bluuebunny/crossref_metadata_2025 huggingface dataset:
Foraging choices of vampire bats in diverse landscapes: potential implications for land‐use change and disease transmission
Authors: Streicker Daniel G. , Allgeier Jacob E.
Published: May 2016

In Latin America, the common vampire bat Desmodus rotundus is the primary reservoir of rabies, a zoonotic virus that kills thousands of livestock annually and causes sporadic and lethal human rabies outbreaks. The proliferation of livestock provides an abundant food resource for this obligate blood‐feeding species that could alter its foraging behaviour and rabies transmission, but poor understanding of the dietary plasticity of vampire bats limits understanding of how livestock influences rabies risk.

We analysed individual‐ and population‐level foraging behaviour by applying δ13C and δ15N stable isotope analysis to hair samples from 183 vampire bats captured from nine colonies in Peru. We also assessed the isotopic distributions of realized prey by analysing blood meals extracted from engorged bats and samples collected from potential prey species. In two adjacent but contrasting areas of the Amazon with scarce and abundant livestock, we used questionnaires to evaluate the incidence of feeding on humans.

Population‐level isotopic signatures suggested substantial among‐site variation in feeding behaviour, including reliance on livestock in some colonies and feeding on combinations of domestic and wild prey in others. Isotopic heterogeneity within bat colonies was among the largest recorded in vertebrate populations, indicating that individuals consistently fed on distinct prey resources and across distinct trophic levels. In some sites, isotopic values of realized prey spanned broad ranges, suggesting that bats with intermediate isotopic values could plausibly be dietary specialists rather than generalists.

Bayesian estimates of isotopic niche width varied up to ninefold among colonies and were maximized where wildlife and livestock were present at low levels, but declined with greater availability of livestock. In the Amazon, the absence of livestock was associated with feeding on humans and wildlife.

Policy implications. We provide the first insights into the foraging behaviour of vampire bats in habitats with common depredation on humans and show how vampire bat foraging may respond to land‐use change. Our results demonstrate risks of rabies transmission from bats to other wildlife and are consistent with the hypothesis that introducing livestock might reduce the burden of human rabies in high‐risk communities.
Caesarean section rates and adverse neonatal outcomes after induction of labour versus expectant management in women with an unripe cervix: a secondary analysis of the HYPITAT and DIGITAT trials
Authors: Bernardes TP , Broekhuijsen K , Koopmans CM , Boers KE , van Wyk L , Tajik P , van Pampus MG , Scherjon SA , Mol BW , Franssen MT , van den Berg PP , Groen H
Published: May 2016

Objective

To evaluate caesarean section and adverse neonatal outcome rates after induction of labour or expectant management in women with an unripe cervix at or near term.

Design

Secondary analysis of data from two randomised clinical trials.

Setting

Data were collected in two nationwide Dutch trials.

Population

Women with hypertensive disease (HYPITAT trial) or suspected fetal growth restriction (DIGITAT trial) and a Bishop score ≤6.

Methods

Comparison of outcomes after induction of labour and expectant management.

Main outcome measures

Rates of caesarean section and adverse neonatal outcome, defined as 5‐minute Apgar score ≤6 and/or arterial umbilical cord pH <7.05 and/or neonatal intensive care unit admission and/or seizures and/or perinatal death.

Results

Of 1172 included women with an unripe cervix, 572 had induction of labour and 600 had expectant management. We found no significant difference in the overall caesarean rate (difference −1.1%, 95% CI −5.4 to 3.2). Induction of labour did not increase caesarean rates in women with Bishop scores from 3 to 6 (difference −2.7%, 95% CI −7.6 to 2.2) or adverse neonatal outcome rates (difference −1.5%, 95% CI −4.3 to 1.3). However, there was a significant difference in the rates of arterial umbilical cord pH <7.05 favouring induction (difference −3.2%, 95% CI −5.6 to −0.9). The number needed to treat to prevent one case of umbilical arterial pH <7.05 was 32.

Conclusions

We found no evidence that induction of labour increases the caesarean rate or compromises neonatal outcome as compared with expectant management. Concerns over increased risk of failed induction in women with a Bishop score from 3 to 6 seem unwarranted.

Tweetable abstract

Induction of labour at low Bishop scores does not increase caesarean section rate or poor neonatal outcome.
The Potential Implications of a Brexit for Future EU Agri‐food Policies
Authors: Matthews Alan
Published: May 2016

This article examines the implications of a possible Brexit for the EU's Common Agricultural Policy and agri‐food sector. Five potential ways in which these implications might be felt are discussed: (1) implications for the future orientation of the CAP in the absence of the UK; (2) implications for the EU budget and the share devoted to the CAP; (3) implications for the future regulatory environment for EU farm and food businesses; (4) implications for agricultural research; and (5) implications for future EU trade and trade relationships. Because the UK is a net contributor to the EU budget, a net importer of agri‐food products from the EU, and punches above its weight in research terms, its withdrawal would have broadly negative effects for the EU farm and food sector. Whether the absence of the UK's voice in the Council of Ministers when discussing future agricultural, trade and regulatory policies would be counted as positive or negative depends on one's policy preferences in these areas. For those advocating a market‐oriented agricultural policy and a regulatory regime strongly anchored in science its withdrawal would be a loss.
Brexit: Breaking Away – Would it Pay?
Authors: Jongeneel Roel , van Berkum Siemen , Vrolijk Hans
Published: May 2016

In the event of a Brexit the UK would have to redefine its trade relationship with the EU and develop its own agricultural policy. We analyse the impacts of a UK–EU Free Trade Arrangement (FTA); a WTO MFN tariff rates scenario; and a UK Trade Liberalisation scenario (UK TL). In each scenario the effects of three different levels of direct payments to farmers are estimated: current levels, 50 per cent reduction and no direct payments. In the FTA and WTO scenarios, UK prices for agricultural products would increase due to the higher trade facilitation costs and the UK's loss of access to EU preferential import regimes, with positive impacts on producers but negative on consumers or users. In the UK TL scenario, prices for animal products tend to decline, while crop prices show an increase relative to the status quo. The effects on farm incomes reflect these changes in prices but incomes ultimately are strongly dependent on choice of agricultural policy with regard to direct payments. Full abolition of direct payments generally more than offsets the positive effects of output price increases on farm incomes. Direct payments of 50 per cent of current levels have more diverse impacts on farm incomes.
Change in Flavonoid Composition and Antioxidative Activity during Fermentation of Onion (Allium cepa L.) by Leuconostoc mesenteroides with Different Salt Concentrations
Authors: Lee Yu Geon , Cho Jeong‐Yong , Kim Young‐Min , Moon Jae‐Hak
Published: May 2016

The aim of this study is to investigate the change in flavonoid composition and antioxidative activity during fermentation of onion (Allium cepa L.) by Leuconostoc mesenteroides with different NaCl concentrations. In order to qualify and quantify the flavonoids during fermentation of onion, 7 flavonoids, [quercetin 3,7‐O‐β‐d‐diglucopyranoside (Q3,7G), quercetin 3,4′‐O‐β‐d‐diglucopyranoside (Q3,4′G), quercetin 3‐O‐β‐d‐glucopyranoside (Q3G), quercetin 4′‐O‐β‐d‐glucopyranoside (Q4′G), isorhamnetin 3‐O‐β‐d‐glucopyranoside (IR3G), quercetin (Q), and isorhamnetin (IR)], were isolated and identified from onion. During fermentation, the contents of flavonoid glucosides (Q3,7G, Q3,4′G, Q3G, Q4′G, and IR3G) gradually decreased, whereas the contents of flavonoid aglycones (Q, IR) gradually increased. Decline rates of the flavonoid glucosides increased with the addition of L. mesenteroides. Furthermore, the activity of β‐glucosidase, which is produced by L. mesenteroides, is dose‐dependently inhibited with different NaCl concentrations during fermentation. The presence of L. mesenteroides enhanced the antioxidative activity of onion as demonstrated using the 1,1‐diphenyl‐2‐picrylhydrazyl, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), and reducing power assays. The enhancement of antioxidative activity was considered because the content of flavonoid aglycones increased during fermentation. However, the addition of NaCl may decrease the antioxidative activity; we surmise that this phenomenon occurs because of the inhibition of β‐glucosidase by NaCl. Therefore, we conclude that the addition of NaCl may be useful for the regulation of antioxidative activity via the control of β‐glucosidase action, during the fermentation of flavonoid glucoside‐rich foods.
Economic evaluation of single‐fraction versus multiple‐fraction palliative radiotherapy for painful bone metastases in breast, lung and prostate cancer
Authors: Collinson Lucie , Kvizhinadze Giorgi , Nair Nisha , McLeod Melissa , Blakely Tony
Published: May 2016

Introduction

Single‐ and multiple‐fraction external beam radiotherapy (SFX‐EBRTandMFX‐EBRT) are palliative treatment options for localized metastatic bone pain.MFXis the preferred choice in many developed countries. Evidence shows little difference in how effectivelySFXandMFXreduce pain. However,SFXis associated with higher retreatment and (in one meta‐analysis) pathological fracture rates.MFXis, however, more time‐consuming and expensive. We estimated the cost‐effectiveness ofSFXversusMFXfor metastatic bone pain in breast, prostate and lung cancer in New Zealand.

Methods

We constructed a Markov microsimulation model to estimate health gain (in quality‐adjusted life‐years orQALYs), health system costs (in real 2011NZdollars) and cost‐effectiveness. The model was populated using effect estimates from randomized controlled trials and other studies, and New Zealand cancer and cost data. Disability weights from the 2010 Global Burden of Disease study were used in estimatingQALYs.

Results

Across all three cancers,QALYgains were similar forSFXcompared toMFX, and per patient costs were less forSFXthanMFX, with a difference ofNZ$1469 (95% uncertainty interval $1112 to $1886) for lung cancer, $1316 ($810 to $1854) for prostate cancer and $1344 ($855 to $1846) for breast cancer. Accordingly, from a cost‐effectiveness perspective,SFXwas the preferable treatment option. Various sensitivity analyses did not overturn the clear preference forSFX.

Conclusion

For all three cancers,SFXwas clearly more cost‐effective thanMFX. This adds to the case for desisting from offeringMFXto patients with metastatic bone pain, from a cost‐effectiveness angle.
Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep
Authors: Carotenuto M , Esposito M , Cortese S , Laino D , Verrotti A
Published: May 2016

Aim

Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls.

Methods

We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers.

Results

Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001).

Conclusion

Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.
Morphometry of skeletal muscle capillaries: the relationship between capillary ultrastructure and ageing in humans
Authors: Bigler M. , Koutsantonis D. , Odriozola A. , Halm S. , Tschanz S. A. , Zakrzewicz A. , Weichert A. , Baum O.
Published: May 2016

Aim

To determine whether the ultrastructure of the capillary system in human skeletal muscle changes during advancing senescence, we evaluated the compartmental and subcompartmental organization of capillaries from vastus lateralis muscle (VL) biopsies of 41 non‐diseased persons aged 23–75 years.

Methods

From each VL biopsy, 38–40 randomly selected capillaries were assessed by transmission electron microscopy and subsequent morphometry with a newly established tablet‐based image analysis technique.

Results

Quantification of the compartmental organization revealed most indicators of the capillary ultrastructure to be only non‐significantly altered (P > 0.05) over age. However, the peri‐capillary basement membrane (BM) was thicker in the older participants than in the younger ones (P ≤ 0.05). Regression analysis revealed a bipartite relationship between the two parameters: a homogenous slight increase in BM thickness up to the age of approximately 50 years was followed by a second phase with more scattered BM thickness values. In 44.5% of the capillary profiles, projections/filopodia of the pericytes (PCs) traversed the BM and invaded endothelial cells (ECs) visible as PC pegs in pale cytoplasm holes (EC sockets). Strikingly, PC pegs were often in proximity to the EC nucleus. In PC profiles, sockets were likewise detected in 14.2% of the capillaries. Within these PC sockets, cellular profiles were frequently seen, which could be assigned to EC filopodia, internal PC curling or PC–PC interactions. Quantification of the occurrence of peg–socket junctions revealed the proportions of empty EC sockets and empty PC sockets to increase (P ≤ 0.05) during ageing.

Conclusion

Our investigation demonstrates advancing senescence to be associated with increase in BM thickness and loss of EC and PC filopodia length in skeletal muscle capillaries.
Human UDP‐Glucuronosyltransferases 1A1, 1A3, 1A9, 2B4 and 2B7 are Inhibited by Diethylstilbestrol
Authors: Zhu Liangliang , Xiao Ling , Li Wenjuan , Zhang Yuan , Han Wenwen , Zhu Yu , Ge Guangbo , Yang Ling
Published: May 2016

Inhibition of UDP‐glucuronosyltransferases (UGTs) can result in many undesired side effects. Diethylstilbestrol (DES), a synthetic oestrogen famous for its multiple toxicities, was once widely administered to women in high dosages and now still gains application in clinics. This study investigated in vitro inhibitory effects of DES on catalytic activities of human UGTs, aiming at disclosing new potential toxic mechanisms on the basis of interactions between DES and metabolizing enzymes. DES (10 μM) could decrease activities of UGT1A1, 1A3, 1A9, 2B4 and 2B7 in catalysing 4‐methylumbelliferone (4‐Mu) glucuronidation. Further kinetic analyses showed that inhibition of these UGTs followed competitive (UGT1A1 and 1A9), mixed (UGT1A3 and 2B4) and non‐competitive (UGT2B7) mechanisms, with Ki values ranging from 0.91 to 4.1 μM. The inhibition potentials of UGT1A9 and 2B7 in human liver microsomes (HLM) were further tested by employing propofol and zidovudine as probe substrates, respectively. The inhibition of human liver microsomal UGT1A9 followed mixed mechanism, with the Ki value of 3.5 μM and α of 4.1. On the other hand, DES displayed non‐competitive inhibition against UGT2B7 in HLM, with the Ki value of 9.8 μM. The risks of in vivo inhibition of human UGTs were also predicted by calculation of plasma C/Ki values. Results suggest that DES can trigger in vivo inhibition of UGT1A1, 1A3, 1A9, 2B4 and 2B7 after the intravenous administration in high doses.
Comparative analysis between RQ‐PCR and digital‐droplet‐PCR of immunoglobulin/T‐cell receptor gene rearrangements to monitor minimal residual disease in acute lymphoblastic leukaemia
Authors: Della Starza Irene , Nunes Vittorio , Cavalli Marzia , De Novi Lucia Anna , Ilari Caterina , Apicella Valerio , Vitale Antonella , Testi Anna Maria , Del Giudice Ilaria , Chiaretti Sabina , Foà Robin , Guarini Anna
Published: May 2016

Real‐time quantitative polymerase chain reaction (RQ‐PCR) is a standardized tool for minimal residual disease (MRD) monitoring in acute lymphoblastic leukaemia (ALL). The applicability of this technology is limited by the need of a standard curve based on diagnostic DNA. The digital droplet PCR (ddPCR) technology has been recently applied to various medical fields, but its use in MRD monitoring is under investigation. In this study, we analysed 50 ALL cases by both methods in two phases: in the first, we established analytical parameters to investigate the applicability of this new technique; in the second, we analysed MRD levels in 141 follow‐up (FU) samples to investigate the possible use of ddPCR for MRD monitoring in ALL patients. We documented that ddPCR has sensitivity and accuracy at least comparable to those of RQ‐PCR. Overall, the two methods gave concordant results in 124 of the 141 analysed MRD samples (88%, P = 0·94). Discordant results were found in 12% borderline cases.

The results obtained prove that ddPCR is a reliable method for MRD monitoring in ALL, with the advantage of quantifying without the need of the calibration curves. Its application in a cohort of patients with a longer FU will conclusively define its clinical predictive value.
Women on the edge: Workplace stress at universities in North America
Authors: Mountz Alison
Published: May 2016

Key Messages

There is an important, under‐explored relationship between deteriorating work conditions in the neoliberal university and the deteriorating well‐being and health of women working at universities.

Women faculty struggle with fertility, mental health and well‐being, and other physical manifestations of stress.

There are many strategies that universities, departments, and individuals can pursue to improve work conditions for all university faculty.
Cognitive Architecture of Belief Reasoning in Children and Adults: A Primer on the Two‐Systems Account
Authors: Low Jason , Apperly Ian A. , Butterfill Stephen A. , Rakoczy Hannes
Published: May 2016

Characterizing the cognitive architecture of human mindreading forces us to address two puzzles in people's attributions of belief: Why children show inconsistent expectations about others' belief‐based actions, and why adults' reasoning about belief is sometimes automatic and sometimes not. The seemingly puzzling data suggest that humans have many mindreading systems that use different models of mental representations. The efficient system is shared by infants, children, and adults, and uses a minimal model of the mind, which enables belief‐like states to be tracked. The flexible system develops late and uses a canonical model, which incorporates propositional attitudes. A given model's operation has signature limits that produce performance contrasts, in children as well as adults, between certain types of mindreading tasks.
NSD1 duplication in Silver–Russell syndrome (SRS): molecular karyotyping in patients with SRS features
Authors: Sachwitz J. , Meyer R. , Fekete G. , Spranger S. , Matulevičienė A. , Kučinskas V. , Bach A. , Luczay A. , Brüchle N.O. , Eggermann K. , Zerres K. , Elbracht M. , Eggermann T.
Published: May 2016

Silver–Russell syndrome (SRS) is a growth retardation syndrome characterized by intrauterine and postnatal growth retardation, relative macrocephaly and protruding forehead, body asymmetry and feeding difficulties. Nearly 50% of cases show a hypomethylation in 11p15.5, in 10% maternal uniparental disomy of chromosome 7 is present. A significant number of patients with SRS features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for SRS genetic testing by molecular karyotyping. Pathogenic variants could be detected in five of them, including a NSD1 duplication in 5q35 and a 14q32 microdeletion. NSD1 deletions are detectable in overgrowth disorders (Sotos syndrome and Beckwith–Wiedemann syndrome), whereas NSD1 duplications are associated with growth retardation. The 14q32 deletion is typically associated with Temple syndrome (TS14), but the identification of a patient in our cohort reflects the clinical overlap between TS14 and SRS. As determination of molecular subtypes is the basis for a directed counseling and therapy, the identification of pathogenic variants in >10% of the total cohort of patients referred for SRS testing and in >16% of characteristic individuals with the characteristic SRS phenotype confirms the need to apply molecular karyotyping in this cohort.
Tea tree oil: contact allergy and chemical composition
Authors: de Groot Anton C. , Schmidt Erich
Published: May 2016

In this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils,TTOhas caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercialTTOare terpinen‐4‐ol, γ‐terpinene, 1,8‐cineole, α‐terpinene, α‐terpineol,p‐cymene, and α‐pinene. FreshTTOis a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α‐terpinene, 1,2,4‐trihydroxymenthane, α‐phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused byTTOdepends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidizedTTO. Co‐reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mixI,Myroxylon pereirae, colophonium, and other essential oils.
Dealing with Cumulative Biodiversity Impacts in Strategic Environmental Assessment: A New Frontier for Conservation Planning
Authors: Whitehead Amy L. , Kujala Heini , Wintle Brendan A.
Published: May 2016

Biodiversity impact assessments under threatened species legislation often focus on individual development proposals at a single location, usually for a single species, leading to inadequate assessments of multiple impacts that accumulate over large spatial scales for multiple species. Regulations requiring ad‐hoc assessments can lead to “death by a thousand cuts,” where biodiversity is degraded by many small impacts that individually do not appear to threaten species’ persistence. Spatial prioritization methods can improve the efficiency of decision‐making by explicitly considering cumulative impacts of multiple proposed developments on multiple species over large spatial scales. We present an assessment approach and a unique case study in which spatial prioritization tools were used to support strategic assessment of a large development plan in Western Australia. The application of the approach helped identify relatively minor alterations to development plans that resulted in reductions in biodiversity impacts and informed expansion of the protected area network. Using these tools to assess trade‐offs between conservation and development will help identify planning footprints that minimize biodiversity losses.
Overweight and obesity: a remaining problem in women treated for severe gestational diabetes
Authors: Hildén K. , Hanson U. , Persson M. , Fadl H.
Published: May 2016

Aim

To analyse the impact of overweight and obesity on the risk of adverse maternal outcomes and fetal macrosomia in pregnancies of women treated for severe gestational diabetes.

Methods

This was a population‐based cohort study including all singleton pregnancies in Sweden without pre‐existing diabetes in the period 1998–2012. Only mothers with an early‐ pregnancy BMI of ≥ 18.5 kg/m² were included. Logistic regression analysis was used to determine odds ratios with 95% CIs for maternal outcomes and fetal growth. Analyses were stratified by maternal gestational diabetes/non‐gestational diabetes to investigate the impact of overweight/obesity in each group.

Results

Of 1 249 908 singleton births, 13 057 were diagnosed with gestational diabetes (1.0%). Overweight/obesity had the same impact on the risks of caesarean section and fetal macrosomia in pregnancies with and without gestational diabetes, but the impact of maternal BMI on the risk of preeclampsia was less pronounced in women with gestational diabetes. Normal‐weight women with gestational diabetes had an increased risk of caesarean section [odds ratio 1.26 (95% CI 1.16–1.37)], preeclampsia [odds ratio 2.03 (95% CI 1.71–2.41)] and large‐for‐gestational‐age infants [odds ratio 2.25 (95% CI 2.06–2.46)]. Risks were similar in the overweight group without gestational diabetes, caesarean section [odds ratio 1.34 (1.33–1.36)], preeclampsia odds ratio [1.76 (95% CI 1.72–1.81)], large‐for‐gestational‐age [odds ratio 1.76 (95% CI 1.74–1.79)].

Conclusions

Maternal overweight and obesity is associated with similar increments in risks of adverse maternal outcomes and delivery of large‐for‐gestational‐age infants in women with and without gestational diabetes. Obese women with gestational diabetes are defined as a high‐risk group. Normal‐weight women with gestational diabetes have similar risks of adverse outcomes to overweight women without gestational diabetes.
Portrayal of Skilled Migrants' Careers in Business and Management Studies: A Review of the Literature and Future Research Agenda
Authors: Crowley‐Henry Marian , O' Connor Edward , Al Ariss Akram
Published: May 2016

A systematic literature review in business and management studies was conducted, which paints a portrait of the existing literature on skilled migrants' host country career experiences. Core themes arising from this review are presented, including labeling inconsistency concerning the population (with researchers using terminology such as ‘skilled migrants,’ ‘immigrant professionals’ and ‘qualified immigrants’ interchangeably); the need for including skilled migrant managers and business professionals in research (rather than concentrating on lower‐level employment categories only); and a more relational, holistic realization of skilled migrants' careers (rather than the current literature's negative portrayal, propounding the image of migrants as exploited or under‐utilized). In underlining the gaps in the literature and research in this area, a research agenda is proposed. The review is relevant for individuals following careers in a foreign country; for organizations employing and developing the careers of internationally mobile employees; and for human resource management professionals supporting international employees.
Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia
Authors: Weckhuysen Sarah , Marsan Elise , Lambrecq Virginie , Marchal Cécile , Morin‐Brureau Mélanie , An‐Gourfinkel Isabelle , Baulac Michel , Fohlen Martine , Kallay Zetchi Christine , Seeck Margitta , de la Grange Pierre , Dermaut Bart , Meurs Alfred , Thomas Pierre , Chassoux Francine , Leguern Eric , Picard Fabienne , Baulac Stéphanie
Published: May 2016

Objective

The discovery of mutations in DEPDC5 in familial focal epilepsies has introduced a novel pathomechanism to a field so far dominated by ion channelopathies. DEPDC5 is part of a complex named GAP activity toward RAGs (GATOR) complex 1 (GATOR1), together with the proteins NPRL2 and NPRL3, and acts to inhibit the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway. GATOR1 is in turn inhibited by the GATOR2 complex. The mTORC1 pathway is a major signaling cascade regulating cell growth, proliferation, and migration. We aimed to study the contribution of GATOR complex genes to the etiology of focal epilepsies and to describe the associated phenotypical spectrum.

Methods

We performed targeted sequencing of the genes encoding the components of the GATOR1 (DEPDC5, NPRL2, and NPRL3) and GATOR2 (MIOS, SEC13, SEH1L, WDR24, and WDR59) complex in 93 European probands with focal epilepsy with or without focal cortical dysplasia. Phospho‐S6 immunoreactivity was used as evidence of mTORC1 pathway activation in resected brain tissue of patients carrying pathogenic variants.

Results

We identified four pathogenic variants in DEPDC5, two in NPRL2, and one in NPRL3. We showed hyperactivation of the mTORC1 pathway in brain tissue from patients with NPRL2 and NPRL3 mutations. Collectively, inactivating mutations in GATOR1 complex genes explained 11% of cases of focal epilepsy, whereas no pathogenic mutations were found in GATOR2 complex genes. GATOR1‐related focal epilepsies differ clinically from focal epilepsies due to mutations in ion channel genes by their association with focal cortical dysplasia and seizures emerging from variable foci, and might confer an increased risk of sudden unexplained death in epilepsy (SUDEP).

Significance

GATOR1 complex gene mutations leading to mTORC1 pathway upregulation is an important cause of focal epilepsy with cortical malformations and represents a potential target for novel therapeutic approaches.
Passerines may be sufficiently plastic to track temperature‐mediated shifts in optimum lay date
Authors: Phillimore Albert B. , Leech David I. , Pearce‐Higgins James W. , Hadfield Jarrod D.
Published: May 2016

Projecting the fates of populations under climate change is one of global change biology's foremost challenges. Here, we seek to identify the contributions that temperature‐mediated local adaptation and plasticity make to spatial variation in nesting phenology, a phenotypic trait showing strong responses to warming. We apply a mixed modeling framework to a Britain‐wide spatiotemporal dataset comprising >100 000 records of first egg dates from four single‐brooded passerine bird species. The average temperature during a specific time period (sliding window) strongly predicts spatiotemporal variation in lay date. All four species exhibit phenological plasticity, advancing lay date by 2–5 days °C−1. The initiation of this sliding window is delayed further north, which may be a response to a photoperiod threshold. Using clinal trends in phenology and temperature, we are able to estimate the temperature sensitivity of selection on lay date (B), but our estimates are highly sensitive to the temporal position of the sliding window. If the sliding window is of fixed duration with a start date determined by photoperiod, we findBis tracked by phenotypic plasticity. If, instead, we allow the start and duration of the sliding window to change with latitude, we find plasticity does not trackB, although in this case, at odds with theoretical expectations, our estimates ofBdiffer across latitude vs. longitude. We argue that a model combining photoperiod and mean temperature is most consistent with current understanding of phenological cues in passerines, the results from which suggest that each species could respond to projected increases in spring temperatures through plasticity alone. However, our estimates ofBrequire further validation.
Climate change amplifies gross nitrogen turnover in montane grasslands of Central Europe in both summer and winter seasons
Authors: Wang Changhui , Chen Zhe , Unteregelsbacher Sebastian , Lu Haiyan , Gschwendtner Silvia , Gasche Rainer , Kolar Allison , Schloter Michael , Kiese Ralf , Butterbach‐Bahl Klaus , Dannenmann Michael
Published: May 2016

The carbon‐ and nitrogen‐rich soils of montane grasslands are exposed to above‐average warming and to altered precipitation patterns as a result of global change. To investigate the consequences of climatic change for soil nitrogen turnover, we translocated intact plant–soil mesocosms along an elevational gradient, resulting in an increase of the mean annual temperature by approx. 2 °C while decreasing precipitation from approx. 1500 to 1000 mm. Following three years of equilibration, we monitored the dynamics of gross nitrogen turnover and ammonia‐oxidizing bacteria (AOB) and archaea (AOA) in soils over an entire year. Gross nitrogen turnover and gene levels of AOB and AOA showed pronounced seasonal dynamics. Both summer and winter periods equally contributed to cumulative annual N turnover. However, highest gross N turnover and abundance of ammonia oxidizers were observed in frozen soil of the climate change site, likely due to physical liberation of organic substrates and their rapid turnover in the unfrozen soil water film. This effect was not observed at the control site, where soil freezing did not occur due to a significant insulating snowpack. Climate change conditions accelerated gross nitrogen mineralization by 250% on average. Increased N mineralization significantly stimulated gross nitrification by AOB rather than by AOA. However, climate change impacts were restricted to the 2–6 cm topsoil and rarely occurred at 12–16 cm depth, where generally much lower N turnover was observed. Our study shows that significant mineralization pulses occur under changing climate, which is likely to result in soil organic matter losses with their associated negative impacts on key soil functions. We also show that N cycling processes in frozen soil can be hot moments for N turnover and thus are of paramount importance for understanding seasonal patterns, annual sum of N turnover and possible climate change feedbacks.
Evaluating confidence in climate‐based predictions of population change in a migratory species
Authors: Saunders Sarah P. , Ries Leslie , Oberhauser Karen S. , Zipkin Elise F.
Published: May 2016

Aim

Forecasting ecological responses to climate change is a common objective, but there are few methods for evaluating confidence in such predictions. For migratory species, in particular, it is also essential to consider the extent of spatial synchrony among separate breeding populations in range‐wide predictions. We develop a quantitative method to evaluate the accuracy of climate‐based ecological predictions and use this approach to assess the extent of spatio‐temporal synchrony among distinct regions within the breeding range of a single migratory population.

Location

We model weekly site‐specific summer abundances (1996–2011) of monarch butterflies (Danaus plexippus) in the Midwestern USA as a function of climate conditions experienced during a shared spring migration/breeding phase in Texas and separate summer recruitment periods in Ohio and Illinois.

Methods

Using negative binomial regression models, we evaluate spatio‐temporal synchrony between monarchs in the two states and develop a novel quantitative assessment approach to determine the temporal predictive strength of our model with BayesianP‐values.

Results

Monarchs breeding in the Midwest exhibit spatio‐temporal synchrony in Ohio and Illinois; cooler spring temperatures, average to above average precipitation in Texas and cooler than average summer temperatures are associated with higher population abundances in both states. At least 10 years of data are needed for adequate model predictability of average future counts. Because annual spring weather conditions in Texas primarily drive yearly abundances, as opposed to localized summer effects, year‐specific counts are often difficult to predict reliably, specifically when predictive spring conditions are outside the range of typical regional conditions.

Main conclusions

Our assessment method can be used in similar analyses to more confidently interpret ecological responses to climate change. Our results demonstrate the relative importance of climatic drivers in predicting abundances of a migratory species and the difficulties in producing reliable predictions of animal populations in the face of climate change.
Serum antinuclear antibody in adult Thais
Authors: Prapinjumrune Chanwit , Prucktrakul Chalakorn , Sooktonglarng Trakarn , Thongprasom Kobkan
Published: May 2016

Objective

This study investigated the presence of antinuclear antibody (ANA) in older Thais compared with middle‐age and younger participants.

Background

Antinuclear antibody represents the first step in the diagnostic testing for lupus erythematosus (LE) and other autoimmune diseases. Due to the lack of reference ANA levels in older, middle‐age and younger Thais healthy participants, this study will be useful for determining the proper diagnostic and treatment criteria.

Methods

There were 28 older (60–76 years), 17 middle‐age (41–59 years) and 13 younger (24–40 years) participants in this study. Immunofluorescence was performed to analyse the ANA staining pattern and titre levels in the participants' blood samples.

Results

The presence of serum ANA was found in 18 of 28 cases (64.3%), four of 17 (23.5%) and one of 13 cases (7.7%) of the older, middle‐age and younger participants, respectively. The difference in the number of serum ANA‐positive participants between the older, middle‐age and younger groups was statistically significant (p < 0.05). Interestingly, the ANA positive in older participants presented more than one staining pattern. The speckled pattern was the most commonly detected ANA staining pattern in the older group, being found in 12 cases followed by cytoplasmic pattern (10 cases), homogeneous pattern (nine cases) and nucleolar pattern (five cases). In the middle‐age group, the speckled pattern was found in four cases, whereas one younger participant presented a nucleolar pattern.

Conclusion

Serum ANA positive was significantly higher in the older group compared with the middle‐age and younger groups. There were variations of the serum ANA staining patterns in the older group.
Routine Anti‐Helicobacter Immunohistochemical Staining is Significantly Superior to Reflex Staining Protocols for the Detection of Helicobacter in Gastric Biopsy Specimens
Authors: Lash Richard H. , Genta Robert M.
Published: May 2016

Background

The role of special stains in the detection of H. pylori is controversial; some pathologists claim that hematoxylin and eosin staining alone is adequate to detect bacteria, while others maintain that immunohistochemical staining must be used on all gastric biopsies. This study was designed to test the hypothesis that hematoxylin and eosin and histochemical special stains have similar sensitivity and that immunohistochemical staining only marginally enhances the detection rate of the organisms.

Materials and Methods

Records of all gastric biopsies examined in a large pathology laboratory between January 1, 2010 and December 31, 2014 were extracted and stratified according to the stain used for the detection of Helicobacter (1. hematoxylin and eosin only; 2. Upfront HP Blue; 3. Upfront HP Blue including reflex immunohistochemistry; 4. Upfront anti‐Helicobacter immunohistochemical staining.

Results

Gastric biopsies from 794,859 endoscopies obtained from 622,945 unique patients were analyzed. The basic demographics of the patients in different staining groups were identical. A total of 56,955 gastric biopsy sets were stained with histochemical stains only, and 731,193 with anti‐Helicobacter immunohistochemical stain; in 4409 of these, an immunohistochemical stain was also performed. In 2302 cases, only hematoxylin and eosin were performed. In this latter group, 7.0% of patients were Helicobacter‐positive; in the upfront HP Blue, the prevalence was 7.8%, whereas patients with upfront immunohistochemistry had a prevalence of 10.2% (p < .0001, compared to hematoxylin and eosin only).

Conclusions

There was a dramatic improvement in detection of H. pylori infection through the use of upfront immunohistochemical stains. Therefore, we contend that the routine use of IHC for all gastric biopsies is an appropriate protocol to ensure that every patient gets the right answer.
Efficacy and safety of entecavir versus tenofovir treatment in chronic hepatitis B patients: A randomized controlled trial
Authors: Sriprayoon Tassanee , Mahidol Chulabhorn , Ungtrakul Teerapat , Chun‐on Pattra , Soonklang Kamonwan , Pongpun Wanvisa , Laohapand Charlie , Dechma Jiraporn , Pothijaroen Charinthip , Auewarakul Chirayu , Tanwandee Tawesak
Published: May 2016

Aim

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are considered among the most potent antiviral agents for the treatment of chronic hepatitis B infection. We aimed to compare treatment efficacy and safety of ETV and TDF in nucleoside‐naïve chronic hepatitis B patients.

Methods

Inclusion criteria were compensated chronic hepatitis B patients who were either hepatitis B e antigen (HBeAg)‐positive or HBeAg‐negative. Exclusion criteria were co‐infection with hepatitis C virus and/or HIV, concurrent malignancy, and decompensated cirrhosis. Virological, biochemical, and serological end‐points at week 96 and 144 were compared. Of 400 patients, 200 patients received ETV and 200 received TDF.

Results

There were no significant differences between the two groups in baseline characteristics including age (41.6 ± 11.5 vs. 41.2 ± 11.6, mean baseline hepatitis B virus DNA (5.91 ± 1.79 vs. 5.94 ± 1.68 log10 IU/mL), mean baseline alanine aminotransferase (68.1 ± 64.1 vs. 76.8 ± 79.8 U/L), and cirrhosis (15.5% vs. 14.5%). At week 144 of treatment, 91 and 94% of the ETV and TDF groups, respectively, achieved undetectable hepatitis B virus DNA. In HBeAg‐positive patients, HBeAg seroconversion could be achieved in 27.4% and 33.7% at week 144 for ETV and TDF groups, respectively. Quantitative hepatitis B surface antigen dropped significantly over 144 weeks of treatment period but only 1.0 to 1.5% experienced hepatitis B surface antigen loss. Safety profiles were consistent with previous reports of monotherapy.

Conclusion

Both ETV and TDF showed potent antiviral activity against hepatitis B. Either ETV or TDF can be recommended as a treatment of choice for patients with chronic hepatitis B. Both drugs were safe and well tolerated.
Antioxidant, immunomodulatory and antiproliferative effects of gelatin hydrolysates from seabass (Lates calcarifer) skins
Authors: Sae‐leaw Thanasak , O'Callaghan Yvonne C. , Benjakul Soottawat , O'Brien Nora M.
Published: May 2016

This study investigated the antioxidant, immunomodulatory and antiproliferative potentials of gelatin hydrolysates from seabass skins in cell model systems. Gelatin hydrolysates were extracted from seabass skins using different processes and enzyme concentrations. The ability of the hydrolysates to protect against H2O2‐induced DNA damage was assessed on U937 cells using the Comet assay, and one of the samples showed DNA protective effects. All samples showed immunomodulatory potential by significantly (P < 0.05) reducing interleukin‐6 (IL‐6) and IL‐1β production in lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cells. Antiproliferative activities of seabass skin hydrolysates were measured using human colon cancer (Caco‐2) and liver cancer (HepG2) cell lines as the model cell cultures. The inhibition of cell proliferation of Caco‐2 and HepG2 cancer cells occurred in a dose‐dependent manner at concentrations of 1–25 mg mL−1. Therefore, seabass skin hydrolysates prepared using an appropriate process could serve as a potential functional food ingredient with various health benefits.
Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model
Authors: Hata Junya , Satoh Yuichi , Akaihata Hidenori , Hiraki Hiroyuki , Ogawa Soichiro , Haga Nobuhiro , Ishibashi Kei , Aikawa Ken , Kojima Yoshiyuki
Published: May 2016

Objectives

To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model.

Methods

Fetal urogenital sinus isolated from 20‐day‐old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time‐dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole‐genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation).

Results

Microarray analyses showed 926 upregulated (>2‐fold change, P < 0.01) and 3217 downregulated genes (<0.5‐fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10−4), response to stimulus (163 genes, P = 7.37 × 10−13) and growth (32 genes, P = 1.93 × 10−5). When we used both normal prostate and non‐transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia‐specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin‐1, interleukin‐2 and interleukin‐5 signaling pathways, KIT signaling pathway, and secretin‐like G‐protein‐coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated.

Conclusion

Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment.
Mechanism of Nanovoid Formation at the ZnO–Glass Interface in Planar Multilayered Structures of AlOx–ZnO–Glass
Authors: Yoon Hong , Lee Hyun Hee , Ahn Yong Nam , Choi Eun‐Ho , Lee Jooyoung , Kim Hyunbin
Published: May 2016

Functional porous materials require easy fabrication methods with controllability of a wide range of pore size and its density for practical applications including optical devices. The Kirkendall effect based on unbalanced material diffusion provides such a possibility in conjunction with material configurations of multilayers. This study reports a formation of nanoscale pores within ZnO films in planar multilayered structures of Al2O3–ZnO‐aluminosilicate glass and demonstrates the mechanism of forming relatively large nanopores in ZnO near the ZnO–glass interface via stress‐promoted Kirkendall diffusion. Experimental characterizations supported by atomic simulation reveal that an enhanced in‐plane tensile stress in the ZnO films with increasing the thickness of the neighboring Al2O3 films can promote the diffusivity of the Zn atoms and the pore growth in the ZnO films. The pore size and location in the intermediate ZnO layer of the Al2O3–ZnO–glass is alterable by simply selecting the thickness of the Al2O3 layer. Promoted diffusion of the Zn atoms enables to fabricate porous planar ZnO films with pore sizes up to a few hundred nm with an enhanced light scattering ability. These findings offer a promising route to produce porous planar films through in‐depth understanding of diffusivity enhancement in glass–metal oxide couples.