bluuebunny/crossref_metadata_2025 huggingface dataset:
Fishing, fast growth and climate variability increase the risk of collapse
Authors: Pinsky Malin L. , Byler David
Published: August 2015

Species around the world have suffered collapses, and a key question is why some populations are more vulnerable than others. Traditional conservation biology and evidence from terrestrial species suggest that slow-growing populations are most at risk, but interactions between climate variability and harvest dynamics may alter or even reverse this pattern. Here, we test this hypothesis globally. We use boosted regression trees to analyse the influences of harvesting, species traits and climate variability on the risk of collapse (decline below a fixed threshold) across 154 marine fish populations around the world. The most important factor explaining collapses was the magnitude of overfishing, while the duration of overfishing best explained long-term depletion. However, fast growth was the next most important risk factor. Fast-growing populations and those in variable environments were especially sensitive to overfishing, and the risk of collapse was more than tripled for fast-growing when compared with slow-growing species that experienced overfishing. We found little evidence that, in the absence of overfishing, climate variability or fast growth rates alone drove population collapse over the last six decades. Expanding efforts to rapidly adjust harvest pressure to account for climate-driven lows in productivity could help to avoid future collapses, particularly among fast-growing species.
Cooperation, clumping and the evolution of multicellularity
Authors: Biernaskie Jay M. , West Stuart A.
Published: August 2015

The evolution of multicellular organisms represents one of the major evolutionary transitions in the history of life. A potential advantage of forming multicellular clumps is that it provides an efficiency benefit to pre-existing cooperation, such as the production of extracellular ‘public goods’. However, this is complicated by the fact that cooperation could jointly evolve with clumping, and clumping could have multiple consequences for the evolution of cooperation. We model the evolution of clumping and a cooperative public good, showing that (i) when considered separately, both clumping and public goods production gradually increase with increasing genetic relatedness; (ii) in contrast, when the traits evolve jointly, a small increase in relatedness can lead to a major shift in evolutionary outcome—from a non-clumping state with low public goods production to a cooperative clumping state with high values of both traits; (iii) high relatedness makes it easier to get to the cooperative clumping state and (iv) clumping can be inhibited when it increases the number of cells that the benefits of cooperation must be shared with, but promoted when it increases relatedness between those cells. Overall, our results suggest that public goods sharing can facilitate the formation of well-integrated cooperative clumps as a first step in the evolution of multicellularity.
Free boundaries in problems with hysteresis
Authors: Apushkinskaya D. E. , Uraltseva N. N.
Published: August 2015

Here, we present a survey concerning parabolic free boundary problems involving a discontinuous hysteresis operator. Such problems describe biological and chemical processes ‘with memory’ in which various substances interact according to hysteresis law. Our main objective is to discuss the structure of the free boundaries and the properties of the so-called ‘strong solutions’ belonging to the anisotropic Sobolev class

with sufficiently large
q
. Several open problems in this direction are proposed as well.
Free boundary problems in shock reflection/diffraction and related transonic flow problems
Authors: Chen Gui-Qiang , Feldman Mikhail
Published: August 2015

Shock waves are steep wavefronts that are fundamental in nature, especially in high-speed fluid flows. When a shock hits an obstacle, or a flying body meets a shock, shock reflection/diffraction phenomena occur. In this paper, we show how several long-standing shock reflection/diffraction problems can be formulated as free boundary problems, discuss some recent progress in developing mathematical ideas, approaches and techniques for solving these problems, and present some further open problems in this direction. In particular, these shock problems include von Neumann's problem for shock reflection–diffraction by two-dimensional wedges with concave corner, Lighthill's problem for shock diffraction by two-dimensional wedges with convex corner, and Prandtl-Meyer's problem for supersonic flow impinging onto solid wedges, which are also fundamental in the mathematical theory of multidimensional conservation laws.
Incompressible limit of a mechanical model of tumour growth with viscosity
Authors: Perthame Benoît , Vauchelet Nicolas
Published: August 2015

Various models of tumour growth are available in the literature. The first type describe the evolution of the cell number density when considered as a continuous visco-elastic material with growth. The second type describe the tumour as a set, and rules for the free boundary are given related to the classical Hele-Shaw model of fluid dynamics. Following previous papers where the material is described by a purely elastic material, or when active cell motion is included, we make the link between the two types of description considering the ‘stiff pressure law’ limit. Even though viscosity is a regularizing effect, new mathematical difficulties arise in the visco-elastic case because estimates on the pressure field are weaker and do not immediately imply compactness. For instance, travelling wave solutions and numerical simulations show that the pressure is discontinuous in space, which is not the case for an elastic material.
Global stability of steady states in the classical Stefan problem for general boundary shapes
Authors: Hadžić Mahir , Shkoller Steve
Published: August 2015

The classical one-phase Stefan problem (without surface tension) allows for a continuum of steady-state solutions, given by an arbitrary (but sufficiently smooth) domain together with zero temperature. We prove global-in-time stability of such steady states, assuming a sufficient degree of smoothness on the initial domain, but without anya priorirestriction on the convexity properties of the initial shape. This is an extension of our previous result (Hadžić & Shkoller 2014Commun. Pure Appl. Math. 68, 689–757 (doi:10.1002/cpa.21522)) in which we studied nearly spherical shapes.
Convergence rates for the classical, thin and fractional elliptic obstacle problems
Authors: Nochetto Ricardo H. , Otárola Enrique , Salgado Abner J.
Published: August 2015

We review the finite-element approximation of the classical obstacle problem in energy and max-norms and derive error estimates for both the solution and the free boundary. On the basis of recent regularity results, we present an optimal error analysis for the thin obstacle problem. Finally, we discuss the localization of the obstacle problem for the fractional Laplacian and prove quasi-optimal convergence rates.
Raising the bar
Authors: Ozarow Daniel , Gibson Trevor , Batra Arun , Mercer Sam
Published: August 2015

Purpose

– Argues that merely complying with legislation is not sufficient to accomplish genuine diversity and that, rather than assuming its benefits will naturally be derived and accepted, diversity must be approached strategically and its advantages communicated effectively to stakeholders to ensure desired outcomes.

Design/methodology/approach

– Considers the business case for diversity, presents a case study of barristers and examines the role of the national equality standard.

Findings

– Advances the view that multi-layered approaches to diversity are essential for its successful implementation.

Practical implications

– Highlights the strong business case for diversity in the workforce, as well as possible social repercussions from failing to ensure that workforces are diverse.

Social implications

– Underlines how young people in European and Anglo-Saxon countries are increasingly demanding to work with colleagues from varied ethnicities, nationalities and sexual orientations who are similar to the peers they socialize with. Diverse workforces have thus become central to talent attraction.

Originality/value

– Presents an interesting case study of barristers and diversity.
The generation game
Authors: Chatrakul Na Ayudhya Uracha
Published: August 2015

Purpose

– Explores the limited value of concepts such as Baby-Boomer, Generation X (Gen X) and Generation Y (Gen Y) and advances the view that life course is more valuable.

Design/methodology/approach

– Examines how young adults in Britain, born between 1975 and 1982, conceptualized the notion of work-life balance as they were about to leave university and enter full-time paid employment.

Findings

– Reveals that the notion of individual choice strongly underpins young adults’ conceptualization of work-life balance and expectations of work-life balance support; while young British and Asian adults largely considered it to be a matter of individual choice, there were variations in their preferences for how to prioritize their impending employment and personal lives; and four emerging patterns of work-life balance orientation preferences were found – balancer, careerist, career-sacrificer and integrator.

Practical implications

– Provides support for the argument that the work-life balance perceptions of young adults who would belong to the so-called Gen Y cannot be generalized and simplified as being either work-centric or life-centric. The picture is a lot more complex given the diversity within this group of young adults.

Social implications

– Highlights how, instead of looking for generational differences (or age-related differences) which can be divisive, it is more useful to look at the issue of multi-generations in a broader way.

Originality/value

– By using a life-course approach instead of a generational approach, is able to take into account how past transitions have shaped the way work-life balance was discussed by the young adults and how anticipated future transitions were expected by the young adults to change their needs and therefore expectations of employer and government support.
Water and carbon storage capacity in Isolatocereus dumortieri (Cactaceae) in an intertropical semiarid zone in Mexico
Authors: Pavón Numa P. , Ayala Christian O. , Martínez‐Falcón Ana Paola
Published: August 2015

In the biosphere reserve Barranca de Metztitlán in Mexico, there is an extensive area with a semiarid scrub. The dominant species is the cactus Isolatocereus dumortieri. This is a key species in the ecosystem, because many species of birds, bats and insects are feeding from its nectar, pollen and fruits during the dry season thanks to their capacity to store water and carbon. However, there is no information about their potential to store water and carbon. The purpose of this study was to estimate the ability of I. dumortieri to store water and carbon. Water content per plant was estimated as 537.64 ± 71.59 L during the dry season and 692.24 ± 92.18 L during the wet season. In the same way the carbon stored per cactus was 16.75 kg ± 7.07 corresponding to 1.25 kg C m2. The results shows the importance of I. dumortieri in maintaining the ecosystem services of the scrub vegetation.
Ancestry and BMI Influences on Facial Soft Tissue Depths for A Cohort of Chinese and Caucasoid Women in Dunedin, New Zealand
Authors: Baillie Louisa J. , Mirijali Seyed Ali , Niven Brian E. , Blyth Phil , Dias George J.
Published: August 2015

This study measured and assessed facial soft tissue depths (FSTDs) in adult female Chinese and New Zealand (NZ) Europeans (Caucasoids). Ultrasound was used to obtain depths at nine landmarks on 108 healthy subjects (51 Chinese, 57 NZ European), erect positioned, of same age group (18–29 years). Height and weight were also recorded. Statistical analysis focused on comparison of tissue depth between the two ancestry groups and the influence of Body Mass Index (BMI) (kg/m2). Results showed mean depth differences at Supra M2 and Infra M2 landmarks significantly greater for Chinese than Caucasoid women for all three BMI Classes (BMI <20, 20 ≤ BMI < 25, 25 ≤ BMI < 30), even BMI <20. For both groups BMI positively correlated with FSTD values at all landmarks except Labrale superius. This study enabled ancestry and BMI influence on FSTDs to be observed and compared for two distinct groups. Results add to knowledge about facial tissue depth variation.
Estimation of Age Using Alveolar Bone Loss: Forensic and Anthropological Applications
Authors: Ruquet Michel , Saliba‐Serre Bérengère , Tardivo Delphine , Foti Bruno
Published: August 2015

The objective of this study was to utilize a new odontological methodological approach based on radiographic for age estimation. The study was comprised of 397 participants aged between 9 and 87 years. A clinical examination and a radiographic assessment of alveolar bone loss were performed. Direct measures of alveolar bone level were recorded using CT scans. A medical examination report was attached to the investigation file. Because of the link between alveolar bone loss and age, a model was proposed to enable simple, reliable, and quick age estimation. This work added new arguments for age estimation. This study aimed to develop a simple, standardized, and reproducible technique for age estimation of adults of actual populations in forensic medicine and ancient populations in funeral anthropology.
Benign thyroid nodules with RAS mutation grow faster
Authors: Puzziello Alessandro , Guerra Anna , Murino Alessia , Izzo Giulia , Carrano Mario , Angrisani Elisabetta , Zeppa Pio , Marotta Vincenzo , Faggiano Antongiulio , Vitale Mario
Published: August 2015

Context

The management of a benign thyroid nodule includes follow‐up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules.

Objective

The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation.

Patients and methods

Genomic DNA obtained by fine‐needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS61 and KRAS13 mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow‐up of 25 months were evaluated according to the presence of RAS mutation.

Results

A RAS mutation was found in 24 thyroid aspirates (30·8%, 8 NRAS61 and 16 KRAS13). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0·017). After a 25‐month mean follow‐up, RAS mutation‐positive nodules displayed faster growth (RAS mutation‐positive vs RAS mutation‐negative % annual growth 27·6% ±32·2% vs 1·0% ±17·0%, P < 0·001).

Conclusions

Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild‐type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management.
BAM! Utilizing the frequency of Benign, Atypical and Malignant diagnoses for quality improvement in the histopathologic diagnosis of melanocytic neoplasms
Authors: Bush James W. , Hunt Edgar L. , Fraga Garth R.
Published: August 2015

Background

Healthcare quality measures are metrics that quantify medical outcomes. There is a need for performance indicators in the diagnosis of melanocytic neoplasms. We sought to determine whether the atypical to malignant diagnosis ratio (AMR) and benign to malignant diagnosis ratio (BMR) could identify differences between practitioners within a group as well as individual diagnostic drift.

Methods

Diagnoses of melanocytic neoplasms from 2013 and 2014 by two dermatopathologists were prospectively subclassified as benign, atypical or malignant and reported on a monthly basis to the pathologists. Case diagnoses of melanocytic neoplasms from 2012 and 2009 were retrospectively subclassified as benign, atypical or malignant for comparison.

Results

A total of 33,169 cases were used in this study. Interpathologist AMR and BMR were significantly different. One pathologist demonstrated a significant increase in AMR over time.

Conclusion

AMR and BMR metrics are potential performance indicators that can measure pathologist uncertainty, identify diagnostic drift and provide a surrogate measure of the relative risk level of laboratory patient populations. If applied to multiple laboratories, AMR and BMR metrics could help inform physicians' choice of dermatopathology laboratory and provide a method for comparative analysis between laboratories.
HLA B51 is associated with faster AIDS progression among newly diagnosed HIV‐infected individuals in Manitoba, Canada
Authors: Keynan Y. , Rueda Z. V. , Bresler K. , Becker M. , Kasper K.
Published: August 2015

Human leucocyte antigen (HLA) alleles influence the rate of CD4 decline among HIV‐infected individuals. We investigated the association between HLA B35 and HLA B51 and the rate of CD4 decline and/or opportunistic infections, among 294 HIV‐positive individuals from Manitoba, Canada. All individuals presenting with a CD4 count >200 cells μL−1, who had at least two CD4 counts, and no evidence of co‐infection were included. Individuals bearing HLA B35 or HLA B51 were compared to controls. A multivariate model demonstrated that HLA B35 allele was associated with a hazard ratio of 2.05 (95% CI 1.31–3.18) for reaching AIDS and HLA B51 allele with HR of 2.03 (95% CI 1.18–3.49) for reaching the same end‐point. High prevalence of HLA B35 was seen in the patient population receiving care in Manitoba. Our observations confirm the association of HLA B35 with rapid disease progression. We report, for the first time, faster CD4 decline among individuals with HLA B51 allele.
How Environmental Management Competitive Pressure Affects a Focal Firm's Environmental Innovation Activities: A Green Supply Chain Perspective
Authors: Dai Jing , Cantor David E. , Montabon Frank L.
Published: August 2015

Recently, environmental management offers firms a source of competitive advantage in the marketplace. The development of environmental innovations is critical to the success of today's firms. Drawing on the Schumpeterian perspective of competition, this research examines how the perception of rival firms' green success influences a firm to pursue and produce environmental innovation through its green supply chain integration activities. Using survey data from 230 firms, a conceptual model is developed and tested using structural equation modeling. We find that the firms in our sample do perceive pressure from their competitors' success in environmental management activities, and thus take supply chain action to pursue integration activities. By differentiating incremental and radical environmental innovation, this study also reveals the role of three dimensions of green supply chain integration (internal, supplier, and customer integration of green product development) on incremental and radical environmental innovation separately. Specifically, findings suggest that green supply chain integration has a positive impact on developing incremental environmental innovation, while only customer integration has a significant positive impact on developing radical environmental innovation.
Optimization of Characteristic Wavelengths in Prediction of Lycopene in Tomatoes Using Near‐Infrared Spectroscopy
Authors: Li Tianhua , Zhong Chongzhe , Lou Wei , Wei Min , Hou Jialin
Published: August 2015

To improve the predictive ability and robustness of the near‐infrared correction model and to simplify the model, the backward interval partial least squares, the synergy interval partial least squares, the uninformative variable elimination partial least squares and the genetic algorithm partial least square (GA‐PLS) methods were used to select the characteristic wavelengths in the prediction of lycopene in tomatoes. The optimal characteristic variables and regression model were determined by the model evaluation parameters. The best model was set up using the GA‐PLS method. Compared with the model based on the full spectra, the variables used were reduced from 1,816 to 142, the correlation coefficient increased from 0.7104 to 0.9072, the root mean square errors of cross‐validation and prediction decreased from 21.58 to 8.76 and from 22.03 to 8.93, respectively. The experimental results showed that the use of GA‐PLS method, in the selection of characteristic variables of tomato lycopene, could effectively reduce the number of variables, decrease model complexity and improve the predictive precision.

Practical Applications

Using near‐infrared spectroscopy could quickly detect the lycopene contents of tomatoes. By extracting spectra characteristic wavelengths, it could reduce the irrelevant information variables and improve the accuracy of measurement of lycopene in tomatoes.
Neuronal acid‐induced [Zn2+]i elevations calibrated using the low‐affinity ratiometric probe FuraZin‐1
Authors: Kiedrowski Lech
Published: August 2015

The experiments were carried out on primary cultures of murine cortical neurons from cryopreserved preparations obtained from embryonic‐day‐16 fetuses. To calibrate acid‐induced intracelluar [Zn2+] ([Zn2+]i) elevations, a low affinity (Kd = 39 μM at pH 6.1) ratiometric Zn2+ probe, FuraZin‐1, was used. A pHi drop from 7.2 to 6.1 caused [Zn2+]i elevations reaching 2 μM; when the thiol‐reactive agent N‐ethylmaleimide (NEM) was subsequently applied, [Zn2+]i increased further to 5.6 μM; analogous acid‐ and NEM‐induced [Zn2+]i elevations could also be detected but not calibrated, using the high affinity Zn2+ probe FluoZin‐3. The data indicate that NEM causes Zn2+ release from ligands that chelate Zn2+ at pH 6.1. ATP could also chelate Zn2+ at pH 6.1 because its pKa is about 6.8. Therefore, it was tested whether an ATP depletion affects the acid‐induced [Zn2+]i elevations. The ATP depletion was induced by inhibiting mitochondrial and glycolytic ATP production. Interestingly, an almost complete ATP depletion (confirmed using a luciferin/luciferase assay) failed to affect the acid‐induced [Zn2+]i increases. These data suggest that the total amount of Zn2+ accumulated in intracellular ATP‐dependent stores (Zn2+‐ATP complexes and organelles that accumulate Zn2+ in an ATP‐dependent manner) is negligible compared to the amount of Zn2+ accumulated in the acid‐sensitive intracellular ligands.

image

In vitro, upon acidification, Zn2+‐cysteine complexes release Zn2+ and ATP chelates the released Zn2+. However, in vivo (cultured neurons), an ATP depletion failed to enhance acid‐induced [Zn2+]i elevations. These [Zn2+]i elevations were calibrated using a low affinity ratiometric probe FuraZin‐1; they reached 2 µM levels and increased to 5 µM when a thiol‐reactive agent, N‐ethylmaleimide, compromised Zn2+ binding by cysteines.
Evaluating the use of key performance indicators to evidence the patient experience
Authors: McCance Tanya , Hastings Jack , Dowler Hilda
Published: August 2015

Aims and objectives

To test eight person‐centred key performance indicators and the feasibility of an appropriate measurement framework as an approach to evidencing the patient experience.

Background

The value of measuring the quality of patient care is undisputed in the international literature, however, the type of measures that can be used to generate data that is meaningful for practice continues to be debated. This paper offers a different perspective to the ‘measurement’ of the nursing and midwifery contribution to the patient experience.

Design

Fourth generation evaluation was the methodological approach used to evaluate the implementation of the key performance indicators and measurement framework across three participating organisations involving nine practice settings.

Methods

Data were collected by repeated use of claims, concerns and issues with staff working across nine participating sites (n = 18) and the senior executives from the three partner organisations (n = 12). Data were collected during the facilitated sessions with stakeholders and analysed in conjunction with the data generated from the measurement framework.

Results

The data reveal the inherent value placed on the evidence generated from the implementation of the key performance indicators as reflected in the following themes: measuring what matters; evidencing the patient experience; engaging staff; a focus for improving practice; and articulating and demonstrating the positive contribution of nursing and midwifery.

Conclusions

The implementation of the key performance indicators and the measurement framework has been effective in generating evidence that demonstrates the patient experience. The nature of the data generated not only privileges the patient voice but also offers feedback to nurses and midwives that can inform the development of person‐centred cultures.

Relevance to clinical practice

The use of these indicators will produce evidence of patient experience that can be used by nurse and midwives to celebrate and further inform person‐centred practice.
Sampling interval affects the estimation of movement parameters in four species of African snakes
Authors: Alexander G. J. , Maritz B.
Published: August 2015

Movement patterns in animals have been studied extensively, but differences in sampling frequencies produce datasets that are not always directly comparable. Because information is collected as point coordinates, measures of movement generally underestimate actual distances moved, especially when sampling frequency is low. Many animals, including most snakes, move from one location to another in discrete bouts of movement interspersed by relatively long periods of immobility. The impact of sampling interval on measures of movement in such studies remains poorly quantified, severely limiting appropriate contrasts among species, populations or individuals. We collected data during telemetry studies of four African snake species (Bitis arietans, B. schneideri, Python natalensis and Gonionotophis capensis) to assess the impact of sampling frequency on two measures of movement (mean daily displacement, MDD; moves per month, MM), which we assessed by subsampling our datasets to simulate different sampling frequencies. For each species, we analysed two subgroups defined by their movement profiles yielding eight experimental species groups. We found significant effects of sampling interval on MDD and MM with the magnitude of the effect (b) of sampling interval ranging from −0.025 to −0.138 among species groups, producing errors of up to 10%. For MM, b estimates ranged between −0.313 and 0.032, yielding error estimates of up to 40%. Our study reveals the potential for sampling interval to significantly impact measures of movement. Moreover, this error can vary dramatically among species, sexes or seasons, emphasizing the importance of taking cognizance of sampling interval in movement studies. We propose a method whereby researchers explicitly account for such effects by reporting measures of displacement and movement frequency corrected to a standardized daily sampling interval to account for this error and better facilitate meta‐analysis. This will facilitate a more holistic understanding of the movement ecology of infrequently moving animals.
Father's involvement and its effect on early breastfeeding practices in Viet Nam
Authors: Bich Tran Huu , Hoa Dinh Thi Phuong , Ha Nguyen Thanh , Vui Le Thi , Nghia Dang Thi , Målqvist Mats
Published: August 2015

Fathers have an important but often neglected role in the promotion of healthy breastfeeding practices in developing countries. A community‐based education intervention was designed to mobilize fathers' support for early breastfeeding. This study aimed to evaluate an education intervention targeting fathers to increase the proportion of early breastfeeding initiation and to reduce prelacteal feeding. Quasi‐experimental study design was used to compare intervention and control areas located in two non‐adjacent rural districts that shared similar demographic and health service characteristics in northern Viet Nam. Fathers and expectant fathers with pregnant wives from 7 to 30 weeks gestational age were recruited. Fathers in the intervention area received breastfeeding education materials, counselling services at a commune health centre and household visits. They were also invited to participate in a breastfeeding promotion social event. After intervention, early breastfeeding initiation rate was 81.2% in the intervention area and 39.6% in the control area (P < 0.001). Babies in the intervention area were more likely to be breastfed within the first hour after birth [odds ratio (OR) 7.64, 95% confidence interval (CI) 4.81–12.12] and not to receive any prelacteal feeding (OR 4.43, 95% CI 2.88–6.82) compared with those in the control area. Fathers may positively influence the breastfeeding practices of mothers, and as a resource for early childcare, they can be mobilized in programmes aimed at improving the early initiation of breastfeeding.
Periconceptional folic acid fortification for the risk of gestational hypertension and pre‐eclampsia: a meta‐analysis of prospective studies
Authors: Yang Xiaorong , Chen Hui , Du Yihui , Wang Shuting , Wang Zhiping
Published: August 2015

Published literatures report controversial results about the association of folic acid–containing multivitamins with gestational hypertension and pre‐eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre‐eclampsia. The Q test and I2 statistic were used to examine between‐study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98–1.09, P = 0.267] and pre‐eclampsia (RR = 0.99, 95% CI: 0.90–1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43–0.76, P < 0.001) and pre‐eclampsia (RR = 0.64, 95% CI: 0.48–0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta‐analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large‐scale randomised controlled trials.
Multigene synergism increases the isoflavone and proanthocyanidin contents of Medicago truncatula
Authors: Gou Lanming , Zhang Rongxue , Ma Lei , Zhu Fugui , Dong Jiangli , Wang Tao
Published: August 2015

Isoflavones and proanthocyanidins (PAs), which are flavonoid derivatives, possess many health benefits and play important roles in forage‐based livestock production. However, the foliage of Medicago species accumulates limited levels of both isoflavones and PAs. In this study, biosynthesis of isoflavone and PA in Medicago truncatula was enhanced via synergy between soya bean isoflavone synthase (IFS1); two upstream enzymes, chalcone synthase (CHS) and chalcone isomerase (CHI); and the endogenous flavanone 3‐hydroxylase (F3H). Constitutive expression of GmIFS1 alone resulted in ectopic accumulation of the isoflavone daidzein and large increases in the levels of the isoflavones formononetin, genistein and biochanin A in the leaves. Furthermore, coexpression of GmIFS1 with GmCHS7 and GmCHI1A generally increased the available flux to flavonoid biosynthesis and resulted in elevated isoflavone, flavone and PA contents. In addition, down‐regulation of MtF3H combined with coexpression of GmIFS1, GmCHS7 and GmCHI1A led to the highest isoflavone levels (up to 2 μmol/g fresh weight in total). Taken together, our results demonstrate that multigene synergism is a powerful means to enhance the biosynthesis of particular flavonoids and can be more broadly applied to the metabolic engineering of forage species.
Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes
Authors: Grim S.A. , Layden J.E. , Roth P. , Gallitano S. , Adams W. , Clark N.M.
Published: August 2015

Background

The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population.

Methods

A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy.

Results

Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94–274.94, P < 0.001). Documented completion of first‐line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first‐line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05–0.77, P = 0.02).

Conclusion

Based on medical record documentation, completion of first‐line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first‐line therapy because of adverse effects.
Exaggerated pulmonary vascular response to acute hypoxia in older men
Authors: Balanos George M. , Pugh Keith , Frise Matthew C. , Dorrington Keith L.
Published: August 2015

New Findings

What is the central question of this study?

Pulmonary arterial pressure is higher in older than younger humans and predicts mortality. It is also increased by acute hypoxia, which causes constriction of the pulmonary vasculature. We asked whether this pulmonary vascular response to hypoxia is greater in older humans.

What is the main finding and its importance?

Using Doppler echocardiography in 12 younger (∼20 years old) and nine older men (∼55 years old) exposed to 20 min of moderate isocapnic hypoxia, we demonstrated that older men showed a significantly greater rise in pulmonary arterial pressure during alveolar hypoxia than younger men. Future studies should examine the pathophysiological importance of increased hypoxic pulmonary vasoconstriction with age.

Resting pulmonary arterial pressure increases with age in humans. In the general population, higher values are associated with increased mortality, and in common cardiopulmonary diseases, such as congestive heart failure and chronic obstructive pulmonary disease, the presence of pulmonary arterial hypertension portends a worse outcome. Pulmonary arterial pressure increases during alveolar hypoxia, as a consequence of constriction in the pulmonary vasculature. We hypothesized that older men have more vigorous hypoxic pulmonary vasoconstriction than younger men. Twelve younger (20.5 ± 0.5 years old) and nine older men (55.8 ± 2.1 years old) were exposed for 20 min on different days to isocapnic hypoxia (end‐tidal  = 50 mmHg) and isocapnic euoxia (end‐tidal  = 100 mmHg); each was preceded (baseline) and followed by 5 min of isocapnic euoxia. Systolic pulmonary arterial pressure and cardiac output were measured continuously using Doppler echocardiography. Systolic pulmonary arterial pressure was greater during baseline euoxic measurements in older participants (27.8 ± 0.8 versus 24.1 ± 0.7 mmHg, P = 0.001) and also increased more during hypoxia in older participants (15.2 ± 1.3 versus 9.6 ± 0.9 mmHg, P = 0.011). Cardiac output did not differ between the two groups during baseline measurements (P = 0.60) or hypoxia (P = 0.49). All data are means ± SEM. The increased magnitude of hypoxic pulmonary vasoconstriction demonstrated with age has implications for individuals wishing to ascend to high altitude or travel by air, for those suffering from conditions in which global alveolar hypoxia is a feature and for patients requiring general anaesthesia.
Antisocial and Prosocial Behavior in Sport: The Role of Motivational Climate, Basic Psychological Needs, and Moral Disengagement
Authors: Hodge Ken , Gucciardi Daniel F.
Published: August 2015

The purpose of this investigation was to examine whether the relationships between contextual factors and basic psychological needs were related to antisocial and prosocial behavior in sport. A two-study project employing Bayesian path analysis was conducted with competitive athletes (Study 1, n = 291; Study 2, n = 272). Coach and teammate autonomy-supportive climates had meaningful direct relations with need satisfaction and prosocial behavior. Coach and teammate controlling climates had meaningful direct relations with antisocial behavior. Need satisfaction was both directly and indirectly related with both prosocial and antisocial behavior, whereas moral disengagement was directly and indirectly related with antisocial behavior. Overall, these findings reflected substantial evidence from the literature on self-determination theory that autonomy-supportive motivational climates are important environmental influences for need satisfaction, and are important correlates of prosocial behavior in sport, whereas controlling coach and teammate climates, along with moral disengagement, were important correlates of antisocial behavior in sport.
The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents
Authors: Bengtsson-Palme Johan , Angelin Martin , Huss Mikael , Kjellqvist Sanela , Kristiansson Erik , Palmgren Helena , Larsson D. G. Joakim , Johansson Anders
Published: August 2015

Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance ofProteobacteriain 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producingEscherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
RapidIn VitroEvolution of Human Cytomegalovirus UL56 Mutations That Confer Letermovir Resistance
Authors: Chou Sunwen
Published: August 2015

Letermovir (LMV) is an experimental cytomegalovirus terminase inhibitor undergoing phase 3 clinical trials. Viral mutations have been described at UL56 codons 231 to 369 that confer widely variable levels of LMV resistance. In this study, 15 independent experiments propagating an exonuclease mutant viral strain in escalating LMV concentrations replicated 6 of the 7 published UL56 mutations and commonly elicited additional resistance-conferring mutations at UL56 codons 231, 236, 237, 244, 257, 261, 325, and 329. Mutations were first detected earlier in LMV (median, 3 passages) than in 8 parallel experiments with foscarnet (median, 15 passages). As LMV concentrations increased, the typical initial UL56 change F261L, which confers low-grade resistance, combined or was replaced with mutations conferring higher-grade resistance, eventually enabling normal viral growth in 30 μM LMV (>5,000-fold the 50% effective concentration [EC50] for the wild type). At high LMV concentrations, the UL56 changes C325F/R were commonly detected, as well as a combination of changes at codons 236, 257, 329, and/or 369. Recombinant viruses containing individual UL56 mutations and combinations were constructed to confirm their resistance phenotypes and normal growth in cell culture. Several double and triple mutants showed much higher LMV resistance than the respective single mutants, particularly those including changes at both codons 236 and 257. The multiplicity of pathways to high-grade LMV resistance with minimal viral growth impact suggests a low viral genetic barrier and the need for close monitoring during treatment of active infection.
Comparative Genomic Analysis of Meningitis- and Bacteremia-Causing Pneumococci Identifies a Common Core Genome
Authors: Kulohoma Benard W. , Cornick Jennifer E. , Chaguza Chrispin , Yalcin Feyruz , Harris Simon R. , Gray Katherine J. , Kiran Anmol M. , Molyneux Elizabeth , French Neil , Parkhill Julian , Faragher Brian E. , Everett Dean B. , Bentley Stephen D. , Heyderman Robert S.
Published: August 2015

Streptococcus pneumoniae
is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. Here, we used whole-genome sequencing of 140 isolates of
S. pneumoniae
recovered from bloodstream infection (
n
= 70) and meningitis (
n
= 70) to compare their genetic contents. By fitting a double-exponential decaying-function model, we show that these isolates share a core of 1,427 genes (95% confidence interval [CI], 1,425 to 1,435 genes) and that there is no difference in the core genome or accessory gene content from these disease manifestations. Gene presence/absence alone therefore does not explain the virulence behavior of pneumococci that reach the meninges. Our analysis, however, supports the requirement of a range of previously described virulence factors and vaccine candidates for both meningitis- and bacteremia-causing pneumococci. This high-resolution view suggests that, despite considerable competency for genetic exchange, all pneumococci are under considerable pressure to retain key components advantageous for colonization and transmission and that these components are essential for access to and survival in sterile sites.
NanI Sialidase, CcpA, and CodY Work Together To Regulate Epsilon Toxin Production by Clostridium perfringens Type D Strain CN3718
Authors: Li Jihong , Freedman John C. , McClane Bruce A.
Published: August 2015

Clostridium perfringens
type D strains are usually associated with diseases of livestock, and their virulence requires the production of epsilon toxin (ETX). We previously showed (J. Li, S. Sayeed, S. Robertson, J. Chen, and B. A. McClane, PLoS Pathog 7:e1002429, 2011,
http://dx.doi.org/10.1371/journal.ppat.1002429
) that BMC202, a
nanI
null mutant of type D strain CN3718, produces less ETX than wild-type CN3718 does. The current study proved that the lower ETX production by strain BMC202 is due to
nanI
gene disruption, since both genetic and physical (NanI or sialic acid) complementation increased ETX production by BMC202. Furthermore, a sialidase inhibitor that interfered with NanI activity also reduced ETX production by wild-type CN3718. The NanI effect on ETX production was shown to involve reductions in
codY
and
ccpA
gene transcription levels in BMC202 versus wild-type CN3718. Similar to CodY, CcpA was found to positively control ETX production. A double
codY
ccpA
null mutant produced even less ETX than a
codY
or
ccpA
single null mutant. CcpA bound directly to sequences upstream of the
etx
or
codY
start codon, and bioinformatics identified putative CcpA-binding
cre
sites immediately upstream of both the
codY
and
etx
start codons, suggesting possible direct CcpA regulatory effects. A
ccpA
mutation also decreased
codY
transcription, suggesting that CcpA effects on ETX production can be both direct and indirect, including effects on
codY
transcription. Collectively, these results suggest that NanI, CcpA, and CodY work together to regulate ETX production, with NanI-generated sialic acid from the intestines possibly signaling type D strains to upregulate their ETX production and induce disease.

IMPORTANCE
Clostridium perfringens
NanI was previously shown to increase ETX binding to, and cytotoxicity for, MDCK host cells. The current study demonstrates that NanI also regulates ETX production via increased transcription of genes encoding the CodY and CcpA global regulators. Results obtained using single
ccpA
or
codY
null mutants and a
ccpA
codY
double null mutant showed that
codY
and
ccpA
regulate ETX production independently of one another but that
ccpA
also affects
codY
transcription. Electrophoretic mobility shift assays and bioinformatic analyses suggest that both CodY and CcpA may directly regulate
etx
transcription. Collectively, results of this study suggest that sialic acid generated by NanI from intestinal sources signals ETX-producing
C. perfringens
strains, via CcpA and CodY, to upregulate ETX production and cause disease.