bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Human Respiratory Syncytial Virus Cell Entry Inhibitor by Using a Novel Lentiviral Pseudotype System
Authors: Haid Sibylle , Grethe Christina , Bankwitz Dorothea , Grunwald Thomas , Pietschmann Thomas
Published: December 2015

Lentiviral budding is governed by group-specific antigens (Gag proteins) and proceeds in the absence of cognate viral envelope proteins, which has been exploited to create pseudotypes incorporating envelope proteins from nonlentiviral families. Here, we report the generation of infectious lentiviral pseudoparticles incorporating human respiratory syncytial virus (hRSV) F protein alone (hRSV-Fpp) or carrying SH, G, and F proteins (hRSV-SH/G/Fpp). These particles recapitulate key infection steps of authentic hRSV particles, including utilization of glycosaminoglycans and low-pH-independent cell entry. Moreover, hRSV pseudoparticles (hRSVpp) can faithfully reproduce phenotypic resistance to a small-molecule fusion inhibitor in clinical development (BMS-433771) and a licensed therapeutic F protein-targeting antibody (palivizumab). Inoculation of several human cell lines from lung and liver revealed more than 30-fold differences in susceptibility to hRSVpp infection, suggesting differential expression of hRSV entry cofactors and/or restriction factors between these cell types. Moreover, we observed cell-type-dependent functional differences between hRSVpp carrying solely F protein or SH, G, and F proteins with regard to utilization of glycosaminoglycans. Using hRSVpp, we identified penta-
O
-galloyl-β-
d
-glucose (PGG) as a novel hRSV cell entry inhibitor. Moreover, we show that PGG also inhibits cell entry of hRSVpp carrying F proteins resistant to BMS-433771 or palivizumab. This work sheds new light on the mechanisms of hRSV cell entry, including possible strategies for antiviral intervention. Moreover, hRSVpp should prove valuable to dissect hRSV envelope protein functions, including the interaction with cell entry factors.

IMPORTANCE
Lentiviral pseudotypes are highly useful to specifically dissect the functions of viral and host factors in cell entry, which have been exploited for numerous viruses. Here, we successfully created hRSVpp and show that they faithfully recapitulate key characteristics of parental hRSV cell entry. Importantly, hRSVpp accurately mirror hRSV resistance to small-molecule fusion inhibitors and clinically approved therapeutic antibodies. Moreover, we observed highly different susceptibilities of cell lines to hRSVpp infection and also differences between hRSVpp types (with F protein alone or with SH, G, and F proteins) in regard to cell entry. This indicates differential expression of host factors determining hRSV cell entry between these cell lines and highlights the fact that the hRSVpp system is useful to explore the functional properties of hRSV envelope protein combinations. Therefore, this system will be highly useful to study hRSV cell entry and host factor usage and to explore antiviral strategies targeting hRSV cell entry.
Supporting decisions to increase the safe discharge of children with febrile illness from the emergency department: a systematic review and meta-analysis
Authors: Irwin A D , Wickenden J , Le Doare K , Ladhani S , Sharland M
Published: December 2015

Background

Despite fewer serious infections presenting to the children's emergency department (ED), hospital admissions of children with febrile illness have increased. We review evidence for the use of decision rules to increase the safe discharge of these children from the ED.

Methods

A systematic review of prospective studies of decision rules for the discharge of children with febrile illness, and prediction rules for the diagnosis of serious infections in children presenting to ED. We reviewed the MEDLINE database, Cochrane Library and hand searched the bibliographies of related studies. The search was limited to the English language.

Results

Thirty-three studies were identified. Fourteen reported low-risk criteria to rule out serious bacterial infection (SBI) in infants less than 3 months of age. In this group, clinical tools such as the Rochester and Philadelphia criteria support the safe discharge of low-risk infants without empirical antibiotics. Seventeen studies reported prediction rules in older children, though only four included children over 3 years. Two impact studies based upon multivariable prediction models failed to demonstrate any impact on rates of discharge from ED.

Conclusions

The use of clinical prediction models can improve discrimination between serious and self-limiting infections in children. The application of low-risk thresholds may help to rule out serious infections and discharge children from the ED without empirical antibiotics. A growing evidence base for prediction rules has so far failed to translate into validated rules to aid decision-making. Future work should evaluate decision rules in well designed impact studies, focusing on the need for hospital admission and antibiotic therapy.
The psychological response to injury in student athletes: a narrative review with a focus on mental health
Authors: Putukian Margot
Published: December 2015

Background

Injury is a major stressor for athletes and one that can pose significant challenges. Student athletes must handle rigorous academic as well as athletic demands that require time as well as significant physical requirements. Trying to perform and succeed in the classroom and on the playing field has become more difficult as the demands and expectations have increased. If an athlete is injured, these stressors increase.

Main thesis

Stress is an important antecedent to injuries and can play a role in the response to, rehabilitation and return to play after injury. The psychological response to injury can trigger and/or unmask mental health issues including depression and suicidal ideation, anxiety, disordered eating, and substance use/abuse. There are barriers to mental health treatment in athletes. They often consider seeking help as a sign of weakness, feeling that they should be able to ‘push through’ psychological obstacles as they do physical ones. Athletes may not have developed healthy coping behaviours making response to injury especially challenging.

Purpose

I discuss the current state of knowledge regarding the psychological response to injury and delineate resources necessary to direct the injured athlete to a mental health care provider if appropriate.
Starting antidepressant use: a qualitative synthesis of UK and Australian data
Authors: Anderson Claire , Kirkpatrick Susan , Ridge Damien , Kokanovic Renata , Tanner Claire
Published: December 2015

Objective

To explore people's experiences of starting antidepressant treatment.

Design

Qualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time.

Participants

108 men and women aged 22–84 who had taken antidepressants for depression.

Setting

Respondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011.

Results

People expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option.

Conclusions

Our paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients’ their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the prospect of taking antidepressants, especially during the uncertain first few weeks of treatment.
Research is ‘a step into the unknown’: an exploration of pharmacists’ perceptions of factors impacting on research participation in the NHS
Authors: Lowrie Richard , Morrison Graeme , Lees Rosalind , Grant Christopher H , Johnson Chris , MacLean Fiona , Semple Yvonne , Thomson Alison , Harrison Heather , Mullen Alexander B , Lannigan Norman , Macdonald Sara
Published: December 2015

Objective

This study explored National Health Service (NHS) pharmacists’ perceptions and experiences of pharmacist-led research in the workplace.

Design

Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis.

Setting

Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority.

Results

The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity.

Conclusions

Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports.
Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study
Authors: Dressler Dirk , Rychlik Reinhard , Kreimendahl Fabian , Schnur Nicole , Lambert-Baumann Judith
Published: December 2015

Objective

To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period.

Design

Prospective, non-interventional, open-label, parallel-group study.

Setting

47 centres in Germany.

Participants

Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy.

Intervention

Conventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required.

Main outcome measures

The main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained.

Results

Muscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16–27% (conventional therapy). Median improvement in functional disability was –1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy.

Conclusions

IncobotulinumtoxinA combined with rehabilitation and oral medication produces a much more robust improvement in all aspects of arm spasticity than conventional antispastic treatment. Effects are stable over a period of 1 year, whereas adverse effects are negligible. IncobotulinumtoxinA should be considered the treatment of choice for poststroke arm spasticity.
Patient satisfaction and perceived quality of care: evidence from a cross-sectional national exit survey of HIV and non-HIV service users in Zambia
Authors: Dansereau Emily , Masiye Felix , Gakidou Emmanuela , Masters Samuel H , Burstein Roy , Kumar Santosh
Published: December 2015

Objective

To examine the associations between perceived quality of care and patient satisfaction among HIV and non-HIV patients in Zambia.

Setting

Patient exit survey conducted at 104 primary, secondary and tertiary health clinics across 16 Zambian districts.

Participants

2789 exiting patients.

Primary independent variables

Five dimensions of perceived quality of care (health personnel practice and conduct, adequacy of resources and services, healthcare delivery, accessibility of care, and cost of care).

Secondary independent variables

Respondent, visit-related, and facility characteristics.

Primary outcome measure

Patient satisfaction measured on a 1–10 scale.

Methods

Indices of perceived quality of care were modelled using principal component analysis. Statistical associations between perceived quality of care and patient satisfaction were examined using random-effect ordered logistic regression models, adjusting for demographic, socioeconomic, visit and facility characteristics.

Results

Average satisfaction was 6.9 on a 10-point scale for non-HIV services and 7.3 for HIV services. Favourable perceptions of health personnel conduct were associated with higher odds of overall satisfaction for non-HIV (OR=3.53, 95% CI 2.34 to 5.33) and HIV (OR=11.00, 95% CI 3.97 to 30.51) visits. Better perceptions of resources and services were also associated with higher odds of satisfaction for both non-HIV (OR=1.66, 95% CI 1.08 to 2.55) and HIV (OR=4.68, 95% CI 1.81 to 12.10) visits. Two additional dimensions of perceived quality of care—healthcare delivery and accessibility of care—were positively associated with higher satisfaction for non-HIV patients. The odds of overall satisfaction were lower in rural facilities for non-HIV patients (OR 0.69; 95% CI 0.48 to 0.99) and HIV patients (OR=0.26, 95% CI 0.16 to 0.41). For non-HIV patients, the odds of satisfaction were greater in hospitals compared with health centres/posts (OR 1.78; 95% CI 1.27 to 2.48) and lower at publicly-managed facilities (OR=0.41, 95% CI=0.27 to 0.64).

Conclusions

Perceived quality of care is an important driver of patient satisfaction with health service delivery in Zambia.
Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: protocol for a systematic review and individual patient data network meta-analysis
Authors: Veroniki Areti Angeliki , Straus Sharon E , Ashoor Huda M , Hamid Jemila S , Yu Catherine , Tricco Andrea C
Published: December 2015

Introduction

The choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual's needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM.

Methods and analysis

We will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1Cand severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement.

Ethics and dissemination

The results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations.

PROSPERO registry number

CRD42015023511.
Declines in stillbirth and neonatal mortality rates in Europe between 2004 and 2010: results from the Euro-Peristat project
Authors: Zeitlin Jennifer , Mortensen Laust , Cuttini Marina , Lack Nicholas , Nijhuis Jan , Haidinger Gerald , Blondel Béatrice , Hindori-Mohangoo Ashna D
Published: December 2015

Background

Stillbirth and neonatal mortality rates declined in Europe between 2004 and 2010. We hypothesised that declines might be greater for countries with higher mortality in 2004 and disproportionally affect very preterm infants at highest risk.

Methods

Data about live births, stillbirths and neonatal deaths by gestational age (GA) were collected using a common protocol by the Euro-Peristat project in 2004 and 2010. We analysed stillbirths at ≥28 weeks GA in 22 countries and live births ≥24 weeks GA for neonatal mortality in 18 countries. Per cent changes over time were assessed by calculating risk ratios (RR) for stillbirth, neonatal mortality and preterm birth rates in 2010 vs 2004. We used meta-analysis techniques to derive pooled RR using random-effects models overall, by GA subgroups and by mortality level in 2004.

Results

Between 2004 and 2010, stillbirths declined by 17% (95% CI 10% to 23%), with a range from 1% to 39% by country. Neonatal mortality declined by 29% (95% CI 23% to 35%) with a range from 9% to 67%. Preterm birth rates did not change: 0% (95% CI −3% to 3%). Mortality declines were of a similar magnitude at all GA; mortality levels in 2004 were not associated with RRs.

Conclusions

Stillbirths and neonatal deaths declined at all gestational ages in countries with both high and low levels of mortality in 2004. These results raise questions about how low-mortality countries achieve continued declines and highlight the importance of improving care across the GA spectrum.
Effect of short-term positive airway pressure on blood pressure in controlled hypertensive patients with obstructive sleep apnoea syndrome: a prospective cohort study
Authors: de Morais Lima José Heriston , da Cruz Santos Amilton , Barros Sandra Emília Benício , Soares de Abreu Morais Pollyana , Figueiroa José Natal , Alves João Guilherme B
Published: December 2015

Background

Obstructive sleep apnoea syndrome (OSAS) is associated with cardiovascular disease, especially in patients with high blood pressure. Continuous positive airway pressure (CPAP) seems to contribute to blood pressure control in patients with OSAS, mainly those with uncontrolled hypertension. However, the effect of CPAP on controlled hypertensive patients with OSAS is not known.

Objective

To evaluate the effects of CPAP on blood pressure of controlled hypertensive patients with OSAS.

Design

Prospective cohort study.

Patients

36 recently diagnosed patients with OSAS and hypertension controlled with oral antihypertensive medication.

Methods

CPAP was performed for 5 days. Systolic and diastolic blood pressure were recorded at baseline and 5 days later using 24 h ambulatory blood pressure measurement.

Results

Mean (SD) 24 h systolic blood pressure was reduced from 128.9 (3.4) to 126.5 (3.5), p<0.001 and mean (SD) 24 h diastolic blood pressure was reduced from 86.9 (3.3) to 84.8 (3.3), p<0.001. A reduction in the proportion of ‘non-dippers’ in the participants was registered (from 40.6% at baseline to 18.2%).

Conclusions

A short course of CPAP may reduce systolic and diastolic blood pressure in patients with OSAS and controlled hypertension.

Trial registration number

RBR – 386qsg; Brazilian Clinical Trials Registry (REBEC).
TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis
Authors: Wcisło-Dziadecka Dominika , Zbiciak-Nylec Martyna , Brzezińska-Wcisło Ligia , Mazurek Urszula
Published: December 2015

Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments for psoriasis. In particular, adalimumab, etanercept and infliximab are promising therapeutic options for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional treatment strategies and they can significantly improve the quality of lives in patients with this disease.
Systolic blood pressure response after high-intensity interval exercise is independently related to decreased small arterial elasticity in normotensive African American women
Authors: Carter Stephen J. , Goldsby TaShauna U. , Fisher Gordon , Plaisance Eric P. , Gower Barbara A. , Glasser Stephen P. , Hunter Gary R.
Published: January 2016

Aerobic exercise transiently lowers blood pressure. However, limited research has concurrently evaluated blood pressure and small arterial elasticity (SAE), an index of endothelial function, among African American (AA) and European American (EA) women the morning after (i.e., ≈22 h later) acute bouts of moderate-intensity continuous (MIC) and high-intensity interval (HII) exercise matched for total work. Because of greater gradients of shear stress, it was hypothesized that HII exercise would elicit a greater reduction in systolic blood pressure (SBP) compared to MIC exercise. After baseline, 22 AA and EA women initiated aerobic exercise training 3 times/week. Beginning at week 8, three follow-up assessments were conducted over the next 8 weeks at random to measure resting blood pressure and SAE. In total all participants completed 16 weeks of training. Follow-up evaluations were made: (i) in the trained state (TS; 8–16 weeks of aerobic training); (ii) ≈22 h after an acute bout of MIC exercise; and (iii) ≈22 h after an acute bout of HII exercise. Among AAs, the acute bout of HII exercise incited a significant increase in SBP (mm Hg) (TS, 121 ± 14 versus HII, 128 ± 14; p = 0.01) whereas responses (TS, 116 ± 12 versus HII, 113 ± 9; p = 0.34) did not differ in EAs. After adjusting for race, changes in SAE were associated (partial r = −0.533; p = 0.01) with changes in SBP following HII exercise. These data demonstrate an acute, unaccustomed bout of HII exercise produces physiological perturbations resulting in a significant increase in SBP that are independently associated with decreased SAE among AA women, but not EA women.
Linearly Many Edge-Faults in 2-Bijective Connection Networks
Authors: Medarametla Dhruv , Cheng Eddie , Cheng Steven , Wu Lawrance
Published: December 2015

The class of 2-bijective connection networks (2BC networks) is defined recursively as follows: Let [Formula: see text] and for [Formula: see text], let [Formula: see text] be the set of all graphs that can be constructed by taking two (possibly the same) elements [Formula: see text] and [Formula: see text] from [Formula: see text] (if we take the same element, we will assume they are two different copies and so [Formula: see text] remains empty) with two bijections [Formula: see text] and [Formula: see text] to form the graph [Formula: see text] where [Formula: see text] and [Formula: see text] such that [Formula: see text]. This class of networks includes the class of augmented cubes. We study the structural properties of the resulting graph when “many” edges are deleted from such a network. We then mention some applications.
Shell model and Hartree–Fock calculations for some exotic nuclei
Authors: Alzubadi Ali A. , Latooffi Nabeel F. , Radhi R. A.
Published: December 2015

Mass density distributions, the associated nuclear radii and elastic electron scattering form factors of light exotic nuclei, [Formula: see text]Li, [Formula: see text]Be, [Formula: see text]Be and 8B have been calculated using shell model (SM) and Hartree–Fock (HF) methods. We consider truncated spsdpf no core SM and WBP two-body effective interaction to give the SM wave functions. The single-particle matrix elements have been calculated with Skyrme-Hartree–Fock (SHF) potential with different parametrizations. It is shown that the calculated densities and form factors are in fine agreement with experimental data. This agreement can be interpreted as the adequacy of the HF mean-field approximation for exotic nuclei.
An Interval Approximation Approach for a Multiobjective Programming Model with Fuzzy Objective Functions
Authors: Luhandjula M. K.
Published: December 2015

Research in optimization under uncertainty is alive. It assumes different shapes and forms, all concurring to the general goal of designing effective and efficient tools for handling imprecision in an Optimization setting. In this paper we present a new approach for dealing with multiobjective programming problems with fuzzy objective functions. Similar to many approaches in the literature, our approach relies on the deffuzification of involved fuzzy quantities. Our improvement stem from the choice of a deffuzification operator that captures essential features of fuzzy parameters at hand rather than those that yield single values, leading to a loss of many useful information. Two oracles play a pivotal role in the proposed method. The first one returns a near interval approximation to a given fuzzy number. The other one delivers a Pareto Optimal solution of the resulting multiobjective program with interval coefficient. A numerical example is also provided for the sake of illustration.
Parametric Matroid of Rough Set
Authors: Liu Yanfang , Zhao Hong , Zhu William
Published: December 2015

Rough set is mainly concerned with the approximations of objects through an equivalence relation on a universe. Matroid is a generalization of linear algebra and graph theory. Recently, a matroidal structure of rough sets is established and applied to the problem of attribute reduction which is an important application of rough set theory. In this paper, we propose a new matroidal structure of rough sets and call it a parametric matroid. On the one hand, for an equivalence relation on a universe, a parametric set family, with any subset of the universe as its parameter, is defined through the lower approximation operator. This parametric set family is proved to satisfy the independent set axiom of matroids, therefore a matroid is generated, and we call it a parametric matroid of the rough set. Through the lower approximation operator, three equivalent representations of the parametric set family are obtained. Moreover, the parametric matroid of the rough set is proved to be the direct sum of a partition-circuit matroid and a free matroid. On the other hand, partition-circuit matroids are well studied through the lower approximation number, and then we use it to investigate the parametric matroid of the rough set. Several characteristics of the parametric matroid of the rough set, such as independent sets, bases, circuits, the rank function and the closure operator, are expressed by the lower approximation number.
Cyber education
Authors: Alvarez Isabel Borges , Silva Nuno S. Alves , Correia Luisa Sampaio
Published: January 2016

The constant and rapid investments in Information and Communication Technologies (ICTs) have allowed the growth in the quality of information response available within the internet which requires considering and addressing the physical, financial, socio-demographic, cognitive, design, institutional, political and cultural types of access. The main purpose of this paper is to revise actual and new emerging ICTs and the use of its application tools in Education which is dominated by the linear paradigm in interaction and information as interactivity is not being accepted as a guiding principle. The concept of e-learning rests on the idea that pedagogy technologically sustained includes enough knowledge with regard to the wishes of learning processes, which are a process of mind embedded in a culture and also challenges and not just concepts. Learning is a process that humans have been trying to master for many centuries. However, there are so many different ways to do the process that it is sometimes very hard to determine which one is the best of a given situation. One such type of learning is heuristic learning. Through this method the students should discover things for themselves, through problem solving, inductive reasoning, or simply by trial and error. Discovering things by yourself, knowing from experience rather than books. In many situations it seems that heuristic learning is the most suitable when one really believes in something when one experiences it himself. That is what heuristic learning is really all about. This type of learning model, in an online format, is tailored to the adult learner who typically has a sense of self-direction related to individual interests, goals, strengths, and previous experience. Also the pedagogical theory of connectivism was born as a response to very fast ICT development which strongly influences education and which approach to problem solving is based on the use of simulation animations, making students change parameters and verify or seek the problem solving, applying their need of intuitive searching by the heuristic method; information is assigned by image without the application of long texts. After a series of simulation experiments, the students verify their results with a calculation and a real experiment.
Including teaching ethics into pedagogy
Authors: Kesar Shalini
Published: January 2016

This paper's discusses five real business capstone projects that were designed to provide an educational experiential learning to include ethics and professionalism in the pedagogy. This class comprised senior undergraduate Computer Science (CS) and Information Systems (IS) students. The projects involved teamwork and lasted fifteen weeks. The aim of the capstone curriculum was to foster a teaching environment to: 1) include interdisciplinary partnership among university departments; 2) cultivate local industry alliances; 3) encourage students' analysis and synthesis of skills and knowledge in a real business setting project. The National Society for Experiential Education (NSEE) practices were used while developing the curriculum and their eight Guiding Principles of Ethical Practices are used to describe the initial findings and lesson learned.
Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons
Authors: Telezhkin Vsevolod , Schnell Christian , Yarova Polina , Yung Sun , Cope Emma , Hughes Alis , Thompson Belinda A. , Sanders Philip , Geater Charlene , Hancock Jane M. , Joy Shona , Badder Luned , Connor-Robson Natalie , Comella Andrea , Straccia Marco , Bombau Georgina , Brown Jon T. , Canals Josep M. , Randall Andrew D. , Allen Nicholas D. , Kemp Paul J.
Published: December 2015

Although numerous protocols have been developed for differentiation of neurons from a variety of pluripotent stem cells, most have concentrated on being able to specify effectively appropriate neuronal subtypes and few have been designed to enhance or accelerate functional maturity. Of those that have, most employ time courses of functional maturation that are rather protracted, and none have fully characterized all aspects of neuronal function, from spontaneous action potential generation through to postsynaptic receptor maturation. Here, we describe a simple protocol that employs the sequential addition of just two supplemented media that have been formulated to separate the two key phases of neural differentiation, the neurogenesis and synaptogenesis, each characterized by different signaling requirements. Employing these media, this new protocol synchronized neurogenesis and enhanced the rate of maturation of pluripotent stem cell-derived neural precursors. Neurons differentiated using this protocol exhibited large cell capacitance with relatively hyperpolarized resting membrane potentials; moreover, they exhibited augmented: 1) spontaneous electrical activity; 2) regenerative induced action potential train activity; 3) Na+ current availability, and 4) synaptic currents. This was accomplished by rapid and uniform development of a mature, inhibitory GABAA receptor phenotype that was demonstrated by Ca2+ imaging and the ability of GABAA receptor blockers to evoke seizurogenic network activity in multielectrode array recordings. Furthermore, since this protocol can exploit expanded and frozen prepatterned neural progenitors to deliver mature neurons within 21 days, it is both scalable and transferable to high-throughput platforms for the use in functional screens.
Oligomerization of the Sec7 domain Arf guanine nucleotide exchange factor GBF1 is dispensable for Golgi localization and function but regulates degradation
Authors: Bhatt Jay M. , Viktorova Ekaterina G. , Busby Theodore , Wyrozumska Paulina , Newman Laura E. , Lin Helen , Lee Eunjoo , Wright John , Belov George A. , Kahn Richard A. , Sztul Elizabeth
Published: December 2015

Members of the large Sec7 domain-containing Arf guanine nucleotide exchange factor (GEF) family have been shown to dimerize through their NH2-terminal dimerization and cyclophilin binding (DCB) and homology upstream of Sec7 (HUS) domains. However, the importance of dimerization in GEF localization and function has not been assessed. We generated a GBF1 mutant (91/130) in which two residues required for oligomerization (K91 and E130 within the DCB domain) were replaced with A and assessed the effects of these mutations on GBF1 localization and cellular functions. We show that 91/130 is compromised in oligomerization but that it targets to the Golgi in a manner indistinguishable from wild-type GBF1 and that it rapidly exchanges between the cytosolic and membrane-bound pools. The 91/130 mutant appears active as it integrates within the functional network at the Golgi, supports Arf activation and COPI recruitment, and sustains Golgi homeostasis and cargo secretion when provided as a sole copy of functional GBF1 in cells. In addition, like wild-type GBF1, the 91/130 mutant supports poliovirus RNA replication, a process requiring GBF1 but believed to be independent of GBF1 catalytic activity. However, oligomerization appears to stabilize GBF1 in cells, and the 91/130 mutant is degraded faster than the wild-type GBF1. Our data support a model in which oligomerization is not a key regulator of GBF1 activity but impacts its function by regulating the cellular levels of GBF1.
Orai channel-mediated Ca2+ signals in vascular and airway smooth muscle
Authors: Spinelli Amy M. , Trebak Mohamed
Published: December 2015

Orai (Orai1, Orai2, and Orai3) proteins form a family of highly Ca2+-selective plasma membrane channels that are regulated by stromal-interacting molecules (STIM1 and STIM2); STIM proteins are Ca2+ sensors located in the membrane of the endoplasmic reticulum. STIM and Orai proteins are expressed in vascular and airway smooth muscle and constitute the molecular components of the ubiquitous store-operated Ca2+ entry pathway that mediate the Ca2+ release-activated Ca2+ current. STIM/Orai proteins also encode store-independent Ca2+ entry pathways in smooth muscle. Altered expression and function of STIM/Orai proteins have been linked to vascular and airway pathologies, including restenosis, hypertension, and atopic asthma. In this review we discuss our current understanding of Orai proteins and the store-dependent and -independent signaling pathways mediated by these proteins in vascular and airway smooth muscle. We also discuss the current studies linking altered expression and function of Orai proteins with smooth muscle-related pathologies.
Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming
Authors: Choi Kevin , Weber Jean-Michel
Published: December 2015

This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed ( Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production ( Raglucose) and disposal ( Rdglucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucritor the cost of transport. Results show that graded swimming causes no change in Raand Rdglucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg−1·min−1and boost glucose disposal to 40.1 ± 13 μmol·kg−1·min−1. These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucritbecause the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise.
Transforming growth factor-β1 and diabetic nephropathy
Authors: Chang Albert S. , Hathaway Catherine K. , Smithies Oliver , Kakoki Masao
Published: December 2015

Transforming growth factor-β1 (TGF-β1) is established to be involved in the pathogenesis of diabetic nephropathy. The diabetic milieu enhances oxidative stress and induces the expression of TGF-β1. TGF-β1 promotes cell hypertrophy and extracellular matrix accumulation in the mesangium, which decreases glomerular filtration rate and leads to chronic renal failure. Recently, TGF-β1 has been demonstrated to regulate urinary albumin excretion by both increasing glomerular permeability and decreasing reabsorption in the proximal tubules. TGF-β1 also increases urinary excretion of water, electrolytes and glucose by suppressing tubular reabsorption in both normal and diabetic conditions. Although TGF-β1 exerts hypertrophic and fibrogenic effects in diabetic nephropathy, whether suppression of the function of TGF-β1 can be an option to prevent or treat the complication is still controversial. This is partly because adrenal production of mineralocorticoids could be augmented by the suppression of TGF-β1. However, differentiating the molecular mechanisms for glomerulosclerosis from those for the suppression of the effects of mineralocorticoids by TGF-β1 may assist in developing novel therapeutic strategies for diabetic nephropathy. In this review, we discuss recent findings on the role of TGF-β1 in diabetic nephropathy.
αKlotho deficiency in acute kidney injury contributes to lung damage
Authors: Ravikumar Priya , Li Liping , Ye Jianfeng , Shi Mingjun , Taniguchi Masatomo , Zhang Jianning , Kuro-o Makoto , Hu Ming Chang , Moe Orson W. , Hsia Connie C. W.
Published: December 2015

αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI.
Postoperative Etoricoxib versus Ketoprofen Administration for Pain Management after Total Knee Arthroplasty: A Randomized, Double-Blind Controlled Study
Authors: Cionac Florescu Simona , Anastase Denisa Madalina , Munteanu Ana Maria , Stoica Cristian Ioan
Published: December 2015

Objective. This randomized double-blind study compared the analgesic efficacy and tolerability of etoricoxib versus ketoprofen in 165 patients with elective total primary knee arthroplasty. Methods. After ethical committee approval, 165 patients were randomized in 3 groups: the etoricoxib group (E) receiving etoricoxib 120 mg/day, at the end of surgery and in the first postoperative day; the ketoprofen group (K) receiving ketoprofen 2 pills of 100 mg/day, the first at the end of surgery and then 1 pill every 12 hours in the surgery day and the first postoperative day; the placebo group (P). All groups received postoperatively the same analgesia protocol when NRS is over 3 with IV Perfalgan and morphine. The effectiveness was evaluated by the time from the initiation of spinal anesthesia until the first analgesic dose, the total amount of morphine administered in the surgery day and the first postoperative day, and the frequency of patients with side effects and necessary amount of adjuvant medication. Results. The baseline demographic characteristics were similar among the 3 groups. In both study days etoricoxib provided an analgesic effect superior to placebo and to ketoprofen, the total administered morphine being significantly lower in etoricoxib group. There were no statistically significant differences between groups regarding the side effects.
A New Method to Simulate Free Surface Flows for Viscoelastic Fluid
Authors: Cao Yu , Ren Xiao-Guang , Guo Xiao-Wei , Wang Miao , Wang Qian , Xu Xin-Hai , Yang Xue-Jun
Published: December 2015

Free surface flows arise in a variety of engineering applications. To predict the dynamic characteristics of such problems, specific numerical methods are required to accurately capture the shape of free surface. This paper proposed a new method which combined the Arbitrary Lagrangian-Eulerian (ALE) technique with the Finite Volume Method (FVM) to simulate the time-dependent viscoelastic free surface flows. Based on an open source CFD toolbox called OpenFOAM, we designed an ALE-FVM free surface simulation platform. In the meantime, the die-swell flow had been investigated with our proposed platform to make a further analysis of free surface phenomenon. The results validated the correctness and effectiveness of the proposed method for free surface simulation in both Newtonian fluid and viscoelastic fluid.
Iterative Learning Control with Desired Gravity Compensation under Saturation for a Robotic Machining Manipulator
Authors: Ernesto Horacio , Pedro Jimoh O.
Published: December 2015

This paper proposes the design of a hybrid iterative learning controller for a four-degree-of-freedom (DOF) robotic machining manipulator (RMM). It combines a nonlinear saturated(sat)proportional + integral + derivative (PID) control with desired gravity compensation (dgc) and proportional + derivative- (PD-) based iterative learning control (ILC). Thesat(PID)control is the primary component that maintains the local stability of the entire RMM system and the PDILC component provides robustness to parameter variations and uncertainties in the robot dynamics. Global asymptotic stability of the proposed control algorithm is conducted using Lyapunov direct method and LaSalles invariance principle. Simulation results show the effectiveness and robustness of the proposed hybrid iterative learning controller. It is also shown that the proposed controller achieved better tracking performances compared to conventionalsat(PDdgc)feedback controller.