bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of consent practices in cluster randomized trials: Improvements are needed in ethical conduct and reporting
Authors: Taljaard Monica , Chaudhry Shazia H , Brehaut Jamie C , Weijer Charles , Boruch Robert , Donner Allan , Eccles Martin P , McRae Andrew D , Saginur Raphael , Zwarenstein Merrick , Grimshaw Jeremy M
Published: December 2013

Background

Informed consent procedures in cluster randomized trials (CRTs) are considerably more complicated than in individually randomized trials. In a CRT, the units of randomization, intervention, and observation may differ in a single trial; there can be multiple levels of participants (individual and cluster level); consent may be required separately for intervention and data collection; and there may be practical constraints to seeking informed consent, for example, due to cluster-level interventions or the sheer size of clusters.

Purpose

We aimed to document consent practices at individual and cluster levels, assess the adequacy of reporting consent in trial publications, and assess associations with two trial characteristics that may influence consent requirements in CRTs: presence or absence of study interventions and presence or absence of data collection procedures at individual and cluster levels.

Methods

We reviewed a random sample of 300 CRTs published during 2000–2008. We sent survey questionnaires to 285 unique authors of these trials to gather detailed information about consent procedures used in each trial.

Results

In all, 182 authors (64%) responded. Overall, 93% (95% confidence interval (CI): 88.8%−96.6%) indicated that participant consent had been sought for some aspects of the study. Consent was less frequently sought for a study intervention (70% of respondents) than for data collection (88%). More than half of the respondents (52%) indicated that consent had been sought at both cluster and individual levels. There was strong evidence for under-reporting of consent in trial publications: only 63% of all trial publications reported that informed consent had been sought for some aspect of the study. The odds ratios (ORs) summarizing the association of the two trial characteristics with cluster-level participant consent were weak (OR = 1.17, p = 0.70 for presence of cluster-level study intervention and OR = 1.54, p = 0.29 for data collection); on the other hand, the ORs summarizing the associations with individual-level consent were strong (OR = 6.2, p < 0.0001 for presence of individual-level intervention and OR = 14.7, p < 0.0001 for data collection).

Limitations

In all, 36% of authors did not respond to the survey; to the extent that consent practices in their trials were different than in respondents’ trials, our results may be biased.

Conclusions

There is a need for improvements in research practices in CRTs as well as their reporting. There may be a lack of clarity about consent requirements at the cluster level in particular. With the publication of the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, researchers and research ethics committees now have access to comprehensive ethics guidelines specific to CRTs.
Usage of generics in Ireland: Recent trends and policy developments
Authors: Brick Aoife , Gorecki Paul K , Nolan Anne
Published: December 2013

In 2011, the Irish State spent €1.9bn on pharmaceuticals, amounting to approximately 13% of total public health expenditure. Over the period 2000–2010, Ireland experienced one of the fastest growth rates in per capita pharmaceutical expenditure in the OECD. Concern over pharmaceutical expenditure in Ireland has led to a number of policy changes, targeting primarily the price of pharmaceuticals. More recently, there has been much concern over the low rates of generic usage in Ireland. In 2009, 34% of multiple-source off-patent pharmaceuticals dispensed under the main State pharmaceutical reimbursement schemes in Ireland were generics, in comparison with 71% in the UK. Up to now, the potential for significant savings through the increased use of generics in Ireland has been limited as the price of off-patent pharmaceuticals (including generic pharmaceuticals) was set at a small discount to the patent-holder price. Legislation to introduce a system of reference pricing and generic substitution for 20 leading off-patent pharmaceuticals has recently been enacted. However, reference prices have yet to be set, and so the full scale of any potential savings under the Health (Pricing and Supply of Medical Goods) Act 2013 has yet to be determined. In advance of the new legislation, there has been evidence of a substantial increase in the use of generics in Ireland, although the precise reasons driving this increase are unclear.
Getting started with research “Writing-up the results of your research”
Authors: Browne Jacinta E
Published: December 2013

This paper gives an overview of the considerations and practical aspects of writing up the results of your research, which may be of interest to those beginning their research career or simply carrying out a research project for the first time as part of an academic qualification. It outlines practical steps for both writing up the results of your research as an academic report and thereafter disseminating your results more widely as a peer-reviewed scientific publication.
Seeing past the appendix: the role of ultrasound in right iliac fossa pain
Authors: EK White , L MacDonald , G Johnson , V Rudralingham
Published: December 2013

Acute right iliac fossa pain is a common surgical presentation. The presentation is often non-specific and encompasses a wide differential, which creates a diagnostic challenge. Ultrasound is commonly the initial cross-sectional imaging modality and can be used as a tool to triage patients appropriately; assessing for appendicitis and other salient findings, which may indicate an alternative condition. Additionally, the dynamic nature of this imaging modality enables patient interaction. Following a systematic assessment of the abdomen and pelvis, a more focused interrogation of the right iliac fossa is performed. In this pictorial review, we illustrate the sonographic features of appendicitis and other conditions that can mimic appendicitis in its presentation. This highlights that through a systematic approach, it is possible to distinguish between these different pathologies, enabling clinicians to optimally manage the patient.
Generalized Myoclonus
Authors: Inoa Violiza , McCullough Louise D.
Published: December 2013

Movement disorders have been reported as rare complications of stroke. The basal ganglia have been implicated in the pathophysiology of most post-stroke dyskinesias. We outline different types of post-stroke myoclonus and their possible pathophysiology. A middle-aged man developed generalized myoclonus after an ischemic stroke in the superior midbrain and subthalamic nuclei. Spontaneous resolution was seen by 72 hours. A lesion to the subthalamic nuclei disrupted the normal thalamic inhibition, which likely led to the involuntary movements seen in our patient. In this case, myoclonus was generalized, which, to the best of our knowledge, has not been reported in the literature as a direct consequence of focal stroke.
First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks
Authors: Nicholas Jacqueline Ann , Racke Michael Karl , Imitola Jamie , Boster Aaron Lee
Published: December 2013

Natalizumab (NTZ) is a highly effective disease modifying therapy for the treatment of relapsing forms of multiple sclerosis (MS). Despite evidence to support its use as first-line therapy, risk of NTZ-associated progressive multifocal leukoencephalopathy (PML) has largely contributed to it being relegated to a second-line position. Recent preliminary data may allow for a more accurate analysis of JC virus (JCV) risk stratification of a given patient’s PML risk. Herein we propose an algorithm to help guide clinicians through this decision-making process. We recommend that NTZ be considered for first-line use in JCV antibody negative MS patients, JCV ‘low positive’ MS patients without prior exposure to immunosuppression and for a limited period (12–24 months) in JCV ‘high positive’ MS patients with an aggressive disease course . We caution against first-line use in JCV antibody ‘high positive’ patients beyond 12–24 months and any JCV antibody positive patient with a history of prior immunosuppression.
Gender Differences in the Spillover Between Romantic Experiences, Work Experiences, and Individual Adjustment Across Emerging Adulthood
Authors: Shulman Shmuel , Laursen Brett , Dickson Daniel J.
Published: December 2013

This study examines the interplay between negative romantic experiences, negative work experiences, and anxiety/depressive symptoms at three time points across ages 24–29 in a sample of 176 Israeli emerging adults. Males ( n = 96) and females ( n = 80) described different patterns of longitudinal spillover between work, romantic relationships, and well-being. For males, higher levels of negative romantic experiences predicted increases in negative work experiences, and higher levels of anxiety and depressive symptoms predicted increases in negative romantic experiences. For females, higher levels of negative work experiences predicted increases in later negative romantic experiences. For both males and females, higher levels of negative work experiences predicted later increases in anxiety and depressive symptoms. Findings of this study conducted on emerging adults align with existing research on work–family spillover and its effects on individual well-being.
Work, Romantic Relationships, and Life Satisfaction in Argentinean Emerging Adults
Authors: Facio Alicia , Resett Santiago
Published: December 2013

Few studies have jointly examined the development of love and work in emerging adulthood and even less so in the majority world. This article provides data about how love and work are related within each domain, across domains, and to life satisfaction in emerging adults from an understudied ecology, Argentina. For this purpose, 272 randomly selected Argentineans reported on romantic relationships, work satisfaction, and life satisfaction at age 23 and 27. On both occasions, satisfaction in the romantic domain was a better predictor of concurrent life satisfaction than work. At age 23, love but not work added modestly to the prediction of life satisfaction 4 years later. A much stronger stability was found in love than in work domain. Consistent with the segmentation model, but not with the spillover model, no cross-domain associations were detected over time. Results are discussed in light of important features of the Argentinean macrosystem.
Polyphosphate suppresses complement via the terminal pathway
Authors: Wat Jovian M. , Foley Jonathan H. , Krisinger Michael J. , Ocariza Linnette Mae , Lei Victor , Wasney Gregory A. , Lameignere Emilie , Strynadka Natalie C. , Smith Stephanie A. , Morrissey James H. , Conway Edward M.
Published: December 2013

Key Points

Polyphosphate suppresses complement via the terminal pathway by destabilizing C5b,6, thereby reducing the lytic capacity of the membrane attack complex. Polyphosphate, a novel negative regulator of complement, bridges coagulation and complement and is a potential therapeutic target.
Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications
Authors: Thol Felicitas , Bollin Robin , Gehlhaar Marten , Walter Carolin , Dugas Martin , Suchanek Karl Josef , Kirchner Aylin , Huang Liu , Chaturvedi Anuhar , Wichmann Martin , Wiehlmann Lutz , Shahswar Rabia , Damm Frederik , Göhring Gudrun , Schlegelberger Brigitte , Schlenk Richard , Döhner Konstanze , Döhner Hartmut , Krauter Jürgen , Ganser Arnold , Heuser Michael
Published: December 2013

Key Points

Mutations in genes of the cohesin complex are recurrent mutations in AML with a strong association with NPM1 mutations. Cohesin gene mutations have no clear prognostic impact in AML patients.
Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin
Authors: Cines Douglas B. , Lebedeva Tatiana , Nagaswami Chandrasekaran , Hayes Vincent , Massefski Walter , Litvinov Rustem I. , Rauova Lubica , Lowery Thomas J. , Weisel John W.
Published: December 2013

Key Points

In contracted clots and thrombi, erythrocytes are compressed to close-packed polyhedral structures with platelets and fibrin on the surface. Polyhedrocytes form an impermeable seal to stem bleeding and help prevent vascular obstruction but confer resistance to fibrinolysis.
Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia
Authors: Kadakkuzha Beena M , Akhmedov Komolitdin , Capo Tom R , Carvalloza Anthony C , Fallahi Mohammad , Puthanveettil Sathyanarayanan V
Published: December 2013

Background

Despite the advances in our understanding of aging-associated behavioral decline, relatively little is known about how aging affects neural circuits that regulate specific behaviors, particularly the expression of genes in specific neural circuits during aging. We have addressed this by exploring a peptidergic neuron R15, an identified neuron of the marine snail Aplysia californica. R15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine, serotonin and glutamate and is characterized by its action potential bursts.

Results

We examined changes in gene expression in R15 neurons during aging by microarray analyses of RNAs from two different age groups, mature and old animals. Specifically we find that 1083 ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons. Comparison with human signaling networks using pathway analyses have identified three major networks [(1) cell signaling, cell morphology, and skeletal muscular system development (2) cell death and survival, cellular function maintenance and embryonic development and (3) neurological diseases, developmental and hereditary disorders] altered in old R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify expression levels of candidate regulators involved in transcription (CREB1) and translation (S6K) showed that aging is associated with a decrease in expression of these regulators, and similar analysis in three other neurons (L7, L11 and R2) showed that gene expression change during aging could be bidirectional.

Conclusions

We find that aging is associated with bidirectional changes in gene expression. Detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human-relevant signaling pathways in R15 that are affected during aging. Evaluation of gene expression changes in different neurons suggests specific transcriptomic signature of single neurons during aging.
Satellite clinics in academic ophthalmology programs: an exploratory study of successes and challenges
Authors: Kuo Irene C
Published: December 2013

Background

Major academic ophthalmology departments have been expanding by opening multi-office locations (“satellites”). This paper offers a first glimpse into satellites of academic ophthalmology departments.

Methods

Leaders of seven medium to large, geographically diverse departments agreed to participate. One- to two-hour phone interviews were conducted to assess the features of their satellite practices.

Results

Success as clinical entities, profitability, and access to patients were stated goals for most satellites. In approximate descending order, refractive surgery, retina, oculoplastics, and pediatric ophthalmology were the most common subspecialties offered. Faculty staffing ranged from recruitment specifically for satellites to rotation of existing faculty. Except for a department with only one academic track, satellite doctors were a mix of tenure and mostly non-tenure track faculty. According to these department leaders, scholarly productivity of satellite faculty was similar to that of colleagues at the main campus, though research was more community-based and clinical in nature. Fellowship but little resident education occurred at satellites. Though it was agreed that satellite practices were integral to department finances, they accounted for a smaller percentage of revenues than of total departmental visits.

Conclusions

Satellite offices have offered access to a better payor mix and have boosted the finances of academic ophthalmology departments. Challenges include maintaining collegiality with referring community physicians, integrating faculty despite geographic distance, preserving the department’s academic “brand name,” and ensuring consistent standards and operating procedures. Satellite clinics will likely help departments meet some of the challenges of health care reform.
How do couples influence each other’s physical activity behaviours in retirement? An exploratory qualitative study
Authors: Barnett Inka , Guell Cornelia , Ogilvie David
Published: December 2013

Background

Physical activity patterns have been shown to change significantly across the transition to retirement. As most older adults approach retirement as part of a couple, a better understanding of how spousal pairs influence each other’s physical activity behaviour in retirement may help inform more effective interventions to promote physical activity in older age. This qualitative study aimed to explore and describe how couples influence each other’s physical activity behaviour in retirement.

Methods

A qualitative descriptive study that used purposive sampling to recruit seven spousal pairs with at least one partner of each pair recruited from the existing EPIC-Norfolk study cohort in the east of England, aged between 63 and 70 years and recently retired (within 2-6 years). Semi-structured interviews with couples were performed, audio-recorded, transcribed verbatim and analysed using data-driven content analysis.

Results

Three themes emerged: spousal attitude towards physical activity, spouses’ physical activity behaviour and spousal support. While spouses’ attitudes towards an active retirement were concordant, attitudes towards regular exercise diverged, were acquired across the life course and were not altered in the transition to retirement. Shared participation in physical activity was rare and regular exercise was largely an individual and independent habit. Spousal support was perceived as important for initiation and maintenance of regular exercise.

Conclusions

Interventions should aim to create supportive spousal environments for physical activity in which spouses encourage each other to pursue their preferred forms of physical activity; should address gender-specific needs and preferences, such as chances for socialising and relaxation for women and opportunities for personal challenges for men; and rather than solely focusing on promoting structured exercise, should also encourage everyday physical activity such as walking for transport.
The Older Persons’ Transitions in Care (OPTIC) study: pilot testing of the transition tracking tool
Authors: Reid Robert Colin , Cummings Garnet E , Cooper Sarah L , Abel Stephanie L , Bissell Laura J , Estabrooks Carole A , Rowe Brian H , Wagg Adrian , Norton Peter G , Ertel Mike , Cummings Greta G
Published: December 2013

Background

OPTIC is a mixed method Partnership for Health System Improvement (http://www.cihr-irsc.gc.ca/e/34348.html) study focused on improving care for nursing home (NH) residents who are transferred to and from emergency departments (EDs) via emergency medical services (EMS). In the pilot study we tested feasibility of concurrently collecting individual resident data during transitions across settings using the Transition Tracking Tool (T3).

Methods

The pilot study tracked 54 residents transferred from NHs to one of two EDs in two western Canadian provinces over a three month period. The T3 is an electronic data collection tool developed for this study to record data relevant to describing and determining success of transitions in care. It comprises 800+ data elements including resident characteristics, reasons and precipitating factors for transfer, advance directives, family involvement, healthcare services provided, disposition decisions, and dates/times and timing.

Results

Residents were elderly (mean age = 87.1 years) and the majority were female (61.8%). Feasibility of collecting data from multiple sources across two research sites was established. We identified resources and requirements to access and retrieve specific data elements in various settings to manage data collection processes and allocate research staff resources. We present preliminary data from NH, EMS, and ED settings.

Conclusions

While most research in this area has focused on a unidirectional process of patient progression from one care setting to another, this study established feasibility of collecting detailed data from beginning to end of a transition across multiple settings and in multiple directions.
Exposure to environmental tobacco smoke (ETS) and risk of lung cancer in Montreal: a case–control study
Authors: Al-Zoughool Mustafa , Pintos Javier , Richardson Lesley , Parent Marie-Élise , Ghadirian Parviz , Krewski Daniel , Siemiatycki Jack
Published: December 2013

Background

The objective of the present study was to examine the association between environmental tobacco smoke (ETS) and risk of lung cancer among never smokers, defined as subjects who smoked less than 100 cigarettes in their lifetime.

Methods

We conducted a population-based case–control study on lung cancer in Montreal, Canada (1996–2000) including 1,203 cases and 1513 controls. The present analysis is restricted to the 44 cases and 436 population controls who reported never smoking and completed the questionnaire on lifetime ETS exposure. Collected information included duration and intensity of exposure from multiple sources: inside home (parents, spouses, roommates and any other co-resident) and outside homes (in vehicles, social settings, and workplace). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated between ETS and lung cancer, adjusting for age, sex, socioeconomic status (SES), and proxy respondent.

Results

Overall there was no association between ETS cumulative exposure from all sources (measured in pack-years) and lung cancer: OR = 0.98 (95%CI: 0.40-2.38), comparing upper with lower tertiles of exposure. While there were no elevated ORs associated with ever having lived with parents who smoked (OR = 0.62; 95%CI: 0.32-1.21) or with spouses who smoked (OR = 0.39; 95%CI: 0.18-0.85), ETS exposure from sources outside homes was associated with a slight, although non-significant increased risk: OR = 2.30 (95%CI: 0.85-6.19) for the upper 50% exposed. There were no clear differences in ORs by age at exposure to ETS or by histologic type of tumour, though numbers of subjects in subgroup analyses were too small to provide reliable estimates.

Conclusion

No clear association between lifetime ETS exposure from all sources and increased risk of lung cancer was found in the current study.
Follicular expression of follicle stimulating hormone receptor variants in the ewe
Authors: Sullivan Rachael R , Faris Brian R , Eborn Douglas , Grieger David M , Cino-Ozuna Ada G , Rozell Timothy G
Published: December 2013

Background

Several alternatively-spliced mRNA transcripts of the follicle stimulating hormone receptor (FSHR) have been identified in sheep, including FSHR-1 (G protein-coupled form), FSHR-2 (dominant negative form), and FSHR-3 (growth factor type-1 form). Our objective was to determine which of these variants is predominantly expressed in follicles collected from ewes at various times after estrus.

Methods

Suffolk-cross ewes (n = 8) were allowed to come into estrus naturally and were euthanized 24 (n = 3), 36 (n = 3), or 48 (n = 2) hours after the onset of estrus. All visible follicles were measured, aspirated and pooled according to follicular diameter: small (<= 2.0 mm), medium (2.1-4.0 mm), large (4.1-6.0 mm), and preovulatory (> = 6.1 mm). Aspirated cells were separated from follicular fluid by centrifugation. Total RNA was extracted from cell pellets and reverse transcribed. The resulting cDNA was subjected to qPCR, using primer sets designed to amplify each variant specifically. Gene expression was normalized to that of beta–actin within samples, and compared by analysis of variance with the level of significant differences set at p < .05.

Results

Relative expression of FSHR-3 exceeded that of both FSHR-1 and FSHR-2 in medium follicles, and tended to be higher in small follicles (p = .09) regardless of time after onset of estrus, and thus results from different time points were pooled. Expression of FSHR-3 was greater than that of FSHR-2 and luteinizing hormone receptor (LHR) in small and medium follicles. Expression of LHR was greatest in preovulatory follicles.

Conclusions

These experiments show that in addition to the well characterized G protein-coupled form of the FSHR, alternatively spliced variants of the FSHR may participate in follicular dynamics during follicular waves of the sheep estrous cycle. Furthermore, these results indicate that an “alternatively” spliced form of the FSHR (FSHR-3) is the predominant form of the FSHR in the sheep.
DISCOVER trial– Distal resection of the pancreas with or without coverage of the pancreatic remnant: study protocol of a randomised controlled trial
Authors: Hassenpflug Matthias , Bruckner Thomas , Knebel Philip , Diener Markus K , Büchler Markus W , Werner Jens
Published: December 2013

Background

Distal pancreatectomy for benign and malignant tumours is the second most common surgical procedure on the pancreas. Postoperative pancreatic fistulas (POPF) represent the most significant clinical complication, causing prolongation of hospital stay and the need for additional diagnostic and therapeutic procedures. Although various techniques for preventing POPF have been evaluated, to date, there is no available technique that ensures closure of the pancreatic remnant.

Methods/Design

DISCOVER will aim to investigate differences in the postoperative course after a distal pancreatectomy comparing the standard surgical technique with an alternative technique that provides additional coverage of the pancreatic remnant by the falciform ligament. The primary endpoint of this trial will be the rate of POPF. As secondary endpoints, incidence of postoperative morbidity and mortality, length of hospital stay, and quality of life will be assessed.

DISCOVER is a single-centre, randomised, controlled surgical trial. For statistical analysis, a binary logistic regression model will be used. With a level of significance of 5% and a power of 80%, a sample size of 75 patients per group has been identified as necessary.

Discussion

The findings of this trial will help to evaluate the usefulness of the coverage procedure at reducing the rate of POPF. The results could influence the standard procedure for remnant closure after distal pancreatectomy.

Trial-registration

Clinical trials register (DRKS-ID: DRKS00000546)
Integrating human omics data to prioritize candidate genes
Authors: Chen Yong , Wu Xuebing , Jiang Rui
Published: December 2013

Background

The identification of genes involved in human complex diseases remains a great challenge in computational systems biology. Although methods have been developed to use disease phenotypic similarities with a protein-protein interaction network for the prioritization of candidate genes, other valuable omics data sources have been largely overlooked in these methods.

Methods

With this understanding, we proposed a method called BRIDGE to prioritize candidate genes by integrating disease phenotypic similarities with such omics data as protein-protein interactions, gene sequence similarities, gene expression patterns, gene ontology annotations, and gene pathway memberships. BRIDGE utilizes a multiple regression model with lasso penalty to automatically weight different data sources and is capable of discovering genes associated with diseases whose genetic bases are completely unknown.

Results

We conducted large-scale cross-validation experiments and demonstrated that more than 60% known disease genes can be ranked top one by BRIDGE in simulated linkage intervals, suggesting the superior performance of this method. We further performed two comprehensive case studies by applying BRIDGE to predict novel genes and transcriptional networks involved in obesity and type II diabetes.

Conclusion

The proposed method provides an effective and scalable way for integrating multi omics data to infer disease genes. Further applications of BRIDGE will be benefit to providing novel disease genes and underlying mechanisms of human diseases.
CVDHD: a cardiovascular disease herbal database for drug discovery and network pharmacology
Authors: Gu Jiangyong , Gui Yuanshen , Chen Lirong , Yuan Gu , Xu Xiaojie
Published: December 2013

Background

Cardiovascular disease (CVD) is the leading cause of death and associates with multiple risk factors. Herb medicines have been used to treat CVD long ago in china and several natural products or derivatives (e.g., aspirin and reserpine) are most common drugs all over the world. The objective of this work was to construct a systematic database for drug discovery based on natural products separated from CVD-related medicinal herbs and to research on action mechanism of herb medicines.

Description

The cardiovascular disease herbal database (CVDHD) was designed to be a comprehensive resource for virtual screening and drug discovery from natural products isolated from medicinal herbs for cardiovascular-related diseases. CVDHD comprises 35230 distinct molecules and their identification information (chemical name, CAS registry number, molecular formula, molecular weight, international chemical identifier (InChI) and SMILES), calculated molecular properties (AlogP, number of hydrogen bond acceptor and donors, etc.), docking results between all molecules and 2395 target proteins, cardiovascular-related diseases, pathways and clinical biomarkers. All 3D structures were optimized in the MMFF94 force field and can be freely accessed.

Conclusions

CVDHD integrated medicinal herbs, natural products, CVD-related target proteins, docking results, diseases and clinical biomarkers. By using the methods of virtual screening and network pharmacology, CVDHD will provide a platform to streamline drug/lead discovery from natural products and explore the action mechanism of medicinal herbs. CVDHD is freely available at http://pkuxxj.pku.edu.cn/CVDHD.
NGA-West2 Models for Ground Motion Directionality
Authors: Shahi Shrey K. , Baker Jack W.
Published: December 2013

The NGA-West2 research program, coordinated by the Pacific Earthquake Engineering Research Center (PEER), is a major effort to produce refined models for predicting ground motion response spectra. This study presents new models for ground motion directionality developed as part of that project. Using a database of recorded ground motions, empirical models have been developed for a variety of quantities related to direction-dependent spectra. A model is proposed for the maximum spectral acceleration observed in any orientation of horizontal ground motion shaking ( Sa RotD100), which is formulated as a multiplicative factor to be coupled with the NGA-West2 models that predict the median spectral accelerations over all orientations ( Sa RotD50). Models are also proposed for the distribution of orientations of the Sa RotD100 value, relative to the fault and the relationship between Sa RotD100 orientations at differing periods. Discussion is provided regarding how these results can be applied to perform seismic hazard analysis and compute realistic target spectra conditioned on different parameters.
Hydrodynamic shear removal of the nuisance stalk‐forming diatom Didymosphenia geminata
Authors: Cullis James D. S. , Crimaldi John P , McKnight Diane M.
Published: December 2013

Lay Abstract

Variability of flow is important in maintaining diversity of stream ecosystems. One reason for this is that periodic high flows result in the removal of algae growing on the stream bed (i.e., the substrate), leaving a patchwork of different species and habitat conditions. This is particularly true for nuisance algae such as Didymosphenia geminata that can grow quickly to blanket the stream bed restricting the available space for other organisms to live and feed. These nuisance species are thought, however, to be well adapted to the normal variability or regulation of flow, particularly in high‐gradient mountain streams. It is hypothesized that algal removal during these high‐flow events is limited and that effective removal requires much higher flows that result in the physical disturbance of the substrate and the mechanical scouring of the algae growing on the stream bed. We set out to examine this hypothesis by placing rocks attached with D. geminata colonies into a laboratory flow chamber. We then subjected the samples to increasing flows and determined the amount of material removed as the flow rate increased. We then investigated the relationship between the increasing applied shear stress (the force per unit area across the stream bed) and the amount of organic material removed. Our results showed that the removal due to elevated shear stress alone was low, up to the maximal levels of that which could be achieved in the flow chamber. A comparison with the estimated shear stress in the stream from where the samples were taken showed that removal was likely to be low up to a flow equal to the average annual maximum flow in the river and coinciding with the onset of widespread physical disturbance of the substrate. The results of this study have significance for understanding the ecosystem dynamics of streams and the potential use of flushing flows from reservoirs as a management tool for the mitigation of blooms of nuisance algal species such as D. geminata.
Aerobic Oxidation of Sulfides to Sulfoxides Catalyzed by Gold/Manganese Oxides
Authors: Taketoshi Ayako , Concepción Patricia , García Hermenegildo , Corma Avelino , Haruta Masatake
Published: December 2013

Although selective oxidation of sulfides to sulfoxides with molecular oxygen is a difficult reaction due to the overoxidation to sulfone, manganese oxides were found to catalyze the aerobic oxidation of sulfides to sulfoxides in 1,2-dichlorobenzene at 100 °C with a high selectivity above 99%. The catalytic activity depends on the preparation methods and conditions of manganese oxides but not on the valences of manganese. The deposition of Pd and Pt on manganese oxides was detrimental, whereas the deposition of Au enhanced the catalytic activity and selectivity.
Computational Study of the Binding Mechanism of Complement C3b with Antigen
Authors: Matsubara Toshiaki , Sasamoto Chisato
Published: December 2013

The reaction mechanism of the covalent binding of complement component 3 (C3) with antigen, which significantly contributes to the immune system by enhancing the phagocytosis of phagocytes, is examined by density functional theory (B3LYP). The covalent binding reaction takes place by the cleavage of the hydroxy O–H bond of the antigen on the thioester bond of the C3b formed by the activation of C3. We performed the calculations assuming a mechanism II that mimics that of serine protease in addition to the conventional mechanism I. Our calculations suggest that the conventional mechanism I proceeds with little participation of a His residue contrary to the previous consensus. Mechanism I, which has a large energy barrier of more than 30 kcal mol−1, is not realistic. On the other hand, in mechanism II, the energy barrier is about 10 kcal mol−1, due to an efficient mediation of a His residue by the collaboration with a neighboring Glu residue. Therefore, the covalent binding reaction of the activated C3b with the antigen was thought to proceed by mechanism II we proposed rather than by the conventional mechanism I.
Conversion of l-Cysteinato RhIII4ZnII4 Octanuclear to RhIII2AgI3 Pentanuclear Structure by AgI Ions
Authors: Yamashita Ukyo , Lee Pei-Shan , Kuwamura Naoto , Yoshinari Nobuto , Konno Takumi
Published: December 2013

Treatment of a sulfur-bridged RhIII4ZnII4 octanuclear complex, (Δ)4-K6[(Zn4O){Rh(l-cys-κ2N,S)3}4] (K6[1]; H2cys: cysteine) with AgI in an acidic aqueous medium gave a new RhIII2AgI3 pentanuclear complex, (Δ)2-H4[Ag3{Rh(l-cys-κ2N,S)3}2]NO3 ([H42]NO3). The structure in [H42]+ that possesses unique, multiple intermolecular interactions was determined by X-ray crystallography.
Exploration of Electronic Functionalities in Metal Oxides by Combinatorial Lattice Engineering
Authors: Kawasaki Masashi
Published: December 2013

A review is given for our originally-developed thin film technology, “combinatorial lattice engineering.” This is extended from a conventional pulsed laser deposition, where the surface of a sintered oxide tablet (target) is irradiated with focused laser pulses and the evaporated precursors are condensed on a heated substrate to grow single crystalline thin films. By this method, it has become possible to concurrently synthesize many oxide thin films on a substrate at different locations (segments) with such diversities as composition, growth conditions, and the sequence of heterostructures. By inserting a masking system between the target and substrate and computer controlling the mask motion as well as target switching, one can integrate many oxide thin film segments on the substrate. Starting from the background of and demand for this technology as well as the advancement of the key ingredient technology, i.e., atomically regulated epitaxial growth of oxide thin films, the concept and examples of this combinatorial lattice engineering are introduced highlighting the representative demonstration on magnetic, photonic, and electronic functionalities, especially emphasizing the benefit of this combinatorial technology. In addition, further progress of device physics triggered by the combinatorial discoveries are introduced, for example, electric field control of magnetism, bright ultraviolet light emitting devices, and quantum effects in oxide semiconductors.
Variola virus E3L Zα domain, but not its Z-DNA binding activity, is required for PKR inhibition
Authors: Thakur Meghna , Seo Eun Joo , Dever Thomas E.
Published: December 2013

Responding to viral infection, the interferon-induced, double-stranded RNA (dsRNA)–activated protein kinase PKR phosphorylates translation initiation factor eIF2α to inhibit cellular and viral protein synthesis. To overcome this host defense mechanism, many poxviruses express the protein E3L, containing an N-terminal Z-DNA binding (Zα) domain and a C-terminal dsRNA-binding domain (dsRBD). While E3L is thought to inhibit PKR activation by sequestering dsRNA activators and by directly binding the kinase, the role of the Zα domain in PKR inhibition remains unclear. Here, we show that the E3L Zα domain is required to suppress the growth-inhibitory properties associated with expression of human PKR in yeast, to inhibit PKR kinase activity in vitro, and to reverse the inhibitory effects of PKR on reporter gene expression in mammalian cells treated with dsRNA. Whereas previous studies revealed that the Z-DNA binding activity of E3L is critical for viral pathogenesis, we identified point mutations in E3L that functionally uncouple Z-DNA binding and PKR inhibition. Thus, our studies reveal a molecular distinction between the nucleic acid binding and PKR inhibitory functions of the E3L Zα domain, and they support the notion that E3L contributes to viral pathogenesis by targeting PKR and other components of the cellular anti-viral defense pathway.
Patient perspectives on the promptness and quality of care of road traffic incident victims in Peru: a cross-sectional, active surveillance study
Authors: Miranda J Jaime , Rosales-Mayor Edmundo , Quistberg D Alex , Paca-Palao Ada , Gianella Camila , Perel Pablo , Lopez Luis , Luna Diego , Best Pablo , Huicho Luis ,   PIAT Working Group
Published: December 2013

Background: Road injuries are the second-leading cause of disease and injury in the Andean region of South America. Adequate management of road traffic crash victims is important to prevent and reduce deaths and serious long-term injuries.

Objective: To evaluate the promptness of health care services provided to those injured in road traffic incidents (RTIs) and the satisfaction with those services during the pre-hospital and hospital periods.

Methods: We conducted a cross-sectional study with active surveillance to recruit participants in emergency departments at eight health care facilities in three Peruvian cities: a large metropolitan city (Lima) and two provincial cities (an urban center in the southern Andes and an urban center in the rainforest region), between August and September 2009. The main outcomes of interest were promptness of care, measured by time between injury and each service offered, as well as patient satisfaction measured by the Service Quality (SERVQUAL) survey. We explored the association between outcomes and city, type of health care facility (HCF), and type of provider.

Results: We recruited 644 adults seeking care for RTIs. This active surveillance strategy yielded 34% more events than anticipated, suggesting under-reporting in traditional registries. Median response time between a RTI and any care at a HCF was 33 minutes overall and only 62% of participants received professional care during the initial “golden” hour after the RTI. After adjustment for various factors, there was strong evidence of higher global dissatisfaction levels among those receiving care at public HCFs compared to private ones (odds ratio (OR) 5.05, 95% confidence interval (CI) 1.88-13.54). This difference was not observed when provincial sites were compared to Lima (OR 1.41, 95% CI 0.42-4.70).

Conclusions: Response time to RTIs was adequate overall, though a large proportion of RTI victims could have received more prompt care. Overall, dissatisfaction was high, mainly at public institutions indicating much need for improvements in service provision.
Prmt7 is dispensable in tissue culture models for adipogenic differentiation
Authors: Hu Yu-Jie , Sif Saïd , Imbalzano Anthony N.
Published: December 2013

Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyze monomethylation, asymmetric dimethylation, and symmetric dimethylation on arginine residues. Protein arginine methyltransferase 7 (Prmt7) is categorized as a type II and type III enzyme that produces symmetric dimethylated arginine and monomethylated arginine, respectively. However, the biological role of Prmt7 is not well characterized. We previously showed that Prmt5, a type II Prmt that associates with Brg1-based SWI/SNF chromatin remodeling complex, is required for adipocyte differentiation. Since Prmt7 also associates with Brg1-based SWI/SNF complex and modifies core histones, we hypothesized that Prmt7 might play a role in transcriptional regulation of adipogenesis. In the present study, we determined that the expression of Prmt7 did not change throughout adipogenic differentiation of C3H10T1/2 mesenchymal cells. Knockdown or over-expression of Prmt7 had no effect on lipid accumulation or adipogenic gene expression in differentiating C3H10T1/2 cells or in C/EBPα-reprogrammed NIH3T3 fibroblasts. Based on these results, we conclude that Prmt7, unlike Prmt5, is dispensable for adipogenic differentiation in tissue culture models.
Effectiveness of Higher Education in the European Union Countries in Context of National Competitiveness
Authors: Jantoń-Drozdowska Elżbieta , Majewska Maria
Published: December 2013

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EquineReview
Authors: Rendle David
Published: December 2013

Introduction: This edition of Equine Review considers papers on phenylbutazone use in horses and human health, use of gentamicin in foals, stent bandaging following colic surgery and predicting foaling in mares.
Equal rights to paid parental leave and caring fathers- the case of Iceland
Authors: Arnalds Ásdís A. , Eydal Guðný Björk , Gíslason Ingólfur V.
Published: December 2013

In 2000 the Icelandic parliament adopted unanimously a new and radical law on parental leave. The leave was extended from six months to nine; divided between the parents so that fathers were allotted three months, mothers three and the remaining three divided between the two. One reason given for this division was to try to ensure that children received care from both parents. From the results of a questionnaire answered by parents who had their first child in 1997, 2003 or 2009 it was estimated whether the intention of the law was put into practice. The results indicate that the division of care between parents, from birth until three years, has changed in the intended direction and that this is mainly due to the law. The results also showed that this is least common among parents that do not live together. However, even amongst these parents the division of care is more equal among those who had their first child in 2009 than those who had their first in 1997. Finally, the results show that there is a direct correlation between the length of leave taken by the father and his involvement in care afterwards. Overall, these results indicate that the law has had the intended effect of providing children with care from both parents.
Performance of Direct Estradiol Immunoassays with Human Male Serum Samples
Authors: Handelsman David J , Newman Julie D , Jimenez Mark , McLachlan Robert , Sartorius Gideon , Jones Graham R D
Published: December 2013

BACKGROUND

Steroid immunoassays originally required solvent extraction, chromatography, and structurally authentic tracers to avoid interference from steroid cross-reactivity and matrix effects. The demand for steroid assays has driven assay simplification, bypassing this triplet of validity criteria to allow use of unextracted serum, which has introduced bias and nonspecificity at low steroid concentrations. We aimed to evaluate the performance of commercial direct estradiol (E2) immunoassays relative to the reference method of LC-MS and compared serum E2 measurements from each assay with biomarkers of estrogen action.

METHODS

We measured serum E2 in duplicate using 5 commercial direct immunoassays and LC-MS in a nested cohort of 101 healthy, asymptomatic men >40 years old from the Healthy Man Study. For each immunoassay, we evaluated the detectability and distribution of serum E2 measurements, CV, and bias (relative to LC-MS) by Passing–Bablok regression and deviance plots.

RESULTS

Three assays detected E2 in all samples, whereas E2 was detected in only 53% and 72% of samples by 2 other assays. All 5 assays had positive biases, ranging from 6% to 74%, throughout their ranges. CVs were lower with 4 immunoassays than with LC-MS. LC-MS, but none of the direct immunoassays, correlated with serum testosterone and sex steroid–binding globulin.

CONCLUSIONS

The positive bias of direct E2 immunoassays throughout their working range reflects the nonspecific effects of steroid cross-reactivity and/or matrix interference arising from the violation of the triplet validity criteria for steroid immunoassay.