bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding Regulatory T Cells Alleviates Chikungunya Virus-Induced Pathology in Mice
Authors: Lee Wendy W. L. , Teo Teck-Hui , Her Zhisheng , Lum Fok-Moon , Kam Yiu-Wing , Haase Doreen , Rénia Laurent , Rötzschke Olaf , Ng Lisa F. P.
Published: May 2015

Chikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.

IMPORTANCEChikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+T cells through induction of anergy in CHIKV-specific CD4+Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.
A retrospective observational analysis to identify patient and treatment-related predictors of outcomes in a community mental health programme
Authors: Green Stuart A , Honeybourne Emmi , Chalkley Sylvia R , Poots Alan J , Woodcock Thomas , Price Geraint , Bell Derek , Green John
Published: May 2015

Objectives

This study aims to identify patient and treatment factors that affect clinical outcomes of community psychological therapy through the development of a predictive model using historic data from 2 services in London. In addition, the study aims to assess the completeness of data collection, explore how treatment outcomes are discriminated using current criteria for classifying recovery, and assess the feasibility and need for undertaking a future larger population analysis.

Design

Observational, retrospective discriminant analysis.

Setting

2 London community mental health services that provide psychological therapies for common mental disorders including anxiety and depression.

Participants

A total of 7388 patients attended the services between February 2009 and May 2012, of which 4393 (59%) completed therapy, or there was an agreement to end therapy, and were included in the study.

Primary and secondary outcome measures

Different combinations of the clinical outcome scores for anxiety Generalised Anxiety Disorder-7 and depression Patient Health Questionnaire-9 were used to construct different treatment outcomes.

Results

The predictive models were able to assign a positive or negative clinical outcome to each patient based on 5 independent pre-treatment variables, with an accuracy of 69.4% and 79.3%, respectively: initial severity of anxiety and depression, ethnicity, deprivation and gender. The number of sessions attended/missed were also important factors identified in recovery.

Conclusions

Predicting whether patients are likely to have a positive outcome following treatment at entry might allow suitable modification of scheduled treatment, possibly resulting in improvements in outcomes. The model also highlights factors not only associated with poorer outcomes but inextricably linked to prevalence of common mental disorders, emphasising the importance of social determinants not only in poor health but also poor recovery.
Values in breast cancer screening: an empirical study with Australian experts
Authors: Parker Lisa , Rychetnik Lucie , Carter Stacy
Published: May 2015

Objective

To explore what Australian experts value in breast screening, how these values are conceptualised and prioritised, and how they inform experts’ reasoning and judgement about the Australian breast-screening programme.

Design

Qualitative study based on interviews with experts.

Participants

33 experts, including clinicians, programme managers, policymakers, advocates and researchers selected for their recognisable influence in the Australian breast-screening setting.

Setting

Australian breast-screening policy, practice and research settings.

Results

Experts expressed 2 types of values: ethical values (about what was good, important or right) and epistemological values (about how evidence should be created and used). Ethical values included delivering benefit, avoiding harm, promoting autonomy, fairness, cost effectiveness, accountability, professionalism and transparency. Epistemological values informed experts’ arguments about prioritising and evaluating evidence methodology, source population and professional interests. Some values were conceptualised differently by experts: for example, delivering benefit could mean reducing breast cancer mortality, reducing all-cause mortality, reducing mortality in younger women, reducing need for aggressive treatment, and/or reassuring women they were cancer free. When values came into conflict, experts prioritised them differently: for example, when experts perceived a conflict between delivering benefits and promoting autonomy, there were differences in which value was prioritised. We explain the complexity of the relationship between held values and experts’ overall views on breast cancer screening.

Conclusions

Experts’ positions in breast screening are influenced by evidence and a wide range of ethical and epistemological values. We conclude that discussions about values should be a regular part of breast-screening review in order to build understanding between those who hold different positions, and provide a mechanism for responding to these differences.
Cost-effectiveness of a nurse-led internet-based vascular risk factor management programme: economic evaluation alongside a randomised controlled clinical trial
Authors: Greving J P , Kaasjager H A H , Vernooij J W P , Hovens M M C , Wierdsma J , Grandjean H M H , van der Graaf Y , de Wit G A , Visseren F L J
Published: May 2015

Objective

To assess the cost-effectiveness of an internet-based, nurse-led vascular risk factor management programme in addition to usual care compared with usual care alone in patients with a clinical manifestation of a vascular disease.

Design

Cost-effectiveness analysis alongside a randomised controlled trial (the Internet-based vascular Risk factor Intervention and Self-management (IRIS) study).

Setting

Multicentre trial in a secondary and tertiary healthcare setting.

Participants

330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with ≥2 treatable vascular risk factors not at goal.

Intervention

The intervention consisted of a personalised website with an overview and actual status of patients’ vascular risk factors, and mail communication with a nurse practitioner via the website for 12 months. The intervention combined self-management support, monitoring of disease control and pharmacotherapy.

Main outcome measures

Societal costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness.

Results

Patients experienced equal health benefits, that is, 0.86 vs 0.85 QALY (intervention vs usual care) at 1 year. Adjusting for baseline differences, the incremental QALY difference was −0.014 (95% CI −0.034 to 0.007). The intervention was associated with lower total costs (€4859 vs €5078, difference €219, 95% CI −€2301 to €1825). The probability that the intervention is cost-effective at a threshold value of €20 000/QALY, is 65%. At mean annual cost of €220 per patient, the intervention is relatively cheap.

Conclusions

An internet-based, nurse-led intervention in addition to usual care to improve vascular risk factors in patients with a clinical manifestation of a vascular disease does not result in a QALY gain at 1 year, but has a small effect on vascular risk factors and is associated with lower costs.

Trial registration number

NCT00785031.
Psychosocial interventions for disruptive behavioural problems in children living in low- and middle-income countries: study protocol of a systematic review
Authors: Burkey Matthew D , Hosein Megan , Purgato Marianna , Adi Ahmad , Morton Isabella , Kohrt Brandon A , Tol Wietse A
Published: May 2015

Introduction

Disruptive behaviour disorders (DBDs) are among the most common forms of child psychopathology and have serious long-term academic, social, and mental health consequences worldwide. Psychosocial treatments are the first line of evidence-based treatments for DBDs, yet their effectiveness often varies according to patient sociodemographic characteristics, practice setting, and implementation procedures. While a large majority of the world's children live in low- and middle-income countries (LMIC), most studies have evaluated psychosocial treatments for DBDs in high-income Anglo countries.

Methods and analysis

The primary objective of this systematic review is to assess the effects of psychosocial treatments for DBDs in children and adolescents (under age 18) diagnosed with oppositional defiant disorder, conduct disorder, or other disruptive behavioural problems living in LMIC. The secondary objectives are to: (1) describe the range and types of psychosocial treatments used to address DBDs in LMIC and (2) identify key dissemination and implementation factors (adaptation processes, training/supervision processes, and financial costs). All controlled trials comparing psychosocial treatments versus waiting list, no treatment, or treatment as usual in children living in LMIC will be included. Studies will be identified using the methods outlined in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines without restrictions on language, publication type, status, or date of publication. The primary outcome measures will be disruptive behavioural problems (eg, oppositionality, defiance, aggression or deceit). Secondary outcomes will be positive mental health outcomes (eg, prosocial behaviour), function impairment, institutionalisation (or hospitalisation), academic outcomes and caregiver outcomes.

Ethics and dissemination

This study uses data from published studies; therefore ethical review is not required. Findings will be presented in a published manuscript.

Trial registration number

PROSPERO CRD42014015334.
The outcomes of recent patient safety education interventions for trainee physicians and medical students: a systematic review
Authors: Kirkman Matthew A , Sevdalis Nick , Arora Sonal , Baker Paul , Vincent Charles , Ahmed Maria
Published: May 2015

Objective

To systematically review the latest evidence for patient safety education for physicians in training and medical students, updating, extending and improving on a previous systematic review on this topic.

Design

A systematic review.

Data sources

Embase, Ovid Medline and PsycINFO databases.

Study selection

Studies including an evaluation of patient safety training interventions delivered to trainees/residents and medical students published between January 2009 and May 2014.

Data extraction

The review was performed using a structured data capture tool. Thematic analysis also identified factors influencing successful implementation of interventions.

Results

We identified 26 studies reporting patient safety interventions: 11 involving students and 15 involving trainees/residents. Common educational content included a general overview of patient safety, root cause/systems-based analysis, communication and teamwork skills, and quality improvement principles and methodologies. The majority of courses were well received by learners, and improved patient safety knowledge, skills and attitudes. Moreover, some interventions were shown to result in positive behaviours, notably subsequent engagement in quality improvement projects. No studies demonstrated patient benefit. Availability of expert faculty, competing curricular/service demands and institutional culture were important factors affecting implementation.

Conclusions

There is an increasing trend for developing educational interventions in patient safety delivered to trainees/residents and medical students. However, significant methodological shortcomings remain and additional evidence of impact on patient outcomes is needed. While there is some evidence of enhanced efforts to promote sustainability of such interventions, further work is needed to encourage their wider adoption and spread.
CQUIN audit for prescription of antibiotics for urinary tract infections in an acute medical assessment unit
Authors: Oppenheimer Maylin , Rezwan Nivin
Published: May 2015

Urinary tract infections (UTI) are a common presentation in a medical assessment unit, and we wanted to check compliance with hospital guidelines for antibiotic prescribing in patients presenting to hospital with urinary tract infection. The guidelines are based on local organisms and sensitivities. A retrospective audit of 40 patient records with positive urine cultures from July to August 2013 showed that 20% of patients with culture confirmed UTI were not given antibiotics at all. Of those prescribed antibiotics, 25% were non-compliant with local policy, and nearly one in two patients received more than one antibiotic. Furthermore, stop dates were not stated on 77% of the drug charts and duration of treatment ranged from one to 11 days.

Interventions were then introduced in the form of group teaching sessions, proactive checks by Trust pharmacists and widely distributed posters, and the same data sets collected for April to March 2014 to assess for efficacy of the interventions. On re-auditing, 35% patients were not prescribed any antibiotics. However, compliance with local policy was 100%, including 100% drug charts having a stop/review date stated. The overall duration of treatment now ranged from one to seven days, and fewer than one in four patients had more than one antibiotic.

Our results showed that improvement was needed in antibiotic stewardship, in particular with regards to compliance with the local guidelines and documentation of prescription. We have demonstrated that it is possible to improve compliance through teaching, by displaying information prominently, and vigilance by the clinical team. The outcome of this is a decreased number and duration of antibiotics prescribed, which has benefits for the patients, the hospital, and the community as a whole. Further work would include interventions to improve the number of patients who are missing antibiotic prescriptions altogether.
Hepatitis C: improving the quality of screening in a community hospital by implementing an electronic medical record intervention
Authors: Shahnazarian Vahe , Karu Eric , Mehta Parag
Published: May 2015

Both the Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force (USPSTF) have recommended that adults born between the years of 1945-1965 should receive one-time testing for Hepatitis C Virus (HCV). In fact, Governor Andrew Cuomo of the State of New York had signed a bill on October 23, 2013 which mandated NY hospitals and healthcare providers to offer HCV testing to all “Baby Boomers.” For our project, we wanted to increase our community hospital's compliance with this law and improve the quality of patient care in doing so.

An electronic medical record intervention was implemented in conjunction with our information technology services department. This intervention would flag eligible patients and would run them through a predetermined algorithm to see if they needed HCV testing. Multiple plan, do, study, act (PDSA) cycles were run during the length of the study and many changes were made in order to achieve maximum effect.

We ended up increasing our HCV testing rate from 47.2% (pre-intervention) to 87.9% (final month of the study), which was statistically significant with a p-value of <0.0000001. We also ended up with a framework that is both generalizable to other projects and is also self-sustaining, so that it can continue to run itself once all the project members have finished working there as house staff.
Quality improvement education to improve performance on ulcerative colitis quality measures and care processes aligned with National Quality Strategy priorities
Authors: Greene Laurence , Moreo Kathleen
Published: May 2015

Studies on inflammatory bowel disease (IBD) have reported suboptimal approaches to patient care. In the United States, the findings have motivated leading gastroenterology organizations to call for initiatives that support clinicians in aligning their practices with quality measures for IBD and priorities of the National Quality Strategy (NQS).

We designed and implemented a quality improvement (QI) education program on ulcerative colitis in which patient charts were audited for 30 gastroenterologists before (n = 300 charts) and after (n = 290 charts) they participated in QI-focused educational activities. Charts were audited for nine measures, selected for their alignment with four NQS priorities: making care safer, ensuring patient engagement, promoting communication, and promoting effective treatment practices. Four of the measures, including guideline-directed vaccinations and assessments of disease type and activity, were part of the CMS Physician Quality Reporting System (PQRS). The other five measures involved counseling patients on various topics in ulcerative colitis management, documentation of side effects, assessment of adherence status, and simplification of dosing. The gastroenterologists also completed baseline and post-education surveys designed to assess qualitative outcomes.

One of the educational interventions was a private audit feedback session conducted for each gastroenterologist. The sessions were designed to support participants in identifying measures reflecting suboptimal care quality and developing action plans for improvement. In continuous improvement cycles, follow-up interventions included QI tools and educational monographs.

Across the nine chart variables, post-education improvements ranged from 0% to 48%, with a mean improvement of 15.9%. Survey findings revealed improvements in self-reported understanding of quality measures and intentions to apply them to practice, and lower rates of perceived significant barriers to high-quality care. The findings indicate the potential for QI education to support gastroenterologists in improving their performance on key measures of care quality for patients with ulcerative colitis.
Brain drain: final year medical students’ intentions of training abroad
Authors: Bojanic Ana , Bojanic Katarina , Likic Robert
Published: May 2015

Background

In Croatia, a new European Union (EU) member state since July 2013, there is already a shortage of around 3280 doctors to reach the European average.

Objectives

To investigate the emigration intentions of the current cohort of final year medical students at Zabreb School of Medicine.

Methods

An electronic questionnaire was used in June 2013 to assess the attitudes of 232 final year medical students towards working conditions abroad and expectations for career opportunities in Croatia following accession to the EU.

Results

With an overall response rate of 87%, more than half of the surveyed students (106/202, 53%) intended to travel abroad, either for specialty (52/202, 26%) or subspecialty (54/202, 27%) training. More female students (58/135, 43%) than male students (17/62, 27%) indicated they would not emigrate. Most attractive emigration destinations were: Germany (34/121, 28%), USA (19/121, 16%), the UK (19/121, 16%), Switzerland (16/121, 13%) and Canada (11/121, 9%). The most important goals that respondents aimed to achieve through training abroad were to excel professionally (45/120, 38%), to prosper financially (20/120, 17%) and to acquire new experiences and international exposure (31/120, 26%).

Conclusions

Students’ motivating factors, goals for and positive beliefs about training abroad, as well as negative expectations regarding career opportunities in Croatia, may point towards actions that could be taken to help make Croatia a country that facilitates medical education and professional career development of young doctors.
Synthesis, characterization, and anticancer properties of organometallic Schiff base platinum complexes
Authors: Jean Stéphanie , Cormier Kevin , Patterson Alyssa E. , Vogels Christopher M. , Decken Andreas , Robichaud Gilles A. , Turcotte Sandra , Westcott Stephen A.
Published: May 2015

A small family of organometallic platinum complexes containing a chloride, cis-cyclooctene, and a Schiff base ligand have been prepared and characterized fully. Three aliphatic amines and four aromatic amines were chosen as representative examples. All complexes were stable in air except for 7, derived from the pinacol-protected 4-aminophenylboronate ester 4-H2NC6H4Bpin (pin = 1,2-O2C2Me4), which decomposed via B–C bond cleavage. Both complexes 4 (derived from aniline) and 7 were further characterized by single-crystal X-ray diffraction studies and confirmed the square planar nature of the platinum centre whereby the chloride ligand lies trans to the deprotonated hydroxyl group of the Schiff base ligand. The imine functionality is trans to the organic cyclooctene group. Complex 3, which contained the longest aliphatic chain studied (an octyl group), was the most promising for inducing apoptosis in the malignant MB231 breast cancer cell line. Conversely, complexes 4–6, which contained aromatic groups, were the most active against renal cell carcinoma (RCC) cell lines.
Application of bacteriophages to reduce biofilms formed by hydrogen sulfide producing bacteria on surfaces in a rendering plant
Authors: Gong Chao , Jiang Xiuping
Published: May 2015

Hydrogen sulfide producing bacteria (SPB) in raw animal by-products are likely to grow and form biofilms in the rendering processing environments, resulting in the release of harmful hydrogen sulfide (H2S) gas. The objective of this study was to reduce SPB biofilms formed on different surfaces typically found in rendering plants by applying a bacteriophage cocktail. Using a 96-well microplate method, we determined that 3 SPB strains of Citrobacter freundii and Hafnia alvei are strong biofilm formers. Application of 9 bacteriophages (107 PFU/mL) from families of Siphoviridae and Myoviridae resulted in a 33%–70% reduction of biofilm formation by each SPB strain. On stainless steel and plastic templates, phage treatment (108 PFU/mL) reduced the attached cells of a mixed SPB culture (no biofilm) by 2.3 and 2.7 log CFU/cm2 within 6 h at 30 °C, respectively, as compared with 2 and 1.5 log CFU/cm2 reductions of SPB biofilms within 6 h at 30 °C. Phage treatment was also applied to indigenous SPB biofilms formed on the environmental surface, stainless steel, high-density polyethylene plastic, and rubber templates in a rendering plant. With phage treatment (109 PFU/mL), SPB biofilms were reduced by 0.7–1.4, 0.3–0.6, and 0.2–0.6 log CFU/cm2 in spring, summer, and fall trials, respectively. Our study demonstrated that bacteriophages could effectively reduce the selected SPB strains either attached to or in formed biofilms on various surfaces and could to some extent reduce the indigenous SPB biofilms on the surfaces in the rendering environment.
Asymmetric statistical features of the Chinese domestic and international gold price fluctuation
Authors: Cao Guangxi , Zhao Yingchao , Han Yan
Published: May 2015

Analyzing the statistical features of fluctuation is remarkably significant for financial risk identification and measurement. In this study, the asymmetric detrended fluctuation analysis (A-DFA) method was applied to evaluate asymmetric multifractal scaling behaviors in the Shanghai and New York gold markets. Our findings showed that the multifractal features of the Chinese and international gold spot markets were asymmetric. The gold return series persisted longer in an increasing trend than in a decreasing trend. Moreover, the asymmetric degree of multifractals in the Chinese and international gold markets decreased with the increase in fluctuation range. In addition, the empirical analysis using sliding window technology indicated that multifractal asymmetry in the Chinese and international gold markets was characterized by its time-varying feature. However, the Shanghai and international gold markets basically shared a similar asymmetric degree evolution pattern. The American subprime mortgage crisis (2008) and the European debt crisis (2010) enhanced the asymmetric degree of the multifractal features of the Chinese and international gold markets. Furthermore, we also make statistical tests for the results of multifractatity and asymmetry, and discuss the origin of them. Finally, results of the empirical analysis using the threshold autoregressive conditional heteroskedasticity (TARCH) and exponential generalized autoregressive conditional heteroskedasticity (EGARCH) models exhibited that good news had a more significant effect on the cyclical fluctuation of the gold market than bad news. Moreover, good news exerted a more significant effect on the Chinese gold market than on the international gold market.
High-Speed and Area-Efficient Reconfigurable Multiplexer Bank for RAM-Based Finite State Machine Implementations
Authors: Senhadji-Navaro Raouf , Garcia-Vargas Ignacio
Published: May 2015

This work is focused on the problem of designing efficient reconfigurable multiplexer banks for RAM-based implementations of reconfigurable state machines. We propose a new architecture (called combination-based reconfigurable multiplexer bank, CRMUX) that use multiplexers simpler than that of the state-of-the-art architecture (called variation-based reconfigurable multiplexer bank, VRMUX). The performance (in terms of speed, area and reconfiguration cost) of both architectures is compared. Experimental results from MCNC finite state machine (FSM) benchmarks show that CRMUX is faster and more area-efficient than VRMUX. The reconfiguration cost of both multiplexer banks is studied using a behavioral model of a reconfigurable state machine. The results show that the reconfiguration cost of CRMUX is lower than that of VRMUX in most cases.
Big free groups are almost free
Authors: Tlas Tamer
Published: May 2015

It is shown that the big free group (the set of countably-long words over a countable alphabet) is almost free, in the sense that any function from the alphabet to a compact topological group factors through a homomorphism. This statement is in fact a simple corollary of the more general result proven below on the extendability of homomorphisms from subgroups (of a certain kind) of the big free group to a compact topological group.
On the temperature dependence of the absorption cross-section for black holes in string theory
Authors: Moura Filipe
Published: May 2015

We study the low frequency absorption cross-section of spherically symmetric nonextremal d-dimensional black holes. In the presence of α′ corrections, this quantity must have an explicit dependence on the Hawking temperature of the form 1/TH. This property of the low frequency absorption cross-section is shared by the D1-D5 system from type IIB superstring theory already at the classical level, without α′ corrections. We apply our formula to the simplest example, the classical d-dimensional Reissner–Nordström solution, checking that the obtained formula for the cross-section has a smooth extremal limit. We also apply it for a d-dimensional Tangherlini-like solution with α′3 corrections.
The Perception of the Contextual Factors as Predictor of Entrepreneurial Intent: Evidences from an Empirical Survey
Authors: Thomas Antonio , Passaro Renato , Scandurra Giuseppe
Published: May 2015

Identifying people interested into starting-up a business is becoming more and more relevant. As widely recognized, two key aspects affecting on start-up are the role of the external context factors and the influence of entrepreneurial competencies.

With this in mind, the paper shows an application of the Theory of Planned Behaviour with the aim to assess factors believed to affect entrepreneurial intent among engineering students. As the use of well thought-out and research-tested intent models is believed to provide a good means of examining the precursors to business start-up, the survey provides a test of the robustness of the intent approach and then examines the influence of some predictors within the contextual factors.

Consistently with other leading articles, the results evidence that attitudes and perceived behavioural control effectively predicts entrepreneurial intent, while social norms have no effects. As regards the role of contextual factors and entrepreneurial competencies, they exhibit indirect effects on intent via entrepreneurial attitudes and perceived behavioural control. Thus, their contribution to favour academic entrepreneurship is confirmed. The result of the study also has valuable implications for the university system.
Transformative Capacity of Entrepreneurship Education in Two Different Cultural Settings — Morphogenetic Analysis of Egypt and Finland
Authors: Kurczewska Agnieszka , Kyrö Paula , Abbas Amal
Published: May 2015

In this paper we investigate the dynamics of the transformative capacity of entrepreneurship education by studying the interplay between structure (society and the education system) and agency (individuals — students) that takes place in two different cultural settings: Finland and Egypt. By adopting the morphogenetic theory and by combining the etic-emic approach we compare society and the education system in these countries, and analyse Finnish and Egyptian students' views on entrepreneurship. The results indicate that structural conditioning is strong in both societies and students' views tend to follow the national policy rather than show any tendency to transform it. Thus the national policy may be an efficient tool with which to advance entrepreneurship education. The findings lead to the anticipation that while in Egypt entrepreneurship education offers opportunities for morphogenesis within and by crossing the borders of the social classes, in Finland morphostasis is more likely to take place in the future.
Buckling of Standing Tapered Timoshenko Columns with Varying Flexural Rigidity Under Combined Loadings
Authors: Sun D.-L. , Li X.-F. , Wang C. Y.
Published: May 2015

The stability of a nonuniform column subjected to a tip force and axially distributed loading is investigated based on the Timoshenko beam theory. An emphasis is placed on buckling of a standing column with varying cross-section and variable material properties under self-weight and tip force. Four kinds of columns with different taper ratios are analyzed. A new initial value method is suggested to determine critical tip force and axial loading at buckling. The effectiveness of the method is confirmed by comparing our results with those for Euler–Bernoulli columns for the case of sufficiently large shear rigidity. The effects of shear rigidity, taper ratio, and gravity loading on the buckling loads of a heavy standing or hanging column are examined.
Image denoising via analytical form of adaptive generalized Gaussian random vectors in AWGN with MMSE estimator for local adaptive parameter
Authors: Kittisuwan Pichid
Published: May 2015

In this paper, we present new Bayesian estimators for adaptive generalized Gaussian (GG) random vectors in additive white Gaussian noise (AWGN). The derivations are an extension of existing results for Pearson type VII random vectors in AWGN. Pearson type VII random vectors is one of the distribution that successfully use for image denoising. However, Pearson type VII distribution have higher-order moment in statistical parameter for fitted the data such as mean, variance and kurtosis. In our literature, where high-order statistics were used, better performance can be obtained but with much higher computational complexity. In fact, adaptive GG random vectors is similar to Pearson type VII random vectors. However, the special case of adaptive GG random vectors has only first few statistical moments such as adaptive parameter. So, the proposed method can be calculated very fast, without any complex step. In fact, the adaptive parameter of adaptive GG density is the function of standard deviation. Here, we employ minimum mean square error (MMSE) estimation to calculate local observed variances with gamma density prior for local observed variances and Gaussian distribution for noisy wavelet coefficients. In our experiments, our proposed method gives promising denoising results with moderate complexity.
The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model
Authors: Nakatsu Yusuke , Seno Yasuyuki , Kushiyama Akifumi , Sakoda Hideyuki , Fujishiro Midori , Katasako Aya , Mori Keiichi , Matsunaga Yasuka , Fukushima Toshiaki , Kanaoka Ryuhei , Yamamotoya Takeshi , Kamata Hideaki , Asano Tomoichiro
Published: May 2015

Xanthine oxidase (XO) is an enzyme involved in the production of uric acid (UA) from purine nucleotides. Numerous recent studies have revealed the likelihood of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) to be related to hyperuricemia. However, it remains unclear whether elevated serum UA during the development of NAFLD or NASH is a cause or a consequence of these diseases. In this study, the XO inhibitor febuxostat was administered to two types of NASH model mice. Febuxostat exerted a strong protective effect against NASH development induced by a high-fat diet containing trans fatty acid (HFDT). In contrast, methionine choline-deficient-diet-induced NASH development not accompanied by hyperuricemia showed no UA normalization, suggesting that the ameliorating effect of febuxostat occurs via the normalization of hyperuricemia itself and/or accompanying molecular mechanism(s) such as oxidative stress. In the HFDT-fed mice, hyperuricemia, elevated alanine aminotransferase, and increased Tunnel-positive cells in the liver were normalized by febuxostat administration. In addition, upregulation of fatty acid oxidation-related genes, fibrotic change, and increases in collagen deposition, inflammatory cytokine expressions, and lipid peroxidation in the HFDT-fed mice were also normalized by febuxostat administration. Taken together, these observations indicate that administration of febuxostat has a protective effect against HFDT-induced NASH development, suggesting the importance of XO in its pathogenesis. Thus XO inhibitors are potentially potent therapies for patients with NASH, particularly that associated with hyperuricemia.
High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse
Authors: Leelahavanichkul Asada , Somparn Poorichaya , Bootprapan Tanabodee , Tu Hongbin , Tangtanatakul Pattarin , Nuengjumnong Ratchanok , Worasilchai Navaporn , Tiranathanagul Khajohn , Eiam-ong Somchai , Levine Mark , Chinampon Ariya , Srisawat Nattachai
Published: May 2015

Amphotericin B (Ampho B) is a fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically. We tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression in patients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with <11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage, liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.
Nephron-specific deletion of the prorenin receptor causes a urine concentration defect
Authors: Ramkumar Nirupama , Stuart Deborah , Calquin Matias , Quadri Syed , Wang Shuping , Van Hoek Alfred N. , Siragy Helmy M. , Ichihara Atsuhiro , Kohan Donald E.
Published: May 2015

The prorenin receptor (PRR), a recently discovered component of the renin-angiotensin system, is expressed in the nephron in general and the collecting duct in particular. However, the physiological significance of nephron PRR remains unclear, partly due to developmental abnormalities associated with global or renal-specific PRR gene knockout (KO). Therefore, we developed mice with inducible nephron-wide PRR deletion using Pax8-reverse tetracycline transactivator and LC-1 transgenes and loxP flanked PRR alleles such that ablation of PRR occurs in adulthood, after induction with doxycycline. Nephron-specific PRR KO mice have normal survival to ∼1 yr of age and no renal histological defects. Compared with control mice, PRR KO mice had 65% lower medullary PRR mRNA and protein levels and markedly diminished renal PRR immunofluorescence. During both normal water intake and mild water restriction, PRR KO mice had significantly lower urine osmolality, higher water intake, and higher urine volume compared with control mice. No differences were seen in urine vasopressin excretion, urine Na+ and K+ excretion, plasma Na+, or plasma osmolality between the two groups. However, PRR KO mice had reduced medullary aquaporin-2 levels and arginine vasopressin-stimulated cAMP accumulation in the isolated renal medulla compared with control mice. Taken together, these results suggest nephron PRR can potentially modulate renal water excretion.
Furosemide-induced urinary acidification is caused by pronounced H+ secretion in the thick ascending limb
Authors: de Bruijn Pauline I. A. , Larsen Casper K. , Frische Sebastian , Himmerkus Nina , Praetorius Helle A. , Bleich Markus , Leipziger Jens
Published: May 2015

The loop diuretic furosemide inhibits NaCl reabsorption in the thick ascending limb (TAL). In addition, furosemide acidifies the urine, which is traditionally explained by increased Na+ loading to the distal tubule causing an activation of H+ secretion via H+-ATPase in α-intercalated cells. The inability to acidify urine in response to furosemide serves to diagnose distal renal tubular acidosis (dysfunction of α-intercalated cells). Since the TAL is important for acid/base regulation, we speculated that it is involved in furosemide-induced urinary acidification. Luminal furosemide (100 μM) caused major, stable, and reversible intracellular alkalization (7.27 ± 0.06 to 7.6 ± 0.04) in isolated perfused murine medullary TAL and pronounced H+ secretion. This H+ secretion was fully inhibited with luminal amiloride (1 mM) and the Na+/H+ exchanger (NHE)3-specific antagonist #4167 (1 μM). Moreover, furosemide triggered a substantial drop of intracellular Na+ concentration in the medullary TAL. These results suggest that the furosemide-induced H+ secretion is a consequence of a drop in intracellular Na+ concentration, increasing the driving force for NHE3. Intriguingly, in whole animal experiments, furosemide-induced urinary acidification and net acid excretion were markedly reduced by specific NHE3 inhibition. Furthermore, the furosemide-induced urinary acidification was partially preserved during epithelial Na+ channel inhibition with benzamil. These results provide new insights in the mechanism of furosemide-induced urinary acidification and emphasize the role of the TAL in renal acid/base handling.
Different target-discrimination times can be followed by the same saccade-initiation timing in different stimulus conditions during visual searches
Authors: Tanaka Tomohiro , Nishida Satoshi , Ogawa Tadashi
Published: May 2015

The neuronal processes that underlie visual searches can be divided into two stages: target discrimination and saccade preparation/generation. This predicts that the length of time of the prediscrimination stage varies according to the search difficulty across different stimulus conditions, whereas the length of the latter postdiscrimination stage is stimulus invariant. However, recent studies have suggested that the length of the postdiscrimination interval changes with different stimulus conditions. To address whether and how the visual stimulus affects determination of the postdiscrimination interval, we recorded single-neuron activity in the lateral intraparietal area (LIP) when monkeys ( Macaca fuscata) performed a color-singleton search involving four stimulus conditions that differed regarding luminance (Bright vs. Dim) and target-distractor color similarity (Easy vs. Difficult). We specifically focused on comparing activities between the Bright-Difficult and Dim-Easy conditions, in which the visual stimuli were considerably different, but the mean reaction times were indistinguishable. This allowed us to examine the neuronal activity when the difference in the degree of search speed between different stimulus conditions was minimal. We found that not only prediscrimination but also postdiscrimination intervals varied across stimulus conditions: the postdiscrimination interval was longer in the Dim-Easy condition than in the Bright-Difficult condition. Further analysis revealed that the postdiscrimination interval might vary with stimulus luminance. A computer simulation using an accumulation-to-threshold model suggested that the luminance-related difference in visual response strength at discrimination time could be the cause of different postdiscrimination intervals.
Reduced postactivation depression of soleus H reflex and root evoked potential after transcranial magnetic stimulation
Authors: Andrews Jennifer C. , Stein Richard B. , Roy François D.
Published: May 2015

Postactivation depression of the Hoffmann (H) reflex is associated with a transient period of suppression following activation of the reflex pathway. In soleus, the depression lasts for 100–200 ms during voluntary contraction and up to 10 s at rest. A reflex root evoked potential (REP), elicited after a single pulse of transcutaneous stimulation to the thoracolumbar spine, has been shown to exhibit similar suppression. The present study systematically characterized the effect of transcranial magnetic stimulation (TMS) on postactivation depression using double-pulse H reflexes and REPs. A TMS pulse reduced the period of depression to 10–15 ms for both reflexes. TMS could even produce postactivation facilitation of the H reflex, as the second reflex response was increased to 243 ± 51% of control values at the 75-ms interval. The time course was qualitatively similar for the REP, yet the overall increase was less. While recovery of the H reflex was slower in the relaxed muscle, the profile exhibited a distinct bimodal shape characterized by an early peak at the 25-ms interval, reaching 72 ± 23% of control values, followed by a trough at 50 ms, and then a gradual recovery at intervals > 50 ms. The rapid recovery of two successively depressed H reflexes, ∼25 ms apart, was also possible with double-pulse TMS. The effect of the TMS-induced corticospinal excitation on postactivation depression may be explained by a combination of pre- and postsynaptic mechanisms, although further investigation is required to distinguish between them.
Chemical Compositions of Dew and Scavenging of Particles in Changchun, China
Authors: Xu Yingying , Zhu Hui , Tang Jie , Lin Yingzi
Published: May 2015

Dew and rain water were collected during 2013 and 2014 in Changchun, China. The dew was analyzed and the following parameters were measured: pH, EC, TDS, major anions (F−, Cl−,SO42-, andNO3-), and major cations (NH4+, Na+, K+, Ca2+, and Mg2+). The mean pH, EC, and TDS values of dew were comparable with the values for rainwater. The pH values of dew and rain were 6.72 and 6.16, respectively. Both EC (308 μS/cm) and TDS (154 mg/L) of dew were higher than those in rain samples. The concentration of main ions in dew was 1.5–5.7 times higher than levels in rainwater. The near-neutral pH values in dew were caused by the neutralization of acidity and buffering by the alkaline elements of soil origin (Ca2+). This neutralization was confirmed by a strong correlation between the acidic ions (SO42-andNO3-) and the major cations (Ca2+and Mg2+). Natural dust made an important contribution to the ions present in dews, but the presence of sulfate concentrations that are notably higher than rain water (up to 1584.5 μeq/L) indicated a significant contribution of anthropogenic sources. Dew has the ability to capture particulates, and the purifying effect on the underlying surface was obvious.
Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, andIn VitroDisease Modeling
Authors: Yap May Shin , Nathan Kavitha R. , Yeo Yin , Lim Lee Wei , Poh Chit Laa , Richards Mark , Lim Wei Ling , Othman Iekhsan , Heng Boon Chin
Published: May 2015

Human pluripotent stem cells (hPSCs) derived from either blastocyst stage embryos (hESCs) or reprogrammed somatic cells (iPSCs) can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as forin vitromodeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulatein vivoconditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.