NF1 modelA −37849.50819 p~0~ = 0.97375, p~1~ = 0.02506, p~2~ = 0.00116, p~3~ = 0.00003 ω~0~ = 0.02414, ω~1~ = 1.00000, ω~2~ = 171.64068 Yes 3 \> 0.50, 1 \> 0.95, 0 \> 0.99 **Rabbit Extant Branch** MLH1 modelA −19516.63525 p~0~ = 0.80595, p~1~ = 0.18541, p~2~ = 0.00703, p~3~ = 0.00162 ω~0~ = 0.05262, ω~1~ = 1.00000, ω~2~ = 7.52747 Yes 5 \> 0.05, 3 \> 0.95, 0 \> 0.99 MUTYH modelA −15911.6175 p~0~ = 0.61027, p~1~ = 0.37605, p~2~ = 0.00846, p~3~ = 0.00522 ω~0~ = 0.07703, ω~1~ = 1.00000, ω~2~ = 998.99697 Yes 5 \> 0.50, 4 \> 0.95, 3 \> 0.99 SDHC modelA −3822.683246 p~0~ = 0.57771, p~1~ = 0.06636, p~2~ = 0.31926, p~3~ = 0.03667 ω~0~ = 0.12047, ω~1~ = 1.00000, ω~2~ = 3.59059 Yes 51 \> 0.50, 10 \> 0.95, 8 \> 0.99 ATM modelA −69582.95152 p~0~ = 0.81572, p~1~ = 0.18045, p~2~ = 0.00313, p~3~ = 0.00069 ω~0~ = 0.09930, ω~1~ = 1.00000, ω~2~ = 7.41594 Yes 6 \> 0.50, 0 \> 0.95, 0 \> 0.99 BHD modelA −13523.51719 p~0~ = 0.90728, p~1~ = 0.05930, p~2~ = 0.03137, p~3~ = 0.00205 ω~0~ = 0.02817, ω~1~ = 1.00000, ω~2~ = 6.50017 Yes 10 \> 0.50, 7 \> 0.95, 1 \> 0.99 **Site-specific Analyses** CDH1 m8 −16589.88768 p = 0.21848, p~0~ = 0.99291, p~1~ = 0.00709, q = 0.80842 ω=4.53766 Yes 15 \> 0.5, 1 \> 0.95, 0 \> 0.99 PMS1 m8 −26480.39761 p = 0.61337, p~0~ = 0.93580, p~1~ = 0.06420, q = 1.93110 ω=1.32691 Yes 25 \> 0.50, 1 \> 0.95, 0 \> 0.99 PMS2 m8 −27449.3651 p = 0.29104, p~0~ = 0.91064, p~1~ = 0.08936, q = 1.31619 ω=1.28855 Yes 37 \> 0.50, 1 \> 0.95, 0 \> 0.99 MUTYH m8 −15797.6226 p = 0.37255, p~0~ = 0.97242, p~1~ = 0.02758, q = 1.00900 ω=2.44412 Yes 18 \> 0.5, 1 \> 0.95, 0 \> 0.99 TP53 m8 −8688.19126 p = 0.40362, p~0~ = 0.94645, p~1~ = 0.05355, q = 1.77507 ω=1.97385 Yes 13 \> 0.5, 3 \> 0.95, 0 \> 0.99 The model of best fit is summarized below for those genes with evidence of positive selection. The lineage-specific results for each lineage tested from the Euarchontoglires ancestor to modern lineages are shown in the top panel and the site-specific results are shown in the bottom panel. The model abbreviations are as per main text. P refers to the number of free parameters estimated in that model. BEB = Bayes Empirical Bayes estimations. The number of positively selected sites identified can be found the final column, sites are separated by the posterior probability cutoffs of 0.50, 0.95, and 0.99. In the following section, we have analyzed the positively selected sites for those genes with evidence of lineage-specific positive selection in the context of their potential functional relevance for those genes. This was carried out for all genes where functional sites and/or domains have been elucidated. All sites described were calculated via Bayes Empirical Bayes (BEB) analysis (unless otherwise specified). In all cases we are assessing the potential functional importance of residues based on their sequence position. There are instances where we identify stretches of protein sequence under positive selection - there is a possibility that these sites may have very different functions despite their sequence position. For a total 16 of the 22 genes there were partial or complete 3D structures available. However, many of the positively selected sites identified were located in regions that were not yet fully resolved at the structural level, and so only the 3D model for STK11 is given. ### Positive selection in the Euarchontoglires Ancestral branch The most ancestral branch tested was the Euarchontoglires ancestral branch, i.e. the ancestor of the Primate, Rodent and Glires clades as depicted in Figure [1](#F1){ref-type="fig"}. The STK11 alignment consists of 18 taxa and was the only gene that showed evidence of positive selection in this ancestral lineage. STK11 (Serine/Threonine-protein kinase 11) plays an essential role in G1 cell cycle arrest and acts as a tumor suppressor. It phosphorylates and activates members of the AMPK-related subfamily of protein kinases \[[@B43],[@B44]\],). Mutations in STK11 cause Peutz-Jeghers syndrome (PJS), this is a rare autosomal dominant disorder characterized by multiple gastrointestinal hamartomatous polyps and an increased risk of various neoplasms including gastrointestinal cancer \[[@B45],[@B46]\]. From the literature we currently know of 17 sites across this gene that when mutated are associated with colon-cancer. The Euarchontoglires ancestral lineage has 1.1% of sites under positive selection (ω \> \> 1). The positively selected residues were located on the 3D structure of this enzyme (See Figure [1](#F1){ref-type="fig"} inset). Position 206 with a Posterior Probability (PP) = 0.889 is a hydrophobic Alanine or Valine in Euarchontoglires species and is a negatively charged Glutamic acid or positively charged Lysine in non-Euarchontoglires species. This residue also lies in close proximity to sporadic cancer site A205T and colorectal cancer site D208N in Human \[[@B47]\]. Positively selected position 301 in Euarchontoglires (P = 0.885) is present in Euarchontoglires species as an Arginine residue and all non-Euarchontoglires as an uncharged Glutamine residue. Site 301 is close to R297K and region 303--306 both of which have been implicated in PJS \[[@B48]\]. ### Positive selection in the Primate Ancestral branch The branch leading from the Euarchontoglires ancestor towards the primates was analyzed, we have termed this branch the ancestral Primate branch as depicted in Figure [1](#F1){ref-type="fig"}. The CDH1 dataset consists of 15 taxa and following LRT analyses showed evidence of lineage-specific positive selection in 1.1% of sites in the Primate Ancestor (ω=10.21). Positively selected sites were compared to human Swiss-Prot entry (P12830) and it was found that position 604, with a PP of 0.549, falls in close proximity to gastric cancer variant R598Q \[[@B49]\]. At position 604 Primates have a negatively charged Glutamic acid while non-primates have a polar uncharged Glutamine. ### Positive selection in the Hominidae Ancestral branch The next branch in the primate clade is that leading to modern great apes, i.e. Hominidae, as depicted in Figure [1](#F1){ref-type="fig"}. This lineage also showed evidence of positive selection again in the STK11 gene in 0.51% of sites, with ω \> \> 1. See Figure [2(a)](#F2){ref-type="fig"} and Table [2](#T2){ref-type="table"}. The positively selected positions were compared to the human Swiss-Prot sequence (Q15831). Position 347 represents a radical substitution, as the Hominidae code for an Alanine (a small hydrophobic residue) whereas the Murinae lineage encode an Arginine at this position (a basic, hydrophilic, and positively charged residue). For positively selected site 378, the ancestral Hominidae lineage encodes the polar residue Serine, while the closely related species studied encode the small amphiphilic Glycine. The functions of these specific sites have not been reported thus far in the literature but are likely to be of considerable interest as they mark adaptations unique to the ancestral Hominidae. {#F2} A second gene showing evidence of positive selection in the Hominidae ancestral branch is the VHL dataset consisting of 18 taxa. The VHL gene encodes Von Hippel-Lindaue tumour suppressor protein. Mutations occurring in this gene can result in von Hippel-Lindau disease (VHDL) - a dominantly inherited familial cancer syndrome \[[@B50]\]. VHL exhibited weak evidence of positive selection with 1.1% of sites in the ancestral Hominidae lineage under positive selection. There was one amino acid that had low coverage in the alignment (present only in 6/18 species), as this is a very weak results we have not expanded upon it any further. ### Positive selection in the Extant Primate branches Analysis of modern non-human primates also identified positive selection in a number of genes. In VHL positive selection was detected in the Chimpanzee lineage where 1.2% of sites have ω \> \> 1, and also in the Marmoset lineage where 5.5% sites have ω \> \> 1. Sites under positive selection were compared against human Swiss-Prot entry (P40337), however the region (1--60) was only represented by 11/18 species in the alignment and therefore we do not have sufficient confidence in these positions to explore these sites in more detail. The MSH6 gene dataset contained 19 taxa and showed evidence of positive selection in both the Gorilla and Marmoset lineages each displaying 3.2% of sites with ω \> \> 1. Gorilla and Marmoset extant lineages were compared against human (P52701) Swiss-Prot entry. No relevant functional information could be extracted from positively selected sites in Gorilla, however 2/45 positively selected sites in Marmoset fall in close proximity to cancer variants. In marmoset, positively selected site 803 (PP = 0.551) coincides with Human colorectal cancer variants D803G \[[@B51]\] and V800A \[[@B52]\]. Position 803 in Marmoset is a negatively charged Glutamic acid while in all other mammals it is a small negatively charged Aspartic acid. Positively selected site 1099 in Marmoset (PP = 0.614) is located between human colorectal cancer variants R1095H \[[@B53]\] and T1110C \[[@B54]\]. MSH2 alignment consists of 18 taxa. The function of the MSH2 protein is in post-replicative DNA mismatch repair system (MMR). Mutations in MSH2 result in hereditary non-polyposis colorectal cancer type 1 (HNPCC1) \[[@B55]\]. Lineage-specific positive selection was identified in 1.5% of sites within the extant Gorilla lineage with ω \> \> 1. Positively selected sites were compared against human Swiss-Prot sequence (P43246). All 15 of the BEB identified sites occur between amino acid position 124--142 which overlaps with the region containing variants N127S, N139S and I145M associated with HNPCC1 \[[@B55]\]. Tuberous sclerosis 2 protein (TSC2) interacts with TSC1 protein and mutations in this gene can cause tuberous sclerosis type 2 \[[@B56]\]. The alignment of TSC2 consisted of 19 taxa. Lineage-specific positive selection was identified in the following extant lineages, the percentage of sites under positive selection in each lineage is shown in brackets, in all cases ω \> \> 1: Chimpanzee lineage (0.2%), Gorilla (1.3%), Orangutan (0.29%), and, Marmoset (1.1%). Positively selected sites were compared against human Swiss-Prot sequence (P49815) however the functional information was not available to contextualize these results. ATM acts as a DNA checkpoint sensor by activating checkpoint signaling upon double strand breaks \[[@B57]\]. The alignment of ATM consisted of 18 taxa and positive selection was detected in the following lineages (again the percentage of the alignment under positive selection is shown in brackets): Gorilla (1.4%, ω \> \> 1), Marmoset (0.21%, ω \> \> 1), and Rabbit (0.38%, ω = 7.42). BEB significant sites were compared to human (Q13315) and mouse (Q62388) Swiss-Prot entries to determine the functional relevance of selected sites. In the Gorilla lineage positively selected site 2067 (PP = 0.787), where in humans a substitution of Alanine to Aspartate in this same position can result in Ataxia telangiectasia (AT) which is a severe disease that causes weakened immune function and greater predisposition to cancer \[[@B57]\]. No other functionally relevant information was found upon comparison of Swiss-Prot information against either Marmoset or Rabbit. The extant Orangutan lineage also showed evidence of positive selection in the TSC1 gene for 1.2% of its alignment (ω \> \> 1). Positively selected sites were compared against human Swiss-Prot sequence (Q92574) and mouse Swiss-Prot sequence (Q9EP53) however there was insufficient information to extrapolate the potential functional impact of these sites. Human population level analysis using HapMap data ------------------------------------------------- Genes displaying evidence of positive selection in lineages leading to *Homo sapiens,* i.e. the primate and Hominidae lineages (STK11, CDH1 and VHL), were further analyzed to determine if there is evidence for ongoing positive directional selection in modern day human populations. The integrated haplotype score, iHS \[[@B42]\], was calculated for each SNP in STK11, CDH1 and VHL genes across African Yorubu (Y), East Asian (A) and European (C) populations. One intronic SNP in the SDK11 gene, had an iHS score of +2.0385 in European populations. In the CDH1 gene, two intronic SNPs with iHS scores of +2.0433 and +2.5838 respectively were identified in the East Asian populations. iHS scores of greater than +2 indicate that these alleles are segregating at a significant rate within their given populations. No population level directional selection was identified in the VHL gene in modern humans. ### Positive selection in the Ancestral Muridae branch The ancestral Muridae branch marks the most recent common ancestor of modern mouse, rat and guinea pig species and is depicted in Figure [1](#F1){ref-type="fig"}. Tuberous sclerosis 1 protein (TSC1) interacts with TSC2 and acts as a tumour suppressor gene \[[@B56]\]. Defects in TSC1 cause tuberous sclerosis type 1 which is an autosomal dominant multi-system disorder. There were a total of 18 taxa analysed in for the TSC1 gene and 0.59% of sites in the Muridae ancestral lineage were identified with ω \> \> 1. As before for TSC1: positively selected sites were compared against human Swiss-Prot sequence (Q92574) and mouse Swiss-Prot sequence (Q9EP53) however there was insufficient information to extrapolate potential functional impacts of these sites. ### Positive selection in the Ancestral Murinae branch The ancestral Murinae branch defines the most recent common ancestor of mouse and rat. In total there were two genes identified as being under positive selection in the Murinae lineage. The first is the MSH6 gene that acts as a DNA mismatch repair protein and is a component of the post--replicative DNA mismatch repair system \[[@B58]\]. MSH6 also heterodimerizes with MSH2 to form MutS-alpha, a protein complex that functions by binding to DNA mismatches and initiating DNA repair \[[@B59]\]. Mutations in MSH6 have been reported to cause HNPCC type 5 \[[@B60]\], atypical HNPCC, and familial colorectal cancers (suspected or incomplete HNPCC) \[[@B61]\]. The MSH6 dataset consists of 19 taxa. Lineage-specific analysis of the ancestral Murinae lineage revealed 0.42% of the sites (3 residues) in MSH6 under positive selection, ω \> \> 1 (see Table [2](#T2){ref-type="table"}). The corresponding Swiss-Prot sequence (P54276) lacked functional details for these positions, therefore, potential functional effects remain unknown. However, examination of the alignment at this position revealed the substitution of residues with unrelated biochemical properties at these positions. At positively selected site 374 (numbered as per Swiss-Prot entry), the Murinae lineage has a Proline whereas remaining species tested encode either Glutamic acid, Aspartic acid, or Lysine. As Proline produces "kinks" in the α-helical regions of proteins, such a substitution could alter the protein structure substantially. Positively selected site 759 is a Leucine in the Murinae, all other non-outgroup species encode aliphatic residues (Isoleucine or Valine). The ancestral Murinae has a Cysteine at Swiss-Prot position 1259 while all other species have an Alanine at this position. These residues are of specific interest for further *in vitro* functional assaying given their uniqueness to the rodent clade and their retention in all modern rodents tested. The second gene with evidence of positive selection on the ancestral Murinae lineage is the SDHC (Succinate dehydrogenase cytochrome b 560 subunit, mitochondrial) gene. The SDHC function is to act as a membrane-anchoring subunit for the SDH protein. Defects in this protein are reported in paragangliomas and gastric stromal sarcomas \[[@B62]\]. The dataset for the SDHC consists of 16 taxa. Lineage-specific positive selection was detected in the ancestral Murinae lineage with 4.2% of sites (9 residues) in this protein with ω \> \> 1 (Table [2](#T2){ref-type="table"}). Comparison with the human sequence from Swiss-Prot (Q99643) and mouse sequence (Q9CZB0) placed 8 of these sites either in transmembrane or topological domains across the gene, with the additional positively selected residue (position 128) neighboring a metal binding site at position 127. ### Positive selection in the Extant Rabbit branch The SDHC gene again showed evidence of positive selection, this time in the extant Rabbit lineage with 35.59% of sites under positive selection (ω = 3.59). 15/51 positively selected sites were identified as occurring within 10 amino acid positions of the metal binding site 127, also mentioned in the ancestral Murinae analysis. While there are extremely high levels of positive selection identified in the rabbit lineage, no other relevant functional information could be gleaned from the databases at this point. The MUTYH alignment consisted of 21 taxa and showed evidence of lineage-specific positive selection in 1.4% of sites in the extant Rabbit lineage (ω \> \> 1). Positively selected sites were compared to human (Q9UIF7) and mouse (Q99P21) Swiss-Prot entries, however no relevant functional information could be extrapolated. Radical substitutions occurred in all 5 BEB sites in the extant Rabbit lineage, three of which are at positions 485--487 in the Nudix hydrolase domain. The MLH1 gene codes for a critical protein involved with the post-replicative DNA mismatch repair system. Defects in this gene result in hereditary non-polyposis colorectal cancer type 2 (HNPCC2) \[[@B63]\]. The alignment of MLH1 consists of 19 taxa and again positive selection was detected in the extant rabbit lineage in 0.87% of sites (ω = 7.53). Positively selected sites were compared against human Swiss-Prot sequence (P40692) and mouse Swiss-Prot sequence (Q9JK91). At amino acid position 120, Rabbit has a polar uncharged Serine residue while all other species tested have a hydrophobic Alanine residue. This positively selected site falls in a region dense with HNPCC2 variants at positions A111V, T116K, T117M, Y126N, A128P \[[@B63]-[@B65]\]. Positively selected residues in Rabbit: 209, 478 and 514, each fall within 8 amino acid positions of HNPCC2 variants: V213M, R474Q and V506A \[[@B66]\]. And position 478 identified as under positive selection also lies in close proximity to a colorectal cancer variant R472I \[[@B67]\]. Finally, the BHD gene showed evidence of positive selection in the extant Rabbit lineage. The function of the BHD gene is still largely unknown, however it is thought that it may be a tumour suppressor and it may be involved in colorectal tumorigenesis \[[@B68]\]. The alignment consisted of 20 taxa and positive selection was detected in 3.34% of sites (ω = 6.5), again unique to the Rabbit lineage. BEB significant sites were compared to human (Q8NFG4) and mouse (Q8QZS3) Swiss-Prot entries to determine their functional relevance. All 10 of the positively selected sites in Rabbit occur in a small region from position 61--83 and border a known human cancer variant at position 79 that when mutated from Serine to Tryptophan results in sporadic colorectal carcinoma. ### Positive selection in the Extant Rodent and Guinea Pig branches MADH4 is the co-activator and mediator of signal transduction by TGF-beta. Defects in MADH4 result in pancreatic, colorectal, juvenile polyposis syndrome, juvenile intestinal polyposis and primary pulmonary hypertension \[[@B69],[@B70]\]. The Rat lineage has lineage-specific positive selection in the MADH4 gene where 5.1% of sites are evolving with ω \> \> 1 (number of taxa = 16). Positively selected sites were compared to human (Q13485) and mouse (P97471) Swiss-Prot entries. The majority of positively selected residues in this protein are sequential with 18/24 sites under positive selection in the rat lineage within 10 amino acid positions of the natural human variant 493. When position 493 is mutated from Aspartate to Histidine pancreatic carcinoma is induced \[[@B71]\]. NF1 is thought to be a regulator of RAS activity \[[@B72]\]. Defects in NF1 can cause colorectal carcinoma and breast cancer \[[@B70]\]. The NF1 dataset consists of 17 taxa. Lineage-specific positive selection was identified in 0.92% of sites in Rat (ω \> \> 1) and 0.12% of sites in guinea pig (ω \> \> 1). BEB significant sites were compared to human (P21359) and mouse (Q04690) Swiss-Prot sequences, however there was no functionally relevant information available. TSC1 also shows evidence of positive selection in the extant guinea pig lineage where 1.2% of the sites have ω \> \> 1. As before, the positively selected sites were compared against human Swiss-Prot sequence (Q92574) and mouse Swiss-Prot sequence (Q9EP53) however there was insufficient information to extrapolate potential functional impacts of these sites. ### Results of site-specific selective pressure analyses The site-specific results may be beneficial to those working on rational mutagenesis and/or the identification of functionally important regions in these colon cancer associated genes and so these results have been summarized. We have identified five genes that have signatures of site-specific positive selection, namely: CDH1, MUTYH, PMS1, PMS2 and TP53, representing \~23% of the dataset. For each of these five genes, the model of best fit was the site-heterogeneous model "model 8", see Table [2](#T2){ref-type="table"} for summary. Defects in the CDH1 member of the Cadherin family are linked to hereditary diffuse gastric cancer \[[@B24],[@B28]\]. The CDH1 alignment contained 15 taxa and site-specific analyses revealed 0.71% sites evolving under strong positive selection, ω = 4.54, see Table [2](#T2){ref-type="table"}. We compared these sites to the human Swiss-Prot entry (P12830) to obtain relevant functional information, see Figure [2(b)](#F2){ref-type="fig"}. The vast majority of positively selected sites (12 sites) in the protein are within the extracellular topological domain (positions 155--709). Many of these positively selected sites are in close proximity to natural cancer variants. For example, position 421 is under position selection and resides within a region (418--423) known to be missing in gastric carcinoma samples \[[@B73]\]. Positions 457, 465, and 467 are under positive selection and map in close proximity to natural variant E463Q found in gastric carcinoma samples \[[@B49]\]. Position 700 resides within the metalloproteinase cleavage site (700--701) of CDH1. Position 735 is in close proximity to a gamma-secretase/PS1 cleavage site (731--732) \[[@B74]\], and position 553 is in close proximity to a glycosylation site (558), essential for the posttranslational modification of proteins \[[@B75]\]. In the CDH1 gene, the majority of species tested (8/15) have hydrophobic residues (Isoleucine, Valine, Leucine) at position 553, the glires group (mouse, rat, guinea pig and rabbit) have small residues (Alanine, Serine, Threonine), but human, gorilla, and dog have large aromatic residues (Phenylalanine) that could significantly alter the protein structure and may affect binding at the glycosylation site at position 558. The MUTYH dataset consisted of 21 taxa and site-specific analysis identified 18 sites under positive selection (ω = 2.44), representing 2.8% of the MUTYH protein (Table [2](#T2){ref-type="table"}). A total of 10 unique sites are reported as natural cancer variants in human (Q9UIF7), see Figure [2(c)](#F2){ref-type="fig"}. Positively selected sites 406 and 412 are in close proximity to natural cancer variants at positions 402 and 411. Positively selected sites 521, 528 and 538 also map in close proximity to natural variants, 526 and 531 respectively. Also of note are the replacement substitutions observed at Swiss-Prot positions 406 and 412, these are radical with potential effects on protein structure. At position 406 there is a large aromatic Trytophan in Primates, and a hydrophobic Leucine and Valine present in the Glires. At position 412 there is an hydrophobic Leucine in Primates and a positively charged Histidine in the Glires. PMS1 (postmeiotic segregation increased 1) encodes a DNA mismatch repair protein and this dataset consists of 20 taxa. Defects in PMS1 are reported to cause hereditary non-polyposis colorectal cancer type 3 (HNPCC3) \[[@B76]\]. Analysis of PMS1 identified site-specific model of codon evolution model 8 as best fit, estimating 25 positively selected sites (6.4% of the alignment) with ω = 1.33 (Table [2](#T2){ref-type="table"}). We compared these sites against human Swiss-Prot sequence P54277. Positively selected site 387 resides in close proximity to position 394 - a natural variant (M394T) reported in incomplete HNPCC and HNPCC3 \[[@B77]\]. Due to limited functional data it was unfeasible to study the remaining 24 sites. However, due to PMS1 function in DNA mismatch repair, these positively selected sites could prove ideal as candidates for mutagenesis studies in the future. Mismatch repair endonuclease PMS2 (postmeiotic segregation increased 2) is a component of the post-replicative DNA mismatch repair system \[[@B78]\]. Defects in PMS2 are reported in HNPCC \[[@B76]\]. The PMS2 dataset contained 21 taxa and site-specific analysis identified 8.9% of sites under positive selection in this PMS2 protein, ω = 1.29 (Table [2](#T2){ref-type="table"}). Functional relevance of these sites was determined by comparison to Human Swiss-Prot sequence (P54278). The vast majority of sites (32) reside within the 430--645 region of the alignment. This region of the alignment is highly variable and could not be not improved manually. Functional characterization for this region is also lacking and therefore we could not assess functional relevance. Outside this region, two positively selected sites, 402 and 406 (PP = 0.632 and 0.728 respectively) flank a phosphoserine modification site (403) \[[@B79]\]. Both substitutions are radical and could affect the function at position 403. TP53 (cellular tumor antigen p53) acts as a tumor suppressor by inducing apoptosis or arresting growth depending on the physiological circumstances and cell type \[[@B80]\]. The TP53 protein (P04637) is 393 residues in length with 343 of these sites reported as natural variants that cause/lead to cancer including but not limited to colorectal and gastric cancers \[[@B41],[@B81],[@B82]\]. In our analysis of TP53 we have 16 taxa. Mutations in this gene radically affect function and therefore we would expect to find evidence of strong purifying selection across sites and lineages. However, results indicate that site specific positive selection is at work with 13 sites under positive selection, ω = 1.97. See Figure [2(d)](#F2){ref-type="fig"} and Table [2](#T2){ref-type="table"} for detailed analyses. On inspection of these 14 sites, we determine that 11 are located within the first region of the protein (positions 1--83), a region responsible for interaction with the methyltransferase HRMT1L2 and the recruiting of promoters to the TP53 gene \[[@B83]\]. We identified a cluster of positively selected sites, namely positions 46 and 47, along with an additional 7 sites within ten residues 39, 52, 53, 54, 55, 56, and 59 (see Additional file [4](#S4){ref-type="supplementary-material"}). Mutation of position 46 can abolish phosphorylation by HIPK2 and acetylation of K-382 by CREBBP \[[@B84]\]. Region 66--110 of TP53 is involved in interaction with WWOX protein and we have identified two sites (Swiss-Prot positions: 72 and 81), under positive selection within this region. Positively selected position 129, is located within a region reported to interact with HIPK1 (100--370) and AXIN1 (116--292), and in addition is also located within a region (positions 113--236) that is required for interaction with FBX042. Positively selected residue 355 is located within the CARM1 interaction region (300--393), the HIPK2 interacting region (319--360), and the oligomerization region (325--356). Conclusion ========== The results we have presented are indicative of selective pressures acting in a lineage-specific manner. The positively selected sites we have identified in this study frequently reside in regions of functional importance, such as glycosylation sites, protease cleavage sites, and sites known to interact with proteins involved in DNA damage repair pathways. Also of note, positively selected residues are frequently located at, or in close proximity to, known cancer associated sites although the statistical significance of these coincidences cannot be concluded with such a small sample sizes. Larger sample sizes and more complete functional information will be hugely beneficial in resolving whether these positively selected residues are most likely positioned to or at variants associated with cancer. In using the mouse as a model organism for colon cancer, we are making an assumption that the orthologs in both species are functioning in precisely the same way despite \~ 180 MY of independent evolution. We found no evidence of functional divergence in the extant human and mouse lineages for the genes analyzed. However, upon testing the lineages leading from the MRCA of mouse and human, i.e. Euarchontoglires, positive selection has occurred on certain ancestral branches and in specific extant lineages. In the ancestral lineages of primates, rodents and glires there is evidence of positive selection in 6 of the 22 genes tested (this includes the VHL result but as from Table [2](#T2){ref-type="table"} it is clear that this is a weak result). In total, considering all lineages analyzed including extant lineages, we have detected lineage-specific positive selection in 64% of the genes analyzed (i.e. 14/22 genes). Studies on the levels of polymorphism observed in *Drosophila* species indicate that positive selection is pervasive in this species with positive selection present in \~25% of the genes \[[@B85]\]. Previous studies on the levels of positive selection in primates compared to rodents and in the Hominidae reveal much lower levels of positive selection in the range of 5-9% of genes in the genome \[[@B7],[@B8]\]. If these previous analyses were to act as a measurement of expectation then we should have identified only 1 gene under positive selection in this dataset that is comprised of mammals for the most part (taking the Drosophila data as the upper bound we would expect in the region of 6 genes with evidence of positive selection). On grouping the cancer associated genes according to their involvement in functional pathways we determined that the MMR DNA damage response pathway has evidence of positive selection in 3 components of the pathway -- 2 of which are site-specific and one of which is specific to the ancestral Murinae lineage suggesting a specific selective pressure in this clade for this process. The site-specific analyses identified a total of 5 genes that are positively selected: CDH1, MUTYH, PMS1, PMS2 and TP53. These results are important for contributing to our understanding of fundamental functions of these proteins and have provided potential targets for rational mutagenesis. Overall, these results indicate that the function of certain proteins associated with colon cancer display distinct lineage-specific patterns of substitution indicative of positive selection in the ancestral human and mouse lineages. There are a number of selective pressures on any given protein that can contribute to patterns of substitution that are "*falsely"* indicative of positive selection. The necessity to continue to interact with protein partners may be a strong driving force in the evolution of the proteins in this study as many form functional complexes with one another or other proteins \[[@B86]\]. Compensatory mutations may also contribute to elevated levels of ω \[[@B87]\]. The effective population size (*N*~*e*~) of the species tested vary enormously, with estimations for modern human populations in the range of *N*~*e*~ = 7,500 to 3,100 \[[@B88]\], while estimations for modern mouse populations range from *N*~*e*~ = 58,000 to 25,000 \[[@B89]\] and this large difference in *N*~*e*~ may also contribute to detection of false positives. We have also detected weak evidence for ongoing selective pressure in the human genome on the STK11 and CDH1, but these signals of selection may be artifacts of the very small effective population size of modern humans. Smaller *N*~*e*~ values are associated with increased fixation of slightly deleterious substitutions and subsequent elevated ω values \[[@B90]\]. Such slightly deleterious mutations in turn can lead to additional compensatory substitutions that become fixed. Teasing apart substitutions that have become fixed due to positive selection from slightly deleterious substitutions fixed due to small *N*~*e*~*\[*\[[@B91]\] will aid in a more complete understanding of protein evolution in the future. Abbreviations ============= BEB: Bayes empirical bayes; *dN*: Nonsynonymous substitutions per nonsynonymous site; *dS*: Synonymous substitutions per synonymous sites; LRT: Likelihood ratio test; ML: Maximum likelihood; MY: Millions of years; *N*~*e*~: Effective population size; NEB: Naïve empirical bayes; PP: Posterior probability. Competing interests =================== The authors declare no conflict of interest. Authors' contributions ====================== CCM and KS carried out all data assembly. KS, CCM and AEW carried out all homolog identification and MSAs. CCM carried out all data quality and phylogeny analyses. CCM, KS, AEW, and TAW carried out all selective pressure analyses and designed the necessary software. ML carried out all structural analyses. All authors participated in drafting the manuscript. MJO\'C conceived of the study, its design and coordination and drafted the manuscript. All authors read and approved the final manuscript. Supplementary Material ====================== ###### Additional file 1 **Details of the data used in the analysis, the 21 species and their genome coverage.** Orthologs that were not found by the Ensembl genome browser are labeled in black, orthologs identified are shown in white. ###### Click here for file ###### Additional file 2 **Complete set of all multiple sequence alignments used in the analysis.** The data is presented on a gene-by-gene basis in nexus format. ###### Click here for file ###### Additional file 3 Likelihood ratio tests performed and their associated significance values. ###### Click here for file ###### Additional file 4 **Full set of models, associated likelihood scores and parameter estimates for all genes in the colon cancer gene dataset.** This information is given alphabetically on a gene-by-gene basis. All estimated parameters, Likelihood values and BEB or NEB sites are listed. ###### Click here for file ###### Additional file 5 **Full set of recombination test results on a per gene and per species basis.** The value highlighted in yellow for TP53 represents a region where recombination was detected with reasonable confidence that also coincided with a positively selected residue (i.e. false positive). ###### Click here for file Acknowledgements ================ We would like to thank the Irish Research Council for Science, Engineering and Technology (Embark Initiative Postgraduate Scholarship CCM RS2000172) and DCU O'Hare scholarship (KS) for financial support. CCM is funded by the Irish Research Council for Science, Engineering and Technology (Embark Initiative Postgraduate scholarship RS2000172 to CCM). TAW is funded by School of Biotechnology and Pierse Trust Scholarships at DCU. MJO'C and AEW are funded by Science Foundation Ireland RFP: EOB2673. MJO\'C would also like to thank SFI Travel fellowship 10/RFP/EOB2673 - STTF 11. We would like to thank the SFI/HEA Irish Centre for High-End Computing (ICHEC) for processor time and technical support for both phylogeny reconstruction and selective pressure analyses. We would like to thank the SCI-SYM centre at DCU for processor time.

Q: vlookup or index match to list names one below the other as an Array I am trying to list names below the other that satisfy a score. In my case it needs to be over 7, I am using =INDEX($B$2:$B$16, SMALL(IF($E$2<=$C$2:$C$16, ROW($B$2:$B$16)-MIN(ROW($B$2:$B$16))+1, ""), ROW(A1))) as an array. The output im getting is getting stuck at Test2. What am I doing wrong. Is there an easier way to do this A: I tend to prefer a single-cell array-formula approach in such cases, i.e. via entering the appropriate array formula in cell G2 only, then copying down as required. If you were to do likewise, your current formula would work as required. However, when entered as a multi-cell array formula, i.e. via first selecting the required range (e.g. G2:G8), then entering the formula in the formula bar followed by committing, the construction you are using for SMALL's k parameter, i.e.: ROW(A1) will not be processed in a row-relative manner, as desired; in fact, for each instance of the formula, it will remain precisely as above, and not - as is the case when we copy down the equivalent single-cell version - update to, successively: ROW(A2) ROW(A3) ROW(A4) ... etc. If you insist on continuing to use a multi-cell array formula here, you will need to use either the unqualified ROW for this parameter, i.e.: =INDEX($B$2:$B$16,SMALL(IF($E$2<=$C$2:$C$16,ROW($B$2:$B$16)-MIN(ROW($B$2:$B$16))+1,""),ROW()-1)) or, since the above is not very robust, nor flexible (unqualified, ROW() is dependent upon the row in which the formula resides; hence, in your case, since your first formula is in row 2, we need to offset this value by -1), we can use the much better (though slightly longer): =INDEX($B$2:$B$16,SMALL(IF($E$2<=$C$2:$C$16,ROW($B$2:$B$16)-MIN(ROW($B$2:$B$16))+1,""),ROW($B$2:$B$16)-MIN(ROW($B$2:$B$16))+1)) In any case, even for the single-cell version, ROW is a poorer choice than ROWS for generating incremental integers (https://excelxor.com/2014/08/25/row-vs-rows-for-consecutive-integer-generation/), though sadly ROWS too is not an option for the multi-cell version, which is one of the reasons why I personally tend to prefer a series of single-cell array formulas over a single multi-cell one. My personal preference would be the single-cell array formula: =INDEX(B:B,SMALL(IF($E$2<=$C$2:$C$16,ROW($B$2:$B$16)),ROWS($1:1))) and copied down, though I would also probably add a clause to mask errors in cells beyond the expected number of returns, e.g.: =IF(ROWS($1:1)>A$1,"",INDEX(B:B,SMALL(IF($E$2<=$C$2:$C$16,ROW($B$2:$B$16)),ROWS($1:1)))) where A1 contains a formula to count the number of expected returns, e.g.: =COUNTIF($C$2:$C$16,">="&$E$2) which is preferable (and especially so over large ranges) to a resource-heavy IFERROR set-up (https://superuser.com/questions/812727/look-up-a-value-in-a-list-and-return-all-multiple-corresponding-values). And I should also say that I would use a slightly different version if the data being queried formed part of an Excel Table. Regards

Q: Firebase auth onUpdate cloud function for when a user updates their email I need to run a Firebase function whenever my user updates their email address, except auth only has onCreate and onDelete. How can I react to email updates? A: It's not possible today to directly react to an email address changing in Firebase Authentication. If you'd like to see that as a feature, please file a feature request. You can react to it indirectly by having your app listen to authentication events (Android), take the User object delivered to your listener, and write the user's email address to a RealtimeDatabase location (or Firestore document) for that user's UID. Then, you can have a database trigger that tracks the location of your users in the database, and react to the change there.

Q: Why does the Ubuntu Software Center deliver an outdated version of TeX Live? Possible Duplicate: Why don't the Ubuntu repositories have the latest versions of software? Starting from a fresh install of Ubuntu 12.04.1 in late August, I have used the Ubuntu Software Center to install the so-called "decent selection" of TeX Live and also some additional TeX Live packages. To my astonishment I have now realized that (at least some of) the TeX Live packages are outdated! The Ubuntu Software Center states the version of the TeX Live distribution to be "texlive 2009-15". An example of an outdated file is fontspace.sty, on my system that file is dated 2008-08-09 but I have been informed that there is e.g. a version dated 2011-02-26 (see answer given to the question Problem with XeTeX (LaTeX) and system fonts at http://tex.stackexchange.com). Two questions: Why does the Ubuntu Software Center deliver an outdated version of the TeX Live distribution? How to update the TeX Live distribution to the latest and greatest version? A: Install it manually using the instructions from the TeX Live Website. See also here.

Nguyen PH, Avula R, Headey D, Tran LM, Ruel MT, Menon P. Progress and inequalities in infant and young child feeding practices in India between 2006 and 2016. Matern Child Nutr. 2018;14(S4):e12663 10.1111/mcn.12663 30499255 ###### Key messages This study uses two of India\'s nationally representative household surveys conducted 10 years apart (2006 and 2016) to examine trends and changes in inequalities for IYCF practices overtime and identify factors that may explain differences in IYCF across socio‐economic groups.Our findings highlight significant improvements in breastfeeding practices and closing of equity gaps in EBF, mainly due to improvements in Q5. Although the equity gaps in complementary feeding practices also narrowed, complementary feeding shows slow progress and poor practices across all segments of society.These results call for special efforts to further improve breastfeeding, and concerted actions to address all aspects of complementary feeding across SES quintiles. 1. INTRODUCTION {#mcn12663-sec-0002} =============== Appropriate nutrition during early life, including adequate infant and young child feeding (IYCF) practices, is essential for optimal growth and development. Despite strong technical guidance and recommendations for age‐appropriate IYCF practices for children below 2 years (Pan American Health Organization, [2003](#mcn12663-bib-0022){ref-type="ref"}; World Health Organization \[WHO\], [2008](#mcn12663-bib-0034){ref-type="ref"}), global progress on these practices has been slow. Socio‐economic inequalities in malnutrition and access to effective nutrition and health services continue to exist throughout the world (Black et al., [2013](#mcn12663-bib-0005){ref-type="ref"}; Victora et al., [2018](#mcn12663-bib-0031){ref-type="ref"}; Victora & Somers, [2015](#mcn12663-bib-0030){ref-type="ref"}). Children living in resource‐poor settings are generally at a greater disadvantage than their wealthier counterparts with respect to living conditions, access to preventive care and complementary feeding practices (Barros, Victora, Scherpbier, & Gwatkin, [2010](#mcn12663-bib-0004){ref-type="ref"}), although poorer households are often more likely to breastfeed and to do so for longer periods of time. Reducing inequality---which is at the heart of a wide range of Sustainable Development Goals---is therefore critical for achieving nutrition goals (Global Nutrition Report, [2017](#mcn12663-bib-0007){ref-type="ref"}). India, a country with 1.3 billion population, contributes to two thirds of the global burden of undernutrition and ranks high among the most unequal countries in the world on consumption expenditure, income, and wealth (Himanshu, [2018](#mcn12663-bib-0009){ref-type="ref"}; World Bank, [2010](#mcn12663-bib-0035){ref-type="ref"}). In addition to socio‐economic factors, geographic inequalities such as state‐specific or urban and rural residence disparities influence nutrition outcomes and their determinants, including access to health services and preventive and curative interventions. For example, neonatal mortality is higher among low‐income compared with high‐income states (Million Death Study Collaborators et al., [2010](#mcn12663-bib-0015){ref-type="ref"}). The prevalence of stunting also varies widely across states and across rural and urban areas, with higher burden among the poor, especially among the urban poor (Kanjilal, Mazumdar, Mukherjee, & Rahman, [2010](#mcn12663-bib-0012){ref-type="ref"}). In India, inequalities in socio‐economic status (SES) and place of residence are particularly evident for access and use of antenatal care (ANC) services, which favour the rich and urban populations as seen in the higher average number of ANC visits and higher quality of ANC among these population groups (Viegas Andrade, Noronha, Singh, Rodrigues, & Padmadas, [2012](#mcn12663-bib-0032){ref-type="ref"}). Although there is ample documentation of socio‐economic and regional inequalities in maternal and child health in India, there is limited evidence on inequalities in IYCF practices. A study using the 2005--2006 India National Family Health Survey (NFHS) reported that high wealth index and urban residence were associated with lower prevalence of exclusive breastfeeding (EBF) (Patel et al., [2012](#mcn12663-bib-0024){ref-type="ref"}). Similarly, evidence from 36 developing countries, including India, showed that although complementary feeding practices are generally better in urban areas compared with rural areas, breastfeeding (BF) practices are consistently worse (Smith, Ruel, & Ndiaye, [2005](#mcn12663-bib-0026){ref-type="ref"}). However, these studies examined inequalities for urban/rural and wealth quintile separately and focused on relative ratios, rather than more robust measures that take into account the cumulative population wealth distribution. Hence, a more in‐depth assessment of inequalities in IYCF practices, considering intersectionality (López & Gadsden, [2016](#mcn12663-bib-0014){ref-type="ref"}) between wealth and residence, is essential for strategic investment, and targeting and planning of interventions to close the equity gap. In this study, we address this knowledge gap by focusing on three objectives: (a) examine trends in IYCF practices between 2006 and 2016, (b) assess the changes in absolute and relative socio‐economic inequalities in IYCF practices in both rural and urban areas, and (c) identify factors associated with socio‐economic inequalities that explain differences in IYCF practices. 2. METHODS {#mcn12663-sec-0003} ========== 2.1. Data sources {#mcn12663-sec-0004} ----------------- This paper uses nationally representative data from the India 2005--2006 NFHS‐3 (International Institute for Population Sciences \[IIPS\], [2007](#mcn12663-bib-0010){ref-type="ref"}) and the 2015--2016 NFHS‐4 (IIPS, [2017](#mcn12663-bib-0011){ref-type="ref"}), conducted by the IIPS, under the stewardship of the Ministry of Health and Family Welfare (MoHFW), Government of India. These surveys contain extensive data on population, health, and nutrition, and a range of underlying determinants. The NFHS‐3 survey consisted of data from 109,041 sample households and was representative at the state level. The NFHS‐4 survey is unique in being the first national survey to be representative at both state and district levels, gathering data from 601,509 households. These surveys are also representative at urban/rural levels. Both surveys used a stratified two‐stage sample design. The first stage involved selection of primary sampling units, which were the villages in rural areas and the Census Enumeration Blocks in urban areas. Within each stratum, villages or blocks were selected from the sampling frame with probability proportional to population size. The second stage involved the random selection of 22 households with systematic sampling method from each primary sampling unit where a complete household mapping and listing operation was conducted prior to the main survey. Each survey contained four well‐structured separate datasets for households, men, women aged 15--49 years, and children under 5 years of age. Because this paper focuses on IYCF practices, analyses were restricted to the mother--child dyads in which the child was under 24 months old (*n* = 18,474 in NFHS‐3 and 93,659 in NFHS‐4). 2.2. Variables {#mcn12663-sec-0005} -------------- ### 2.2.1. Outcome variables {#mcn12663-sec-0006} IYCF practices were assessed using the standard WHO indicators (WHO, [2008](#mcn12663-bib-0034){ref-type="ref"}), on the basis of the maternal recall of all foods and liquids given to children in the 24 hr prior to the survey. The two key BF indicators were (a) early initiation of BF (EIBF---defined as the proportion of infants who were put to the breast within 1 hr of birth) and (b) EBF (defined as the proportion of infants 0--6 months of age who were fed only breast milk). In order to examine the BF pattern, we categorized BF status into exclusive (as defined above), BF + plain water, BF + nonmilk liquid, BF + other milk, BF + formula, BF + solid/semisolid foods, and no BF (United Nations Children\'s Fund \[UNICEF\], [in press](#mcn12663-bib-0028){ref-type="ref"}). We constructed five complementary feeding indicators for children 6--23 months old: (a) timely introduction of complementary foods (defined as the proportion of infants aged 6--8 months who received solid, semisolid, or soft foods in the previous 24 hr), (b) minimum dietary diversity (defined as children who consumed foods from four or more food groups out of seven food groups in the previous 24 hr), (c) minimum meal frequency as appropriate for age, (d) minimum acceptable diet (defined as children who the both minimum dietary diversity and age‐appropriate minimum meal frequency), and (e) consumption of iron‐rich food (WHO, [2008](#mcn12663-bib-0034){ref-type="ref"}). We also reported specific foods and the total number of food groups consumed by the target child in the previous day. ### 2.2.2. Variables used for equity analyses {#mcn12663-sec-0007} A household SES index was constructed using the principal component analysis method, extracting from multiple variables including house and land ownership, housing structure, access to services (electricity, gas, water, and sanitation services), and ownership of 17 assets (car, motorbike, bicycle, television, radio, computer, refrigerator, watch, mobile phone, fan, bed, mattress, table, chair, press cooker, sewing machine, and water pump) and livestock (cow, goat, chicken; Filmer & Pritchett, [2001](#mcn12663-bib-0006){ref-type="ref"}; Vyas & Kumaranayake, [2006](#mcn12663-bib-0033){ref-type="ref"}). Principal component analysis was applied to both rounds of data to construct a consistent SES index. The first principal component explained 65% of the variance and was used to divide household SES into quintiles, stratified by urban and rural areas; the lowest quintile (Q1) represented the poorest 20% of the pooled population, and the highest quintile (Q5) represented the richest 20%. ### 2.2.3. Potential factors associated with changes in IYCF practices {#mcn12663-sec-0008} The selection of potential determinants of changes in IYCF practices was guided by the conceptual framework, particularly the UNICEF ([1990](#mcn12663-bib-0027){ref-type="ref"}) and Lancet Nutrition Series (Black et al., [2013](#mcn12663-bib-0005){ref-type="ref"}). In this paper, we used four groups: (a) household factors, (b) maternal factors, (c) child factors, and (d) health and nutrition services. Household‐level variables included area of residence (rural, urban), religion, scheduled caste/tribal (designated groups of historically disadvantaged people in India), number of children \< 5 years, and household SES. Maternal characteristics included age, age at first birth (at 18 years or older), education, occupation, and access to information. Mothers\' occupation was only available for \~20% of sample in 2016 and, therefore, was excluded from the analyses. Access to information was measured by the proportion of mothers reporting to watch TV, listen to radio, or read newspaper daily. Child factors included child age, sex, and birth order. We examined several nutrition and health services across the continuum of care (pregnancy, delivery, and early childhood). Services received during pregnancy included at least four ANC visits, iron and folic acid (IFA) consumption (at least 100 IFA tablets during the last pregnancy), neonatal tetanus protection, deworming, weight monitoring, and BF counselling by front‐line workers. Indicators related to services during delivery included skilled birth attendance and caesarean section. Institutional delivery was not examined because it was highly correlated with skilled birth attendance. Indicators related to early childhood services included full immunization, paediatric IFA and vitamin A supplementation, and deworming. A score of 1 was given for each service that mothers received during pregnancy or early childhood, and the average score for each period was used in the analyses. We also examined Integrated Child Development Services (ICDS) services, specifically food supplementation for pregnant or lactating mothers and children. Due to the age specificity of IYCF practices, nutrition and health services during pregnancy were used for modelling BF practices, and nutrition and health services during early childhood were used for modelling complementary feeding practices. 2.3. Data analysis {#mcn12663-sec-0009} ------------------ We used several complementary methods to analyse the data. First, we used graphical methods to document changes in the age profile of IYCF patterns and regression models to examine changes in IYCF indicators over time. We also tested for differences in various determinants between 2006 and 2016 using linear regression models (for continuous variables) and logistic regression models (for categorical variables), adjusting for standard errors for the cluster sampling design and sampling weights used in the survey. Second, we estimated the absolute gap (difference between the wealthiest and poorest quintiles \[Q5 − Q1\]) and the slope index of inequality (SII) to explore absolute SES inequalities in IYCF practices for rural and urban separately. We calculated relative gap (Q5/Q1 ratios) and the concentration index (CIX) to examine relative SES inequalities (O\'Donnell, Doorslaer, Wagstaff, & Lindelow, [2008](#mcn12663-bib-0020){ref-type="ref"}; O\'Donnell, O\'Neill, Van Ourti, & Walsh, [2016](#mcn12663-bib-0021){ref-type="ref"}). Although absolute and relative gaps are simple indices that allow to convey results to nontechnical audiences and public health experts, these measures do not capture the intermediate population groups (e.g., Q2--Q4) and are sensitive to changes in the number of individuals in each stratification category (Barros & Victora, [2013](#mcn12663-bib-0003){ref-type="ref"}). The SII and CIX account for the entire SES distribution of the sample by wealth score (Barros & Victora, [2013](#mcn12663-bib-0003){ref-type="ref"}), with SII expressed in percentage points and CIX as a range between −1 and +1 (with 0 representing equality between the rich and the poor, and positive values indicating a prorich distribution). CIX values are multiplied by 100 for presentation. The SII was estimated by using a regression approach, and the CIX was calculated using analogous approach by ranking individuals according to SES position. These two measures were also used to assess whether inequalities increased or declined over time. Third, we explored the underlying factors associated with recent changes in SES inequalities by examining quintile‐specific changes between 2006 and 2016 for these factors. Finally, we conducted bivariate and multivariable regression analyses and found that associations between SES and IYCF practices were highly significant in the bivariate models but became insignificant in multivariable models, suggesting potential mediation effects. Therefore, we applied path analyses to assess the complex relationships between SES status and underlying factors of IYCF and with three key IYCF outcomes (EIBF, EBF, and minimum dietary diversity). We estimated the models separately for each survey round and pooled (combining the data from both rounds). Given that differences between the separate and pooled models were minimal, we only report the pooled results. All analyses were performed using Stata Version 15.1. All regression models were adjusted for standard errors for the cluster sampling design and sampling weights used in the survey. 3. RESULTS {#mcn12663-sec-0010} ========== The characteristics of the study population by survey round are presented in Table [1](#mcn12663-tbl-0001){ref-type="table"}. There were several significant economic and social changes from 2006 to 2016 in India, especially in relation to household SES, urbanization, women\'s education, age at first marriage, and access to information. We also observed significant and in many cases large improvements over time in access, use, and coverage of nutrition and health services across the continuum of care. For example, the percentage of mothers receiving four ANC visits increased by \~15 percentage points, consumption of IFA supplements during pregnancy doubled (from 15% to 30%), and BF counselling during pregnancy increased by more than threefold (from 13% to 42%). There were also remarkable improvements in coverage of child immunization (from 35% to 50%), vitamin A (from 22% to 60%) and paediatric IFA supplementation (from 5% to 26%), and deworming (8% to 28%). There was a large increase (close to threefold) in the percentage of women and children receiving food supplementation during pregnancy, lactation, or early childhood. ###### Characteristics of the study sample, by survey year Characteristic 2006 2016 ----------------------------------------------------------------- ------------------------ -------------------------------------------------------------------- Household No. of children \< 5, *n* 1.59 \[1.57, 1.61\] 1.51[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[1.51, 1.52\] SES index,[a](#mcn12663-note-0002){ref-type="fn"} *n* −0.53 \[−0.56, −0.49\] 0.03[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[0.02, 0.05\] Religion (Hindu), % 78.88 \[77.06, 80.70\] 78.57 \[77.85, 79.29\] Religion (Muslim), % 16.28 \[14.51, 18.05\] 16.70 \[16.01, 17.38\] Scheduled caste/tribe, % 70.99 \[69.40, 72.57\] 76.41[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[75.80, 77.01\] Reside in urban areas, % 23.23 \[21.21, 25.25\] 26.93[\*\*](#mcn12663-note-0005){ref-type="fn"} \[25.99, 27.88\] Mothers Age, years 25.05 \[24.91, 25.19\] 25.65[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[25.59, 25.70\] Education, years 4.29 \[4.12, 4.46\] 6.66[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[6.60, 6.73\] Age at first birth ≤ 18, % 43.93 \[42.45, 45.41\] 21.26[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[20.78, 21.75\] Working outside the home[b](#mcn12663-note-0003){ref-type="fn"} 32.78 \[30.36, 33.20\] 16.46[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[15.59, 17.33\] Access to information, % 39.85 \[38.32, 41.39\] 54.63[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[54.02, 55.25\] Child Gender (male), % 53.07 \[51.91, 54.22\] 52.66 \[52.12, 53.20\] Age, months 14.43 \[14.30, 14.55\] 14.46 \[14.40, 14.51\] Birth order, *n* 2.69 \[2.63, 2.75\] 2.18 \[2.17, 2.20\] Nutrition and health services During pregnancy At least 4 ANC visits, % 35.55 \[33.81, 37.28\] 50.18[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[49.49, 50.87\] Consumed 100+ IFA, % 15.28 \[14.24, 16.32\] 30.09[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[29.45, 30.73\] Weighed at least once, % 48.30 \[46.26, 50.35\] 75.39[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[74.83, 75.95\] Neonatal tetanus protection, % 79.33 \[77.89, 80.78\] 87.87[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[87.46, 88.29\] Deworming, % 3.82 \[3.35, 4.30\] 17.85[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[17.32, 18.38\] Breastfeeding counselling, % 13.16 \[12.13, 14.19\] 41.90[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[41.23, 42.57\] Delivery Institutional birth, % 39.89 \[38.04, 41.74\] 82.32[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[81.81, 82.83\] Skilled birth attendance, % 47.94 \[46.09, 49.80\] 84.26[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[83.80, 84.72\] Caesarean section, % 8.91 \[8.16, 9.66\] 18.64[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[18.10, 19.18\] Early childhood Full immunization, % 35.00 \[33.53, 36.47\] 50.26[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[49.67, 50.86\] Vitamin A supplementation, % 21.79 \[20.58, 23.01\] 60.34[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[59.72, 60.96\] Paediatric IFA, % 4.81 \[4.27, 5.35\] 25.75[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[25.16, 26.34\] Paediatric deworming, % 7.74 \[6.91, 8.57\] 27.52[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[26.92, 28.11\] Food supplementation For pregnant women, % 20.15 \[18.88, 21.42\] 53.73[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[53.09, 54.36\] For lactating mothers, % 15.38 \[14.28, 16.49\] 48.51[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[47.88, 49.13\] For children, % 18.84 \[17.65, 20.04\] 52.59[\*\*\*](#mcn12663-note-0004){ref-type="fn"} \[51.97, 53.20\] *Note*. ANC: antenatal care; IFA: iron and folic acid; SES: socio‐economic status. The SES index was obtained from the principal component analysis, and it has *M* = 0 and *SD* = 1. Data only available for subsample of women in 2016 (*n* = 16,466). *p* \< 0.001. *p* \< 0.01. *p* \< 0.05. Between 2006 and 2016, there was a significant improvement in BF practices. EIBF nearly doubled (from 23% to 42%), and EBF increased from 46% to 55% (Figure [1](#mcn12663-fig-0001){ref-type="fig"}), mainly due to reduction in feeding water, milk, or nonmilk liquids (Figure [2](#mcn12663-fig-0002){ref-type="fig"}). However, worryingly, nearly 5% of infants in all quintiles were not breastfed at all in 2016. Prelacteal feeding in the first 3 days after birth was very common in 2006, practised by 57% in 2006, but reduced sharply to 21% in 2016 (Table [S1](#mcn12663-supitem-0001){ref-type="supplementary-material"}). The largest reductions in commonly fed prelacteals were fresh milk (32% to 13%), honey (14% to 3%), sugar water (11% to 2%), and plain water (9% to 3%). {#mcn12663-fig-0001} {#mcn12663-fig-0002} Complementary feeding is of a major concern, with nearly a 10‐percentage‐point decline in timely introduction of semisolid foods (55% to 45%) and in minimum meal frequency (42% to 36%) between 2006 and 2016 (Figure [1](#mcn12663-fig-0001){ref-type="fig"}). Minimum acceptable diet (\~9%) is extremely low and did not change over time. Minimum dietary diversity increased slightly (15% to 21%), mainly due to increased consumption of eggs (5% to 15%), vitamin A‐rich fruit and vegetables (35% to 40%), and other fruits and vegetables (15% to 24%; Figure [S1](#mcn12663-supitem-0001){ref-type="supplementary-material"}). Table [2](#mcn12663-tbl-0002){ref-type="table"} presents estimates of absolute and relative inequality indices for key IYCF practices as well as the SII and CIX by rural and urban areas and by survey year. Figure [3](#mcn12663-fig-0003){ref-type="fig"} visualizes these IYCF practices in the equiplots where each dot represents the prevalence of a given IYCF practice for a quintile subgroup and the distance between the dots is the gap between the quintiles. Most IYCF practices (except for EBF) exhibited prorich inequality patterns where recommended practices were higher among the rich than among the poor within urban and rural populations. Gaps between Q5 and Q1 for EIBF were larger for rural (17%) compared with urban areas (8%) in 2006 but narrower in 2016 in both areas. EBF showed a different pattern where in 2006 EBF was higher among the lower SES compared with the higher SES (Q5--Q1: −15% in rural and −10% in urban or SII: −19% and −12%, respectively), but these gaps were much smaller in 2016, mostly due to improvements in EBF in Q5, especially in rural areas. ###### Inequity gaps in infant and young child feeding practices between 2006 and 2016, by SES quintile and rural/urban residence Indicators Area Year Q1 Q5 Q5--Q1 SII Q5/Q1 CIX ----------------------------------- ------- ------- ------- -------- --------------------------------------------------- ---------------------------------------------------- --------------------------------------------------- -------------------------------------------------- Early initiation of breastfeeding Rural 2006 15.75 32.95 17.20 17.42[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2.09 3.57[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 38.39 45.59 7.20 9.26[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.19 1.58[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 25.63 33.54 7.91 10.72[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.31 1.37[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 47.67 42.19 −5.48 −2.08 0.89 −0.88[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Exclusive breastfeeding Rural 2006 51.92 36.43 −15.49 −19.44[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 0.70 2.85[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 54.97 55.19 0.22 −2.23 1.00 −0.09 Urban 2006 43.12 33.08 −10.04 −11.75[\*](#mcn12663-note-0010){ref-type="fn"} 0.77 1.64[\*](#mcn12663-note-0010){ref-type="fn"} 2016 51.55 53.81 2.26 4.02 1.04 0.45 Timely introduction of SSSF Rural 2006 48.52 72.21 23.69 27.30[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.49 3.50[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 33.86 48.34 14.48 15.62[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.43 3.00[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 53.40 82.75 29.35 36.83[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.55 6.48[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 48.84 59.01 10.17 15.64[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.21 1.48[\*\*](#mcn12663-note-0009){ref-type="fn"} Minimum meal frequency Rural 2006 41.07 49.15 8.08 12.27[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.20 1.53[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 31.37 38.20 6.83 6.18[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.22 1.32[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 39.56 43.38 3.82 27.08[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.10 3.81[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 37.29 44.27 6.98 10.02[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.19 1.48[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Minimum dietary diversity Rural 2006 8.26 29.85 21.59 19.78[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 3.61 3.14[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 12.97 24.36 11.39 12.45[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.88 2.24[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 17.20 32.06 14.86 21.78[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.86 3.27[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 20.76 29.71 8.95 11.20[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.43 1.49[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Minimum acceptable diet Rural 2006 4.53 18.03 13.50 12.91[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 3.98 1.98[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 5.84 10.86 5.02 5.31[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.86 1.00[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 9.54 17.09 7.55 13.83[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.79 1.67[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 9.41 13.43 4.02 5.68[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.43 0.76[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Consumption of iron‐rich foods Rural 2006 13.78 36.26 22.48 20.42[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2.63 3.31[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 10.73 28.69 17.96 20.52[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2.67 3.65[\*\*\*](#mcn12663-note-0008){ref-type="fn"} Urban 2006 22.62 43.94 21.32 25.67[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.94 4.22[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 2016 21.67 34.81 13.14 17.93[\*\*\*](#mcn12663-note-0008){ref-type="fn"} 1.61 2.09[\*\*\*](#mcn12663-note-0008){ref-type="fn"} *Note*. CIX: concentration index; Q: quintile; SES: socio‐economic status; SSSF: semisolid and solid food; SII: slope of inequity index. *p* \< 0.001. *p* \< 0.01. *p* \< 0.05. {#mcn12663-fig-0003} Absolute gaps between the richest and poorest quintiles were wide for timely introduction of solid/semisolid foods in 2006 using both the Q5--Q1 (24% for rural and 29% for urban areas) and the SII summary measures (27% for rural and 37% for urban areas). In 2016, there was a decline in the timely initiation of complementary foods across quintiles and in both urban and rural areas (with a greater magnitude of decline in rural areas). There was also a narrowing of the gaps between quintiles in both urban and rural areas. Similar declines in the proportion of children with minimum meal frequency between 2006 and 2016 were also observed, but reductions in the wealth inequality gap were smaller than for timely initiation of complementary foods. Minimum dietary diversity and consumption of iron‐rich foods also had a large gap in 2006 where children belonging to Q5 consumed two to four times more than did those in the Q1, and the gap between the two extreme quintiles was \~20%. These gaps narrowed in 2016, but levels are low among all quintiles and lower in 2016 compared with 2006 for the highest SES quintile in both urban and rural areas. The proportion of children with minimum acceptable diet was very low (\<20% even among Q5 in both urban and rural areas) and declined between 2006 and 2016 for the highest two SES quintiles. In terms of specific food groups, the largest wealth gaps were for dairy consumption in both urban and rural areas ([Figure S2](#mcn12663-supitem-0001){ref-type="supplementary-material"}). The magnitude of the gap was reduced in 2016 for both areas, and the percentage of children consuming dairy was higher in urban areas for all SES quintiles. The consumption of food groups other than starchy staples was low for all segments of society (\<10% for flesh foods, \<20% for eggs, \<30% for legumes, and \<40% for vitamin A‐rich fruits and vegetables) and did not show much difference between rural--urban groups or the 2006 and 2016 surveys. Figure [4](#mcn12663-fig-0004){ref-type="fig"} shows the wealth and urban/rural differentials for a select number of determinants of IYCF practices at the two survey times. For most of the determinants (except food supplementation), the Q5 quintile showed higher coverage, and urban areas performed better than did rural areas. Results from path analyses pooling the 2006 and 2016 surveys (Figure [5](#mcn12663-fig-0005){ref-type="fig"} and [Figure S3](#mcn12663-supitem-0001){ref-type="supplementary-material"}) show significant positive associations between SES quintiles and mother\'s education (*β* = 3.4), access to information (*β* = 0.22 to 0.25), and nutrition and health services (*β* = 0.03 to 0.05). These factors, in turn, are positively associated with IYCF practices. For example, compared with women who did not use nutrition and health services during pregnancy, those who used the services were 29% more likely to initiate early BF and 10% more likely to exclusively breastfeed. Similarly, children who used the services were 16% more likely to achieve minimum diet diversity than were those who did not. The relationship between SES quintiles, food supplementation, and IYCF practices was complex. Because ICDS services are more widely used by the poor, food supplementation was higher in lower quintiles and in rural areas, but receiving food supplementation was positively associated with IYCF practices (*β* = 5.1 for EIBF, 3.0 for EBF, and 1.5 for minimum dietary diversity). {#mcn12663-fig-0004} {#mcn12663-fig-0005} 4. DISCUSSION {#mcn12663-sec-0011} ============= Our analysis of India\'s nationally representative household surveys conducted 10 years apart (2006 and 2016) showed significant improvements in BF practices, especially among the wealthier quintile and a closing of the equity gap in EBF. Although a narrowing of the equity gaps was also found in complementary feeding practices, this remains a critical concern, showing deterioration over time in timely introduction of solid/semisolid foods, slow progress on minimum dietary diversity and minimum acceptable diets, and overall poor complementary feeding practices across all segments of society. SES appears to be an important driver of both BF and complementary feeding practices operating through a complex series of sociodemographic factors, greater access and use of health and nutrition services, and access to information pathways. Although programme and policy strategies in India are well aligned with global guidance on IYCF and provide a vision for intervention scale‐up (Avula, Oddo, Kadiyala, & Menon, [2017](#mcn12663-bib-0002){ref-type="ref"}), progress in improving IYCF practices has been mixed, and several practices remain suboptimal. Prior research using the 2005--2006 NFHS documented poor IYCF practices in India and strong associations between most IYCF practices and SES status and maternal education (Patel et al., [2010](#mcn12663-bib-0023){ref-type="ref"}). Strikingly, our results suggest that progress since 2006 has largely been limited to BF practices, and especially so among the wealthiest groups (Q5), whereas the proportion of children introduced to complementary foods in a timely fashion and achieving minimum meal frequency declined, and dietary diversity improved only marginally. We find indicative evidence that improvements in BF were driven by improved access to, and use of, health and nutrition services during pregnancy for the lowest SES quintiles. This suggests that targeting of the services to poorer socio‐economic groups improved over time. Among the wealthier quintile (Q5), however, use of health services did not increase in urban areas and increased only marginally in rural areas between 2006 and 2016, suggesting that quality, rather than greater use of counselling on EBF, may have improved over time. The closing of the equity gap in EBF is a remarkable story, but still only about half of all children 0--6 months of age in our urban and rural samples were exclusively breastfed at the time of the survey in 2016. Thus, strengthening health and nutrition programmes in India to support optimal IYCF practices through counselling is important, especially for BF and those aspects of complementary feeding that are amenable to behaviour change even when resources are limited (for instance, timely introduction of semisolid and solid food). For dietary diversity, it is likely that economic and cultural factors are major constraints to adoption of optimal practices. Carefully designed, culturally sensitive counselling and awareness raising are essential. Young children tend to be fed household diets in many low‐ and middle‐income countries (Nguyen et al., [2013](#mcn12663-bib-0019){ref-type="ref"}), probably for economic reasons. Purchasing special nutrient‐rich foods for young children may be prohibitively expensive for poor households and is not justified. Recent research shows that animal‐sourced foods (ASFs), for example, are expensive in low‐income countries, with calories from ASFs being typically five to 10 times more expensive than calories from staple cereals (Headey, Alderman, Maitra, & Rao, [2017](#mcn12663-bib-0008){ref-type="ref"}). Although some ASFs such as dairy and poultry products are cheaper in India than in most low‐ or middle‐income countries (because India is now a major producer of these foods), it does not mean that they are within reach for the poorest segments of the population. Cash transfers could be one of the mechanisms to improve household diet. An evidence review of cash transfers vis‐à‐vis food transfers suggests that unconditional and conditional cash transfers improve household food consumption and dietary diversity (Alderman, [2016](#mcn12663-bib-0001){ref-type="ref"}). Evidence that this translates into improvements in young children\'s diets, however, is scant. The NFHS data suggest that around one third of all Indian women report never consuming meat or eggs, and 11% report never consuming dairy, indicating a set of truly vegetarian families where promotion of ASFs is not an option. However, among the remaining two thirds of families, removing additional constraints (economic and cultural), preventing the feeding of ASF products to young children could contribute to filling some of the critical gaps in complementary feeding practices that exist among this age group. The worsening of complementary feeding practices in India occurred even in the context of increasing use of health services and of the ICDS programme. We found that receiving food supplements from the ICDS was associated with improved IYCF practices. It is possible that additional efforts to improve the composition and uptake of the complementary food supplements in the ICDS programme, or to include additional ASFs, could help increase children\'s dietary diversity through public provisioning of such foods. Some state governments have been proactive in introducing eggs into the ICDS programme (Khera, [2015](#mcn12663-bib-0013){ref-type="ref"}), and there may be further scope to scale up the use of a variety of ASFs in ICDS and other programmes. The ICDS and health platforms in India, both of which have high coverage in many states, could also play a much stronger role in supporting complementary feeding behaviours by strengthening the behaviour change communication and community mobilization components of the programme. The evidence on the impact of strategies deployed within or alongside the ICDS to address IYCF behaviours is limited (Avula et al., [2017](#mcn12663-bib-0002){ref-type="ref"}), but ample evidence now exists of group‐based and individual counselling strategies in India that have been successful at improving complementary feeding practices (Nair et al., [2017](#mcn12663-bib-0018){ref-type="ref"}; Vazir et al., [2013](#mcn12663-bib-0029){ref-type="ref"}). Adapting these for scale‐up through the ICDS platform, or in collaboration with the ICDS, could help close the gaps in IYCF knowledge and practices. However, given that these programme platforms are generally propoor, it is also imperative to examine ways to improve the reach of IYCF counselling even among the upper quintiles, where IYCF practices are still poor and have even worsened over time. This will require additional strategies such as working with private providers/paediatricians, the media, and other platforms. Our findings on inequality in child feeding are consistent with more conventional economic analyses of inequality in India. Historically, household consumption data suggested that inequality in India was not especially high by international standards, but the more recent switch to income‐based inequality measures revealed that economic inequality in India was among the highest in the world (Himanshu, [2018](#mcn12663-bib-0009){ref-type="ref"}). India\'s rapid economic growth has also coincided with rising inequality, although growth in consumption among the bottom 40% has been reasonably rapid, at 3.2% per year over 2004--2011, compared with 3.7% for the population as a whole (World Bank, [2016](#mcn12663-bib-0036){ref-type="ref"}). The past decade has also seen the introduction or scale‐up of major poverty reduction efforts, including reforms to the Public Distribution Scheme, National Rural Employment Guarantee Scheme, and significant shifts in occupations and urbanization. However, both secular and economic trends and the quality of poverty reduction programmes vary markedly across states. Despite the efforts of government to improve access to health care among women and children, especially for the underserved population (MoHFW, [2005](#mcn12663-bib-0016){ref-type="ref"}), we still found substantial SES inequalities in use of nutrition and health care services in both urban and rural areas, a finding consistent with a previous review (Sanneving, Trygg, Saxena, Mavalankar, & Thomsen, [2013](#mcn12663-bib-0025){ref-type="ref"}). In addition, although these services improved in the last decade, the coverage remains suboptimal, such as BF counselling during pregnancy (42%) or interventions during early childhood (25--60%). Further improvement in access to nutrition and health services along the continuum of care, particularly for the poor, can have potential impacts on IYCF practices. Our study has several unique strengths. We use two rounds of large nationally representative datasets to explore changes in IYCF practices for different SES groups. The NFHS has several strengths in this regard, including consistency in a wide range of key indicators, national and state representativeness, and scope for measuring SES through well‐established asset indices (Filmer & Pritchett, [2001](#mcn12663-bib-0006){ref-type="ref"}). For inequity analyses, we used both simple methods (absolute inequity Q5--Q1 and relative inequity Q5/Q1) that can be easily conveyed to lay audiences and advocate to policymakers, and the advanced methods (SII and CIX) that account for the overall frequency of the outcomes that have changed markedly over time in our analyses. Results from different analyses were consistent and complemented each other, confirming the decline in inequalities in IYCF over the last 10 years. The pathway analyses also shed light on the different mechanisms by which SES may affect IYCF practices and is a novel application to this particular issue. This study has some limitations. The measurement of IYCF practices could be prone to bias from maternal recall or social desirability in reporting. However, there is some evidence that the EBF indicator is accurate (Moore et al., [2007](#mcn12663-bib-0017){ref-type="ref"}), and complementary feeding indicators were widely used in programme monitoring and evaluations. The NFHS contains rich information on maternal and child health and nutrition, but it is more limited in terms of sociocultural data and does not include any information on nutrition knowledge or exposure to counselling interventions. Thus, the dataset does not have the needed information to examine the influences of these factors on IYCF practices. Finally, the sample size in NFHS‐4 is much larger than that in NFHS‐3; it is possible that this might influence inequality metrics. To overcome that concern, however, we merged all the asset variables from both survey rounds and used the factor scores from this to create the quintiles from each round of data. That way, we ensure that a Q1 person in 2015 is indeed about as poor as a Q1 person in 2005. 5. CONCLUSION {#mcn12663-sec-0012} ============= Improvements in BF and the narrowing of equity gaps in IYCF practices, especially in EBF in India, are significant achievements. However, ensuring the health and well‐being of India\'s large birth cohort will require efforts to further improve BF, and concerted actions to address all aspects of complementary feeding across SES quintiles. CONFLICTS OF INTEREST {#mcn12663-sec-0014} ===================== The authors declare that they have no conflicts of interest. CONTRIBUTIONS {#mcn12663-sec-0015} ============= PHN conceived the idea, conducted the statistical analyses, and wrote significant sections of the manuscript. RA conducted literature review, reviewed the statistical analyses, and wrote part of the manuscript. LMT conducted the statistical analyses and prepared tables and figures for the manuscript. DH reviewed the statistical analyses, supported interpretation, and wrote part of the manuscript. MTR supported data interpretation and reviewed and edited the manuscript. PM reviewed the statistical analyses, supported data interpretation, and reviewed and edited the manuscript. All authors read and approved the final submitted manuscript. Supporting information ====================== ###### Supplementary Table 1: Changes in prelacteal feeding practices during the first 3 days between 2006 and 2016 Supplementary Figure 1: Changes in food group consumption between 2006 and 2016 Supplementary Figure 2: Inequality trends in food group consumption between 2006 and 2016, by SES quintile and rural/urban residence Supplementary Figure 3: Path models for early initiation of breastfeeding ###### Click here for additional data file.

Q: C++ OpenGL array of coordinates to draw lines/borders and filled rectangles? I'm working on a simple GUI for my application on OpenGL and all I need is to draw a bunch of rectangles and a 1px border arround them. Instead of going with glBegin and glEnd for each widget that has to draw (which can reduce performance). I need to know if this can be done with some sort of arrays/lists (batch data) of coordinates and their color. Requirements: Rectangles are simple filled with one color for every corner or each corner with a color. (mainly to form gradients) Lines/borders are simple with one color and 1px thick, but they may not always closed (do not form a loop). Use of textures/images is excluded. Only geometry data. Must be compatible with older OpenGL versions (down to version 1.3) Is there a way to achieve this with some sort of arrays and not glBegin and glEnd? I'm not sure how to do this for lines/borders. I've seen this kind of implementation in Gwen GUI but it uses textures. Example: jQuery EasyUI Metro Theme A: In any case in modern OpenGL you should restrain to use old fashion API calls like glBegin and the likes. You should use the purer approach that has been introduced with core contexts from OpenGL 3.0. The philosophy behind it is to become much closer to actual way of modern hardware functionning. DiretX10 took this approach, somehow OpenGL ES also. It means no more lists, no more immediate mode, no more glVertex or glTexCoord. In any case the drivers were already constructing VBOs behind this API because the hardware only understands that. So the OpenGL core "initiative" is to reduce OpenGL implementation complexity in order to let the vendors focus on hardware and stop producing bad drivers with buggy support. Considering that, you should go with VBO, so you make an interleaved or multiple separated buffer data to store positions and color information, then you bind to attributes and use a shader combination to render the whole. The attributes you declare in the vertex shader are the attributes you bound using glBindVertexBuffer. good explanation here: http://www.opengl.org/wiki/Vertex_Specification The recommended way is then to make one vertex buffer for the whole GUI and every element should just be put one after another in the buffer, then you can render your whole GUI in one draw call. This is how you will get the best performance. Then if your GUI has dynamic elements this is no longer possible exept if using glUpdateBufferSubData or the likes but it has complex performance implications. You are better to cut your vertex buffer in as many buffers that are necessary to compose the independent parts, then you can render with uniforms modified between each draw call at will to configure the change of looks that is necessary in the dynamic part.

A conventional technique for coating a phosphor on an LED, as shown in FIG. 1, includes directly applying a polymer material 20 such as epoxy, etc., into which the phosphor is mixed, onto an LED 10, and then, curing the polymer material 20. The conventional method of coating a phosphor on an LED has a problem that the polymer material 20 including the phosphor cannot be easily patterned. Therefore, in the conventional phosphor coating method, the phosphor must be applied to the entire surface after completion of wire bonding. In this case, when the LED to which the phosphor is applied cannot have desired performance (for example, in color, uniformity of color, etc.), the LED, which is expensive due to the wire bonding, is wasted, and thus, the overall manufacturing cost increases. In addition, the conventional method of coating a phosphor on the LED 10 is not appropriate for mass production. More specifically, in the conventional phosphor coating method, since the polymer material 20 including the phosphor must be separately coated onto each LED, the coating is expensive. Further, the conventional method of coating a phosphor on the LED 10 has a problem in that the thickness of the polymer material 20 including the phosphor cannot be easily adjusted. When the thickness of the polymer material 20 including the phosphor increases, intensity of light having a frequency varied by the phosphor increases, and when the thickness of the polymer material 20 including the phosphor decreases, intensity of light having a frequency varied by the phosphor decreases. Therefore, since the thickness of the polymer material 20 including the phosphor is an important factor for determining colors finally obtained from the LED 10, the thickness must be precisely controlled. In particular, since the light is emitted from side surfaces of the LED 10 as well as an upper surface thereof, the thickness of the polymer material 20 including the phosphor disposed on the side surfaces of the LED 10 as well as the thickness of the polymer material 20 including the phosphor disposed on the upper surface of the LED 10 must be precisely controlled. Furthermore, since the polymer material 20 including the phosphor is applied onto the LED 10 to a non-uniform thickness in the conventional method of coating a phosphor on the LED 10, uniform colors cannot be obtained. For example, when a white light is obtained by mixing a blue light emitted from a blue LED 10 and a yellow light obtained by a yellow phosphor, the white light with yellow color is transmitted to an observer 1 of FIG. 1 since the thickness of the polymer material 20 including the phosphor is large, and the white light with blue color is transmitted to an observer 2 of FIG. 1 since the thickness of the polymer material 20 including the phosphor is small.

ELECTIONS 27TH CONGRESSIONAL DISTRICT Rogan (Via Videotape), Schiff Debate Senior Health Issues Rep. James E. Rogan (R-Glendale) traded jabs with Democratic challenger Adam Schiff on Thursday over patients' rights legislation and prescription drug plans, with Rogan making his attack in a videotaped message shown to a group of 60 senior citizens in Pasadena. Still in Washington, D.C., because of the federal budget impasse, Rogan taped a message shown to members of the Pasadena Seniors Curriculum in which he charged that state Sen. Schiff (D-Burbank) backs legislation that would limit seniors' choices for prescription drug benefits and would increase the liability of employers who provide health insurance. Rogan said he opposed the Norwood-Dingell patients' bill of rights because he fears it would increase liability for employers, allowing them to be sued more easily by employees over health insurance coverage. "The trial lawyers who would make billions of dollars off of these frivolous lawsuits are backing Adam Schiff," Rogan told the seniors, saying he instead supports two other patients' rights bills that do not subject employers to additional liability. In a telephone interview later, Schiff said the Norwood-Dingell bill is the better alternative to "HMO-industry backed" bills supported by Rogan, and he said there is language in the bill to protect employers from liability. "Sixty-eight Republican members of Congress joined in supporting this bipartisan bill," Schiff said of Norwood-Dingell. "I don't see how [Rogan] can explain how such a strong group of his colleagues feel he is on the wrong side of this issue." Rogan also said legislation backed by Schiff to provide prescription drug benefits for Medicare recipients would unreasonably limit the choices of seniors to a government-run program. The congressman said he supports a plan that would give seniors the option to "choose from dozens of low-cost private insurance plans . . . without forcing them into a government-run HMO with a one-size-fits-all approach." Schiff said the bill backed by Rogan is a pharmaceutical industry plan that would provide insurance companies tax incentives without guaranteeing they would provide affordable prescription drugs to Medicare recipients. "Mr. Rogan would give seniors the choice of having no drug benefit," Schiff said. "It doesn't require anybody to provide a benefit to anyone." Rogan was hoping to return to his district today, but campaign spokesman Jeff Solsby said Congress may work into the weekend, so even a Saturday return is uncertain. Solsby said the congressman is getting help from state Sen. Bill Murrow (R-Carlsbad), who is scheduled to bring Orange County supporters to the 27th Congressional District on Saturday to walk precincts for the incumbent. Meanwhile, U.S. Sen. Dianne Feinstein (D-Calif.), who is facing a challenge from Rep. Tom Campbell (R-San Jose), has agreed to appear at a get-out-the-vote rally for Schiff and other local legislative candidates at a Democratic Party office in Pasadena on Saturday.

SEARCH ALL LYBIO’S HERE Mormon.org - He Is The Gift – Christmas Video – #ShareTheGift "http://Lybio.net The Accurate Source To Find Transcript To Mormon.org - He Is The Gift – Christmas Video – #ShareTheGift." [Mormon.org - He Is The Gift – Christmas Video – #ShareTheGift] THE FIRST GIFT WAS NOT WRAPPED. HAD NO BOW. WASN'T PURCHASED ONLINE. OR IN A STORE. THE FIRST GIFT OF CHRISTMAS WAS A SIMPLE GIFT. … [Read more...]

Lanta Marine Park View Resort & Spa is located on Kantiang Beach, Koh Lanta on the southern end of the island, with mountainous views cascading down to white sands and turquoise seas. This is a friendly family run resort will try to accommodate your every need in order for you to have an enjoyable stay we will provide you with a relaxed retreat, an action filled adventure or a non stop partying experience. Accommodation and facilities: Fantastic view over the sea from the bungalow! Reservation service: Date: Feb 15, 2016written by: Johansson Date of stay: Feb 25, 2014 Accommodation and facilities: Very nice bungalows with beautiful view over the bay, but the restaurant was closed and the management was not very efficient. Reservation service: Good Date: Mar 04, 2014written by: Harriet Falck Rehn Date of stay: Mar 09, 2012 Accommodation and facilities: good choice despite bad comments, bungalow and bath were clean, some music from a beac bar was ok, nice view, we enjoyed our stay, staff do not realy speak english, breakfast was ok, restaurant seemed open but no guests so wi did ot try it but nice restaurants and coffeeshops arround Reservation service: worked well Date: Mar 18, 2012written by: Sabine Rahn Date of stay: Feb 10, 2012 Accommodation and facilities: Do not expect too much of this hotel is a budget accommodation in a beautiful place! The hotel is located in the south of the island, near the national park! From the bus station in Saponge takes you to a machine with an open body (previously needed to specify that a transfer to the hotel). The hotel consists of bungalows situated on a hill (quite steep stairs from the beach) with views of the sea and the beach! Quite decent bungalows with garden view, if you do not plan to stay all day in the room! Even the cheapest bungalows installed new air conditioning! The bathrooms are in need of repair, but it can survive, so they perform their function fully, hot and cold water is always in stock! Three types of breakfast with a beautiful view! Wonderful, nemnogolyudnom beach! On the main street behind the hotel shop 7/11 and lots of lovely inexpensive restaurants! A great place to spend a few days and visit the nearby islands. Reservation service: Date: Feb 15, 2012written by: Tetiana Date of stay: Dec 24, 2011 Accommodation and facilities: The upper (cheaper) cabins are not clean. The beds are smelly,the shower and toilet were not that clean (It was old, but i do not mind that). Since we d already booked we were given the option to move to the more expensive cleaner cabins fore extra cash. We noticed that we paid more than we would have if we would have booked directly via a website. We will NOT come back at Lanta Marina! The Bay very beautifull. Although in the water is seemed like very tiny needles were puncturing the skin. Not every one experiences this. Reservation service: Booking works well! Date: Apr 10, 2012written by: Martijn Reinoud Platenkamp Date of stay: Dec 21, 2011 Accommodation and facilities: At the end we only stay 1 night, the room was really dirty, bathroom was a nightmare. And the worst was that workers from the hotel decide to make a party untill 1am!!!!! Never again Reservation service: Perfect, fast and easy Date: Dec 25, 2011written by: Daniel Riera Marsa Date of stay: Feb 22, 2011 Accommodation and facilities: Nice beach and site. Nice restaurang placement with wonderful view over the sea. The staff was a little bit too laidback and could impprove its service attitude. Reservation service: Perfect administration Date: Mar 06, 2011written by: Per Lindholm Date of stay: Feb 10, 2011 Accommodation and facilities: Very noisy in the whole bay til 00:30h (Liveband is playing) 2 days in a room we don t have booked between 2 bars. Noisy with no chance to sleep til 04:30h in the morning. Thats the reason for my choices Bad Service and not so good location Accommodation and facilities: Very nice place, we loved beeing att Lanta marine. Nice people working there, very cool and laid back style, friendly. Reservation service: It was easy, quick answers and reservations Date: Jan 02, 2011written by: Margaretha Vinberg Date of stay: Dec 04, 2010 Accommodation and facilities: we had a pleasnt stay and as a family run operation it isnt as professionally run but its entirely a good value. As a older guest i have one recomendation. they are in the process of buiding a aircon resturant and bar, but they really need to buy new beds instead and upgrade the bathrooms. The bed left me feeling tortured and a bit angry when they are spending money on other things Reservation service: easy no problem Date: Dec 08, 2010written by: Ron Wagner Phensinee Rattanapoo Date of stay: Nov 27, 2010 Accommodation and facilities: This hotel was recommended by a good friend. The view was beautiful (seaview bungalow), but we had to climb a lot of stairs to our Bungalow (B7). So if you have a bad condition ask for a bungalow closer to the reception. Staff is friendly and helps you carry your suitcases up and down your bungalow! Anything you ask for, they do what they can. The beach is lovely, but no parasols or shadow, ask for a parasol at the reception (one to borrow for free). We would defenitly go there again. Reservation service: Easy, clear and fast.. Date: Dec 11, 2010written by: Patricia Blijleven Currency: Enter arrival and departure dates Arrival date / Check-in: Departure date / Check-out: Length of stay: nights adult / child's AGE:Enter the AGE of the child:Example, for a child 7 years old, enter: 7 Example for more than 1 child:2 children aged 8 and 9 years, enter: 8,9 Please enter the children's AGE,not the number of children.child age 2-11. This hotel has special rates for some markets. Please set your nationality: Welcome to . . . Lanta Marine Park View Resort A warm welcome greets you to one of Koh Lanta's most attractive resorts with breath taking views over the most secluded beach on the island. Lanta Marine Park is at the southern end of the island, with mountainous views cascading down to white sands and turquoise seas. This friendly family run resort will try to accommodate your every need in order for you to have an enjoyable stay we will provide you with a relaxed retreat, an action filled adventure or a non stop partying experience. ACCOMMODATION :: Garden View - 10 Units :: The Garden View rooms are pleasant alternatives for the budget traveler. Our well-maintained wood and bamboo bungalows are clean and inexpensive, nestled in our lush tropical garden. Each with private toilet and shower these traditional 'beach style' bungalows are the accommodation of choice for backpackers and long-term residents. Rooms can add extra bed. :: Sea View Bungalow - 8 Units :: Sea View Bungalows are in our tropical garden among the flowers and butterflies. Each room stands on stilts, allowing a view of the sea. All of these rooms are available with air conditioning, fan, mini-fridge and hot water shower. Rooms can add extra bed. :: Bay Front Bungalow - 8 Units :: Bay Front Bungalow offer stunning views of Kantiang Bay, each with a private cliff-side balcony. Also available with air conditioning these rooms feature sliding glass doors to let in the cooling sea breeze. Each cottage features fan, mini-fridge and hot water shower. Rooms can add extra bed. :: Deluxe Bay Front (Family) - 2 Units :: Treat yourself in our family-sized Deluxe Bay Front, only steps from the beach. These large glass-front rooms are air-conditioned for your comfort and feature spacious and recently renovated bathrooms. Perfect for a family vacation or a special couples' getaway. Each suite features fan, mini-fridge and hot water shower. Rooms can add extra bed. RESTAURANT & BAR :: Bay View Restaurant :: Our Bay View Restaurant offers a tiered dining room with unmatched views of Kantiang Bay all day long. We offer a full menu of both Thai and Western cuisine supervised by a Thai and European management team to ensure the highest quality of preparation and taste. In the evenings our Seafood Barbecue and Salad Bar offer the finest selection of fresh seafood, grilled to your specifications. The Bay View Restaurant is also available for private functions and group dinners. :: Shroom Bar :: Our wood and bamboo Shroom Bar is one of Kantiang Bay's number one night spots. With a variety of levels to choose from it's the perfect spot to chill out, have a meal or groove the night away. Featuring a full selection of beer, wine, spirits and fresh-squeezed fruit juices, the Shroom Bar can quench even the most discerning thirst. Available for parties it's the perfect venue to celebrate that special occasion with friends and relatives. The Shroom bar is open from midday until the early morning hours. SERVICES & FACILITIES Many services are available from us here at the resort including motorbike and jeep rental, laundry service, internet and international phone calls, massage, safety deposit box, room service, taxi service to Ban Saladan, currency exchange, travel and ticket information and Thai cooking instructions. We try to give you all the help and service in which you require. :: Activities :: At Marine Park there are many activities which you can enjoy, you can have a relaxing time on the beach with safe swimming and some snorkeling, but if you feel you would like to go out and explore there are many things you can do including: National park, sea gypsy village, Tiger cave, elephant trekking, waterfall and exploring the island is an activity in its self. LOCATION MAP No beach and located up on the hill. The guest can walk down from the hill around 100 meters to the beach.

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From voting to healthcare, music to energy production, blockchain may just change the way we run our lives Voting A blockchain allows the authentication of transactions without them needing to be administered or guaranteed by a central authority. Ballot boxes and current online voting platforms are vulnerable to manipulation; now a startup called Follow My Vote is developing a blockchain-based system to ensure security, transparency and mathematically accurate election results. Facebook Twitter Pinterest Up on the roof: solar panels in Park Slope, Brooklyn. Photograph: Clinton Nguyen Power generation Applied to power generation, blockchain enables homeowners to sell back energy to the grid without going via an energy provider or manage their own microgrids that are independent from the established system. Lo3Energy runs a project in Brooklyn, New York, where homeowners can buy and sell energy they have generated with rooftop solar panels. The blockchain allows them to set their own price – and to do so without a price-setting, commission-taking intermediary. Facebook Twitter Pinterest Definition of sound: blockchain could give control – and 100% of revenue – back to recording artists. Photograph: Paul Bradbury/Getty Images/Caiaimage Music streaming Just got the hang of Spotify? Prepare to have your listening habits disrupted again by blockchain-based music streaming services. Instead of a service such as Apple Music or Spotify taking a cut, a blockchain system called Voise is enabling artists to set a price of which they receive 100% when a user streams their music. Facebook Twitter Pinterest Goodbye to all that: the keeping and sharing of medical records may soon be revolutionised. Photograph: Alamy Healthcare A patient’s medical records are often scattered between GPs, clinics and labs. A blockchain-based health record could be read and updated from multiple locations or services and would contain a note of who made each addition to the record. The patient can opt to take charge of the data and choose whom to share it with. At MIT, researchers are developing such a system, called MedRec, that will integrate with current healthcare computer set-ups. Facebook Twitter Pinterest Smile please: a UN worker scans the iris of a Syrian girl registering as a refugee at a camp in Jordan. Photograph: UNHCR Aid In 2012, the then secretary-general of the UN, Ban Ki-moon, estimated that 30% of development aid was lost to corruption. The UN has a number of blockchain-based projects looking to solve issues in delivering aid. Last year, in a UN world food programme pilot project, Syrian refugees in a Jordan camp were given an allowance in cryptocurrency. When making purchases at the camp supermarket, their identities were authenticated by iris scans and their spending deducted from their allowance. This cuts down on transaction fees for the UN and reduces the frequency of fraud and theft.

using System; using System.Collections.Generic; using System.Linq; using System.Text; namespace VRage.Library.Collections { /// <summary> /// Automatically resizing array when accessing index. /// </summary> public class MyIndexArray<T> { T[] m_internalArray; public float MinimumGrowFactor = 2; public T[] InternalArray { get { return m_internalArray; } } public int Length { get { return m_internalArray.Length; } } public T this[int index] { get { return index >= m_internalArray.Length ? default(T) : m_internalArray[index]; } set { var oldSize = m_internalArray.Length; if (index >= oldSize) { int newSize = Math.Max((int)Math.Ceiling(MinimumGrowFactor * oldSize), index + 1); Array.Resize(ref m_internalArray, newSize); } m_internalArray[index] = value; } } public MyIndexArray(int defaultCapacity = 0) { m_internalArray = defaultCapacity > 0 ? new T[defaultCapacity] : EmptyArray<T>.Value; } public void Clear() { Array.Clear(m_internalArray, 0, m_internalArray.Length); } public void ClearItem(int index) { m_internalArray[index] = default(T); } /// <summary> /// Trims end of array which contains default elements. /// </summary> public void TrimExcess(float minimumShrinkFactor = 0.5f, IEqualityComparer<T> comparer = null) { comparer = comparer ?? EqualityComparer<T>.Default; int i; for (i = m_internalArray.Length - 1; i >= 0; i--) { if (!comparer.Equals(m_internalArray[i], default(T))) break; } int newSize = i + 1; if (newSize <= m_internalArray.Length * minimumShrinkFactor) { Array.Resize(ref m_internalArray, newSize); } } } }

Q: Photoshop-style brushes in OpenGL I am trying to implement free-hand sketching (it should look like a pencil). I did some research and I'm surprised there is so little info about this on the internet. The best information I got was by drawing in Photoshop and observing the result. I think Photoshop works something similar like this: 1) Each brush has its own pixel map, telling what opacity has each pixel 2) Settings (like weight, color etc.) apply to this pixel map before drawing 3) When pressing the mouse, Photoshop starts slowly filling the pixels under the pointer according to the pixel map given opacities 4) When drawing fast (so that the distance between two mouse frames is bigger than the fill ratio), Photoshop somehow interpolates the brush so that it looks homogeneous. I am not sure, but I think it also applies some kind of transformations to the pattern, because the line does not look regular. Another effect I would like to implement is the line getting thinner before the pencil lifts (based on the speed of the pencil) - just as in real life. I will appreciate any hints about: 1) How precisely Photoshop brushes (or a similar tool) work 2) Any open-source tools which do something similar 3) Keywords to look for (apparently I am googling with the wrong words) Here a link I found in the research process (unfortunately closed source): http://www.youtube.com/watch?v=3RPphJxxscY A: 1) How precisely photoshop brushes (or a similar tool) work Your guesses were quite accurate 2) Any open-source tools which do something similar The GIMP http://www.gimp.org 3) Keywords to look for (apparently I am googling with the wrong words) natural drawing tool simulation

Alterations of tau and VASP during microcystin-LR-induced cytoskeletal reorganization in a human liver cell line. Previously, we have reported alterations to HSP27 during Microcystin-LR (MC-LR)-induced cytoskeletal reorganization in the human liver cell line HL7702. To further elucidate the detailed mechanism of MC-LR-induced cytoskeletal assembly, we focused on two cytoskeletal-related proteins, Tau and VASP. These two proteins phosphorylated status influences their ability to bind and stabilize cytoskeleton. We found that MC-LR markedly increased the level of Tau phosphorylation with the dissociation of phosphorylated Tau from the cytoskeleton. Furthermore, the phosphorylation of Tau induced by MC-LR was suppressed by an activator of PP2A and by an inhibitor of p38 MAPK. VASP was also hyperphosphorylated upon MC-LR exposure; however, its phosphorylation appeared to regulate its cellular localization rather than cytoskeletal dynamics, and its phosphorylation was unaffected by the PP2A activator. These data suggest that phosphorylated Tau is regulated by p38 MAPK, possibly as a consequence of PP2A inhibition. Tau hyperphosphorylation is likely an important factor leading to the cytoskeletal destabilization triggered by MC-LR and the role of VASP alteration upon MC-LR exposure needs to be studied further. To our knowledge, the finding that Tau is implicated in cytoskeletal destabilization in MC-LR-treated hepatocytes and MC-LR-induced VASP's alteration has not been reported previously.

Amesenchymal hamartoma of the liver is an uncommon benign tumor mostly occurring in children, primarily in the first two years of life. It is thought to be a developmental anomaly of the portal connective tissue rather than a true neoplasm, and is composed of both mesenchymal and epithelial components ([@B1]). Most of the reported cases of a hepatic mesenchymal hamartoma have described a large multiloculated mass with variable septa and cystic spaces ([@B1]-[@B5]). Rarely, a predominantly solid form of a mesenchymal hamartoma containing a larger amount of hepatocytes has been reported in the literature ([@B6]-[@B9]). Although several reports have described the radiological findings of a mesenchymal hamartoma of the liver ([@B3]-[@B6]), little is known about the spectrum of radiological findings in a series of cases. The aim of this study was to describe a spectrum of the radiological findings of a mesenchymal hamartoma of the liver in children. MATERIALS AND METHODS ===================== Subjects -------- We retrospectively reviewed the radiological and clinical findings of 13 patients with a pathologically confirmed mesenchymal hamartoma of the liver. The institutional review board approved the review of the radiological and clinical data for this study and waived the requirement for informed consent. A computed hospital information system was used to identify all patients with a pathologically proved mesenchymal hamartoma during a 15-year period. The pathological diagnosis for a mesenchymal hamartoma was based on overgrowth of the mesenchymal stroma and the proliferation of architecturally abnormal bile ducts with or without a cystic change, accompanied by periductal collaring of the stromal cells ([@B1], [@B9]). Imaging and Analysis -------------------- Three pediatric radiologists retrospectively reviewed the radiological features of the hepatic mesenchymal hamartomas by consensus. CT scans were obtained with various third generation CT scanners at 80-120 mA, 100-120 kVp, and 5- to 10-mm thick sections. CT scans were obtained after an intravenous bolus injection of contrast media and portal venous phase scans of the liver were available for all patients. Pre-contrast CT scans were available for ten patients. CT images of the tumor were evaluated for location, size, presence of septa within the cystic portion, CT attenuation of the tumor relative to the surrounding hepatic parenchyma (low, iso, or high), pattern of contrast-enhancement (homogeneous or heterogeneous enhancement of the solid portion, and septal enhancement of the cystic portion) and presence of calcification on a pre-contrast CT scan. According to the extent of cystic component on the CT scans, we classified each tumor into one of three types: 1) multiseptated cystic - a purely cystic tumor with multiple thin septa; 2) mixed cystic and solid-a partially cystic tumor with irregular thick septa; 3) solid-a purely solid tumor without a cystic portion. The cystic portion was defined as an area of low attenuation that showed 0-40 Hounsfield units (HU) of CT attenuation value. We classified the septal thickness as follows: thin (\< 2 mm in thickness) or thick (\> 2 mm in thickness). Ultrasonographic (US) scans of nine patients were available for review. Among them, seven patients had a color or power Doppler US examination. US images were evaluated for the presence of capsule, internal content of the cystic portion (echogenic debris or fluid-fluid level), septal thickness within the cystic portion, and the echogenicity of the solid portion. Intratumoral vascularity was evaluated by the use of Doppler US. Pathological Correlation ------------------------ An experienced hepatobiliary pathologist reviewed the histological sections. The amount of mesenchymal stroma, the presence or absence of duct proliferation, the amount of hepatocytes, and the presence or absence of vascular proliferation was evaluated. The amount of mesenchymal stroma and hepatocytes were evaluated semi-quantitatively: little in \< 10% of the mesenchymal hamartoma, moderate in 10-50% of the mesenchymal hamartoma and abundant in \> 50% of the mesenchymal hamartoma. The age of the patients, size of the tumor and various histological findings were compared with the imaging features of the hepatic mesenchymal hamartomas among the three CT types using the Kruskall-Wallis test. Statistical analysis was performed with SPSS 11.5 for Windows (SPSS Inc., Chicago, IL). A two-tailed *p*-value of \< 0.05 was considered to be statistically significant. RESULTS ======= Clinical Findings ----------------- The subjects were seven boys and six girls, aged from 6 months to 7 years 6 months (mean age: 3 years 2 months). There was no significant difference of age (*p* = 0.93) among the three CT types of tumors. The patients presented with abdominal distension (n = 8), a palpable mass (n = 3) or an incidentally detected tumor during US (n = 2) for other clinical indications: a patient (case 8) with Peutz-Jeghers syndrome, and a patient (case 13) that had a Kasai operation for biliary atresia at one month of age, respectively. The serum level of alpha-fetoprotein, total and direct bilirubin level, alkaline phosphatase level, and level of transaminases (aspartate transaminase and alanine transaminase) were normal in all except two patients that had an elevated level of alpha-fetoprotein: the patient with biliary atresia (case 13) and a 9-month-old girl (case 5). Hepatitis B surface antigen was negative in all patients. In all patients, the tumors were surgically resected. Clinical features of the patients are summarized in [Table 1](#T1){ref-type="table"}. All patients had a solitary hepatic tumor. The tumor occurred in the right lobe of the liver in nine patients and in the left lobe in four patients. Splenomegaly, ascites and retroperitoneal lymphadenopathy were noted in one patient that had biliary atresia. Imaging Characteristics ----------------------- The longest diameter of the tumors ranged from 1.8 to 20 cm (mean 13.0 cm) and was larger than 10 cm in 11 patients (85%). There was no significant difference in the size of the tumors (*p* = 0.79) among the three CT types of tumors. The tumor was multiseptated cystic in four patients (31%) ([Fig. 1](#F1){ref-type="fig"}), mixed solid and cystic in five patients (38%) ([Figs. 2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}), and solid in four patients (31%) ([Figs. 4](#F4){ref-type="fig"}, [5](#F5){ref-type="fig"}). In four patients with a multiseptated cystic tumor, US (n = 1) showed a well-defined tumor with variable cystic spaces and multiple thin septa in the liver ([Fig. 1A](#F1){ref-type="fig"}). All of these tumors showed fine enhancing septa within the cystic tumor on post-contrast CT ([Fig. 1B](#F1){ref-type="fig"}). Neither calcification nor a solid portion was detected in these patients. In five patients with a mixed cystic and solid tumor, US (n = 5) showed a well-defined tumor with variable-sized cystic spaces, irregularly thick septa, and a solid portion of variable extent with heterogeneous hyperechogenicity ([Figs. 2A](#F2){ref-type="fig"}, [3A](#F3){ref-type="fig"}). In three patients, internal debris with fluid-fluid level was seen in the cystic portion of the tumor ([Figs. 2A, 2C](#F2){ref-type="fig"}). On color and power Doppler US (n = 4), linear vascular flow was detected along the thick septa ([Fig. 2B](#F2){ref-type="fig"}) and in the solid portion. On CT, thick septa within the cystic portion ([Fig. 2D](#F2){ref-type="fig"}) and the solid portion of the tumor ([Fig. 3C](#F3){ref-type="fig"}) showed heterogeneous enhancement. A tiny nodular intratumoral calcification was seen in one patient (case 8) ([Fig. 3B](#F3){ref-type="fig"}). In four patients with a solid tumor, US (n = 3) showed a well-defined, isoechoic tumor (n = 1) or slightly hyperechoic (n =2 ) ([Fig. 5A](#F5){ref-type="fig"}) tumors. Color or power Doppler US (n = 3) showed central ([Fig. 5B](#F5){ref-type="fig"}) or peripheral vascularity in two patients and one patient, respectively. These tumors showed low attenuation on a pre-contrast CT scan in all patients, except for one with a high attenuating lesion. At post-contrast CT, tumors were heterogeneously enhanced in all patients ([Figs. 4B](#F4){ref-type="fig"}, [5C](#F5){ref-type="fig"}). In the patient that had biliary atresia (case 13), the tumor appeared as a 1.8-cm sized enhancing nodule with a peripheral rim of low attenuation at post-contrast CT ([Fig. 5C](#F5){ref-type="fig"}). No demonstrable tumor capsule was seen in any patients. Pathological Correlation ------------------------ The mesenchymal hamartomas showed multiple variable sized cystic portions within the tumor in their gross morphology ([Figs. 1C](#F1){ref-type="fig"}, [2E](#F2){ref-type="fig"}, [3D](#F3){ref-type="fig"}). Each mesenchymal hamartoma with a multiseptated cystic appearance contained various amounts of myxoid or collagenous stroma and showed proliferation of the malformed bile ducts with periductal collaring of the stromal cells ([Fig. 1D](#F1){ref-type="fig"}). All of the four patients with a multiseptated cystic tumor contained a small amount of hepatocytes (\< 10%) on a semiquantitative evaluation. The mesenchymal hamartomas with a mixed solid and cystic appearance also contained various amounts of myxoid or collagenous stroma and showed proliferation of the malformed bile ducts with periductal collaring of the stromal cells ([Fig. 2F](#F2){ref-type="fig"}). Among five patients with a mixed type mesenchymal hamartoma, the amount of hepatocytes was small in three patients and moderate in two patients. In four patients with a solid mesenchymal hamartoma, a moderate (n = 3) amount or abundant amount (n = 1) of hepatocytes was found in the cords, islands or lobular pattern. The solid tumor also contained various amounts of mesenchymal stroma and proliferation of the small bile duct was seen ([Fig. 4D](#F4){ref-type="fig"}). In one patient with an enhancing nodule with a peripheral rim of low attenuation (case 13), the enhancing portion revealed a large amount hepatocytes histologically with a rim of myxoid stroma. The amount of hepatocytes was significantly different among the multiseptated cystic, mixed solid and cystic, and solid tumors (*p* = 0.042). The other pathological findings such as the amount of mesenchymal stroma, the presence of a bile duct or vessel proliferation were not statistically significant among the three groups of the different imaging spectrum. DISCUSSION ========== A mesenchymal hamartoma is the second most common benign hepatic tumor in children and accounts for 8% of all hepatic tumors in children ([@B10]-[@B14]). Histologically, a mesenchymal hamartoma appears as a disordered arrangement of mesenchyme, bile ducts and hepatocytes ([@B1]-[@B3], [@B9], [@B15]). Cords of normal-appearing hepatocytes are separated by zones of loose poorly cellular mesenchyme. The porous nature of a mesenchymal hamartoma permits accumulation of fluid. Cystic degeneration of the mesenchyme with resultant fluid accumulation from obstruction and dilatation of the lymphatics and/or by entrapped bile ducts may lead to enlargement of the tumor ([@B12]). The margin between the liver and the tumor is distinct; however, a true capsule is generally not present ([@B2]). The level of serum alpha-fetoprotein, which is believed to be secreted by the proliferating hepatocytes within the tumor, can be elevated ([@B13], [@B14]). A multiseptated cystic appearance, which may be a typical finding of mesenchymal hamartoma, is rarely seen in other hepatic tumors in children. Intratumoral calcification, which can be frequently detected in hepatoblastomas (over 50%) or infantile hemangioendotheliomas (up to 40%) ([@B11]), has been reported very rarely for a mesenchymal hamartoma. Chung et al. ([@B8]) described the CT findings of a mesenchymal hamartoma containing central and peripheral calcifications in a 57-year-old woman. Konez et al. ([@B15]) also described the CT findings of the multiseptated cystic form of a mesenchymal hamartoma with a septal calcification in a 10-year-old boy. In this series, a tiny calcification within the tumor was seen only in one patient. Although a mesenchymal hamartoma present most frequently as a multiseptated cystic or mixed solid and cystic tumor ([@B1]-[@B5]), it can rarely occur as a solid tumor ([@B6]-[@B9]). In this study, according to the extent of the cystic component on CT scans, we classified each tumor into one of three types for evaluating the imaging spectrum of this tumor. In this study, the tumor was totally solid in 31% of the patients, and one case of a solid mesenchymal hamartoma (case 11) showed features of a so-called \"mixed hamartoma.\" The mixed hamartoma is a rare hamartomatous lesion composed of all cellular components of the normal liver, including a larger amount of hepatocytes, ductal proliferation, and hepatocellular-ductal transition. The mixed hamartoma and mesenchymal hamartoma may be in one disease spectrum, since there is some overlapping in the histological features of both hamartomas ([@B16], [@B17]). In children with a solid mesenchymal hamartoma, radiological differential diagnosis should include various hepatic tumors such as a hepatoblastoma, a hepatocellular carcinoma, an infantile hemangioendothelioma, a hepatic adenoma, or a focal nodular hyperplasia. Heterogeneous enhancement and absence of a tumor capsule in a mesenchymal hamartoma can be helpful in the differential diagnosis from other tumors. As in one of our patients that had biliary atresia and a solid mesenchymal hamartoma (case 13), Lack ([@B18]) described a mesenchymal hamartoma in a 5-month-old girl with biliary atresia, which was found incidentally during an exploratory laparotomy for obstructive jaundice. The cystic component of this tumor was either very small or undetectable. Lack ([@B18]) showed an interest in this case because one of the theories for development of a mesenchymal hamartoma is biliary obstruction ([@B19]). In conclusion, a mesenchymal hamartoma of the liver in children can show a wide spectrum of radiological features from a multiseptated cystic tumor to a mixed solid and cystic tumor, and even a solid tumor. {#F1} {#F2} {#F3} {#F4} {#F5} ###### Summary of the Clinical and Radiological Features of Children with a Mesenchymal Hamartoma of the Liver  Note.-Distension = abdominal distension, Detected at US = incidentally detected at US, Septa = septal enhancement of cystic tumor, Heterogeneous-Septa = heterogeneous enhancement of the solid portion and septa , Heterogeneous = heterogeneous enhancement of a solid tumor, N/A = not available, ND = Doppler US examination was not done, ^†^ = focal calcification on precontrast CT, ^\*^ = elevated alpha fetoprotein.

Do not depend on the eBay Buyer Vehicle Protection Program. It’s not that I don’t believe eBay will protect you, they have a vested financial interest in doing so, it’s that there are a lot of variables and a lot of things that can go wrong. In fact, whenever you buy anything, the protection policies should never come into play because you should only enter into a transaction that you are 100% confident in. If there is a inkling of foul play, don’t buy the car. If the guy sounds funny or is not entirely forthcoming when you ask a question, don’t buy the car. If you’re on the fence about the vehicle, for whatever reason, do not buy the car. Vehicle Purchase Protection Ensures that you receive the vehicle you paid for, with coverage up to $20,000 against fraud or material misrepresentation. That’s the guarantee that eBay provides, with a $100 deductible. But if you look closely, it only protects you if the seller commits fraud or misrepresents the vehicle. A lot of times, the listing will state “As-Is” and so that absolves the seller of any problems that he or she didn’t know about beforehand. Let’s say you purchase a car and it has a huge scratch that the seller didn’t mention. Well, that’s something that the seller can’t pretend to not have known about. But what if the problem is a small leak in the coolant line that ruptures, causes your car to overheat, and you blow a head gasket? Well, that small leak isn’t something that the seller would necessarily know about, especially if the leak was small and grew over time. The repairs to your car would be in the thousands of dollars but you can’t hold the seller liable because he or she didn’t know. So, bottom line, if you would buy the car without the protection program, buy the car. If you see a car that you would only buy if you had eBay’s protection program, skip it. Do yourself a favor and skip it. No money is worth the headaches that a potential “mysterious” problem would bring. I’ll let you in on a little known secret about the relationship between the Buy It Now and Reserve Prices for eBay Motors auctions, the Reserve Price is usually around $500-$1000 under the Buy It Now price, based on empirical evidence. You can safely ignore the current price because most cars worth anything will not be listed without a reserve price (there are exceptions of course) and so unless the reserve has been met, it won’t be sold. If you see that the Buy It Now for the car is more than a grand over what you want to pay for it, chances are you won’t be able to get the car for that price this time around. My suggestion? Watch the auction, if it doesn’t sell then the seller will likely drop the Buy It Now price a few hundred bucks and relist. You may even want to call him up and ask him how much he is looking to get for the car and, if you’ve done your homework, may be able to suggest to him that the price he is waiting for is a little too high given your research. Unless you are low-balling the seller, he or she will likely hear what you have to say and may be willing to sell it to you outright. So you’ve done the research, located an auction with a seller (who is a dealer) whom you trust based on some telephone conversations (risky, but better than relying on feedback numbers), and now are ready to plunk down a bid and potentially buy yourself a nice shiny new (to you) ride. Be forewarned that the final auction price will definitely not be the total you will have to shell out to get that ride onto the road. When I purchased my Toyota Celica for $16,000 I still had to pay an additional $1,300 (8.125%) in taxes, shipping, and fees. (and I found an incredible price for shipping too!) State Sales Tax: The biggest non-auction-related cost will be sales tax. In Maryland, this is a nice 5% payment that you will be required to make to the state whenever you register the vehicle. If you bought it from an in-state seller who collected it, then you simply present the receipt and Maryland will accept that as payment. For a $15,000 vehicle, 5% is $750 so please make sure you figure that into your costs.(Click to continue reading…) As I mentioned earlier, the feedback system is a little less valuable for purchasing vehicles simply because private party sellers oftentimes don’t sell a lot of cars and representatives of dealers, who do sell a lot of cars, will rely on the dealership’s name and not their own feedback. That being said, feedback still plays an important role in assessing the risk of a particular seller. Also, with this and any other high dollar item, you will need to contact the seller. Most, if not all, vehicle sellers will list a phone number and, hopefully, their name. You have to talk to the seller at least once.(Click to continue reading…) In part 2 of the Buying Cars on Ebay series, I’ll dissect an Ebay Motors auction listing which can be a little overwhelming. An Ebay Motors auction listing is very similar to any other auction listing in that it’ll have a standard set of information (mileage, transmission, trim, etc.) but it’s the description that you must make careful note of. In this particular regard, the professionalism and transparency of the auction is paramount. The standard information is the same for all vehicles and looks similar to a book or other commodity type auction (DVDs, concert tickets, etc.). Take this auction for a 2004 Celica for example. The standard information is mileage, transmission, doors, interior, year, warranty, title, condition, engine, VIN (important!), interior and exterior color, and inspection. There is also a list of the standard and added optional equipment on the vehicle. That’s the extent of the required information. As you can see, that auction doesn’t look as professional as this auction for a 2005 Celica GT Hatchback and the difference is the first is an auction from a private seller and the second is an auction from Precision Toyota of Tucson. Note key and critical differences. Attribute First Auction Second Auction # Photos 10 18 Contact Phone # Yes Yes Words in Descr. 87 297 Terms & Conditions No Yes Seller Individual Dealer And that’s just the superficial details of the vehicle. Photos are important because that’s all you get to see of a car in an Ebay auction. You want to see, at a bare minimum, two photos: one of the VIN and one of the odometer. While they can always switch it on you, at least you know they have the car in their possession. Second, the contact information is critical because before I’m going to commit this much money for anything I’ll want to talk to the seller on the phone (that’ll be for a later article). I put in the number of words description only because the more detailed the description the better. Of the 87 words in the first auction, half was fluff and meaningless, whereas all 297 words of the second auction were descriptive (though part of that was standard specs for the Celica such as trunk space). It’s not a discriminator but it’s a sign of professionalism. If you can’t spend more than 20 minutes to put together a nice useful description of your car then how much time are you willing to spend on the other things? Lastly, Terms & Conditions are critical in a transaction like this and they’re standard for dealership listings. Read them over very carefully because if you notice on the second auction, there’s a DOC Fees of $279.00. You had to switch tabs from General to Terms in order to see it. They’re not trying to trick you because T&C is exactly where that information will be and should be listed. Read over a whole bunch of auctions to get a feel for the types of information given. A lot of private party auctions will have some personal information (I’m selling because I’m moving, my girlfriend dumped me, etc.) but that’s not obviously as important as the specs of the car. If you’re tentative about shelling out so much on an auction, remember that you can always limit your search to vehicles being sold by dealerships. This is Part 1 on the Buying A Car On Ebay Series and this one goes through the process of pricing research so that you’ll know how to take advantage of Ebay. I’ll identify what I considered the three “markets” of used vehicles, help pricing vehicles, and how to take advantages of the differences between the different markets. This step isn’t specifically Ebay-related and should be the first step in any car buying process. With the advent of online car buying research sites, finding the price of your target vehicle is relatively straightforward. If you break up the pool of used vehicles, you’re limited to a dealer used vehicle and a private party used vehicle (coincidentally, these are categories of pricing available on Kelley Blue Book). Within the private party used vehicle, you have local and long distance sellers. In the past, long distance wouldn’t be an option but with the growth of these sites and of Ebay, buying a used car long distance is now easier (albeit with a bit of added risk). For the discussion below, I’ll be looking solely at Toyota Celica’s made within the last five years (2000 – 2005). Dealer Used Vehicles Price will always be higher but risk will be lower (a typical tradeoff). 1. Check CarMax – CarMax reminds me of the Best Buy for used and new vehicles. They have a no haggle price and are very friendly, they aren’t like the horror stories you hear about dealerships with a lot of pressure. At one point I asked what CarMax’s commission structure was and the sales clerk told me! What’s nice about CarMax is the sheer number of cars available so you can do some price comparisons. There are two ’03 Toyota Celica’s listed Autos listed: 1) Blue Automatic 20k at $16,998, 2) Yellow Automatic 15k at $17,998, 3) Blue Automatic 13K at $17,998. (there are more but this is sufficient) What you can learn is that 5-7k in mileage will cost approximately $1,000 in price and you can use this general barometer as a scale. It is generally accepted that typical mileage usage in a year is 12k-15k – any higher usage and most places will consider it a high mileage vehicle. Remember that benchmark number. 2. Check CarsDirect (or any of the car list websites): Just like the airline ticket websites, I think they all use the same database of vehicles so anyone you pick will give you similar data. You just want to know the basic going rate for the vehicle make and model in your area. A search for Toyota Celica’s in my area code on a site like this shows private party and dealer used vehicles. Year Make/Model/Trim Price Trans Miles ’04 Toyota Celica GT $17,995 Auto 23k ’03 Toyota Celica GT $16,995 Auto 42k ’03 Toyota Celica GT $19,488 Manual 19k ’02 Toyota Celica GT $12,922 Manual 61k ’02 Toyota Celica GTS $14,995 Manual 59k Prices will vary but I’ve found dealerships usually have worse deals than CarMax, there are exceptions of course, because CarMax deals in high volume and will take a smaller cut. For example, the CarsDirect listing of a ‘03 Toyota Celica GT Auto 42k was $16,995 compared to a CarMax ’03 Toyota Celica GT Auto 20k listed at $16,998. Granted, you can’t just look at transmission and mileage but the same price for 20k difference in mileage is significant. (Also recall that 42k in miles was put in probably under 3 years of service). Private Party Used Vehicles I’d suggest your local Craigslist or the local paper’s classified advertisements for good deals on vehicles. The selection will of course be limited but you can find some real gems. I’m afraid I don’t have much experience but you should get a general idea of the going rate. Finally, you can always rely on the numbers given to you by Kelley Blue Book or an Edmunds.com True Market Value but remember that they’re averages. (if you do a search for used vehicles on those sites, you’re typically rerouted to another site) Your mileage will vary. Summary: This quick research will inform you that in general, an ’03 Toyota Celica Automatic with average mileage will probably run you around $17,000 not including all the ancillaries (taxes, title, etc.). Armed with this information, you can start looking on Ebay to see if the risk is worth it. (I bought a ’03 Celica Automatic with 15k mileages for $16,000 a little over a year ago) Incidentally, there is a 2003 Toyota Celica GT Hatchback with 36k miles (Manual) listed with a Buy It Now of $16,900. In the next installment, I’ll discuss the importance of contacting the seller prior to bidding or buying the vehicle they’ve listed. The more I talk to people the more I realize how “surprising” it was that I’ve purchased two vehicles on Ebay and thought that the perfunctory discussion of my Ebay car buying experience wasn’t thorough enough. In the coming days and weeks, I’ll write in detail about the second of my two purchases which was a 2003 Toyota Celica in Nov/Dec of 2004. Right off the bat, I want to warn you that buying anything, especially high-dollar items like cars, on Ebay is risky. The feedback system is weaker for low volume items like cars because unless the seller is a representative of a dealer, you won’t find many sellers with 100+ feedback who just sells cars. The time frames for cars, shipment and such, is much longer and thus the 35-day fraud protection window is that much smaller. If you’re not buying local you can’t see the car (you rely on photos) and you depend on the Carfax report to be accurate which may or may not be the case. There are significant risks to buying a car on Ebay but the rewards may outweigh them. Currently Published Parts: Part 1:Vehicle Choice & Research – This part isn’t strictly Ebay related and should be a part of every car search, it gives you a good idea of how much you should be paying for the vehicle you want. Part 2:Dissecting An Auction Listing – There are distinct pieces of information and characteristics about an auction that you must look for. The auction listing should give you warning signs if there are any with a particular auction. Part 3:Feedback & Contacting The Seller – I don’t trust Ebay’s feedback system when it comes to auto auctions, before you bid you must talk to the seller and get a feel for what kind of person he or she is. I call it the pre-Ebay feedback system, use it. Part 4:Hidden Costs – I discuss the multitude of hidden costs that might not come to mind and will greatly increase the price of your vehicle, such as shipping. The Fall semester at Johns Hopkins’ MBA program just ended today and I’m going through the usual end-of-the-semester ritual of selling my gently used textbooks for dimes and quarters on the dollar. I never really sat down and investigated which service would give me the most bang for my buck until now and I still think I am making the right choices. While I was pretty sure what their commissions were and how each service operated, having sold items on Amazon, Ebay and Half.com before; I never looked in close detail at the numbers.

China auto industry gradually opening China has announced that it will reduce tariffs on imported automobiles from a current rate of 25% to 15% from July 1st. Additionally, tariffs on imports of auto parts will also be reduced to 6% from the current range of 8% to 25%. This has been lauded as a response to U.S. trade complaints. But in reality this decision has been some time in coming, and does not represent a trade concession so much as an incremental opening of China's economy and a step by China's government to encourage continued consumption growth. A staff member steps out from the Rolls Royce luxury car during the China Auto China in Beijing, Thursday, April 26, 2018.[Photo: AP/Andy Wong] In early April at the Boao Forum for Asia, President Xi Jinping stated that "This year we will significantly lower import tariffs on motor vehicles and reduce import tariffs on some other products," and that "We will import more products that are competitive and needed by our people." Regardless of demands by US negotiators to balance the trade deficit between China and the US, we are likely to see continued small steps by China to reduce restrictions on foreign imports as part of a longer-term strategy to drive domestic consumption. This is not because China is caving to US demands for a balanced trade relationship. The last few years have seen a massive shift in China's economy away from an overreliance on exports and investment towards a growth model that is based on consumer spending. Last year, consumption accounted for between 58% and 59% of China's GDP. In 2018 this number is on track to cross 60%. For China, this transition to consumption-based growth is critical due to the uncertainty of export growth, the challenge of switching from basic manufacturing to more complex value-added manufacturing and because investment in infrastructure projects is no longer resulting in sustained economic growth. As a result, we are seeing the government take steps to encourage consumer spending. Some of these steps will include reductions in tariffs that will ultimately benefit China's trade partners. The result of reduced tariffs within the auto sector will mean that foreign automakers like BMW and Tesla, which currently import a relatively higher proportion of the vehicles that they sell in China, will benefit. This means luxury models will become slightly more affordable for Chinese consumers. However, it is unlikely that this action will do much to change the plans of global automakers, or shift trade numbers between China and the US, as foreign auto makers have spent the last decade investing heavily in JV partnerships with Chinese firms to boost production in China. This is order to bypass tariffs. In fact, only around 4% of all vehicles sold in China are imported. Additionally, as Chinese demand for cars grows, many automakers have also moved their design and development operations to China to better meet the needs of Chinese consumers. An increasing number of new vehicles are also being developed specifically for production and sale in China. From the perspective of foreign automakers, lower tariffs will be seen as a step forward. However, the vast majority have already committed substantial resources to developing production capacity inside China, meaning a reduction of tariffs at this stage is unlikely to change automakers' long-term plans towards shifting production to China. This makes a coming tariff reduction for cars imported into China an easy win for president Xi Jinping. China is essentially doing what it had always planned to do. From the outside, this may make it look as though China is being conciliatory towards the US in trade negotiations, even if this small reduction in tariffs will not really change the status quo for American companies or American job creation. Meanwhile, president Trump and the rest of his negotiating team have failed to get on the same page in their negotiation strategies, failing to secure real long-term concessions that would balance trade or perhaps - more importantly - balance long-term competitiveness in key industries. In the end, Chinese consumers win, as they gain access to a wider range of choices and better prices. China wins because it takes a small step towards opening its markets, and car companies get to sell more high-margin products. However, the trade relationship between China and the US doesn't really change. China's approach to development has always been one of taking gradual steps towards a larger objective. This is something the Trump administration could learn from, rather than chasing quick wins that appear good in the short-term, but do little to help over the long-run. With Chinese automakers also taking the lead in the development of next generation EV vehicles, it will also be interesting to see what the future holds for China's domestic auto industry, as it should be poised to benefit from both the lowering of tariffs on auto parts, which may make their product cheaper, as well as lower pricing hurdles enough to convince consumers to pay premium prices as well.

INTRODUCTION {#sec1} ============ *L*egionella is an opportunistic pathogen that can cause legionellosis ([@B1]). Legionellosis refers to two distinct clinical syndromes: Legionnaires\' disease (LD) and Pontiac fever. The vast majority of the clinical isolates in Europe ([@B2][@B3][@B4]) and the United States ([@B5]) constitute Legionella pneumophila serogroup 1 (SG1). In Australia, New Zealand, and Thailand, Legionella longbeachae is an important cause of disease ([@B6][@B7][@B8]). Legionella bacteria are ubiquitous in natural matrices and manmade water systems ([@B9]). Some of these systems and matrices can act as sources of Legionella infection and include cooling towers ([@B10]), whirlpools ([@B11]), thermal springs ([@B12]), and wastewater treatment plants ([@B13]). Potting soil is also a source of L. longbeachae infection ([@B14], [@B15]). In source investigations, alongside epidemiological evidence, a genotypic match between environmental and clinical strains is needed to identify the source of infection. Tracking the source of infection for sporadic cases of LD has proven to be hard ([@B16]). Studies in the Netherlands, England, and Wales showed that common clinical L. pneumophila strains are only rarely found in the environment ([@B17], [@B18]). In these studies, L. pneumophila genotypes isolated from patients were compared with genotypes isolated from the environment. The environmental sources of Legionella in these studies comprised manmade water systems (domestic water distribution systems, cooling towers, and spa pools). L. pneumophila sequence type 47 (ST47) is the ST that is most frequently isolated from patients in the Netherlands (26.9% of clinical isolates available for typing) ([@B16]). Strikingly, since the start of the National Legionella Outbreak Detection Programme in the Netherlands in 2002, this ST was only found three times in the environment during outbreak investigations, which concerned outdoor whirlpools that were involved in two combined outbreaks of LD and Pontiac fever and one solitary case of LD. As all three whirlpools were located outside, it was hypothesized that the outdoor environment was an influence, and after further investigation, L. pneumophila ST47 was isolated from a soil sample from the garden of the most recent outbreak ([@B19]). It was suggested that the ST47 strain was transmitted from garden soil to the whirlpool by wind or by people entering the whirlpool with soil on their feet. It is possible that garden soil plays a role in Legionella infection. Although potting soil is a well-studied reservoir and known source of Legionella, not much is known about Legionella in garden soil. Hughes and Steele ([@B20]) showed the presence of Legionella in six garden soils that were mixed with composted materials. Furthermore, there is evidence that natural soil is a reservoir and source of Legionella. Wallis and Robinson ([@B21]) reported on a LD patient that had worked at a plant nursery in the week prior to illness. A L. pneumophila strain with an indistinguishable genotypic profile, determined by pulsed-field gel electrophoresis (PFGE), was isolated from a field in which the patient had spent time potting plants. In several other studies L. pneumophila strains have been isolated from natural soil ([@B22][@B23][@B25]). In two of these studies, some of the obtained sequence types (STs) had previously been detected in cases of LD ([@B22], [@B23]). The aim of the current study was to investigate garden soil as a reservoir of viable, clinically relevant Legionella bacteria. Garden soils were sampled throughout the year. Furthermore, we studied whether L. pneumophila could persist in soil over time by resampling Legionella-positive gardens after several months. An amoebal coculture method was applied to detect Legionella bacteria in the soil. Amoebal coculture has been proven successful for the isolation of Legionella bacteria in samples, such as soil, with a lot of background flora ([@B26], [@B27]). MATERIALS AND METHODS {#sec2} ===================== Sampling of garden soils. {#sec2-1} ------------------------- Garden soil samples were collected over a period of 1 year (February 2014 to January 2015). In order to obtain a large and diverse number of samples, colleagues from the National Institute for Public Health and the Environment and from the Regional Public Health Laboratory Kennemerland were asked to supply soil samples from their own gardens and/or the gardens of friends and family. Samples were to consist of soil from a soil bed at any place within their own garden, irrespective of type of garden, cultivation, or planting. Sterile spoons and jars were provided and were accompanied by an instruction form and short questionnaire. Participants were asked to sample the upper 2 cm of soil at one place in the garden. Upon arrival, the samples were stored at 4°C until analysis. If L. pneumophila was isolated from a garden, then the owners were asked to resample their garden after several months at the same location as the first sampling. Pretreatment of the samples. {#sec2-2} ---------------------------- Prior to analyses, 5 g of each soil sample was resuspended in 5 ml of sterile distilled water. These suspensions were vortexed for approximately 10 s and incubated at room temperature for 1 h. The soil suspensions were vortexed again just before amoebal coculture. Amoebal coculture method. {#sec2-3} ------------------------- The amoebal coculture method for the detection of Legionella was performed as described previously ([@B27]). Briefly, Acanthamoeba castellanii ATCC 30234 (American Type Culture Collection, Manassas, VA, USA) was grown in 75-cm^2^ culture flasks (Corning Inc., New York, NY, USA) with 15 ml of peptone-yeast extract-glucose (PYG) broth at 25°C. Prior to the infection, the PYG broth was removed, and the amoebae were resuspended in 15 ml Page\'s amoebal saline (PAS) ([@B28]). The amoebae suspension was centrifuged at 850 × *g* for 10 min, and the pellet was subsequently resuspended in 15 ml PAS. This washing step was repeated 2 times. Cells were seeded in a 12-well microplate (Corning) at a density of 5 × 10^5^ cells/ml of PAS. In each well, 1 ml of PAS with amoebae was inoculated with 100 μl of sample, and each sample was tested in triplicate (three wells). Thus, amoebae were inoculated with a total of 300 μl of the suspension. By testing 300 μl of the soil suspension, 0.3 g of the soil sample was tested. The theoretical detection limit was therefore 3.3 CFU/g soil. The amoebal plates were incubated at 32°C. As a negative control, one well with amoebae was not inoculated with a sample. After 3 days of incubation, 100 μl of each suspension was subcultured on a new plate with freshly seeded amoebae. After another 3 days of incubation at 32°C, 100 μl of each well was serially diluted 10-fold in PAS. Of the 10^4^-, 10^5^-, 10^6^-, 10^7^-, and 10^8^-fold dilutions, 100 μl was plated on buffered charcoal yeast extract (BCYE) plates (Oxoid Ltd., Hampshire, United Kingdom). The 10^5^- and 10^6^-fold dilutions were also cultured on glycine-vancomycin-polymyxin B-cycloheximide (GVPC) plates (Oxoid Ltd., Hampshire, United Kingdom). After 4 and 7 days of incubation at 37°C, the BCYE and GVPC plates were inspected for Legionella-like colonies with a stereo microscope (magnification, 40×; Olympus). Confirmation and typing of Legionella isolates. {#sec2-4} ----------------------------------------------- Suspected Legionella colonies were tested for their inability to grow on BCYE medium without cysteine (Oxoid Ltd., Hampshire, United Kingdom). Strains that were unable to grow on the medium without cysteine were further subtyped by polyclonal antisera (L. pneumophila SG1, SG2 to SG14, and Legionella spp.) coupled to latex beads (Legionella latex test; Oxoid Limited, Hampshire, England) and subsequently stored at −70°C. The strains were later identified by matrix-assisted laser desorption ionization--time of flight mass spectrometry (MALDI-TOF MS). Strains that could not be recultured prior to MALDI-TOF MS identification and that showed no clear agglutination response in the latex test were confirmed with a Legionella species-specific PCR targeting the 5S rRNA gene ([@B29]). L. pneumophila isolates were genotyped by the standard sequence-based typing (SBT) method of the European Working Group for Legionella Infections (EWGLI) using seven genes (*flaA*, *pilE*, *asd*, *mip*, *mompS*, *proA*, and *neuA*) ([@B30], [@B31]). The SBT profiles were generated using the high-throughput multilocus sequence typing (HiMLST) method that employs next-generation sequencing ([@B32]). L. pneumophila SG1 isolates were also subtyped by monoclonal antibody (MAb) subgrouping using the Dresden MAb panel ([@B33]). Statistical analysis. {#sec2-5} --------------------- Univariate and multivariate logistic regressions were performed as described by Hosmer and Lemeshow ([@B34]). Univariate analysis was used to identify potential associations between the positivity of gardens for Legionella and questionnaire and weather variables. The weather variables, i.e., precipitation and ambient temperature related to sampling days, were obtained from the Royal Netherlands Meteorological Institute (KNMI). For each garden, data were selected from the weather station closest to that garden. Continuous variables (garden age and weather characteristics) were categorized into classes of approximately equal size. Variables with a univariate *P* value of ≤0.25 (two-tailed likelihood ratio test) were selected for multivariate logistic regression. Prior to the multivariate analysis, the correlation coefficients of all variable combinations were determined, where a correlation coefficient of 0.25 or lower was considered noninterfering in the multivariate analysis. Subsequently, backward elimination was used until the remaining variables exhibited a significant association with a *P* value of \<0.05 (two-tailed likelihood-ratio test). The statistical analyses were performed using SAS software v.9.3 (SAS Institute, Cary, NC, USA). RESULTS {#sec3} ======= Isolation of Legionella spp. and L. pneumophila from garden soils. {#sec3-1} ------------------------------------------------------------------ Over 12 months, a total of 177 unique gardens were sampled. Per month, between 10 and 20 samples were submitted by our colleagues, with an average of 15 (see [Table 1](#T1){ref-type="table"}). In total, 22 of 177 samples (12%) were positive for Legionella spp. Out of these 22 positive samples, seven (32%) contained L. pneumophila (garden samples 1, 4, 5, 8, 13, 18, and 22; see [Table 2](#T2){ref-type="table"}). Both L. pneumophila SG1 and non-SG1 isolates were obtained, and 15 different STs were identified. In five of these samples, other Legionella species were also detected besides L. pneumophila, namely, L. longbeachae (4 samples), L. sainthelensi (2 samples), Legionella bozemanii (1 sample), and Legionella feeleii (1 sample). In the remaining 15 samples, several Legionella species were detected ([Table 2](#T2){ref-type="table"}), including L. sainthelensi (7 samples), L. feeleii (2 samples), L. bozemanii (1 sample), Legionella cincinnatiensis (1 sample), Legionella anisa (1 sample), and Legionella wadsworthii (1 sample). For 3 of the 15 samples, Legionella could not be further typed by MALDI-TOF MS because the bacteria could not be recultured. ###### Numbers of Legionella species-positive and L. pneumophila-positive garden soil samples per month[^*a*^](#T1F1){ref-type="table-fn"} Sampling yr Sampling mo Mean temp (°C) (range) Total precipitation (mm) No. of samples analyzed No. of Legionella species-positive samples (no. of L. pneumophila-positive samples) ------------- ------------- ------------------------ -------------------------- ------------------------- ------------------------------------------------------------------------------------- 2014 February 6.5 (3.9--10) 66.4 14 2 (1) March 8.4 (4.5--14.7) 25.7 16 1 (0) April 12.1 (7.2--17.1) 58.4 16 4 (2) May 13.2 (7.9--19.9) 102.0 15 0 (0) June 16.2 (13--21.6) 30.3 16 2 (1) July 19.8 (15--26.4) 137.1 20 3 (0) August 16.1 (12.4--20.5) 149.0 10 2 (1) September 15.9 (21.6--19.3) 20.5 16 3 (0) October 13.4 (9.9--17.3) 74.9 16 0 (0) November 8.2 (2.5--14.8) 46.8 15 2 (1) December 4.8 (−1.2--11.5) 99.5 11 2 (0) 2015 January 4.0 (−2.8--9.9) 115.7 12 1 (1) Total 177 22 (7) The mean ambient temperature (°C) per sampling month and the total precipitation (mm) per month are indicated ([@B35]). ###### Detected Legionella species in garden soil samples Sampling mo and yr Garden soil sample Legionella spp.[^*a*^](#T2F1){ref-type="table-fn"} L. pneumophila serogroup(s) (no. colonies analyzed) Sequence type(s) -------------------- -------------------- ---------------------------------------------------- ----------------------------------------------------- ------------------------------------------- February 2014 1 L. pneumophila 1 (9) 84, 477, 863 L. pneumophila 2--14 (2) 465, 710 L. longbeachae NA[^*b*^](#T2F2){ref-type="table-fn"} NA 2 L. sainthelensi NA NA March 2014 3 L. cincinnatiensis NA NA April 2014 4 L. pneumophila 1 (6) 84, 115, 477, 2028, 2032 L. pneumophila 2--14 (12) 863, X[^*c*^](#T2F3){ref-type="table-fn"} L. bozemanii NA NA L. feeleii NA NA 5 L. pneumophila 2--14 (8) 2025, 2026, X 6 L. wadsworthii NA NA 7 L. sainthelensi NA NA June 2014 8 L. pneumophila 1 (2) 84, 710 L. pneumophila 2--14 (1) 462 L. longbeachae NA NA 9 L. sainthelensi NA NA July 2014 10 L. feeleii NA NA 11 L. sainthelensi NA NA 12 Legionella spp.[^*d*^](#T2F4){ref-type="table-fn"} NA NA August 2014 13 L. pneumophila 2--14 (4) 710 L. longbeachae NA NA L. sainthelensi NA NA 14 L. sainthelensi NA NA September 2014 15 L. sainthelensi NA NA 16 Legionella spp.[^*d*^](#T2F4){ref-type="table-fn"} NA NA 17 Legionella spp.[^*d*^](#T2F4){ref-type="table-fn"} NA NA November 2014 18 L. pneumophila 1 (15) 84, 477, 1856, 2022, 2029 L. pneumophila 2--14 (3) 84, 115, 710 L. longbeachae NA NA L. sainthelensi NA NA 19 L. feeleii NA NA L. anisa NA NA December 2014 20 L. sainthelensi NA NA 21 L. bozemanii NA NA January 2015 22 L. pneumophila 1 (2) 84 Species were typed by MALDI-TOF MS. NA, not applicable. X, a sequence type could not be retrieved due to failure of amplification of one or more gene targets. Legionella spp. were not further typed because the bacteria could not be recultured. Positive samples were found throughout the year (see [Table 1](#T1){ref-type="table"}). The ambient mean daily temperatures on sampling days ranged from −1.9°C to 22.8°C ([@B35]). Positive garden soil samples were taken on days with ambient mean temperatures ranging between 0.7°C and 21.5°C. The precipitation sums of the 14 days preceding the sampling day varied between 0 and 113 mm for all sampling days and between 2 and 81 mm for the sampling days at which Legionella was detected. Resampling L. pneumophila-positive garden soils. {#sec3-2} ------------------------------------------------ Six of the seven L. pneumophila-positive gardens were resampled after several months, and four again tested positive for Legionella (gardens 1, 4, 13, and 18; see [Table 3](#T3){ref-type="table"}). One of the L. pneumophila-positive gardens was not resampled because this garden was found to be positive at the end of the project. For three of the four gardens, L. pneumophila was again isolated in the second sampling (gardens 1, 13, 18). Garden 1 was resampled four times throughout the year and was found to be positive for L. pneumophila on all occasions. Several L. pneumophila STs were detected, with ST477 present on all four occasions and ST710 and ST84 present on three out of four occasions. L. longbeachae was also isolated on all 4 samplings of garden 1. ###### Persistence of Legionella species in gardens 1, 4, 13, and 19, sampled on 2 to 4 occasions Garden Sampling parameters First sampling Second sampling Third sampling Fourth sampling -------- ------------------------ --------------------------------------------------------------------- --------------------------------------- -------------------- ------------------------ 1 Sampling date (mo, yr) February 2014 September 2014 November 2014 February 2015 Detected species L. pneumophila SG1 L. pneumophila SG1 L. pneumophila SG1 L. pneumophila SG1 L. pneumophila SG2--14 L. pneumophila SG2--14 L. longbeachae L. pneumophila SG2--14 L. longbeachae L. longbeachae L. longbeachae Sequence types 84, 465, 477, 710, 863 84, 477, 710 84, 115, 477 477, 710 4 Sampling date (mo, yr) April 2014 September 2014 Detected species L. pneumophila SG1 L. feeleii L. pneumophila SG2--14 L. sainthelensi L. bozemanii L. feeleii Sequence type(s) 84, 115, 477, 863, 2028, 2032, X[^*a*^](#T3F1){ref-type="table-fn"} NA[^*b*^](#T3F2){ref-type="table-fn"} 13 Sampling date (mo, yr) August 2014 January 2015 Detected species L. pneumophila SG2--14 L. pneumophila SG1 L. longbeachae L. pneumophila SG2--14 L. sainthelensi L. bozemanii L. dumoffi Sequence type(s) 710 84, 115, 710, 2080, X 18 Sampling date (mo, yr) November 2014 March 2015 Detected species L. pneumophila SG1 L. pneumophila SG1 L. pneumophila SG2--14 L. longbeachae L. longbeachae L. feeleii L. sainthelensi Sequence types 84, 115, 477, 710, 1856, 2022, 2029 2022, X X, a sequence type could not be retrieved due to failure of amplification of one or more gene targets. NA, not applicable. Clinical relevance of L. pneumophila isolates. {#sec3-3} ---------------------------------------------- A total of 70 L. pneumophila isolates were typed by SBT. For five isolates, a ST could not be retrieved due to the failure of amplification of one or more gene targets. The remaining 65 isolates were classified into 15 different STs (see [Table 4](#T4){ref-type="table"}). According to the EWGLI SBT database ([@B36]) (accessed on 17 February 2016), eight of these STs (ST84, ST115, ST462, ST465, ST477, ST710, ST863, and ST1856) were previously isolated from patients. Some STs were found regularly in garden soils, namely, ST84, ST115, ST477, and ST710. ST84 was detected most often; of the seven L. pneumophila-positive gardens, ST84 was found in all but one. Of the L. pneumophila SG1 isolates, 16 were MAb 3/1 positive and 10 were MAb 3/1 negative (see Table S1 in the supplemental material, which shows all of the typing data of the L. pneumophila garden isolates). ###### Isolated sequence types from garden soils and clinical relevance of the sequence types according to the EWGLI SBT database[^*a*^](#T4F1){ref-type="table-fn"} Sequence type No. of gardens[^*b*^](#T4F2){ref-type="table-fn"} No. of patients[^*c*^](#T4F3){ref-type="table-fn"} --------------- --------------------------------------------------- ---------------------------------------------------- 84 6 13 115 4 8 710 4 2 477 3 4 863 2 1 462 1 1 465 1 2 1856 1 1 2022 1 0 2025 1 0 2026 1 0 2028 1 0 2029 1 0 2032 1 0 2080 1 0 The database was accessed on 17 February 2016 ([@B36]). Number of gardens from which the sequence type was isolated. Number of patients from which the sequence type was isolated according to the EWGLI SBT database. A value of 0 indicates that no clinical strains were reported. Univariate and multivariate analyses. {#sec3-4} ------------------------------------- The questionnaire covered the following variables: characteristics of the garden (type, size, location, age), use of potting soil/compost, origin of used potting soil/compost, use of other fertilizers (e.g., manure, artificial fertilizer), use of pesticides/herbicides, use of tap water for watering, presence of an outdoor whirlpool, season of sampling, and frequency of gardening in gardening season (see Table S2 in the supplemental material). The owners of all 177 sampled gardens filled in the questionnaire. In addition, eight weather variables were analyzed, namely, precipitation sum on the sampling day, precipitation sum in the 14 days preceding the sampling day, ambient temperature (minimum, mean, maximum) on the sampling day, and ambient temperature (minimum, mean, maximum) in the 14 days preceding the sampling day. Six of the examined variables reached a *P* value of ≤0.25 in the univariate logistic regression and were analyzed in the multivariate analysis, i.e., garden size, garden age, use of potting soil/compost, use of other fertilizers, precipitation sum on the sampling day, and mean temperature in the 14 days preceding the sampling day (see Table S2 in the supplemental material). One variable (surrounding area) had a prevalence of zero in two out of three categories and could not be analyzed in the multivariate model. Correlations between all variables appeared to be low (i.e., *r* ≤ 0.25). Multivariate logistic regression analysis identified none of the variables to be statistically significantly associated with the presence of Legionella in the gardens. DISCUSSION {#sec4} ========== Viable Legionella strains, including L. pneumophila, were isolated by amoebal coculture from 12% of 177 investigated garden soils in the Netherlands, indicating that garden soil is a reservoir of Legionella bacteria. The majority of the isolated L. pneumophila SG1 strains were found to be MAb 3/1 positive. MAb 3/1 positivity is considered an indication of virulence since this monoclonal antibody recognizes a virulence-associated epitope ([@B33]). Eight STs found in garden soils were clinically relevant according to the EWGLI SBT database ([@B36]). However, the STs that are most often detected in patients in the Netherlands (ST1, ST47, and ST62) ([@B16]) were not detected in garden soils. Of the 15 detected STs in this study, three were also found in patients in the Netherlands (ST84, ST115, and ST477). However, these STs are relatively uncommon; they were found in three patients, four patients, and one patient, respectively (since 2005). Strikingly however, these three clinically relevant STs belonged to the most frequently isolated STs in garden samples (see [Table 4](#T4){ref-type="table"}). It is possible that some conditions in garden soils are favorable for the growth of these clinically relevant STs. So, although garden soil is probably not the source of most infections with L. pneumophila in the Netherlands, it should be taken into account that it may play a role in Legionella transmission to humans, which warrants further investigation. L. sainthelensi was found most often in garden soil; it was isolated from 10 of the 22 positive gardens (see [Tables 2](#T2){ref-type="table"} and [3](#T3){ref-type="table"}). L. sainthelensi can be infectious to humans ([@B37], [@B38]) and was first isolated in the United States from fresh water ([@B39]). L. pneumophila was the second most isolated species, and L. longbeachae was the third. Strikingly, L. longbeachae was always detected in combination with L. pneumophila. Legionella bacteria were detected in garden soils throughout the year. No association was found between Legionella-positive gardens and temperature or precipitation. Evidence was found that L. pneumophila can persist in garden soil. For three gardens, L. pneumophila was detected again after 4 to 7 months, and for one garden, L. pneumophila was found on four sampling occasions over a period of 1 year. Interestingly, Legionella was absent from garden soils in rural areas, whereas 14.6% of garden samples in urban areas were positive for Legionella (see Table S2 in the supplemental material, variable "surrounding area"). However, since only 9 gardens in rural areas were investigated, no firm conclusion can be drawn about the differences in Legionella presence in rural versus urban areas. Legionella was also absent from gardens in mixed areas (gardens located at the edge of a village, adjacent to a rural area). It is possible that Legionella in garden soil originates from compost or potting soil. One Australian study, by Hughes and Steele ([@B20]), showed the presence of Legionella in six garden soils, of which five contained L. pneumophila. These soils were mixed with composted materials that were found to contain Legionella. Compost ([@B20], [@B40], [@B41]) and potting soil ([@B42][@B43][@B44]) are reservoirs of Legionella, and it is possible that Legionella is introduced into garden soil by the use of compost or potting soil in the garden. To investigate this possibility, genotypes isolated from garden soils can be compared to genotypes isolated from composts and potting soils. In this study, compost or potting soil samples were provided by the garden owners when available, but they were only analyzed when the compost/potting soil was ever applied to the area where the soil sample was taken and when the soil sample was found to be positive for L. pneumophila. For the seven L. pneumophila-positive gardens, only one potting soil sample was analyzed but not found to be positive. Furthermore, no association was found between Legionella-positive gardens and the reported use of potting soil or compost. We found only one publication that used SBT to type two L. pneumophila strains that were isolated from composted materials ([@B40]). Interestingly, these were ST84, the most frequently isolated ST in this study. In contrast to the limited number of garden soil studies, several studies have investigated natural soil as a reservoir of L. pneumophila ([@B22][@B23][@B24], [@B27]). No ST similarities were observed between the reported STs in these studies and the current study. A limitation of the use of an amoebal coculture method for the isolation of Legionella is that selectivity for certain Legionella strains might be introduced. It is possible that certain STs replicate better in A. castellanii than other STs, resulting in an outcome that is not representative of the natural situation. However, selectivity was not shown in a previous study in which a batch of 23 different L. pneumophila strains was tested ([@B26]). The batch was comprised of different monoclonal subtypes, both positive and negative for MAb 3/1, and 16 different STs. These strains, including the clinically relevant ST1 and ST47, were all shown to replicate similarly in amoebal coculture with A. castellanii. Another drawback of the amoebal coculture method is its limited sensitivity since only a small amount of soil is investigated per sample. However, for soil samples, amoebal coculture seems to be the best method in order to obtain isolates. In previous studies, we have shown that for samples containing many other bacteria, like soil, amoebal coculture has a higher positivity rate than culture techniques that are based solely on agar plates ([@B26], [@B27]). Another limitation of amoebal coculture is that only a restricted number of samples can be investigated since it is a rather laborious method. Therefore, only one sample per garden was analyzed, while multiple samples would probably have influenced the positivity rate. A more thorough investigation may have been done using molecular techniques, like PCR. However, molecular methods do not render isolates, which are necessary for typing purposes. Due to these limitations, including low sensitivity and the restricted number of samples, an accurate estimate of the true prevalence of Legionella in garden soils cannot be made. In order to study the prevalence, another sampling strategy and other analysis methods should be chosen. The significance of the presence of Legionella in garden soils to public health is not clear. No patients are known to have been infected by Legionella originating from garden soil. In several older publications, natural soil was considered to be a possible source of infection ([@B25], [@B45][@B46][@B49]) because excavation sites were believed to be associated with LD cases ([@B50], [@B51]). However, these studies provided no or little evidence for soil as a source of Legionella ([@B9]). One more recent study provided evidence for infection caused by L. pneumophila originating from natural soil ([@B21]). The infective strain was isolated from a field where the LD case had spent several days potting plants. In conclusion, garden soil is a reservoir of L. pneumophila and Legionella spp. and may be an alternative source of Legionella that is not considered in source investigations, especially for some soil-specific strains like ST84, ST115, and ST477. Whether the presence of Legionella in garden soil has an impact on public health is not clear; no cases are linked to Legionella in garden soil, and none of the most prevalent Dutch clinical strains were identified in garden soil in this study. A case-control study may reveal whether gardening or working with garden soil is a risk factor for contracting LD, warranting targeted interventions. Prevalence should be studied in more detail, and Legionella concentrations in garden soil should be determined. Furthermore, it should be investigated how soil and other environmental conditions, i.e., weather characteristics, influence viability, growth, and virulence of Legionella in garden soil. Furthermore, it is important to investigate if and how Legionella bacteria can aerosolize from soil and which gardening activities might pose a risk. Supplementary Material ====================== ###### Supplemental material Supplemental material for this article may be found at <http://dx.doi.org/10.1128/AEM.00595-16>. We sincerely thank all of our colleagues and their friends and family for providing garden soil samples. We also thank P. Visser for technical assistance with the soil analyses. We have no actual or potential competing interests regarding this study. [^1]: **Citation** van Heijnsbergen E, van Deursen A, Bouwknegt M, Bruin JP, de Roda Husman AM, Schalk JAC. 2016. Presence and persistence of viable, clinically relevant Legionella pneumophila bacteria in garden soil in the Netherlands. Appl Environ Microbiol 82:5125--5131. doi:[10.1128/AEM.00595-16](http://dx.doi.org/10.1128/AEM.00595-16).

Procedure: Reconstitute the target protein (0.1-1 mg) in 10 ul of 6 M Guanidine- HCl, 25 mM Ammonium Bicarbonate, pH 8.0 (The amount of protein depends on how complex your protein mixture is, you need to obtain a final concentration of >10 fmol/ l of each protein in the protein mixture after you finish the final step of the digestion).

Q: Why does using a raw form tag rather than Using(Html.BeginForm) break client-side validation I found out that after replacing @using (Html.BeginForm) with the regular <form> tags broke the client-side validation. When I viewed the source, the html output is the same, except for the re-ordering of the tags. Why would this prevent the client-side validation from working? A: Because when you call Html.BeginForm it sets a form context variable which has the effect that helpers such as TextBoxFor, CheckBoxFor, ... emit HTML5 data-* attributes when generating their corresponding input fields. Try for example using one of those helpers without a form and you will see that the input doesn't have any HTML5 data-* attributes which are used by client side validation. You could cheat by manually creating the form context: @{ViewContext.FormContext = new FormContext();} <form ....> @Html.EditorFor(x => x.Foo) <button type="submit">OK</button> </form> But hey, why would you need to manually hardcode a form instead of using the corresponding helpers which will take care of properly generating urls, methods, encoding, ...?

Blackhawks killing it short-handed A past weakness strong so far with just 1 power-play goal allowed in 23 chances January 28, 2013|By Chris Kuc, Chicago Tribune reporter The parade to the penalty box began midway through the second period and didn't end until shortly before the intermission. It was during that span in Sunday night's 2-1 overtime victory over the Red Wings that Blackhawks penalty killers muffled four consecutive Red Wings power plays — including 43 seconds of a two-man advantage for Detroit — in what was just the latest example of how times have changed for the Hawks while short-handed. Last season the Hawks killed an anemic 78.1 percent of penalties, bad enough for 27th in the NHL. After six games — all victories — to start 2013, the Hawks have yielded one power-play goal in 23 times short-handed. That 95.6 percent success rate was good enough for second in the league heading into Monday night's games. So what exactly has changed from last season? Some positioning, some mindsets and some personnel. None are working as well together killing penalties as Michael Frolik and Marcus Kruger. Between them, they have one goal and two assists but can be considered two of the more valuable players for the Hawks. Among the team's forwards, Kruger and Frolik rank 1-2 in ice time while short-handed at 3:17 and 3:10, respectively, per game. "We just try to outwork (opponents)," Kruger said. "We take pride in doing the preparation before the games on everything about their power play. That's an ongoing process all year so we have to keep building on that." The Hawks have taken steps to attack puck-carriers in bursts to foil opponents' power plays, and they change units quickly to maximize energy. "We didn't have that much time to practice it, but we try to stick to the plans: Clear the puck 200 feet and make quick changes," Frolik said. "We want to play high-energy PK and put the pressure on (opponents) when we have a chance. So far, it's working." Defensively, Niklas Hjalmarsson (3:22) and Johnny Oduya (3:20) lead the way while short-handed. The major minutes between those four players have helped the Hawks' top players who also see time killing penalties — Jonathan Toews, Patrick Sharp, Marian Hossa and Duncan Keith, among others — conserve energy for five-on-five play "It seems like we have a little bit more of an active PK instead of (being) predictable and our top guys aren't out there logging hard minutes," Quenneville said. Good penalty killing starts and stops with goaltending and starter Corey Crawford has been more than up to the task in the early going. Crawford has not allowed more than two goals in any of his five starts this season. He also has the best view — from the crease — of what is working well on the kill. "We're able to force teams to the outside," Crawford said. "It seems like every time a team tries something through the middle, we're able to cut it off or get a stick on it."

New Wishlist Description Children under 2 years old or children on breastfeeding: One 40mg tab per day One pack of Potassium Iodine lasts for 10 days Expiry: 06.2020 Individually sealed Recommneded stockpile: 30 days per each person POTASSIUM IODINE 40-125MG (Nuke Pills, iOSAT, SSKI, ThyroSafe, ThyroShield) is used for protection of the thyroid gland from the harmful effects of the radioactive iodine from nuclear disasters such as Fukushima and other potential nuclear disasters that may happen in the future. Radioactive iodine is one of the major contaminant that is released in case of nuclear disasters. When radioactive partciles are inhaled, iodine accumulates in the thyroid gland increasing the development of thyroid cancer. Potassium iodide, if taken in an appropriate dosage and in a timely manner, can completely block the accumulation of radioactive iodine in the thyroid gland and prevent the risk of thyroid cancer. USES Radioactive Protection of the Thyroid Build Up Prevention of Radioactive Iodine Emergency Use During Nuclear Fallout GUARANTEE & EXPIRY DATE100% Original from the Russian Government Institute PharmZaschitaAll packs are air tight sealed and expire up to 06.2020. DESCRIPTIONPotassium Iodide is a metal halide composed of potassium and iodide with thyroid protecting and expectorant properties. Potassium iodide can block absorption of radioactive iodine by the thyroid gland through flooding the thyroid with non-radioactive iodine and preventing intake of radioactive molecules, thereby protecting the thyroid from cancer causing radiation. In addition, this agent acts as an expectorant by increasing secretion of respiratory fluids resulting in decreased mucus viscosity. PACKAGING & DOSAGEAdults and children over 2 years old: One 125mg tab per dayChildren under 2 years old or children on breastfeeding: One 40mg tab per dayMost effective 12 hours before imminent nuclear fallout or within 15 minutes of inhaling radioactive particles.Keep the tablets in a ready location or carry with you when going outside of home. SIDE EFFECTSLong term use of high doses of Potassium Iodine may lead to development of iodine-induced hyperthyroidism (especially in elderly).On rare ocassions allergic reactions may occur. The MHRA and FDA has not evaluated or endorsed this product. Please consult your physician prior to using this or any other nutritional supplements or medications. STORAGE Storage at no higher than 25C degrees. Keep away from direct sunlight. Keep locked and away from children. This is a sample pack for Noopept. NOOPEPT is a nootropic with neuroprotective properties. It improves memory and learning ability by influencing all the phases of the process: initial processing of...

Making an appearance And there he was outside of the building when fans rushed over wonder if he jumped ship. They clamoured and screamed at his presance. " Oh my God when did you join this company?" Wyld in his typical gear of a black dress shirt, baggy jeans from his Wyld-Wear line complete with work boots wallet chain and rollex watch grinned when he took the pen and papers. Singing them he scribbled his name and they all looked on with glee, " No I have't signed on just here to look at the ones trying to keep up with the competition. I'm looknig forward to a one day meeting with that fat ass Juggernaut." A fan of Juggies stood up to Wuld and spouted, " He's not fat. He'll crush you where you..." " He'll be stopped like all of them. I'm not gonna talk crap about these folks here. They're all talented and top teir contenders. I wish I joined this company long before I ended up in DWF because I'd be facing off with these guys and doing what I do best." They clamoured at seeing THE best DWF offered today. Autographs being signed Wyld smiled and looked over his shoulder seeing more fans rush over. " Oh my God I can't believe you ditched that shitty elitist fed and came here!" " I'm still with them. I came by to simply scout competition." He signed on and enjoyed the attention. But then the halls of GTWF never expected to see a face like Wyld's pop up here and he savored every moment. The Alpha Dog made his presance known and he was about to do more because he was looking for someone.

Q: How do I perform an atomic operation using the Datomic database? TL;DR I want the function: "update Y ONLY IF Y=10", otherwise it fails. Example: imagine the timeline being T1, T2 and T3. At time T1, the entity X contains the attribute Y=10, at time T2 the attribute is Y=14. My aim is to apply a complex operation in Y (assume that this operation is the sum of 1). I read the value of Y at T1, which is 10 and place this value in a queue to be processed. At T3, when the complex operation is completed and the result is 11, I will update the attribute Y. If I simply update the attribute, the value Y=14 that was at T2, it will be mistakenly discarded. However, at T3, upon updating, I want to be sure that the final value is Y=10, otherwise I have to read Y=14 at T2 for reprocessing. I know about Database Functions to make atomic read-modify-update processing, but this approach is not good if the operation is complex and need to be done distributed (after put in a queue). What I want is something equivalent to Conditional Writes in DynamoDB. A: With regard to Felipe's comment "a transaction function that insert only if or throw exception", can you not just use the built-in one see :db.fn/cas?

Q: Select row with ALL non-zero columns only in R I am relatively new to R and want to get all the rows that have ALL columns with non-zero values so basically a row that has even a single column with zero or NA value; I dont want that row at all. Here is how my dataframe looks like; Any help is really appreciated. EDITED : After executing dput(head(mydata,20)); it looks something like below structure(list(Q3_1 = c("1", "1", "1", "5", "6", "3", "2", "", "", "", "", "", "", "", ""), Q6_1 = c("2", "2", "1", "2", "6", "3", "2", "", "", "", "", "", "", "", ""), Q12_1 = c("1", "1", "8", "7", "1", "4", "7", "", "", "", "", "", "", "", ""), Q15_1 = c("1", "1", "4", "5", "1", "9", "8", "", "", "", "", "", "", "", ""), Q18_1 = c("2", "2", "1", "6", "4", "9", "3", "", "", "6", "", "", "", "", ""), Q21_1 = c("1", "1", "2", "3", "3", "4", "8", "", "", "", "", "", "", "", ""), Q24_1 = c("1", "1", "1", "2", "2", "8", "8", "", "", "", "", "", "", "", ""), Q27_1 = c("1", "2", "3", "4", "5", "2", "9", "", "", "", "", "", "", "", ""), Q30_1 = c("2", "2", "2", "2", "2", "2", "2", "", "", "", "", "", "", "", ""), Q36_1 = c("6", "2", "2", "2", "2", "6", "6", "", "", "4", "", "", "", "9", "7" ), Q39_1 = c("10", "2", "2", "2", "2", "2", "2", "4", "2", "", "", "3", "7", "10", "9"), Q42_1 = c("1", "2", "3", "4", "5", "6", "7", "9", "5", "4", "", "", "7", "", "5"), Q45_1 = c("1", "2", "2", "2", "2", "2", "2", "", "", "5", "", "", "8", "4", ""), Q48_1 = c("7", "2", "3", "4", "5", "6", "8", "", "6", "", "5", "", "1", "8", ""), Q51_1 = c("1", "2", "3", "8", "3", "4", "4", "9", "8", "6", "4", "8", "1", "7", "7"), Q54_1 = c("1", "2", "3", "7", "4", "4", "4", "1", "4", "6", "", "1", "", "", "2"), Q60_1 = c("1", "2", "3", "3", "3", "3", "3", "3", "6", "", "", "10", "", "", "9"), Q63_1 = c("1", "1", "1", "1", "1", "1", "1", "1", "1", "", "", "1", "5", "", ""), Q66_1 = c("4", "4", "4", "7", "6", "4", "4", "7", "3", "", "7", "", "4", "", "1"), Q69_1 = c("3", "3", "5", "4", "7", "4", "5", "5", "5", "", "", "", "7", "", "1"), Q72_1 = c("3", "4", "5", "4", "5", "6", "6", "3", "8", "", "8", "1", "", "7", "6"), Q74_1 = c("4", "5", "5", "5", "2", "4", "5", "4", "4", "5", "4", "3", "3", "5", "2"), Q75_1 = c("5", "2", "3", "5", "4", "3", "4", "4", "3", "4", "1", "2", "2", "4", "5" ), Q76_1 = c("1", "2", "1", "4", "5", "2", "5", "1", "2", "5", "5", "2", "2", "2", "5")), row.names = c(5L, 7L, 9L, 11L, 12L, 16L, 17L, 18L, 21L, 24L, 26L, 32L, 34L, 35L, 40L), class = "data.frame") A: I would first change your blank "" values to NA missing values, then the functions na.omit or complete.cases can be used to do what you want: mydata[mydata == ""] <- NA # then either of these should work result1 <- na.omit(mydata) result2 <- mydata[complete.cases(mydata), ] You may want to address the "" earlier in your workstream - the function you use to read the data into R (maybe read.csv() or similar) probably has a way to specify that blanks should be treated as missing values. For read.csv, you would use na.strings = "". Right now, all your columns are character class, and you probably want to change them to numeric after getting rid of the blanks. If you use the na.strings = "", your columns will automatically be loaded as numeric columns.

Q: Hide/Show field base on drop down in PHP while loop with JQuery I have data array in PHP foreach loop, And every set of data (tr) I have a dropdown field which I named it brand_new[], this drop down field will show/hide my account_no field which is temporarily hidden because of style='display:none', When the user selects brand_new the account_no field will hide, when user selects repo the account_no will show. This is what I've done so far. PHP foreach ($result as $r) { echo "<tr> <td align='center'>$r->model</td> <td align='center'>$r->color</td> <td align='center'>$r->engine_no</td> <td align='center'>$r->chassis_no</td> <td align='center'> <select class='new' name='brand_new[]'> <option>Choose</option> <option value='brand_new'>Brand New</option> <option value='repo'>Repo</option> </select> </td> <td> <div id='repo' class='search_item' style='display:none'> <input type='text' name='account_no' required> </div> </td> </tr> "; } Javascript <script type="text/javascript"> $(document).ready(function() { // Search by dates function var search = $('.new') search.change(function() { $('.search_item').hide() $('#' + $(this).val()).show() }); }); </script> View page source <table class="table"> <thead> <tr> <th class="text-center"><h4>Model</h4></th> <th class="text-center"><h4>Color</h4></th> <th class="text-center"><h4>Engine Number</h4></th> <th class="text-center"><h4>Chassis Number</h4></th> <th class="text-center"><h4>Brand New</h4></th> <th class="text-center"><h4>Account No. (repo)</h4></th> </tr> </thead> <tbody> <tr> <td align='center'>BARAKO 2</td> <td align='center'>RED</td> <td align='center'>100</td> <td align='center'>100</td> <td align='center'> <select class='new' name='brand_new[]'> <option>Choose</option> <option value='brand_new'>Brand New</option> <option value='repo'>Repo</option> </select> </td> <td> <div id='repo' class='search_item' id='search_item' style='display:none'> <input type='text' name='account_no' required></div> </td> </tr> <tr> <td align='center'>BARAKO 2</td> <td align='center'>RED</td> <td align='center'>200</td> <td align='center'>200</td> <td align='center'> <select class='new' name='brand_new[]'> <option>Choose</option> <option value='brand_new'>Brand New</option> <option value='repo'>Repo</option> </select> </td> <td> <div id='repo' class='search_item' id='search_item' style='display:none'> <input type='text' name='account_no' required></div> </td> </tr> <tr> <td align='center'>BARAKO 2</td> <td align='center'>RED</td> <td align='center'>300</td> <td align='center'>300</td> <td align='center'> <select class='new' name='brand_new[]'> <option>Choose</option> <option value='brand_new'>Brand New</option> <option value='repo'>Repo</option> </select> </td> <td> <div id='repo' class='search_item' id='search_item' style='display:none'> <input type='text' name='account_no' required> </div> </td> </tr> </tbody> </table> My Problem is only the first row of data loop are working, and the rest are not. A: Two things about ids: An element can only have one id An id can only be used once on a page So this is invalid: <div id='repo' class='search_item' id='search_item' style='display:none'> All you have to use is a class (and FYI its better to add that display:none to a stylesheet rather than apply it inline but thats up tok you): <div class='search_item' style='display:none'> Once your HTML is set up better you can use the following JS: // Search by dates function var search = $('.new') search.change(function() { var selected = $(this).val(); if(selected == "repo"){ $(this).closest("tr").find(".search_item").show(); }else{ $(this).closest("tr").find(".search_item").hide(); } }); You need to navigate to the right .search_item of $(this) which is the selected dropdown. To do this you can simply do: $(this).closest("tr").find(".search_item").show(); You could also do: $(this).parent().next().find(".search_item").show(); But if you were to ever add in another td in between the two or changed the markup it would throw off your script. By traversing backwards to the "closest" tr and then descending down to .search_item you can assure that this code will work regardless of extra markup being added. FIDDLE

Q: Prevent Page Expanding Frame in Windows 8 XAML App within ScrollView I'm creating a basic application to test some functionality in a XAML based Windows 8 app. I have created the following structure to simplify my example but in the real app it'll be more complex: <Page x:Name="pageRoot" x:Class="ScrollingTest.Xaml.MainPage" DataContext="{Binding DefaultViewModel, RelativeSource={RelativeSource Self}}" xmlns="http://schemas.microsoft.com/winfx/2006/xaml/presentation" xmlns:x="http://schemas.microsoft.com/winfx/2006/xaml" xmlns:local="using:ScrollingTest.Xaml" xmlns:common="using:ScrollingTest.Xaml.Common" xmlns:d="http://schemas.microsoft.com/expression/blend/2008" xmlns:mc="http://schemas.openxmlformats.org/markup-compatibility/2006" mc:Ignorable="d"> <Grid Background="{ThemeResource ApplicationPageBackgroundThemeBrush}"> <ScrollViewer HorizontalScrollMode="Auto" HorizontalScrollBarVisibility="Auto" VerticalScrollMode="Disabled" VerticalScrollBarVisibility="Hidden" Margin="0,0,0,10" VerticalContentAlignment="Stretch" BorderBrush="#FF0BC8FF" BorderThickness="1" Grid.Row="1" > <Frame Content="Frame" Name="theFrame" Margin="100" Width="3000" BorderBrush="Red" BorderThickness="1" ScrollViewer.VerticalScrollMode="Enabled" ScrollViewer.VerticalScrollBarVisibility="Visible" /> </ScrollViewer> </Grid> </Page> The page, which is loaded into the Frame is of variable height (it contains a listview). The issue is that as the height of the sub-page increases, so does the height of the ScrollViewer, meaning that the content is forced off the bottom of the screen. What I'd want to achieve is horizontal scrolling for the parent but then use vertical scrolling on the sub-page. In the real application there will be many sub-pages, probably within a grid. It seems that putting the frame inside a ScrollViewer breaks the frame's internal scrolling capabilities. If anyone could let me know of either a better way to achieve my end result or of some property I need to change then I'd be very grateful. A: I ended up using the solution from the following comment: XAML: Limiting size of control nested in ScrollViewer (to scroll nested within the ScrollViewer) Height="{Binding ElementName=scrollViewer, Path=ActualHeight}" Not really what I wanted as this doesn't cope automatically when changing the orientation but it will have to do. The other option is to handle the SizeChanged event of the page and update the height from the event handler (theFrame.Height = scrollViewer.ActualHeight). That way it copes with changing the orientation as well.

1. Field of the Invention The present invention relates to fluidized catalytic cracking of hydrocarbon charge stocks. More particularly, it relates to fluidized catalytic cracking wherein a substantial portion of the hydrocarbon charge is converted to hydrogen and wherein said hydrogen is recovered substantially free of contaminant gases, particularly nitrogen. 2. Discussion of Prior Art Fluidized catalytic cracking of hydrocarbon liquids ranging from naphtha through residuum stocks is well known. In such processes, a portion of the hydrocarbon charge is converted to hydrogen and low molecular weight hydrocarbons such as methane, ethylene and ethane. Although the weight percent of charge converted to hydrogen is small (in the range of 0.5-2 wt. percent), the volume of hydrogen is considerable, considering the low molecular weight of hydrogen and the total weight of hydrocarbon charge to a fluidized catalytic cracking unit. That is, the hydrogen yield from a fluidized catalytic cracking unit charging 100,000 B/D hydrocarbon is in the range of 1.5 to 10 million SCF/D hydrogen. This hydrogen is, however, contaminated with other light gases, such as C.sub.1 -C.sub.2 hydrocarbons, nitrogen, carbon monoxide, carbon dioxide and hydrogen sulfide. Also, the hydrogen is recovered at a relatively low pressure. Heretofore recovery of the hydrogen as a product has not been economical, but with increased energy costs, such hydrogen recovery is more attractive. In copending application Ser. No. 918,989, filed June 26, 1978 (now U.S. Pat. No. 4,206,038), a method for stripping hot, regenerated catalyst with an acid gas, such as CO.sub.2 and/or H.sub.2 S is disclosed wherein nitrogen and carbon monoxide contaminants are prevented from entering a fluidized catalytic cracking reaction zone, such that subsequently, hydrogen product may be recovered free of such non-condensible gases. Consequently, hydrogen of commercial purity may be recovered from a fluidized catalytic cracking unit. Cracking hydrocarbon charge stocks in Fluidized Catalytic Cracking units in the presence of cracking catalysts contaminated with metals such as iron, nickel and vanadium for production of hydrogen-rich gas streams is known. For example, see U.S. Pat. Nos. 2,998,380 and 3,050,457. In such processes, low quality charge stocks such as residuum containing compounds of nickel, iron, and vanadium are cracked at low or high severities for producing gas streams rich in hydrogen and for producing cycle oils free of metal contaminants. In many fluidized catalytic cracking processes, particularly those charging low quality charge stocks, such as metals contaminated residuum, increased hydrogen yields are desirable. Particularly in situations where such hydrogen may be employed in other refining processes.

A housing development and soccer stadium (right) would be built alongside the Gentrification Death Star (left) in a new proposal. Rafael Viñoly Architects, via New York YIMBY If you’re still wrapping your brain around the math behind the New York Islanders’ “give us cheap state land and we’ll build an arena complex on it” proposal, get ready for the Bronx version. According to information leaked to the developer-fetish blog New York YIMBY, Stephen Ross’s Related Companies and Keith “Piano District” Rubinstein’s Somerset Partners are hoping to team up with the New York City Football Club to build a mixed-rate housing development and soccer stadium on the South Bronx waterfront — while proposing a discounted land deal that, as in the Islanders case, could cost New York taxpayers hundreds of millions of dollars in lost rent and property taxes. An Empire State Development spokesperson told the Voice that the agency hasn’t even issued an official Request for Proposals (RFP) for the site, let alone approve any — it’s still sorting through the initial expressions of interest it got from developers — so this is a very early salvo on the part of NYCFC and its partners. But this initial proposal is worth watching if only because it follows the Islanders’ template of using private money for construction costs while asking for state aid in the form of cheap land. The proposal, dubbed Harlem River Yards because that’s just how the megadevelopment name generator works now, would take a 12.8-acre defunct rail yard adjacent to the Willis Avenue Bridge and couple it with adjacent waterfront property to create the latest South Bronx waterfront redevelopment plan: a 22-story apartment tower featuring 1,279 market-rate units and 550 “affordable and workforce” apartments, plus a 26,000-seat stadium for the MLS team, which since its debut three years ago has been stuck playing in less-than-ideal conditions at Yankee Stadium. The site, which was acquired by the state Department of Transportation from the Penn Central rail system in 1982, took its first steps toward going on the market in November 2016, when the ESD issued a Request for Expressions of Interest — what the state does before sending out an RFP — to “maximize the economic benefit of the site while preserving the intermodal footprint of the site” — translated, that’s “build stuff on it while still letting trains go through.” Today’s YIMBY story is the first news since then regarding any potential bids. Related (owned by Miami Dolphins owner and noted giant bug exoskeleton enthusiast Stephen Ross), Somerset, and NYCFC didn’t reply to Voice queries by publication time, so for the moment we’re left to decipher the actual plan from the tidbits sprinkled into the YIMBY story. Two of these items are potentially worrisome for anyone concerned about their tax dollars going toward private sports projects: Aside from any massive state tax breaks, Mrs. Lincoln, there’s a fair bit to like about the plan: The site is just a short walk from the 3rd Avenue-138th Street 6 train stop location, and 30 percent affordable units is somewhat better than usual, assuming “affordable” is actually affordable for South Bronx residents. But there’s just as much to be concerned about — cramming in even more luxury housing along the waterfront could accelerate already-soaring gentrification in Port Morris, and the stadium itself would seem to be a tight fit on a site restricted by East 132nd Street on one side and the Harlem River on the other. So while it’s still early in the process — ESD couldn’t even provide a timetable for issuing an RFP on the site, let alone for making a final decision — this project is definitely well worth keeping an eye on.

Clinical results of the intra cytoplasmic sperm injection (ICSI) at Baqai Institute of Reproduction and Developmental Sciences (BIRDS). To analyse the results of the new revolutionary technique of Intra Cytoplasmic Sperm Injection (ICSI) for male infertility. Furthermore, to find out the ways of reducing cost of the expensive methods of Assisted Reproductive Techniques. This is an analytical study of results of 71 patients (86 Cycles) of ICSI performed in first year of its launching in Baqai Institute of Reproduction and Developmental Sciences (BIRDS) from May 1997 to April 1998. Men with semen reports of parameters less than WHO criteria were treated including Azoospermic men. After ICSI procedure a fertilisation rate of 58.9% was achieved in 86 cycles. A total of 17 clinical pregnancies were had from the transfer of fresh embryos. This includes three pregnancies from Surgical Sperm Collection in azoospermic men. Cost could be reduced by avoiding high dosage of drugs and by cutting out serial serum estrogen levels. Ultrasonic assessment for follicle monitoring is equally satisfactory. ICSI proved to be the only successful treatment for men with poor semen quality. It is giving nearly 20% chances of fatherhood in a man who was labeled infertile previously. Results are promising and will be improving with time. The cost could be reduced to an extent by cutting down drug doses and laboratory investigations without compromising the results.

THE BUM'S RUSH It was Wednesday, and grease was the word. That meant one thing: the Mexico City Lounge (or Cafe, depending on which sign you pay attention to), in the 2100 block of Larimer Street, where the weekly taco specials draw people from all walks of life. In this instance, the walk was from several blocks away: the Westword office, in the heart of lower downtown, just before the area was tagged with the more marketable appellation of "LoDo." Two equally disheveled colleagues and I left the office one day at lunchtime, heading over on 18th Street to Larimer, where a left turn actually led to sidewalks (those along Blake and Market stopped abruptly in those days) and the Mexico City...past the Step 13 building, past the pawn shops, past the bums recreating horizontally in front of a liquor store. As we stepped over one, he saluted our passage: "The British are coming! The British are coming!" Although this was many lunches and several years ago, Denver's bums--folks who would spit on the touchy-feely title of "homeless"--have yet to lose their sense of humor. They have, however, lost some of their favorite haunts. Because this fellow was right: The British were coming. And so was everyone else who wanted a piece of Denver's booming downtown. Specifically, the parts of downtown that are booming thanks to the renaissance of LoDo and, in a not entirely related development, the area around the seven-month-old Coors Field. Even the Mexico City got into the swing of things: A few years ago, its nod to urban renewal involved taking a notch out of the building next door and adding a total of six new seats. While other parts of downtown crumble (anyone want to buy a used paraboloid?) or cutesify (Union Station is slated to become the home of a TGIFriday's, of all things), the area around upper Larimer has kept its character. Now known as the Ballpark Neighborhood, it's fought hard to keep a grip on its heritage--and a hand in its destiny. But the game isn't over. After all, plans are in the works. On Monday night, Denver City Council weighed the Northeast Downtown Plan, a project four years in the making and two years too late to have any real effect on the ballpark that forms its western boundary. And next month, the first draft of the Lower Downtown Neighborhood Plan, funded by $100,000 in state gambling money, is due at the office of the Lower Downtown District...about two years too late. The man with that LoDo plan is Bill Lamont, today a consultant but ten years ago the head of Denver's planning department. In those days, the city thought that lower downtown's salvation lay in building a convention center behind Union Station. When voters put an end to that, the 1985 Downtown Plan called for the formation of the Lower Downtown District. But it was the hard work of dozens of businesses and residents that really made LoDo work. Meanwhile, the 1985 master plan, like most plans, gathered dust on city shelves. The initial research for Lamont's current plan focuses on four case studies: Pioneer Square and Pike Place Market in Seattle, Fort Point Waterfront in Boston, and the South of Market District in San Francisco. (Nice work if you can get it.) But early drafts also make it clear that planners have set their sights a lot closer to home. One envisions expanding the Lower Downtown District to the west--to the blocks just off Wynkoop occupied by Union Station and the Ice House and the old Union Pacific building that now houses the ChopHouse, land specifically excluded when the district was formed (and land in the process blessed with some unusual zoning exemptions, including one that would allow the construction of two twenty-story towers). Another draft proposal--marked with a question mark--calls for expanding the district to the north, into the Ballpark Neighborhood. The British are coming. Karle Seydel, director of the neighborhood association, got wind of the invasion when a developer called and told him that one Lower Downtown District draft listed expansion into the area as a "second" priority. "It's a little disconcerting to someone who's spent six and a half years trying to create the Ballpark Neighborhood," Seydel says. "They've extended their area of thought into this area without any kind of discussion with the neighborhood association." It was tough enough, he adds, getting the city to include the group in the Northeast Downtown planning process. And now the well-heeled barbarians--including Arnold Schwarzenegger, who plans to bring Planet Hollywood to his property a block away in LoDo and has even hired the stadium district's John Lehigh to head the project--are at the gate. "I think it's great that they've got the dollars," Seydel says of the Lower Downtown study. But he can't help thinking of all the times the tiny shops of North Larimer have had to scrape and scrap for every amenity. While the Lower Downtown District hosts wine-and-cheese receptions, the Ballpark Neighborhood had to raffle off televisions--not hot ones--to help pay for its fall street fair. While ballpark projects spill off in almost every other direction, this neighborhood has had to fight for every strip of sidewalk, every bit of landscaping. It is only because of the neighborhood's willingness to fight (to the point of threatening to sue the city and RTD) that 20th Street turned into an attractive avenue rather than a speedway. It is only because of the neighborhood's commitment to its century-old roots that most of Larimer is not a parking lot. "For a downtown to have a character and a culture, it has to have different neighborhoods," Seydel says. "We've still got some true grit." Lower downtown may drop the notion of swallowing the Ballpark Neighborhood. But the empire-building does not end there. Over at the Downtown Denver Partnership, downtown's booster group, there's talk of taking over the Lower Downtown District; with its eye also turned to the property just across the tracks from LoDo, the partnership has already established a Central Platte Valley Development Council. The British are coming. Up on Larimer, where flim-flam men and bunko artists have practiced their arts for a century, neighbors keep a wary eye on the people who would plan for their future now that the future looks so bright. And in the meantime, they get on with their business.

The future is launching in the UK! It made me smile to see the promise of ‘the future’ emblazoned across the bottom of a bright yellow envelope. Will there be enough to write about from a European perspective? Will the UK team meet the US edition’s standards in graphic design and increasingly rare moments of typographic brilliance? Will we see neon ink? Will we have to suffer politicians showing that they understand how online fits into their vision for creative Britain and trying resuscitate and channel Harold Wilson’s ‘white heat of technology’ speech from four decades ago? Will they avoid the temptation to interview Sir Alan Sugar and Sir Clive Sinclair as part of tribute to the golden age of the British PC?

Q: StencilJS Props not populating in JSX I've been learning and practicing Stencil JS and I'm creating a card component. I have several props that are meant to populate the card's content. While the card and its styling show up fine when I render the page the card does now show any of the props I passed through. The Components code... import { Component, Host, h, Prop } from '@stencil/core'; @Component({ tag: 'proj-slider', styleUrl: 'proj-slider.css', shadow: true }) export class ProjSlider { @Prop() cardImage: string; @Prop() title: string; @Prop() link1: string; @Prop() linkText1: string; @Prop() link2: string; @Prop() linkText2: string; render() { return ( <div class="maincont"> <div class="maintext"> <img src={this.cardImage}/><br/> {this.title} </div> <div class="linkbox"> <div class="link"><a href={this.link1}>{this.linkText1}</a> </div> <div class="link"><a href={this.link2}>{this.linkText1}</a> </div> </div> </div> ); } } The Call to the Component in the JSX of another Component. <proj-slider cardImage="https://i.imgur.com/NPV7bmk.png" title="Calculator" link1="alexmercedcoder.com" linkText1="git" link2="alexmercedcoder.com" linkText2="live"></proj-slider> The code as it stands show the card and doesn't throw any errors but doesn't display the content from the props. A: Your problem is that attributes in HTML doesn't have uppercase letters. So when you do prop variables with uppercase letters they won't be uppercase in HTML instead they are seperated by "-" @Prop() cardImage: string; @Prop() linkText1: string; @Prop() linkText2: string; These three are not cardImage, linkText1, linkText2 attributes in the HTML tag instead they are: card-image, link-text1, link-text2 So your Tag would be: <proj-slider card-image="https://i.imgur.com/NPV7bmk.png" title="Calculator" link1="alexmercedcoder.com" link-text1="git" link2="alexmercedcoder.com" link-text2="live"></proj-slider> Update Since the title tag lead to the error I want to add an example here how you can actually use the title tag anyway: import { ..., Host } from '@stencil/core'; @Prop({reflect:true, mutable: true}) title:string; private hostElement: HTMLElement; render() { return ( <Host ref={(el) => this.hostElement = el as HTMLElement}> YOUR HTML LIKE IT WAS BEFORE </Host> ) } componentDidUpdate(){ if(this.hostElement) this.title = this.hostElement.getAttribute("title"); } The Host tag is like the later rendered proj-slider tag. When you save it as a variable you can access the attributes that the tag has. Maybe you have to use a different lifecyclehook but the concept works. By the way the If depends on the hook you choose.

Q: Perl: fork(), avoiding zombie processes, and "No child processes" error I have a Perl app that's been running largely untroubled on a RH system for a few years. In one place, I have to run a system command that can take take many minutes to complete, so I do this in a child process. The overall structure is like this: $SIG{CHLD} = 'IGNORE'; # Ignore dead children, to avoid zombie processes my $child = fork(); if ($child) { # Parent; return OK $self->status_ok(); } else { # Child; run system command # do a bunch of data retrieval, etc. my $output; my @command = # generate system command here use IPC::System::Simple 'capture'; eval { $output = capture(@command); }; $self->log->error("Error running @command: $@") if $@; # success: log $output, carry on } We recently changed some of our infrastructure, although not in ways that I expected would have any influence on this. (Still running on RH, still using nginx, etc.) However, now we find that almost every instance of running this code fails, logging 'Error running {command}: failed to start: "No child processes" at /path/to/code.pl'. I've looked around and can't figure out what the right solution is for this. There was a suggestion to change $SIG{CHLD} from 'IGNORE' to 'DEFAULT', but then I have to worry about zombie processes. What is causing the "No child processes" error, and how do we fix this? A: There was a suggestion to change $SIG{CHLD} from 'IGNORE' to 'DEFAULT', but then I have to worry about zombie processes. This isn't true. A zombie process is a process that has ended, but hasn't been reaped by its parent yet. A parent reaps its children using wait(2), waitpid(2) or similar. capture waits for its child to end, so it doesn't leave any zombie behind. In fact, the error you are getting is from waitpid. capture is waiting for the child to end to reap it and collect its error code, but the you instructed the OS to clean up the child as soon as it completes, leaving waitpid with no child to reap and no error code to collect. To fix this problem, simply place local $SIG{CHLD} = 'DEFAULT'; before the call to capture.

Swanton Wind, the company that hopes to develop a wind turbine farm here, has stumbled on its first step of the permitting process. In late 2011, Travis Belisle, working with VERA Renewables, installed a 130-foot meteorological station at the top of Rocky Ridge, which is also the planned site for the turbines. The tower has collected data on wind speeds and current for more than three years. Swanton Wind and its consultants failed to obtain a critical permit from the Public Service Board for the tower. A Public Service Board (PSB) order, issued on March 9, 2010, requires all applicants planning to construct “temporary meteorological stations” to address the project’s “effect on esthetics, historic sites, air and water purity, the natural environment, and the public health and safety.” Swanton Wind’s Tower was not subject to this scrutiny. Travis Belisle said that he was unaware that a Certificate of Public Good (CPG, the permit issued by the PSB) was required for the project. “To be honest with you, I called the town zoning administrator and he said if it was a temporary tower, he did need anything from me,” Belisle said. “If it needs a CPG we’ll get one. I hired VERA Renewables and they’re the ones I’m relying on to do this right. If we made a mistake, we’ll fix it, no matter what it costs.” The town zoning administrator plays no part in permitting electrical generation facilities or temporary meteorological towers. Still, it makes little sense for Belisle’s team to dodge the PSB on the meteorological tower. The review process is streamlined and public comment is strictly limited to the tower itself and is not allowed to wander into plans for any future wind generation facility. And the penalties for failing to acquire a CPG can be onerous. If the PSB determines that the violation substantially harmed or might have harmed “the public health, safety, or welfare, the interests of utility customers, [or] the environment,” it could impose a penalty of $40,000 on the project plus an additional $10,000 per day if the violation is continuing.” The total penalty is capped at the larger of $100,000 or one one-hundredth of the gross revenues of the project. “It’s going to cost me $1.2 to $1.5 million just to permit this project,” Belisle said. “It makes no sense to ignore this first step.” Martha Staskus of VERA (Vermont Environmental Research Associates) Renewables, which is working on the project with Belisle, said that there was confusion about the changing requirements around 2010 and 2011. “At the time there was some question of whether a CPG was required for a project like Travis’s,” she said. “I don’t think anyone at the time [2011] thought that this would be a large, commercial wind project. At that time, we were planning a smaller, net-metered project, which didn’t need a CPG. No one thought it would be windy enough on a 900-foot hill top for a project this size. But technology has improved a lot since then and we can do a lot more on this site.” “There was no intention to not follow the rule,” she said. Staskus said that VERA is now making arrangements to bring the tower down. She hopes it will be done by early August. “All that we need the tower for is acoustic monitoring equipment which will be re-sited at tree canopy level,” she said. Staskus confirmed that they have gathered all of the wind data they need to assess the viability of the project. At least two neighbors feel that a fine and removal of a now superfluous tower is not enough penalty for Belisle. Some of them purchase their homes after 2011 when the tower was installed. Many have complained that Belisle did not give them fair notice of his plans for the ridgeline, though Belisle disputes that. Said Dustin Lang: “He’s been flying under the radar, collecting data, without the public being told about it for years now. We’ve missed an opportunity to object and to prepare for what is coming. To me, should be like a trial. If evidence is gathered illegally, he shouldn’t be allowed to use it. He should have to start over from square one.” Source: By MATTHEW PREEDOM, St. Albans Messenger Correspondent This article is the work of the source indicated. Any opinions expressed in it are not necessarily those of National Wind Watch. The copyright of this article is owned by the author or publisher indicated. Its availability here constitutes a "fair use" as provided for in section 107 of the U.S. Copyright Law as well as in similar "fair dealing" exceptions of the copyright laws of other nations, as part of National Wind Watch's noncommercial effort to present the environmental, social, scientific, and economic issues of large-scale wind power development to a global audience seeking such information. For more information, click here. Send takedown inquiry or request to excerpt to query/wind-watch.org. Send general inquiries and comments to query/wind-watch.org.

We are aiming at biological discoveries and often develop tools and resources to make this happen. We usually work in new or emerging areas; for example we have projects that integrate drugs (and other small molecules) with cellular and phenotypic information to predict new uses for old drugs (e.g. Campillos et al., 2008, Science) or find biomolecules that cause disease or side effects. We study temporal and spatial aspects of protein networks to identify biological principles that determine function and evolution (e.g. de Lichtenberg et al., 2005, Science; Jensen et al., 2006, Nature; Kuehner et al., 2009, Nature). We study environmental aspects via comparative metagenomics (Tringe et al., 2005, Science; von Mering et al., 2007, Science; Qin et al., 2010, Nature) and hope to find marker genes for various diseases like obesity and cancer, and also to understand microbial community interactions, with application potential for human health and well-being. For example, our recent discovery of enterotypes - three distinct community compositions in the human gut analogous to blood groups (Arumugam et al., 2011 Nature) – was considered as one of the breakthroughs of 2011 by Science because it might explain different responses of people to drug intake and diet. In TARA OCEANS, we apply our know how in bioinformatics, networks and metabolomics to the analysis of Global Ocean Functional Biodiversity (Raes et al. MSB 2011, Gianoulis et al. PNAS 2009).

Basal Ganglia dysfunctions in movement disorders: What can be learned from computational simulations. The basal ganglia are a complex neuronal system that is impaired in several movement disorders, including Parkinson's disease, Huntington's disease, and dystonia. Empirical studies have provided valuable insights into the brain dysfunctions underlying these disorders. The systems-level perspective, however, of how patients' motor, cognitive, and emotional impairments originate from known brain dysfunctions has been a challenge to empirical investigations. These causal relations have been analyzed via computational modeling, a method that describes the simulation of interacting brain processes in a computer system. In this article, we review computational insights into the brain dysfunctions underlying Parkinson's disease, Huntington's disease, and dystonia, with particular foci on dysfunctions of the dopamine system, basal ganglia pathways, and neuronal oscillations. © 2016 International Parkinson and Movement Disorder Society.

Spinal decompression therapy is a FDA approved non-invasive, non-surgical treatment for certain kinds of chronic back pain and neck pain. It is very effective and safe for various backbone related problems such as slipped discs, disc bulge, spinal stenosis, sciatica, spondylolisthesis and others without the risks that are associated with anesthesia, surgery, injections, infection or prescribed medicine. This therapy works by stretching the spine slowly and gently by taking off the pressure from the vertebrae and compressed discs and it facilitate the transfer of nutrients, oxygen and fluids back to the disc. This therapy is been widely recognized to be very effective by the general medical practitioners and chiropractors. The spinal decompression therapy is done primarily using traction that is been generated by the traction machine. The traction machine is like a table or a regular inclining platform with rollers or variety of attachments. The basic idea of this therapy is to relieve the pressure from the spinal column and to induce pressure on the individual areas for setting the dislocated disc. The machines that are controlled by computer are used for applying a traction force in order to reduce the pressure between the discs. This therapy is worked on the principle that when the force is applied to the lumbar spine then it creates a negative pressure in the center. It then creates a vacuum which moves the slipped disc and lowers the nerve compression. Before the treatment, the patients are evaluated in order to determine if they are the candidate. Their x-rays, medical history MRI/CT scans are reviewed carefully. If a person is a candidate for the therapy then an individual treatment plan is been created for their specific needs. The typical plan is between 10 to 30 treatments. It is important for the patient to complete their treatment plan even if they start improving early. During each session, the patients experience multiple cycle of treatment which take around 15 to 20 minutes to complete. It takes about 3 to 5 minutes between each cycle. The equipment that is used for this type of therapy is been designed to apply precisely-controlled tension along the axis of the spinal column that creates decompression on the intervertebral discs. This therapy helps to restore proper functioning of the injured disc which is done by the help of a Decompression Table. The injured discs are stretched gently apart during the pull that produces a suction force inside the disc.

Silver Retirement Medallion The Silver Retirement Medallion is awarded by the Central Intelligence Agency for a career of 25, but less than 35, years or more with the Agency. See also Awards and decorations of the United States government References Category:Retirement medallions of the Central Intelligence Agency

Verse of Loan The Verse of Loan () is verse 282 in chapter Al-Baqara. This verse is the longest verse at the longest chapter in Quran. The concept of borrowing was explained in the verse. The context of the verse يَا أَيُّهَا الَّذِينَ آمَنُوا إِذَا تَدَايَنتُم بِدَيْنٍ إِلَىٰ أَجَلٍ مُّسَمًّى فَاكْتُبُوهُ ۚوَلْيَكْتُب بَّيْنَكُمْ كَاتِبٌ بِالْعَدْلِ ۚ وَلَا يَأْبَ كَاتِبٌ أَن يَكْتُبَ كَمَا عَلَّمَهُ اللَّـهُ ۚ فَلْيَكْتُبْ وَلْيُمْلِلِ الَّذِي عَلَيْهِ الْحَقُّ وَلْيَتَّقِ اللَّـهَ رَبَّهُ وَلَا يَبْخَسْ مِنْهُ شَيْئًا ۚ فَإِن كَانَ الَّذِي عَلَيْهِ الْحَقُّ سَفِيهًا أَوْ ضَعِيفًا أَوْ لَا يَسْتَطِيعُ أَن يُمِلَّ هُوَ فَلْيُمْلِلْ وَلِيُّهُ بِالْعَدْلِ ۚ وَاسْتَشْهِدُوا شَهِيدَيْنِ مِن رِّجَالِكُمْ ۖ فَإِن لَّمْ يَكُونَا رَجُلَيْنِ فَرَجُلٌ وَامْرَأَتَانِ مِمَّن تَرْضَوْنَ مِنَ الشُّهَدَاءِ أَن تَضِلَّ إِحْدَاهُمَا فَتُذَكِّرَ إِحْدَاهُمَا الْأُخْرَىٰ ۚ وَلَا يَأْبَ الشُّهَدَاءُ إِذَا مَا دُعُوا ۚ وَلَا تَسْأَمُوا أَن تَكْتُبُوهُ صَغِيرًا أَوْ كَبِيرًا إِلَىٰ أَجَلِهِ ۚ ذَٰلِكُمْ أَقْسَطُ عِندَ اللَّـهِ وَأَقْوَمُ لِلشَّهَادَةِ وَأَدْنَىٰ أَلَّا تَرْتَابُوا ۖ إِلَّا أَن تَكُونَ تِجَارَةً حَاضِرَةً تُدِيرُونَهَا بَيْنَكُمْ فَلَيْسَ عَلَيْكُمْ جُنَاحٌ أَلَّا تَكْتُبُوهَا ۗ وَأَشْهِدُوا إِذَا تَبَايَعْتُمْ ۚ وَلَا يُضَارَّ كَاتِبٌ وَلَا شَهِيدٌ ۚ وَإِن تَفْعَلُوا فَإِنَّهُ فُسُوقٌ بِكُمْ ۗ وَاتَّقُوا اللَّـهَ ۖ وَيُعَلِّمُكُمُ اللَّـهُ ۗ وَاللَّـهُ بِكُلِّ شَيْءٍ عَلِيمٌ O ye who believe! When ye deal with each other, in transactions involving future obligations in a fixed period of time, reduce them to writing Let a scribe write down faithfully as between the parties: let not the scribe refuse to write: as Allah Has taught him, so let him write. Let him who incurs the liability dictate, but let him fear His Lord Allah, and not diminish aught of what he owes. If they party liable is mentally deficient, or weak, or unable Himself to dictate, Let his guardian dictate faithfully, and get two witnesses, out of your own men, and if there are not two men, then a man and two women, such as ye choose, for witnesses, so that if one of them errs, the other can remind her. The witnesses should not refuse when they are called on (For evidence). Disdain not to reduce to writing (your contract) for a future period, whether it be small or big: it is juster in the sight of Allah, More suitable as evidence, and more convenient to prevent doubts among yourselves but if it be a transaction which ye carry out on the spot among yourselves, there is no blame on you if ye reduce it not to writing. But take witness whenever ye make a commercial contract; and let neither scribe nor witness suffer harm. If ye do (such harm), it would be wickedness in you. So fear Allah; For it is Good that teaches you. And Allah is well acquainted with all things. If ye are on a journey, and cannot find a scribe, a pledge with possession (may serve the purpose). And if one of you deposits a thing on trust with another, let the trustee (faithfully) discharge his trust, and let him Fear his Lord conceal not evidence; for whoever conceals it, - his heart is tainted with sin. And Allah knoweth all that ye do. Exegesis Some concepts that were mentioned in the verse are as following: Whenever there is a loan transaction for a specific period of time, it must be formally written down. Both of lender and debtor must trust the writer. In other hand, writer must to be equitable and just write the facts of borrowing terms. Important thing is that information of writer about rules of borrowing. Writer's knowledge and awareness about the rules and regulations of borrowing is essential. He has to know them at the best. There must be two witnesses, when a document is signed by lender and debtor. Witnesses should be two men or one man and two women. The security of the writer must to be guaranteed and there is any allowance to bothering him because of administering justice. The length of the contract should be stated exactly. See also Qard al-Hasan The verse of Ikmal al-Din The verse of Wilayah The warning verse Verse of brotherhood The verse of purification Muhammad in the Quran The verse of evil eye The obedience verse The verse of Mawadda References Category:Quranic verses Category:Islamic ethics Category:Shia Islam Category:Sunni Islam Category:Sharia Category:Al-Baqara

Host defense mechanisms in the peritoneal cavity of continuous ambulatory peritoneal dialysis patients. 1. This article provides a review of studies on peritoneal white blood cells (WBC) in CAPD patients. To some extent these studies support the concept that the peritoneal cavity of these patients contains adequate-functioning WBC that can provide effective antimicrobial defenses when they are studied in dialysate-free media. Commercially available dialysis solutions significantly impair WBC function. In some patients with high incidences of peritonitis, there appears to be reduced bactericidal capacity of their peritoneal macrophages. CAPD seems to contribute to a state of both macrophage and lymphocyte activation in the peritoneal cavity. The clinical consequences of this chronic activation are not known.

Designing Liposomes To Suppress Extracellular Matrix Expression To Enhance Drug Penetration and Pancreatic Tumor Therapy. During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via coassembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids. By utilizing the MMP-2-rich pathological environment, the pirfenidone (PFD) loaded MRPL (MRPL-PFD) can specifically release PFD at the pancreatic tumor site and down-regulate the multiple components of ECM expressed by the PSCs. This resulted in a significant increase in the penetration of gemcitabine into the tumor tissue and enhanced the efficacy of gemcitabine for pancreatic tumor. Our design tailored for antifibrosis of pancreatic cancer may provide a practical approach to build functional liposomes through supramolecular assembly, and regulation of ECM may be a promising adjuvant therapeutic strategy for pancreatic and other ECM-rich tumors.

Back to the future with Commodore Amiga Mini PC Back to the future with Commodore Amiga Mini PC. If you remember the earlier days of home computing, apple II/e, Tandy 1000, Toshiba T1100, Atari 520ST, Commodore Vic-20, Commodore C64/C128, you will remember the Commodore Amiga. The Amiga was Commodore’s flagship pc, many early adopters of […]

Those of you who’ve been checking out my projects might have noticed that I wrote my latest one in C++. The two previous projects I had written in Haskell. So why the switch? I’ll write down a small summary of the pros and cons of the both languages that influenced my decision. I’ll start with the things that spoke for Haskell. Haskell, in general, allows a lot more abstract, safer, higher level way of programming. Of course, you already knew this, but it’s still worth mentioning. Hackage has tons of useful packages which makes using libraries and all the associated bureaucracy really simple. (Hackage is basically a repository consisting of almost all open sourced Haskell programs and libraries.) Combine this with cabal, which downloads, compiles and installs the dependencies for you automatically. C++ compile times, especially with Boost, are abysmal. And now for the cons, or, put in a more positive light, pros for C++. It’s much easier to reason about performance in C++ than in Haskell. This is given, I guess, and the simple solution is to become a Haskell champion who can spot a space leak a mile away, but it bothers me nevertheless. There was a nice post and thread at Haskell cafe a while back about this. Writing portable code in Haskell is not as easy as with C++. With portable I mean 1) code that runs on x86 across operating systems (Windows, Linux and Mac), and 2) code that runs across architectures (x86, ARM, MIPS, etc.). While portability is not as trendy anymore as it once was, I still have the twisted opinion that high quality code in a higher level language absolutely must be portable, otherwise it’s not high quality, and the Haskell ecosystem currently has limited support for writing portable code. Portable across operating systems is relatively simple with Haskell using GHC (although there are exceptions), but portable across architectures is a pain. GHC, the defacto standard Haskell compiler, actively supports only x86 and doesn’t cross compile. Some of the other Haskell compilers do compile across architectures, but they don’t support all the GHC extensions (which are used by a lot of Hackage packages) and often have a huge performance gap with GHC, which leaves me with zero Haskell compilers I’m 100% happy with. Don’t get me wrong, I still appreciate GHC and think it’s magical, but there’s room for improvement. The Haskell libraries are in a constant flux. I’ve been writing Haskell code for a couple of years now, and each time a new GHC version came out, the old code broke. Usually the libraries included with GHC are updated and the interface was changed. Or GHC behaves a bit differently regarding some minor points and the code breaks. Or cabal, which has its main releases together with GHC, has some new features and the code breaks. There are plans for fixing the libraries once and for all (I can’t find the link now), which I think is a great idea, but when they do (and until they do), there’ll be breakage again. Cabal, while great in general, has its problems, namely what cdsmith felicitously dubbed Haskell’s own DLL hell. As can be seen from the list, the negative issues I see concerning Haskell are mostly not about the language itself but the infrastructure. That makes sense, I guess; Haskell, although it has a great community, is a less used language, especially in the industry, which makes it more difficult to establish an infrastructure that can compete with the one of, say, C++. The problems I have with C++, on the other hand, concern the language itself, which, although useful, is not really what one might consider the crown jewel of language design. The infrastructure is at least something that can be fixed.

Live The Life! The original LTL selection of hand-picked surf accommodation and real estate on walking distance from worldclass surf . LiveTheLife, means living the life you really, really want. For the LiveTheLife team, that means living close to the surf and being free. Being free to do what we love and to go where we want. With the Livehelife ... Ecuador and the Galapagos Islands offer contrasting surfing environments. The Galapagos are quiet, remote quite fickle and rocky whilst Ecuador can be party-mad and offers a multitude of accessible sandy beach barrels through to long points and reefs. They do however share the same exposure to both north and south swells; both will suffer decay before reaching their shores but what does arrive, as a consequence is of high quality, losing much of the short period associated with locally generated swells. November to march being the primary swell season. Ecuador's surfing is focused around the northern reaches of the country and the famous surf town of Atacames. Water temperatures between the Galapagos and Ecuador are also divergent (20-25ºC or 68-77ºF), the former being in the path of the Humboldt Current and a good few degrees cooler. Tradewinds blow from a southerly direction all year, swinging more easterly for the Galapagos and westerly for Ecuador, though mornings are typically offshore on the mainland. Surf Schools Schools with qualified surf instructors offering lessons and courses with equipment hire to individuals or groups, whether you are a total beginner, an intermediate surfer or an experienced surfer looking to improve your ability.

// Distributed under the terms of the MIT license // Test case submitted to project by https://github.com/practicalswift (practicalswift) // Test case found by fuzzing class A { var d = a( { let a { [ { { } } var { class case ,

The triggering of Article 50 in the UK was seen as a watershed moment for many UK lenders, partly in that it would signal a seismic shift in operations and infrastructure. However, the development was also hypothesized as a moment when UK lenders and banks operating in the country would start to unveil their plan to relocate within the sphere of the EU. Credit Suisse has for months mulled over its options on where to relocate to. The most likely landing spots to relocate a segment of its operations to have been Frankfurt, Dublin, or Amsterdam. The decision is no clearer today than it was months ago. Suggested articles The need to relocate was brought on by British PM, Theresa May, who extinguished any hope of lenders retaining passporting rights with the EU. With European lenders based out of the UK, the decision looks to be a challenging one as many contemplate setting up shop elsewhere in continental Europe. Exodus Plans? Despite May seemingly forcing the hand of many lenders, neither Credit Suisse nor others have really outlined many plans in 2017 as to where they are looking to shift their focus. Rather, Credit Suisse has focused on shoring up its retention in the form of an expanded bonus program, even during a time when other rivals are gutting their payouts. Still, Credit Suisse has continued to cut a sizable number of jobs, not even relegated to the London area, which has been the epicenter for layoffs over the past two years. Last month the lender jettisoned several equities roles in Hong Kong and Tokyo as well. Unfortunately for industry rivals, shareholders, or others looking for cues, Credit Suisse has been remarkably silent as to its end game or strategy in 2017 and is no closer in making a formal decision. Its almost a foregone conclusion some segment or portion of its business will need to shift locales out of London, though there presently does not exist another city with the same caliber and benefits afforded by the UK capital.

All relevant data are within the paper and its Supporting Information files. Introduction {#sec001} ============ Soil-transmitted helminthiasis (STH) and schistosomiasis are two of the most prevalent neglected tropical diseases with more than 1 billion and over 250 million people affected worldwide, respectively \[[@pntd.0005953.ref001], [@pntd.0005953.ref002]\]. Their collective global burden is 6 million disability-adjusted life years \[[@pntd.0005953.ref003]\], with school-aged children at the highest risk of associated morbidity. Control efforts have intensified over the past 15 years, with preventive chemotherapy serving as the main pillar \[[@pntd.0005953.ref004]--[@pntd.0005953.ref006]\]. Information about the spatial and temporal distribution of STH and schistosomiasis are important to guide interventions. Moreover, it is necessary to know which age groups contribute most to transmission, in terms of helminth egg output, in order to effectively use the available resources. There are two approaches to obtain this information. First, large-scale, standardized studies including all age groups with intense sampling which, however, is difficult to pursue due to the high cost. Second, reanalysis of data from previously published studies. Inference is hampered by the paucity of quality data \[[@pntd.0005953.ref007]--[@pntd.0005953.ref009]\]. Individual-level data are usually not reported; instead, only the number of participants tested positive for a specific helminth infection is considered. In addition, diagnosis relies on the Kato-Katz technique \[[@pntd.0005953.ref010]\], i.e., counting of helminth eggs in a small amount of stool. This approach, however, has a low, setting-dependent sensitivity, which is governed by variation in day-to-day production of eggs per worm, non-random distribution of eggs within a stool sample, decay of eggs in the sample due to methods and duration of the experimental procedure, transportation, and storage \[[@pntd.0005953.ref011]--[@pntd.0005953.ref015]\]. Collecting multiple stool samples over consecutive days increases the accuracy but there are no guidelines on the optimal number of samples \[[@pntd.0005953.ref016], [@pntd.0005953.ref017]\]. Consequently, the comparison of studies that employed different sampling efforts, which is necessary for monitoring progress of control programs, is hampered. Statistical modeling can help studying the age-prevalence and its dependence on the diagnostic error but has been restricted by the aforementioned limitations that compromise the quality of the data \[[@pntd.0005953.ref007], [@pntd.0005953.ref018]\]. Although the qualitative shape of helminthiasis age-prevalence curves is known, there has been little progress in the application of quantitative transmission models, especially for STH infections \[[@pntd.0005953.ref019]--[@pntd.0005953.ref022]\]. Furthermore, the dependency of the intensity of the infection on the diagnostic sensitivity has been largely neglected. The negative binomial distribution has commonly been used to fit helminth egg count data. For example, De Vlas and Gryseels \[[@pntd.0005953.ref012]\] and Levecke et al. \[[@pntd.0005953.ref023]\] proposed models that separate the measurement process from the true underlying infection intensity distribution. However, none of the preceding models are able to infer on the dependence of the sensitivity of the Kato-Katz method for repeated stool sampling on infection intensity. We developed a model for fecal egg-count (FEC) data, which quantifies the relation between sampling effort, infection intensity, and diagnostic sensitivity. The model separates the infected from the non-infected individuals and the measurement process from the infection status. Variability due to egg output, experimental conditions, and aggregation within a population are taken into account. We calculate the 'true' prevalence and other biological and transmission-related parameters based on the probability of false-negatives. Our model improves estimation of the age-related disease burden and provides inputs for mathematical transmission models. Materials and methods {#sec002} ===================== Ethics statement {#sec003} ---------------- This study consists of a secondary analysis of published data. Ethics approval, written informed consent procedures, and treatment of infected individuals have been described elsewhere \[[@pntd.0005953.ref024]--[@pntd.0005953.ref027]\]. Data {#sec004} ---- We tested our model performing a secondary analysis of individual level FEC data from three separate studies in medium and high transmission settings in Côte d'Ivoire conducted in 1998, 2002, and 2011, respectively. All data used were from baseline surveys with no previous mass drug administration in the area. The studies took place in Fagnampleu \[[@pntd.0005953.ref024], [@pntd.0005953.ref025]\], Zouatta \[[@pntd.0005953.ref026]\], and Azaguié \[[@pntd.0005953.ref027]\]. Based on the Kato-Katz assay, hookworm prevalence varied from 11.4% to 59.0%, and mean or infected population based infection intensity from 280 eggs per gram of stool (EPG) to 396 EPG. For *S. mansoni*, prevalence varied from 35.6% to 76.3%, and infection intensity from 152 EPG to 307 EPG. Between two and four stool samples were collected and analyzed on consecutive days of a total of 1423 participants. Azaguié and Zouatta were surveys performed in the full age range from 0 to 90 years, while Fagnampleu only included school-aged children. Prevalence of *Ascaris lumbricoides* and *Trichuris trichiura* were too low to be analyzed. Summary measures are included in [Table 1](#pntd.0005953.t001){ref-type="table"}, a more detailed description can be found in [S1 Appendix](#pntd.0005953.s001){ref-type="supplementary-material"}, and the individual level data used is included in [S1 Table](#pntd.0005953.s002){ref-type="supplementary-material"}. 10.1371/journal.pntd.0005953.t001 ###### Resulting parameters of the simulations (mean and 95% BCI[^1^](#t001fn001){ref-type="table-fn"}) parameters of the mean infection and of the prevalence of *S. mansoni* and hookworm in Azaguié, Zouatta, and Fagnampleu in Côte d'Ivoire. Observed prevalence is the ratio of positively tested individuals in the original study, observed mean infection the arithmetic mean egg count of the individuals with a positive test. {#pntd.0005953.t001g} *S. mansoni* Hookworm ---------------------------------------------------------------------- ------------------- ------------------- ------------------- ------------------- ------------------- -------------------- Observed prevalence (%) 35.6 (31.4, 39.8) 40.8 (36.7, 44.9) 76.3 (71.8, 80.5) 11.4 (8.6, 14.2) 35.4 (31.5, 39.4) 59.0 (53.9, 64.1) Estimated 'true' prevalence (%) 49.3 (40.4, 61.2) 59.6 (50.7, 69.3) 83.8 (78.3, 89.3) 14.3 (10.9, 18.5) 43.7 (38.6, 49.2) 62.2 (56.6, 67.6) Observed mean infection (EPG)[^3^](#t001fn003){ref-type="table-fn"} 179 (171, 188) 152 (141, 163) 307 (289, 325) 396 (326, 466) 331 (301, 361) 283 (260, 306) Estimated mean infection (EPG)[^4^](#t001fn004){ref-type="table-fn"} 132 (101, 167) 104 (84, 128) 282 (249, 321) 220 (150, 316) 261 (208, 325) 262 (221, 312) Sensitivity[^5^](#t001fn005){ref-type="table-fn"} 1 sample (%) 59.4 (47.6, 70.2) 48.0 (40.8, 55.8) 70.2 (66.1, 74.1) 57.1 (44.5, 68.8) 47.1 (41.7, 52.5) 53.8 (50.1, 57.7) 2 samples (%) 72.9 (59.5, 84.6) 62.3 (53.5, 71.3) 83.5 (79.3, 87.3) 81.0 (69.1, 90.1) 71.8 (65.9, 77.3) 78.5 (74.59, 81.9) 3 samples (%) \- 69.0 (59.8, 78.2) 88.2 (84.2, 91.8) \- 84.9 (80.0, 89.1) 89.9 (87.3, 92.2) 4 samples (%) \- \- 90.7 (86.8, 94.0) \- \- 95.2 (93.6, 96.6) Day-to-day variation (*r*) 1.10 (0.80, 1.46) 0.83 (0.67, 1.02) 0.87 (0.77, 0.99) 0.25 (0.15, 0.37) 0.15 (0.13, 0.19) 0.20 (0.17, 0.23) Aggregation (*α*) 0.09 (0.05, 0.13) 0.08 (0.05, 0.11) 0.05 (0.04, 0.07) 0.22 (0.04, 0.90) 0.32 (0.06, 1.23) 0.19 (0.05, 0.68) ^1^ Parameter posterior mean estimates and 95% Bayesian credible interval ^2^ *k* is the number of samples taken in a study; *N* the number of participants with at least one sample ^3^ The observed mean infection is the mean egg count of all individuals tested positive in at least one Kato-Katz thick smear ^4^ The estimated mean infection is *μ*~*f*~ + *μ*~*m*~ ^5^ The sensitivity was calculated using [eq 4](#pntd.0005953.e006){ref-type="disp-formula"} Model {#sec005} ----- We utilized a hierarchical Bayesian model to address the objectives given in the introduction. Let *Y*~*ij*~ be the FEC, i.e., the number of helminth eggs found in sample *j* in individual *i*, *k*~*i*~ the number of stool samples from individual *i*, and *x*~*i*~ the age of individual *i*. We assumed that a population consists of a proportion of infected individuals *p*, i.e., people that carry at least one pair of worms, and that of uninfected individuals. Thus *p* is interpreted as the prevalence. Each infected individual has a characteristic infection intensity λ~*i*~, measured in units of mean eggs per sample and assumed to be distributed within the population according to a shifted gamma distribution, given by $$\begin{array}{r} \begin{array}{cl} \lambda_{i} & {= v_{i} + \mu_{m}} \\ v_{i} & {\sim \text{Gamma}\left( \mu_{f} \cdot \alpha,\alpha \right)} \\ & {= \frac{\alpha^{\mu_{f} \cdot \alpha}}{\Gamma\left( \mu_{f} \cdot \alpha \right)}\, v_{i}^{\mu_{f} \cdot \alpha - 1}\,\exp\left( - \alpha \cdot v_{i} \right)} \\ \end{array} \\ \end{array}$$ with a mean number of eggs *μ*~*f*~ + *μ*~*m*~ in an infected individual, variance $\frac{\mu_{f}}{\alpha}$ that corresponds to the aggregation of infection intensities, and hence, the aggregation of worms within the population. The shift parameter *μ*~*m*~ is the mean number of eggs per sample that can be expected from an individual carrying exactly one female worm and thus the minimal possible infection intensity. Direct inference on the worm load is not possible in this frame as the dependence on mean egg output is non-linear and not well known \[[@pntd.0005953.ref028]\]. The process of taking *k*~*i*~ samples from an infected individual *i* with infection intensity λ~*i*~ is modeled by a negative binomial distribution with mean λ~*i*~ and a variance given by $\lambda_{i} + \lambda_{i}^{2}/r$. *r* reflects the additional variation, due to changes in the day-to-day helminth eggs output, the aggregation of eggs in stool, and the precise experimental procedure but not the within-population variation which is given by *α*. If a perfectly random distribution of the eggs and perfect measurement is assumed *r* → ∞, the measurement process becomes a Poisson process. By including the uninfected, the model is written as $$\begin{array}{r} {\mathbf{Y}_{\mathbf{i}} \sim \left\{ \begin{array}{ll} {\left( 1 - p \right) + p \cdot \text{NB}\left( 0,\lambda_{i},r \right)^{k_{i}}} & {\text{,}\text{if} I_{i} = 0} \\ {p \cdot \prod\limits_{j = 1}^{k_{i}}\text{NB}\left( Y_{ij},\lambda_{i},r \right)} & {\text{,}\text{if} I_{i} = 1} \\ \end{array}\operatorname{} \right.} \\ \end{array}$$ which corresponds to a zero-inflated negative binomial model with *p* corresponding to the mixing proportion. *NB* is the negative binomial distribution and *I*~*i*~ the result of the Kato-Katz test over all samples from an individual. They are defined as follows: $$\begin{aligned} I_{i} & {= \begin{cases} 0 & {,\mspace{180mu}\text{if}\mspace{180mu}\text{max}\left( \mathbf{Y}_{\mathbf{i}} \right) = 0} \\ 1 & {,\mspace{180mu}\text{if}\mspace{180mu}\text{max}\left( \mathbf{Y}_{\mathbf{i}} \right) \neq 0} \\ \end{cases}} \\ {\text{NB}\left( {y,\lambda,r} \right)} & {= \left( \begin{array}{l} \begin{array}{l} {y + r - 1} \\ y \\ \end{array} \\ \end{array} \right)\left( \frac{\lambda}{\lambda + r} \right)^{y}\left( \frac{r}{r + \lambda} \right)^{r}} \\ \end{aligned}$$ False-negatives are included in the model as repeated zero measurements for an infected individual. Thus, the sensitivity depending on the number of repeated measurements becomes $$\begin{matrix} {s_{i}\left\lbrack k_{i} \right\rbrack = 1 - \text{NB}\left( {0,\lambda_{i},r} \right)^{k_{i}} = 1 - \left( \frac{r}{\lambda_{i} + r} \right)^{k_{i} \cdot r}} \\ \end{matrix}$$ where *s* is the sensitivity, and *k* and λ vary for each individual. Low-rank thin-plate splines are used to study the age dependence of *p*, *μ*~*f*~, *r*, and *α*. For a detailed derivation of the spline model, see Crainiceanu et al. \[[@pntd.0005953.ref029]\]. The representation of *p* is $$\begin{array}{r} {\operatorname{logit}\left( p_{i} \right) = \beta_{0} + \beta_{1}\, x_{i} + \sum\limits_{m = 1}^{M}{u_{m}\,\left( x_{i} - \kappa_{m} \right)^{3}}} \\ \end{array}$$ where **Θ**~1~ = (*β*~0~, *β*~1~, *u*~1~, ..., *u*~*M*~)^*T*^ is the vector of regression coefficients and *κ*~1~ \< ⋯ \< *κ*~*M*~ are the fixed knots. The other parameters can be represented analogously using logarithmic or linear spline models. The spline regression makes only a few very general assumptions about the shape of the curve, e.g., continuity and differentiability, and is therefore able to infer without requiring prior knowledge about the biology of the process, i.e., the transmission model. The minimum eggs per sample *μ*~*m*~ is fixed to the average egg output of a worm divided by an average amount of feces per day, multiplied by the weight of a sample. For hookworm, *μ*~*m*~ is 5 eggs in a sample which corresponds to 120 EPG and for *S. mansoni*, *μ*~*m*~ is 0.03 eggs which corresponds to 0.72 EPG \[[@pntd.0005953.ref030], [@pntd.0005953.ref031]\]. We choose the following semi-informative priors for the model: gamma for *r* with mean 1 and variance 1; normal for log(*α*) with mean 0 and variance 1; gamma for *μ*~*f*~ with mean 2 and variance 4; normal for *β*~0,1~ with mean 0 and variance 1; normal for *u*~1,...,*M*~ with mean 0 and variance *τ*, where *τ* is distributed as a gamma with mean 2 and variance 4. The results were not sensitive to the specific shape of the priors. Bayesian inference was performed using Markov chain Monte Carlo (MCMC) simulations implemented in Stan \[[@pntd.0005953.ref032]\]. Validity of the model was checked using simulated data. Models with splines on *p*, *μ*~*f*~, *r*, and *α* were run to check for age dependence. *μ*~*f*~, *r*, and *α* showed no significant age dependence and were set as independent of age for the simulations presented in the results section. *μ*~*m*~ was varied from 1 egg to 6 eggs for hookworm and from 0.01 eggs to 0.1 eggs for *S. mansoni*, which also showed no significant influence. The lower limit of 0.01 eggs per slide for *S. mansoni* corresponds to roughly 100 eggs in 500 g of stool. The upper limit of 0.1 eggs per slide corresponds to 1000 eggs per 500 g of stool therefore any value larger than 0.1 is most likely unrealistic for a single worm pair. The model was run with a total of 25 chains, with 20,000 iterations each, of which 2,000 where used as warm up and adaption, for each study and for each of the two infections separately. Convergence was achieved, and assessed using Gelman + Rubin diagnostics and visual inspection of the chains \[[@pntd.0005953.ref033]\]. Results {#sec006} ======= We applied a Bayesian hierarchical model to FEC data from three studies carried out in Zouatta, Azaguié and Fagnampleu in Côte d'Ivoire, as described in the "Materials and methods" section. Parameter posterior mean estimates and 95% Bayesian credible interval (BCI) are summarized in [Table 1](#pntd.0005953.t001){ref-type="table"}. Estimated 'true' prevalence and its relation to age {#sec007} --------------------------------------------------- The three studies are from different hookworm transmission settings with observed prevalence of 11.4% and mean infection intensity of an infected individual of 396 EPG for Azaguié, 35.4% and 331 EPG for Zouatta, and 59.0% and 283 EPG for Fagnampleu. Based on our model, we estimated the 'true' hookworm prevalence at 14.3% (95% BCI 10.9--18.5%), 43.7% (95% BCI 38.6--49.2%), and 62.2% (95% BCI 56.6--67.6%), for Azaguié, Zouatta, and Fagnampleu, respectively. The estimated mean infection intensity does not significantly differ from one study to another and mean estimates ranged from 220 EPG to 262 EPG (see [Table 1](#pntd.0005953.t001){ref-type="table"}). Age-prevalence curves in [Fig 1](#pntd.0005953.g001){ref-type="fig"} from the three studies show similar features such as a steep increase from birth till an equilibrium is reached at ages of around 20 years for Zouatta, and 45 years for Azaguié. The prevalence stays constant till an age of about 60 years from where the rate of infection declines. For Fagnampleu only the initial steep increase is visible due to the fact that no individuals older than 15 years were included. {#pntd.0005953.g001} For *S. mansoni*, the Azaguié and Zouatta studies show similar transmission levels with an observed prevalence of 35.6% and 40.8% and observed mean infection intensity of 179 EPG and 152 EPG, respectively. In contrast, the study in Fagnampleu had a prevalence of 76.3% and a mean infection intensity of 307 EPG. We estimated a 'true' prevalence of 49.3% (95% BCI 40.4--61.2%) and a mean infection intensity of 132 EPG (95% BCI 101--167 EPG) for Azaguié, 59.6% (95% BCI 50.7--69.3%) and 104 EPG (95% BCI 84--128 EPG) for Zouatta, and 83.8% (95% BCI 78.3--89.3%) and 282 EPG (249--321 EPG) for Fagnampleu. The estimated age-prevalence curves displayed in [Fig 2](#pntd.0005953.g002){ref-type="fig"} show similar qualitative features. The prevalence increases up to a peak between the ages of 15 and 20 years, and subsequently declines slowly up to an age of 60 years, followed by a stronger decrease. The lower prevalence after the peak is not significant but it appears both in the Azaguié and Zouatta data. {#pntd.0005953.g002} Variations in egg output {#sec008} ------------------------ For hookworm, the day-to-day variation given by *r* is consistent across study sites, ranging from 0.15 (95% BCI 0.13--0.17) to 0.25 (95% BCI 0.15--0.37) (see [Table 1](#pntd.0005953.t001){ref-type="table"}), indicating strong overdispersion. The aggregation of egg output within the population is also consistent across the studies with *α* estimates ranging from 0.19 (95% BCI 0.05--0.68) to 0.32 (95% BCI 0.06--1.23). For *S. mansoni* the day-to-day variation is consistent across studies and significantly different from hookworm with values ranging from 0.83 (95% BCI 0.67--1.02) to 1.10 (95% BCI 0.80--1.46). The aggregation of infections within the population shows no significant differences between studies with *α* ranging from 0.05 (95% BCI 0.04--0.07) to 0.09 (95% BCI 0.05--1.13), which indicates a significantly higher variance than for hookworm. Estimated sensitivity and its relation to infection intensity {#sec009} ------------------------------------------------------------- For hookworm, the estimates of the diagnostic sensitivity of Kato-Katz did not vary between locations. Based on a single Kato-Katz thick smear, sensitivity estimates were in the range of 47% to 57%, for two samples obtained from different days from 72% to 81%, for three samples estimates were within the range of 85% to 90%, and for four samples around 95%. For *S. mansoni*, data from Azaguié and Zouatta revealed similar sensitivity estimates within the range of 48% to 59% for one Kato-Katz thick smear, 62% to 73% for two samples, and 69% for three samples. Fagnampleu has a higher sensitivity of 70%, 84%, 88%, and 91% for one, two, three, and four samples, respectively (see [Table 1](#pntd.0005953.t001){ref-type="table"}). The sensitivity of the Kato-Katz technique for different infection intensities was calculated using [eq 4](#pntd.0005953.e006){ref-type="disp-formula"} and is plotted in [Fig 3](#pntd.0005953.g003){ref-type="fig"}. For hookworm the dependence on infection intensity is weak, e.g., only increasing from 40% to 55% from a very light infection of 120 EPG to a still light infection of 500 EPG. For moderate and heavy infections (\>2000 EPG) the sensitivity did not significantly improve with infection intensity. However, the sensitivity can be greatly increased by examining several stool samples, e.g., for an infection intensity of 360 EPG the sensitivity can raise from 50% based on a single sample to 75% for two samples, and 92.5% for three samples. {#pntd.0005953.g003} The sensitivity was strongly associated with *S. mansoni* infection intensity. In particular, for very light infections (\<5 EPG), it was below 50% even after three samples. For light infections (\<100 EPG), it was still heavily dependent on infection intensity. For moderate infections (100--399 EPG), two samples gave a high sensitivity above 90%. Heavy infections (\>400 EPG) were reliably detected (i.e. \>99%) by testing two samples. [Fig 4](#pntd.0005953.g004){ref-type="fig"} shows the overall sensitivity in a population with a day-to-day variation of *r* = 1.0 and a population aggregation of *α* = 0.07 as a function of the mean infection intensity in the population. For lower transmission settings with 100 EPG comparable to Zouatta, the sensitivity after four samples is still below 75%. However, sensitivity rose to more than 95% for a setting with a mean infection intensity of over 300 EPG. {#pntd.0005953.g004} Discussion {#sec010} ========== We present a model which determines the relation between the sensitivity of the Kato-Katz technique and intensity of *S. mansoni* and hookworm infections. The model takes into account day-to-day variations in helminth egg output and within population aggregation of worms. Additionally, we were able to test various parameters for age-dependence, especially the age structure of the prevalence. The overall sensitivity point estimates for hookworm corroborate with estimates derived from latent class modeling approaches. Tarafder et al. \[[@pntd.0005953.ref034]\] give an estimate of 65% sensitivity in a setting with 35% prevalence where no infection intensity is given, and Nikolay et al. \[[@pntd.0005953.ref035]\] estimated the sensitivity for one sample at 59.5%, for two at 74.2%, and for three samples at 74.3%. For *S. mansoni* in a setting with an observed prevalence of 33%, Lamberton et al. \[[@pntd.0005953.ref036]\] predict a sensitivity of 29.6% for one sample, 51.9% for two samples, 70.4% for three samples, and 77.8% for four samples in agreement with our estimates for Zouatta and Azaguié. The same authors predicted a much higher sensitivity of 83.5%, 97.8%, and 100% for one, two, or three samples, respectively in a setting with 95% prevalence in agreement with our estimates for Fagnampleu. Glinz et al. \[[@pntd.0005953.ref037]\] also predicted a sensitivity of 70% for a single Kato-Katz thick smear in a high transmission setting with prevalence close to 90%, which is again consistent with our estimates for Fagnampleu. Our estimates are in agreement with those given in the literature. However, the added value of our modeling approach is that we can predict the sensitivity depending on infection intensity and the 'true' prevalence in various settings and we can understand the factors influencing the sensitivity for hookworm and *S. mansoni*. There are three main parameters that directly influence the sensitivity, i.e., the minimum infection intensity, the day-to-day variation, and population aggregation. These parameters are specific for *S. mansoni* and hookworm. The minimum infection *μ*~*m*~, which is fixed to 0.03 eggs per sample for *S. mansoni* and 5 eggs per sample for hookworm, is based on estimates of egg output for a single worm. The estimates carry a large uncertainty which were shown to be non-critical for the results. The low output of eggs per worm in *S. mansoni* makes it almost impossible to detect light infections with only a few female worms. The low sensitivity for light infections can also be seen in [Fig 3](#pntd.0005953.g003){ref-type="fig"} where the three *S. mansoni* curves show very low sensitivity when approaching 0 EPG. For hookworm, the output of a single female worm is about 5 eggs per sample, which already leads to a reasonable probability for detection. The parameter *r* is determined by the day-to-day variation. The three studies agree on a value between 0.17 and 0.19 for hookworm and between 0.8 and 0.99 for *S. mansoni*. Both values conclusively contradict a Poisson process which has *r* → ∞ and could be interpreted as worms producing and excreting eggs randomly. Thus, our model clearly indicates that a worm produces eggs in a clustered fashion. A single pair of *S. mansoni* produces in the order of 100 eggs per day \[[@pntd.0005953.ref030]\], while a female hookworm sheds around 10,000 eggs \[[@pntd.0005953.ref031]\]. Thus, an infection that manifests itself with a similar egg count for both diseases indicates a much higher number of *S. mansoni* compared to hookworm. This difference in worm numbers has important implications, because the variation in egg output of a single worm is partly averaged out over the population of worms that produce eggs independently in an individual. The much lower variation in day-to-day output of *S. mansoni* can therefore be explained by the, on average, larger number of worms in an infected individual. The larger variation for hookworm leads to a lower sensitivity of the Kato-Katz technique for this helminth species for a similar infection intensity. Thus, the increase in sensitivity due to repeated sampling is much larger for hookworm (see [Fig 3](#pntd.0005953.g003){ref-type="fig"}). The population aggregation parameter *α* describes the distribution of worm output within the population. A small value indicates a relatively wider distribution, while a larger value indicates a more uniform distribution. The estimate of *α* has larger uncertainty for hookworm compared to *S. mansoni*, most likely due to the large day-to-day variation for the former species. Furthermore, *α* is overall larger for hookworm compared to *S. mansoni* indicating that egg output is more evenly distributed among individuals infected with hookworm than for *S. mansoni*. These results are in agreement with findings by Krauth et al. \[[@pntd.0005953.ref015]\]. The severity of disease burden at a location is generally given by two parameters, prevalence and intensity of infections. If negative individuals are included in the calculation of the mean infection intensity the high number of zeros will skew the mean downwards, especially in lower prevalence settings. Thus, a strong correlation to the prevalence will be induced, making the mean infection intensity to be a mixed measure of prevalence and infection intensity. We decided to only include positive individuals in the mean infection intensity to separate the effects of the sensitivity on observed prevalence from that on infection intensity. Therefore, we decided to estimate the mean infection intensity from only positive individuals. It is evident from our estimates that the sensitivity of the Kato-Katz technique in hookworm is dominated by the large day-to-day variation in egg output and has only a weak dependence on infection intensity. Thus, increasing the number of samples is an effective strategy to increase sensitivity even in low transmission settings for hookworm. In contrast, for *S. mansoni* the infections that give false-negative results are largely those with light intensity. Increasing the number of samples to more than two does only marginally improve the sensitivity because the sensitivity is limited by the low density of eggs and not the variation in excretion and production. However, taking two thick smears from the same samples at 100 EPG mean infection intensity would increase the sensitivity from 50% to 70% for a comparably low additional effort. For mean infection intensities below 100 EPG no directly representative data was included in this model study. Nevertheless, extrapolations to low prevalence and infection intensity settings are valid because the model considers individual-level data. In a high intensity setting there are still many individuals with low intensity infections, and therefore our model includes information on the full range of infection intensities. Thus, inference about a low intensity and prevalence population consisting primarily of light infections is possible without making unreasonable extrapolations. For infections with an intensity above 240 EPG, the strong relation between infection intensity and sensitivity suggests that the sensitivity for two samples is close to 100%, ensuring that the most heavily infected individuals are detected and can be treated. Still, the results indicate a possibility of bias when comparing different study sites. The infection intensity-dependent sensitivity will become increasingly important in the new era with the goal to eliminate STH and schistosomiasis \[[@pntd.0005953.ref038], [@pntd.0005953.ref039]\]. In the study sites of Zouatta and Azaguié, the observed mean infection of *S. mansoni* was moderate compared to Fagnampleu. Hence, it is conceivable that there was a comparably larger share of light infections that were missed due to the low sensitivity of the Kato-Katz technique, and therefore, the 'true' mean infection intensity will be even lower. Moreover, the difference between estimated and observed prevalence is also larger due to the higher number of missed cases. For Fagnampleu, the observed mean infection intensity and therefore the overall sensitivity are high. Thus, the estimates agree with the observations and the 'true' prevalence is only slightly higher than the one observed. For hookworm, the likelihood of correctly diagnosing a heavy infection is still larger than for a light infection. Accordingly, the difference between the observed and the estimated mean infection intensity is larger the fewer the number of samples taken. Our estimates of the underlying 'true' age-prevalence for *S. mansoni* and for hookworm are in agreement with those obtained from transmission models \[[@pntd.0005953.ref019], [@pntd.0005953.ref040]\] and from latent class statistical models \[[@pntd.0005953.ref041]\]. For example, the *S. mansoni* age-prevalence is comparable to those obtained by the Yang et al. \[[@pntd.0005953.ref042]\] models, which differentiate between the influence of water contact patterns and the acquired immunity. However, due to large uncertainty in older age groups, our results do not allow choosing the transmission model, which resembles best. For hookworm, a peak shift, as proposed by Woolhouse \[[@pntd.0005953.ref043]\], is clearly visible in our age-prevalence curve. The decreasing prevalence at older age is apparent in all locations but it has yet to be discussed in greater detail in the literature. It could indicate a significantly lower life expectancy for infected individuals although other explanations and confounding factors are conceivable but cannot be tested with the available data. Conclusions {#sec011} ----------- The proposed model succeeds in predicting the intensity-dependent sensitivity of the Kato-Katz technique directly from the day-to-day variation in helminth egg output. Hence, the model is able to explain the differences between the sensitivity of hookworm and *S. mansoni*. The sensitivity of Kato-Katz for hookworm is dominated by a high day-to-day variation. We recommend collecting at least two stool samples over subsequent days combined with the given sensitivity values to estimate 'true' prevalence. For *S. mansoni* infection the sensitivity is largely driven by light infections that are hard to detect by a single Kato-Katz thick smear. We also recommend collecting two samples due to almost perfect sensitivity for moderate and heavy infections and low benefit of additional samples for light infections. We predict that improving the sensitivity for *S. mansoni* can be achieved more cost effectively by increasing the number of Kato-Katz thick smears from the same stool sample instead of increasing the number of samples taken. Additionally, it is necessary to take into account the infection intensity-dependent sensitivity of Kato-Katz for *S. mansoni* when comparing data from several studies. Including the infection dependence becomes more important when close to elimination due to the larger changes in sensitivity of Kato-Katz with infection intensity. A further consequence of the results is due to the fact that the guidelines of WHO are defined in terms of observed prevalence. An observed prevalence of e.g. 10% for *S. mansoni*, which is the lower limit for yearly MDA, is indicative of a 'true' prevalence of roughly 14%, 20%, and 29% for 200 EPG, 100 EPG, and 50 EPG, respectively. Hence, the observed prevalence is a measure of both, the 'true' prevalence and the infection intensity. We advise the disentanglement of these two components by defining thresholds separately for 'true' prevalence and infection intensity. The results also suggest that the current disease burden estimates underestimate the true prevalence. The spline model for age-dependence used in this study can be replaced by appropriate transmission models to determine which age groups should be treated and how frequently that has to happen to increase the intervention effectiveness. The model can be further extended to analyze studies with multiple Kato-Katz thick smears performed per stool sample and thus separate day-to-day from within-sample variation. This would enable us to address the question of how repeated testing of the same sample compares to taking several samples in order to reduce cost and increase compliance. Supporting information {#sec012} ====================== ###### A more detailed description of the study sites and data collection procedures. (PDF) ###### Click here for additional data file. ###### Individual level data of the three studies sites. (XLSX) ###### Click here for additional data file. [^1]: The authors have declared that no competing interests exist.

Russell Galley, managing director, Halifax Community Bank, said: "The annual rate of growth has picked up for the second consecutive month, rising from 2.6% in August to 4% in September. "The average house price is now £225,109 - the highest on record. House prices in the three months to September were 1.4% higher than in the previous quarter, the fastest quarterly increase since February. "While the quarterly and annual rates of house price growth have improved, they are lower than at the start of the year. "UK house prices continue to be supported by an ongoing shortage of properties for sale and solid growth in full-time employment. "However, increasing pressure on spending power and continuing affordability concerns may well dampen buyer demand." Mr Galley also highlighted recent speculation on the possibility of an increase in the Bank of England base rate. But he said: "We do not anticipate this will have a significant effect on transaction volumes." Howard Archer, chief economic adviser at EY ITEM Club, said he expects house price growth to be "relatively muted" over the rest of the year, with a "modest" increase of 2% to 3% in 2018. He said: "Housing market activity is likely to be hampered by fragile consumer confidence and limited willingness to engage in major transactions." Samuel Tombs, chief UK economist at Pantheon Macroeconomics, said: "We expect most of the pick-up in Halifax's index to unwind over the coming months." Mark Harris, chief executive of mortgage broker SPF Private Clients, said: "Mortgage rates continue to be competitive although swap rates have started edging up on the back of all the talk about interest rate hikes." Mr Harris said that with some lenders having raised mortgage rates or being poised to do so: "Borrowers looking for one of the cheapest fixed-rate mortgages may wish to move sooner rather than later to secure one."

Email Share 791 Shares A federal district court ruled Monday in favor of the transgender sister of the singer who performed at President Trump’s inaugural festivities seeking to use the bathroom at her Pennsylvania school consistent with her gender identity — but not on the same terms as the contention in similar litigation before the U.S. Supreme Court. In a 48-page decision, U.S. District Judge Mark Hornak issued a preliminary injunction in favor of Juliet Evancho — the sister of Jackie Evancho — and Elissa Ridenour, who are both transgender females, as well as another transgender male plaintiff identified as A.S. “The Plaintiffs appear to the Court to be young people seeking to do what young people try to do every day-go to school, obtain an education, and interact as equals with their peers,” Hornak writes. Although Pine-Richland High School in Pennsylvania initially allowed Evancho and her fellow plaintiffs to use the restroom consistent with their gender identity, the school was forced to change its policy in September after the board, under pressure from anti-LGBT groups, enacted Resolution 2, which requires students to either use facilities corresponding to their biological sex or unisex facilities. In October 2016, Lambda Legal filed the lawsuit against Pine-Richland High School over the change in policy on the basis it discriminates against the plaintiffs under the 14th Amendment and Title IX of the 1972 Education Amendments on the basis of sex. Joining Lambda in filing the lawsuit were Tracie Palmer and David C. Williams with Kline & Specter P.C. The court, which suspended enforcement of Resolution 2 as the case continues through the court, also denied the Pine-Richland School District’s request to dismiss the case. Omar Gonzalez-Pagan, who represents the transgender student as staff attorney for Lambda Legal, said the court ruling is a “huge win” for the plaintiff students who “will be able once again to use the bathroom that matches who they are.” “Not withstanding the Trump Administration’s misguided and cruel actions last week, the court today found that the school’s policy barring transgender students from the restroom that matches who they are violates the equal protection clause of the U.S. Constitution,” Gonzalez-Pagan said. The ruling is significant after the Trump administration recently rescinded guidance instructing schools that they must allow transgender kids to use the bathroom consistent with their gender identity and litigation filed by transgender student Gavin Grimm, who is suing to use the boys’ room in his school in Gloucester County, Va. But Hornak, an Obama appointee, declined to rule in favor of Evancho and fellow plaintiffs on the basis of the prohibition on sex discrimination under Title IX of the Education Amendments of 1972, which forms the basis of the litigation pending before the Supreme Court and the Obama-era guidance the Trump administration rescinded. “Put plainly, the law surrounding the Regulation and its interpretation and application to Title IX claims relative to the use of common restrooms by transgender students, including the impact of the 2017 Guidance, is at this moment so clouded with uncertainty that this Court is not in a position to conclude which party in this case has the likelihood of success on the merits of that statutory claim,” Hornak wrote. Instead, Hornak ruled in favor of the plaintiff students based on a determination that denying them access to the restroom consistent with their gender identity likely contravenes the Equal Protection Clause of the U.S. Constitution. “Like ‘sex,’ as to these Plaintiffs, gender identity is neither transitory nor temporary,” Hornak writes. “Further, what buttresses that conclusion is the fact that the school community as a whole treats these Plaintiffs in all other regards consistently with their stated gender identities, along with the reality that these Plaintiffs live all facets of their lives in a fashion consistent with their stated and experienced gender identities. These are all factors that have informed the judgments of other courts in applying the intermediate scrutiny Equal Protection analysis in the case of classifications involving transgender status, and in this Court’s estimation, they apply here.” Rachel Hathhorn, a spokesperson for the Pine-Richland School District, had few words in the response to the ruling, but said the school district would comply. “The district will implement the order issued through the United States District Court for the Western District of Pennsylvania,” Hathhorn said. Jackie Evancho performed at Trump’s inaugural festivities despite criticism from Trump supporters who objected to her transgender sister and Trump opponents who believed she shouldn’t contribute to the inaugural festivities based in part on Trump’s anti-LGBT positions. Elissa praised the court in a statement for allowing her to use the restroom consistent with her gender identity without stigmatization or fear of reprisal from her school. “This is wonderful news and a tremendous relief that we can now use the bathroom without feeling isolated and humiliated,” Elissa said. “The past months have been incredibly stressful, and this was all so unnecessary. There was no problem before, and we are confident there will be no problem now.”

Profile - Federico Graziani Published: 06 April, 2009 Federico Graziani is in charge of the wine list at Milan's famous Il Luogo di Aimo e Nadia. Already the author of two books, he's currently continuing his research into the world of wine by studying for his MW. Federico Graziani is in charge of the wine list at Milan's famous Il Luogo di Aimo e Nadia. Already the author of two books, he's currently continuing his research into the world of wine by studying for his MW. What first got you interested in wine?I started the first course of my sommelier studies when I was 15 years old. My parents had to sign a document that allowed me to 'taste' wines. I guess it was just curiosity at the time, then, through experience, I got really passionate about it. How did you end up in your current job?After three years in London, working with Stefano Cavallini at the Halkin Hotel, then Teca in Mayfair and the launch of Isola, I was given a great opportunity at Milan's Cracco Restaurant so I decided to return to Italy. One year after the opening, I moved to a restaurant with a simpler, more genuine cuisine, Aimo e Nadia. They gave me the opportunity to work with them and let me study oenology at the University of Milan. Do you have a wine world hero? If so, who is it - and why?I guess I have at least 100! There are so many great people in the wine business, but if I had to choose one it would be Giuseppe Rinaldi, a cultured, ironic and romantic Barolo producer. What makes a great sommelier?Experience and curiosity, but first of all, humility. You never know who's sitting in the restaurant at the table with your regular guest. What's your proudest professional achievement?Being allowed to study with the Institute of Masters of Wine. But I'm also very proud of my second book, 'Vini d'Autore'. What makes a great wine list?I believe a great wine list should be wide and deep, a selection of the best wines from all around the world (but not necessarily the most expensive). A wine list should represent both the experience of the sommelier and his taste. Is there any kind of wine you wouldn't want on your list?I dislike wines made in order to obtain high scores without giving the wine drinker pleasure and drinkability. How much emphasis do you attach to matching wines with food - and what's the best way of helping customers steer their way to appropriate wine choices?I believe that as long as the client approves of the match that wine pairing is very important but that one shouldn't be fanatical about it. And it's important to remember that there is not just one perfect match: it depends on the sequence of the menu and not just on each individual dish. What's the oddest request you've ever had from a customer?It was many years ago. A costumer asked me to get some Coke to accompany their Chateau Latour 1990. I put the bottle of soft drink next to the glass and left. I felt very sad. What do you drink at home?Anything good. It could be white or red, it depends on how I feel that day. More often than not, it's Champagne. What would be your desert island wine?Domaine Ponsot's Clos de la Roche 1985. And what would you want to eat with it?Sweetbread caramelised with hazelnuts and Torcolato sauce. To die for.

DES MOINES — President Donald Trump’s reelection campaign was a key focus of 2020 caucuses being held statewide Monday night by Iowa Republicans. Although the vast majority of attention on this year’s Iowa caucus campaigns was focused on Democratic candidates vying to oppose Trump, the Republican Party of Iowa still scheduled meetings for nearly 1,700 precincts so the party faithful could have their voices heard. What those Iowa Republicans said Monday: They were overwhelmingly behind the President. The Associated Press called the caucus victory in Trump's favor at 7:26 p.m. Iowa GOP spokesman Aaron Britt said attendance Monday night was expected to be nowhere near the size of the large crowds that participated in the highly contested 2016 Iowa GOP caucuses, which were won by Texas Sen. Ted Cruz with Trump coming in second. That’s because Trump’s nomination this year has been more of a given, he said. Trump was boosted in Iowa on Monday by a statewide blitz of 80 presidential campaign surrogates that included much of the president’s cabinet. At Northview Middle School in Ankeny, Lara Trump, who is a senior adviser to the president’s 2020 campaign, was a scheduled speaker. She is married to Eric Trump, one of Trump’s sons. President Donald Trump speaks to the crowd during a campaign rally on Thursday, Jan. 30, 2020, at the Knapp Center in Des Moines. Trump is being opposed nationally for the Republican presidential nomination by two veteran GOP politicians: former Massachusetts Gov. Bill Weld and former U.S. Rep. Joe Walsh from Illinois, a conservative radio host. But neither Weld nor Walsh demonstrated much of an ability to generate enthusiasm among Iowa Republicans for their candidacy. In addition, Trump’s impeachment trial, which is expected to end this week with his acquittal by the U.S. Senate, appears to have done little or no damage to his reelection prospects among Republicans. A packed audience of more than 7,000 cheered Trump during a rally last week at Drake University in Des Moines, where he railed against the “lunacy and the madness of the totally sick left.” Story continues Surveys show Trump remains popular among conservatives. A November Des Moines Register/CNN/Mediacom Iowa Poll found 76% of registered Republicans who didn’t plan to attend the Democratic caucuses said they will definitely vote to reelect Trump. Trump carried Iowa by more than 9 percentage points in the 2016 general election against Democratic nominee Hillary Clinton, although Democratic nominee Barack Obama carried Iowa in both 2008 and 2012 as he won two presidential terms. This article originally appeared on Des Moines Register: Iowa caucus: Donald Trump wins with overwhelming Republican support

Improved radiocarbon analyses of modern human hair to determine the year-of-death by cross-flow nanofiltered amino acids: common contaminants, implications for isotopic analysis, and recommendations. In forensic investigation, radiocarbon ((14)C) measurements of human tissues (i.e., nails and hair) can help determine the year-of-death. However, the frequent use of cosmetics can bias hair (14)C results as well as stable isotope values. Evidence shows that hair exogenous impurities percolate beyond the cuticle layer, and therefore conventional pretreatments are ineffective in removing them. We conducted isotopic analysis ((14)C, δ(13)C, δ(15)N and C/N) of conventionally treated and cross-flow nanofiltered amino acid (CFNAA)-treated samples (scalp- and body-hair) from a single female subject using fingernails as a reference. The subject studied frequently applies a permanent dark-brown dye kit to her scalp-hair and uses other care products for daily cleansing. We also performed pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) analyses of CFNAA-treated scalp-hair to identify contaminant remnants that could possibly interfere with isotopic analyses. The conventionally treated scalp- and body-hair showed (14)C offsets of ~21‰ and ~9‰, respectively. These offsets confirm the contamination by petrochemicals in modern human hair. A single CFNAA extraction reduced those offsets by ~34%. No significant improvement was observed when sequential extractions were performed, as it appears that the procedure introduced some foreign contaminants. A chromatogram of the CFNAA scalp-hair pyrolysis products showed the presence of petroleum and plant/animal compound residues, which can bias isotopic analyses. We have demonstrated that CFNAA extractions can partially remove cosmetic contaminants embedded in human hair. We conclude that fingernails are still the best source of keratin protein for year-of-death determinations and isotopic analysis, with body-hair and/or scalp-hair coupled with CFNAA extraction a close second.

1. Field of the Invention This invention relates generally to a technique for storing object instances of an object-oriented programming language in a relational database schema. In particular, the present invention describes a method and apparatus for storing object instances in an object-oriented programming language such as C++ in a relational database using a language such as SQL (Structured Query Language), although the present invention should not be limited to these particular languages. 2. Background of the Invention With the advent of object-oriented programming (OOP) languages, the software design paradigm has shifted such that computer systems executing a particular application are viewed as a collection of individual objects, which achieve the desired application function by exchanging messages among themselves. Object-oriented design and programming is described in Object Oriented Design with Applications, by Grady Booch, The Benjamin/Cummings Publishing Company, Inc., 1990. Often, it is necessary or desirable to store objects in some form of persistent storage, such as on a computer tape or disk. Most source-level languages that support object orientation do so only in memory, through the class concept. However, when it becomes necessary to store a persistent representation of objects, after the memory holding the in-core representation of the object has been relinquished by the application processes, there is in general no language support. No standard format has been defined for storage of persistent objects in, say, a disk file in an operating system. This function is sought to be achieved by object-oriented databases, whose aim is to store persistent objects in a transportable format independent of both the underlying file system structure as well as the application's memory representation. However, object-oriented databases are currently an immature technology, and are not expected to reach maturity until some time after this writing. Accordingly, there exists a need to provide for a mechanism to provide persistent storage for objects in an OOP environment. Relational database products currently represent a relatively mature and popular technology with which application developers have extensive familiarity. As object-oriented programming languages (such as C++ and Smalltalk) gain rapid acceptance and application development moves to object orientation, it is expected that there will be a demand for techniques to store persistent object definitions within the schema of a Relational Database Management System at least until the time when object-oriented database technology wins sufficient developer confidence to be used in a production environment and probably far beyond. In addition, many developers have substantial investments in relational database technology. Those who wish to move to object oriented applications may be able to preserve substantial portions of their development by utilizing relational database technology which is already developed. The current invention addresses the need for such persistent storage in an object-oriented programming environment and defines an automatic mapping and an interface definition for this purpose, among other things. This allows for the easy storage of persistent representations of objects defined in source constructs of an object-oriented programming language, within the schema of a relational database. In addition to providing for persistent storage, the present invention provides a mechanism to make object-oriented data available for manipulation in relational database management environments by providing a translator function.

Generally, polarizing lenses block polarized light generated when natural light is reflected, and are therefore used for their anti-glare effects or light reducing effects. In recent years, taking advantage of such effects of polarizing lenses, they have been used particularly for protection from polarized light outdoors, for example for protection against polarized light reflected from snow surfaces at a ski resort, or protection from diffuse reflection from water surfaces during fishing, or for protection against reflected light from oncoming cars when driving a car. Additionally, in other fields, polarizing lenses are used for many things, including sunglasses and fashion glasses with the objective of reducing light. As a transparent resin constituting these polarizing lenses, diethylene glycol bis(allyl carbonate) resin, being a resin with a lower specific gravity than glass at 1.32, having excellent heat resistance, water resistance, solvent resistance, and workability, and further having vision correction effects, and still further optimal for productivity of small quantities of diverse products, is primarily used. Diethylene glycol bis(allyl carbonate) resin polarizing lenses are generally manufactured by the method (cast polymerization) described in Patent Publication 1, wherein, after fitting molds into both sides of a gasket, and placing a polarizing film between the two molds, the space is filled with diethylene glycol bis(allyl carbonate) monomer wherein a polymerization initiator has been mixed and dissolved, and the monomer is cured by polymerization. Alternatively, there are cases where polarizing lenses are manufactured by adhesively joining together two lenses with a polarizing film sandwiched in between, as described in Patent Publication 2. [Patent Publication 1] Japanese Unexamined Patent Publication No. S61-235113 [Patent Publication 2] Japanese Unexamined Patent Publication No. 2001-249227

An asymmetric formal synthesis of fasicularin. An asymmetric formal synthesis of fasicularin (1) is described. This natural product, isolated from the extracts of the marine invertebrate Nephteis fasicularis, has shown modest cytotoxicity towards Vero cells. Fasicularin is among only two members of the cylindricine family of natural products, along with lepadiformine (2), to possess a trans A-B ring junction. Key steps of this approach to 1 involve a siloxy-epoxide semipinacol rearrangement of 5 to 6, a B-alkyl Suzuki-Miyaura coupling reaction by using enol trifluoromethanesulfonate 19 and a substrate-directed hydrogenation reaction of 24. This formal synthesis also highlights the difficulty in the incorporation of the thiocyanate functionality present in 1.

GRADES OR AGES: Grade 5. SUBJECT MATTER: Social studies; economic development of the United States and Canada. ORGANIZATION AND PHYSICAL APPEARANCE: The major portion of the guide, which develops the unit, is laid out in three columns, one each for topics, activities, and materials. Other sections are in list form. The guide is mimeographed and staple-bound with a paper cover. OBJECTIVES AND ACTIVITIES: General objectives for the unit are listed on the first page. Each group of activities in the second column is related to a topic in the first column. INSTRUCTIONAL MATERIALS: Each group of materials listed in the third column is related to one or more activities. In addition, three appendixes contain curriculum materials. STUDENT ASSESSMENT: A one-page section entitled"Evaluation" lists ideas students should understand and skills they should possess by the end of the unit. OPTIONS: The guide is prescriptive as to course content and timing. Activities and materials listed are optional. Also, a short section lists several supplemental activities. (RT)

Short- and mid-term outcomes of robotic-assisted total mesorectal excision for the treatment of rectal cancer. Our experience after 198 consecutive cases. Robot-assisted total mesorectal excision is a safe alternative for rectal cancer treatment. Nevertheless, substantial data is still missing. Our aim was to assess the perioperative and oncological outcomes of the routine use of the robotic-assisted approach for rectal cancer treatment. 198 Consecutive robotic rectal resections were performed between January 2011 and April 2015 in patients with stage I-IV disease. We prospectively evaluated peri and postoperative data, pathological findings and mid-term oncological outcomes. 36 Abdominoperineal Amputations, 28 High Anterior Resections, 131 Low Anterior Resections and 3 Hartmann operations were performed. Mean age, ASA, BMI and distance form anal verge were respectively 67.5 years, ASA II, 26.95 kg/m(2) and 5.9 cm. 71.2% Patients received neoadjuvant therapy. Mean OR time was 294 minutes. Conversion occurred in 4.5%. Mean postoperative stay was 8 days. 36 Patients required blood transfusion with a mean of 162 ml. Complications Clavien III-IV were 12.1%. 8 complete responses were observed, 50 UICC class I, 84 class II, 51 class III and 13 class IV. Mean lymph node harvested were 11.7. Mean distal margin was 3.3 cm. 11 Circumferential margins were affected in UICC class III-IV patients. Postoperative mortality was 0.5%. Local recurrence was observed in 5% patients. Median follow-up was 27.6 months. Single institution descriptive study. The routine use of robotic assisted laparoscopic surgery may help to achieve lower conversion rates with lower ventral hernia rates and similar oncological outcomes using a minimally invasive approach in a non-selected group of patients with non-selected rectal tumours.

Admissions Boise State creates opportunities. We’re here to help you make the most of the time, money, and energy you invest in your education — and in your future. Visit our Admissions page often and enjoy your exploration of Boise State. You’ll discover it’s a smart choice. Department of Management The nonprofit management minor is a 20 credit focus on nonprofit management and community development efforts. Students from ALL majors can use this minor to pursue their interests in all manner of philanthropy and community development in a variety of policy areas. Classes are offered in the summer, fall, and spring. The nonprofit minor now has 68 students. That number is expected to grow as fall and spring nonprofit courses will be offered for the first time. Suciu, Christy. (Presenter/Author), Baughn, Chris. (Author), The Business of Social and Environmental Innovation 2014 Conference, “Design Thinking and Models of Entrepreneurial Innovation,” University of Cape Town, Graduate School of Business, Cape Town, South Africa. (Presented: October 23, 2014). Buchanan, Mark. (Author), Conference on Social Responsibility, “CSR and the Social Contract: New Lenses for Stakeholder Analysis and Strategic Management,” Milgard School of Business, University of Washington, Tacoma; Tacoma, WA. (Presented: July 10, 2014). Peer-Reviewed/Refereed. Meredith Taylor, a returning member of the management department, is publishing two new works: Carbon free energy development and the role of small modular reactors: A review and decision framework for deployment in developing countries in Renewable & Sustainable Energy Reviews this March, 2015. King Cotton in International Trade: The Political Economy of Dispute Resolution at the WTO will be the inaugural book in the World Trade Institute’s new series Global Studies in International Economic Law with Brill Publishing.

Q: iOS Simulator crashing in compile I'm new to xcode and this forum, so sorry for my unprofessional language. I have a problem with the iOS simulator crashing when I'm trying to run an app. It does not always happen, when I've just started working on a project everything's fine. But then suddenly after I just change something minor in the code the iOS simulator crashes as soon as it starts (compiling works). Xcode then takes me to the debugging page and also shows a lot of output in the bottom-right-corner-window (which I don't know what it's called). I don't get anything of the output, it says something about NSencryption. Once the iOS simulator has started crashing it will crash every time it starts running that project/app. Even if I undo my changes I did when it stopped working and even if I erase all of my code and everything looks like a new project, IT JUST WON'T RUN. Tried to call Apple support to solve this problem, but they said I should post a question in a forum, hope you can help me as I am really getting tired of this, I can't build anything. Btw I've tried to reset the iOS simulator but the same problem continues to occur. Here is the output I get from the 'console': Btw, please tell me if any of this code is sensible and I will remove it. 2015-03-26 17:39:52.727 Testing123[19815:4331412] *** Terminating app due to uncaught exception 'NSUnknownKeyException', reason: '[<Testing123.ViewController 0x7f93ea8272c0> setValue:forUndefinedKey:]: this class is not key value coding-compliant for the key addFive.' *** First throw call stack: ( 0 CoreFoundation 0x00000001026e1a75 __exceptionPreprocess + 165 1 libobjc.A.dylib 0x0000000104239bb7 objc_exception_throw + 45 2 CoreFoundation 0x00000001026e16b9 -[NSException raise] + 9 3 Foundation 0x0000000102afcd43 -[NSObject(NSKeyValueCoding) setValue:forKey:] + 259 4 CoreFoundation 0x000000010262b5e0 -[NSArray makeObjectsPerformSelector:] + 224 5 UIKit 0x000000010323b4ed -[UINib instantiateWithOwner:options:] + 1506 6 UIKit 0x0000000103099a88 -[UIViewController _loadViewFromNibNamed:bundle:] + 242 7 UIKit 0x000000010309a078 -[UIViewController loadView] + 109 8 UIKit 0x000000010309a2e9 -[UIViewController loadViewIfRequired] + 75 9 UIKit 0x000000010309a77e -[UIViewController view] + 27 10 UIKit 0x0000000102fb9509 -[UIWindow addRootViewControllerViewIfPossible] + 58 11 UIKit 0x0000000102fb98a1 -[UIWindow _setHidden:forced:] + 247 12 UIKit 0x0000000102fc5f8c -[UIWindow makeKeyAndVisible] + 42 13 UIKit 0x0000000102f700c2 -[UIApplication _callInitializationDelegatesForMainScene:transitionContext:] + 2732 14 UIKit 0x0000000102f72e3e -[UIApplication _runWithMainScene:transitionContext:completion:] + 1349 15 UIKit 0x0000000102f71d35 -[UIApplication workspaceDidEndTransaction:] + 179 16 FrontBoardServices 0x0000000105deb243 __31-[FBSSerialQueue performAsync:]_block_invoke + 16 17 CoreFoundation 0x0000000102616c7c __CFRUNLOOP_IS_CALLING_OUT_TO_A_BLOCK__ + 12 18 CoreFoundation 0x000000010260c9c5 __CFRunLoopDoBlocks + 341 19 CoreFoundation 0x000000010260c785 __CFRunLoopRun + 2389 20 CoreFoundation 0x000000010260bbc6 CFRunLoopRunSpecific + 470 21 UIKit 0x0000000102f717a2 -[UIApplication _run] + 413 22 UIKit 0x0000000102f74580 UIApplicationMain + 1282 23 Testing123 0x00000001025051ee top_level_code + 78 24 Testing123 0x000000010250522a main + 42 25 libdyld.dylib 0x0000000104a15145 start + 1 ) libc++abi.dylib: terminating with uncaught exception of type NSException (lldb) This is the code that gives me this error: ` import UIKit class ViewController: UIViewController { override func viewDidLoad() { super.viewDidLoad() // Do any additional setup after loading the view, typically from a nib. } override func didReceiveMemoryWarning() { super.didReceiveMemoryWarning() // Dispose of any resources that can be recreated. } }` Here is the project A: You haven't given many details, but here's how to start resolving your problem. The bottom of your Xcode app has a debugger window. In that window, messages from the app will display. When your app crashes, it will print out a stack trace which shows what happened just prior to the crash. When posting here, you'll want to include that in your post. Within that crash log, the top portion will tell you what the problem was--typical issues are nil values or calling something outside a range. Looking further down in the crash log, you'll usually see system stuff (UIKit, etc.). Look at the most recent method called in the class YOU created. Then, find that method in your code and add a breakpoint next to it. The breakpoint will stop execution of your code when it gets to that spot. At the top of the debugger window in the bottom portion of your screen, you'll see a few buttons. One of them is "step over". When you hit your breakpoint, use the "step over" button to execute your code one line at a time. When you get to your problem, it'll crash. You'll also want to Google the error the debug console spits out. 9 times out of 10, someone's encountered the issue you're encountering and you'll be able to proceed towards resolution of your problem. If that doesn't get the problem solved, you'll want to post here with details and the problematic methods. Another thing I'd recommend doing is learning how to use GitHub. When I started learning this (and I still AM learning it), git seemed like overkill, but in hindsight it would have been a good idea to learn how to use git from the start. You'll be able to create branches to work on features in your software and merge them to a "master" when you've got new features working. When I was starting, I would get fairly far along, I'd make a minor change and I'd break a bunch of stuff--that will still happen with Git, but you'll have a version of the software that functions. Using Git, you'll be able to always have a stable version that works and you can add features without worrying about blowing up your entire project. Good luck! Update for new info: Your starting point would be Googling this: Terminating app due to uncaught exception 'NSUnknownKeyException', reason: ViewController setValue:forUndefinedKey:]: this class is not key value coding-compliant for the key. Also, the import UIKit should be #import UIKit. I suspect this post will steer you in the right direction. What does this mean? "'NSUnknownKeyException', reason: … this class is not key value coding-compliant for the key X" Solution: You have a ViewController.swift file, but your storyboard file is 1) incorrectly named and 2) doesn't have any scenes on it. Here's what you need to do: 1) rename the storyboard file "Main.storyboard" 2) add a View Controller scene on storyboard, as you currently have no scenes on your storyboard. You do this by dragging & dropping View Controller from the lower right-hand portion of the screen. 3) When your ViewController scene is highlighted, at the top right-hand portion of your screen you should see some buttons. One of them is called "Attributes Inspector". Make sure "Is Initial View Controller" is checked. One button over to the left is "Identity Inspector". Make sure class is set to ViewController. I'll say it again. If you want to learn iOS, I'd recommend learning GitHub first. Additionally, Stanford University has a free iOS course taught by a guy who worked closely with Steve Jobs which you'll probably find helpful. If it's "too much" starting out, I'd suggest picking up a Big Nerd Ranch book or looking at Ray Wenderlich's website.

Viniphenol A, a complex resveratrol hexamer from Vitis vinifera stalks: structural elucidation and protective effects against amyloid-β-induced toxicity in PC12 cells. Stilbenes have received much attention during the last two decades following the discovery of resveratrol in wine. Since then, there have been a growing number of papers reporting various biological activities of naturally occurring stilbenes. The aim of this study was to determine new minor stilbenes from Vitis vinifera stalks. Purification of these compounds was achieved by means of centrifugal partition chromatography, a versatile separation technique that does not require a solid stationary phase. Viniphenol A (1), a new resveratrol hexamer, was isolated along with five oligostilbenoids identified in V. vinifera for the first time, ampelopsin C, davidiol A, leachianol F, leachianol G, and E-maackin, a dimer with an unusual dioxane moiety, and 14 known hydroxystilbenes. The structure and stereochemistry of viniphenol A were determined on the basis of spectroscopic data analysis and molecular modeling under NMR constraints. Viniphenol A showed protective effects against amyloid-β-induced toxicity in PC12 cell cultures.

Q: Resources for graphical languages / Penrose notation / Feynman diagrams / birdtracks? There is an idea I've recently gotten interested in that doesn't seem to have a good agreed-upon name ("diagrammatic algebra?"). It centers around the use of two-dimensional diagrams of dots, possibly boxes, and arrows, and is related to (in no particular order) knot theory, braided monoidal categories, quantum groups and Hopf algebras, subfactors, planar algebras, and (topological) quantum field theory. However, it also has a more accessible aspect: it can be used as an elegant notation for working with $\text{Vect}$ (a particularly ubiquitous braided monoidal category; see question #6139), and at least one textbook has used a variant of it to develop the basics of Lie theory. There is also John Baez's Physics, Topology, Logic, and Computation: a Rosetta Stone, and another accessible introduction to some of these ideas is Kock's Frobenius Algebras and 2D Topological Quantum Field Theories. These ideas have also been used to understand quantum mechanics. This is all pretty fascinating to me. These are elegant and beautiful ideas, and it seems to me that they are badly in need of unification and accessible exposition (something like Selinger's A survey of graphical languages for monoidal categories, but maybe with a more historical and/or expository bent). Beyond Baez's paper, does anyone know of any resources like that? Where can I learn more about what you can do with these diagrams that doesn't necessarily require a lot of background? Related: how should I TeX these diagrams? A: I find the area your question covers very interesting and am looking forward to seeing what answers people come up with. I thought I would supplement my rather minimal answer from a few days ago. I'm not really providing any work that links all these ideas together, rather I'm giving some useful references for your quest. Peter Freyd and David Yetter (1989). "Braided Compact Closed Categories with Applications to Low-Dimensional Topology". Advances in Mathematics 77: 156–182. A. Joyal and R. Street, The geometry of tensor calculus, Advances in Math. 88 (1991) 55-112 André Joyal and Ross Street. "The Geometry of Tensor calculus II". Synthese Lib 259: 29–68. André Joyal, Ross Street, Dominic Verity (1996). "Traced monoidal categories". Mathematical Proceedings of the Cambridge Philosophical Society 3: 447–468. In fact, many things by Ross Street Functorial Knot Theory: Categories of Tangles, Coherence, Categorical Deformations, and Topological Invariants (Series on knots & everything) by David N. Yetter (Author) Many works by Bob Coecke and Samson Abramsky (eg. Temperley-Lieb algebra: From knot theory to logic and computation via quantum mechanics) are certainly accessible. The Catsters youtube channel, especially the presentations on string diagrams Functorial boxes in string diagrams by Paul-Andre Mellies Invited talk at the Computer Science Logic 2006 conference in Szeged, Hungary. Lecture Notes in Computer Science 4207, Springer Verlag. Masahito Hasegawa, Martin Hofmann and Gordon Plotkin Finite Dimensional Vector Spaces are Complete for Traced Symmetric Monoidal Categories Mostly these reference cover the Tensor/Monoidal Category line. I've certainly seen other work, but am less familiar with it. A: For LaTeXing the diagrams, Tikz is extremely versatile and usable. I'd start there. A: I'll echo supercooldave's vote for TikZ. For applications to knot theory, Kassel's longer book is great, as is his short book with Rosso and Turaev on quantum groups and knots. Kauffman's book Knots and Physics also has some nice parts. You should be sure to read Penrose's original paper where he introduced the notation: R. Penrose. Applications of Negative Dimensional Tensors. Combinatorial mathematics and its applications. D.J.A. Welsh, ed. Mathematical Institute, Oxford, Academic Press, London, 1971. pp. 221-244. Of course, for (linear) algebra, there's Cvitanovic's book. I call it a "linear algebra" book in the same way that the right way to understand much of Lie algebra theory is as graduate level linear algebra. I think that Joyal and Street are the correct names for proving that planar diagrams exactly capture monoidal category theory. So diagrammatic languages are not just for Vect, but for almost any category. To make the last comment more precise, I recently went to a talk by Bruno Vallette on "properads". One of his points was that such things (a blend between props and operads) on the one hand can basically capture any algebraic structure that you like, and on the other hand are naturally described with these graphs and diagrams.

Leave a Message Testimonials Post Your Testimonial Nice & cool place with the full term satisfaction of both mind & money & above all yours skin the healthy relationship shared between the customer and all the didis. Ms. Naina Shahi Best spa in the world, because it is full of merits, love, affection, and above all customer satisfaction which is main quality of it... Ms.Smita Rungta Its really difficult to express the essence of satisfaction. My face was covered with pimples, but after ozone treatment my skin was improved. Juvena is the second name of satisfaction and healthy relationship of client and staff of Juvena is excellent example of perfection. My best wishes are always with Juvena. Juvena has created the awesomeness in field of beauty.Thanks Tanu Shukla First of all thanks , it is so good for me & my skin there is drastic improvement of myself in my confidence and I have no words how much better I feel. Once again thanks a lot for giving me such a good treatment. Amrita Srivastava Then: Earlier when people would stare me for more than 5 sec I felt my hair or fare must be wrong or out of place. Now guess can not help the shiny hair nor the good skin. Thank you for making me feel good about my self. From everyone, learnt new things that made me feel good and believe there is always room for improvement. H.teresa What else to say maam Juvena is a beautiful place. It soothes every person internally.The respect for individuality is seen and the positivity grows with every visit of the customer. I have a great time every time I visit Juvena...Thank you Mridul pandey No words I have not seen such amazing products so far, and the services are just reflection of the commitment. Juvena is indeed the best Tanu Shukla I am simply in love with Juvena...I can bet once u start your visit at Juvena you simply can not ignore it....The herbal treatment are worth you spend...Once you feel the magic of Juvena you can not go elsewhere....From a true Juvena lover... Supreeti mayak Srivastava Having visited various parlours & spas across India, Juvena has been the best experience so far for me. The genuineness and commitment of the team is really commendable. If you are in Gorakhpur, i will recommend to visit this place once. The products and services will definitely delight you.All the best team Kalyani Agarwal The environment as well as service provided during my bridal package was very good. The staff is co-opreative the care, positivity, the way she made me beautiful is memorable . Jagrati I have come in juvena Herbals first time & I am totally satisfied from here and I want to come here again and again . Thank You Nidhi I am satisfied with Juvena team. Sapna Bajaj I am satisfied from here this place makes dream come true. Seema chaubey यहाँ आकर मझे अच्छा लगा | Nidhi Agarwal I have come in Juvena Herbals first time & I am totally satisfied from here and I want to come here again & again ."Its very good spa". Thanks Nidhi Singh As the name goes Juvena Herbals the package which I took was rejuvenation. It made me felt more confident and special than before. Shweta Dubey The first visit to Juvena made me feel as if I have come to skin specialist. The treatment & guidance given here is very effective . I sincerely appreciate the dedication & support provided by the Juvena Team to each & every customer ."Thanks to Juvena & Mrs. Medha Singh" Shipra Diwedi Too good. the beauticians are very much efficient in the work . The level of comfort they give with the warmth attitude is very much appreciable. Kalpana Singh It made a lot difference to my overall body & skin. I am really satisfied and happy that this kind of complete care is available in Gorakhpur. Thanks a lot. Daraksha It was really great to be here. Never expected what was done. Felt like heaven .Staff are very joyful, coordinating and supportive. Would really love to visit once again . The Best was "Russian Bath".Keep it up. A good job.God Bless You ! Shyama Upadhyay Good Madhulika Anand Friendly & would like to say that the environment over here is just cool.Staffs are good and always very professional to the clients. It is really a great experience for me from last 15 days excellent work. Last but not the least special thanks to Medha Didi who has given me love care & pampered me like a sis... Abhilasha Juvena is the best clinic in U.P according to me .Every body is very friendly here I love to come here. Madhubala shukla Juvena is a Jannat in juvena every person is so sweet and their work is marvellous I am lucky because Juvena in my city. God bless you Shipra I went through the 7 days Pre-bridal treatment it was an amazing experience for me. I had a great time here . I liked this treatment and staff as well. All are very sweet and hardworking. All the very best for Juvena Rachana Subbia There is a phrase "Beauty lies in your own eyes" and eyes can believe whatever it can see I must say its amazing to see difference in my own skin, personality as well as confidence level.I would like to pay my vote of thanks to whole JUVENA TEAM for their excellent behavior, commitment for work & making a Real Difference in my life. Last but not the least heartily Thanks & Congrats for your efforts to making Beauty Appreciable. Priyanka Kushwaha Sweet Medha Di & Lovely staff I would like to say that I got complete satisfaction and care here. I am lucky that I got chance to come here and I will try my best to come here again and again.Good work done by everyone Shazia Khan Dearest & Everloving Medha Aunty "I will miss you all" I know juvena since my childhood and every time I visited I got a new experience of how to look more beautiful . Though I never followed the diet chart... then also i want to look beautiful. Thanks for all your guidance and care. Kusum Pandey I feel nice here. After taking mexo I feel my self very light. As if i have reduce a big part of my body .Now Its my heartily wish to reduce my self at any cost. Sumita Roongta There is no other substitute of Juvena.I like Mexo therapy too much. Anuradha Shukla It is comfortable & hygienic here. Staff is very cooperative . I love this place. Chaitali After taken Russian bath i feel very relax , comfortable. Priyanka Srivastava I am coming to juvena when i was just 12 years of age one thing I can assure everybody i.e. "U can trust Medha Di & her advice blindly".This parlor is best among the rest... So if you are searching for a good parlor want to see the satisfactory change, come to Juvena & discover your glowing skin. Khushboo Singh Seema Srivastava The products used are herbal and good for skin. Shikha Srivastava I had a wonderful experience with a wonderful staff and their services. All the products are excellent and I enjoyed a lot.And this bonding will be never ending. Thanks a lot for all & thanks caring a lot Ruhina Dutta Abha Srivastava Frankie Heley It was good experience the services is very good and the staff members are very cooperative . I enjoyed a lot. Thank you Ranjana Yadav It was good experience .I like Russian bath most. I enjoyed too much. Anchal Pandey The services is very good. staff members are cooperative . i enjoyed a lot. thank you NISHU It was truly wonderful and blissful to have the privilege of spending time with all of you and enjoying your services. I am feeling blessed. I am felling beautiful and this feeling of mine proves that all of you have WON. Thank you. Dr. Monika Srivastava Its a very good experience I enjoyed this. I think Juvena is really providing a good quality of beauty and health services in Gorakhpur. All the staff members are very caring & cooperative the products used here is also excellent. Thanks a lot. Puspanjali The overall experience was really good. The team work is really appreciable because staff work with full of devotion and patience. I love their work & everyones care & concern for the bride. Ankita Srivastava Hello Medha D & Team, I took 7 days pre-bridal package here.The initial days of package I will rate it excellent but gradually as package proceeds my satisfaction level was a bit lessen, so the overall rating for the package is very good.The staff is very friendly and the make-up done here are "Excellent".Surely it is "No.1 herbal clinic" as the results are not only acclaimed but felt. All the very best for your future endeavors. Supriti Singh Very good feeling in these 7 days and all the team members are very cooperative and treat very nicely the products are very good but please add meso in the 7 days bridal pack that will be more effective to the brides. Else all is good & excellent. Saumya Agarwal I have visited or have taken the weight reduction programme in Juvena . The whole treatment procedure was awesome in this time the feeling was another I have taken bridal package for 7 days. I feel the staff members are so good and kind people will see the result in my wedding. The result is awesome. Thank you all staff members & all Didis and especially Medha Didi that she opened Juvena in Gorakhpur. Shilpa Agarwal Overall package was excellent that I feel when I touch my skin.It was fabulous experience .Teamwork was great. There was always a sense that expert is sitting. Miss u Medha Di a lot. for all your products and advises & services hope this journey will be continued... CHITRA I am really very-very thankful to you as well as your staff.Your staff is very caring understanding and very much friendly towards me.They gave me comfort they all are always smiling. My best wishes are always with u. Pratibha Trpathi Your staff is very caring and very friendly towards me. I am very thankful to you as well as your staff. Shumita sumbul You people have been very much professional. Very good & just keep it up. Medha Di Love u Mrs. Sarita vidhyarthi this was my first experience in your parlous. i have spended five days here. my experience from the reciving door to exit was very good, your services & hospitality and staff behaviour specially personal tuch makes you different from others your spa sectionis very caring. i cant nominate one person whole section has very wonderful behaviours. thank you Mitali Khare Your bridal treatment team is really good. Mine was 7 days russian bath . I am satisfied with the services. Best wishes Akansha sinha The bridal package of Juvena is awesome. I had opted for 15 days package & really the amount paid for that is worth as I see the effects on my face as well as body. The team is also very good all the team members are very mature & cooperative .Things are good here. At present I am in Gorakhpur for few days but in future whenever I will be in Gkp for facial and russian bath i will opt Juvena last but not the least the products of Juvena are good & economical.Best wishes Shweta mall The bridal package of Juvena is like a miracle.I have taken it for first time and seen the enormous effect of it. The beauty gets enhanced & confidence gets boost up.I am really impressed all the staff members love, care & affection. My all best wishes are with you.Hope whenever I will visit here after my marriage I will get the same response. Pragya agarwal I am thankful to Juvenas products It works very well & suits skin. Awesome results I found in my skin and hair. Priyanka pandey It was a nice & wonderful experience to have a facial done from your new branch. Your staff was caring especially work done by Sapna is commendable. Keep it up Moksha Jain Excellent A+ Sonam Reheja Experienced 7 days Pre-Bridal package and it was fabulous Russian Bath gives you a refreshing feel and the staff is so friendly. No wastage of time quick attendance impressed by the services hence brought my mother too. Highly recommended. Superb ambiance. Regards & loads of love. Prabheer kaur chathia excellent Shahla khan Its amazing . Loved it. The best way to pamper yourself!! Anchal Jaiswal Medha G it was really wonderful meeting you. Good services, good staff. Russian bath it was really like "jannat ki sair". I wish I could stay more.I wish you good luck . Thank you so much. Kiran Kumar Wish I would be more regular to this place. Thank you so much Medha Ji for always giving a wonderful experience. Sangita Tiwar Best services I ever had taken. Employees are caring and cooperative . I wish that your services are available in each & every cities. Thanks a lot • Abhilasha upadhyay Excellent • Garima singh I am thankful to the CEO Mrs. Medha Singh for the environment as well as service provided during my bridal package. The staff is co-operative the care, positivity, the way she made me beautiful is memorable ….I would request her to open the criteria venue makeup as I am only comfortable and satisfied with her guidance. Mam I love you & will be always looking forward for you in my life. And I wish all the best for your future. Juvena Rocks!!! • Jagriti Goyal it’s a very effective and perfect product. • Reena gupta I am extremely happy with service and care provided in this salon. I would like to thank each member of Juvena for this extremely good work. • Kusum Pandey Dearest & loving medha aunty “ I’ll miss you all” I know juvena since my childhood and everytime I visited I get a new experience of how to look more beautiful . though I never followed up the diet chart. Then also I want to look beautiful. Thanks for all your guidance and care. • Rosy singh Sweet Medha di & lovely staff, I would like to say that I got complete satisfaction and care here. I am lucky that I got chance to come here and I’ll try my best to come here again & again. • Shazia Khan The First visit to Juvena made me felt as if I have come to some skin specialist . The treatment & guideline given here is very effective. I sincerely appreciate the dedication & support provided by the juvena team to each & every customer. Thanks to juvena and mrs. Medha Singh. Shilpa Dwedi The First visit to Juvena made me felt as if I have come to some skin specialist . The treatment & guideline given here is very effective. I sincerely appreciate the dedication & support provided by the juvena team to each & every customer. Thanks to juvena and mrs. Medha Singh. Shilpa Dwedi I have come in juvena Herbals first time & I am totally satisfied from here and I want to come here again and again .its a very good spa.Thanks. Nidhi Singh I love Juvena as its my second home, after a hectic week or month its rejuvenation to visit Juvena. I am a client of your from one year and I am so glad about my decision. I love all your products and services.Your products are my favorite like marrow pack and bridal ubtan.I saw and feel a change in my skin and I have started loving and pampering myself all thanks to the guidance of Medha Mam as well as Geeta Mam.Your team is also very dedicated and hard working.Mam you not only guide for external health of skin but you also suggest for diet and relaxation.I love you Juvena-my second home. Payal Sharma Too good; the buticians are very much efficient in the work . the level of comfort they give with us . Warmth attitude is very much appreciable. kalpana singh Dear Medha Di & Sweet staff… Juvena is a “jannnat” in juvena every person is so sweet 7 their work is marvelous …. I am lucky because juvena in my city… So always be happy and god bless you to everybody…. Shipra Juvena is the best clinic in U.P. according to me everybody is very friendly here. I love to come here. Madhulata shukla Firstly I would like to say that the environment over here is just cool. Staffs are good and always very professional to the clients. Its really a great experience for me from last 15 days excellent work….last but not least special thanks to Medha Didi who has given me love , care & pampered me like a sis…. Thank you. Abhilasha There should be something more than stars to express your work. Mam u r blessed with an extra ordinary talent of making people beautiful and u master this art. Amazing Work. Loads of love n happiness. Sukriti Singh Quiet Satisfactory Services though I am new to the clinic Medha Mam & the team never let me feel that I was there for the first time I got every thing more than I expected & paid less than expect,really every one here is so disciplined .Will recommend every one the quality & the service I experienced here never experienced before.Thankyou So Much For Being So Nice!!! Navya Kashyap This is the best place where we find the best beauty services.....excellent personal service with lot of care.....staff is very friendly and caring and medhaji u r a charismatic personality.....i loved my airbrush makeup done by you on my wedding day....would definetely send u the pics....it was appreciated by everyone......:) THANKYOUUUU Sangeeta Mishra Dwivedi On my wedding day Medha mam makes me look like a princess My look was completely changed on both engagement and wedding ceremony Feels like top of this world got thousands of compliments surely believe that I made the right choice to get ready there My experience was awesome Juvena rocks Thankyou so much Medha mam and her team for their endeavors for making my special day memorable Your services available is very good,staff is friendly and as i have sensitive skin..i find this palour the best place for getting any product.May you get flying colours in life. Pratïma Yogï Preeti Having visited various parlours & spas across India, Juvena has been the best experience so far for me. The genuineness and commitment of the team is really commendable. If you are in Gorakhpur, I will recommend to visit this place once. The products and services will definitely delight you.All the best team :) Kalyani Agarwal What else to say maam!!Juvena is a beautiful place. It soothes every person internally.the respect for individuality is seen and the positivity grows with every visit of the customer.I have a great time every time i visit juvena...Thank you Mridul Pandey This is the first time I am experiencing your services.Never got a chance before. And I would first like to thank you for taking care of me n secondly want to congratulate you for such a stupendous job that you doing.Each member of your team is commendable and expert in their job and demonstrate customer centricity. Wish you more luck and success. Can not wait to see your branch in Gurgaon. Kannu Priya T. Srivastava I have no words to define... Excellent & superb is all I can say after experiencing any & every treatment in Juvena Herbal. Here skin treatment are done in very different way than the other parlours. I am in love with the all & every product I had used..it is really very different products from all other products available in the market. Thank u Medha Mam so much.. I always prefer and suggest Juvena Herbal over any other parlour wherever in India because it gives the most important thing which is "satisfaction" Thank u mam so much.

Indians all over the country celebrate Gandhi's birthday with prayers and various social activities as a mark of respect to Gandhi, famed as the torchbearer of India's fight against British rule - Photogallery Indians all over the country celebrate Gandhi's birthday with prayers and various social activities as a mark of respect to Gandhi, famed as the torchbearer of India's fight against British rule. (BCCL) Indians all over the country celebrate Gandhi's birthday with prayers and various social activities as a mark of respect to Gandhi, famed as the torchbearer of India's fight against British rule. (BCCL)

Using PHP as an htaccess Alternative Pantheon sites use NGINX to concurrently serve requests. The NGINX web server ignores distributed configuration files such as .htaccess for reduced resource consumption and increased efficiency. This configuration is standard across all Pantheon sites, and modifications to the nginx.conf file are not supported. Manage Configuration with PHP Using .htaccess is generally not recommended - even for sites running Apache. As a rule of thumb, we recommend using PHP logic to accomplish configuration changes instead. Some advantages of redirecting via PHP instead of .htaccess include: Logic and decisions can be made that a web server would have no context for, as it's executable code with application state awareness. Conditional logic, regular expressions, and much more are possible. Configuration tends to be more maintainable as Drupal and WordPress developers are typically literate in PHP, but very few people are naturally fluent in Apache2 rewrite rules and conditions. Since settings.php and wp-config.php are parsed very early in the bootstrap process, redirects like this are "cheap" with low overhead. If you use a 301 redirect, Varnish will cache it as well.

Q: Why when using Jenkins dockerfile agent does it run container with invalid user? I have a pretty standard Dockerfile: FROM python:3.6.5 WORKDIR /src COPY . /src ... install and configure things ... and a pretty standard Jenkinsfile pipeline { agent none stages { stage('Test') { agent { dockerfile true } steps { dir('/src') { sh 'pwd' // any command } } } } } However when this is run in Jenkins (I should mention I'm currently testing using a local Jenkins instance in a docker container) the Dockerfile builds successfully but when Jenkins attempts to run the step I get the following output: [Pipeline] withDockerContainer Jenkins seems to be running inside container aaee62f2a28e29b94c13fcdc08c1a82ef7baed48beabe54579db07b2fbd26b23 $ docker run -t -d -u 1000:1000 -w "/var/jenkins_home/workspace/My Project" --volumes-from aaee62f2a28e29b94c13fcdc08c1a82ef7baed48beabe54579db07b2fbd26b23 -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** -e ******** 12724611f0bf2363c9eee7288654e43eca2aabaf cat $ docker top 4e29bc102d8f4e6b4ffc142fc06eb706e95b00fa6190b2927f4f79f0cfa53af5 -eo pid,comm [Pipeline] { [Pipeline] withEnv [Pipeline] { [Pipeline] dir Running in /src [Pipeline] { [Pipeline] sh [Pipeline] } [Pipeline] // dir [Pipeline] } [Pipeline] // withEnv [Pipeline] } $ docker stop --time=1 4e29bc102d8f4e6b4ffc142fc06eb706e95b00fa6190b2927f4f79f0cfa53af5 $ docker rm -f 4e29bc102d8f4e6b4ffc142fc06eb706e95b00fa6190b2927f4f79f0cfa53af5 which is not expected, and when the step is "finished" there is the following failure message: java.nio.file.AccessDeniedException: /src at sun.nio.fs.UnixException.translateToIOException(UnixException.java:84) at sun.nio.fs.UnixException.rethrowAsIOException(UnixException.java:102) at sun.nio.fs.UnixException.rethrowAsIOException(UnixException.java:107) at sun.nio.fs.UnixFileSystemProvider.createDirectory(UnixFileSystemProvider.java:384) at java.nio.file.Files.createDirectory(Files.java:674) at java.nio.file.Files.createAndCheckIsDirectory(Files.java:781) at java.nio.file.Files.createDirectories(Files.java:767) at hudson.FilePath.mkdirs(FilePath.java:3273) at hudson.FilePath.access$1300(FilePath.java:213) at hudson.FilePath$Mkdirs.invoke(FilePath.java:1254) at hudson.FilePath$Mkdirs.invoke(FilePath.java:1250) at hudson.FilePath.act(FilePath.java:1078) at hudson.FilePath.act(FilePath.java:1061) at hudson.FilePath.mkdirs(FilePath.java:1246) at org.jenkinsci.plugins.durabletask.FileMonitoringTask$FileMonitoringController.<init>(FileMonitoringTask.java:181) at org.jenkinsci.plugins.durabletask.BourneShellScript$ShellController.<init>(BourneShellScript.java:221) at org.jenkinsci.plugins.durabletask.BourneShellScript$ShellController.<init>(BourneShellScript.java:210) at org.jenkinsci.plugins.durabletask.BourneShellScript.launchWithCookie(BourneShellScript.java:131) at org.jenkinsci.plugins.durabletask.FileMonitoringTask.launch(FileMonitoringTask.java:99) at org.jenkinsci.plugins.workflow.steps.durable_task.DurableTaskStep$Execution.start(DurableTaskStep.java:305) at org.jenkinsci.plugins.workflow.cps.DSL.invokeStep(DSL.java:268) at org.jenkinsci.plugins.workflow.cps.DSL.invokeMethod(DSL.java:176) at org.jenkinsci.plugins.workflow.cps.CpsScript.invokeMethod(CpsScript.java:122) at sun.reflect.NativeMethodAccessorImpl.invoke0(Native Method) at sun.reflect.NativeMethodAccessorImpl.invoke(NativeMethodAccessorImpl.java:62) at sun.reflect.DelegatingMethodAccessorImpl.invoke(DelegatingMethodAccessorImpl.java:43) at java.lang.reflect.Method.invoke(Method.java:498) at org.codehaus.groovy.reflection.CachedMethod.invoke(CachedMethod.java:93) at groovy.lang.MetaMethod.doMethodInvoke(MetaMethod.java:325) at groovy.lang.MetaClassImpl.invokeMethod(MetaClassImpl.java:1213) at groovy.lang.MetaClassImpl.invokeMethod(MetaClassImpl.java:1022) at org.codehaus.groovy.runtime.callsite.PogoMetaClassSite.call(PogoMetaClassSite.java:42) at org.codehaus.groovy.runtime.callsite.CallSiteArray.defaultCall(CallSiteArray.java:48) at org.codehaus.groovy.runtime.callsite.AbstractCallSite.call(AbstractCallSite.java:113) at org.kohsuke.groovy.sandbox.impl.Checker$1.call(Checker.java:157) at org.kohsuke.groovy.sandbox.GroovyInterceptor.onMethodCall(GroovyInterceptor.java:23) at org.jenkinsci.plugins.scriptsecurity.sandbox.groovy.SandboxInterceptor.onMethodCall(SandboxInterceptor.java:155) at org.kohsuke.groovy.sandbox.impl.Checker$1.call(Checker.java:155) at org.kohsuke.groovy.sandbox.impl.Checker.checkedCall(Checker.java:159) at org.kohsuke.groovy.sandbox.impl.Checker.checkedCall(Checker.java:129) at org.kohsuke.groovy.sandbox.impl.Checker.checkedCall(Checker.java:129) at com.cloudbees.groovy.cps.sandbox.SandboxInvoker.methodCall(SandboxInvoker.java:17) at WorkflowScript.run(WorkflowScript:23) at ___cps.transform___(Native Method) at com.cloudbees.groovy.cps.impl.ContinuationGroup.methodCall(ContinuationGroup.java:57) at com.cloudbees.groovy.cps.impl.FunctionCallBlock$ContinuationImpl.dispatchOrArg(FunctionCallBlock.java:109) at com.cloudbees.groovy.cps.impl.FunctionCallBlock$ContinuationImpl.fixArg(FunctionCallBlock.java:82) at sun.reflect.GeneratedMethodAccessor143.invoke(Unknown Source) at sun.reflect.DelegatingMethodAccessorImpl.invoke(DelegatingMethodAccessorImpl.java:43) at java.lang.reflect.Method.invoke(Method.java:498) at com.cloudbees.groovy.cps.impl.ContinuationPtr$ContinuationImpl.receive(ContinuationPtr.java:72) at com.cloudbees.groovy.cps.impl.ConstantBlock.eval(ConstantBlock.java:21) at com.cloudbees.groovy.cps.Next.step(Next.java:83) at com.cloudbees.groovy.cps.Continuable$1.call(Continuable.java:174) at com.cloudbees.groovy.cps.Continuable$1.call(Continuable.java:163) at org.codehaus.groovy.runtime.GroovyCategorySupport$ThreadCategoryInfo.use(GroovyCategorySupport.java:129) at org.codehaus.groovy.runtime.GroovyCategorySupport.use(GroovyCategorySupport.java:268) at com.cloudbees.groovy.cps.Continuable.run0(Continuable.java:163) at org.jenkinsci.plugins.workflow.cps.SandboxContinuable.access$101(SandboxContinuable.java:34) at org.jenkinsci.plugins.workflow.cps.SandboxContinuable.lambda$run0$0(SandboxContinuable.java:59) at org.jenkinsci.plugins.scriptsecurity.sandbox.groovy.GroovySandbox.runInSandbox(GroovySandbox.java:136) at org.jenkinsci.plugins.workflow.cps.SandboxContinuable.run0(SandboxContinuable.java:58) at org.jenkinsci.plugins.workflow.cps.CpsThread.runNextChunk(CpsThread.java:182) at org.jenkinsci.plugins.workflow.cps.CpsThreadGroup.run(CpsThreadGroup.java:332) at org.jenkinsci.plugins.workflow.cps.CpsThreadGroup.access$200(CpsThreadGroup.java:83) at org.jenkinsci.plugins.workflow.cps.CpsThreadGroup$2.call(CpsThreadGroup.java:244) at org.jenkinsci.plugins.workflow.cps.CpsThreadGroup$2.call(CpsThreadGroup.java:232) at org.jenkinsci.plugins.workflow.cps.CpsVmExecutorService$2.call(CpsVmExecutorService.java:64) at java.util.concurrent.FutureTask.run(FutureTask.java:266) at hudson.remoting.SingleLaneExecutorService$1.run(SingleLaneExecutorService.java:131) at jenkins.util.ContextResettingExecutorService$1.run(ContextResettingExecutorService.java:28) at jenkins.security.ImpersonatingExecutorService$1.run(ImpersonatingExecutorService.java:59) at java.util.concurrent.Executors$RunnableAdapter.call(Executors.java:511) at java.util.concurrent.FutureTask.run(FutureTask.java:266) at java.util.concurrent.ThreadPoolExecutor.runWorker(ThreadPoolExecutor.java:1149) at java.util.concurrent.ThreadPoolExecutor$Worker.run(ThreadPoolExecutor.java:624) at java.lang.Thread.run(Thread.java:748) Finished: FAILURE The problem appears to be with this line: docker run -t -d -u 1000:1000 there is no user with UID 1000 on the container built by the Dockerfile, commands are run by root and therefore with the directory change to /src the "user" that jenkins specifies has no access to the files. How do you prevent Jenkins from trying to use -u 1000:1000 by default? or what steps should I take to resolve this issue. I could in theory add a chmod 777 into the dockerfile but this seems like an ugly workaround Update: I added RUN chmod -R 777 /src to my Dockerfile but the issue remains. If I run the container manually from inside the docker Jenkins container: docker run -it -u 1000:1000 -w "/var/jenkins_home/workspace/My Project" --volumes-from aaee62f2a28e29b94c13fcdc08c1a82ef7baed48beabe54579db07b2fbd26b23 12724611f0bf2363c9eee7288654e43eca2aabaf /bin/bash and cd /src I have access to the files and can do e.g. touch newfile without issues. The java.nio.file.AccessDeniedException: /src still appears in the logs though A: It seems that you can override/pass docker arguments according to this, so you might try this in order to override the default using uid/gid args: A string. Runtime arguments to pass to docker run. This option is valid for docker and dockerfile. agent { dockerfile { args '-u 0:0' // or try to make it -u root } }

Q: Wrapping Antd Component I want to wrap antd component eg. Input into MyInput so I can add support for new pros and classNames, however it stoped working when I put then inside of the Form MyInput.js import { Input } from 'antd'; function MyInput({ className='', ...rest }) { const computedClassName = 'my-input '+className; return ( <Input className={computedClassName} {...rest} /> ); } MyInput.defaultProps = Input.defaultProps; MyInput.propTypes = Input.propTypes; MyInput.Group = Input.Group; MyInput.Search = Input.Search; MyInput.TextArea = Input.TextArea; Now if I put <MyInput /> inside of <Form/> it stops working DEMO I tried to debug, looks like the saveRef function in rc-form/lib/createBaseForm is receiving null as component argument, so this makes me feel is a ref problem, but I'm not sure how to fix it :S A: Nevermind I found the answer... As per Refs documentation refs doesnt work on stateless components, change it to class and worked

Q: How to call query-replace-regexp inside a function? I tend to use query-replace-regexp over an entire buffer rather than at the current position so I regularly use the sequence C-< (beginning-of-buffer), then C-r (query-replace-repexp). I'd like to make another function bound to C-S-r (C-R) which does this for me. I thought that if I simply wrapped it all together such as: (defun query-replace-regexp-whole-buffer () "query-replace-regexp from the beginning of the buffer." (interactive) (beginning-of-buffer) (query-replace-regexp)) that this would be adequate, unfortunately though I'm getting some errors. query-replace-regexp-whole-buffer: Wrong number of arguments: #[(regexp to-string &optional delimited start end) "Å Æ Ç& " [regexp to-string delimited start end perform-replace t nil] 10 1940879 (let ((common (query-replace-read-args (concat "Query replace" (if current-prefix-arg " word" "") " regexp" (if (and transient-mark-mode mark-active) " in region" "")) t))) (list (nth 0 common) (nth 1 common) (nth 2 common) (if (and transient-mark-mode mark-active) (region-beginning)) (if (and transient-mark-mode mark-active) (region-end))))], 0 I can't really see what I'm doing wrong, hopefully someone can help. A: When called from Lisp, query-replace-regexp expects to be passed regular expression and the intended replacement as arguments. If you want to emulate the questions asked when invoked interactively, you need to use call-interactively: (defun query-replace-regexp-whole-buffer () "query-replace-regexp from the beginning of the buffer." (interactive) (goto-char (point-min)) (call-interactively 'query-replace-regexp)) Also note that one should never call beginning-of-buffer from Lisp code; it will do unnecessary work, such as pushing the mark and printing a message.

0)? -1 Let i(r) = 11 + 0*r + 3*r - 1. Let g(s) = -6*s - 19. Let b(y) = -3*g(y) - 5*i(y). Give b(-5). -8 Let s(g) = -5*g**3 - 2*g**2 + 1. Suppose 8*m = 6*m. Suppose -4 = -4*p - m. Determine s(p). -6 Let s(u) = 2*u - 1 + 2 + 3. Suppose -g + 6*g - 22 = -3*i, i - 14 = -5*g. Calculate s(i). 12 Let s(z) = 2 + 12*z - 12*z + 4*z. Let a be ((-72)/(-60))/((-2)/5). Determine s(a). -10 Let v be (-126)/(-27)*(-3)/(-2). Let i = v - 1. Let p(m) = 6*m - 23. Let q(o) = -3*o + 11. Let f(l) = -3*p(l) - 7*q(l). Give f(i). 10 Let g(j) = 4*j + 2. Let y(l) = -10*l - 6. Let p(a) = -8*g(a) - 3*y(a). Determine p(0). 2 Let g(k) = k**3 + 8*k**2 + 6*k - 1. Let m(v) = 2*v**2 + 3*v - 4. Let w be m(2). Let q(n) = w*n - 5*n + 5*n - 2 + 5. Let b be q(-1). Calculate g(b). 6 Let i(a) be the first derivative of -13*a**2/2 - 4*a - 879. Calculate i(-2). 22 Let t(p) = -p**2 - p + 1. Let a(z) = z - 8. Let u be a(-4). Let k be 0*(u/4)/(-6). Let l be k + (-2 - -3)*-3. What is t(l)? -5 Let j(z) = z + 4. Let u be j(-2). Suppose 0 = u*v + 4*v - 42. Let n(f) = -f**2 + 8*f + 3. What is n(v)? 10 Let s(o) = -o**3 - 7*o**2 - 8*o - 3. Let k be s(-9). Let d(p) = 229*p + 0 + 7*p**2 - 4*p**2 - k*p - 3. Calculate d(3). 18 Let o(s) = 3. Let k(w) = w + 1. Let x(p) = -2*k(p) - o(p). Let b(h) = 2*h**2 + 14*h + 7. Let z be b(-6). What is x(z)? 5 Let w(n) = -2*n**3 - 25*n**2 - 23*n + 6. Let h(l) = l**3 + 13*l**2 + 12*l - 3. Let y(z) = -5*h(z) - 3*w(z). Calculate y(-9). -3 Let x(s) = -2 + 3*s - 2*s + 0*s. Let v(u) = -u + 4. Let z(d) = 2*v(d) + 5*x(d). What is z(-2)? -8 Let v(u) = -u**3 - 5*u**2 - 5*u + 2. Let c(b) = -b**2 + 9*b - 1. Let l be c(9). Let s be l/3*(6 - -6). What is v(s)? 6 Let w(o) be the third derivative of -1/60*o**5 - 2/3*o**3 + 0*o + 1/4*o**4 + 0 + 2*o**2. Give w(6). -4 Let t(f) = 18 + 4 - 6 - 3 - 2*f. Suppose m + 110 = 6*m. Let x = -13 + m. Calculate t(x). -5 Let x(j) = -4*j**2 + 10*j - 11. Let h be x(2). Let p(n) be the first derivative of -n**3/3 - 7*n**2/2 - 5*n + 1. Calculate p(h). -5 Let h(q) = -q**2 + q + 4. Suppose 5*z + 45 = 14*z. Determine h(z). -16 Let l be (18/(-15))/((-12)/40). Let t(y) = y - 2. Let d(k) = 2*k + 15. Let r(x) = x + 5. Let b(j) = 3*d(j) - 8*r(j). Let u(n) = l*b(n) + 9*t(n). What is u(0)? 2 Let u = -13 + 16. Let i(b) = -3*b - u*b + 4*b - 5 + 4*b. Let w be 7 + (-1 - 1/1). What is i(w)? 5 Suppose 292 - 304 = 12*u. Let f(p) = 2*p**3 - 2*p**2 - p - 1. Determine f(u). -4 Let x = -21 - -10. Let q(j) = j + 13. Determine q(x). 2 Suppose 4*n + h + 40 = -h, 12 = -2*n + 3*h. Let p(f) be the third derivative of -f**5/60 - 3*f**4/8 - 5*f**3/6 + 2*f**2. Determine p(n). -5 Let z(j) be the third derivative of -j**7/2520 + j**6/90 + 11*j**5/120 - 19*j**4/24 + 8*j**2. Let m(x) be the second derivative of z(x). Give m(10). -9 Suppose i + 5 = -i - 3*t, -t = 1. Let g(f) = -53*f + 1. Determine g(i). 54 Let f(c) = 0*c + 2 + 8*c + 2*c - 8*c. What is f(4)? 10 Let n(q) = -12*q**2 - 2*q - 1. Let x(z) = -4*z + 4. Let f be x(2). Let u be (0 + (-3)/(-12))*f. Calculate n(u). -11 Let v(f) be the third derivative of f**5/60 - f**4/24 + 7*f**3/3 + f**2. Let x be 3*-2*5/(-10)*1. Let o be (-2 - -2)/(-7 + x). Determine v(o). 14 Let t(p) be the second derivative of -p**4/12 - 7*p**3/6 + p**2/2 - 4*p. Let a(m) = -2*m + 14. Let o = -16 + 26. Let k be a(o). Determine t(k). 7 Let p be (-60)/180*(2 + (-20)/(-2)). Let j(b) = b**2 - 2*b - 5. Calculate j(p). 19 Let j(t) = -46 + 4 + 41 - t. Determine j(8). -9 Let o(y) = -4*y**2 + 7*y + 1. Let h(l) = -11*l**2 + 22*l + 1. Let u(f) = -3*h(f) + 8*o(f). Give u(9). -4 Let o be 2/29 + (-28)/406. Let p(h) be the third derivative of 5/6*h**3 - 1/60*h**5 + 0*h - 2*h**2 + o + 1/4*h**4. Give p(7). -2 Let a(l) = l**2 + 22*l + 41. Let w be a(-19). Let f(z) = -3*z - 53. Let n be f(w). Let s(r) = 3*r + 3. Determine s(n). -12 Let z(d) be the third derivative of -d**4/24 + 2*d**3/3 + 2*d**2. Let a be (-2)/3 + (-8)/(-12). Suppose a*p = p. What is z(p)? 4 Let x(w) = w**3 + 4*w**2 + 3*w - 1. Let i be x(-2). Let y(f) = 283*f - 2*f**2 + 12*f**3 - 283*f + i. What is y(1)? 11 Let x(a) be the first derivative of a**2 - 1. Suppose 22*w - 17*w = 20. Determine x(w). 8 Let x(j) be the second derivative of 5*j**3/6 + j**2/2 + 2*j. Let o(d) = d**3 - 7*d**2 + 6*d + 7. Let w be o(6). Suppose -w = 3*q - 1. Give x(q). -9 Let v(t) = 12 - 12 + 32 + 714*t + 708*t - 1425*t. What is v(10)? 2 Let r be (0 + 4/(-8))*2. Let x(b) = -13*b - 1. Let n(o) = -13*o - 1. Let t(k) = 7*n(k) - 6*x(k). Determine t(r). 12 Suppose -4*s = -93 - 11. Suppose 24 - s = 2*f. Let t(n) be the third derivative of -3*n**4/8 + n**3/6 - n**2. Calculate t(f). 10 Let y(k) = -2*k**2 + k - 2. Let c(l) = 3*l**2 - l + 1. Let b(w) = 3*c(w) + 4*y(w). Let s(x) = -5*x + 26. Let j be s(6). Calculate b(j). 7 Let n(z) = -z**2 - z. Let y(t) = -2*t**2 - 8*t + 4. Let x(j) = 3*n(j) - y(j). Let o = -5 + 9. Suppose h = -o*r + 12, -3*r + 32 = 4*h + 10. Calculate x(h). 0 Let s(w) = 63*w - 189*w + 1 + 65*w + 64*w. Determine s(-1). -2 Let i(h) be the second derivative of h**5/20 + 17*h**4/12 - 19*h**3/6 - 10*h**2 + 2*h - 14. Give i(-18). -2 Let a(b) = -b**3 - 8*b**2 - 8*b + 1. Suppose -33 = 7*h - 18*h. Suppose q + h = -4. Calculate a(q). 8 Let b(h) = h**3 - 6*h**2 + 6*h. Let i = 2 - -1. Let s be (45/6)/(2/4). Let u be s/5 + (i - 2). Determine b(u). -8 Let b be -3 + (-4)/8*2. Let h(w) = -2*w + 15. Let r(y) be the third derivative of -y**4/8 + 8*y**3/3 - 4*y**2. Let g(n) = b*h(n) + 3*r(n). Give g(0). -12 Suppose 146 = 16*j + 98. Let u(o) = o**2 + o - 8. What is u(j)? 4 Let x(c) = -2*c**3 + 4*c**2 + 2*c - 4. Suppose 10*b - 5*b + 20 = 0. Let g be b/14 - 46/(-14). Give x(g). -16 Let m(l) be the first derivative of -1/3*l**3 - l + 7 - 2*l**2. What is m(-4)? -1 Let l(b) be the third derivative of b**6/120 - b**5/15 + 2*b**3/3 + 99*b**2. Give l(3). -5 Let n(b) = -b - 1. Let i = -36 - -48. Let y(l) = -4*l - 12. Let r(u) = i*n(u) - y(u). Let v be 3/4 - (-2)/8. Determine r(v). -8 Let h(j) = -2*j. Let g(s) = 7*s - 4. Let r(t) = g(t) + 3*h(t). Let u = 4 + -7. Let d be (u - 0)/((-2)/2). Calculate r(d). -1 Let i(y) = 2*y - 29 + 11*y - 3*y + 9 - y**2 - y. Give i(8). -12 Let r(a) = -a - 11. Let b be r(-17). Let w be ((-4)/3)/((-2)/b). Let y(z) = w*z**2 + 13*z**3 - 4 - 2*z - 12*z**3 + 3 - 4. Determine y(-4). 3 Let t(i) = 3*i**2 + 5*i - 5. Suppose 19 = 5*m - b, -3*m = 3*b - 6 - 9. Let l be t(m). Let c(x) = -l*x**2 + 60*x**2 - 2 + 1 - x**3. Determine c(-3). -1 Let j(c) be the second derivative of 13*c**4/12 + c**2/2 + 19*c. Give j(-1). 14 Let h(a) = 8. Let v(n) = n + 9. Let y(x) = 3*h(x) - 2*v(x). Let g be y(5). Let o(d) be the first derivative of d**2 + d - 1. Calculate o(g). -7 Let f(z) = -318*z**2 + z**3 - 319*z**2 + 642*z**2. Give f(-5). 0 Let n(r) = 2*r**3 + 13*r**2 + 10*r - 23. Let v be n(-5). Let c(z) be the second derivative of -2*z + 0 - 1/12*z**4 - z**v - 5/6*z**3. What is c(-4)? 2 Let z(b) be the first derivative of b**3/3 - 5*b**2/2 - 6*b + 1. Let n = 10 - 0. Suppose -h + n = h. Calculate z(h). -6 Let u be 23/7 - 2/7. Let c(v) = -6*v + 8 + 1 - 15. Let s(p) = -2*p - 2. Let g(d) = 3*c(d) - 10*s(d). Calculate g(u). 8 Let b(l) be the second derivative of l**7/840 - 7*l**6/360 + l**5/120 - 3*l**4/8 - 25*l**3/6 - 5*l. Let w(n) be the second derivative of b(n). Calculate w(7). -2 Let l(j) be the second derivative of 2/3*j**3 + 1/20*j**5 + 5/2*j**2 + 5/12*j**4 + 0 + 11*j. Give l(-4). 5 Let a(t) = -t**3 - t**2 - 1. Let w be a(-2). Let h be 16/2*(-12)/24. Let f = h + w. Let b(r) = -9*r + 1. Determine b(f). 10 Let n(y) = 65*y + 26. Let a(x) = 53*x + 27. Let d(u) = -5*a(u) + 4*n(u). Calculate d(-10). 19 Let s(x) = x**2 - 2*x - 1. Let n(l) = -3*l - 9. Let i be n(-8). Let u = -10 + i. Suppose -k - 5*a = -2*k - 6, 0 = -3*k + u*a - 8. Calculate s(k). 2 Let c(w) = -w**3 - 2*w**2 + 5*w + 2. Let g(k) = -2*k + 9. Suppose 0*m + 27 = m. Suppose -o - m = -5*o + y, 2*o - 9 = -y. Let i be g(o). Determine c(i). -4 Suppose -22 = -5*c + 4*m, m - 32 = -2*c - 3*c. Let w(p) = -5*p**2 + 5*p + 7. Let d(r) = -4*r**2 + 5*r + 6. Let i(z) = -4*d(z) + 3*w(z). Give i(c). 3 Let g(d) = d**2 + 8*d + 4. Let z be -1*(-7 - -5)*(-7)/2. Calculate g(z). -3 Let u(x) = -1 + x - 1824*x**2 + 3517*x**2 - 1692*x**2. Let p = -3 - -1. Give u(p). 1 Let t(i) = -6*i**2 + 1. Let k be (2/3)/(4/282). Let a = 46 -

Q: Integer number too large Hi I'm having trouble understanding why this isn't working if(Long.parseLong(morse) == 4545454545){ System.out.println("2"); } Where morse is just a String of numbers. The problem is it says Integer number too large: 4545454545, but I'm sure a Long can be much longer than that. A: You need to use 4545454545l or 4545454545L to qualify it as long. Be default , 4545454545 is an int literal and 4545454545 is out of range of int. It is recommended to use uppercase alphabet L to avoid confusion , as l and 1 looks pretty similar You can do : if(Long.valueOf(4545454545l).equals(Long.parseLong(morse)) ){ System.out.println("2"); } OR if(Long.parseLong(morse) == 4545454545l){ System.out.println("2"); } As per JLS 3.10.1: An integer literal is of type long if it is suffixed with an ASCII letter L or l (ell); otherwise it is of type int (§4.2.1). A: If your integer value is larger than 2147483647, as your literal is then you need to use a long literal: 4545454545L ...note the L at the end, which is the difference between a long and an int literal. A lower case l works too, but is less readable as it's easily confused with a 1 (not a great thing when you're dealing with a number!)

Four Ga. officers face felony charges Four DeKalb County law enforcement officers were indicted Monday on charges ranging from smuggling drugs into the county jail to lying in a police report. Two county police officers, a Doraville officer and a county sheriff's deputy were named in the indictments. All face felony charges. "It is unfortunate that there are a few bad apples in the bunch, but it is important to note that in many instances the departments identified and investigated the wrongdoers themselves," DeKalb District Attorney Gwen Keyes Fleming said in a statement. Zachary Kronenberger, a four-year officer with the DeKalb County Police Department, is accused of violating his oath by trying to bribe another officer to fix a traffic ticket. That officer reported the offer to superiors, according to police. DeKalb police Officer Mark Maphet was charged with drunken driving and criminal damage to property stemming from an off-duty dispute over a parking spot last December, police said. Maphet allegedly scratched a woman's car with his key, according to a police report. The report also states that Maphet left a note for the woman containing racial slurs. Kronenberger and Maphet could not be reached for comment Monday. Police spokesman Sgt. Charles Dedrick said the two officers are no longer on the force. Sheriff's Deputy Jimmy Lee Butler Jr. was fired in November 2005 following an investigation by the sheriff's office. He allegedly brought drugs, tobacco and other banned items into the DeKalb County Jail. Butler is no longer with the Sheriff's Department, said spokeswoman Mikki Jones. He could not be reached for comment Monday. Doraville police Officer Bill E. Carty is accused of filing a false report. The indictment says Carty falsely accused a man of trying to run him over with a vehicle. Doraville police officials did not respond to calls for comment Monday on Carty's status. Carty could not reached for comment.

O ne of the reasons I love grinding through academic brewing papers is because sometimes findings from multiple studies can come together and inspire something new for me to try. This happens organically as I go down rabbit holes on unrelated topics and start connecting the dots. The great part about writing for the blog and my book is that it forces me to not only read the studies but try to explain them to others and think more broadly about how the results might be put into practice by brewers. This is exactly what happened when I was researching hop thiols for a chapter in the book. Looking at the findings from multiple papers, I suggested it might be worth experimenting with a hoppy lager with a dash of wine yeast for multiple science-based reasons, which this post explores. Since I suggested the experiment in the book, I thought I better take my own advice and give it a shot! Before getting into it, I first need to thank my good friend Spencer Love for helping me out with this batch, hopefully, we can team up on a few more brews for articles like this! I have to admit something though. I’m not the biggest fan of lagers. It’s kind of a running joke at Sapwood if somebody brings in a lager (or something with lactose) it goes to Mike automatically. In fact, we just brewed our first lager at Sapwood, which doubled my career lager brew count total to two batches. Don’t get me wrong, I totally get the appeal for a well-brewed pilsner, for example. But, I’d always rather have something with hops, it’s just who I am : ) I even joked for a while that I wasn’t even going to mention the word lager in the book, but then the research had to spoil it for me as I got too excited about the potential for the lager brewed for this post, which is now appropriately named Thiol Driver. What’s in this post? First I go through some of the research that inspired this particular brew, which will explain why the recipe was crafted as it was. Then the recipe and tasting notes for Thiol Driver follow the science discussion. Spoiler, it’s pretty good! The Hop-Derived Ester 2MIB Although studied slightly less in the literature, various esters from hops can impact final beer flavors and aromas just like hop thiols and terpenoids. One of the hop-derived esters that’s gotten some attention is 2MIB (2-methylbutyl isobutyrate) because of its ability to give a beer apricot-like flavors. So, which hop varieties have more of this particular ester? One paper brewed single-hopped beers in order to determine final 2MIB concentrations for different hop varieties used in the whirlpool. Only Southern Cross tested above the threshold (which is 78 ug/L). Other varieties that were below the threshold, but still had relatively high levels of 2MIB, were (in order from highest) Pacific Jade, Polaris, Huell Melon, Riwaka, and Waimea and could all be other varieties to play with for late hopping if trying to push the apricot-like ester. Yeast strains may also play a role in the final hop-derived ester concentrations, as one study looked at 2MIB in ale and lager fermentations. The results showed that a Pilsner fermented with a “standard lager yeast strain,” resulted in more 2MIB than the ale, which was fermented with an English strain. Although the increase wasn’t massive, the beers had the same dry hopping and the lager strain resulted in approximately a 17% 2MIB increase. This is exactly why I chose to ferment Thiol Driver with a standard lager yeast (S-23 SafLager German Lager). A 2018 BrewingScience paper also looked at the role of two different yeast strains (WLP001 California Ale and WLP029 German Ale/Kolsch) and the concentrations of terpenes, esters, and thiols paired with early fermentation dry hopping. They dry hopped with either Cascade or Hallertau Mittelfrüh on day three of fermentation and then tested the beer for its compounds. The Kolsch strain in the study outperformed the ale strain in final 2MIB concentrations, which suggests it may also be a strain worth trying in a beer like this to push 2MIB. I would love to see follow-up testing with the lager strain used in Thiol Driver! Synergy Between Hop Esters and Thiols The synergy between compounds is another area of exciting hop research, particularly because researchers are finding that hop thiols can actually lower the taste threshold of fruity terpenoids. One such paper looking specifically at Nelson Sauvin, which is unique in that it’s rich in the thiol 3-sulfanyl-4-methylpentan-1-ol (3S4MP). The authors tested the possible synergistic impact of the thiol when dosed with other known hop compounds. Specifically, a solution with 40 ng/L (the threshold) of 3S4MP was compared to solutions with the same amount of 3S4MP in addition to other compounds (linalool, 2MIB, and geraniol), some below their thresholds. Focusing on the paper’s findings as it relates to 2MIB, the authors found that the presence of the Nelson Sauvin thiol (3S4MP) actually enhanced the flavors of 2MIB, even though 2MIB was dosed below the threshold. This enhancement of flavor via synergy is interesting because it suggests that 3S4MP is acting as a flavor enhancer to 2MIB, boosting its flavor potential above the actual concentration. The findings above are why Thiol Driver is hopped with Southern Cross in the whirlpool, potentially pushing the apricot-like 2MIB ester close to or above its taste threshold. Thiol Driver is then dry-hopped twice with Nelson Sauvin to impart its unique 3S4MP thiol which should even further push the sensory experience of 2MIB! Thiols and Fermentation Temperature Although I go into much more detail regarding hop thiols and biotransformation in the book, here are the main three hop-derived thiols studied with their descriptors: 4MMP – Boxtree, ribes, and blackcurrants. 3MH – Grapefruit and gooseberry. 3MHA – Passion fruit and guava. 3MHA is converted from 3MH during fermentation with the right yeast strain that has been tested to produce β-lyase during fermentation. A commercial enzyme can also be used with normal ale strains (like Rapidase Expression Aroma). Now, what’s of most interest to me regarding thiols and using a lager strain (in addition to the potential for more 2MIB) is a finding that lower fermentation temperatures may help to raise final hop thiol concentrations. Remember that lagers ferment at lower temperatures than ale strains. A paper that examined whether thiol concentrations increase or decrease based on fermentation temperature dosed test beers with Mosaic hops at the onset of fermentation (early dry hopping) and measured thiols 3MH and 3MHA. The authors found that almost twice the amount of 3MHA was measured in the beer fermented at 59°F (15°C) compared to the one at 71°F (21°C) with a wheat beer yeast (Tum 68). Specifically, the above paper found that the tropical and desirable 3MHA (which is converted from 3MH) went from 4 ng/l to 8 ng/l at the lower temperature. This might not seem like much, but with a low threshold for 3MHA (9 ng/l), you can see why it’s important. Also, because 3MHA is converted from 3MH, it’s equally important that the 3MH concentration also increased when fermented at the cooler temperature going from 31 ng/l to 37 ng/l. Obviously, the more you can push the 3MH the more potential for 3MHA (especially with the right yeast strain or with a commercial enzyme). The passionfruit leaning 3MHA thiol is one that I’m most excited about, so anything I can do to set the stage for it’s production I’m interested in trying. The results above can be somewhat explained by a 2011 paper focusing on the aroma compounds in wheat beer when injected with CO2 at different temperatures (mimicking fermentation). The authors found that the polarity of the compounds played a role in the potential loss during fermentation. The more hydrophilic a compound, the more likely it will remain in the solution during fermentation and be less impacted by temperature increases. This makes sense as studies have shown that in beer and wine must fermentations volatile compounds are partly transported to the surface by CO2 and released into the gas phase. Because thiols have lower boiling points and are less soluble than other solvents like alcohols, you can see why they may be more impacted by increased fermentation temperatures. Wine Yeast and Bioflavoring (VIN 7) Ok, so if using a lager strain we might be able to push 2MIB levels (especially with Southern Cross in the whirlpool), dry-hopping with Nelson Sauvin might synergistically increase the perception of 2MIB, and fermenting at the cooler lager temperature might increase thiol concentration like 3MH, how can we try to increase the conversion to 3MHA? Enter wine yeast and their magical abilities to bioconvert! I’ve leaned heavily on wine research in this area of biotransformation of thiols because they have been looking at the topic for some time. Many of these same thiols we are interested in studying in hops are the same ones they are looking at in wines (mostly white wines). One such study examined seven wine strains for their ability to release volatile thiols, including strains L2056, NTII6, VIN7, VIN13, VL3, X5, and QA23. The results showed that VIN7 released the second most 3MH and had the highest concentration of 3MHA, which was converted from 3MH. So I think we have our winner for Thiol Driver, I used just 8% VIN7 as part of a yeast blend with the lager strain, which is easy to do with dry yeast as you can just measure out the blend in grams. So now we are taking advantage of the cooler lager fermentation temperature for thiol retention and hopefully getting a greater release of thiols with the wine yeast, which also happens to work best at the cooler lager temperatures. I purchased VIN 7 from Scott Laboratories (no association with me, this cracked me up at a recent conference, two people thought Scott Laboratories was a side project of mine). The problem is that it comes in 500-gram bricks, which is fine for me as I can put it to work at Sapwood, but homebrewers don’t need this much. You could get a brick as part of a homebrewer club and split it up amongst the members if it’s something you want to experiment with. Here is the commercial description of VIN 7 : “Ideal for the production of aromatic white wines at low temperatures. VIN 7 releases passion fruit, grapefruit, gooseberry and guava aromas and flavors from their non-aromatic precursors in the must. It is therefore especially recommended for vinification of the following grape varieties: Sauvignon blanc, Chenin blanc and Colombard.” VIN 7 Specifics: Temperature range: 13-16°C (55-61°F) Killer: sensitive Glycerol production: 5 – 7 g/l (medium range)

Multiplexed quantification of plant thylakoid proteins on Western blots using lanthanide-labeled antibodies and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). We have developed a novel calibration method that allows concurrent quantification of multiple proteins by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) after Western blotting. Calibrants were made of nitrocellulose membranes doped with lanthanide standards. Excellent linearity was obtained in the interval from 0 to 24 ng lanthanide cm(-2). Cerium-labeled lysozyme was introduced as an internal reference protein, enabling correction for up to 50% difference in transfer efficiency during the blotting of membranes. The sensitivity of the LA-ICP-MS method was comparable to state-of-the-art chemiluminescence detection and was further improved by a factor of 20, using a polymer tag. Our method allowed reproducible and multiplexed quantification of five thylakoid proteins extracted from chloroplasts of the plant species Arabidopsis thaliana (relative standard deviation (RSD) of ≤ 5% in three independent analytical series). The method was capable of measuring the L subunit in photosystem I of an Arabidopsis mutant containing <5% of this particular protein, relative to the wild type. We conclude that the developed calibration method is highly suited for multiplexed and comparative protein studies, allowing for intermembrane comparisons with high sensitivity and reproducibility.

Thursday, May 18, 2006 "The National Security Agency has created "the largest database ever" with the phone records of millions of Americans provided to the NSA by AT&T, Verizon and Bell South for a price. The NSA says it used the records to trace patterns - data mining - in the hunt for terrorists. The agency got neither warrants nor permission from the secret Foreign Intelligence Surveillance Court. As Republican Judiciary Committee Chairman Arlen Specter admitted, the FISA law "has been violated." But that's not all that is violated. The Fourth Amendment of the Constitution protects the privacy and liberty of Americans. It says the government can't search or seize you without a warrant issued on probable cause to believe you are involved in a crime. This right is the line between a democracy and a police state, where the state can search or seize at will. That is the line that the NSA program erased. President Bush authorized the program and defends it. "We are not trolling through the personal lives of millions of innocent Americans," he said last week. How do we know? The court set up to provide warrants has been ignored. The law set up to regulate the system has been trampled. How do we know the president is telling the truth? Trust us, he says. Trust the president who led us into Iraq on the basis of disinformation and misinformation? Trust the president who just weeks ago told us the NSA program involved only international calls with al-Qaida? The same president who said he'd fire anyone in the White House who helped leak the identity of Valerie Plame, the undercover CIA employee whose husband helped expose Bush's lies about Iraq's nuclear capacity? Now, with Karl Rove in the center of the effort to discredit Wilson and out Plame, the president says he has no comment on a continuing criminal investigation. This isn't a routine Washington dustup. This concerns the trampling of the Fourth Amendment by the government and the sale of our privacy by the phone companies. And it isn't an isolated case. Bush, along with Vice President Dick Cheney, who is the major force behind this thing, believes the president acts above the law in the war on terror. He claims the right to make war without a congressional declaration; to surveil Americans without warrant; to arrest us without probable cause; to hold us without a hearing; to deny us the right to counsel or even to hear the charges against us if the government decides, on the basis of evidence they need not produce, to tag us as accomplices in the war on terror. Now most Americans would gladly sacrifice some of our liberties if it would increase our security against another Sept. 11. Bush counts on that feeling when he acts above the law. But the entire fabric of our freedom is woven into a system of checks and balances. Here, all the checks and balances have been tossed aside. Qwest, the only honorable phone company, refused to cooperate with the NSA in this program without a warrant or permission from the FISA Court. NSA refused to produce either; the FISA court was ignored. The NSA and the administration have simply refused to supply information to Congress, and the lame Republican Congress has refused to hold them accountable. When the Justice Department's independent Office of Professional Responsibility opened an investigation on the lawyers who signed off the program, the White House refused to provide the secrecy clearances needed to have the investigation go forward. "Trust us," the president says, and then he ensures that we have no choice but to trust him, since every legal check and balance is locked out. It is time for accountability. Two public-interest lawyers have sued Verizon for $5 billion for violating the law, which should force the administration to defend the program before an independent court. Don't hold your breath for this Congress to hold hearings. But Democrats should stand up and promise an in-depth series of investigations of this administration and its lawlessness - from Halliburton's making off with billions in sole-source contracts to the cesspool of hidden prisons to the trampling of liberties at home. We wage the war on al-Qaida terrorists in defense of our freedoms. We'd better make certain this administration isn't shredding those freedoms along the way." -------

Two Vilano Beach doctors have donated this building to JASMYN, the Jacksonville Area Sexual Minority Youth Network. The building is located adjacent to JASMYN's current offices in Riverside. Two Vilano Beach doctors have donated a building to JASMYN, the Jacksonville Area Sexual Minority Youth Network. Paul Schilling and James Dutton purchased and donated the building next door to the current JASMYN House on Peninsular Place to meet the nonprofit’s critical need for additional space. The gift includes a portion of the costs associated with the building’s repair and renovation, which is to be complete by late October, according to a news release from JASYMN. “After 12 years in our current location, the number of youth we serve has grown exponentially and we have literally outgrown the building," said executive director Cindy Watson. “ We have immediate needs for more program areas and desperately need additional space to accommodate our increased counseling staff and growing HIV Clinic. The additional building will allow us to dedicate space for these and other services.” The organization, which serves lesbian, gay, bisexual, transgender and questioning youth, is celebrating its 20th year. Board chair Bruce Musser said the additional building is the first major step in a planning and expansion process begun more than a year ago. “Paul and Jay really understand our immediate need and ultimate goals. They hope to support us with an eventual capital campaign that will provide the space we need to truly expand for the future ... space that will provide for our youth programs and services as well as gathering space for use by the community for other programs and events," he said. "We are so grateful for their belief in us and for sharing our vision.” In a joint statement, Schilling and Dutton said “JASMYN is a warm and caring organization providing advocacy services to the at-risk and vulnerable LGBT youth of Jacksonville.” “Their commitment to support and empower LGBT youth is remarkable. This donation represents a celebration of their 20th anniversary and we see it as a strategic step in JASMYN’s future growth," they said in the statement. "We’re so pleased that this building provides the segue they need to move them closer to launching a capital campaign.” JASMYN is currently identifying how the space in each building will be used to optimize staffing, programs and services. The organization will hold a special 20th anniversary celebration on Nov. 8 at Unity Plaza in Riverside. The event will feature the stories of many of the youth who have, with the nonprofit's help, "gone on to lead proud, productive and successful lives," according to the release.

(This story originally appeared in on Mar 26, 2017) CHENNAI: More than 200 individuals and companies have deposited unaccounted money to the tune of Rs 600 crore in various bank accounts in Tamil Nadu and Puducherry after demonetisation was announced on November 8 last year.Most of the accounts in which such deposits were made are in rural Tamil Nadu, but some are in Chennai. Many such instances were reported in suburban areas and districts adjoining cities, said income tax sources.Officers told TOI that an individual in Tiruchengode in Namakkal district deposited Rs 246 crore in a branch of the Indian Overseas Bank."We were following him for more than 15 days after finding that he had deposited cash in a rural branch of the IOB.First, he tried to hide, but after a few days he agreed to join the Pradhan Mantri Garib Kalyan Yojana (PMGKY) and pay 45% of the total money as tax. As per PMGKY , 25% of the money will be retained with the government without any interest," a senior I-T investigation wing official told TOI. The cash deposited by the individual was in old demonetised currencies. There are several similar individuals and companies who have deposited cash in their accounts and accepted that they were unaccounted income."Most of them have joined the PMGKY scheme, which comes to an end on March 31. We hope the total unaccounted money will go up to Rs 1,000 crore before the month end. We are also warning people who are still not on board that the heat will increase from April 1," said the official.Soon after December 31, 2016, all banks in the country were told to send the list of account holders who had deposited cash above Rs 2.5 lakh after demonetisation. "All the lists were sent to our headquarters and with the help of a software we scrutinized it and dispatched them to our regional offices for follow-up action. After we received the TN and Puducherry list, it was divided between investigation wing and the assessment wing in the I-T. All deposits with PAN were taken over by the investigation wing," said the official. Across the country, the I-T department found Rs 85 lakh transactions to be suspicious."In TN and Pondy, we found 28,000 accounts to be suspicious and some of the accounts had deposits in cash to the tune of Rs 85 lakh or move. In the first instance, we send a mail to the account holder asking for details. Most of them have replied and some of the cases have been closed or they have joined the PMGKY scheme accepting that the cash was black money," he said. But in some cases, despite several reminders, the account holders have not replied. "We will wait till the end of the month and go behind them. If they accept on their own, the tax is only 45%. But if we find the money to be unaccounted, then the total tax will be around 83.5%," the official warned.

Brenna Butler, Westminster College senior political science and philosophy major, reflects on her summer courses at American University and internship at the Reason Foundation, an American libertarian research foundation in Washington, D.C. “You may know Westminster’s faculty primarily as excellent teachers, but all of our faculty members are also active scholars, each a respected expert in his or her various field of study,” said Dr. Michael E. Aleprete Jr., first year program coordinator and associate professor of political science. Last semester, a group of students gathered together to discuss potential speakers for one of the oldest surviving collegiate conventions in the country; Westminster College’s 20th Mock Convention. “Karl Rove,” one student suggested. So, they made it happen. Westminster College will host Dr. Rachel Vanderhill, author and assistant professor of political science at Wolford College, at 3:40 p.m.Thursday, April 9 in Mueller Theater, McKelvey Campus Center. The event is open to the public.

This Blog is intended to collect information of my various Intrests,pen my opinion on the information gathered and not intended to educate any one of the information posted,but are most welcome to share there view on them Show statistics for TCP (or) UDP ports using netstat -st (or) -su # netstat -st # netstat -su 4. Display PID and program names in netstat output using netstat -p netstat -p option can be combined with any other netstat option. This will add the “PID/Program Name” to the netstat output. This is very useful while debugging to identify which program is running on a particular port. Note: Use netstat -rn to display routes in numeric format without resolving for host-names. 9. Find out on which port a program is running # netstat -ap | grep ssh (Not all processes could be identified, non-owned process info will not be shown, you would have to be root to see it all.) tcp 1 0 dev-db:ssh 101.174.100.22:39213 CLOSE_WAIT - tcp 1 0 dev-db:ssh 101.174.100.22:57643 CLOSE_WAIT - About Me Hi This is Suresh Kumar Pakalapati . I am a person who is positive about every aspect of life. There are many things I like to do, to see, and to experience. I like to feel the music flowing on my face, I like good books and romantic, action,cartoon movies. I like the land and the nature, And, I like to keep smile on my face. I always wanted to be a great and successful person in the world and I know it is needed More and More education, More work, Success Never come in a short Time.....

Nitrogen-Terminated Diamond (111) Surface for Room-Temperature Quantum Sensing and Simulation. The nitrogen-vacancy (NV) center in diamond has shown great promise of nanoscale sensing applications, however, near-surface NV suffer from relatively short spin coherence time that limits its sensitivity. This is presumably caused by improper surface termination. Using first-principles calculations, we propose that nitrogen-terminated (111) diamond provides electrical inactivity and surface spin noise free properties. We anticipate that the nitrogen-terminated (111) surface can be fabricated by nitrogen plasma treatment. Our findings pave the way toward an improved NV-based quantum sensing and quantum simulation operating at room temperature.

Q: Is there a (necessary) redundancy in the migration format Add x to y? To add the phone column to the tickets table, I can write: ruby script/generate migration AddPhoneToTickets phone:string There seems to be a redundancy here. But is it necessary? Aren't we repeating ourselves by being required to specify "phone" both in the name of the migration (AddPhoneToTickets) as well as in the column definition (phone:string)? A: You're not required to put Phone in the migration name. For example, if you were adding a bunch of contact fields, you could just as easily call it AddContactFieldsToTickets and specify all the fields. It's not specific enough to use the name of the migration for anything but the table name, really.

Field amplified separation in capillary electrophoresis: a capillary electrophoresis mode. In field-amplified injection in capillary electrophoresis (CE), the capillary is filled with two buffering zones of different ionic strength; this induces an amplified electrical field in the low ionic strength zone and a lower field in the high ionic strength zone, making sample stacking feasible. The electroosmotic flow (eof) usually observed in CE, however, displaces the low field zone and induces an extra band broadening preventing any CE separation in the field-amplified zone. These limitations have originated the restricted use of field amplification in CE only for stacking purposes. For the first time, in this work it is theoretically shown and experimentally corroborated that CE separation speed and efficiency can simultaneously be increased if the whole separation is performed in the field-amplified zone, using what we have called field amplified separation in capillary electrophoresis (FAsCE). The possibilities of this new CE mode are investigated using a new and simple coating able to provide near-zero eof at the selected separation pH. Using FAsCE, improvements of 20% for separation speed and 40% for efficiency are achieved. Moreover, a modified FAsCE approach is investigated filling the capillary with the high ionic strength buffer up to the interior of the detection window. Under these conditions, an additional 3-fold increase in sensitivity is also observed. The most interesting results were obtained combining the short-end injection mode and this modified FAsCE approach. Under these conditions, a part of a 3-fold improvement in efficiency and sensitivity, the total analysis time was drastically reduced to 40 s, giving rise to a time reduction of more than 7-fold compared to normal CE. This speed enhancement brings about one of the fastest CE separations achieved using capillaries, demonstrating the great possibilities of FAsCE as a new, sensitive, efficient, and fast CE separation mode.

1. Field of the Invention The present invention relates generally to the field of disposable devices for anchoring bodily mounted drainage tubes such as urinary catheters and the like and, more particularly to a prefabricated device especially configured to facilitate its attachment to the drainage tube, or the like, and to the skin of a patient. 2. Discussion of the Related Art During the course of certain medical procedures, and particularly, after surgery, it is necessary to place drainage devices to prevent accumulation of fluids in various bodily cavities or organs. One of the most common of these, of course, is the urinary catheter which is generally routed through the patient's urethral opening or superpubic ostomy site. It is important to anchor the catheter device so that there is little movement with respect to the insertion site to minimize irritation. In the case of the urinary catheter the tube normally has a very long length and is hooked to a rather large bag, so it is quite easy to catch the catheter and bag which may result in dislodgement of the catheter, which, in turn, causes great pain to the patient and possibly actual physical damage. One common practice associated with immobilizing such things as catheter tubes has been to simply use several sections of adhesive tape to secure the tubing to the patient's body at a convenient spot between the insertion site and the collection bag. An alternative practice with respect to the urinary catheter has been to use a cloth retainer which fastens around the leg and has some form of cloth or plastic catheter holding device attached to it. Both of these approaches, of course, have drawbacks. In the case of the tape, it is cumbersome to use and remove and also, because it is rigid, it does not move with the compliance modulus of the skin. The cloth wrapped around the leg has a tendency to slide downward as the leg naturally narrows from the proximal to the distal approaching the knee. This requires multiple adjustments to keep the leg band in position. In addition, the system does not provide for fixing the catheter tube in place and it tends to slip through the cloth loop and can possibly detach completely with a light pull. This is especially true in view of the fact that to reduce friction between the tube and the tissue it engages at the insertion site, the tube is normally made of reduced friction material such as a silicone plastic or the like or possibly, in the alternative, is coated with a hydrophilic material which causes the material to exhibit a non-stick surface. These developments represent progress with respect to the insertion of the catheter tube into the body in terms of ease and comfort to the patient. However, they also cause difficulties with respect to anchoring the tube because of the increased likelihood of slipping of the catheter tube with respect to the tape or cloth anchor device. The need still exists for a more positive support which retains the quality of being gentle to the patient. Additional devices have also been proposed. A one-piece catheter anchoring tube or holder is disclosed by Johnson in U.S. Pat. No. 4,165,748, in which a piece of material has adhesive on one surface and is in the shape of a narrow bridge of the material that connects two larger spaced rectangular skin addressing segments. The device has two larger segments designed to adhere to the skin of the patient and the narrow or bridge portion uses the adhesive on the skin side directed to adhere to itself, forming a double fold layer. The double layer, in turn, wraps around the tube to be secured and is further provided with fasteners such as snap fasteners or Velcro.RTM. for securing the double thickness loop to itself after encircling the tube. The tube can be released and resecured but must rely on the friction of the tube encircling loop alone to anchor the tube longitudinally once fixed in position. Thus, the tube can be easily dislodged in the directional parallel to its length and slidably displaced while secured in the loop. A further device is shown in U.S. Pat. No. 3,677,250 to Thomas that discloses embodiments in which anchoring or skin adhering sections or patches are provided with integral tabs which are designed to wrap about the tubes to be secured, fixing them tangentially or parallel to the skin against the upper side of the skin anchoring patch. The tabs may permanently adhere to the surface of the tube in a non-reusable manner or, as in one embodiment, a pair of opposing tabs are provided which removably adhere to each other and slidably retain the tube or tubes therebeneath. This one-piece arrangement either does not allow for removal, replacement or adjustment of the tube or, in the case of the removable, readherable embodiment, suffers from the same ease of slidable tube displacement associated with other prior devices.

The five development purchases all look like future housing projects to be built in the next few years. This will help with the inventory shortage and the demand from relocating buyers. Diablo Petroleum purchased a parcel for $1,250,000 to build a new fuel center and retail stores near the growing 24 Road corridor. For years the land in this area just sat, waiting for things to turn around in Grand Junction. Significant high dollar sales include $8,180,000 for the former Rocky Mountain Orthopedic building and $7,335,000 for an apartment building on Main Street. Another apartment building on Bookcliff Ave. sold for $1,100,000 and a retail building on N. River Road sold for $1,600,000. The numbers and past sales for this year show Grand Junction is poised for prominent growth. Interested in purchasing or selling commercial property in the Grand Junction area? Just drop us a note or give us a call. Contact Us grandJunctionhomesguide.com Provides you with the latest tools available. I know you want to do your research before you contact me, so I show you the way to become versed in the Grand Junction Real Estate market. I take a web-based approach to selling real estate because that is where 90% of buyers begin their search. Do you have a general question about Grand Junction Real Estate? Want to know the specifics of a particular home for sale? Interested in selling your home? I want to hear from you!

influxdb: image: influxdb:alpine ports: - 8086:8086

Shares We are always careful to point out that inactive does not equate to harmless when it comes to fake medicine. Even a product that is completely inert, like most homeopathic potions, causes harm in numerous ways. They divert attention and resources away from more effective treatment, may delay proper treatment, cause financial and psychological harm, may endanger species or the environment, and instill pseudoscientific beliefs which lead to further menace. But it is true that fake treatments which are capable of causing direct harm are even worse. In this way doing nothing is a small virtue. I was reminded of this when reading about a new medical scam in Thailand – Energy Cards. The cards are credit-card sized and are claimed to do all the usual things: “The distributors claim these cards can improve the immune system, strengthen the heart and energise the user’s metabolism. The (sic) also claim the card can purify water if it is briefly soaked in it.” The ability to purify water may seem a bit unusual, but remember clean water is a luxury in much of the world. The cards sell for either $35 or $50 equivalent. That is bad enough, and puts the cards in the same category as the magical power wrist bands, or the plastic cards alleged to improve the taste of wine. But these energy cards are worse than worthless. They are actually radioactive. The Thailand Office of Atoms for Peace (OAP) recently put out a PSA on the danger of the cards. The OAP (I suspect something is lost in translation) is essentially their atomic energy regulatory agency. They research and regulate the peaceful use of nuclear science. They warn: Tests on sample cards conducted by the state agency found radiation measuring at 40 microsieverts per hour, which is 350 times higher than the maximum exposure humans should get to radiation a year. The agency also warned against drinking water in which an “energy card” has been dipped, as doing so raises the risk of cancer. It said OAP would take legal action against the distributors once it has gathered enough evidence from its tests on the cards. So far, tests have revealed that the cards contain radioactive metallic elements of uranium and thorium, as well as their “radionuclide” or radioactive isotope. Let’s put that amount of radiation into context. First, I think the “350 times higher” is a mistake. If someone is exposed to 40 microsieverts per hour for an entire year, that results in 350 millisieverts (mSv) total exposure. I think that’s where the “350” comes from. The recommended limit of radiation exposure is 100 mSv per 5 years. So that is 17.5 times the recommended maximum exposure. Another way to look at this is that you would reach your 5-year radiation exposure limit in 104 days of continuous exposure. 100 mSv is also the lowest annual dose that has been clearly shown to increase cancer risk. This means that long term exposure to these cards (from keeping it in your wallet, for example) could lead to unsafe levels of radiation exposure. For further comparison, normal background radiation results in about 3.65 mSv of exposure per year, so the cards result in about 100 times greater than background exposure. A chest X-ray results in 0.1 mSv exposure. A full body CT scan – 10 mSv. But it gets worse, because these cards may also be a source of radioactive contamination. Radioactive exposure simply means that radioactive particles passed through your body. Someone or some thing exposed to radiation, however, is not themselves radioactive. Radioactive contamination, however, results from exposure to particles that are themselves radioactive. The OAP is warning that these cards, which contain uranium and thorium, may result in contamination. This significantly increases the hazard they represent. Radioactive contamination can get into one’s environment and then result in ongoing exposure to radioactivity. If it gets in the water (as recommended by the company selling the cards) or into food, then the contamination can be consumed and become internal, which is much more risky. Further, these cards can release radioactive contamination into the environment, causing further exposure and contamination of food and water supplies. The OAP further reports that these cards are being sold through a pyramid scheme, which is not unusual for snake-oil distributors. The obvious question is – why would the company bother to make their cards with actual uranium and thorium? And how did they source these radioactive elements? Other reports indicate that the cards also contain heavy metals. The company selling the cards, Expert Pro Network, sells other supplements with dubious claims. They claim the cards work through “negative ions”. It is further reported that: Surin, a former police officer, claims to have begun selling the cards after he acquired them from La Genius. La Genius was a Malaysian MLM company that has since collapsed. The cards themselves are reportedly of Indonesian origin, but also contain the words “German Technology” on them. So it may be difficult to track down their origin, but I suspect the OAP is working on it. Perhaps the creators of the cards thought that the radioactivity would be a selling point, because the cards are giving off actual “energy”. This was actual a common form of snake oil around the turn of the last century, soon after radioactivity was discovered. There were radon infused waters, radium containing pendants, and thorium and uranium containing medicines. People extolled the curative powers of these radioactive tonics, all the while slowly killing themselves with radioactivity. These products did not disappear from the shelves until the FDA banned them in 1938. I guess the lesson here is that if you are going to scam people with worthless snake oil, you’re better off making it completely fake, rather than radioactive.

Q: Playback issues in Audacity and other apps I'm running Ubuntu 16.04 on a virtual machine (2 GB RAM, 12 MB video memory) in VirtualBox 5.1. The host OS is macOS Sierra 10.12.5. Whenever I play a sound on Audacity, the output sound is garbled and glitchy for a short while and the playhead jumps a couple of seconds ahead. The sound plays normally after that. I tried reinstalling Audacity from Ubuntu Software. I also tried installing Audacity from the PPA. But the problem persists. I'm experiencing similar issues with other apps as well. For example, in TuxGuitar, the position of the playhead and the actual note being played are not in sync. Does anyone know a way to solve this problem? I would really appreciate any help. Thanks! Ubuntu Version: 16.04 VirtualBox Version: 5.1.22 Virtual Machine Memory: 2 GB Virtual Machine Disk Size: 16 GB Host OS: macOS 10.12.5 A: I had the same problem with Ubuntu 18.04, Audacity 2.1.1 and VirtualBox. I found that by changing Audacity's playback device to "sysdefault" the scratching and jumping goes away.

398 F.2d 286 Benny Lee WHALEN, Appellant,v.UNITED STATES of America, Appellee. No. 18963. United States Court of Appeals Eighth Circuit. July 12, 1968. James P. Brown, St. Louis, Mo., for appellant. Joanne S. Sisk, Atty., Dept. of Justice, Washington, D.C., for appellee; Veryl L. Riddle, U.S. Atty., Irvin L. Ruzicka, Asst. U.S. Atty., St. Louis, Mo., and Lillian C. Scott, Atty., Dept. of Justice, Washington, D.C., on brief. Before MATTHES, MEHAFFY and LAY, Circuit Judges. PER CURIAM. 1 This is an appeal from a judgment entered on a jury verdict finding the appellant guilty of unlawful possession for purpose of sale and unlawful sale and delivery of d-amphetamine sulfate powder, a 'depressant or stimulant drug' within the meaning of 21 U.S.C. 321(v)(2). 2 The illegal sale or possession of depressant or stimulant drugs is prohibited by 21 U.S.C. 331(q)(2) and (3), whether or not the drugs have been sold or shipped in interstate commerce at any time. The sole question here is the constitutionality of the applicable statutes. Appellant contends that they are unconstitutional in that the 1965 amendments to the Federal Food, Drug and Cosmetic Act exceed the constitutional grant of power to Congress over interstate commerce under Article 1, Section 8, Clause 3 of the United States Constitution. 3 The identical question was decided adversely to appellant's contention in White v. United States, 399 F.2d 813 (8th Cir. July 9, 1968). We affirm on the basis of the soundly reasoned opinion in White, supra. See also, Deyo v. United States, 396 F.2d 595 (9th Cir., June 5, 1968).