bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping bias overestimates reference allele frequencies at theHLAgenes in the 1000 Genomes Project phase I data
Authors: Brandt Débora Y. C. , Aguiar Vitor R. C. , Bitarello Bárbara D. , Nunes Kelly , Goudet Jérôme , Meyer Diogo
Published: December 2014

Next Generation Sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the Human Leukocyte Antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population ge-nomics analises, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the SNPs reported by 1000G (phase I) at fiveHLAgenes (HLA-A,-B,-C,-DRB1,-DQB1). We take advantage of the availability ofHLASanger sequencing of 930 of the 1,092 1000G samples, and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls inHLAgenes are incorrect, and that allele frequencies are estimated with an error higher than ±0.1 at approximately 25% of the SNPs inHLAgenes. We found a bias towards overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates, and discuss the outcomes of including those sites in different kinds of analyses. Since theHLAregion is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity.

Data available in public repositories

https://github.com/deboraycb/reliability_hla_1000g
The Neural Marketplace: I. General Formalism and Linear Theory
Authors: Lewis Sarah N. , Harris Kenneth D.
Published: December 2014

We propose a mathematical theory for how networks of neurons in the brain self-organize into functional networks, similarly to the self-organization of supply networks in a free-market economy. The theory is inspired by recent experimental results showing how information about changes to output synapses can travel backward along axons to affect a neuron’s inputs. In neuronal development, competition for such “retroaxonal” signals determines which neurons live and which die. We suggest that in adults, an analogous form of competition occurs between neurons, to supply their targets with appropriate information in exchange for a “payment” returned to them backward along the axon. We review experimental evidence suggesting that neurotrophins may constitute such a signaling pathway in the adult brain.

We construct a mathematical model, in which a small number of “consumer” neurons receive explicit fast error signals while a larger number of “producer” neurons compete to supply them with information, guided by retroaxonal signals from the consumers and from each other. We define a loss function to measure network performance and define the “worth” of a producer to be the increase in loss that would result if that neuron were to fall silent. We show how slow retroaxonal signals can allow producers to estimate their worth, and how these estimates allow the network to perform a form of parallel search over multiple producer cells. We validate our approximations and demonstrate the proposed learning rule using simulations.
Acoustic transfer of protein crystals from agarose pedestals to micromeshes for high-throughput screening
Authors: Cuttitta Christina M. , Ericson Daniel L. , Scalia Alexander , Roessler Christian G. , Teplitsky Ella , Joshi Karan , Campos Olven , Agarwal Rakhi , Allaire Marc , Orville Allen M. , Sweet Robert M. , Soares Alexei S.
Published: December 2014

Acoustic droplet ejection (ADE) is an emerging technology with broad applications in serial crystallography such as growing, improving and manipulating protein crystals. One application of this technology is to gently transfer crystals onto MiTeGen micromeshes with minimal solvent. Once mounted on a micromesh, each crystal can be combined with different chemicals such as crystal-improving additives or a fragment library. Acoustic crystal mounting is fast (2.33 transfers s−1) and all transfers occur in a sealed environment that is in vapor equilibrium with the mother liquor. Here, a system is presented to retain crystals near the ejection point and away from the inaccessible dead volume at the bottom of the well by placing the crystals on a concave agarose pedestal (CAP) with the same chemical composition as the crystal mother liquor. The bowl-shaped CAP is impenetrable to crystals. Consequently, gravity will gently move the crystals into the optimal location for acoustic ejection. It is demonstrated that an agarose pedestal of this type is compatible with most commercially available crystallization conditions and that protein crystals are readily transferred from the agarose pedestal onto micromeshes with no loss in diffraction quality. It is also shown that crystals can be grown directly on CAPs, which avoids the need to transfer the crystals from the hanging drop to a CAP. This technology has been used to combine thermolysin and lysozyme crystals with an assortment of anomalously scattering heavy atoms. The results point towards a fast nanolitre method for crystal mounting and high-throughput screening.
In crystallooptical spectroscopy (icOS) as a complementary tool on the macromolecular crystallography beamlines of the ESRF
Authors: von Stetten David , Giraud Thierry , Carpentier Philippe , Sever Franc , Terrien Maxime , Dobias Fabien , Juers Douglas H. , Flot David , Mueller-Dieckmann Christoph , Leonard Gordon A. , de Sanctis Daniele , Royant Antoine
Published: December 2014

The analysis of structural data obtained by X-ray crystallography benefits from information obtained from complementary techniques, especially as applied to the crystals themselves. As a consequence, optical spectroscopies in structural biology have become instrumental in assessing the relevance and context of many crystallographic results. Since the year 2000, it has been possible to record such data adjacent to, or directly on, the Structural Biology Group beamlines of the ESRF. A core laboratory featuring various spectrometers, named the Cryobench, is now in its third version and houses portable devices that can be directly mounted on beamlines. This paper reports the current status of the Cryobench, which is now located on the MAD beamline ID29 and is thus called the ID29S-Cryobench (where S stands for `spectroscopy'). It also reviews the diverse experiments that can be performed at the Cryobench, highlighting the various scientific questions that can be addressed.
Collaborative Computational Project for Electron cryo-Microscopy
Authors: Wood Chris , Burnley Tom , Patwardhan Ardan , Scheres Sjors , Topf Maya , Roseman Alan , Winn Martyn
Published: December 2014

The Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) has recently been established. The aims of the project are threefold: to build a coherent cryoEM community which will provide support for individual scientists and will act as a focal point for liaising with other communities, to support practising scientists in their use of cryoEM software and finally to support software developers in producing and disseminating robust and user-friendly programs. The project is closely modelled on CCP4 for macromolecular crystallography, and areas of common interest such as model fitting, underlying software libraries and tools for building program packages are being exploited. Nevertheless, cryoEM includes a number of techniques covering a large range of resolutions and a distinct project is required. In this article, progress so far is reported and future plans are discussed.
Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions
Authors: Brown Alan , Long Fei , Nicholls Robert A. , Toots Jaan , Emsley Paul , Murshudov Garib
Published: December 2014

The recent rapid development of single-particle electron cryo-microscopy (cryo-EM) now allows structures to be solved by this method at resolutions close to 3 Å. Here, a number of tools to facilitate the interpretation of EM reconstructions with stereochemically reasonable all-atom models are described. TheBALBESdatabase has been repurposed as a tool for identifying protein folds from density maps. Modifications toCoot, including new Jiggle Fit and morphing tools and improved handling of nucleic acids, enhance its functionality for interpreting EM maps.REFMAChas been modified for optimal fitting of atomic models into EM maps. As external structural information can enhance the reliability of the derived atomic models, stabilize refinement and reduce overfitting,ProSMARThas been extended to generate interatomic distance restraints from nucleic acid reference structures, and a new tool,LIBG, has been developed to generate nucleic acid base-pair and parallel-plane restraints. Furthermore, restraint generation has been integrated with visualization and editing inCoot, and these restraints have been applied to both real-space refinement inCootand reciprocal-space refinement inREFMAC.
How temperature shifts affect parasite production: testing the roles of thermal stress and acclimation
Authors: Paull Sara H. , Raffel Thomas R. , LaFonte Bryan E. , Johnson Pieter T. J.
Published: December 2014

Changes in the magnitude and frequency of temperature shifts with climate change will influence species interactions if species have differential acclimation responses. For example, if parasites acclimate to temperature shifts faster than their hosts, as might be expected due to their smaller sizes and faster metabolisms, temperature variability could lead to increased infection. However, this assumption might not hold if benefits of acclimation are counteracted by energetic costs or thermal stress, underscoring the need for empirical efforts to assess how temperature variability will influence host–parasite interactions.

We used an array of replicate incubators to test how temperature shifts from five acclimation temperatures (13–25 °C) to five performance temperatures (16–28 °C) influenced release of infective stages by the trematode parasite Ribeiroia ondatrae from its snail intermediate host (Helisoma trivolvis) at four time‐points after a temperature shift.

Initially, parasite release was higher at warm temperatures and increased temporarily after infected snails were shifted to higher temperatures, particularly for hosts acclimated to cooler temperatures. However, these effects were transient, such that parasite release at warm temperatures declined steadily over the 7 days following the shift. Warmer temperatures also increased snail mortality.

Parasite release was strongly influenced not only by ambient temperature but also by the thermal history of the host. Prior acclimation to warm temperatures reduced parasite release at warm performance temperatures, contrary to the beneficial acclimation hypothesis. Rather, the observed pattern was likely driven by: (i) energetic costs of prolonged exposure to high temperatures (‘thermal stress’) or (ii) parasites' capacity to ‘store’ infectious stages at cooler temperatures.

The time‐dependent nature of thermal effects on parasite performance highlights the importance of considering the amplitude and frequency of temperature variability for understanding future changes to disease dynamics.
Onwards and upwards – aphid flight trends follow climate change
Authors: Leather Simon R.
Published: December 2014

Two aphid species with contrasting life cycles and responses to climate change. On the right Utamphorophora humboldti, an invasive species from North America (Blackman & Eastop ), where it is host alternating, but in the United Kingdom is almost certainly anholocyclic (continuously parthenogenetic) on grasses. This species has shown the most dramatic advance in flight phenology and has shown the largest population increases. The maple aphid, Periphyllus testudinaceus, on the left, here pictured on horse chestnut, Aesculus hippocastanum, is a native non‐host‐alternating ant‐attended species (Blackman & Eastop ) and has a contracting flight season.

image

Two aphid species with contrasting life cycles and responses to climate change. On the right Utamphorophora humboldti, an invasive species from North America (Blackman & Eastop ), where it is host alternating, but in the United Kingdom is almost certainly anholocyclic (continuously parthenogenetic) on grasses. This species has shown the most dramatic advance in flight phenology and has shown the largest population increases. The maple aphid, Periphyllus testudinaceus, on the left, here pictured on horse chestnut, Aesculus hippocastanum, is a native non‐host‐alternating ant‐attended species (Blackman & Eastop ) and has a contracting flight season.

Bell, J.R., Alderson, L., Izera, D., Kruger, T., Parker, S., Pickup, J., Shortall, C.R., Taylor, M.S., Verrier, P. & Harrington, R. (2015) . Journal of Animal Ecology, 84, 21–34

The world faces an uncertain future; climate change and the concerns about the security of food production feature prominently on political and scientific agendas world‐wide. In this issue, Bell et al. (), drawing on the unique 50‐year data set amassed by the suction trap network run by the Rothamsted Insect Survey (RIS), elucidate the mechanisms advancing aphid phenology under climate change and show how by using biological traits we can make predictions about emerging crop pests. Here, I discuss their findings in the context of phenological coincidence and host plant availability.
Keeping Open by Re-Imagining Laughter and Fear
Authors: Jerak-Zuiderent Sonja
Published: December 2014

Speaking to the debate on the nature of critique, this article is about the struggle to produce an account when listening to and retelling stories. It begins with the disconcertment over listening to a coherent story that emerges in interviews about the development of performance indicators for Dutch hospital care. The indicators are presented as solutions to the problem of unruliness in the healthcare world. Drawing on Helen Verran's work on generative critique I slow down the ‘problem-solution-found’ plot. Instead of contrasting the apparently coherent stories with the complexities of an ‘underlying’ practice of healthcare, I hold on to my initial disconcertment so that ‘fleetingly subtle’ interruptions become entry points for generative critique. Taking Eduardo Viveiros de Castro's understanding of the relation that fear and laughter have to alterity, I show how fear and laughter permit generative critique within seemingly coherent stories. In the case of indicator development, the interviewees ‘laugh away’ what they consider alter from quality and safety in healthcare: having no control over what is going on, polyglotism instead of a common language, and inaction as opposed to taking one's time. Paying attention to disconcerting interruptions generates sensitivity and questions rather than yet another set of (critical) problem-solution-found answers. How can ridiculed (laughed away) subjectivity be acknowledged as important entry points for including alterity in supervision? And how to position the acknowledgement, not as an antidote, but as a way of rendering the fear of alterity generative? Nurturing sensitivities is crucial for keeping open, which means resisting both the sticky tendency of normalizing accounts and the fallacy of misplaced concreteness. I conclude that keeping open by re-imagining critique resonates with the creativity of collective life in actual times and places. Thereby it offers a promising potential for doing worlds differently.
FETAL TESTOSTERONE AND CRIMINALITY: TEST OF EVOLUTIONARY NEUROANDROGENIC THEORY
Authors: Hoskin Anthony W. , Ellis Lee
Published: December 2014

Evolutionary neuroandrogenic (ENA) theory asserts that criminality is a crude form of competitive behavior over resources, status, and mating opportunities. Theoretically, males have been selected for resource acquisitiveness as a result of female preferences for mates who are successful at resource provisioning. ENA theory also asserts that brain exposure to both prenatal and postpubertal androgens (particularly testosterone) promotes all forms of competitiveness, including those that victimize others. The present study was undertaken to test ENA theory by correlating 14 self‐reported measures of offending with a biomarker for fetal testosterone exposure based on the ratio of the 2nd and 4th digits of the right hand (r2D:4D), in a nonrepresentative sample of 445. Both Spearman correlations and negative binomial regressions produced results that largely supported the hypothesized connection between offending and high prenatal androgen exposure, even when findings were analyzed separately by sex. Also, offending was significantly associated with r2D:4D for both males and females. Overall, this study supports the view that exposing the brain to high levels of testosterone and other androgens prenatally elevates the probability of offending later in life.
Variability in Early Do Not Attempt Resuscitation Orders Among Patients With Serious Traumatic Brain Injury
Authors: Dean Dylan , Martinez Michael S. , Newgard Craig D.
Published: December 2014

Objectives

The objective was describe the use of early do not attempt resuscitation (DNAR) orders in patients with serious traumatic brain injury (TBI) and its association with outcomes.

Methods

This was a retrospective cohort study of all serious TBI patients admitted through the emergency department (ED) to acute care hospitals in California between 2002 and 2010 using ED International Classification of Diseases, 9th revision (ICD‐9), admitting diagnosis codes specifying intracranial hemorrhage. DNAR placement within 24 hours of admission was the primary variable of interest. Outcomes included neurosurgical procedures and in‐hospital mortality. Hospital and patient characteristics were analyzed using descriptive statistics and multivariable generalized estimation equation regression models to account for hospital‐level clustering.

Results

Of all 76,962 patients with serious TBI, 71,275 were admitted at 141 hospitals that each cared for at least 10 serious TBI patients annually and formed the primary sample. Early DNAR orders were placed in 7.5% of patients (range = 0 to 36.1% by hospital). Early DNAR use varied by trauma designation: Level I, 4.0% (95% confidence interval [CI] = 3.8% to 4.4%); Level II, 6.7% (95% CI = 6.5% to 7.1%); Level III, 9.7% (95% CI = 8.4% to 11.3%); and nontrauma hospitals, 10.8% (95% CI = 10.6% to 11.3%). Early DNAR was also less likely in teaching hospitals (9.3% vs. 4.3%). These results persisted after accounting for age, year, and hospital‐level clustering. In‐hospital mortality (39.4% vs. 8.7%) and neurosurgical interventions (14.5% vs. 19.7%) also differed for patients with versus without early DNAR orders. Patients 65 years of age and older constituted 87.7% of those with early DNAR orders; our findings remained qualitatively unchanged when restricted to older adults.

Conclusions

Use of early DNAR orders among patients with serious TBI is highly variable by individual hospital and hospital type, suggesting substantial practice variation. Associations with fewer surgical intervention and higher mortality suggest that such practice variation may be contributing to differences in TBI outcomes, particularly among older adults.
Adolescent Patient Preferences Surrounding Partner Notification and Treatment for Sexually Transmitted Infections
Authors: Reed Jennifer L. , Huppert Jill S. , Gillespie Gordon L. , Taylor Regina G. , Holland Carolyn K. , Alessandrini Evaline A. , Kahn Jessica A.
Published: December 2014

Objectives

Important barriers to addressing the sexually transmitted infection (STI) epidemic among adolescents are the inadequate partner notification of positive STI results and insufficient rates of partner testing and treatment. However, adolescent attitudes regarding partner notification and treatment are not well understood. The aim was to qualitatively explore the barriers to and preferences for partner notification and treatment among adolescent males and females tested for STIs in an emergency department (ED) setting and to explore the acceptability of ED personnel notifying their sexual partners.

Methods

This was a descriptive, qualitative study in which a convenience sample of 40 adolescents (18 females, 22 males) 14 to 21 years of age who presented to either adult or pediatric EDs with STI‐related complaints participated. Individualized, semistructured, confidential interviews were administered to each participant. Interviews were audiotaped and transcribed verbatim by an independent transcriptionist. Data were analyzed using framework analysis.

Results

Barriers to partner notification included fear of retaliation or loss of the relationship, lack of understanding of or concern for the consequences associated with an STI, and social stigma and embarrassment. Participants reported two primary barriers to their partners obtaining STI testing and treatment: lack of transportation to the health care site and the partner's fear of STI positive test results. Most participants preferred to notify their main sexual partners of an STI exposure via a face‐to‐face interaction or a phone call. Most participants were agreeable with a health care provider (HCP) notifying their main sexual partners of STI exposure and preferred that the HCP notify the partner by phone call.

Conclusions

There are several adolescent preferences and barriers for partner notification and treatment. To be most effective, future interventions to prevent adolescent STIs should incorporate these preferences and address the barriers to partner notification. In an ED setting, using HCPs to provide partner notification of STI exposures is acceptable to adolescent patients; however, the feasibility of this type of program needs further exploration.
HIV epidemic among drug users in China: 1995–2011
Authors: Wang Lan , Guo Wei , Li Dongmin , Ding Zhengwei , McGoogan Jennifer M. , Wang Ning , Wu Zunyou , Wang Lu ,   China National HIV/AIDS Surveillance Program
Published: December 2014

Aim

To describe trends in the HIV epidemic among drug users (DUs) in China from 1995 to 2011.

Design, Setting and Participants

Data sets from China's national HIV/AIDS case reporting and sentinel surveillance systems as of December 2011 were used separately for descriptive analysis.

Measures

Changes in the geographic distribution of the number of HIV cases and HIV prevalence among injecting drug users (IDUs) and non‐IDUs were examined. We also analysed changes in HIV prevalence among the broader DU population, and drug use‐related behaviours including types of drugs used, recent injecting and recent needle sharing in the context of the rapid scale‐up of DU sentinel sites and national harm reduction programmes.

Findings

The HIV epidemic among China's DUs is still highly concentrated in five provinces. Here, HIV prevalence peaked at 30.3% [95% confidence interval (CI) = 28.6, 32.1] among IDUs in 1999, and then gradually decreased to 10.9% (95% CI = 10.6, 11.2) by 2011. We observed a rapid increase in the use of ‘nightclub drugs’ among DUs from 1.3% in 2004 to 24.4% in 2011. A decline in recent needle sharing among current IDU from 19.5% (95% CI = 19.4, 19.6) in 2006 to 11.3% (95% CI = 11.2, 11.4) in 2011 was found to be correlated with the rapid scale‐up of methadone maintenance treatment (MMT; r(4) = −0.94, P = 0.003) harm reduction efforts.

Conclusions

While HIV prevalence and needle sharing among current injecting drug users in China have declined dramatically and are correlated with the scale‐up of national harm reduction efforts, the recent, rapid increased use of ‘nightclub drugs’ presents a new challenge.
Factors associated with depression and anxiety among patients attending community‐based methadone maintenance treatment in China
Authors: Yin Wenyuan , Pang Lin , Cao Xiaobin , McGoogan Jennifer M. , Liu Michael , Zhang Congbin , Li Zhijun , Li Jianhua , Rou Keming
Published: December 2014

Aim

To estimate the prevalence of, and identify factors associated with, depression and anxiety among community‐based methadone maintenance treatment (MMT) clients in China.

Design

A cross‐sectional survey.

Setting

Nine MMT clinics, three each from three Chinese provinces (Yunnan, Anhui and Jiangsu) between October 2008 and February 2009.

Participants

A total of 1301 MMT clients.

Measurements

A questionnaire, including the Zung Self‐Rating Depression Scale (SDS) and Zung Self‐Rating Anxiety Scale (SAS), and on‐site urine drug testing.

Findings

The prevalence of depression (SDS score ≥ 53) and anxiety (SAS score ≥ 50) in our sample was 38.3% [95% confidence interval (CI) = 35.7, 40.9] and 18.4% (95% CI = 16.3, 20.5), respectively, with 14.2% (95% CI = 12.3, 16.1) displaying symptoms of both. Sample prevalence rates for depression [mean = 49.69, standard deviation (SD) = 10.34] and anxiety (mean = 40.98, SD = 10.66) were higher than the national average for each (t(0.05/2, 1300) = 19.2, P < 0.001 and t(0.05/2, 1300) = 8.0, P < 0.001, respectively). Employing multi‐level modelling techniques, gender (P = 0.03) and employment status (P < 0.001) were found to be associated significantly with depression in a single‐level model; however, in a multi‐level mixed model, only employment status (P < 0.001) was associated with depression. Gender (P = 0.03), education level (P = 0.02), marital status (P = 0.04), employment status (P < 0.001), positive urine drug test results (P = 0.02) and daily methadone dose (P < 0.001) were found to be associated significantly with anxiety in a single‐level model, while only employment status (P < 0.01) and positive results for the urine drug test (P = 0.04) were associated with anxiety in a multi‐level mixed model.

Conclusions

A considerable proportion of methadone maintenance treatment clients in China have experienced depression and anxiety during treatment. There is a need to provide tailored mental health interventions for this high‐risk population.
Predictors of accessing antiretroviral therapy among HIV‐positive drug users in China's National Methadone Maintenance Treatment Programme
Authors: Zhao Yan , Shi Cynthia X. , McGoogan Jennifer M. , Rou Keming , Zhang Fujie , Wu Zunyou
Published: December 2014

Aims

The objective of this study was to examine factors that predict antiretroviral therapy (ART) access among eligible, HIV‐positive methadone maintenance treatment (MMT) clients. We also tested the hypothesis that sustained MMT participation increases the likelihood of accessing ART.

Design

A nation‐wide cohort study conducted from 1 March 2004 to 31 December 2011.

Setting

MMT clients were followed from the time of their enrolment in China's national MMT programme until their death or the study end date.

Participants

Our cohort comprised 7111 ART‐eligible, HIV‐positive MMT clients, 49.2% of whom remained ART‐naive and 50.8% of whom received ART.

Measurements

Demographic variables, drug use history, MMT programme participation and HIV‐related clinical characteristics of study participants who remained naive to ART and those who accessed ART were compared by univariate and multivariable analysis.

Findings

Predictors of accessing ART among this cohort included being retained in MMT at the time of first meeting ART eligibility [adjusted odds ratio (AOR) = 1.84, confidence interval (CI) = 1.54–2.21, P < 0.001] compared to meeting ART eligibility before entering MMT (AOR = 0.98, CI = 0.80–1.21, P = 0.849) or previously entering MMT and dropping out before meeting ART eligibility. Additional predictors were CD4 ≤200 cells/μl when ART‐eligibility requirement was first met (AOR = 1.81, CI = 1.61–2.05, P < 0.001 compared to CD4 = 201–350 cells/μl), and being in a stable partner relationship (married/cohabitating: AOR = 1.14, CI = 1.01–1.28, P = 0.030).

Conclusions

Retained participation in methadone maintenance treatment increases the likelihood that eligible clients will access antiretroviral therapy. These results highlight the potential benefit of colocalization of methadone maintenance treatment and antiretroviral therapy services in a ‘one‐stop‐shop’ model.
Health promotion interventions and policies addressing excessive alcohol use: a systematic review of national and global evidence as a guide to health‐care reform in China
Authors: Li Qing , Babor Thomas F. , Zeigler Donald , Xuan Ziming , Morisky Donald , Hovell Melbourne F. , Nelson Toben F. , Shen Weixing , Li Bing
Published: December 2014

Aims

Steady increases in alcohol consumption and related problems are likely to accompany China's rapid epidemiological transition and profit‐based marketing activities. We reviewed research on health promotion interventions and policies to address excessive drinking and to guide health‐care reform.

Methods

We searched Chinese‐ and English‐language databases and included 21 studies in China published between 1980 and 2013 that covered each policy area from the World Health Organization (WHO) Global Strategy to Reduce the Harmful Use of Alcohol. We evaluated and compared preventive interventions to the global alcohol literature for cross‐national applicability.

Results

In contrast with hundreds of studies in the global literature, 11 of 12 studies from mainland China were published in Chinese; six of 10 in English were on taxation from Taiwan or Hong Kong. Most studies demonstrated effectiveness in reducing excessive drinking, and some reported the reduction of health problems. Seven were randomized controlled trials. Studies targeted schools, drink‐driving, work‐places, the health sector and taxation.

Conclusions

China is the world's largest alcohol market, yet there has been little growth in alcohol policy research related to health promotion interventions over the past decade. Guided by a public health approach, the WHO Global Strategy and health reform experience in Russia, Australia, Mexico and the United States, China could improve its public health response through better coordination and implementation of surveillance and evidence‐based research, and through programmatic and legal responses such as public health law research, screening and early intervention within health systems and the implementation of effective alcohol control strategies.
Predictors of maternal drinking trajectories before and after pregnancy: evidence from a longitudinal study
Authors: Tran Nam T. , Najman Jake M. , Hayatbakhsh Reza
Published: December 2014

Background

Little is known about patterns of change in alcohol consumption and predictors of these patterns over the prenatal to postnatal period.

Aims

To determine trajectories of maternal alcohol consumption before and after pregnancy and predictors of these trajectories.

Materials and Methods

A total of 6597 Australian women were sampled from a longitudinal study. Group‐based trajectory modelling was applied to determine drinking trajectories from prepregnancy, early pregnancy, late pregnancy and 6 months after the birth. Predictors associated with drinking trajectories were examined using multinomial logistic regression.

Results

Three trajectories of maternal alcohol consumption were identified: abstainers/minimal consumption (53.2%), light consumption (39.4%) and heavy consumption (7.4%). The heavy consumption group substantially reduced their consumption in pregnancy but increased their consumption once the baby was born. Some 80.0% of this group were breastfeeding their babies. The light consumption group had only minor changes in their drinking pattern. Lower family income, being married, high frequency of church attendance, low level of adversity, poor health lifestyle, remaining married to original partner and having many children predicted membership of the abstaining/minimal consumption trajectory. Being unmarried, having only one child, having unhealthy health lifestyle and never going to church predicted membership of the heavy consumption group.

Conclusion

Women who consume higher levels of alcohol prior to their pregnancy reduce their consumption once pregnant, but tend to increase their alcohol consumption shortly after the birth. A public health campaign dealing with predictors associated with heavier alcohol consumption and safe breastfeeding targetted at these women is needed.
Screening for congenital heart defects by transabdominal ultrasound – role of early gestational screening and importance of operator training
Authors: Sarkola Taisto , Ojala Tiina H. , Ulander Veli‐Matti , Jaeggi Edgar , Pitkänen Olli M.
Published: December 2014

The majority of congenital heart defects occur without identifiable risk factors. Detection rates are therefore highly dependent on the experience and expertise of the obstetrical screening operator. In the first trimester, the risk of congenital heart defects increases with increasing nuchal thickness (≥2.5 mm detects 44% of major congenital heart defects), but because of the number of false positives, the positive predictive value is only a few percent. The anatomy of major congenital heart defects may be delineated in less than half of the fetuses during early second trimester. The reported yield of congenital heart defects detection during the mid‐gestational routine obstetrical screening has improved over time and detection rates up to 85% of major congenital heart defects have been reported when outflow tract and three‐vessel views are included in conjunction with the four‐chamber view. Improved detection rates have been achieved following screening operator training interventions combined with a low referral threshold to obtain a detailed fetal echocardiographic study.
Age and weight at final discharge from an early discharge programme for stable but tube‐fed preterm infants
Authors: Ahnfeldt AM , Stanchev H , Jørgensen HL , Greisen G
Published: December 2014

Aim

Preterm birth is often associated with prolonged hospitalisation, complicating the parent–child relationship and breastfeeding rates. As a result, an early discharge programme was implemented in the department of neonatology at Rigshospitalet. The infants were stable, but required tube feeding, and during the programme, they received home visits by neonatal nurses. We evaluated the programme, focusing on the infants' well‐being, using weight gain, breastfeeding rates and total duration of hospitalisation as outcomes.

Methods

Over an 11‐year period, 500 infants participated in the programme and they constituted the early discharge group. They were compared with 400 infants discharged from the Naestved and Nykoebing Falster hospitals.

Results

The early discharge group's length of hospitalisation was only three days shorter than the comparison group, but they were eight days younger when they joined the programme (p < 0.0001). Total admission was 21 days longer (p < 0.0001). There was no difference in weight‐for‐age at discharge (p = 0.15), but infants in the early discharge group were more frequently fully or partly breastfed (88% versus 80%, p < 0.005).

Conclusion

While recognising the limited comparability of the two groups, weight‐for‐age at discharge was similar, but the programme appeared to allow better breastfeeding success at the expense of a later final discharge.
Galanin modulates human and murine neutrophil activation in vitro
Authors: Sternberg F. , Lang A. A. , Koller A. , Lang R. , Bianchini R. , Kofler B.
Published: December 2014

Aims

Polymorphonuclear neutrophils are key players in innate immunity. The innate immune system needs to be tightly controlled to ensure proper activation but also no overactivation. Galanin has been shown to regulate inflammatory reactions, and therefore, we aimed to elucidate the expression of galanin and its three receptors (GAL1‐GAL3) in polymorphonuclear neutrophils and to evaluate whether galanin exerts direct or indirect effects on human and murine polymorphonuclear neutrophils.

Methods

Human peripheral polymorphonuclear neutrophils were isolated from fresh blood of healthy donors, and murine polymorphonuclear neutrophils were isolated from bone marrow of C57BL/6N mice. Gene expression was evaluated by qRT‐PCR. As a marker for polymorphonuclear neutrophil activation, CD11b integrin surface expression was measured by FACS analysis. Furthermore, a label‐free technology measuring ligand‐induced dynamic mass redistribution was used to evaluate the response of polymorphonuclear neutrophils to galanin.

Results

GAL2 receptor expression was found in both human and murine polymorphonuclear neutrophils, galanin and GAL3 receptor were exclusively expressed in murine bone marrow polymorphonuclear neutrophils, and GAL1 receptor was not detectable in polymorphonuclear neutrophils of either species. Galanin treatment was not able to induce CD11b integrin surface expression or dynamic mass redistribution in human polymorphonuclear neutrophils and murine bone marrow polymorphonuclear neutrophils. However, galanin treatment significantly enhanced the response of polymorphonuclear neutrophils of both species to interleukin‐8.

Conclusion

Galanin can be regarded as an immunomodulatory peptide as it can sensitize polymorphonuclear neutrophils towards pro‐inflammatory cytokines in humans and mice.
Long‐term vegetation dynamics (40 yr) in the Succulent Karoo, South Africa: effects of rainfall and grazing
Authors: van Rooyen Margaretha W. , Le Roux Annelise , Geldenhuys Conrad , van Rooyen Noel , Broodryk Nadine L. , van der Merwe Helga
Published: December 2014

Questions

Vegetation change in arid regions with a coefficient of rainfall exceeding 33% usually displays non‐equilibrium dynamics, where abiotic factors override internal biotic controls. Irreversible changes have nonetheless also been described for arid regions. What are the contributions of internal/equilibrium vs external/non‐equilibrium factors to vegetation dynamics and can degradation due to overstocking be reversed after removal of livestock?

Location

Goegap Nature Reserve, Namaqualand, South Africa.

Methods

The descending point method was conducted annually from 1974 at two transects. Vegetation change was assessed in terms of vegetation cover, species composition, life‐form composition, range condition, species richness and diversity. Principal coordinates analysis was used to illustrate the trajectories in floristic data, and the effects of stocking density and rainfall were examined with redundancy analysis.

Results

Vegetation cover, species richness and Shannon‐Wiener index of diversity showed an increase and range condition improved with time. These positive changes could be related to the removal of high numbers of livestock and low wildlife numbers in the first years of survey. A gradual decline in the rate of increase in some of these parameters could be related to high grazing pressure during the later monitored years. There was a notable increase in non‐succulent chamaephytes, but the initial increase in succulent chamaephytes was not sustained. The directional change evident in perennial species composition, supports the equilibrium concept, whereby the negative changes induced by heavy grazing were partially reversed. Within the directional change, four quasi‐stable states could be distinguished, which could be reconciled with the state‐and‐transition model. The annual component showed no directional change, but displayed event‐driven, non‐equilibrium dynamics by fluctuating in reaction to the timing and quantity of rainfall.

Conclusions

The vegetation change displayed elements of both equilibrium and non‐equilibrium dynamics, and demonstrated that the effects of heavy grazing in the Succulent Karoo were reversible. Overall, the recovery process proceeded slowly and was primarily detected in the perennial component of the vegetation. The increase in wildlife numbers in the later studied years and decline in perennial vegetation cover stress the need for active management of animal numbers to avoid vegetation degradation.
The endocannabinoid system in renal cells: regulation of Na+ transport by CB1 receptors through distinct cell signalling pathways
Authors: Sampaio L S , Taveira Da Silva R , Lima D , Sampaio C L C , Iannotti F A , Mazzarella E , Di Marzo V , Vieyra A , Reis R A M , Einicker‐Lamas M
Published: December 2014

Background and Purpose

The function of the endocannabinoid system (ECS) in renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the re‐absorption of 70–80% of the filtrate. We studied the effect of compounds modulating the activity of cannabinoid (CB) receptors on the active re‐absorption of Na+ in LLC‐PK1 cells.

Experimental Approach

Changes in Na+/K+‐ATPase activity were assessed after treatment with WIN55,212‐2 (WIN), a non‐selective lipid agonist, and haemopressin (HP), an inverse peptide agonist at CB1 receptors. Pharmacological tools were used to investigate the signalling pathways involved in the modulation of Na+ transport.

Key Results

In addition to CB1 and CB2 receptors and TRPV1 channels, the mRNAs encoding for enzymes of the ECS were also expressed in LLC‐PK1. WIN (10−7 M) and HP (10−6 M) altered Na+ re‐absorption in LLC‐PK1 in a dual manner. They both acutely (after 1 min) increased Na+/K+‐ATPase activity in a TRPV1 antagonist‐sensitive way. WIN's stimulating effect persisted for 30 min, and this effect was partially blocked by a CB1 antagonist or a PKC inhibitor. In contrast, HP inhibited Na+/K+‐ATPase after 30 min incubation, and this effect was attenuated by a CB1 antagonist or a PKA inhibitor.

Conclusion and Implications

The ECS is expressed in LLC‐PK1 cells. Both CB1 receptors and TRPV1 channels regulate Na+/K+‐ATPase activity in these cells, and are modulated by lipid and peptide CB1 receptor ligands, which act via different signalling pathways.
The fibrate gemfibrozil is a NO‐ and haem‐independent activator of soluble guanylyl cyclase: in vitro studies
Authors: Sharina I G , Sobolevsky M , Papakyriakou A , Rukoyatkina N , Spyroulias G A , Gambaryan S , Martin E
Published: December 2014

Background and Purpose

Fibrates are a class of drugs widely used to treat dyslipidaemias. They regulate lipid metabolism and act as PPARα agonists. Clinical trials demonstrate that besides changes in lipid profiles, fibrates decrease the incidence of cardiovascular events, with gemfibrozil exhibiting the most pronounced benefit. This study aims to characterize the effect of gemfibrozil on the activity and function of soluble guanylyl cyclase (sGC), the key mediator of NO signalling.

Experimental Approach

High‐throughput screening of a drug library identified gemfibrozil as a direct sGC activator. Activation of sGC is unique to gemfibrozil and is not shared by other fibrates.

Key Results

Gemfibrozil activated purified sGC, induced endothelium‐independent relaxation of aortic rings and inhibited platelet aggregation. Gemfibrozil‐dependent activation was absent when the sGC haem domain was deleted, but was significantly enhanced when sGC haem was lacking or oxidized. Oxidation of sGC haem enhanced the vasoactive and anti‐platelet effects of gemfibrozil. Gemfibrozil competed with the haem‐independent sGC activators ataciguat and cinaciguat. Computational modelling predicted that gemfibrozil occupies the space of the haem group and interacts with residues crucial for haem stabilization. This is consistent with structure‐activity data which revealed an absolute requirement for gemfibrozil's carboxyl group.

Conclusions and Implications

These data suggest that in addition to altered lipid and lipoprotein state, the cardiovascular preventive benefits of gemfibrozil may derive from direct activation and protection of sGC function. A sGC‐directed action may explain the more pronounced cardiovascular benefit of gemfibrozil observed over other fibrates and some of the described side effects of gemfibrozil.
Renal effects of chronic pharmacological manipulation of CB2 receptors in rats with diet‐induced obesity
Authors: Jenkin K A , O'Keefe L , Simcocks A C , Briffa J F , Mathai M L , McAinch A J , Hryciw D H
Published: December 2014

Background and Purpose

In diabetic nephropathy agonism of CB2 receptors reduces albuminuria and podocyte loss; however, the role of CB2 receptors in obesity‐related nephropathy is unknown. The aim of this study was to determine the role of CB2 receptors in a model of diet‐induced obesity (DIO) and characterize the hallmark signs of renal damage in response to agonism (AM1241) and antagonism (AM630) of CB2 receptors.

Experimental Approach

Male Sprague Dawley rats were fed a high‐fat diet (HFD: 40% digestible energy from lipids) for 10 weeks. In another cohort, after 9 weeks on a HFD, rats were injected daily with either 3 mg·kg−1 AM1241, 0.3 mg·kg−1 AM630 or saline for 6 weeks.

Key Results

Ten weeks on a HFD significantly reduced renal expression of CB2 receptors and renal function. Treatment with AM1241 or AM630 did not reduce weight gain or food consumption in DIO. Despite this, AM1241 significantly reduced systolic BP, peri‐renal adipose accumulation, plasma leptin, urinary protein, urinary albumin, urinary sodium excretion and the fibrotic markers TGF‐β1, collagen IV and VEGF in kidney lysate. Treatment with AM630 of DIO rats significantly reduced creatinine clearance and increased glomerular area and kidney weight (gross and standardized for body weight). Diastolic BP, glucose tolerance, insulin sensitivity, plasma creatinine, plasma TGF‐β1 and kidney expression of fibronectin and α‐smooth muscle actin were not altered by either AM1241 or AM630 in DIO.

Conclusions

This study demonstrates that while agonism of CB2 receptors with AM1241 treatment for 6 weeks does not reduce weight gain in obese rats, it leads to improvements in obesity‐related renal dysfunction.

Linked Articles

This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc
Clonal Diversity and Fine‐scale Genetic Structure in a High Andean Treeline Population
Authors: Peng Yanling , Macek Petr , Macková Jana , Romoleroux Katya , Hensen Isabell
Published: December 2014

Clonal propagation becomes more abundant with increasing altitudes as environmental conditions worsen. To date, little attention has been paid to the way in which clonal propagation affects genetic diversity and the fine‐scale spatial genetic structure (FSGS) of clonal alpine trees. An AFLP study was undertaken to quantify the clonal and genetic diversity and FSGS of the vulnerable treeline species Polylepis reticulata in Ecuador. We successfully genotyped 32 and 75 ramets within 4 m × 100 m (coarse scale) and 4 m × 4 m (fine scale) transects of one population, respectively. Higher genotypic diversity was detected at the coarse scale than at the fine scale, while lower genetic diversity was detected for P. reticulata than other Polylepis spp. at both scales. Significantly stronger FSGS was detected at the ramet level than the genet level for P. reticulata within a spatial distance of 3 m. The studied P. reticulata population showed pronounced FSGS (Sp = 0.012 at the genet level, a statistic reflecting declining pairwise kinship with distance) revealed restricted gene dispersal, which implies restricted seed dispersal for this population, assuming pollen flow is as extensive as that described for other wind‐pollinated tree species. Our results revealed that clonal diversity is a function of both sample size and the spatial scale of the sampling area. The findings highlights that clonal propagation has affected FSGS within a spatial distance of 3 m for this species.