bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional analysis of sulfate reducing and chemolithoautotrophic sulfur oxidizing bacteria in the deep subseafloor
Authors: Orsi William D. , Barker Jørgensen Bo , Biddle Jennifer F.
Published: March 2016

Sulfate reducing bacteria (SRB) oxidize a significant proportion of subseafloor organic carbon, but their metabolic activities and subsistence mechanisms are poorly understood. Here, we report in depth phylogenetic and metabolic analyses of SRB transcripts in the Peru Margin subseafloor and interpret these results in the context of sulfate reduction activity in the sediment. Relative abundance of overall SRB gene transcripts declines strongly whereas relative abundance of ribosomal protein transcripts from sulfate reducing δ‐Proteobacteria peak at 90 m below seafloor (mbsf) within a deep sulfate methane transition zone. This coincides with isotopically heavy δ34S values of pore water sulfate (70‰), indicating active subseafloor microbial sulfate reduction. Within the shallow sulfate reduction zone (0–5 mbsf), a transcript encoding the beta subunit of dissimilatory sulfite reductase (dsrB) was related to Desulfitobacterium dehalogenans and environmental sequences from Aarhus Bay (Denmark). At 159 mbsf we discovered a transcript encoding the reversely operating dissimilatory sulfite reductase α‐subunit (rdsrA), with basal phylogenetic relation to the chemolithoautotrophic SUP05 Group II clade. A diversity of SRB transcripts involved in cellular maintenance point toward potential subsistence mechanisms under low‐energy over long time periods, and provide a detailed new picture of SRB activities underlying sulfur cycling in the deep subseafloor.
Dying Care Nursing Intervention in the Institutional Care of End‐of‐Life Patients
Authors: Kisvetrová Helena , Joanovič Eva , Vévoda Jiří , Školoudík David
Published: March 2016

PURPOSE

To determine the frequency of the Nursing Intervention Classification Dying Care activities performed by nurses with end‐of‐life (EOL) patients.

METHODS

A cross‐sectional, descriptive study using a structured questionnaire to determine the frequencies of Dying Care activities performed by 201 Czech nurses.

FINDINGS

Nurses reported more frequent use of activities focused on the physical comfort of EOL patients. Significant relationships were found between frequencies in some activities and the nurses’ education level, length of work experience, and the department type.

CONCLUSIONS

Nurses reported infrequent use of communication activities with patients and relatives, which is related to the length of practice.

CLINICAL RELEVANCE

It is necessary to focus on communication and psychosocial needs of EOL patients in both pregradual and lifelong nursing education.

CÍL

Zjistit frekvenci aktivit NIC intervence Péče o umírající mezi českými sestry u pacientů v závěru života.

METODY

Průřezová deskriptivní studie využívající strukturovaného dotazníku pro určení frekvence aktivit Péče o umírající prováděné 201 sestrou.

VÝSLEDKY

Sestry u pacientů v závěru života častější využívají aktivity zaměřené na fyzický komfort. Významné vztahy byly nalezeny mezi frekvencí některých aktivit a úrovní vzdělání sester, délkou praxe a typem pracoviště.

ZÁVĚRY

Sestry uváděly nepříliš časté používání komunikačních aktivit s pacienty a příbuznými, což souvisí s délkou jejich praxe.

KLINICKÁ RELEVANCE

Je třeba se zaměřit na komunikaci a psychosociální potřeby pacientů v závěru života jak v pregraduálním tak celoživotním vzdělávání sester.
Nursing Diagnosis Based on Signs and Symptoms of Patients With Heart Disease
Authors: da Costa Cíntia , da Costa Linch Graciele Fernanda , Nogueira de Souza Emiliane
Published: March 2016

PURPOSE

The aim was to identify the main signs and symptoms of cardiac patients hospitalized in a unit of intensive cardiology care in order to infer the main nursing diagnoses (NDs).

METHODS

We performed a cross‐sectional study; the sample consisted of 77 randomly selected records. Those records included only patients hospitalized for cardiovascular causes and with electronic chart available.

FINDINGS

Signs and symptoms identified at admission were psychic (40.3%), compressive dressing on arterial puncture site (33.8%), chest pain (29.9%), tachycardia (22.1%), and hemodynamic instability (20.8%).

CONCLUSIONS AND PRACTICAL IMPLICATIONS

According to the data collected, we were able to infer that acute pain, excess of fluid volume, decreased cardiac output, spontaneous ventilation impaired, anxiety and impaired skin integrity are priority for the NDs in the studied population.

OBJETIVO

identificar os principais sinais e sintomas de pacientes cardíacos internados em uma unidade de cuidados intensivos de cardiologia, visando inferir os diagnósticos de enfermagem prioritários.

MÉTODO

Estudo transversal; a amostra foi composta por 77 registros selecionados aleatoriamente. Incluíram‐se apenas pacientes internados por causa cardiovascular e com registro eletrônico disponível.

RESULTADOS

Os sinais e sintomas identificados na admissão foram psíquicos (40,3%), curativo compressivo em sítio de punção arterial (33,8%), dor torácica (29,9%), taquicardia (22,1%) e instabilidade hemodinâmica (20,8%).

CONCLUSÕES E IMPLICAÇÕES PARA A PRÁTICA

De acordo com os dados levantados foram inferidos Dor Aguda, Volume de Líquidos Excessivo, Débito Cardíaco Diminuído, Ventilação Espontânea Prejudicada, Ansiedade e Integridade da Pele Prejudicada como diagnósticos de enfermagem prioritários para a população estudada.
Joint Analysis of Multiple Traits in Rare Variant Association Studies
Authors: Wang Zhenchuan , Wang Xuexia , Sha Qiuying , Zhang Shuanglin
Published: March 2016

The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant‐by‐variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single‐TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single‐TOW and WSRR.
Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome
Authors: Sousa Vanessa C.S.D. , Carmo Rodrigo F. , Vasconcelos Luydson R.S. , Aroucha Dayse C.B.L. , Pereira Leila M.M.B. , Moura Patrícia , Cavalcanti Maria S.M.
Published: March 2016

The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C‐262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C‐262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0‐F1), 200 had moderate/severe fibrosis (F2‐F4), and 106 had HCC. Genotyping of SNPs was performed by real‐time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.
(How) Can We Estimate the Ideology of Citizens and Political Elites on the Same Scale?
Authors: Jessee Stephen
Published: March 2016

Estimating the ideological positions of political elites on the same scale as those of ordinary citizens has great potential to increase our understanding of voting behavior, representation, and other political phenomena. There has been limited attention, however, to the fundamental issues, both practical and conceptual, involved in conducting these joint scalings, or to the sensitivity of these estimates to modeling assumptions and data choices. I show that the standard strategy of estimating ideal point models using preference data on citizens and elites can suffer from potentially problematic pathologies. This article explores these issues and presents a technique that can be used to investigate the effects of modeling assumptions on resulting estimates and also to impose restrictions on the ideological dimension being estimated in a straightforward way.
In vitrotests for drug hypersensitivity reactions: anENDA/EAACIDrug Allergy Interest Group position paper
Authors: Mayorga C. , Celik G. , Rouzaire P. , Whitaker P. , Bonadonna P. , Rodrigues‐Cernadas J. , Vultaggio A. , Brockow K. , Caubet J. C. , Makowska J. , Nakonechna A. , Romano A. , Montañez M. I. , Laguna J. J. , Zanoni G. , Gueant J. L. , Oude Elberink H. , Fernandez J. , Viel S. , Demoly P. , Torres M. J. ,   In vitro tests for Drug Allergy Task Force of EAACI Drug Interest Group
Published: March 2016

Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, becausein vivotests have a suboptimal sensitivity and can be time‐consuming, expensive and potentially risky, especially drug provocation tests. There are several currently availablein vitromethods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of thesein vitromethods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types ofDHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the availablein vitromethods forDHRdiagnosis. We have found that although there are manyin vitrotests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well‐controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently availablein vitrotests in a large series of well‐characterized patients withDHRand to develop new tests for diagnosis.
The lipid interaction capacity of Sin a 2 and Ara h 1, major mustard and peanut allergens of the cupin superfamily, endorses allergenicity
Authors: Angelina A. , Sirvent S. , Palladino C. , Vereda A. , Cuesta‐Herranz J. , Eiwegger T. , Rodríguez R. , Breiteneder H. , Villalba M. , Palomares O.
Published: March 2016

Background

Sin a 2 (11S globulin) and Ara h 1 (7S globulin) are major allergens from yellow mustard seeds and peanut, respectively. The ability of these two allergens to interact with lipid components remains unknown.

Objective

To study the capacity of Sin a 2 and Ara h 1 to interact with lipid components and the potential effects of such interaction in their allergenic capacity.

Methods

Spectroscopic and SDS‐PAGE binding assays of Sin a 2 and Ara h 1 with different phospholipid vesicles and gastrointestinal and endolysosomal digestions in the presence or absence of lipids were performed. The capacity of human monocyte‐derived dendritic cells (hmoDCs) to capture food allergens in the presence or absence of lipids, the induced cytokine signature, and the effect of allergens and lipids to regulate TLR2‐L‐induced NF‐kB/AP‐1 activation in THP1 cells were analyzed.

Results

Sin a 2 and Ara h 1 bind phosphatidylglycerol (PG) acid but not phosphatidylcholine (PC) vesicles in a pH‐dependent manner. The interaction of these two allergens with lipid components confers resistance to gastrointestinal digestion, reduces their uptake by hmoDCs, and enhances their stability to microsomal degradation. Mustard and peanut lipids favor a proinflammatory environment by increasing the IL‐4/IL‐10 ratio and IL‐1β production by hmoDCs. The presence of mustard lipids and PG vesicles inhibits TLR2‐L‐induced NF‐kB/AP‐1 activation in THP1 cells.

Conclusion

Sin a 2 and Ara h 1 interact with lipid components, which might well contribute to explain the potent allergenic capacity of these two clinically relevant allergens belonging to the cupin superfamily.
Acquiring surgical skills: the history of surgical teaching at the University of Sydney 1883–2014
Authors: Brown Kilian G. M. , Storey Catherine E.
Published: March 2016

There have been at least 10 major revisions of the medical curriculum since the inauguration of the Faculty of Medicine at the University of Sydney in 1883. This study traced the evolution of the teaching of surgery at our institution by examination of the set curriculum of each period; the expectations of student knowledge in the final examination as well as examining some of the insights provided by past students of their surgical experience through their writings. In the early years, medical graduates were qualified to perform operative surgery without any further training, whereas the modern postgraduate medical curriculum provides students with the basis for further surgical training.
Participation in a clinical trial for a child with cancer is burdensome for a minority of children
Authors: van der Geest Ivana M.M. , van den Heuvel‐Eibrink Marry M. , Zwaan C. Michel , Pieters Rob , Passchier Jan , Darlington Anne‐Sophie E.
Published: March 2016

Aim

This study explored how parents who had lost a child to cancer felt about them taking part in a clinical trial.

Methods

A retrospective questionnaire was sent to parents who had lost a child to cancer. They were asked whether their child took part in a clinical trial during their palliative phase, their motives for their child's participation, how they perceived their child's burden and whether they would, hypothetically speaking, enrol again.

Results

The 24 parents of 16 deceased children who had participated in a clinical trial explained their motives for their child's participation. The most common answers, with multiple responses, were treatment for future patients (n = 16), hope for a cure (n = 9) and prolonging their child's life (n = 6). Eight parents said that participating was not burdensome for their child and four said it was very burdensome, with others answering in between. None of the parents would decline participation if they would be in the same situation again.

Conclusion

Performing clinical trials, even in a vulnerable population, such as children with cancer at the end of life, may not always lead to increased burden. None of the parents would in future, given the same circumstances, decline participation in a clinical trial.
Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis
Authors: Singh S. , Heien H. C. , Sangaralingham L. R. , Schilz S. R. , Kappelman M. D. , Shah N. D. , Loftus E. V.
Published: March 2016

Background

Real‐world comparative benefits and risks of infliximab (IFX) and adalimumab (ADA) in patients with ulcerative colitis (UC) are unclear.

Aim

To evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti‐TNF agents.

Methods

Using an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti‐TNF (IFX, ADA) prescription after a 12‐month period without any anti‐TNF treatment (baseline), and with a minimum 6‐month follow‐up after anti‐TNF initiation. Primary outcome measures were: all‐cause and UC‐related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti‐TNF, and serious infections. We performed 2:1 propensity‐score matched Cox proportional hazard analysis, and inverse probability‐of‐treatment weight (IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC‐related medication.

Results

We included 1400 new users of anti‐TNF agents (age, 43 ± 15 years; 52% males), from 2006 to 2014. On propensity‐score matched analysis, there was no significant difference in the risk of UC‐related hospitalisation [IFX vs. ADA; adjusted hazard ratio (aHR), 1.04; 95% confidence interval (CI) 0.71–1.51], corticosteroid use (aHR, 0.85; 95% CI, 0.68–1.06) and serious infections (aHR, 0.62; 95% CI, 0.29–1.34) between IFX‐ and ADA‐treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX – as compared to ADA – treated patients (aHR, 0.82; 95% CI, 0.68–0.99). Results were stable on multiple sensitivity analyses.

Conclusions

In a large retrospective cohort of patients with UC who were new users of anti‐TNF agents, IFX‐treated patients may have lower corticosteroid use than ADA‐treated patients, but risk of hospitalisation and serious infections were comparable.
Systematic review with meta‐analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children
Authors: Urbańska M. , Gieruszczak‐Białek D. , Szajewska H.
Published: March 2016

Background

Not all probiotics are equal.

Aim

To investigate the efficacy of Lactobacillus reuteri DSM 17938 (L. reuteri) in the management of various types of diarrhoeal diseases in children.

Methods

Medline, Embase, the Cochrane Library, trial registries and reference lists of included studies were searched in January 2016, with no language restriction, for randomised controlled trials (RCTs).

Results

Eight RCTs (n = 1229) met the inclusion criteria. In treatment trials, L. reuteri administration reduced the duration of diarrhoea (three RCTs, n = 256, mean difference, MD −24.82 h, 95% CI −38.8 to −10.8) and increased the cure rate on day 1 and day 2. However, heterogeneity and wide confidence intervals call for caution in interpreting results. In preventive trials carried out in hospitalised children, based on the findings from two RCTs (n = 290), there was no significant reduction in the risk of nosocomial diarrhoea, rotavirus diarrhoea or diarrhoea of any origin with L. reuteri administration. Based on one RCT (n = 97), there was no effect of L. reuteri on the risk of antibiotic‐associated diarrhoea. However, the evidence is limited because the overall frequency of diarrhoea was surprisingly low. In preventive studies carried out in apparently healthy children, L. reuteri reduced diarrhoeal outcomes in one RCT; the evidence from another trial was less convincing.

Conclusions

In therapeutic settings, L. reuteri administration reduces the duration of diarrhoea and increases the chance of cure. In preventive settings, L. reuteri has the potential to reduce the risk of community‐acquired diarrhoea in otherwise healthy children.
Effects of chemical additives on the fermentation quality and N distribution of alfalfa silage in south of China
Authors: Li Ping , Ji Shuren , Hou Chen , Tang Haiyang , Wang Qian , Shen Yixin
Published: March 2016

In order to better utilize the last cut alfalfa harvested before killing frost in a high moisture environment, the effects of chemical additives on the quality of alfalfa silage were studied in south of China. The alfalfa was freshly harvested at branching stage, and wilted by dry matter content of about 300 g/kg (fresh matter basis). Silage was prepared by using a small‐scale silage fermentation system, where sucrose, potassium citrate, sodium carbonate, formic acid, acetic acid and propionic acid were used as silage additives, and no additives served as control. These silos were stored at ambient temperature (5‐20°C), and the silage qualities were analyzed after 120 days of fermentation. All additive treatments affected the chemical composition and N distribution, increased the water‐soluble content and crude protein contents, decreased non‐protein nitrogen (NPN) content, and enhanced the in vitro ruminal dry matter digestibility (except for sodium carbonate). Silages treated with organic acids were preserved with significantly (P < 0.05) lower pH value, ethanol content and NPN content compared with control. When the fermentation quality, chemical composition and N distribution were considered, the treatment with sucrose or organic acids resulted in high quality of alfalfa silage ensiled before killing frost, with formic acid having the best effect.
Defining ‘nutraceuticals’: neither nutritious nor pharmaceutical
Authors: Aronson Jeffrey K.
Published: March 2016

There are widespread inconsistencies and contradictions in the many published definitions of ‘nutraceuticals’ and ‘functional foods’, demonstrating wholesale uncertainty about what they actually are. Furthermore, in a 2014 lecture, the inventor of the term ‘nutraceutical’, confessing that nutraceuticals do not work, said that ‘the quest to demonstrate whether … long‐term supplementation [with nutraceuticals] can prevent serious diseases … has come to an end’. Definitions of ‘nutraceuticals’ and related terms, still widely used, should therefore be explored systematically. There are no internationally agreed definitions of ‘nutraceuticals’ and ‘functional foods’, or of similar terms, such as ‘health foods’, or of terms related to herbal products, which are sometimes referred to as ‘nutraceuticals’, compounding the confusion. ‘Nutraceuticals’ and ‘functional foods’ are vague, nondiscriminatory, unhelpful terms; the evidence suggests that they should be abandoned in favour of more precise terms. The term ‘dietary supplement’ is widely used to designate formulations that are also called ‘nutraceuticals’ but it would be better restricted to individual compounds used to treat or prevent deficiencies. ‘Fortified foods’, sometimes called ‘designer foods’, are foods to which compounds of proven therapeutic or preventive efficacy (e.g. folic acid) have been added. Other terms, such as ‘food’, ‘foodstuffs’, ‘eat’, ‘drink’, and ‘nutrition’, are well defined, as are ‘medicinal products’ and ‘pharmaceutical formulations’. Dietary regimens, such as Mediterranean or nitrate‐rich diets or vegetarianism, can affect health. A dietary regimen of this kind can be defined as a programme of food, of a defined kind and/or quantity, prescribed or adopted for the restoration or preservation of health.
Anti‐inflammatory agents in the treatment of bipolar depression: a systematic review and meta‐analysis
Authors: Rosenblat Joshua D , Kakar Ron , Berk Michael , Kessing Lars V , Vinberg Maj , Baune Bernhard T , Mansur Rodrigo B , Brietzke Elisa , Goldstein Benjamin I , McIntyre Roger S
Published: March 2016

Objective

Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti‐inflammatory agents in the treatment of bipolar depression.

Methods

Completed and ongoing clinical trials of anti‐inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti‐inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone.

Results

Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti‐inflammatory drugs (n = 53), omega‐3 polyunsaturated fatty acids (n = 140), N‐acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti‐inflammatory agents on depressive symptoms was −0.40 (95% confidence interval −0.14 to −0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment‐emergent adverse events were reported.

Conclusions

Overall, a moderate antidepressant effect was observed for adjunctive anti‐inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
History of psychosis and previous episodes as potential explanatory factors for neurocognitive impairment in first‐treatment bipolar I disorder
Authors: Demmo Christine , Lagerberg Trine Vik , Aminoff Sofie R , Hellvin Tone , Kvitland Levi R , Simonsen Carmen , Andreassen Ole A , Melle Ingrid , Ueland Torill
Published: March 2016

Objectives

Explanatory factors for the observed neurocognitive impairment in early‐stage bipolar I disorder (BD‐I) have received little attention. The current study investigated neurocognitive functioning in first‐treatment (FT) BD‐I compared to FT schizophrenia (SCZ), and healthy controls (HCs), and the effect of history of psychosis and previous episodes in the two clinical groups.

Methods

A total of 202 FT patients with BD‐I (n = 101) and SCZ spectrum disorder (n = 101), in addition to HCs (n = 101), were included. A comprehensive neurocognitive test battery was used to assess verbal learning and memory, executive functioning, processing speed, and attention and working memory. Neurocognitive functioning and the effect of history of psychosis and number of previous episodes were analyzed using separate multivariate analyses of variance and correlation analysis.

Results

FT patients with BD‐I performed intermediately between FT SCZ spectrum patients and HCs on all measures. Compared to HCs, FT BD‐I showed impaired functioning across all neurocognitive domains. No differences in neurocognitive functioning were observed in psychotic versus nonpsychotic FT patients with BD‐I. With the exception of an association between number of manic episodes and two measures of executive function in FT BD‐I, no associations were found between number of episodes and neurocognitive performance.

Conclusions

Neurocognitive impairments were present in FT BD‐I, and were not explained by history of psychosis or number of previous psychotic or depressive episodes. There were indications that executive function could be associated with number of previous manic episodes.
The effect of CSR evaluations on affective attachment to CSR in different identity orientation firms
Authors: Fryzel Barbara , Seppala Nina
Published: March 2016

The goal of the present research was to examine the way in which organisational identity orientation and corporate social responsibility (CSR) interact to produce affective attachment and related beneficial behaviours among organisational members. Using a questionnaire administered in Poland, it was shown that when CSR activity was viewed as authentic by employees, it led to affective attachment to the organisation's CSR stance, while an instrumental evaluation was correlated with a negative attachment to the CSR stance. The results suggest that CSR motives were particularly important for organisations with relational and collectivistic identity orientations because of the focus of these organisations on mutual or collective good that could be demonstrated through CSR. The results contributed to social identity literature by establishing a clear relationship between the concepts of identity orientation and CSR and showing that only authentic CSR produces affective attachment and behaviours that benefit the organisation.
Biased and Unbiased Estimation in Longitudinal Studies with Informative Visit Processes
Authors: McCulloch Charles E. , Neuhaus John M. , Olin Rebecca L.
Published: March 2016

The availability of data in longitudinal studies is often driven by features of the characteristics being studied. For example, clinical databases are increasingly being used for research to address longitudinal questions. Because visit times in such data are often driven by patient characteristics that may be related to the outcome being studied, the danger is that this will result in biased estimation compared to designed, prospective studies. We study longitudinal data that follow a generalized linear mixed model and use a log link to relate an informative visit process to random effects in the mixed model. This device allows us to elucidate which parameters are biased under the informative visit process and to what degree. We show that the informative visit process can badly bias estimators of parameters of covariates associated with the random effects, while allowing consistent estimation of other parameters.
Label-Noise Resistant Logistic Regression for Functional Data Classification with an Application to Alzheimer's Disease Study
Authors: Lee Seokho , Shin Hyejin , Lee Sang Han
Published: March 2016

Alzheimer's disease (AD) is usually diagnosed by clinicians through cognitive and functional performance test with a potential risk of misdiagnosis. Since the progression of AD is known to cause structural changes in the corpus callosum (CC), the CC thickness can be used as a functional covariate in AD classification problem for a diagnosis. However, misclassified class labels negatively impact the classification performance. Motivated by AD–CC association studies, we propose a logistic regression for functional data classification that is robust to misdiagnosis or label noise. Specifically, our logistic regression model is constructed by adopting individual intercepts to functional logistic regression model. This approach enables to indicate which observations are possibly mislabeled and also lead to a robust and efficient classifier. An effective algorithm using MM algorithm provides simple closed-form update formulas. We test our method using synthetic datasets to demonstrate its superiority over an existing method, and apply it to differentiating patients with AD from healthy normals based on CC from MRI.
Circular Piecewise Regression with Applications to Cell-Cycle Data
Authors: Rueda Cristina , Fernández Miguel A. , Barragán Sandra , Mardia Kanti V. , Peddada Shyamal D.
Published: March 2016

Applications of circular regression models appear in many different fields such as evolutionary psychology, motor behavior, biology, and, in particular, in the analysis of gene expressions in oscillatory systems. Specifically, for the gene expression problem, a researcher may be interested in modeling the relationship among the phases of cell-cycle genes in two species with differing periods. This challenging problem reduces to the problem of constructing a piecewise circular regression model and, with this objective in mind, we propose a flexible circular regression model which allows different parameter values depending on sectors along the circle. We give a detailed interpretation of the parameters in the model and provide maximum likelihood estimators. We also provide a model selection procedure based on the concept of generalized degrees of freedom. The model is then applied to the analysis of two different cell-cycle data sets and through these examples we highlight the power of our new methodology.
Pedagogy first: Realising technology enhanced learning by focusing on teaching practice
Authors: Glover Ian , Hepplestone Stuart , Parkin Helen J. , Rodger Helen , Irwin Brian
Published: March 2016

This paper explores a “pedagogy first” approach to technology enhanced learning developed by Sheffield Hallam University (SHU) as a method to encourage use of, and experimentation with, technology within teaching practice and to promote the mainstreaming of innovative practice. Through a consultative approach where all staff members were invited to contribute, SHU has created a Teaching Approaches Menu that reflects practice at the institution and can be used to explore teaching practice and appropriate supporting technology either by individuals or as part of a facilitated discussion. Background to the project is provided, along with the design philosophy and approach, including a brief review of other frameworks. The Teaching Approaches Menu is introduced, its development outlined, and some initial feedback is presented.
Who or what contributes to student satisfaction in different blended learning modalities?
Authors: Diep Anh‐Nguyet , Zhu Chang , Struyven Katrien , Blieck Yves
Published: March 2016

Different blended learning (BL) modalities and the interaction effect between human and technological factors on student satisfaction need adequately researched to shed more light on successful BL implementation. The objective of the present article is three‐fold: (1) to present a model to predict student satisfaction with BL programs, (2) to examine the interaction effect between the instructor expertise and the learning management system (LMS) on student satisfaction in different BL modes, and (3) to investigate if different modes of BL will exert an influence on students’ perceived achievement goals and satisfaction, their evaluation of the instructors, and the LMS quality. Results show that the instructor expertise, students’ perceived task value and achievement goals are the most influential factors, followed by the LMS quality, instructor support, and students’ general self‐efficacy. Contradictory to previous studies, the LMS quality only has an indirect effect on student satisfaction, via perceived achievement goals. In different BL conditions, the LMS quality has significantly different effect on student satisfaction, when interacting with the instructor expertise. The two modalities of BL programs also yield differences in students’ perceived achievement goals and their demand for the LMS's functionality and design, hence crucial implications for pedagogical practices and institutional policy addressed.
The Discreet Charm of University Autonomy: Conflicting Legacies in the Venezuelan Student Movements
Authors: IVANCHEVA MARIYA P.
Published: March 2016

The recent history of Venezuela's student movements illustrates the paradox of academic autonomy. The student left used autonomy to resist repression during Venezuela's liberal democracy (1958). Yet, after 1998, the former supporters of the parties which had violated that autonomy started to capitalise on it in order to block the progressive reforms. The Bolivarian government's decision not to interfere with autonomous universities, but to create a parallel Bolivarian university system instead replicated one of the reform patterns of previous governments. Despite the government's intention to fight inequality, the reform contributed to further stratification of higher education and polarisation among the student movements.
PERCEIVED INTENTIONALITY IN 2 × 2 EXPERIMENTAL GAMES
Authors: Chuah Swee‐Hoon , Hoffmann Robert , Larner Jeremy
Published: March 2016

We test experimentally whether decisions in 2 × 2 games with mixed equilibria depend on the co‐player being nature or a human agent. Controlling for social preferences, we find differences in decisions in the chicken game and battle of the sexes but not for stag hunt and matching pennies. We attribute these to subjects' perception of the other's intentionality and disapproval avoidance in particular.
Ozanimod (RPC1063) is a potent sphingosine‐1‐phosphate receptor‐1 (S1P1) and receptor‐5 (S1P5) agonist with autoimmune disease‐modifying activity
Authors: Scott F L , Clemons B , Brooks J , Brahmachary E , Powell R , Dedman H , Desale H G , Timony G A , Martinborough E , Rosen H , Roberts E , Boehm M F , Peach R J
Published: March 2016

Background and Purpose

Sphingosine1‐phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non‐selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases.

Experimental Approach

The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6‐trinitrobenzenesulfonic acid colitis and CD4+CD45RBhi T cell adoptive transfer colitis) was assessed.

Key Results

RPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7+ T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half‐life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models.

Conclusions and Implications

S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic.
Identification of a selective glucocorticoid receptor modulator that prevents both diet‐induced obesity and inflammation
Authors: van den Heuvel José K , Boon Mariëtte R , van Hengel Ingmar , Peschier‐van der Put Emma , van Beek Lianne , van Harmelen Vanessa , van Dijk Ko Willems , Pereira Alberto M , Hunt Hazel , Belanoff Joseph K , Rensen Patrick C N , Meijer Onno C
Published: March 2016

Background and Purpose

High‐fat diet consumption results in obesity and chronic low‐grade inflammation in adipose tissue. Whereas glucocorticoid receptor (GR) antagonism reduces diet‐induced obesity, GR agonism reduces inflammation, the combination of which would be desired in a strategy to combat the metabolic syndrome. The purpose of this study was to assess the beneficial effects of the selective GR modulator C108297 on both diet‐induced weight gain and inflammation in mice and to elucidate underlying mechanisms.

Experimental Approach

Ten‐week‐old C57Bl/6 J mice were fed a high‐fat diet for 4 weeks while being treated with the selective GR modulator C108297, a full GR antagonist (RU486/mifepristone) or vehicle.

Key Results

C108297 and, to a lesser extent, mifepristone reduced body weight gain and fat mass. C108297 decreased food and fructose intake and increased lipolysis in white adipose tissue (WAT) and free fatty acid levels in plasma, resulting in decreased fat cell size and increased fatty acid oxidation. Furthermore, C108297 reduced macrophage infiltration and pro‐inflammatory cytokine expression in WAT, as well as in vitro LPS‐stimulated TNF‐α secretion in macrophage RAW 264.7 cells. However, mifepristone also increased energy expenditure, as measured by fully automatic metabolic cages, and enhanced expression of thermogenic markers in energy‐combusting brown adipose tissue (BAT) but did not affect inflammation.

Conclusions and Implications

C108297 attenuates obesity by reducing caloric intake and increasing lipolysis and fat oxidation, and in addition attenuates inflammation. These data suggest that selective GR modulation may be a viable strategy for the reduction of diet‐induced obesity and inflammation.
Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm
Authors: Loudon Brodie L , Noordali Hannah , Gollop Nicholas D , Frenneaux Michael P , Madhani Melanie
Published: March 2016

Many conditions culminate in heart failure (HF), a multi‐organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence‐base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.
A novel protein tyrosine phosphatase 1B inhibitor with therapeutic potential for insulin resistance
Authors: Zhang Xiaolin , Tian Jinying , Li Juan , Huang Liwei , Wu Song , Liang Wei , Zhong Liangwei , Ye Jianping , Ye Fei
Published: March 2016

Background and Purpose

Insulin‐sensitizing drugs are currently limited, and identifying new candidates is a challenge. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling, and its inhibition is anticipated to improve insulin resistance. Here, the pharmacological properties of CX08005, a novel PTP1B inhibitor, were investigated.

Experimental Approach

Recombinant hPTP1B protein was used to study enzyme activity and mode of inhibition. Docking simulation explored the interactions between CX08005 and PTP1B. Insulin sensitivity was evaluated by glucose tolerance test (GTT) in diet‐induced obese (DIO) and KKAy mice; glucose‐stimulated insulin secretion (GSIS), homeostasis model assessment of insulin resistance index (HOMA‐IR) and whole‐body insulin sensitivity (ISWB) were also determined. A hyperinsulinaemic–euglycaemic clamp was performed to evaluate insulin‐stimulated glucose disposal in both whole‐body and insulin‐sensitive tissues. Furthermore, CX08005's effects on muscle, fat and liver cells were determined in vitro.

Key Results

CX08005 competitively inhibited PTP1B by binding to the catalytic P‐loop through hydrogen bonds. In DIO mice, CX08005 ameliorated glucose intolerance dose‐dependently (50–200 mg·kg−1·day−1) and decreased the HOMA‐IR. In KKAy mice, CX08005 (50 mg·kg−1·day−1) improved glucose intolerance, GSIS, ISWB and hyperglycaemia. CX08005 also enhanced insulin‐stimulated glucose disposal, increased glucose infusion rate and glucose uptake in muscle and fat in DIO mice (hyperinsulinaemic–euglycaemic clamp test). CX08005 enhanced insulin‐induced glucose uptake in 3T3‐L1 adipocytes and C2C12 myotubes, and increased phosphorylation of IRβ/IRS1 and downstream molecules in hepatocytes in a dose‐ and insulin‐dependent manner respectively.

Conclusions and Implications

Our results strongly suggest that CX08005 directly enhances insulin action in vitro and in vivo through competitive inhibition of PTP1B.
Tectonic evolution of an intraplate basin: the Lower Tagus Cenozoic Basin, Portugal
Authors: Carvalho João , Pinto Carlos , Dias Ruben , Rabeh Taha , Torres Luis , Borges José , Torres Ricardo , Duarte Henrique
Published: March 2016

This article focuses on the reinterpretation of well, seismic reflection, magnetic, gravimetric, surface wave and geological surface data, together with the acquisition of seismic noise data to study the Lower Tagus Cenozoic Basin tectono‐sedimentary evolution. For the first time, the structure of the base of the basin in its distal and intermediate sectors is unravelled, which was previously only known in the areas covered by seismic reflection data (distal and small part of intermediate sectors). A complex geometry was found, with three subbasins delimited by NNE‐SSW faults and separated by WNW‐ESE to NW‐SE oriented horsts. In the area covered by seismic reflection data, four horizons were studied: top of the Upper Miocene, Lower to Middle Miocene top, the top of the Palaeogene and the base of Cenozoic. Seismic data show that the major filling of the basin occurred during Upper Miocene. The fault pattern affecting Neogene and Palaeogene units derived here points to that of a polyphasic basin. In the Palaeogene, the Vila Franca de Xira (VFX) and a NNE‐SSW trending previously unknown structure (ABC fault zone) probably acted as the major strike‐slip fault zones of the releasing bend of a pull‐apart basin, which produced a WNW‐ESE to NW‐SE fault system with transtensional kinematic. During the Neogene, as the stress regime rotated anticlockwise to the present NW‐SE to WNW‐ESE orientation, the VFX and Azambuja fault zones acted as the major transpressive fault zones and Mesozoic rocks overthrusted Miocene sediments. The reactivation of WNW‐ESE to NW‐SE fault systems with a dextral strike‐slip component generated a series of horsts and grabens and the partitioning of the basin into several subbasins. Therefore, we propose a polyphasic model for the area, with the formation of an early pull‐apart basin during the Palaeogene caused by an Iberia–Eurasia plates collision that later evolved into an incipient foreland basin along the Neogene due to a NW‐SE to WNE‐ESE oriented Iberia–Nubia convergence. This convergence is producing uplift in the area since the Quaternary except for the Tagus estuary subbasin around the VFX fault, where subsidence is observed. This may be due to the locking or the development of a larger component of strike‐slip movement of the NNE‐SSW to N‐S thrust fault system with the exception of the VFX fault, which is more favourably oriented to the maximum compressive stress.