bluuebunny/crossref_metadata_2025 huggingface dataset:
Women with bleeding disorders
Authors: Hermans C. , Kulkarni R.
Published: May 2018

Diagnosis of the genetic status and assessment of potential clotting factor deficiency in haemophilia carriers are performed more easily nowadays. However, delays in providing those diagnosis and appropriate management are often reported despite increased availability of genetic techniques and improved awareness that carriers may have bleeding experiences. Women with von Willebrand disease (VWD) and rare factor deficiencies (RFD) may bleed during pregnancy and following childbirth and in some cases may experience adverse foetal/neonatal outcomes. This review describes the evolution of practice, unmet needs and options for both girls and women in families with haemophilia as well as the clinical and laboratory characteristics during pregnancy and recommendation for the delivery and the postpartum follow‐up in women with VWD and RFD.
A Randomized, Double‐Blind, Placebo‐Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a Treadmill Test in Patients With Stable Angina
Authors: Depre Christophe , Antalik Lubomir , Starling Amaal , Koren Michael , Eisele Osaro , Lenz Robert A. , Mikol Daniel D.
Published: May 2018

Objective

To determine the potential impact of erenumab, a human anti‐calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise‐induced angina, and ST depression in a double‐blind, placebo‐controlled study in patients with stable angina due to documented coronary artery disease.

Background

The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established.

Methods

An exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo. The primary endpoint was the change from baseline in exercise duration as measured by TET with a noninferiority margin of −90 seconds. Safety follow‐up visits occurred through week 12. Eighty‐eight participants were included in the analysis.

Results

LS mean (SE) change in TET was −2.9 [14.8] seconds in the erenumab group and 8.1 [14.4] seconds in placebo; adjusted mean (90% CI) treatment difference was −11.0 (–44.9, 22.9) seconds. The CI lower bound (–44.9 sec) did not reach pre‐defined non‐inferiority margin of −90 seconds, demonstrating that TET change from baseline in the erenumab group was non‐inferior to placebo. There was no difference in time to exercise‐induced angina in erenumab and placebo groups (median [90% CI] time of 500 [420, 540] vs 508 [405, 572] seconds; hazard ratio [90% CI]: 1.11 [0.73, 1.69], P = .69) or time to onset of ≥1 mm ST‐segment depression (median [90% CI] time of 407 [380, 443] vs 420 [409,480] seconds; hazard ratio [95% CI]: 1.14 [0.76, 1.69], P = .59). Adverse events were reported by 27% and 32% of patients in erenumab and placebo groups.

Conclusions

Erenumab did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.
Headache and Ophthalmoparesis: Case Report of an “Atypical” Incomplete Miller–Fisher Syndrome
Authors: Moreno‐Ajona David , Irimia Pablo , Fernández‐Matarrubia Marta
Published: May 2018

Objective

To expand the differential diagnosis of headache and ophthalmoparesis by describing a case report in which anti‐GQ1b was demonstrated to be the cause.

Background

Anti‐GQ1b antibody syndrome refers to a clinical spectrum of conditions that share common mechanisms and overlapping manifestations, including the Miller–Fisher syndrome, pharyngeal‐cervical‐brachial weakness, and Bickerstaff brainstem encephalitis. Rare atypical cases presenting as acute ophthalmoparesis (AO) without ataxia or areflexia have been described. Headache is a rare condition in these disorders.

Methods

A 49‐year‐old woman with no history of headaches began experiencing an acute severe bilateral throbbing headache associated with nausea and photophobia. Five days later, she developed constant binocular horizontal diplopia.

Results

Bilateral paresis of both sixth nerves was noted. Her ocular fundi, tendon reflexes, and other findings of the physical exam were normal. In addition, both a brain MRI performed with gadolinium and a lumbar puncture yielded normal results. Serum anti‐GQ1b IgG was found to be positive. Her symptoms resolved completely following treatment with immunoglobulins (0.4 g/kg/day for 5 days).

Conclusions

This is the first reported case of AO related to anti‐GQ1b antibodies presenting with headache as its initial symptom. The presence of anti‐GQ1b antibodies should be determined in patients with headache and AO of unknown origin. Immunoglobulins could hasten the resolution of symptoms in these patients.
Working experiences of nurses during the Middle East respiratory syndrome outbreak
Authors: Kang Hee Sun , Son Ye Dong , Chae Sun‐Mi , Corte Colleen
Published: May 2018

Aims

To explore working experiences of nurses during Middle East respiratory syndrome outbreak.

Background

Since the first case of Middle East respiratory syndrome was reported on May 20, 2015 in South Korea, 186 people, including health care workers, were infected, and 36 died.

Design

A qualitative descriptive study.

Methods

Seven focus groups and 3 individual in‐depth interviews were conducted from August to December 2015. Content analysis was used.

Results

The following 4 major themes emerged: “experiencing burnout owing to the heavy workload,” “relying on personal protective equipment for safety,” “being busy with catching up with the new guidelines related to Middle East respiratory syndrome,” and “caring for suspected or infected patients with caution.” Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. Unclear and frequently changing guidelines were 1 of the common causes of confusion. Participants expressed that they need to be supported while caring for suspected or infected patients.

Conclusion

This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak.
Staff and patient accounts of PRN medication administration and non‐pharmacological interventions for anxiety
Authors: Martin Krystle , Ham Elke , Hilton N. Zoe
Published: May 2018

Most psychiatric inpatients will receive psychotropic PRN medication during their hospital stay for agitation, anxiety, and/or insomnia. While helpful in some cases, caution is warranted with regard to PRN use due to inherent risks of additional medication; therefore, experts advise that non‐pharmacological interventions should be attempted first where indicated. However, research to date highlights that, in practice, non‐pharmaceutical approaches are attempted in a minority of cases. While some information is known about the practice of PRN administration and the use of and barriers to implementing non‐pharmacological interventions for treating acute psychiatric symptoms, full understanding of this practice is hampered by poor or altogether missing documentation of the process. This study used interviews with patients and staff from two psychiatric hospitals to collect first‐person accounts of administering PRN medication for anxiety, thereby addressing the limitations of relying on documented notation found in previous research. Our results indicate that nurses are engaging in non‐pharmacological interventions more often than had previously been captured in research. However, the types of strategies suggested are not typically evidence based and further, only happening approximately half the time. The barriers to providing such care are centred on two main beliefs about client choice and efficacy of these non‐medical strategies. Implications for research and practice are discussed.
Putin's Peaks: Russian Election Data Revisited
Authors: Kobak Dmitry , Shpilkin Sergey , Pshenichnikov Maxim S.
Published: May 2018

Two years ago, Dmitry Kobak, Sergey Shpilkin and Maxim S. Pshenichnikov uncovered anomalies in Russia's election data. Following President Vladimir Putin's re-election in March this year, they take a fresh look at two new sets of data – but find much the same story within
“Zombie Trucks”: Cleaning up the Working Dead
Authors: Kaur Dipleen , Krall Jenna R.
Published: May 2018

“Zombie” or “glider trucks” bring old engines back to life, but a rule change that requires those engines to meet current emissions standards is stuck in limbo. Dipleen Kaur and Jenna R. Krall discuss the impact this delay may have on pollution and health
Tribal Economies: Water Settlements, Agriculture, and Gaming in the Western U.S.
Authors: Deol Suhina , Colby Bonnie
Published: May 2018

This paper examines patterns in water rights quantification, agriculture, gaming, and economic characteristics across selected Native American nations in the United States (U.S.) to provide a perspective across tribal nations and regions. A unique set of data was analyzed, drawing from the U.S. Census Bureau, U.S. Department of Agriculture, court decrees, water rights data, and other sources. Fifty‐one tribal nations are included in this study, based on availability of data on agricultural and economic indicators. Data analysis indicates the following: 1) tribes with quantified water rights also have higher agricultural revenue, 2) tribes which have quantified their water rights are more likely to also operate a casino, 3) tribes which have quantified their water rights tend to be more commonly located close to major cities, and 4) tribes which operate at least one casino have notably higher annual household income compared to tribes which do not. A number of interesting regional differences are observed: 1) Northwest tribes have significantly higher rates of water quantification than other regions, 2) Midwest tribes have the highest prevalence of casino operations compared to the other areas, and 3) the Southwest has the smallest proportion of tribes with casino operations. This paper identifies patterns across multiple tribal nations and across regions, and does not focus on establishing cause‐and‐effect. Causal relationships among tribal water quantification, farming, gaming, income levels, and unemployment will vary by location and tribe. Identifying cause and effect among different components of tribal economic development warrants further inquiry. The examination of patterns presented here illuminates interesting differences among tribal nations and regions, and provides a broad context for tribal leaders how best to cultivate sustainable, resilient economies and water resource management.
Assessing Tribal College Priorities for Enhancing Climate Adaptation on Reservation Lands
Authors: Fillmore Helen M. , Singletary Loretta , Phillips John
Published: May 2018

On reservation lands, tribal colleges and universities (TCUs) are key to preparing indigenous communities to adapt to the effects of a changing climate. The original mission of TCUs, to improve access to higher education and to sustain the cultural heritage of indigenous people, facilitates close ties between TCU faculty and staff and the indigenous communities they serve. Since 1994, the land‐grant status of TCUs allows access to limited federal funds in support of research, education, and outreach to improve food security, natural resource management, and rural quality of life, while expanding public access to higher education to underserved populations in remote rural areas. This study was designed to assess the priorities for enhancing climate adaptation on reservation lands. It summarizes the results of an assessment implemented at the 2016 Annual First Americans Land‐Grant Consortium Conference. Study participants included faculty, administrators, outreach educators, support staff, and students representing 25 of the 37 TCUs in the United States. Results from this national assessment suggest that in order for TCUs to effectively meet the climate adaptation needs of indigenous communities, additional fiscal and human resource investments are necessary. Specifically, this includes fiscal support to enhance climate science teaching, research, and professional development programs. Additional goals include creating or expanding food‐sovereignty programs, increasing community outreach education, investigating climate change impacts on water resource quality, access, and related ecological services, and exploring renewable and alternative energy opportunities.
Climate Change in the Lumbee River Watershed and Potential Impacts on the Lumbee Tribe of North Carolina
Authors: Emanuel Ryan E.
Published: May 2018

A growing body of research focuses on climate change and Indigenous peoples. However, relatively little of this work focuses on Native American tribes living in the Atlantic Coastal Plain of the United States. The Lumbee Tribe of North Carolina is a large (60,000 member) Native American tribe located on the Coastal Plain in present day North Carolina (U.S.). The tribe has deep connections to the Lumbee River, which flows through a watershed dominated by extensive forested wetlands. In this paper, I outline key issues associated with climate change and water in the region, and I use long‐term climatic and hydrologic datasets and analysis to establish context for understanding historical climate change in the Lumbee River watershed. Downscaled climate model outputs for the region show how further changes may affect the hydrologic balance of the watershed. I discuss these changes in terms of environmental degradation and potential impacts on Lumbee culture and persistence, which has remained strong through centuries of adversity and has also experienced a resurgence in recent years. I close by acknowledging the especially vulnerable position of the Lumbee Tribe as a non‐federal tribe that lacks access to certain resources, statutory protections, and policies aimed at helping Native American tribes deal with climate change and other environmental challenges.
The effect of cooling rate on structural and electrical properties of multiferroic BLF‐PT ceramics
Authors: Shen Shujin , Chen Jianguo , Jian Jie , Luo Feng , Mei Jing , Cheng Jinrong
Published: May 2018

The solid solutions of 0.57(Bi0.8La0.2)FeO3‐0.43PbTiO3 (BLF‐PT) were prepared by the solid‐state reaction process. The as‐sintered ceramics were annealed at 350°C and then cooled in different media. BLF‐PT ceramics cooled in boiling water (BW) and NaCl solutions exhibit the rhombohedral structure with higher domain density, while the tetragonal structure was observed in the specimen cooled in the furnace. Moreover, BLF‐PT ceramics cooled in BW with cooling rate of about 10°C/s exhibit the enhanced electrical properties with dielectric constant εr, remnant polarization Pr, piezoelectric constant d33 of 940, 28 μC/cm2 and 210 pC/N, respectively. Rayleigh analysis was utilized to study of domain wall motion of BLF‐PT ceramics cooled in different media.
Limits to genetic rescue by outcross in pedigree dogs
Authors: Windig J.J. , Doekes H.P.
Published: May 2018

Outcrossing should reduce inbreeding levels and associated negative effects in highly inbred populations. In this study, we investigated the effectiveness of different outcrossing schemes using computer simulations. The inbreeding rate estimated for a 25‐year period of 2.1% per generation in a highly inbred dog breed reduced to 1.8% when a single litter was produced by an outcross without backcrosses. To reduce the inbreeding rate below 1%, more than eight of the 14 litters born yearly in the recipient breed had to be outcrossed. However, outcrossing in pedigree dogs is usually followed by backcrossing and generally involves one or a few litters. Backcrossing reduced the effect of outcrossing considerably. When two litters were produced by an outcross followed by one generation of backcross, the inbreeding rate was 2.0% per generation. Continuously outcrossing was more effective than a single or a few outcrosses. When each newborn litter during 25 years had a 5% chance of being produced by an outcross, the inbreeding rate reduced to −0.2%. To investigate the possibility that new alleles were introduced from the donor population into the recipient population, the fate of different type of alleles (varying from completely lethal to beneficial) before and after an outcross was investigated by first simulating 80 years of natural selection prior to the outcross and then different types of outcross. Because natural selection reduced the frequency of lethal alleles before outcrossing, the introduction of a lethal allele that was segregating in the donor breed but not in the recipient breed occurred rarely. Introduction of slightly detrimental alleles or neutral alleles occurred more frequently. In conclusion, outcrossing only had a limited short‐term effect unless repeated continuously. Nevertheless, it may help to buy time in which the population structure can be changed so that the effective population size increases.
Effects of incorporating environmental cost and risk aversion on economic values of pig breeding goal traits
Authors: Ali B.M. , de Mey Y. , Bastiaansen J.W.M. , Oude Lansink A.G.J.M.
Published: May 2018

Economic values (EVs) of traits, accounting for environmental impacts and risk preferences of farmers, are required to design breeding goals that contribute to both economic and environmental sustainability. The objective of this study was to assess the effects of incorporating environmental costs and the risk preferences of farmers on the EVs of pig breeding goal traits. A breeding goal consisting of both sow efficiency and production traits was defined for a typical Brazilian farrow‐to‐finish pig farm with 1,500 productive sows. A mean‐variance utility function was employed for deriving the EVs at finishing pig level assuming fixed slaughter weight. The inclusion of risk and risk aversion reduces the economic weights of sow efficiency traits (17%) while increasing the importance of production traits (7%). For a risk‐neutral producer, inclusion of environmental cost reduces the economic importance of sow efficiency traits (3%) while increasing the importance of production traits (1%). Genetic changes of breeding goal traits by their genetic standard deviations reduce emissions of greenhouse gases, and excretions of nitrogen and phosphorus per finished pig by up to 6% while increasing farm profit. The estimated EVs could be used to improve selection criteria and thereby contribute to the sustainability of pig production systems.
Implementing computer‐mediated intercultural communication in English education: A critical reflection on its pedagogical challenges
Authors: Lee K.
Published: May 2018

Integrating computer‐mediated intercultural communication (CMIC) activities into language curricula has been discussed as an innovative approach. Despite the increasing number of successful examples reporting positive outcomes of adopting CMIC activities in language‐learning environments, it has also been noted that there are significant pedagogical challenges observed when CMIC activities are introduced into classrooms. However, previous studies tend only to briefly mention some of those challenges and to list general solutions to them, rather than deeply engaging with the issues and their educational and social consequences upon students' learning practices. Thus, this qualitative case study documents diverse pedagogical challenges faced by Korean students and teacher in their English‐as‐a‐foreign language classroom, in which a series of CMIC activities were set up and conducted. The challenges analysed in this paper include the unrealistically high implementation cost, the educational inequality issues created by irreducible gaps in students' socio‐economic backgrounds, and the unresolved struggles to develop positive student subjectivities and linguistic identities. In conclusion, the article proposes three instructional principles, drawn in turn from the two closely interrelated theories: multiliteracies pedagogy and critical pedagogy. Fundamentally, the author argues that effective adoption of CMIC activities needs a more pedagogically, socially, and culturally sensitive approach.
Modelling the impact of new patient visits on risk adjusted access at 2 clinics
Authors: Kolber Michael A. , Rueda Germán , Sory John B.
Published: May 2018

Objective

To evaluate the effect new outpatient clinic visits has on the availability of follow‐up visits for established patients when patient visit frequency is risk adjusted.

Data Sources

Diagnosis codes for patients from 2 Internal Medicine Clinics were extracted through billing data.

Study Design

The HHS‐HCC risk adjusted scores for each clinic were determined based upon the average of all clinic practitioners' profiles. These scores were then used to project encounter frequencies for established patients, and for new patients entering the clinic based on risk and time of entry into the clinics.

Principal Findings

A distinct mean risk frequency distribution for physicians in each clinic could be defined providing model parameters. Within the model, follow‐up visit utilization at the highest risk adjusted visit frequencies would require more follow‐up slots than currently available when new patient no‐show rates and annual patient loss are included. Patients seen at an intermediate or lower visit risk adjusted frequency could be accommodated when new patient no‐show rates and annual patient clinic loss are considered.

Conclusions

Value‐based care is driven by control of cost while maintaining quality of care. In order to control cost, there has been a drive to increase visit frequency in primary care for those patients at increased risk. Adding new patients to primary care clinics limits the availability of follow‐up slots that accrue over time for those at highest risk, thereby limiting disease and, potentially, cost control. If frequency of established care visits can be reduced by improved disease control, closing the practice to new patients, hiring health care extenders, or providing non‐face to face care models then quality and cost of care may be improved.
Quality improvement opportunities for handover practices in birth centres: A case study from a process perspective
Authors: Hitzert Marit , Boesveld Inge C. , Hermus Marieke A. A. , de Graaf Johanna P. , Wiegers Therese A. , Steegers Eric A.P. , Meijboom Berthold R. , Akkermans Henk A.
Published: May 2018

Rationale, aims and objectives

Handovers within and between health care settings are known to affect quality of care. Health care organizations, struggle how to guarantee best care during handovers. The aim of this paper is to evaluate handover practices in Dutch birth centres from a process perspective, to identify obstacles and opportunities for quality improvements.

Methods

This case study in 7 Dutch birth centres was undertaken from a process perspective by conducting observations and using process mapping. This study is part of the Dutch Birth Centre Study.

Results

Solutions to obstacles during handovers from a birth centre to a hospital were identified in at least 1 of the 7 birth centres. Four of the centres had agreements with a hospital for client support when a caregiver in a birth centre was absent. Face‐to‐face communication during handover was observed in 6 of the 7 centres. An electronic health record was noted in 1 centre; joint training of acute situations was available in 2 centres with 3 centres indicating that this was not compulsory. Continuity of caregiver was present in 4 birth centres with postpartum care available in 3 centres.

Conclusions

Ensuring quality during handovers requires a case‐specific process approach. This study reveals distinctive aspects during handovers, concrete obstacles, and potential solutions for quality improvements in inter‐organizational networks, transferrable to birth centres in other countries as well.
Burden of non‐alcoholic fatty liver disease in Australia
Authors: Mahady Suzanne E , Adams Leon A
Published: May 2018

Non‐alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease in the Australian population, although precise estimates of prevalence are lacking. NAFLD may progress to liver fibrosis, cirrhosis, decompensated liver disease, and liver cancer and is becoming an increasingly common indication for liver transplantation in Australia and New Zealand. There is an extrahepatic burden of NAFLD extending beyond the liver, which is manifested by an increased risk of developing cardiovascular disease, diabetes, and chronic renal impairment, all of which are common causes of morbidity in the Australian population. Early recognition of those patients at high risk of developing advanced liver disease is essential in order to target those who will benefit from intensive lifestyle modification. In this review, we present data on the epidemiology of NAFLD within Australia, its associated health burden in terms of hepatic and extrahepatic complications, common clinical presentations, and indications for treatment. We also propose a research agenda that highlights knowledge needed to improve diagnosis and management specific to the Australian context.
Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta‐Analysis and Systematic Review
Authors: Isik Ahmet Turan , Soysal Pinar , Stubbs Brendon , Solmi Marco , Basso Cristina , Maggi Stefania , Schofield Patricia , Veronese Nicola , Mueller Christoph
Published: May 2018

Objectives

To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia

Design

Systematic review and meta‐analysis.

Setting

Two authors independently searched major electronic databases from inception until June 17, 2017, for longitudinal (without a control group) and cohort (with a control group) studies reporting CV outcomes in relation to AChEIs. Randomized controlled trials were excluded because they included relatively healthy subjects.

Participants

Individuals with dementia and controls.

Measurements

Changes in CV parameters were summarized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Event rates were used to assess incidence of hypertension and bradycardia. Incidence of CV events in demented patients versus in healthy controls were compared using hazard ratios (HRs).

Results

Of 4,588 initial hits, 31 studies including 258,540 individuals with dementia and 2,246,592 controls were analyzed. In longitudinal and open‐label studies, AChEIs were associated with a significantly greater incidence of hypertension (n=1,573, 4%, 95% CI=2–8%, I2=47%) and bradycardia (n=13,703, 2%, 95% CI=1–6%, I2=98%). AChEIs were associated with a decrease in heart rate (SMD=–1.77, 95% CI=–3.58–0.03, I2=78%) and an increase in PR interval (SMD=0.10, 95% CI=0.008–0.19, I2=3%) from baseline. During a median follow‐up of 116 weeks, AChEIs were associated with a significantly lower risk of CV events (stroke, acute coronary syndrome, CV mortality; HR=0.63, 95% CI=0.45–0.88, I2=18%), without a significantly greater risk of bradycardic events (HR=1.40, 95% CI=0.76–2.59, I2=98%).

Conclusion

AChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.
How to optimize the design of a quantitative HREM experiment so as to attain the highest precision
Authors: DEN DEKKER A. , SIJBERS J. , VAN DYCK D.
Published: May 2018

Using parameter estimation theory, an expression is derived for the maximum precision with which the position of a single atom can be estimated from high resolution transmission electron microscopy images. This expression, being a complicated function of the object as well as of the microscope parameters and the electron dose, can be used to optimize the design of an HREM experiment so as to attain the highest precision.
Retrograde transport of γ‐secretase from endosomes to the trans‐Golgi network regulates Aβ42 production
Authors: Kanatsu Kunihiko , Hori Yukiko , Ebinuma Ihori , Chiu Yung Wen , Tomita Taisuke
Published: May 2018

The aberrant metabolism of amyloid‐β protein (Aβ) in the human brain has been implicated in the etiology of Alzheimer disease (AD). γ‐Secretase is the enzyme that generates various forms of Aβ, such as Aβ40 and Aβ42, the latter being an aggregation‐prone toxic peptide that is involved in the pathogenesis of AD. Recently, we found that clathrin‐mediated endocytosis of γ‐secretase affects the production and deposition of Aβ42 in vivo, suggesting that the membrane trafficking of γ‐secretase affects its enzymatic activity. However, the detailed intracellular trafficking pathway of γ‐secretase and its contribution to Aβ42 generation remain unclear. Here, we show that Retro‐2, which inhibits the retrograde transport, elevated the Aβ42‐generating activity both in cultured cells and mice brain. However, the result of in vitro γ‐secretase assay using a recombinant substrate suggested that Retro‐2 did not elevate the intrinsic Aβ42‐production activity of γ‐secretase. Immunocytochemistry and cell‐surface biotinylation experiments revealed that γ‐secretase is recycled via the endosome‐to‐trans‐Golgi network transport. In addition, γ‐secretase is retrogradely transported by syntaxin 5/6, known as targets of Retro‐2, independent pathway. Conversely, TPT‐260, which enhances the trafficking function of retromers, lowered Aβ42 levels and the Aβ42/(Aβ40 + Aβ42) ratio in secreted Aβ from cultured cells. Our results strongly suggest that the endosome‐to‐trans‐Golgi network trafficking of γ‐secretase regulates its Aβ42 production activity. Modulation of this trafficking pathway might be a potential target for the development of Aβ42‐lowering AD therapeutics.

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What is the level of burnout that impairs functioning?
Authors: Tyssen R.
Published: May 2018

Click here to view the Review article by West et al.
Does earlier arrival of the retrieval team improve short‐term outcomes in outborn extremely premature infants?
Authors: Sharpe Janet B , Davies Mark W
Published: May 2018

Aim

The risk of mortality and morbidity is increased in outborn, extremely premature infants. We aim to determine whether earlier arrival of the retrieval team after the birth of infants less than 29 weeks gestation improves short‐term mortality and morbidity.

Methods

This is a retrospective analysis of a cohort of infants less than 29 weeks gestation who were retrieved to the Royal Brisbane and Women's Hospital (RBWH) over a 5‐year period. Demographic information regarding the infant and mother, retrieval team arrival time and outcome data was collected. Primary outcomes investigated were mortality prior to discharge from hospital or a composite of mortality or severe intraventricular haemorrhage (IVH).

Results

Data on 105 infants were analysed; 88 infants (83.8%) survived to discharge home, and 79 (75.2%) survived to discharge without severe IVH. On univariate analysis, there was no significant association between age at arrival of the retrieval team and death prior to discharge (P = 0.94) or death prior to discharge or severe IVH (P = 0.83). On logistic regression analysis, age at arrival of retrieval team remained non‐significant for a reduction in death prior to discharge and composite of death or severe IVH (P = 0.70 and P = 0.99, respectively).

Conclusion

The earlier arrival of the retrieval team is not associated with improved short‐term outcomes in outborn, extremely preterm infants who are retrieved and admitted to a tertiary neonatal intensive care unit – for infants where the retrieval team arrived within about 8 h of birth.
Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT1 reduction and Hsp70‐VDR increase
Authors: Prado Natalia Jorgelina , Casarotto Mariana , Calvo Juan Pablo , Mazzei Luciana , Ponce Zumino Amira Zulma , García Isabel Mercedes , Cuello‐Carrión Fernando Darío , Fornés Miguel Walter , Ferder León , Diez Emiliano Raúl , Manucha Walter
Published: May 2018

Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)—an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral‐obstruction (UUO) and sham‐operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT1 up‐regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin‐treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT1 reduction and Hsp70‐VDR increase.
Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption
Authors: Napimoga M. H. , Rocha E. P. , Trindade‐da‐Silva C. A. , Demasi A. P. D. , Martinez E. F. , Macedo C. G. , Abdalla H. B. , Bettaieb A. , Haj F. G. , Clemente‐Napimoga J. T. , Inceoglu B. , Hammock B. D.
Published: May 2018

Background and Objective

Soluble epoxide hydrolase (sEH) is an enzyme in the arachidonate cascade which converts epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 enzymes, to dihydroxy‐eicosatrienoic acids. In the last 20 years with the development of inhibitors to sEH it has been possible to increase the levels of EETs and other EpFAs in in vivo models. Recently, studies have shown that EETs play a key role in blocking inflammation in a bone resorption process, but the mechanism is not clear. In the current study we used the sEH inhibitor (1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea [TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model.

Material and Methods

Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated orally, daily for 15 days, with 1 mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting.

Results

Infected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and molecular markers were downregulated in the gingival tissue in the group treated with 1 mg/kg of TPPU.

Conclusion

The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model.
The epidemiology of hepatitis B and hepatitis C infections in China from 2004 to 2014: An observational population‐based study
Authors: Liu Z. , Yang Q. , Shi O. , Ye W. , Chen X. , Zhang T.
Published: May 2018

Viral hepatitis is a major public health concern in China, but data on national epidemiological characteristics are lacking. We collected reporting incidence data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in China from 2004 to 2014. Empirical mode decomposition (EMD) was performed to accurately describe the reporting incidence trends of HBV and HCV. A mathematical model was used to estimate the relative change in incidence across provinces and age groups. Nationwide, a total of 916 426 hepatitis B cases and 39 381 hepatitis C cases were recorded in 2004; the reporting incidences of HBV and HCV were 70.50/100 000 and 3.03/100 000, respectively. The overall relative changes in HBV and HCV reporting incidences in China from 2004 to 2014 were 0.98 (95% CI 0.96‐1.00, P = .082) and 1.16 (95% CI 1.12‐1.20, P < .001), respectively. Thirteen provinces experienced decline in HBV reporting incidence. Most provinces exhibited an increasing trend in HCV reporting incidence. People aged ≤24 displayed a significant descending trend in HBV reporting incidence; people aged ≥55 exhibited a significant increasing trend. For HCV infection, the reporting incidence increased in all age groups except the 10‐14 age group. In China, the majority of provinces have experienced decline or remained stable in HBV infection but show significant increases in HCV infection. Children and adolescents are well protected from HBV infection, while relatively higher increasing rates are found among older people. HCV is much more prevalent among older people, although its emergence has shifted to younger age groups.
Forum Shopping and Fairness in Mexico–United States Trade Disputes
Authors: Fattore Christina
Published: May 2018

Of all the countries in Latin America, Mexico has the strongest economic ties to the United States, formalized by the creation of the North American Free Trade Agreement in 1994, but this Agreement does not preclude Mexico from targeting the United States in the World Trade Organization's Dispute Settlement Mechanism. In fact, the Agreement's dispute‐settlement system encourages it to do so if the complaint at hand is to have a fair consideration. The North American Free Trade Agreement's dispute‐resolution system goes to a board containing representatives from the three‐member countries, which includes by default the complainant state and the defendant state. Therefore, even though Mexico has the closest economic relationship with the United States of the Latin American states considered in this project, it is also the most likely to target the United States in the World Trade Organization. This article focuses on how trade ties constrain Mexico's use of the Dispute Settlement Mechanism against its largest trade partner.
Estimating Top Income Shares Without Tax Return Data: Mexico Since the 1990s
Authors: Campos‐Vazquez Raymundo M. , Chavez Emmanuel , Esquivel Gerardo
Published: May 2018

This study estimates the income of individuals in the top part of the income distribution in Mexico since 1992. Mexico is the only Organisation for Economic Co‐operation and Development country that does not report publicly income from fiscal sources. To circumvent this problem, we use income information from household surveys but adjust the misrepresentation of top earners using national accounts data. We then estimate incomes of the very rich using interpolations based on a Pareto distribution. Once we correct for the misrepresentation of top earners in the survey, we find that the income share of the top decile has increased in the last two decades. Our findings contradict the conclusion that is usually obtained solely from household survey information. We also find that the income share of top‐1% earners in Mexico is close to 25%, making Mexico one of the countries where the rich take the largest share of total income. Moreover, we find that inequality among the rich in Mexico is larger than in most countries where information is available.
Association between bedtime and the prevalence of newly diagnosed non‐alcoholic fatty liver disease in adults
Authors: Wang Honglei , Gu Yeqing , Zheng Lixiao , Liu Li , Meng Ge , Wu Hongmei , Xia Yang , Bao Xue , Shi Hongbin , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Zhang Qing , Niu Kaijun
Published: May 2018

Background & Aims

Emerging evidence supported that circadian clocks played an important role in the development and progression of non‐alcoholic fatty liver disease (NAFLD). Bedtime is a strong regulator of circadian rhythms, implying that it may contribute to the onset of NAFLD. However, few studies have examined the association between bedtime and NAFLD. The purpose of the study was to determine whether late bedtime is associated with newly diagnosed NAFLD in an adult population.

Methods

This population‐based study was performed in 22 807 participants in Tianjin, China. Bedtime was obtained from a self‐administered questionnaire, and NAFLD was diagnosed by abdominal ultrasonography. Odds ratios of NAFLD for bedtime categories were estimated with multiple logistic regression models.

Results

The prevalence of newly diagnosed NAFLD was 18.8% in the present study. After adjustment for the potential confounders, compared with the reference group (bedtime ≤22:00), the odds ratios (95% confidence intervals) of NAFLD were 1.18 (1.05‐1.32) and 1.42 (1.21‐1.68) for bedtime from 22:00 to 24:00 and ≥24:00, respectively.

Conclusion

Late bedtime was slightly but significantly associated with an increased prevalence of newly diagnosed NAFLD, independently of confounding factors. It is suggested that early bedtime may be beneficial in preventing NAFLD.
Long‐term, spatial marine harvest intensity as an indicator of human impact on shallow rocky reef ecosystems
Authors: Zellmer Amanda J. , Claisse Jeremy T. , Williams Chelsea M. , Pondella Daniel J.
Published: May 2018

As human activities continue to expand globally, there will be increased need to incorporate the impacts of these activities into ecological studies for a holistic understanding of ecosystems. Within the Southern California Bight, as in other highly productive marine ecosystems, fishing has long contributed to the ecology and evolution of marine fish and invertebrate communities. As fishing varies across space and over time, there is a need for a reliable metric that quantifies the spatiotemporal variation in the impact of fishing. Here, we quantify an index of harvest intensity on the highly productive and heavily fished, shallow rocky reefs of Southern California. To this end, we take advantage of two long‐term, spatially explicit, multi‐species datasets collected by the California Department of Fish and Wildlife on commercial and recreational marine harvest, combined with reef‐species survey data and a geospatial reef data layer. Using this approach, we recover predictable patterns for harvest intensity across the Southern California Bight, with harvest intensity decreasing in fishing blocks located at greater distances from the nearest port. Further, our results indicate an important interaction effect between distance to nearest port and year on harvest intensity, suggesting there are important shifts in spatiotemporal patterns over the 30‐year time period. As fishing can have numerous impacts on ecological and evolutionary processes, the observed spatiotemporal variation in harvest intensity illustrates the need for incorporating the contribution of human impacts into marine ecosystem studies.
Modern Russian society in the context of anthroposocietal approach
Authors: MARTYNOVA SVETLANA
Published: May 2018

Social activities define the place of a person in the society. Even small population groups contribute to social changes of an active and independent actor‐individual in postindustrial society. Therefore, the work is relevant and rather interesting for research. The main objective of the work is research of the Tomsk Region from the perspective of an anthroposocietal approach. To achieve this objective, the author used interviews requiring close contact with respondents. In this work, questionnaires were applied as one of the components of interviewing. The sociological survey was conducted among the inhabitants of Tomsk and Seversk. The author found that men were more independent. It was also found that the value transformations were mostly motivated by the global trends. Considering the fact that the shift toward anthroposocietality (commonality of human being‐in‐the‐world) is the global trend, the data of Tomsk Region may be interesting to other scientists for conducting comparative researches.
Gene editing of stem cells for kidney disease modelling and therapeutic intervention
Authors: Lau Ricky WK , Wang Bo , Ricardo Sharon D
Published: May 2018

Recent developments in targeted gene editing have paved the way for the wide adoption of clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein‐9 nucleases (Cas9) as an RNA‐guided molecular tool to modify the genome of eukaryotic cells of animals. Theoretically, the translation of CRISPR‐Cas9 can be applied to the treatment of inherited or acquired kidney disease, kidney transplantation and genetic corrections of somatic cells from kidneys with inherited mutations, such as polycystic kidney disease. Human pluripotent stem cells have been used to generate an unlimited source of kidney progenitor cells or, when spontaneously differentiated into three‐dimensional kidney organoids, to model kidney organogenesis or the pathogenesis of disease. Gene editing now allows for the tagging and selection of specific kidney cell types or disease‐specific gene knock in/out, which enables more precise understanding of kidney organogenesis and genetic diseases. This review discusses the mechanisms of action, in addition to the advantages and disadvantages, of the three major gene editing technologies, namely, CRISPR‐Cas9, zinc finger nucleases and transcription activator‐like effector nucleases. The implications of using gene editing to better understand kidney disease is reviewed in detail. In addition, the ethical issues of gene editing, which could be easily neglected in the modern, fast‐paced research environment, are highlighted.
TGF‐β1 alters DNA methylation levels in promoter and enhancer regions of the WT1 gene in human podocytes
Authors: Hamatani Hiroko , Sakairi Toru , Ikeuchi Hidekazu , Kaneko Yoriaki , Maeshima Akito , Nojima Yoshihisa , Hiromura Keiju
Published: May 2018

Aim

Wilms’ tumour 1 (WT1) is essential for normal podocyte function. Previous reports have demonstrated that the WT1 promoter is often methylated in cancers, leading to transcriptional silencing. Transforming growth factor‐β1 (TGF‐β1) is reported to down‐regulate WT1 expression in podocytes. Based on the hypothesis that epigenetic modification plays a role in this process, we examined whether TGF‐β1 affects the methylation status of WT1 regulatory regions.

Methods

Conditional immortalized human podocytes were treated with TGF‐β1. A human renal proximal tubular epithelial cell line (HK2), which does not express WT1, was used as a control. The degree of DNA methylation of the WT1 promoter, 5′ enhancer, intron 3 enhancer and 3′ enhancer was determined using quantitative methylation‐specific PCR, bisulfite sequencing and pyrosequencing.

Results

Both WT1 mRNA and protein expression were reduced by long‐term treatment with TGF‐β1. The WT1 promoter was hypomethylated, and the 5′ enhancer and intron 3 enhancer were substantially methylated in untreated podocytes. In contrast, in HK2 cells, the WT1 promoter was strongly methylated, and the 5′ enhancer and intron 3 enhancer were less methylated than in untreated podocytes. TGF‐β1 tended to increase WT1 promoter methylation, tended to decrease 5′ enhancer methylation and significantly decreased intron 3 enhancer methylation in podocytes. Methylation levels of the 3′ enhancer did not differ among untreated cells, TGF‐β1‐treated podocytes or HK2 cells.

Conclusion

Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF‐β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF‐β1, which could contribute to podocyte injury.