bluuebunny/crossref_metadata_2025 huggingface dataset:
Children's Play and Culture Learning in an Egalitarian Foraging Society
Authors: Boyette Adam H.
Published: May 2016

Few systematic studies of play in foragers exist despite their significance for understanding the breadth of contexts for human development and the ontogeny of cultural learning. Forager societies lack complex social hierarchies, avenues for prestige or wealth accumulation, and formal educational institutions, and thereby represent a contrast to the contexts of most play research. Analysis of systematic observations of children's play among Aka forest foragers (n = 50, ages 4–16,M = 9.5) and Ngandu subsistence farmers (n = 48, ages 4–16,M = 9.1) collected in 2010 illustrates that while play and work trade off during development in both groups, and consistent patterns in sex‐role development are evident, Aka children engage in significantly less rough‐and‐tumble play and competitive games than children among their socially stratified farming neighbors.
Children's Pragmatic Inferences as a Route for Learning About the World
Authors: Horowitz Alexandra C. , Frank Michael C.
Published: May 2016

This study investigated whether children can infer category properties based on how a speaker describes an individual (e.g., saying something is a “small zib” implies that zibs are generally bigger than this one). Three‐ to 5‐year‐olds (N = 264) from a university preschool and a children's museum were tested on their ability to make this sort of contrast inference. Children made some inferences from adjective choice alone (Experiment 1); performance increased as more cues to contrast were added (Experiments 2 and 3). Control studies show that these findings are not due to the particular properties used or the structure of these tasks (Experiments 4 and 5). These findings suggest that sensitivity to speakers' production choices may help children learn about the world.
The Ontogeny of Cultural Learning
Authors: Legare Cristine H. , Harris Paul L.
Published: May 2016

Developmental research has the potential to address some of the critical gaps in our scientific understanding of the role played by cultural learning in ontogenetic outcomes. The goal of this special section was to gather together leading examples of research on cultural learning across a variety of social contexts and caregiving settings. Although the field of developmental psychology continues to struggle with the persistent problem of oversampling U.S. and Western European populations, we argue that the articles in this special section add to the growing evidence that children everywhere draw on a repertoire of cultural learning strategies that optimize their acquisition of the specific practices, beliefs, and values of their communities. We also identify future directions and outline best practices for the conduct of research on cultural learning.
The pattern of anxiolytic and hypnotic management by Australian general practice trainees
Authors: Holliday Simon M. , Morgan Simon , Tapley Amanda , Henderson Kim M. , Dunlop Adrian J. , van Driel Mieke L. , Spike Neil A. , McArthur Lawrence A. , Ball Jean , Oldmeadow Christopher J. , Magin Parker J.
Published: May 2016

Introduction and Aims

Guidelines recommend anxiolytics and hypnotics (A/H) as second‐line, short‐term medications. We aimed to establish prevalence and associations of A/H prescribing by Australian general practice (GP) trainees.

Design and Methods

A cross‐sectional analysis from a cohort study of vocational trainees from four GP Regional Training Providers during 2010–2013. General practice trainees act as independent practitioners (including for prescribing purposes) while having recourse to advice from a GP supervisor. Practice and trainee demographic data were collected as well as patient, clinical and educational data from 60 consecutive consultations of each trainee each training term. Analysis was at the level of individual problem managed, with the outcome factor being prescription of any anxiolytic or hypnotic.

Results

Overall, 645 registrars (response rate 94.0%) prescribed 68 582 medications in 69 621 consultations (with 112 890 problems managed). A/Hs were prescribed for 1.3% of problems managed and comprised 2.2% of all prescriptions. They were prescribed particularly for insomnia (28.2%) or anxiety (21.8%), but also for many ‘off‐label’ indications. Significant associations of A/H prescriptions were: patient‐level (greater age, Aboriginal and Torres Strait Islander status, English‐speaking background, being new to the trainee but not to the practice); trainee‐level (male) and consultation‐level (longer duration, pre‐existing problem, specialist referral not being made). Prescribing was significantly lower in one of the four Regional Training Providers.

Discussion and Conclusions

GP trainees, inconsistent with most guideline recommendations, prescribe A/Hs mainly as maintenance therapy to unfamiliar and older patients. Our results suggest that changes in management approaches are needed which may be facilitated by support for psychotherapeutic training. [Holliday SM, Morgan S, Tapley A, Henderson KM, Dunlop AJ, van Driel ML, Spike NA, McArthur LA, Ball J, Oldmeadow CJ, Magin PJ. The pattern of anxiolytic and hypnotic management by Australian general practice trainees. Drug Alcohol Rev 2017;36:261-269].
Applying gene flow science to environmental policy needs: a boundary work perspective
Authors: Ridley Caroline E. , Alexander Laurie C.
Published: May 2016

One application of gene flow science is the policy arena. In this article, we describe two examples in which the topic of gene flow has entered into the U.S. national environmental policymaking process: regulation of genetically engineered crops and clarification of the jurisdictional scope of the Clean Water Act. We summarize both current scientific understanding and the legal context within which gene flow science has relevance. We also discuss the process by which scientific knowledge has been synthesized and communicated to decision‐makers in these two contexts utilizing the concept of ‘boundary work’. Boundary organizations, the work they engage in to bridge the worlds of science, policy, and practice, and the boundary objects they produce to translate scientific knowledge existed in both examples. However, the specific activities and attributes of the objects produced varied based on the needs of the decision‐makers. We close with suggestions for how scientists can contribute to or engage in boundary work with policymakers.
The rise and fall of the CD28 superagonist TGN1412 and its return as TAB08: a personal account
Authors: Hünig Thomas
Published: May 2016

Two decades ago, we discovered ‘superagonistic’ monoclonal antibodies specific for the CD28 molecule which are able to polyclonally activate T cells, in particular regulatory T cells, and are therapeutically active in many rodent models of autoimmunity, inflammation, transplantation, and tissue repair. A phase I trial of the human CD28 superagonist TGN1412 failed in 2006 due to an unexpected cytokine release syndrome, but after it became clear that dose‐reduction allows to preferentially address regulatory T cells also in humans, clinical development was resumed under the name TAB08. Here, I recount the story of CD28 superagonist development from a personal perspective with an emphasis on the dramatic events during and after the 2006 phase I trial, the reasons for the failure of preclinical research to warn of the impending cytokine storm, and on the research which allowed resumption of clinical development.
Invasion of exotic piscivores causes losses of functional diversity and functionally unique species in Japanese lakes
Authors: Matsuzaki Shin‐ichiro S. , Sasaki Takehiro , Akasaka Munemitsu
Published: May 2016

Human activities affect not only species richness (SR) but also functional diversity (FD), but the consequences of species loss on FD may vary among communities. The loss of functionally unique species can result in a greater loss of FD, undermining the long‐term persistence of ecosystems.

We quantified the temporal changes in the SR and FD of native fish communities at the lake and drainage basin scales (N = 45), and investigated the relationships among these declines in SR and FD, anthropogenic drivers, and lake morphometric characteristics. We also simulated random species loss and compared the observed FD to the expected FD to examine whether losses of functionally unique species from the lakes and drainage basins had occurred.

Overall, SR and FD at the lake scale decreased by 72.1 and 75.5% from historical to current (since 2000) time periods, respectively, but the loss rates were mitigated at the drainage basin scale because some of the species that have disappeared from lakes persist in the surrounding waterbodies. Of the drivers we considered, the richness of exotic piscivores was the most important predictor of changes in both SR and FD. Increases in exotic piscivore richness reduced the SR and FD.

The consequences of species loss on FD varied among the lakes. Loss of functionally unique species at the lake scale occurred in 18 lakes and tended to be associated with increased exotic piscivore richness. In 5 of the 18 lakes, however, functionally unique species persist in the surrounding waterbodies. The persistence of these species may have the potential to increase the FD of lake fish communities.

Our findings suggest the importance of the strategic management of exotic piscivores and interconnections between lakes and their surrounding waterbodies to ensure the persistence of native fish assemblages and associated ecological functionality.
Case Report: Coexistence of SUNCT and Hypnic Headache in the Same Patient
Authors: Fantini Jacopo , Granato Antonio , Zorzon Marino , Manganotti Paolo
Published: May 2016

Background

Short‐lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co‐occurrence have been described so far.

Case results

A 49‐year‐old woman who has been suffering from SUNCT for years, with alternation of symptomatic periods and remissions, developed a new headache with different clinical features, presenting exclusively during sleep and with a dramatic responsiveness to caffeine, that met the diagnostic criteria for HH.

Conclusions

The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism.
The Greek version of the Gagging Assessment Scale in children and adolescents: psychometric properties, prevalence of gagging, and the association between gagging and dental fear
Authors: Katsouda Maria , Provatenou Efthymia , Arapostathis Konstantinos , Coolidge Trilby , Kotsanos Nikolaos
Published: May 2016

Background

No studies assessing the association between gagging and dental fear are available in pediatric samples.

Aim

To assess the psychometric properties of the Greek version of the Gagging Assessment Scale (GAS), to explore the prevalence of gagging, and to evaluate the relationship between gagging and dental fear in a pediatric sample.

Design

A total of 849 8‐ and 14‐year‐old children filled out a questionnaire consisting of demographic items, the Greek version of the GAS, and the Greek Children's Fear Survey Schedule Dental Subscale (CFSS‐DS); the older children also completed the Greek version of the Modified Dental Anxiety Scale (MDAS). The short form of dentist part of the Gagging Problem Assessment (GPA‐de‐c/SF) was used to objectively assess gagging.

Results

A total of 51 children (6.0%) demonstrated gagging on the GPA‐de‐c/SF. Children rated as gaggers on the GPA‐de‐c/SF had significantly higher GAS scores. There were no relationships between GPA‐de‐c/SF and the CFSS‐DS or MDAS. The GAS ratings were significantly correlated with the CFSS‐DS (rho = 0.420, P < 0.001) and MDAS (rho = 0.429, P < 0.001). The internal consistency was good (Cronbach's alpha = 0.697).

Conclusions

The GAS demonstrated good psychometric properties. Dental fear was correlated with the self‐report gagging assessment, but not with the objective gagging assessment.
Ethics: the perfect mix? Response to Buetow
Authors: Backström Joel , Nykänen Hannes
Published: May 2016

This is a response to Stephen Buetow's comments on our paper ‘Collectivity, evil and the dynamics of moral value’.
Participants' perceptions of an intervention implemented in an Action Research Nursing Documentation Project
Authors: Vabo Grete , Slettebø Åshild , Fossum Mariann
Published: May 2016

Aims and objectives

The aim of this study is to describe healthcare professionals’ experiences and perceptions of an intervention implemented in an action research project conducted to improve nursing documentation practices in four municipalities in Norway.

Background

Documentation of individualized patient care is a continuing concern in healthcare services and could impacts the quality and safety of healthcare. Use of electronic systems has made some aspects of documentation more comprehensive, but creation of an individualized care plan remains a pressing issue.

Design

A qualitative descriptive design was used.

Methods

An action research project was conducted between 2010–2012 to improve the content and quality of nursing documentation in community healthcare services in four municipalities. One year after the project was completed four focus group interviews were conducted with healthcare professionals, one for each involved municipality. Two unit managers were interviewed individually. Qualitative content analysis was used.

Results

Three themes emerged: healthcare professionals perceived competing interest; they experienced that they had to manage complexity and changes; and they highlighted a clear and visible leader as important for success.

Conclusions

Quality improvement activities are essential. Healthcare professionals experience a complicated situation when electronic health record systems do not support workflow. Further research is recommended to focus on the functionality and user interface of electronic health record systems, and on the role of leadership when implementing changes in clinical practice.

Relevance to clinical practice

Stronger cooperation among policymakers, electronic health record system vendors, and healthcare professionals is essential for improving electronic health record systems and documentation practices. Involvement of end‐users in these improvements can make a difference in the way the systems are perceived in the clinical workflow.
Characterization of obstructive sleep apnea–hypopnea syndrome (OSA) population by means of cluster analysis
Authors: Lacedonia Donato , Carpagnano Giovanna Elisiana , Sabato Roberto , Storto Maria Maddalena lo , Palmiotti Giuseppe Antonio , Capozzi Vito , Barbaro Maria Pia Foschino , Gallo Crescenzio
Published: May 2016

Obstructive sleep apnea–hypopnea syndrome (OSA) is being identified increasingly as an important health issue. It is typified by repeated episodes of upper airway collapse during sleep leading to occasional hypoxaemia, sleep fragmentation and poor sleep quality. OSA is also being considered as an independent risk factor for hypertension, diabetes and cardiovascular diseases, leading to increased multi‐morbidity and mortality. Cluster analysis, a powerful statistical set of techniques, may help in investigating and classifying homogeneous groups of patients with similar OSA characteristics. This study aims to investigate the (possible) different groups of patients in an OSA population, and to analyse the relationships among the main clinical variables in each group to better understand the impact of OSA on patients. Starting from a well‐characterized OSA population of 198 subjects afferent to our sleep centre, we identified three different communities of OSA patients. The first has a very severe disease [apnea–hypopnea index (AHI) = 65.91 ± 22.47] and sleep disorder has a strong impact on daily life: a low level of diurnal partial pressure of oxygen (PaO2) (77.39 ± 11.64 mmHg) and a high prevalence of hypertension (64%); the second, with less severe disease (AHI = 28.88 ± 17.13), in which sleep disorders seem to be less important for diurnal PaO2 and have a minimum impact on comorbidity; and the last with very severe OSA (AHI = 57.26 ± 15.09) but with a low risk of nocturnal hypoxaemia (T90 = 11.58 ± 8.54) and less sleepy (Epworth Sleepiness Scale 10.00 ± 4.77).
Judicial Decision Making as Knowledge Work
Authors: Owens B. Robert
Published: May 2016

I review two recent studies of judicial behavior, Posner's How Judges Think (2008) and Epstein, Landes, and Posner's Behavior of Federal Judges (2013). Epstein, Landes, and Posner's volume, the empirically richer of the two books, builds on the conceptual model for explaining judicial behavior put forward in Posner's How Judges Think. I discuss this conceptual model and argue in outline for an alternative model, complementary in part and antagonistic in part to the behaviorist research agenda. Posner and Epstein, Landes, and Posner argue for viewing the judge as a rational actor in a labor market. I argue that analyzing judicial decisions from the perspective of the sociology of knowledge, without axiomatically assuming rationality, will allow us to bring more evidentiary sources to bear on the problem and will allow for a more adequate test of competing theoretical interpretations. Law and society scholars are well positioned to contribute to this line of inquiry.
The L2 Motivational Self System and L2 Achievement: A Study of Saudi EFL Learners
Authors: MOSKOVSKY CHRISTO , ASSULAIMANI TURKI , RACHEVA SILVIA , HARKINS JEAN
Published: May 2016

The research reported in this article explores the relationship between Dörnyei's (2005, 2009) Second Language Motivational Self System (L2MSS) and the L2 proficiency level of Saudi learners of English as a foreign language (EFL). Male and female participants (N = 360) responded to a questionnaire relating to the main components of L2MSS, the ideal L2 self, the ought‐to L2 self, and the L2 learning experience, as well as learners’ intended learning efforts. The participants’ L2 proficiency was then measured with an EFL reading and writing test. Descriptive and inferential analyses of the collected data revealed—as expected—that the components of the L2MSS were a good predictor of the learners’ intended learning efforts. However, the study also established that in this learner population these components were not consistently correlated with L2 achievement. The findings can be treated as evidence that self‐reported motivation does not always have behavioral consequences.
Cross‐genera amplification of informative microsatellite markers from common bean and scarlet runner bean for assessment of genetic diversity in mungbean (Vigna radiata)
Authors: Pratap Aditya , Gupta Sanjeev , Tomar Rakhi , Malviya Nupur , Maurya Ramanuj , Pandey Vankat Raman , Mehandi Suhel , Singh Narendra Pratap
Published: May 2016

Mungbean (V. radiata) is an important Asiatic legume supplying inexpensive protein to a vast majority of vegetarian masses. To increase markers repertoire in mungbean, a study was conducted to analyse 384 microsatellite markers derived from common bean, scarlet runner bean and adzuki bean for their transferability and polymorphism. The results showed that 87 (24.71%) primer pairs could amplify DNA loci of 20 mungbean genotypes including one accession of V. trilobata, while 52 showed reliable banding and polymorphism. These showed different degrees of variability at each locus producing 250 alleles with the number of alleles varying from 2 to 9. The major allele frequency varied from 0.17 to 0.95, while the polymorphic information content of SSRs ranged between 0.09 and 0.86 with an average of 0.60 ± 0.16. UPGMA revealed three major clusters accommodating ~95% of the accessions while one accession of V. trilobata (‘NSB‐007’) did not group with any other genotype describing the discriminating power of informative microsatellites. This study identified a set of useful microsatellite markers to accelerate the genetic studies and breeding programme of mungbean.
Local dispersal of Puccinia striiformis f. sp. tritici from isolated source lesions
Authors: Farber D. H. , Medlock J. , Mundt C. C.
Published: May 2016

Understanding how disease foci arise from single source lesions has not been well studied. Here, single wheat leaves were inoculated with Puccinia striiformis f. sp. tritici urediniospores, and all wheat leaves within two intersecting 0.3 × 3.0 m transects were sampled in eight replicates over 3 years. The lesions observed on each of the top three leaves on plants within 1.5 m from the source lesion were three‐dimensionally mapped. The total number of lesions within a 1.5 m radius was estimated by dividing the number of lesions observed within each 0.025 m‐wide annulus by the fraction of the annulus sampled. The estimated total number of lesions produced within 1.5 m of a single source lesion ranged from 27 to 776, with a mean of 288 lesions. Eighty percent of the lesions were recorded within 0.69 m of the source infection. The proportion of total lesions observed at a given distance from the source was fitted well by the Lomax and Weibull distributions, reflecting the large proportion of lesions arising close to the source, and when fitted by an inverse power distribution had a slope (b) of 2.5. There were more lesions produced on leaves higher in the canopy than on lower leaves, with more lesions being detected above than below the point of inoculation. Simultaneous measurement of lesion gradients and spore dispersal in the final year of the study suggests that this pattern is due to greater susceptibility of upper leaves, rather than increased dispersal to upper leaves.
Blood group A and D negativity are associated with symptomatic West Nile virus infection
Authors: Kaidarova Zhanna , Bravo Marjorie D. , Kamel Hany T. , Custer Brian S. , Busch Michael P. , Lanteri Marion C.
Published: May 2016

BACKGROUND

West Nile virus (WNV) infection is mostly asymptomatic (AS) but 20% of subjects report WNV fever and 1% of patients experience neurologic diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic (S) infections, it is essential to understand prognostic factors influencing S disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. This study investigates the association between the ABO and D blood group status and WNV disease outcome.

STUDY DESIGN AND METHODS

The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 AS and 130 S WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O, and D blood groups and WNV clinical disease outcome.

RESULTS

S WNV+ donors exhibited increased frequencies of blood group A (S 47.6%, AS 36.8%, p = 0.04; odds ratio [OR], 1.56; 95% confidence interval [CI], 1.01‐2.40) and D– individuals (S 21.5%, AS 13.1%, p = 0.03; OR, 1.82; 95% CI, 1.04‐3.18).

CONCLUSION

The findings suggest a genetic susceptibility placing blood group A and D– individuals at risk for the development of S disease outcome after WNV infection.
Reforming Value Added Tax System in Developing World: the Case of Nepal
Authors: Acharya Sanjaya
Published: May 2016

Value Added Tax (VAT) has become an integral part of domestic tax reforms in many developing countries. Taking the case of Nepal, VAT associates a number of refunds to different private sector activities for promoting investment in higher growth and export potential sectors. Total refund, more specifically, export refund has a significant positive impact on the level of GDP. Furthermore, non-agricultural GDP has strong positive influence to VAT C-efficiency ratio. Likewise, higher the VAT gap, lower is the C-efficiency ratio. If C-efficiency is improved coupled with higher compliance, the capability of the government is strengthened in domestic revenue generation.
Validation of a Simulation Model for Analysis of Shading Effects on Photovoltaic Panels
Authors: Nashih Samuel K. , Fernandes Carlos A. F. , Torres João Paulo N. , Gomes João , Costa Branco P. J.
Published: May 2016

Numerical simulation results and modeling on the electrical features of concentrating photovoltaic-thermal (PVT) using the free circuit simulation package from linear technology corporation (LTSPICE) are presented. The effects of partial shading of cell strings and temperature are analyzed, showing very good agreement with the results obtained experimentally in lab, at Lisbon University, and under outdoor testing using similar receivers, at the SME Solarus Sunpower AB, a Swedish company whose mission is the development, production, and marketing of concentrated solar technology to the world market. The potential of the used methodology for the design of the solar cell configuration is emphasized as an important tool to optimize PV and PVT performances in the energy conversion process.
The Effect of Variation of Plyometric Push-Ups on Force-Application Kinetics and Perception of Intensity
Authors: Dhahbi Wissem , Chaouachi Anis , Dhahbi Anis Ben , Cochrane Jodie , Chèze Laurence , Burnett Angus , Chamari Karim
Published: May 2016

Purpose:

To examine differences between ground-reaction-force (GRF)-based parameters collected from 5 types of plyometric push-ups. Between-trials reliability and the relationships between parameters were also assessed.

Methods:

Thirty-seven highly active commando soldiers performed 3 trials of 5 variations of the plyometric push-up in a counterbalanced order: standard countermovement push-up (SCPu), standard squat push-up (SSPu), kneeling countermovement push-up (KCPu), kneeling squat push-up (KSPu), and drop-fall push-up (DFPu). Vertical GRF was measured during these exercises using a portable Kistler force plate. The GRF applied by the hands in the starting position (initial force supported), peak GRF and rate of force development during takeoff, flight time, impact force, and rate of force development impact on landing were determined.

Results:

During standard-position exercises (SCPu and SSPu) the initial force supported and impact force were higher (P < .001) than with kneeling exercises (KCPu, KSPu, and DFPu). The peak GRF and rate of force development during takeoff were higher (P < .001) in the countermovement push-up exercises ([CMP] SCPu, KCPu, and DFPu) than squat push-up exercises ([SP] SSPu and KSPu). Furthermore, the flight time was greater (P < .001) during kneeling exercises than during standard-position exercises. A significant relationship (P < .01) between impact force and the rate of force development impact was observed for CMP and SP exercises (r = .83 and r = .62, respectively). The initial force supported was also negatively related (P < .01) to the flight time for both CMP and SP (r = –.74 and r = –.80, respectively). It was revealed that the initial force supported and the peak GRF during takeoff had excellent reliability; however, other parameters had poor absolute reliability.

Conclusions:

It is possible to adjust the intensity of plyometric push-up exercises and train athletes’ muscle power by correctly interpreting GRF-based parameters. However, caution is required as some parameters had marginal absolute reliability.
Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL
Authors: McComb Scott , Aguadé-Gorgorió Júlia , Harder Lena , Marovca Blerim , Cario Gunnar , Eckert Cornelia , Schrappe Martin , Stanulla Martin , von Stackelberg Arend , Bourquin Jean-Pierre , Bornhauser Beat C.
Published: May 2016

SMAC mimetics simultaneously activate two different cell death pathways in treatment-resistant ALL.
Reproducibility will only come with data liberation
Authors: AlQuraishi Mohammed , Sorger Peter K.
Published: May 2016

Data irreproducibility threatens survival of the biomedical research enterprise and the well-being of patients who require better therapies.
Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice
Authors: Shono Yusuke , Docampo Melissa D. , Peled Jonathan U. , Perobelli Suelen M. , Velardi Enrico , Tsai Jennifer J. , Slingerland Ann E. , Smith Odette M. , Young Lauren F. , Gupta Jyotsna , Lieberman Sophia R. , Jay Hillary V. , Ahr Katya F. , Porosnicu Rodriguez Kori A. , Xu Ke , Calarfiore Marco , Poeck Hendrik , Caballero Silvia , Devlin Sean M. , Rapaport Franck , Dudakov Jarrod A. , Hanash Alan M. , Gyurkocza Boglarka , Murphy George F. , Gomes Camilla , Liu Chen , Moss Eli L. , Falconer Shannon B. , Bhatt Ami S. , Taur Ying , Pamer Eric G. , van den Brink Marcel R. M. , Jenq Robert R.
Published: May 2016

Treating neutropenic fever with broad-spectrum antibiotics after allogeneic hematopoietic stem cell transplant is associated with an increase in graft-versus-host disease in mice and humans.
Remote control of transplanted neurons in Parkinson’s disease
Authors: Martin Ian
Published: May 2016

Regulating the activity of transplanted dopamine neurons using DREADDs enhances rescue of motor defects in a mouse model of Parkinson’s disease.
Type I Interferons in Newborns—Neurotoxicity versus Antiviral Defense
Authors: Bogunovic Dusan
Published: May 2016

In most children and adults, primary infection with herpes simplex virus 1 (HSV-1) is asymptomatic. However, very rarely (incidence of 1 in 1,000,000), it can cause herpes simplex encephalitis (HSE). HSE also occurs in infants but with a much starker incidence of one in three. This age difference in susceptibility to HSV-1-caused HSE is not well understood. In a recent article in
mBio
, authors have identified the choroid plexus as the anatomical site of robust HSV-1 replication in the brain. They point to low levels of type I interferon (IFN) receptor as causal of the lack of HSV-1 replication control in neonates, in contrast to adults. Here, I discuss these findings in the context of human genetic evidence. I point to the balancing act of type I IFN acting as a neurotoxin and an antiviral agent, an evolutionary choice of a lesser evil.
Evolution of Myeloid Cells
Authors: Barreda Daniel R. , Neely Harold R. , Flajnik Martin F.
Published: May 2016

In 1882, Elie Metchnikoff identified myeloid-like cells from starfish larvae responding to the invasion by a foreign body (rose thorn). This marked the origins for the study of innate immunity, and an appreciation that cellular immunity was well established even in these “primitive” organisms. This chapter focuses on these myeloid cells as well as the newest members of this family, the dendritic cells, and explores their evolutionary origins. Our goal is to provide evolutionary context for the development of the multilayered immune system of mammals, where myeloid cells now serve as central effectors of innate immunity and regulators of adaptive immunity. Overall, we find that core contributions of myeloid cells to the regulation of inflammation are based on mechanisms that have been honed over hundreds of millions of years of evolution. Using phagocytosis as a platform, we show how fairly simple beginnings have offered a robust foundation onto which additional control features have been integrated, resulting in central regulatory nodes that now manage multifactorial aspects of homeostasis and immunity.
Strategies Used by Bacteria to Grow in Macrophages
Authors: Mitchell* Gabriel , Chen* Chen , Portnoy Daniel A.
Published: May 2016

Intracellular bacteria are often clinically relevant pathogens that infect virtually every cell type found in host organisms. However, myeloid cells, especially macrophages, constitute the primary cells targeted by most species of intracellular bacteria. Paradoxically, macrophages possess an extensive antimicrobial arsenal and are efficient at killing microbes. In addition to their ability to detect and signal the presence of pathogens, macrophages sequester and digest microorganisms using the phagolysosomal and autophagy pathways or, ultimately, eliminate themselves through the induction of programmed cell death. Consequently, intracellular bacteria influence numerous host processes and deploy sophisticated strategies to replicate within these host cells. Although most intracellular bacteria have a unique intracellular life cycle, these pathogens are broadly categorized into intravacuolar and cytosolic bacteria. Following phagocytosis, intravacuolar bacteria reside in the host endomembrane system and, to some extent, are protected from the host cytosolic innate immune defenses. However, the intravacuolar lifestyle requires the generation and maintenance of unique specialized bacteria-containing vacuoles and involves a complex network of host-pathogen interactions. Conversely, cytosolic bacteria escape the phagolysosomal pathway and thrive in the nutrient-rich cytosol despite the presence of host cell-autonomous defenses. The understanding of host-pathogen interactions involved in the pathogenesis of intracellular bacteria will continue to provide mechanistic insights into basic cellular processes and may lead to the discovery of novel therapeutics targeting infectious and inflammatory diseases.
Candida–Bacteria Interactions: Their Impact on Human Disease
Authors: Allison Devon L. , Willems Hubertine M. E. , Jayatilake J.A.M.S. , Bruno Vincent M. , Peters Brian M. , Shirtliff Mark E.
Published: May 2016

Candidaspecies are the most common infectious fungal species in humans; out of the approximately 150 known species,Candida albicansis the leading pathogenic species, largely affecting immunocompromised individuals. Apart from its role as the primary etiology for various types of candidiasis,C. albicansis known to contribute to polymicrobial infections. Polymicrobial interactions, particularly betweenC. albicansand bacterial species, have gained recent interest in which polymicrobial biofilm virulence mechanisms have been studied including adhesion, invasion, quorum sensing, and development of antimicrobial resistance. These trans-kingdom interactions, either synergistic or antagonistic, may help modulate the virulence and pathogenicity of bothCandidaand bacteria while uniquely impacting the pathogen–host immune response. As antibiotic and antifungal resistance increases, there is a great need to explore the intermicrobial cross-talk with a focus on the treatment ofCandida-associated polymicrobial infections. This article explores the current literature on the interactions betweenCandidaand clinically important bacteria and evaluates these interactions in the context of pathogenesis, diagnosis, and disease management.
First reported association of chronic lymphocytic leukaemia and interstitial granulomatous dermatitis
Authors: Riaz Irbaz Bin , Kamal Muhammad Umar , Segal Robert J , Anwer Faiz
Published: May 2016

Interstitial granulomatous dermatitis (IGD), a rare disease, is well known to be associated with connective tissue disorders, malignancies and several drugs. We describe this first case of IGD in association with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). A 66-year-old woman with a 6-year history of untreated CLL/SLL, presented with a 2-month history of progressively worsening eruption of the left thigh, along with fatigue, lymphadenopathy and night sweats. Skin biopsy showed findings consistent with IGD and infiltration of CLL. The eruption was non-responsive to treatment with antibiotics and local steroids. There was a significant improvement in the rash after an initial cycle of chemotherapy (combination therapy with bendamustine and rituximab) and complete resolution by the third cycle, for the treatment of her CLL. We suggest that the possibility of an underlying haematological malignancy should be investigated in patients with a skin rash non-responsive to conventional therapy.
Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence
Authors: Lie Geoffrey , Morley Thomas , Chowdhury Muhammad
Published: May 2016

An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.
Symptoms of depression and all-cause mortality in farmers, a cohort study: the HUNT study, Norway
Authors: Letnes Jon Magne , Torske Magnhild Oust , Hilt Bjørn , Bjørngaard Johan Håkon , Krokstad Steinar
Published: May 2016

Objectives

To explore all-cause mortality and the association between symptoms of depression and all-cause mortality in farmers compared with other occupational groups, using a prospective cohort design.

Methods

We included adult participants with a known occupation from the second wave of the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag 2 (HUNT2) 1995–1997), Norway. Complete information on emigration and death from all causes was obtained from the National Registries. We used the depression subscale of the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of depression. We compared farmers to 4 other occupational groups. Our baseline study population comprised 32 618 participants. Statistical analyses were performed using the Cox proportional hazards models.

Results

The estimated mortality risk in farmers was lower than in all other occupations combined, with a sex and age-adjusted HR (0.91, 95% CI 0.82 to 1.00). However, farmers had an 11% increased age-adjusted and sex-adjusted mortality risk compared with the highest ranked socioeconomic group (HR 1.11, 95% CI 0.98 to 1.25). In farmers, symptoms of depression were associated with a 13% increase in sex-adjusted and age-adjusted mortality risk (HR 1.13, 95% CI 0.88 to 1.45). Compared with other occupations this was the lowest HR, also after adjusting for education, marital status, long-lasting limiting somatic illness and lifestyle factors (HR 1.08, 95% CI 0.84 to 1.39).

Conclusions

Farmers had lower all-cause mortality compared with the other occupational groups combined. Symptoms of depression were associated with an increased mortality risk in farmers, but the risk increase was smaller compared with the other occupational groups.
Service factors causing delay in specialist assessment for TIA and minor stroke: a qualitative study of GP and patient perspectives
Authors: Wilson Andrew , Coleby Dawn , Regen Emma , Phelps Kay , Windridge Kate , Willars Janet , Robinson Tom
Published: May 2016

Objective

To understand how service factors contribute to delays to specialist assessment following transient ischaemic attack (TIA) or minor stroke.

Design

Qualitative study using semistructured interviews, analysis by constant comparison.

Setting

Leicester, UK.

Participants

Patients diagnosed with TIA or minor stroke, at hospital admission or in a rapid-access TIA clinic (n=42), general practitioners (GPs) of participating patients if they had been involved in the patients’ care (n=18).

Data

Accounts from patients and GPs of factors contributing to delay following action to seek help from a healthcare professional (HCP).

Results

The following categories of delay were identified. First, delay in assessment in general practice following contact with the service; this related to availability of same day appointments, and the role of the receptionist in identifying urgent cases. Second, delays in diagnosis by the HCP first consulted, including GPs, optometrists, out-of-hours services, walk-in centres and the emergency department. Third, delays in referral after a suspected diagnosis; these included variable use of the ABCD2(Age, Blood pressure, Clinical features, Duration, Diabetes) risk stratification score and referral templates in general practice, and referral back to the patients’ GP in cases where he/she was not the first HCP consulted.

Conclusions

Primary and emergency care providers need to review how they can best handle patients presenting with symptoms that could be due to stroke or TIA. In general practice, this may include receptionist training and/or triage by a nurse or doctor. Mechanisms need to be established to enable direct referral to the TIA clinic when patients whose symptoms have resolved present to other agencies. Further work is needed to improve diagnostic accuracy by non-specialists.
The costs of inequality: whole-population modelling study of lifetime inpatient hospital costs in the English National Health Service by level of neighbourhood deprivation
Authors: Asaria Miqdad , Doran Tim , Cookson Richard
Published: May 2016

Background

There are substantial socioeconomic inequalities in both life expectancy and healthcare use in England. In this study, we describe how these two sets of inequalities interact by estimating the social gradient in hospital costs across the life course.

Methods

Hospital episode statistics, population and index of multiple deprivation data were combined at lower-layer super output area level to estimate inpatient hospital costs for 2011/2012 by age, sex and deprivation quintile. Survival curves were estimated for each of the deprivation groups and used to estimate expected annual costs and cumulative lifetime costs.

Results

A steep social gradient was observed in overall inpatient hospital admissions, with rates ranging from 31 298/100 000 population in the most affluent fifth of areas to 43 385 in the most deprived fifth. This gradient was steeper for emergency than for elective admissions. The total cost associated with this inequality in 2011/2012 was £4.8 billion. A social gradient was also observed in the modelled lifetime costs where the lower life expectancy was not sufficient to outweigh the higher average costs in the more deprived populations. Lifetime costs for women were 14% greater than for men, due to higher costs in the reproductive years and greater life expectancy.

Conclusions

Socioeconomic inequalities result in increased morbidity and decreased life expectancy. Interventions to reduce inequality and improve health in more deprived neighbourhoods have the potential to save money for health systems not only within years but across peoples’ entire lifetimes, despite increased costs due to longer life expectancies.
α‐Chloralose poisoning in a cat
Authors: Grau‐Roma Llorenç , Stephens Adam , Wessmann Annette , Carmichael Nick , de Brot Simone
Published: May 2016

A five‐year‐old domestic cat with acute unexplainable neurological signs was presented for postmortem examination. Clinically, the cat showed an acute onset of ataxia, depressed mentation and continuous twitching/seizure activity in the morning after having been outside overnight. Despite immediate treatment, the cat progressed within 24 hours to a comatose state, opisthotonus and severe miosis unresponsive to light. Given a poor prognosis, euthanasia was elected. Gross findings were disappointing and consisted of a non‐specific lung oedema and congested lungs and spleen. Surprisingly, within the stomach and intestines, fragments of cockshafers were found. Histological examination confirmed the gross findings and additionally showed evidence of mild brain oedema, but failed to identify a cause for the severe clinical signs. In a final attempt to solve the case, a urine sample was tested for toxic substances and it was found to contain a significant amount of α‐chloralose. This finding was unexpected.
Sex difference in substrate oxidation during low-intensity isometric exercise in young adults
Authors: Sarafian Delphine , Schutz Yves , Montani Jean-Pierre , Dulloo Abdul G. , Miles-Chan Jennifer L.
Published: May 2016

Low-intensity physical activity is increasingly promoted as an alternative to sedentary behavior. However, much research to date has focused on moderate- to vigorous-intensity physical activity, and in particular dynamic work, with the effect of low-intensity isometric exercise (<4 METs) on substrate utilization yet to be explored. Here we investigate the effects of such exercise on respiratory quotient (RQ) and determine the extent of intra- and inter-individual variability in response. Energy expenditure, RQ, and substrate oxidation were measured by ventilated-hood indirect calorimetry at rest and in response to standardized, intermittent, low-level isometric leg-press exercises at 5 loads (+5, +10, +15, +20, +25 kg) in 26 healthy, young adults. Nine participants repeated the experiment on 3 separate days to assess within-subject, between-day variability. There was no significant difference in energy cost and heart rate responses to low-intensity isometric exercise (<2 METs) between men and women. However, a sex difference was apparent in terms of substrate oxidation – with men increasing both fat and carbohydrate oxidation, and women only increasing fat oxidation while maintaining carbohydrate oxidation at baseline, resting levels. This sex difference was repeatable and persisted when substrate oxidation was adjusted for differences in body weight or body composition. Individual variability in RQ was relatively low, with both intra- and inter-individual coefficients of variation in the range of 3%–6% in both sexes. These results suggest that women preferentially increase fat oxidation during low-level isometric exercise. Whether such physical activity could be incorporated into treatment/prevention strategies aimed at optimizing fat oxidation in women warrants further investigation.
Response modification factors for steel buckling restrained braced frames designed as per the 2010 National Building Code of Canada
Authors: Moni Moniruzzaman , Moradi Saber , Alam M. Shahria
Published: May 2016

This paper evaluates the overstrength, ductility, and response modification factors for low to mid-rise buckling restrained braced frames (BRBFs) designed as per the 2010 National Building Code of Canada. In addition to nonlinear static pushover analyses, dynamic time history analyses are performed to assess the seismic performance of four-, six-, and eight-story BRBFs. Different bracing configurations, including chevron (inverted-V) and split-X braces, are considered for the building frames with varied frame span lengths of 6 m and 8 m. The results confirm that the prescribed design values for overstrength and ductility factors provide reasonable estimations of the lower bound for these factors. The response modification factor obtained in this study ranged from 4.8 to 6 for different frames. The results also indicate that the response modification factor decreases with the increase of story height and span length. Moreover, bracing configurations may slightly affect the response modification factor for BRBFs.