bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the difference made by conservation initiatives: protected areas and their environmental and social impacts
Authors: Ferraro Paul J. , Pressey Robert L.
Published: October 2015

Success in conservation depends on our ability to reduce human pressures in areas that harbour biological diversity and ecosystem services. Legally protecting some of these areas through the creation of protected areas is a key component of conservation efforts globally. To develop effective protected area networks, practitioners need credible, scientific evidence about the degree to which protected areas affect environmental and social outcomes, and how these effects vary with context. Such evidence has been lacking, but the situation is changing as conservation scientists adopt more sophisticated research designs for evaluating protected areas' past impacts and for predicting their future impacts. Complementing these scientific advances, conservation funders and practitioners are paying increasing attention to evaluating their investments with more scientifically rigorous evaluation designs. This theme issue highlights recent advances in the science of protected area evaluations and explores the challenges to developing a more credible evidence base that can help societies achieve their goals of protecting nature while enhancing human welfare.
Measuring benefits of protected area management: trends across realms and research gaps for freshwater systems
Authors: Adams Vanessa M. , Setterfield Samantha A. , Douglas Michael M. , Kennard Mark J. , Ferdinands Keith
Published: October 2015

Protected areas remain a cornerstone for global conservation. However, their effectiveness at halting biodiversity decline is not fully understood. Studies of protected area benefits have largely focused on measuring their impact on halting deforestation and have neglected to measure the impacts of protected areas on other threats. Evaluations that measure the impact of protected area management require more complex evaluation designs and datasets. This is the case across realms (terrestrial, freshwater, marine), but measuring the impact of protected area management in freshwater systems may be even more difficult owing to the high level of connectivity and potential for threat propagation within systems (e.g. downstream flow of pollution). We review the potential barriers to conducting impact evaluation for protected area management in freshwater systems. We contrast the barriers identified for freshwater systems to terrestrial systems and discuss potential measurable outcomes and confounders associated with protected area management across the two realms. We identify key research gaps in conducting impact evaluation in freshwater systems that relate to three of their major characteristics: variability, connectivity and time lags in outcomes. Lastly, we use Kakadu National Park world heritage area, the largest national park in Australia, as a case study to illustrate the challenges of measuring impacts of protected area management programmes for environmental outcomes in freshwater systems.
The good, the bad and the ugly of marine reserves for fishery yields
Authors: De Leo Giulio A. , Micheli Fiorenza
Published: October 2015

Marine reserves (MRs) are used worldwide as a means of conserving biodiversity and protecting depleted populations. Despite major investments in MRs, their environmental and social benefits have proven difficult to demonstrate and are still debated. Clear expectations of the possible outcomes of MR establishment are needed to guide and strengthen empirical assessments. Previous models show that reserve establishment in overcapitalized, quota-based fisheries can reduce both catch and population abundance, thereby negating fisheries and even conservation benefits. By using a stage-structured, spatially explicit stochastic model, we show that catches under quota-based fisheries that include a network of MRs can exceed maximum sustainable yield (MSY) under conventional quota management if reserves provide protection to old, large spawners that disproportionally contribute to recruitment outside the reserves. Modelling results predict that the net fishery benefit of MRs is lost when gains in fecundity of old, large individuals are small, is highest in the case of sedentary adults with high larval dispersal, and decreases with adult mobility. We also show that environmental variability may mask fishery benefits of reserve implementation and that MRs may buffer against collapse when sustainable catch quotas are exceeded owing to stock overestimation or systematic overfishing.
Measuring impact of protected area management interventions: current and future use of the Global Database of Protected Area Management Effectiveness
Authors: Coad Lauren , Leverington Fiona , Knights Kathryn , Geldmann Jonas , Eassom April , Kapos Valerie , Kingston Naomi , de Lima Marcelo , Zamora Camilo , Cuardros Ivon , Nolte Christoph , Burgess Neil D. , Hockings Marc
Published: October 2015

Protected areas (PAs) are at the forefront of conservation efforts, and yet despite considerable progress towards the global target of having 17% of the world's land area within protected areas by 2020, biodiversity continues to decline. The discrepancy between increasing PA coverage and negative biodiversity trends has resulted in renewed efforts to enhance PA effectiveness. The global conservation community has conducted thousands of assessments of protected area management effectiveness (PAME), and interest in the use of these data to help measure the conservation impact of PA management interventions is high. Here, we summarize the status of PAME assessment, review the published evidence for a link between PAME assessment results and the conservation impacts of PAs, and discuss the limitations and future use of PAME data in measuring the impact of PA management interventions on conservation outcomes. We conclude that PAME data, while designed as a tool for local adaptive management, may also help to provide insights into the impact of PA management interventions from the local-to-global scale. However, the subjective and ordinal characteristics of the data present significant limitations for their application in rigorous scientific impact evaluations, a problem that should be recognized and mitigated where possible.
Impact evaluation to communicate and improve conservation non-governmental organization performance: the case of Conservation International
Authors: McKinnon Madeleine C. , Mascia Michael B. , Yang Wu , Turner Will R. , Bonham Curan
Published: October 2015

The rising prominence of more rigorous approaches to measuring conservation outcomes has included greater adoption of impact evaluation by conservation non-governmental organizations (CNGOs). Within the scientific literature, however, little consideration has been given to the unique and specific roles of CNGOs in advancing impact evaluation. We explore these issues in the context of one CNGO—Conservation International (CI)—and its experiences producing, using and funding impact evaluations over the past decade. We examine the contributions of impact evaluation to CI's mission at three different stages of CI's strategy: innovation, demonstration and amplification. Furthermore, we review incentives and barriers encountered by CI in its 10+ years' experience in impact evaluation. More coordinated and strategic use of impact evaluation by CNGOs would facilitate learning and promote accountability across the conservation community.
Socio-economic and ecological impacts of global protected area expansion plans
Authors: Visconti Piero , Bakkenes Michel , Smith Robert J. , Joppa Lucas , Sykes Rachel E.
Published: October 2015

Several global strategies for protected area (PA) expansion have been proposed to achieve the Convention on Biological Diversity's Aichi target 11 as a means to stem biodiversity loss, as required by the Aichi target 12. However, habitat loss outside PAs will continue to affect habitats and species, and PAs may displace human activities into areas that might be even more important for species persistence. Here we measure the expected contribution of PA expansion strategies to Aichi target 12 by estimating the extent of suitable habitat available for all terrestrial mammals, with and without additional protection (the latter giving the counterfactual outcome), under different socio-economic scenarios and consequent land-use change to 2020. We found that expanding PAs to achieve representation targets for ecoregions under a Business-as-usual socio-economic scenario will result in a worse prognosis than doing nothing for more than 50% of the world's terrestrial mammals. By contrast, targeting protection towards threatened species can increase the suitable habitat available to over 60% of terrestrial mammals. Even in the absence of additional protection, an alternative socio-economic scenario, adopting progressive changes in human consumption, leads to positive outcomes for mammals globally and to the largest improvements for wide-ranging species.
Coevolutionary landscape inference and the context-dependence of mutations in beta-lactamase TEM-1
Authors: Figliuzzi M. , Jacquier H. , Schug A. , Tenaillon O. , Weigt M.
Published: October 2015

The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared to recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared to approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20 from the mutated site, reaching thus far beyond residues in direct physical contact.
Projection-specific visual feature encoding by layer 5 cortical subnetworks
Authors: Lur Gyorgy , Vinck Martin A. , Tang Lan , Cardin Jessica A. , Higley Michael J.
Published: October 2015

Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives distinct versions of sensory information. We usedin vivocalcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex. While there is overlap across the groups, on average corticotectal (CT) cells exhibit lower contrast thresholds and broader tuning for orientation and spatial frequency in comparison to corticostriatal (CS) cells, while corticocortical (CC) cells have intermediate properties. Noise correlational analyses support the hypothesis that CT cells integrate information across diverse layer 5 populations, whereas CS and CC cells form more selectively interconnected groups. Overall, our findings demonstrate the existence of functional subnetworks within layer 5 that may differentially route visual information to behaviorally relevant downstream targets.
A probabilistic method for testing and estimating selection differences between populations
Authors: He Yungang , Wang Minxian , Huang Xin , Li Ran , Xu Hongyang , Xu Shuhua , Jin Li
Published: October 2015

Human populations around the world encounter various environmental challenges and, consequently, develop genetic adaptations to different selection forces. Identifying the differences in natural selection between populations is critical for understanding the roles of specific genetic variants in evolutionary adaptation. Although numerous methods have been developed to detect genetic loci under recent directional selection, a probabilistic solution for testing and quantifying selection differences between populations is lacking. Here we report the development of a probabilistic method for testing and estimating selection differences between populations. By use of a probabilistic model of genetic drift and selection, we showed that logarithm odds ratios of allele frequencies provide estimates of the differences in selection coefficients between populations. The estimates approximate a normal distribution, and variance can be estimated using genome-wide variants. This allows us to quantify differences in selection coefficients and to determine the confidence intervals of the estimate. Our work also revealed the link between genetic association testing and hypothesis testing of selection differences. It therefore supplies a solution for hypothesis testing of selection differences. This method was applied to a genome-wide data analysis of Han and Tibetan populations. The results confirmed that both the EPAS1 and EGLN1 genes are under statistically different selection in Han and Tibetan populations. We further estimated differences in the selection coefficients for genetic variants involved in melanin formation and determined their confidence intervals between continental population groups. Application of the method to empirical data demonstrated the outstanding capability of this novel approach for testing and quantifying differences in natural selection.
In situX-ray data collection and structure phasing of protein crystals at Structural Biology Center 19-ID
Authors: Michalska Karolina , Tan Kemin , Chang Changsoo , Li Hui , Hatzos-Skintges Catherine , Molitsky Michael , Alkire Randy , Joachimiak Andrzej
Published: October 2015

A prototype of a 96-well plate scanner forin situdata collection has been developed at the Structural Biology Center (SBC) beamline 19-ID, located at the Advanced Photon Source, USA. The applicability of this instrument for protein crystal diffraction screening and data collection at ambient temperature has been demonstrated. Several different protein crystals, including selenium-labeled, were used for data collection and successful SAD phasing. Without the common procedure of crystal handling and subsequent cryo-cooling for data collection atT= 100 K, crystals in a crystallization buffer show remarkably low mosaicity (<0.1°) until deterioration by radiation damage occurs. Data presented here show that cryo-cooling can cause some unexpected structural changes. Based on the results of this study, the integration of the plate scanner into the 19-ID end-station with automated controls is being prepared. With improvement of hardware and software,in situdata collection will become available for the SBC user program including remote access.
Workplace and leadership perceptions between men and women
Authors: Kiser Angelina I. T.
Published: October 2015

Purpose

– The purpose of this paper is to examine the attitudinal differences between men and women with respect to work issues and leadership and the implications that these outlooks have in the US (USA) workforce. While studies have been conducted to show how men and women differ in the work and leadership styles, attitudes can affect how workers and leaders are treated and may explain why people behave the way that they do.

Design/methodology/approach

– Using data from the 2010-2012 World Values Survey (WVS-6), comparisons were performed with the Mann-Whitney U test to determine if there were significant differences in attitudes and perceptions of work and leadership between men and women in the USA based on five questions concerning attitudes toward men and women in the workforce. The sample consisted of 1,070 males and 1,139 females who responded to questions using a Likert scale-rating system.

Findings

– There were significant differences between males and females at the p
<
0.01 level for four of the five questions. Men were more likely to believe that men have more rights to jobs when jobs are scarce. Women believed more than men that having a job was the best way for a woman to be independent. Men believed that they made better political leaders. Men also believed that they made better business executives. However, there was no significant difference in the question about women making more than men. Neither felt strongly that a woman earning more money than her husband would cause problems.

Originality/value

– The research provides insight into factors that might affect how men and women perceive both their own group and the other group. It is important to ensure that gender perceptions are evaluated to address issues that may still persist and contribute to gender inequality in the workplace and how behaviors and attitudes of each gender affect roles and norms.
Investor Confidence as a Determinant of China's Urban Housing Market Dynamics
Authors: Zheng Siqi , Sun Weizeng , Kahn Matthew E.
Published: October 2015

China's urban housing market dynamics suggest that evolving investor confidence may be a relevant demand shifter. Such investors are continually updating their beliefs about the state of the macroeconomy and the policy uncertainty related to national and local housing policies. We build a 35 Chinese city real estate confidence index that varies over time and across cities. This index predicts subsequent house price appreciation and new housing sales. We document evidence of heterogeneous effects of investor confidence depending on a city's demographics and the city's elasticity of housing supply. Our results based on a new household‐level expectations survey bolster the case that investor expectations are an important determinant of real estate price dynamics.
Thermal survival limits of young and mature larvae of a cold stenothermal chironomid from the Alps (Diamesinae: Pseudodiamesa branickii [Nowicki, 1873])
Authors: Lencioni Valeria , Bernabò Paola
Published: October 2015

The threats posed by climate change make it important to expand knowledge concerning cold and heat tolerance in stenothermal species from habitats potentially threatened by temperature changes. Thermal limits and basal metabolism variations were investigated in Pseudodiamesa branickii (Diptera: Chironomidae) under thermal stress between ‐20 and 37 °C. Supercooling point (SCP), lower (LLTs) and upper lethal temperatures (ULTs), and oxygen consumption rate were measured in overwintering young (1st and 2nd instar) and mature (3rd and 4th instar) larvae from an Alpine glacier‐fed stream. Both young and mature larvae were freezing tolerant (SCPs = ‐7.1 °C and ‐6.4 °C, respectively; LLT100  ‐20 °C) and thermotolerant (ULT50 = 31.7 ± 0.4, 32.5 ± 0.3, respectively). However, ontogenetic differences in acute tolerance were observed. The LLT50 calculated for the young larvae (= ‐7.4 °C) was almost equal to their SCP (= ‐7.1 °C) and the overlapping of the proportion of mortality curve with the CPIF curve highlighted that the young larvae are borderline between freezing tolerance and freezing avoidance. Furthermore, a lower ULT100 in the young larvae (of ca. 1 °C), suggests that they are less thermotolerant than mature larvae. Finally, young larvae exhibit a higher oxygen consumption rate (mgO2/gAFDM/h) at any temperature tested and are overall less resistant to oxygen depletion compared to mature larvae at ≥10 °C. These findings suggest that mature larvae enter into a dormant state by lowering their basal metabolism until environmental conditions improve in order to save energy for life cycle completion during stressful conditions.
Paradoxical association of dairy intake between men and women with the incidence of hypertension: A three‐year follow up in Tehran Lipid and Glucose Study
Authors: Mirmiran Parvin , Golzarand Mahdieh , Bahadoran Zahra , Ataee Maryam , Azizi Fereidoun
Published: October 2015

Aim

Gender differences in the association between dairy intake and the incidence of hypertension (HTN) are unclear. The present study aimed to investigate the association of total dairy and dairy products intake, between men and women with the incidence of HTN in the Tehran Lipid and Glucose Study after a three‐year follow up.

Methods

In this prospective study of 1087 normotensive adults, information about dairy intake was collected using a validated semi‐quantitative food frequency questionnaire. Blood pressure was measured at baseline and again after three years of follow up. The association between the three‐year incidence of HTN and dairy intake was assessed by a logistic regression model, adjusted for potential confounders.

Results

In men, the three‐year incidence of HTN increased in the highest quartile of total dairy compared with the lowest quartile (1.89, 95% CI: 1.01–3.57), whereas in women this incidence significantly decreased in the highest quartile of total dairy and low‐fat dairy compared with the lowest quartile (0.53, 95% CI: 0.31–0.90 and 0.56, 95% CI: 0.34–0.92, respectively). Incidence of HTN was increased in the highest quartile of milk compared with the lowest quartile only in men (2.39, 95% CI: 1.28–4.45).

Conclusions

Our findings indicated that higher consumption of total dairy and low‐fat dairy was inversely associated with the three‐year incidence of HTN in women, whereas higher intakes of total dairy significantly increased the risk of HTN in men. In addition, intake of milk in men and cheese in women was positively associated with HTN.
Disentangling Contributions of Bar Attendance, Drinking, and Other Factors to Elevated Acute Alcohol Problems on the U.S.–Mexico Border
Authors: Mills Britain A. , Caetano Raul , Vaeth Patrice A. C. , Reingle Gonzalez Jennifer M.
Published: October 2015

Background

Levels of drinking are unusually elevated among young adults on the U.S.–Mexico border, and this elevation can be largely explained by young border residents' unusually high frequency of bar attendance. However, this explanation complicates interpretation of high alcohol problem rates that have also been observed in this group. Because bar environments can lower the threshold for many types of problems, the extent to which elevated alcohol problems among young border residents can be attributed to drinking per se—versus this common drinking context—is not clear.

Methods

Data were collected from multistage cluster samples of adult Mexican Americans on and off the U.S.–Mexico border (current drinker N = 1,351). After developing structural models of acute alcohol problems, estimates were subjected to path decompositions to disentangle the common and distinct contributions of drinking and bar attendance to problem disparities on and off the border. Additionally, models were estimated under varying degrees of adjustment to gauge the sensitivity of the results to sociodemographic, social‐cognitive, and environmental sources of confounding.

Results

Consistent with previous findings for both drinking and other problem measures, acute alcohol problems were particularly elevated among young adults on the border. This elevation was entirely explained by a single common pathway involving bar attendance frequency and drinking. Bar attendance did not predict acute alcohol problems independently of drinking, and its effect was not moderated by border proximity or age. The common indirect effect and its component effects (of border youth on bar attendance, of bar attendance on drinking, and of drinking on problems) were surprisingly robust to adjustment for confounding in all parts of the model (e.g., fully adjusted indirect effect: b = 0.11, SE = 0.04, p < 0.01).

Conclusions

Bar attendance and associated increases in drinking play a key, unique role in the high levels of acute alcohol problems among the border's young adult population that cannot be entirely explained by sociodemographic or social‐cognitive characteristics of young border residents, by contextual effects of bars on problems, or by broader neighborhood factors. Bar attendance in particular may represent an early modifiable risk factor that can be targeted to reduce alcohol problem disparities in the region.
Applied scope of practice of oral health therapists, dental hygienists and dental therapists
Authors: Teusner DN , Amarasena N , Satur J , Chrisopoulos S , Brennan DS
Published: October 2015

Background

Oral health therapists (OHTs) are an emerging workforce whose training incorporates the skills of dental hygienists (DHs) and dental therapists (DTs). There are concerns that OHTs are underutilized. This study compares the employment characteristics and applied practice scope of OHTs with those of DTs and DHs.

Methods

Members of two professional associations representing DHs, DTs and OHTs, were surveyed by mail. Data collected included demographic and employment characteristics and clinical activity on a typical practice day. Applied practice scope was described by calculating the proportion of practitioners that had provided ≥1 of a selected range of key services. Log binomial regression was used to compare OHTs to DTs and DHs.

Results

The response rate was 60.6% (n = 1083) and of these 90.9% were employed. Preventive services dominated service provision. The proportion of OHTs that provided fluoride applications (77%) was higher than the proportion of DTs (53%, p < 0.05), and was not significantly different from the proportion of DHs (70%). The proportion of OHTs that provided (48%) fissure sealants was lower than the proportion of DTs (70%) and substantially higher than the proportion of DHs (10%, p > 0.05).

Conclusions

Overall, the applied practice scope of OHTs appeared to differ from DTs and DHs.
Allergic manifestation 15 years after early intervention with hydrolyzed formulas – theGINIStudy
Authors: von Berg A. , Filipiak‐Pittroff B. , Schulz H. , Hoffmann U. , Link E. , Sußmann M. , Schnappinger M. , Brüske I. , Standl M. , Krämer U. , Hoffmann B. , Heinrich J. , Bauer C.‐P. , Koletzko S. , Berdel D. ,   the GINIplus study group
Published: October 2015

Background

Data on the long‐term impact of hydrolyzed formulas on allergies are scarce.

Objective

To assess the association between early intervention with hydrolyzed formulas in high‐risk children and allergic outcomes in adolescence.

Methods

GINItrial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF‐W,eHF‐W), extensive casein hydrolyzate (eHF‐C) or standard cow′s milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent‐reported physician‐diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models.

Results

Between 11 and 15 years, the prevalence of asthma was reduced in theeHF‐C group compared toCMF(odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26–0.89), which is consistent with the spirometric results. The cumulative incidence ofARwas lower ineHF‐C (risk ratio (RR) 0.77, 95%CI0.59–0.99]) and theARprevalence inpHF‐W (OR0.67, 95%CI0.47–0.95) andeHF‐C (OR0.59, 95%CI0.41–0.84). The cumulative incidence of eczema was reduced inpHF‐W (RR0.75, 95%CI0.59–0.96) andeHF‐C (RR0.60, 95%CI0.46–0.77), as was the eczema prevalence between 11 and 15 years ineHF‐C (OR0.42, 95%CI0.23–0.79). No significant effects were found in theeHF‐W group on any manifestation,nor was there an effect on sensitization with any formula.

Conclusion

In high‐risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.
Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD
Authors: Håkansson B. , Montgomery M. , Cadiere G. B. , Rajan A. , Bruley des Varannes S. , Lerhun M. , Coron E. , Tack J. , Bischops R. , Thorell A. , Arnelo U. , Lundell L.
Published: October 2015

Background

Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro‐oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti‐reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients.

Aim

To perform a double‐blind sham‐controlled study in GERD patients who were chronic PPI users.

Methods

We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6‐month follow‐up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis.

Results

The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P < 0.001. After 6 months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised.

Conclusion

Transoral incisionless fundoplication (TIF2) is effective in chronic PPI‐dependent GERD patients when followed up for 6 months.

Clinicaltrials.gov: CT01110811
Establishment and evaluation of a stable steroidogenic goat Leydig cell line
Authors: Zhou Jinhua , Dai Rui , Lei Lanjie , Lin Pengfei , Lu Xiaolong , Wang Xiangguo , Tang Keqiong , Wang Aihua , Jin Yaping
Published: October 2015

Leydig cells play a key role in synthesizing androgen and regulating spermatogenesis. The dysfunction of Leydig cells may lead to various male diseases. Although primary Leydig cell cultures have been used, their finite lifespan hinders the assessment of long‐term effects. In the present study, primary goat Leydig cells (GLCs) were immortalized via the transfection of a plasmid containing the human telomerase reverse transcriptase (hTERT) gene. The expressions ofhTERTand telomerase activity were evaluated in transduced GLCs (hTERT‐GLCs). These cells steadily expressed thehTERTgene and exhibited longer telomere lengths at passage 55 that were similar to those of HeLa cells. The hTERT‐GLCs at passages 30 and 50 expressed genes that encoded key proteins, enzymes and receptors that are inherent to normal Leydig cells, for example, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side‐chain cleavage enzyme (P450scc), 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and LH‐receptor (LH‐R). Additionally, the immortalized goat Leydig cells secreted detectable quantities of testosterone in response to hCG stimulation. Furthermore, this cell line appeared to proliferate more quickly than the control cells, although no neoplastic transformation occurredin vitro. We concluded that the GLCs immortalized with hTERT retained their original characteristics and might provide a useful model for the study of Leydig cell function.
The Association Between Common Labor Drugs and Suckling When Skin‐to‐Skin During the First Hour After Birth
Authors: Brimdyr Kajsa , Cadwell Karin , Widström Ann‐Marie , Svensson Kristin , Neumann Monica , Hart Elaine A. , Harrington Sarah , Phillips Raylene
Published: October 2015

Background

Intrapartum drugs, including fentanyl administered via epidural and synthetic oxytocin, have been previously studied in relation to neonatal outcomes, especially breastfeeding, with conflicting results. We examined the normal neonatal behavior of suckling within the first hour after a vaginal birth while in skin‐to‐skin contact with mother in relation to these commonly used drugs. Suckling in the first hour after birth has been shown in other studies to increase desirable breastfeeding outcomes.

Method

Prospective comparative design. Sixty‐three low‐risk mothers self‐selected to labor with intrapartum analgesia/anesthesia or not. Video recordings of infants during the first hour after birth while being held skin‐to‐skin with their mother were coded and analyzed to ascertain whether or not they achieved Stage 8 (suckling) of Widström's 9 Stages of newborn behavior during the first hour after birth.

Results

A strong inverse correlation was found between the amount and duration of exposure to epidural fentanyl and the amount of synthetic oxytocin against the likelihood of achieving suckling during the first hour after a vaginal birth.

Conclusions

Results suggest that intrapartum exposure to the drugs fentanyl and synthetic oxytocin significantly decreased the likelihood of the baby suckling while skin‐to‐skin with its mother during the first hour after birth.
Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers
Authors: van Wonderen K. E. , Geskus R. B. , van Aalderen W. M. C. , Mohrs J. , Bindels P. J. E. , van der Mark L. B. , ter Riet G.
Published: October 2015

Background

In 2008, the European Respiratory Society Task Force proposed the terms multiple‐trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24‐month stability and predictiveness for asthma.

Methods

In total, 565 preschoolers (1‐, 2‐ and 3‐year‐olds) in primary care with respiratory symptoms were followed until the age of 6 years when asthma was diagnosed. MTW status and EVW status were determined using questionnaire data collected at baseline and after one and 2 years. We distinguished 3 phenotypes and determined their 24‐month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes’ associations with asthma.

Results

Two hundred and eighty‐one children had complete information. MTW and EVW were stable in 10 of 281 (3.6%) and 24 of 281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7–119) and 3.6 (1.2–11.3) times greater than those for children free of wheeze (for at least 1 year). ICS was associated with increased stability of MTW and EVW.

Conclusions

Stable multiple‐trigger and stable episodic viral wheeze are relatively uncommon. However, 1‐ to 3‐year‐olds with stable MTW are at much increased risk of asthma.
Anti‐OX40L alone or in combination with anti‐CD40L and CTLA4Ig does not inhibit the humoral and cellular response to a major grass pollen allergen
Authors: Gattringer M. , Baranyi U. , Pilat N. , Hock K. , Klaus C. , Ramsey H. E. , Wrba F. , Valenta R. , Wekerle T.
Published: October 2015

Background

IgE‐mediated allergy is a common disease characterized by a harmful immune response towards otherwise harmless environmental antigens. Induction of specific immunological non‐responsiveness towards allergens would be a desirable goal. Blockade of costimulatory pathways is a promising strategy to modulate the immune response in an antigen‐specific manner. Recently, OX40 (CD134) was identified as a costimulatory receptor important in Th2‐mediated immune responses. Moreover, synergy between OX40 blockade and ‘conventional’ costimulation blockade (anti‐CD40L, CTLA4Ig) was observed in models of alloimmunity.

Objective

We investigated the potential of interfering with OX40 alone or in combination with CD40/CD28 signals to influence the allergic immune response.

Methods

The OX40 pathway was investigated in an established murine model of IgE‐mediated allergy where BALB/c mice are repeatedly immunized with the clinically relevant grass pollen allergen Phl p 5. Groups were treated with combinations of anti‐OX40L, CTLA4Ig and anti‐CD40L. In selected mice, Tregs were depleted with anti‐CD25.

Results

Blockade of OX40L alone at the time of first or second immunization did not modulate the allergic response on the humoral or effector cell levels but slightly on T cell responses. Administration of a combination of anti‐CD40L/CTLA4Ig delayed the allergic immune response, but antibody production could not be inhibited after repeated immunization even though the allergen‐specific T cell response was suppressed in the long run. Notably, additional blockade of OX40L had no detectable supplementary effect. Immunomodulation partly involved regulatory T cells as depletion of CD25+ cells led to restored T cell proliferation.

Conclusions and Clinical Relevance

Collectively, our data provide evidence that the allergic immune response towards Phl p 5 is independent of OX40L, although reduction on T cell responses and slightly on the asthmatic phenotype was detectable. Besides, no relevant synergistic effect of OX40L blockade in addition to CD40L/CD28 blockade could be detected. Thus, the therapeutic potential of OX40L blockade for IgE‐mediated allergy appears to be ineffective in this setting.
Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes
Authors: Haller M J , Atkinson M A , Wasserfall C H , Brusko T M , Mathews C E , Hulme M , Cintron M , Shuster J , McGrail K , Posgai A , Schatz D
Published: October 2015

Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4+ : CD8+ T cell ratio or the ratio of naive : memory (CD45RA+/CD45RO+) CD4+ T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.
Negotiating Illness in Medical Interactions: Narrative Styles of two Children with Leukaemia
Authors: Rindstedt Camilla
Published: October 2015

The illness narratives presented in this paper were video‐recorded as part of child patient–staff interaction, during more than a year of ethnographic fieldwork at a paediatric oncology centre. The two children tended to ‘do illness’ differently, producing different types of narrative accounts. One of them presented accounts that invoked ‘fight’ metaphors, whereas the other one invoked patient identities. Also, the medical staff deployed different interactional strategies with different children in response to their narrative constructions of themselves and their leukaemia.
Constraints of philanthropy on determining the distribution of biodiversity conservation funding
Authors: Larson Eric R. , Howell Stephen , Kareiva Peter , Armsworth Paul R.
Published: October 2015

Caught between ongoing habitat destruction and funding shortfalls, conservation organizations are using systematic planning approaches to identify places that offer the highest biodiversity return per dollar invested. However, available tools do not account for the landscape of funding for conservation or quantify the constraints this landscape imposes on conservation outcomes. Using state‐level data on philanthropic giving to and investments in land conservation by a large nonprofit organization, we applied linear regression to evaluate whether the spatial distribution of conservation philanthropy better explained expenditures on conservation than maps of biodiversity priorities, which were derived from a planning process internal to the organization and return on investment (ROI) analyses based on data on species richness, land costs, and existing protected areas. Philanthropic fund raising accounted for considerably more spatial variation in conservation spending (r2= 0.64) than either of the 2 systematic conservation planning approaches (r2= 0.08–0.21). We used results of one of the ROI analyses to evaluate whether increases in flexibility to reallocate funding across space provides conservation gains. Small but plausible “tax” increments of 1–10% on states redistributed to the optimal funding allocation from the ROI analysis could result in gains in endemic species protected of 8.5–80.2%. When such increases in spatial flexibility are not possible, conservation organizations should seek to cultivate increased support for conservation in priority locations. We used lagged correlations of giving to and spending by the organization to evaluate whether investments in habitat protection stimulate future giving to conservation. The most common outcome at the state level was that conservation spending quarters correlated significantly and positively with lagged fund raising quarters. In effect, periods of high fund raising for biodiversity followed (rather than preceded) periods of high expenditure on land conservation projects, identifying one mechanism conservation organizations could explore to seed greater activity in priority locations. Our results demonstrate how limitations on the ability of conservation organizations to reallocate their funding across space can impede organizational effectiveness and elucidate ways conservation planning tools could be more useful if they quantified and incorporated these constraints.
Identification and functional characterization of novel transcriptional enhancers involved in regulating human GLI3 expression during early development
Authors: Anwar Saneela , Minhas Rashid , Ali Shahid , Lambert Nicholas , Kawakami Yasuhiko , Elgar Greg , Azam Syed Sikandar , Abbasi Amir Ali
Published: October 2015

The zinc‐finger transcription factor GLI3 acts as a primary transducer of Sonic hedgehog (Shh) signaling in a context‐dependent combinatorial fashion. GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs. Previously, we reported a subset of human intronic cis‐regulators controlling many known aspects of endogenous Gli3 expression in mouse and zebrafish. Here we demonstrate in a transgenic zebrafish assay the potential of two novel tetrapod‐teleost conserved non‐coding elements (CNEs) docking within GLI3 intronic intervals (intron 3 and 4) to induce reporter gene expression at known sites of endogenous Gli3 transcription in embryonic domains such as the central nervous system (CNS) and limbs. Interestingly, the cell culture based assays reveal harmony with the context dependent dual nature of intra‐GLI3 conserved elements. Furthermore, a transgenic zebrafish assay of previously reported limb‐specific GLI3 transcriptional enhancers (previously tested in mice and chicken limb buds) induced reporter gene expression in zebrafish blood precursor cells and notochord instead of fin. These results demonstrate that the appendage‐specific activity of a subset of GLI3‐associated enhancers might be a tetrapod innovation. Taken together with our recent data, these results suggest that during the course of vertebrate evolution Gli3 expression control acquired a complex cis‐regulatory landscape for spatiotemporal patterning of CNS and limbs. Comparative data from fish and mice suggest that the functional aspects of a subset of these cis‐regulators have diverged significantly between these two lineages.
How Inheriting Affects Bequest Plans
Authors: Stark Oded , Nicinska Anna
Published: October 2015

We present and test the idea that bequest planning is linked with the experience of inheriting. We consider ‘a family tradition of bequeathing’ as a channel through which the intention to bequeath is moulded by and is positively correlated with the experience of inheriting. Using data from the Survey on Health, Ageing and Retirement in Europe (SHARE), we find that the experience of inheriting enhances the intention to bequeath, independently of the positive impact of wealth. We also find that the expectation of inheriting has a positive impact on the intention to bequeath, controlling for the expected increase in wealth on account of future inheritances.
Economic, structural and socio‐psychological determinants of protests in Russia during 2011–2012
Authors: Hagemann Harald , Kufenko Vadim
Published: October 2015

This empirical analysis is based on the latent variable framework to identify key determinants of protests in Russia during 2011–2012. We derive logistic regressions from the revolution constraints based on economic (the political Kuznets Curve) and socio‐psychological (grievance) theories of protest. Our findings suggest a positive linear relationship between income and income inequality, contradicting the Kuznets curve. Our estimations show that inequality, share of the poor, the relation of the governor's family income to the average family income, distance to Moscow and accumulated human capital increase the risk of protest, whereas transfers and subsidies decrease these risks.
Targeting of cell metabolism in human acute myeloid leukemia – more than targeting of isocitrate dehydrogenase mutations and PI3K/AKT/mTOR signaling?
Authors: Hauge Michelle , Bruserud Øystein , Hatfield Kimberley Joanne
Published: October 2015

Targeting of cellular metabolism has emerged as a possible strategy in the treatment of human malignancies, and several experimental studies suggest that this therapeutic approach should also be considered in acute myeloid leukemia (AML). Clinical studies of metabolic intervention in AML patients with isocitrate dehydrogenase mutations have shown promising results. Moreover, metabolic targeting of the PI3K/AKT/mTOR signaling pathway as an anticancer strategy has been extensively studied. In this review, we focus on other emerging therapeutic alternatives for metabolic inhibition in human AML, in particular targeting of glycolysis and the AMP kinase signaling pathway. Pharmacological drugs for these metabolic interventions are already available and they seem to have an acceptable toxicity, even when used in combination with conventional chemotherapy. Future clinical studies of these therapeutic strategies should focus on the following: (i) heterogeneity of patients and the possibility that this treatment is most effective only for certain subsets of patients, (ii) toxic effects in AML patients with an existing disease‐induced bone marrow failure prior to treatment, and (iii) whether this strategy should be used as part of a potentially curative treatment and/or as disease‐stabilizing treatment to prolong survival in elderly or unfit patients.