bluuebunny/crossref_metadata_2025 huggingface dataset:
Wealth, education and urban–rural inequality and maternal healthcare service usage in Malawi
Authors: Yaya Sanni , Bishwajit Ghose , Shah Vaibhav
Published: August 2016

Background

Malawi is among the 5 sub-Saharan African countries presenting with very high maternal mortality rates, which remain a challenge. This study aims to examine the impact of wealth inequality and area of residence (urban vs rural) and education on selected indicators of maternal healthcare services (MHS) usage in Malawi.

Methods

This study was based on data from the 5th round of Multiple Indicator Cluster Surveys (MICS) conducted in 2013–2014 in Malawi. Study participants were 7572 mothers aged between 15 and 49 years. The outcome variable was usage status of maternal health services of the following types: antenatal care, skilled delivery assistance and postpartum care. Univariate, bivariate and multivariate methods were used to describe the pattern of MHS usage in the sample population. Association between household wealth status, education as well as the type of residence, whether urban or rural, as independent variables and usage of MHS as dependent variables were analysed using the generalised estimating equations (GEE) method.

Results

Mean age of the sample population was 26.88 (SD 6.68). Regarding the usage of MHS, 44.7% of women had at least 4 ANC visits, 87.8% used skilled delivery attendants and 82.2% of women had used postnatal care. Regarding the wealth index, about a quarter of the women were in the poorest wealth quintile (23.6%) while about 1/6 were in the highest wealth quintile (15%). Rate of usage for all 3 types of services was lowest among women belonging to the lowest wealth quintile. In terms of education, only 1/5 completed their secondary or a higher degree (20.1%) and nearly 1/10 of the population lives in urban areas (11.4%) whereas the remaining majority live in rural areas (88.6%). The rates of usage of MHS, although reasonable on an overall basis, were consistently lower in women with lower education and those residing in rural areas.

Conclusions

Maternal health service usage in Malawi appears to be reasonable, yet the high maternal mortality rate is disturbing and calls for analysing factors hindering the achievement of maternal health-related Sustainable Development Goals (SDGs). The findings of this study underscore the need to minimise the wealth inequality, urban–rural divide and the low level of education among mothers to improve the usage of MHS. An equity-based policy approach considering the sociodemographic inequity in terms of wealth index, education and urban–rural divide might prove beneficial in further improving the MHS usage, as well as addressing the possible issues of quality gaps in MHS, which might be beneficial towards reducing maternal mortality. It should be noted that the study of quality gaps in MHS is beyond the scope of this paper and calls for further research in this arena.
Impact of including or excluding both-armed zero-event studies on using standard meta-analysis methods for rare event outcome: a simulation study
Authors: Cheng Ji , Pullenayegum Eleanor , Marshall John K , Iorio Alfonso , Thabane Lehana
Published: August 2016

Objectives

There is no consensus on whether studies with no observed events in the treatment and control arms, the so-called both-armed zero-event studies, should be included in a meta-analysis of randomised controlled trials (RCTs). Current analytic approaches handled them differently depending on the choice of effect measures and authors' discretion. Our objective is to evaluate the impact of including or excluding both-armed zero-event (BA0E) studies in meta-analysis of RCTs with rare outcome events through a simulation study.

Method

We simulated 2500 data sets for different scenarios varying the parameters of baseline event rate, treatment effect and number of patients in each trial, and between-study variance. We evaluated the performance of commonly used pooling methods in classical meta-analysis—namely, Peto, Mantel-Haenszel with fixed-effects and random-effects models, and inverse variance method with fixed-effects and random-effects models—using bias, root mean square error, length of 95% CI and coverage.

Results

The overall performance of the approaches of including or excluding BA0E studies in meta-analysis varied according to the magnitude of true treatment effect. Including BA0E studies introduced very little bias, decreased mean square error, narrowed the 95% CI and increased the coverage when no true treatment effect existed. However, when a true treatment effect existed, the estimates from the approach of excluding BA0E studies led to smaller bias than including them. Among all evaluated methods, the Peto method excluding BA0E studies gave the least biased results when a true treatment effect existed.

Conclusions

We recommend including BA0E studies when treatment effects are unlikely, but excluding them when there is a decisive treatment effect. Providing results of including and excluding BA0E studies to assess the robustness of the pooled estimated effect is a sensible way to communicate the results of a meta-analysis when the treatment effects are unclear.
Effectiveness of a multidisciplinary critical pathway based on a computerised physician order entry system for ST-segment elevation myocardial infarction management in the emergency department: a retrospective observational study
Authors: Park Yoo Seok , Chung Sung Phil , You Je Sung , Kim Min Joung , Chung Hyun Soo , Hong Jung Hwa , Lee Hye Sun , Wang Jinwon , Park Incheol
Published: August 2016

Objectives

The purpose of this study was to investigate whether a multidisciplinary organised critical pathway (CP) for ST-segment elevation myocardial infarction (STEMI) management can significantly attenuate differences in the duration from emergency department (ED) arrival to evaluation and treatment, regardless of the arrival time, by eliminating off-hour and weekend effects.

Design

Retrospective observational cohort study.

Setting

2 tertiary academic hospitals.

Participants

Consecutive patients in the Fast Interrogation Rule for STEMI (FIRST) program.

Interventions

A study was conducted on patients in the FIRST program, which uses a computerised physician order entry (CPOE) system. The patient demographics, time intervals and clinical outcomes were analysed based on the arrival time at the ED: group 1, normal working hours on weekdays; group 2, off-hours on weekdays; group 3, normal working hours on weekends; and group 4, off-hours on weekends.

Primary and secondary outcome measures

Clinical outcomes categorised according to 30-day mortality, in-hospital mortality and the length of stay.

Results

The duration from door-to-data or FIRST activation did not differ significantly among the 4 groups. The median duration between arrival and balloon placement during percutaneous coronary intervention did not significantly exceed 90 min, and the proportions (89.6–95.1%) of patients with door-to-balloon times within 90 min did not significantly differ among the 4 groups, regardless of the ED arrival time (p=0.147). Moreover, no differences in the 30-day (p=0.8173) and in-hospital mortality (p=0.9107) were observed in patients with STEMI.

Conclusions

A multidisciplinary CP for STEMI based on a CPOE system can effectively decrease disparities in the door-to-data duration and proportions of patients with door-to-balloon times within 90 min, regardless of the ED arrival time. The application of a multidisciplinary CP may also help attenuate off-hour and weekend effects in STEMI clinical outcomes.
Bayesian model averaging method for evaluating associations between air pollution and respiratory mortality: a time-series study
Authors: Fang Xin , Li Runkui , Kan Haidong , Bottai Matteo , Fang Fang , Cao Yang
Published: August 2016

Objective

To demonstrate an application of Bayesian model averaging (BMA) with generalised additive mixed models (GAMM) and provide a novel modelling technique to assess the association between inhalable coarse particles (PM10) and respiratory mortality in time-series studies.

Design

A time-series study using regional death registry between 2009 and 2010.

Setting

8 districts in a large metropolitan area in Northern China.

Participants

9559 permanent residents of the 8 districts who died of respiratory diseases between 2009 and 2010.

Main outcome measures

Per cent increase in daily respiratory mortality rate (MR) per interquartile range (IQR) increase of PM10concentration and corresponding 95% confidence interval (CI) in single-pollutant and multipollutant (including NOx, CO) models.

Results

The Bayesian model averaged GAMM (GAMM+BMA) and the optimal GAMM of PM10, multipollutants and principal components (PCs) of multipollutants showed comparable results for the effect of PM10on daily respiratory MR, that is, one IQR increase in PM10concentration corresponded to 1.38% vs 1.39%, 1.81% vs 1.83% and 0.87% vs 0.88% increase, respectively, in daily respiratory MR. However, GAMM+BMA gave slightly but noticeable wider CIs for the single-pollutant model (−1.09 to 4.28 vs −1.08 to 3.93) and the PCs-based model (−2.23 to 4.07 vs −2.03 vs 3.88). The CIs of the multiple-pollutant model from two methods are similar, that is, −1.12 to 4.85 versus −1.11 versus 4.83.

Conclusions

The BMA method may represent a useful tool for modelling uncertainty in time-series studies when evaluating the effect of air pollution on fatal health outcomes.
Motion analysis in the field of dentistry: a kinematic comparison of dentists and orthodontists
Authors: Nowak J , Erbe C , Hauck I , Groneberg D A , Hermanns I , Ellegast R , Ditchen D , Ohlendorf D
Published: August 2016

Objectives

To conduct a kinematic comparison of occupational posture in orthodontists and dentists in their workplace.

Design

Observational study.

Setting

Dentist surgeries and departments of orthodontics at university medical centres in Germany.

Participants

A representative sample of 21 (10 female, 11 male) dentists (group G1) and 21 (13 female, 8 male) orthodontists (G2) with one male dropout in G2.

Outcome measures

The CUELA (computer-assisted acquisition and long-term analysis of musculoskeletal loads) system was used to analyse occupational posture. Parallel to the recording through the CUELA system, a software-supported analysis of the activities performed (I: treatment; II: office; III: other activities) was carried out. In line with ergonomic standards the measured body angles are categorised into neutral, moderate and awkward postures. Activities between the aforementioned groups are compared using the stratified van Elteren U test and the Wilcoxon–Mann–Whitney U test. All p values are subject to the Bonferroni–Holm correction. The level of significance is set at 5%.

Results

The percentage of time spent on activities in categories I–II–III was as follows: dentists 41%–23%–36% and orthodontists 28%–37%–35%. The posture analysis of both groups showed, for all percentiles (P5–95), angle values primarily in the neutral or moderate range. However, depending on the activity performed, between 5% and 25% of working hours were spent in unfavourable postures, especially in the head-and-neck area. Orthodontists have a greater tendency than dentists to perform treatment activities with the head and torso in unfavourable positions. The statistically significant differences between the two groups with regard to the duration and the relevance of the activities performed confirm this assumption for all three categories (p<0.01, p<0.05).

Conclusions

Generally, both groups perform treatment activities in postures that are in the neutral or medium range; however, dentists had slightly more unfavourable postures during treatment for a greater share of their work day.
Improving the performance of community health workers in humanitarian emergencies: a realist evaluation protocol for the PIECES programme
Authors: Gilmore Brynne , Adams Ben Jack , Bartoloni Alex , Alhaydar Bana , McAuliffe Eilish , Raven Joanna , Taegtmeyer Miriam , Vallières Frédérique
Published: August 2016

Introduction

Understanding what enhances the motivation and performance of community health workers (CHWs) in humanitarian emergencies represents a key research gap within the field of human resources for health. This paper presents the research protocol for the Performance ImprovEment of CHWs in Emergency Settings (PIECES) research programme. Enhancing Learning and Research in Humanitarian Action (ELRHA) funded the development of this protocol as part of their Health in Humanitarian Crises (R2HC) call (No.19839). PIECES aims to understand what factors improve the performance of CHWs in level III humanitarian emergencies.

Methods and analysis

The suggested protocol uses a realist evaluation with multiple cases across the 3 country sites: Turkey, Iraq and Lebanon. Working with International Medical Corps (IMC), an initial programme theory was elicited through literature and document reviews, semistructured interviews and focus groups with IMC programme managers and CHWs. Based on this initial theory, this protocol proposes a combination of semistructured interviews, life histories and critical incident narratives, surveys and latent variable modelling of key constructs to explain how contextual factors work to trigger mechanisms for specific outcomes relating to IMC's 300+ CHWs' performance. Participants will also include programme staff, CHWs and programme beneficiaries. Realist approaches will be used to better understand ‘what works, for whom and under what conditions’ for improving CHW performance within humanitarian contexts.

Ethics and dissemination

Trinity College Dublin's Health Policy and Management/Centre for Global Health Research Ethics Committee gave ethical approval for the protocol development phase. For the full research project, additional ethical approval will be sought from: Université St. Joseph (Lebanon), the Ethics Committee of the Ministry of Health in Baghdad (Iraq) and the Middle East Technical University (Turkey). Dissemination activities will involve a mixture of research feedback, policy briefs, guidelines and recommendations, as well as open source academic articles.
Compliant flooring to prevent fall-related injuries: a scoping review protocol
Authors: Lachance Chantelle C , Jurkowski Michal P , Dymarz Ania C , Mackey Dawn C
Published: August 2016

Introduction

Fall-related injuries can have serious consequences for older adults, including increased risk of dependence in daily activities and mortality. Compliant flooring is a passive intervention that may reduce the incidence and severity of fall-related injuries in healthcare settings, including acute and long-term care, but few sites have implemented compliant flooring, in part because synthesised evidence about key performance aspects has not been available.

Methods and analysis

We will conduct a scoping review to address the question: what is presented about the biomechanical efficacy, clinical effectiveness, cost-effectiveness, and workplace safety associated with compliant flooring systems that aim to prevent fall-related injuries? We will conduct a comprehensive and systematic literature search of academic databases (AgeLine, CINAHL, EBM Reviews, MEDLINE (Ovid), SportDiscus and Web of Science) and grey literature (clinical trial registries, theses/dissertations, abstracts/conference proceedings and relevant websites). 2 team members will independently screen records (first titles and abstracts, then full text) and extract data from included records. Numerical and narrative analyses will be presented by theme (biomechanical efficacy, clinical effectiveness, cost-effectiveness, workplace safety).

Ethics and dissemination

This scoping review responds to the information needs of healthcare decision-makers tasked with preventing fall-related injuries. This review will summarise evidence about compliant flooring as a potential intervention for preventing fall-related injuries in older adults and identify gaps in evidence and new avenues for research. Results will be especially useful in long-term care, but also applicable in acute care, assisted living and home care. We will disseminate the review's findings via open-access publications, conference presentations, a webinar, a Stakeholder Symposium and a Knowledge-to-Action Report.
Trend study on the association between hospital admissions and the health of Dutch older adults (1995–2009)
Authors: Galenkamp Henrike , Deeg Dorly J H , de Jongh Renate T , Kardaun Jan W P F , Huisman Martijn
Published: August 2016

Objectives

An increase in hospital admission rates in older people may reflect improved access to healthcare, but also declining health trends in the older population. Owing to a lack of individual-level data, the latter possibility has received little attention. The current study examines associations between health status and hospitalisation rates of older adults in the Netherlands.

Design

Observational individual-level data linked to hospital register data.

Setting

Data from 1995 to 2009 from the nationally representative Longitudinal Aging Study Amsterdam were linked to the Dutch Hospital Discharge Register.

Participants

A total of 5681 observations of 2520 respondents across 4 measurement points (each with a follow-up of 36 months; ages 65–88 years).

Outcome measures

The contribution of health, demographic, psychosocial and lifestyle characteristics to time trends in hospitalisation was assessed in multivariate models.

Results

Between 1995 and 2009, the percentage with 1 or more overnight admissions (planned or acute) increased slightly from 38.1% to 39.7%. This was due to an increase in acute admission only (22.2–27.0%). Increased prevalences of chronic diseases, functional limitations and polypharmacy accounted for part of the observed increase in acute admissions. In addition, a more than doubled prevalence of day admissions over time was observed (12.3–28.3%), a trend that was unrelated to changes in individual characteristics.

Conclusions

This trend study showed a contribution of declines in population health to increases in acute hospital admissions. Since these declines did not provide a full explanation, healthcare reforms and increases in treatment possibilities in this period are likely to have contributed as well.
Parent and caregiver perspectives on home-based newborn care in low-income settings: protocol for a systematic review of qualitative studies
Authors: Bazzano Alessandra N , Felker-Kantor Erica , Kaji Aiko , Saldanha Lisa
Published: August 2016

Introduction

Newborn health and survival are closely linked to essential newborn care provided within the first days and weeks of an infant's life by parents and caregivers at home and within the community. Newborn care practices are often socially and culturally determined and have been explored in qualitative and formative research related to improving neonatal survival. We aim to provide a comprehensive review of qualitative studies on parent and caregiver experiences of newborn care practices with a view to identifying barriers and facilitators that may impact on newborn health. The rationale is that providing this information will be useful for intervention design and programme scale up for newborn survival.

Methods and analysis

We will systematically review qualitative studies reporting on newborn care practices. The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement will be used for reporting the stages of the review and dissemination. The search period will include all studies published from 2006 to 2016. Study selection will incorporate the ENTREQ and Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines and quality assessment will be completed using Critical Appraisal Skills Programme (CASP) guidelines. Pending the identification of sufficient data of good quality, we will conduct a full synthesis of the studies identified by the review.

Ethics and dissemination

The results will be disseminated through peer-reviewed publications, conference presentation and directly to organisations involved in newborn health. Formal ethical approval from the author's institution is not required, as no primary data or identifying data will be collected.

Trial registration number

CRD42016035674.
Mobility, proprioception, strength and FMS as predictors of injury in professional footballers
Authors: Yeung Jonathan , Cleves Andrew , Griffiths Hywell , Nokes Len
Published: August 2016

Background

The premise of this study was to investigate if anthropometric variables such as mobility, proprioception, strength and modified Functional Movement Screen (mFMS) could be used as primary indicators of injury risk in an English Championship division football team. This study focused on moderate injuries occurring in the lower extremities, during the 2014/2015 competitive season.

Methods

To differentiate between minor, moderate and severe injuries, this study classified moderate injuries as an injury with an average injury severity of 2–28 days. This study is composed of 4 individual investigations. Each variable was assessed against 2 groups: injured (n=6) and non-injured (n=10). The 2 groups were compiled from the first team, with the criteria that each participant of this study required: full preseason assessment and injury history for the time period, 1 July 2014 to 19 March 2015. A Mann-Whitney U test (0.05% significance) was applied to statistically analyse if each variable showed any variation across the 2 groups. Effect size was estimated with Cliff's d.

Results

Strength asymmetry displayed significant difference (p=0.007), mobility, proprioception and mFMS did not (p=0.263, p=0.792 and p=0.181, respectively). Mean scores for mobility, proprioception, strength asymmetry and mFMS for injured versus non-injured players (effect size) were: 40.00 vs 38.00 (0.37), 10.33 vs 10.20 (0.10), 61.13 vs 30.40 (0.80) and 7.33 vs 8.90 (−0.4), respectively.

Conclusions

This study found no relationship between mobility/proprioception and injury risk; however, strength asymmetry was statistically significant in predicting injury and mFMS exhibited enough positive difference for recommendation of further investigation.
Exploring the association of hospice care on patient experience and outcomes of care
Authors: Kleinpell Ruth , Vasilevskis Eduard E , Fogg Louis , Ely E Wesley
Published: August 2016

Objective

To examine the association of the use of hospice care on patient experience and outcomes of care. Promoting high-value, safe and effective care is an international healthcare imperative. However, the extent to which hospice care may improve the value of care is not well characterised.

Methods

A secondary analysis of variations in care was conducted using the Dartmouth Atlas Report, matched to the American Hospital Association Annual Survey Database to abstract organisational characteristics for 236 US hospitals to examine the relationship between hospice usage and a number of variables that represent care value, including hospital care intensity index, hospital deaths, intensive care unit (ICU) deaths, patient satisfaction and a number of patient quality indicators. Structural equation modelling was used to demonstrate the effect of hospice use on patient experience, clinical and efficiency outcomes.

Results

Hospice admissions in the last 6 months of life were correlated with a number of variables, including increases in patient satisfaction ratings (r=0.448, p=0.01) and better pain control (r=0.491, p=0.01), and reductions in hospital days (r=−0.517, p=0.01), fewer hospital deaths (r=−0.842, p=0.01) and fewer deaths occurring with an ICU admission during hospitalisation (r=−0.358, p=0.01). The structural equation model identified that use of hospice care was inversely related to hospital mortality (−0.885) and ICU mortality (−0.457).

Conclusions

The results of this investigation demonstrate that greater use of hospice care during the last 6 months of life is associated with improved patient experience, including satisfaction and pain control, as well as clinical outcomes of care, including decreased ICU and hospital mortality.
Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1
Authors: Joneja Upasana , Vranic Semir , Swensen Jeffrey , Feldman Rebecca , Chen Wangjuh , Kimbrough Jeffrey , Xiao Nianqing , Reddy Sandeep , Palazzo Juan , Gatalica Zoran
Published: August 2016

Aims

Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions.

Methods

We profiled 297 samples (MBC (n=75), TNBC (n=106), human epidermal growth factor receptor 2 (HER2)-positive breast cancers (n=32) and hormone-positive breast cancers (n=84)) by next-generation sequencing. Immunohistochemistry for PD-L1 and programmed cell death 1 (PD-1) expression was performed using automated procedures.

Results

The most commonly mutated genes in MBCs includedTP53(56%) andPIK3CA(23%). Pathogenic mutations in other genes, includingHRAS,FBXW7,PTEN,AKT1andSMAD4, were rare. PD-L1 expression was detected in a significantly higher proportion of MBCs (46%) than in other subtypes (6% each in hormone-positive and HER2-positive breast cancers, and 9% in TNBC, not otherwise specified, p<0.001). PD-1-positive tumour infiltrating lymphocytes (TILs) varied greatly in MBCs.

Conclusions

Comprehensive profiling of a large cohort of this rare subtype of breast carcinoma highlighted the predominance ofTP53mutation and increased PD-L1 expression in carcinoma cells. These results can be exploited in clinical trials using immune checkpoint inhibitors.
Effects of lactoferrin in 6 patients with refractory bacterial vaginosis
Authors: Otsuki Katsufumi , Imai Noriaki
Published: August 2016

We previously reported that lactoferrin (LF) could be effective for preventing preterm delivery and intrauterine infections, based on data derived from mice and rabbits. Here we describe 6 women with a history of multiple pregnancy losses or preterm delivery and refractory bacterial vaginosis, who received prebiotic LF therapy and delivered an infant normally. Five of the women were pregnant and one was not at the time of this study. The Ethics Committee at Showa University Hospital and Showa University Koto Toyosu Hospital approved the therapeutic protocol. Vaginal suppositories and oral prebiotic LF were administered to patients who were refractory to conventional treatment for vaginosis and had a history of late miscarriages and very early preterm delivery due to refractory vaginitis and chorioamnionitis. LF significantly improved the vaginal bacterial flora. Lactobacillus, which was detectable in the vaginas of all patients after one month of LF therapy, gradually became dominant. The findings from these 6 patients suggest that administering LF to humans could help prevent refractory vaginitis, cervical inflammation, and preterm delivery.
Effect of solvent polarity on the fluorescence quenching of TMC molecule by aniline in benzene–acetonitrile mixtures
Authors: Sidarai Ashok H. , Desai Vani R. , Hunagund Shirajahammad M. , Basanagouda Mahantesha , Kadadevarmath Jagadish S.
Published: August 2016

The fluorescence quenching of coumarin derivative, 6-methoxy-4-p-tolyloxymethyl-chromen-2-one by aniline is carried out in different solvent mixtures of benzene and acetonitrile at room temperature. The quenching is found to be appreciable and a positive deviation from linearity is observed in the Stern–Volmer plot in all the solvent mixtures. Various rate constants for fluorescence quenching processes have been estimated using a sphere of action static quenching model and a finite sink approximation model. From the positive deviation of linear Stern–Volmer plots and dependence of rate constants on the polarity of the solvents, it has been inferred that the quenching process is diffusion-limited, and static as well as dynamic quenching processes are responsible for the observed positive deviation in the Stern–Volmer plot. Further, both models have been found to agree well with transient state also in pure acetonitrile and benzene solvents.
Non-equilibrium phase and entanglement entropy in 2D holographic superconductors via gauge–string duality
Authors: Mazhari Najmeh Al Sadat , Momeni Davood , Myrzakulov Ratbay , Gholizade Hosein , Raza Muhammad
Published: August 2016

An alternative method of developing the theory of non-equilibrium two-dimensional holographic superconductor is to start from the definition of a time-dependent AdS3 background. As originally proposed, many of these formulae were cast in exponential form, but the adoption of the numeric method of expression throughout the bulk serves to show more clearly the relationship between the various parameters. The time dependence behavior of the scalar condensation and Maxwell fields are fitted numerically. A usual value for Maxwell field on AdS horizon is exp(–bt), and the exponential log ratio is therefore 10−8 s−1. The coefficient b of the time in the exponential term exp(–bt) can be interpreted as a tool to measure the degree of dynamical instability; its reciprocal 1/b is the time in which the disturbance is multiplied in the ratio. A discussion of some of the exponential formulae is given by the scalar field ψ(z, t) near the AdS boundary. It may be possible that a long interval would elapse in the system, which tends to the equilibrium state, where the normal mass and conformal dimensions emerged. A somewhat curious calculation has been made to illustrate the holographic entanglement entropy for this system. The foundation of all this calculation is, of course, a knowledge of multiple (connected and disconnected) extremal surfaces. There are several cases in which exact and approximate solutions are jointly used; a variable numerical quantity is represented by a graph, and the principles of approximation are then applied to determine related numerical quantities. In the case of the disconnected phase with a finite extremal area, we find a discontinuity in the first derivative of the entanglement entropy as the conserved charge J is increased.
Vibrational spectra and phonon dispersion analysis of a single-walled zigzag carbon nanotube: A first principles study
Authors: Sharma Deepa , Jaggi Neena
Published: August 2016

This paper reports a vibrational spectroscopic study on a zigzag single-walled carbon nanotube (SWCNT) using the first-principles method based on density functional theory (DFT). The most suitable exchange correlation functional for DFT analysis was determined by comparing the predicted value of band gap of the SWCNT under study with the experimental value reported in the literature. General gradient approximation functional in combination with revised Perdew–Burke–Ernzerh sub-functional was found to give the best results. Using this optimum combination, phonon density of states and phonon dispersion curves have been determined. The analysis of results obtained focuses on symmetry considerations, group theory analysis, segregation of Raman active and infrared (IR) active vibrational modes and interpretation of the Raman and IR spectra obtained. The earlier approaches to the problem rely upon the zone folding technique and force constant models in which structural relaxation factor is not taken care of. An ab initio approach has been adopted by the authors in this work, which is advantageous as it neither depends on some predefined parameter nor does it ignore the structural relaxation factor. Analysis of the Raman spectrum reveals some additional peaks other than the commonly known radial breathing mode, D, G, and G′ bands in the SWCNT spectra, which have been recently reported to be observed experimentally also. Similarly, the theoretically developed IR spectrum for the simulated SWCNT is also in agreement with experimental observations. The methodology presented thus provides a very useful and novel simulation route to predict the vibrational modes, Raman spectra, and IR spectra of SWCNTs theoretically.
North American ginseng (Panax quinquefolius) suppresses β-adrenergic-dependent signalling, hypertrophy, and cardiac dysfunction
Authors: Tang Xilan , Gan Xiaohong Tracey , Rajapurohitam Venkatesh , Huang Cathy Xiaoling , Xue Jenny , Lui Edmund M.K. , Karmazyn Morris
Published: August 2016

There is increasing evidence for a beneficial effect of ginseng on cardiac pathology. Here, we determined whether North American ginseng can modulate the deleterious effects of the β-adrenoceptor agonist isoproterenol on cardiac hypertrophy and function using in vitro and in vivo approaches. Isoproterenol was administered for 2 weeks at either 25 mg/kg per day or 50 mg/kg per day (ISO25 or ISO50) via a subcutaneously implanted osmotic mini-pump to either control rats or those receiving ginseng (0.9 g/L in the drinking water ad libitum). Isoproterenol produced time- and dose-dependent left ventricular dysfunction, although these effects were attenuated by ginseng. Improved cardiac functions were associated with reduced heart masses, as well as prevention in the upregulation of the hypertrophy-related fetal gene expression. Lung masses were similarly attenuated, suggesting reduced pulmonary congestion. In in vitro studies, ginseng (10 μg/mL) completely suppressed the hypertrophic response to 1 μmol/L isoproterenol in terms of myocyte surface area, as well as reduction in the upregulation of fetal gene expression. These effects were associated with attenuation in both protein kinase A and cAMP response element-binding protein phosphorylation. Ginseng attenuates adverse cardiac adrenergic responses and, therefore, may be an effective therapy to reduce hypertrophy and heart failure associated with excessive catecholamine production.
Activity of eastern chipmunks (Tamiasstriatus) during the summer and fall
Authors: LaZerte S.E. , Kramer D.L.
Published: August 2016

Measuring activity of small mammals in the field is challenging because they are often out of view. We used a novel method, based on temperatures of collar radio transmitters, to quantify the proportion of time eastern chipmunks (Tamias striatus (L., 1758)) spent active, curled up resting, and torpid during the summer and fall of 2 years in southern Quebec. Time active over the 24 h day was lower in a nonmast (8%) than a mast (26%) year. In the mast year, activity varied strongly from a low of 7% during the summer lull to a high of 35% in the fall. Chipmunks that exploited a feeder had higher activity (33%) than chipmunks that did not (19%). Activity was higher during the day, but some activity occurred at night. Daily activity patterns varied strongly among seasonal periods. There was no evidence of torpor during the summer lull. Torpor started much earlier in the nonmast than in the mast year and occurred more at night than during the day. Overall, our study suggests that activity in this food-storing hibernator is positively influenced by food availability and indicates that thermosensitive radiotelemetry is a promising method for recording continuous activity.
Methods for Nonparametric and Semiparametric Regressions with Endogeneity: A Gentle Guide
Authors: Chen Xiaohong , Qiu Yin Jia Jeff
Published: August 2016

This article reviews recent advances in estimation and inference for nonparametric and semiparametric models with endogeneity. It first describes methods of sieves and penalization for estimating unknown functions identified via conditional moment restrictions. Examples include nonparametric instrumental variables (NPIV) regression, nonparametric quantile IV regression, and many more semi/nonparametric structural models. Asymptotic properties of the sieve estimators and the sieve Wald, quasi-likelihood ratio hypothesis tests of functionals with nonparametric endogeneity are presented. For sieve NPIV estimation, the rate-adaptive data-driven choices of sieve regularization parameters and the sieve score bootstrap uniform confidence bands are described. Finally, simple sieve variance estimation and overidentification tests for the semiparametric two-step generalized method of moments are reviewed. Monte Carlo examples are also included.
Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats
Authors: Spradley Frank T. , Sasser Jennifer M. , Musall Jacqueline B. , Sullivan Jennifer C. , Granger Joey P.
Published: August 2016

Although obesity increases the risk for hypertension in pregnancy, the mechanisms responsible are unknown. Increased nitric oxide (NO) production results in vasodilation and reduced blood pressure during normal pregnancy in lean rats; however, the role of NO is less clear during obese pregnancies. We examined the impact of obesity on NO synthase (NOS)-mediated regulation of blood pressure during pregnancy by testing the hypothesis that NOS activity, expression, and regulation of vascular tone and blood pressure are reduced in obese pregnant rats. At gestational day 19, melanocortin-4 receptor (MC4R)-deficient obese rats (MC4R) had greater body weight and fat mass with elevated blood pressure and circulating sFlt-1 levels compared with MC4R pregnant rats. MC4R pregnant rats also had less circulating cGMP levels and reduced total NOS enzymatic activity and expression in mesenteric arteries. Despite decreased biochemical measures of NO/NOS in MC4R rats, NOS inhibition enhanced vasoconstriction only in mesenteric arteries from MC4R rats, suggesting greater NOS-mediated tone. To examine the role of NOS on blood pressure regulation in obese pregnant rats, MC4R and MC4R pregnant rats were administered the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg/l) from gestational day 14 to 19 in drinking water. The degree by which l-NAME raised blood pressure was similar between obese and lean pregnant rats. Although MC4R obese pregnant rats had elevated blood pressure associated with reduced total NOS activity and expression, they had enhanced NOS-mediated attenuation of vasoconstriction, with no evidence of alterations in NOS-mediated regulation of blood pressure.
Endothelin research and the discovery of macitentan for the treatment of pulmonary arterial hypertension
Authors: Clozel Martine
Published: August 2016

Endothelin receptor antagonists (ERAs) are used for the treatment of pulmonary arterial hypertension (PAH). Macitentan, a dual (ETA+ETB) ERA approved for the long-term treatment of PAH, was discovered through a tailored research program aimed at improving efficacy and safety over the existing ERAs. The goal of improved efficacy was based on the understanding that not only the ETA receptor but also the ETB receptor contributed to the hemodynamic and structural changes induced by endothelin-1 (ET-1) in pathological conditions and on the predefined requirements for optimal tissue penetration and binding kinetics of the antagonist. The goal of improved safety was based on the discovery of the role of ETB receptors in vascular permeability and vasopressin release and on the elucidation of the mechanism by which bosentan (the first approved oral dual ETA/ETB ERA) caused liver enzyme changes. Our intention was to design a molecule that would block ETA and ETB receptors optimally and would not interfere with bile salt elimination. This review takes us through the drug discovery journey that led to the discovery, development, and registration of macitentan.
The inferior olive is essential for long-term maintenance of a simple motor skill
Authors: Chen Xiang Yang , Wang Yu , Chen Yi , Chen Lu , Wolpaw Jonathan R.
Published: August 2016

The inferior olive (IO) is essential for operant down-conditioning of the rat soleus H-reflex, a simple motor skill. To evaluate the role of the IO in long-term maintenance of this skill, the H-reflex was down-conditioned over 50 days, the IO was chemically ablated, and down-conditioning continued for up to 102 more days. H-reflex size just before IO ablation averaged 62(±2 SE)% of its initial value ( P < 0.001 vs. initial). After IO ablation, H-reflex size rose to 75–80% over ∼10 days, remained there for ∼30 days, rose over 10 days to above its initial value, and averaged 140(±14)% for the final 10 days of study ( P < 0.01 vs. initial). This two-stage loss of down-conditioning maintenance correlated with IO neuronal loss ( r = 0.75, P < 0.01) and was similar to the loss of down-conditioning that follows ablation of the cerebellar output nuclei dentate and interpositus. In control (i.e., unconditioned) rats, IO ablation has no long-term effect on H-reflex size. These results indicate that the IO is essential for long-term maintenance of a down-conditioned H-reflex. With previous data, they support the hypothesis that IO and cortical inputs to cerebellum combine to produce cerebellar plasticity that produces sensorimotor cortex plasticity that produces spinal cord plasticity that produces the smaller H-reflex. H-reflex down-conditioning appears to depend on a hierarchy of plasticity that may be guided by the IO and begin in the cerebellum. Similar hierarchies may underlie other motor learning.
Comparison of the color selectivity of macaque V4 neurons in different color spaces
Authors: Sanada Takahisa M. , Namima Tomoyuki , Komatsu Hidehiko
Published: August 2016

Chromatic selectivity has been studied extensively in various visual areas at different stages of visual processing in the macaque brain. In these studies, color stimuli defined in the Derrington-Krauskopf-Lennie (DKL) color space with a limited range of cone contrast were typically used in early stages, whereas those defined in the Commission Internationale de l'Eclairage (CIE) color space, based on human psychophysical measurements across the gamut of the display, were often used in higher visual areas. To understand how the color information is processed along the visual pathway, it is necessary to compare color selectivity obtained in different areas on a common color space. In the present study, we tested whether the neural color selectivity obtained in DKL space can be predicted from responses obtained in CIE space and whether stimuli with limited cone contrast are sufficient to characterize neural color selectivity. We found that for most V4 neurons, there was a strong correlation between responses measured using the two chromatic coordinate systems, and the color selectivities obtained with the two stimulus sets were comparable. However, for some neurons preferring high- or low-saturation colors, stimuli defined in DKL color space did not adequately capture the neural color selectivity. This is mainly due to the use of stimuli within a limited range of cone contrast. We conclude that regardless of the choice of color space, the sampling of colors across the entire gamut is important to characterize neural color selectivity fully or to compare color selectivities in different areas so as to understand color representation in the visual system.
Interactive effect of acute pain and motor learning acquisition on sensorimotor integration and motor learning outcomes
Authors: Dancey Erin , Murphy Bernadette , Andrew Danielle , Yielder Paul
Published: August 2016

Previous work has demonstrated differential changes in early somatosensory evoked potentials (SEPs) when motor learning acquisition occurred in the presence of acute pain; however, the learning task was insufficiently complex to determine how these underlying neurophysiological differences impacted learning acquisition and retention. To address this limitation, we have utilized a complex motor task in conjunction with SEPs. Two groups of 12 participants ( n = 24) were randomly assigned to either a capsaicin (capsaicin cream) or a control (inert lotion) group. SEP amplitudes were collected at baseline, after application, and after motor learning acquisition. Participants performed a motor acquisition task followed by a pain-free retention task within 24–48 h. After motor learning acquisition, the amplitude of the N20 SEP peak significantly increased ( P < 0.05) and the N24 SEP peak significantly decreased ( P < 0.001) for the control group while the N18 SEP peak significantly decreased ( P < 0.01) for the capsaicin group. The N30 SEP peak was significantly increased ( P < 0.001) after motor learning acquisition for both groups. The P25 SEP peak decreased significantly ( P < 0.05) after the application of capsaicin cream. Both groups improved in accuracy after motor learning acquisition ( P < 0.001). The capsaicin group outperformed the control group before motor learning acquisition ( P < 0.05) and after motor learning acquisition ( P < 0.05) and approached significance at retention ( P = 0.06). Improved motor learning in the presence of capsaicin provides support for the enhancement of motor learning while in acute pain. In addition, the changes in SEP peak amplitudes suggest that early SEP changes reflect neurophysiological alterations accompanying both motor learning and mild acute pain.
Is realistic neuronal modeling realistic?
Authors: Almog Mara , Korngreen Alon
Published: August 2016

Scientific models are abstractions that aim to explain natural phenomena. A successful model shows how a complex phenomenon arises from relatively simple principles while preserving major physical or biological rules and predicting novel experiments. A model should not be a facsimile of reality; it is an aid for understanding it. Contrary to this basic premise, with the 21st century has come a surge in computational efforts to model biological processes in great detail. Here we discuss the oxymoronic, realistic modeling of single neurons. This rapidly advancing field is driven by the discovery that some neurons don't merely sum their inputs and fire if the sum exceeds some threshold. Thus researchers have asked what are the computational abilities of single neurons and attempted to give answers using realistic models. We briefly review the state of the art of compartmental modeling highlighting recent progress and intrinsic flaws. We then attempt to address two fundamental questions. Practically, can we realistically model single neurons? Philosophically, should we realistically model single neurons? We use layer 5 neocortical pyramidal neurons as a test case to examine these issues. We subject three publically available models of layer 5 pyramidal neurons to three simple computational challenges. Based on their performance and a partial survey of published models, we conclude that current compartmental models are ad hoc, unrealistic models functioning poorly once they are stretched beyond the specific problems for which they were designed. We then attempt to plot possible paths for generating realistic single neuron models.