bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation of Lean Six Sigma Methodologies for the Evaluation of Veterans Choice Program at 3 Urban Veterans Affairs Medical Centers
Authors: Ball Sherry L. , Stevenson Lauren D. , Ladebue Amy C. , McCreight Marina S. , Lawrence Emily C. , Oestreich Taryn , Lambert-Kerzner Anne C. 
Published: April 2017

Objective:
The Veterans Health Administration (VHA) is adapting to meet the changing needs of our Veterans. VHA leaders are promoting quality improvement strategies including Lean Six Sigma (LSS). This study used LSS tools to evaluate the Veterans Choice Program (VCP), a program that aims to improve access to health care services for eligible Veterans by expanding health care options to non-VHA providers.

Research Design:
LSS was utilized to assess the current process and efficiency patterns of the VCP at 3 VHA Medical Centers. LSS techniques were used to assess data obtained through semistructured interviews with Veterans, staff, and providers to describe and evaluate the VCP process by identifying wastes and defects.

Results:
The LSS methodology facilitated the process of targeting priorities for improvement and constructing suggestions to close identified gaps and inefficiencies. Identified key process wastes included inefficient exchange of clinical information between stakeholders in and outside of the VHA; poor dissemination of VCP programmatic information; shortages of VCP-participating providers; duplication of appointments; declines in care coordination; and lack of program adaptability to local processes. Recommendations for improvement were formulated using LSS.

Conclusions:
This evaluation illustrates how LSS can be utilized to assess a nationally mandated health care program. By focusing on stakeholder, staff, and Veteran perspectives, process defects in the VCP were identified and improvement recommendations were made. However, the current LSS language used is not intuitive in health care and similar applications of LSS may consider using new language and goals adapted specifically for health care.
Multiple Sources of Prescription Payment and Risky Opioid Therapy Among Veterans
Authors: Becker William C. , Fenton Brenda T. , Brandt Cynthia A. , Doyle Erin L. , Francis Joseph , Goulet Joseph L. , Moore Brent A. , Torrise Virginia , Kerns Robert D. , Kreiner Peter W. 
Published: April 2017

Background:
Opioid overdose and other related harms are a major source of morbidity and mortality among US Veterans, in part due to high-risk opioid prescribing.

Objectives:
We sought to determine whether having multiple sources of payment for opioids—as a marker for out-of-system access—is associated with risky opioid therapy among veterans.

Research Design:
Cross-sectional study examining the association between multiple sources of payment and risky opioid therapy among all individuals with Veterans Health Administration (VHA) payment for opioid analgesic prescriptions in Kentucky during fiscal year 2014–2015.

Measures:
Source of payment categories: (1) VHA only source of payment (sole source); (2) sources of payment were VHA and at least 1 cash payment [VHA+cash payment(s)] whether or not there was a third source of payment; and (3) at least one other noncash source: Medicare, Medicaid, or private insurance [VHA+noncash source(s)]. Our outcomes were 2 risky opioid therapies: combination opioid/benzodiazepine therapy and high-dose opioid therapy, defined as morphine equivalent daily dose ≥90 mg.

Results:
Of the 14,795 individuals in the analytic sample, there were 81.9% in the sole source category, 6.6% in the VHA+cash payment(s) category, and 11.5% in the VHA+noncash source(s) category. In logistic regression, controlling for age and sex, persons with multiple payment sources had significantly higher odds of each risky opioid therapy, with those in the VHA+cash having significantly higher odds than those in the VHA+noncash source(s) group.

Conclusions:
Prescribers should examine the prescription monitoring program as multiple payment sources increase the odds of risky opioid therapy.
Patient-derived tumor xenografts of lymphoproliferative disorders: are they surrogates for the human disease?
Authors: Pizzi Marco , Inghirami Giorgio 
Published: April 2017

Purpose of review
Patient-derived tumor xenografts (PDTXs) have emerged as powerful platforms in medical oncology. A plethora of PDTXs were generated to study solid cancers, but limited data are as yet available on hematological diseases. The aim of this review is to describe the state of art of lymphoma PDTXs, discussing future directions for the development of integrated/personalized cancer programs.

Recent findings
In the last decades, several PDTXs of lymphoproliferative disorders have been produced. Most studies focused on acute lymphoblastic leukemias, but consistent results have recently been obtained also for indolent and aggressive B-/T-cell lymphomas. These models have contributed to characterize lymphoma biology and therapy, despite technical and scientific issues have partially limited their application (e.g. high costs, relatively low engraftment rates, lack of human-derived tumor microenvironment, clonal selection of engrafted cells, limited characterization of tumor grafts). In the next future, such limitations should be overcome by new technical approaches and dedicated multiinstitutional programs.

Summary
PDTXs represent an unprecedented opportunity to study the biology and clinical management of lymphoproliferative disorders. Many of the current models display limitations, which will be resolved by rigorous approaches and comprehensive libraries, recapitulating the extreme heterogeneity of such neoplasms.
Regulation of the hematopoietic stem cell lifecycle by the endothelial niche
Authors: Ramalingam Pradeep , Poulos Michael G. , Butler Jason M. 
Published: April 2017

Purpose of review
Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions.

Recent findings
Studies employing genetic vascular models have unequivocally confirmed that ECs provide the essential instructive cues for HSC emergence during embryonic development as well as adult HSC maintenance during homeostasis and regeneration. Aging of ECs may impair their ability to maintain HSC function contributing to the development of aging-associated hematopoietic deficiencies. These findings have opened up new avenues to explore the therapeutic application of ECs. ECs can be adapted to serve as an instructive platform to expand bona fide HSCs and also utilized as a cellular therapy to promote regeneration of the hematopoietic system following myelosuppressive and myeloablative injuries.

Summary
ECs provide a fertile niche for maintenance of functional HSCs throughout their lifecycle. An improved understanding of the EC-HSC cross-talk will pave the way for development of EC-directed strategies for improving HSC function during aging.
Experiences of Oncology and Palliative Care Nurses When Supporting Parents Who Have Cancer and Dependent Children
Authors: Arber Anne , Odelius Anki 
Published: April 2017

Background:
It is important not to ignore the impact of parental cancer on children, and this is where oncology and palliative care nurses can play a key role, providing support to parents as a regular aspect of oncological nursing care.

Objectives:
This study explored the experience, needs, and confidence of nurses working in acute cancer services when supporting parents with cancer who have dependent children.

Methods:
Two focus group interviews were conducted with oncology and palliative care nurses in 1 acute hospital trust in the south of England.

Results:
Nurses described how they identified with their patients as a parent themselves. This identification with patients added to the emotionally charged context of care and resulted in nurse avoidance of the troubling issue of dependent children. Nurses identified the importance of peer support with regular opportunities to reflect on practice when dealing with issues relevant to parents and children.

Conclusions:
Oncology and palliative care nurses take a reactive approach to family centred care, taking their cue from patients to initiate or request support for their children.

Implications for Practice:
Guidance was needed on children’s developmental stages and how to communicate with children of different ages. In addition, guidance was needed on assessing family needs and access to up to date resources. To enable nurses to engage with the issue of children, strategies of peer support and further educational opportunities need to be implemented.
Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome*
Authors: Carcillo Joseph A. , Halstead E. Scott , Hall Mark W. , Nguyen Trung C. , Reeder Ron , Aneja Rajesh , Shakoory Bita , Simon Dennis 
Published: April 2017

Objectives:
We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis.

Design:
Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes.

Setting:
Tertiary children’s hospital PICU.

Patients:
One hundred consecutive severe sepsis admissions.

Interventions:
Clinical data were recorded daily, and blood was collected twice weekly.

Measurements and Main Results:
Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002).

Conclusions:
Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.
Community-Level HIV Stigma as a Driver for HIV Transmission Risk Behaviors and Sexually Transmitted Diseases in Sierra Leone: A Population-Based Study
Authors: Daniel Kelly J. , Reid Michael J. , Lahiff Maureen , Tsai Alexander C. , Weiser Sheri D. 
Published: April 2017

Introduction:
Although HIV stigma has been identified as an important risk factor for HIV transmission risk behaviors, little is known about the contribution of community-level HIV stigma to HIV transmission risk behaviors and self-reported sexually transmitted diseases (STDs) or how gender may modify associations.

Methods:
We pooled data from the 2008 and 2013 Sierra Leone Demographic and Health Surveys. For HIV stigma, we examined HIV stigmatizing attitudes and HIV disclosure concerns at both individual and community levels. Outcomes of HIV transmission risk behaviors were recent condom usage, consistent condom usage, and self-reported STDs. We assessed associations with multivariable logistic regressions. We also analyzed gender as an effect modifier of these associations.

Results:
Of 34,574 respondents, 24,030 (69.5%) who had heard of HIV were included in this analysis. Community-level HIV stigmatizing attitudes and disclosure concerns were associated with higher odds of self-reported STDs (adjusted odds ratio = 2.07; 95% confidence interval: 1.55 to 2.77; adjusted odds ratio = 2.95; 95% confidence interval: 1.51 to 5.58). Compared with men, community-level HIV stigmatizing attitudes among women were a stronger driver of self-reported STDs (interaction P = 0.07). Gender modified the association between community-level HIV disclosure concerns and both recent and consistent condom usage (interaction P = 0.03 and P = 0.002, respectively). Community-level HIV disclosure concerns among women were observed to be a driver of risky sex and self-reported STDs.

Conclusions:
This study shows that community-level HIV stigma may be a driver for risky sex and self-reported STDs, particularly among women. Our findings suggest that community-held stigmatizing beliefs and HIV disclosure concerns among women might be important targets for HIV stigma reduction interventions.
Assessing the role of inhibition in stabilizing neocortical networks requires large-scale perturbation of the inhibitory population
Authors: Sadeh Sadra , Silver R. Angus , Mrsic-Flogel Thomas , Richard Muir Dylan 
Published: April 2017

AbstractNeurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011) and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This “balance” between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations they perform. Networks of neurons combining an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs; Tsodyks et al. 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). We re-examined this question by investigating how cortical network models consisting of many neurons behave following perturbations, and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed in order to robustly detect an ISN regime in cortex. We propose that wide-field optogenetic suppression of inhibition under a promoter targeting all inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms.Significance statementMany useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an “inhibition-stabilized network” or “ISN” regime). However, recent experimental results suggest this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism, and found that in order to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs, targetting a majority of inhibitory neurons, may be able to resolve this question.
Case fatality as an indicator for the human toxicity of pesticides - a systematic review on the availability and variability of severity indicators of pesticide poisoning
Authors: Moebus Susanne , Boedeker Wolfgang 
Published: April 2017

AbstractObjectiveTo investigate if case fatality and other indicators of severity of human pesticide poisonings can be used to prioritize pesticides of public health concern. To study the heterogeneity of data across countries, cause of poisonings, and treatment facilities.MethodsWe searched literature databases as well as the internet for studies on case-fatality and severity scores of pesticide poisoning. Studies published between 1990 and 2014 providing information on active ingredients in pesticides or chemical groups of active ingredients were included. The variability of case-fatality-ratios was analyzed by computing the coefficient of variation as the ratio of the standard deviation to the mean.FindingsWe identified 145 studies of which 67 could be included after assessment. Case-fatality-ratio (CFR) on 68 active ingredients and additionally on 13 groups of active ingredients were reported from 20 countries. Mean CFR for group of pesticides is 12 %, for single pesticides 15 %. Of those 12 active ingredients with a CFR above 20 % only two are WHO-classified as “extremely hazardous” or “highly hazardous”, respectively. Two of seven pesticides considered “unlikely to present hazard in normal use” show CFR above 20 %. The variability of reported case fatality was rather low.ConclusionAlthough human pesticide poisoning is a serious public health problem an unexpected small number of publications report on the clinical outcomes. However, CFR of acute human pesticide poisoning are available for several groups of pesticides as well as for active ingredients and show little variability. Therefore the CFR might be utilized to prioritize highly hazardous pesticides especially since there is limited correspondence between the animal-test-based hazard classification and the human CFR of the respective pesticide. Reporting of available poisoning data should be improved, human case-fatality data are a reasonable tool to be included systematically in pesticide registration and regulation.
Individual variation of natural D. melanogaster associated bacterial communities
Authors: Wang Yun , Staubach Fabian 
Published: April 2017

AbstractD. melanogaster has become an important model organism to study host-microbe interaction. However, we still know little about the natural microbial communities that are associated with D. melanogaster. Especially, information on inter-individual variation is still lacking because most studies so far have used pooled material from several flies. Here, we collected bacterial 16S rRNA gene community profiles from a set of 32 individuals from a single population and compare the variation to that of samples collected from different substrates and locations. While community differences were on average larger between samples collected from different substrates, there was still a surprising amount of variation of microbial communities between individual flies. The samples clustered into two groups suggesting that there are yet unknown factors that affect the composition of natural fly associated microbial communities and need research.ImportanceD. melanogaster is an important model organism in evolutionary biology and also for the study of host-microbe interaction. In order to connect these to aspects of D. melanogaster biology, it is crucial to better understand the natural D. melanogaster microbiota because only the natural microbiota can affect the evolution of the host. We present, to our knowledge, the first data set that captures inter-individual variation of D. melanogaster associated bacterial communities. Clustering of communities into two larger groups suggests that there are important drivers of these communities that we do not understand yet suggesting in return that more research on the natural microbiota of D. melanogaster is needed.
Last and corresponding authorship practices in ecology
Authors: Duffy Meghan A. 
Published: April 2017

AbstractAuthorship is intended to convey information regarding credit and responsibility for manuscripts. However, while there is general agreement within ecology that the first author is the person who contributed the most to a particular project, there is less agreement regarding whether being last author is a position of significance and regarding what is indicated by someone being the corresponding author on a manuscript. Using an analysis of papers published inAmerican Naturalist,Ecology,Evolution,andOikos,I found that: 1) the number of authors on papers is increasing over time; 2) the proportion of first authors as corresponding author has increased over time, as has the proportion of last authors as corresponding author; 3) 84% of papers published in 2016 had the first author as corresponding author; and 4) geographic regions differed in the likelihood of having the first (or last) author as corresponding author. I also carried out an online survey to better understand views on last and corresponding authorship. This survey revealed that most ecologists view the last author as the “senior” author on a paper (that is, the person who runs the research group in which most of the work was carried out), and most ecologists view the corresponding author as the person taking full responsibility for a paper. However, there was substantial variation in views on authorship, especially corresponding authorship. Given these results, I suggest that discussions of authorship have as their starting point that the first author will be corresponding author and the senior author will be last author. I also suggest ways of deciding author order in cases where two senior authors contributed equally.
Transcriptome-wide prediction of lncRNA-RNA interactions by a thermodynamics algorithm
Authors: Antonov Ivan , Marakhonov Andrey , Zamkova Maria , Skoblov Mikhail , Medvedeva Yulia 
Published: April 2017

AbstractMotivationThe discovery of thousands of long noncoding RNAs (lncRNAs) in mammals raises a question about their functionality. It has been shown that some of them function post-transcriptionally via formation of inter-molecular duplexes. Sequence alignment tools are frequently used for transcriptome-wide prediction of RNA-RNA interactions. However, such approaches have poor prediction accuracy since they ignore RNA secondary structure and interaction energy. On the other hand, application of the thermodynamics-based algorithms to long transcripts is not computationally feasible on a large scale.ResultsHere we describe a new computational pipeline ASSA that combines sequence alignment and thermodynamics tools for efficient prediction of RNA-RNA interactions between long transcripts. ASSA outperforms four other tools in terms of the Area Under the Curve. ASSA predictions for the lncRNAHOTAIRconfirm that it binds to the chromatin through hybridization with the nascent transcripts. Analysis of the 49 murine lncRNA knockdown experiments reveals one transcript that may regulate its targets via RNA-RNA interactions.AvailabilityASSA is available athttp://assa.sourceforge.net/.Contactivan.antonov@gatech.edu