bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fresh versus old red cell transfusions: what have the recent clinical trials found?
Authors: Shah Akshay , McKechnie Stuart , Brunskill Susan J. , Stanworth Simon J. 
Published: August 2016

Purpose of review
Red blood cell transfusion is a common treatment for anaemia worldwide, but concerns continue to be raised about adverse effects of cellular blood components, which are biological products. One hypothesis for the adverse effects associated with blood transfusion is the harmful effects of storage on red cells that have been demonstrated in laboratory and animal studies. Over the past few years, a number of more significant randomized controlled trials comparing ‘fresh’ versus ‘older’ blood have been published in an attempt to address the clinical consequences of storage age, with two further large trials ongoing.

Recent findings
These recent trials enrolled approximately 4000 participants across a variety of populations – cardiac surgical, critically ill, paediatric and acute hospitalized in-patients. All trials achieved statistically significant separation of red cell storage duration between both groups. The results of all these trials have found no clinical benefit to using fresher red cells when compared with older or standard-issue red cells. However, certain subgroups of patients either receiving red cells stored at more extreme ages of storage or those with additional risks for impaired microcirculations (critically ill elderly, severe sepsis and major haemorrhage) were either underrepresented or not included in these trials.

Summary
At present, on the basis of recent trials, there is no indication for blood transfusion services to implement preferential utilization of fresher red cell units.
Utilizing a Collaborative Learning Model to Promote Early Extubation Following Infant Heart Surgery*
Authors: Mahle William T. , Nicolson Susan C. , Hollenbeck-Pringle Danielle , Gaies Michael G. , Witte Madolin K. , Lee Eva K , Goldsworthy Michelle , Stark Paul C. , Burns Kristin M. , Scheurer Mark A. , Cooper David S. , Thiagarajan Ravi , Sivarajan V. Ben , Colan Steven D. , Schamberger Marcus S. , Shekerdemian Lara S. 
Published: August 2016

Objective:
To determine whether a collaborative learning strategy-derived clinical practice guideline can reduce the duration of endotracheal intubation following infant heart surgery.

Design:
Prospective and retrospective data collected from the Pediatric Heart Network in the 12 months pre- and post-clinical practice guideline implementation at the four sites participating in the collaborative (active sites) compared with data from five Pediatric Heart Network centers not participating in collaborative learning (control sites).

Setting:
Ten children’s hospitals.

Patients:
Data were collected for infants following two-index operations: 1) repair of isolated coarctation of the aorta (birth to 365 d) and 2) repair of tetralogy of Fallot (29–365 d). There were 240 subjects eligible for the clinical practice guideline at active sites and 259 subjects at control sites.

Interventions:
Development and application of early extubation clinical practice guideline.

Measurements and Main Results:
After clinical practice guideline implementation, the rate of early extubation at active sites increased significantly from 11.7% to 66.9% (p < 0.001) with no increase in reintubation rate. The median duration of postoperative intubation among active sites decreased from 21.2 to 4.5 hours (p < 0.001). No statistically significant change in early extubation rates was found in the control sites 11.7% to 13.7% (p = 0.63). At active sites, clinical practice guideline implementation had no statistically significant impact on median ICU length of stay (71.9 hr pre- vs 69.2 hr postimplementation; p = 0.29) for the entire cohort. There was a trend toward shorter ICU length of stay in the tetralogy of Fallot subgroup (71.6 hr pre- vs 54.2 hr postimplementation, p = 0.068).

Conclusions:
A collaborative learning strategy designed clinical practice guideline significantly increased the rate of early extubation with no change in the rate of reintubation. The early extubation clinical practice guideline did not significantly change postoperative ICU length of stay.
Early Kidney Allograft Dysfunction (Threatened Allograft): Comparative Effectiveness of Continuing Versus Discontinuation of Tacrolimus and Use of Sirolimus to Prevent Graft Failure: A Retrospective Patient-Centered Outcome Study
Authors: Wali Ravinder K. , Prentice Heather A. , Reddivari Venkata , Baffoe-Bonnie Geroge , Drachenberg Cinthia I. , Pappadimitriou John C. , Ramos Emilio , Cooper Matthew , Jonsson Johann , Bartlett Stephen , Weir Matthew R. 
Published: August 2016

Background
Due to lack of treatment options for early acute allograft dysfunction in the presence of tubular-interstitial injury without histological features of rejection, kidney transplant recipients are often treated with sirolimus-based therapy to prevent cumulative calcineurin inhibitor exposure and to prevent premature graft failure.

Methods
We analyzed transplant recipients treated with sirolimus-based (n = 220) compared with continued tacrolimus-based (n = 276) immunosuppression in recipients of early-onset graft dysfunction (threatened allograft) with the use of propensity score-based inverse probability treatment weighted models to balance for potential confounding by indication between 2 nonrandomized groups.

Results
Weighted odds for death-censored graft failure (odds ratio [OR], 1.20; 95% confidence interval [95% CI], 0.66-2.19, P = 0.555) was similar in the 2 groups, but a trend for increased risk of greater than 50% loss in estimated glomerular filtration rate from baseline in sirolimus group (OR, 1.90; 95% CI, 0.96-3.76; P = 0.067) compared with tacrolimus group. Sirloimus group compared with tacrolimus group had increased risk for death with functioning graft (OR, 2.01; 95% CI, 1.29-3.14; P = 0.002) as well as increased risk of late death (death after graft failure while on dialysis) (OR, 2.39; 95% CI, 1.59-3.59; P < 0.001). Analysis of subgroups based on the absence or presence of T cell–mediated rejection or tubulointerstitial inflammation in the index biopsy, or the use of different types of induction agents, and all subgroups had increased risk of death with functioning graft and late death if exposed to sirolimus-based therapy.

Conclusions
Use of sirolimus compared with tacrolimus in recipients with early allograft dysfunction during the first year of transplant may not prevent worsening of allograft function and could potentially lead to poor survival along with increased risk of late death.
20/40 or Better Visual Acuity After Optic Neuritis: Not as Good as We Once Thought?
Authors: Sabadia Sakinah B. , Nolan Rachel C. , Galetta Kristin M. , Narayana Kannan M. , Wilson James A. , Calabresi Peter A. , Frohman Elliot M. , Galetta Steven L. , Balcer Laura J. 
Published: August 2016

Background:Although patients with acute optic neuritis (ON) recover high-contrast visual acuity (HCVA) to 20/40 or better in 95% of affected eyes, patients with a history of ON continue to note subjective abnormalities of vision. Furthermore, substantial and permanent thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) is now known to occur early in the course of ON. We measured vision-specific quality of life (QOL) in patients with a history of acute ON and recovery of VA to 20/40 or better in their affected eyes to determine how these QOL scores relate to RNFL and GCL thickness and low-contrast letter acuity (LCLA) across the spectrum of visual recovery.Methods:Data from an ongoing collaborative study of visual outcomes in multiple sclerosis and ON were analyzed for this cross-sectional observational cohort. Patients and disease-free control participants completed the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, as well as VA and LCLA testing for each eye separately and binocularly. Optical coherence tomography measures for each eye included peripapillary RNFL thickness and macular GCL + inner plexiform layer (GCL + IPL) thickness.Results:Patients with a history of acute ON and recovery to 20/40 or better VA (n = 113) had significantly reduced scores for the NEI-VFQ-25 (83.7 ± 15.4) and 10-Item Neuro-Ophthalmic Supplement (74.6 ± 17.4) compared with disease-free controls (98.2 ± 2.1 and 96.4 ± 5.2,P< 0.001, linear regression models, accounting for age and within-patient, intereye correlations). Most patients with 20/40 or better visual recovery (98/112, 88%) had monocular HCVA in their affected eye of 20/20 or better. Although patients with 20/50 or worse HCVA recovery demonstrated the worst performance on low-contrast acuity, affected eye RNFL and GCL + IPL thickness, and QOL scales, these measures were also significantly reduced among those with 20/40 or better HCVA recovery compared with controls.Conclusions:Patients with a history of ON and “good” visual recovery, defined in the literature as 20/40 or better HCVA, are left with clinically meaningful reductions in vision-specific QOL. Such patient-observed deficits reflect the underlying significant degrees of retinal axonal and neuronal loss and visual dysfunction that are now known to characterize ON even in the setting of maximal HCVA recovery. There remains an unmet therapeutic need for patients with ON.
Using approximate Bayesian computation to quantify cell-cell adhesion parameters in a cell migratory process
Authors: Ross Robert J. H. , Baker R. E. , Parker Andrew , Ford M. J. , Mort R. L. , Yates C. A. 
Published: August 2016

AbstractIn this work we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell-cell interactions. This is important as cell-cell interactions, such as adhesion and repulsion, have been shown to play an important role in cell migration. Initially, we demonstrate with a model of anidealexperiment that we are able to identify model parameters for agent motility and adhesion, given we choose appropriate summary statistics. Following this, we replace our model of an ideal experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental repeats. The results presented in this work therefore describe timeandcost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, the results presented in this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell-cell adhesion or repulsion are known to play a significant role.
Contextual Fear Conditioning in Zebrafish
Authors: Kenney Justin W. , Scott Ian C. , Josselyn Sheena A. , Frankland Paul W. 
Published: August 2016

AbstractZebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects learning and memory in adult fish. Here, we develop a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by inhibition of (N-methyl-D-aspartate) NMDA receptors, lasts at least 14 days, and exhibits extinction. Furthermore, fish of various background strains (AB, Tu, and TL) are able to acquire fear conditioning, but differ in fear extinction rates. Taken together, we find that contextual fear conditioning in zebrafish shares many similarities with the widely used contextual fear conditioning paradigm in rodents. Combined with the amenability of genetic manipulation in zebrafish, we anticipate that our paradigm will prove to be a useful complementary system in which to examine the molecular basis of vertebrate learning and memory.
Survival of Captive Chimpanzees: Impact of Location and Transfers
Authors: Lauer Michael S. 
Published: August 2016

AbstractTo inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.
DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning
Authors: Arloth Janine , Eraslan Gökcen , Andlauer Till F.M. , Martins Jade , Iurato Stella , Kühnel Brigitte , Waldenberger Melanie , Frank Josef , Gold Ralf , Hemmer Bernhard , Luessi Felix , Nischwitz Sandra , Paul Friedemann , Wiendl Heinz , Gieger Christian , Heilmann-Heimbach Stefanie , Kacprowski Tim , Laudes Matthias , Meitinger Thomas , Peters Annette , Rawal Rajesh , Strauch Konstantin , Lucae Susanne , Müller-Myhsok Bertram , Rietschel Marcella , Theis Fabian J. , Binder Elisabeth B. , Mueller Nikola S. 
Published: August 2016

AbstractGenome-wide association studies (GWAS) identify genetic variants associated with quantitative traits or disease. Thus, GWAS never directly link variants to regulatory mechanisms, which, in turn, are typically inferred during post-hoc analyses. In parallel, a recent deep learning-based method allows for prediction of regulatory effects per variant on currently up to 1,000 cell type-specific chromatin features. We here describe “DeepWAS”, a new approach that directly integrates predictions of these regulatory effects of single variants into a multivariate GWAS setting. As a result, single variants associated with a trait or disease are, by design, coupled to their impact on a chromatin feature in a cell type. Up to 40,000 regulatory single-nucleotide polymorphisms (SNPs) were associated with multiple sclerosis (MS, 4,888 cases and 10,395 controls), major depressive disorder (MDD, 1,475 cases and 2,144 controls), and height (5,974 individuals) to each identify 43-61 regulatory SNPs, called deepSNPs, which are shown to reach at least nominal significance in large GWAS. MS- and height-specific deepSNPs resided in active chromatin and introns, whereas MDD-specific deepSNPs located mostly to intragenic regions and repressive chromatin states. We found deepSNPs to be enriched in public or cohort-matched expression and methylation quantitative trait loci and demonstrate the potential of the DeepWAS method to directly generate testable functional hypotheses based on genotype data alone. DeepWAS is an innovative GWAS approach with the power to identify individual SNPs in non-coding regions with gene regulatory capacity with a joint contribution to disease risk. DeepWAS is available at https://github.com/cellmapslab/DeepWAS.
Exaggerated CpH Methylation in the Autism-Affected Brain
Authors: Ellis Shannon E. , Gupta Simone , Moes Anna , West Andrew B. , Arking Dan E. 
Published: August 2016

AbstractThe etiology of autism, a complex neurodevelopmental disorder, remains largely unexplained. Here, we explore the role of CpG and CpH (H=A, C, or T) methylation within autism-affected cortical brain tissue. While no individual site of methylation was significantly associated with autism after multi-test correction, methylated CpH di-nucleotides were markedly enriched in autism-affected brains (~2-fold enrichment at p <0.05 cut-off, p=0.002). These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.
Relevance and evolution of adaptive markets hypothesis: a review
Authors: Dhankar Raj S. , Shankar Devesh 
Published: August 2016

Purpose
The purpose of this paper is to discuss the relevance and evolution of adaptive markets hypothesis (AMH) that has gained traction in the recent years, as it provides a dynamic perspective to the concept of informational efficiency.

Design/methodology/approach
This paper discusses several issues related to the concept of informationally efficient markets that have indicated efficient market hypothesis to be an incomplete portrayal of stock market behavior.

Findings
The authors find that a strict and perpetual adherence to informational efficiency is highly unlikely, and AMH provides a much more plausible description of the behavior of stock markets.

Originality/value
The authors provide a description of studies that examine the testable implications of AMH.
Linking microbial diversity and functionality of arctic glacial surface habitats
Authors: Lutz Stefanie , Anesio Alexandre M. , Edwards Arwyn , Benning Liane G. 
Published: August 2016

SummaryDistinct microbial habitats on glacial surfaces are dominated by snow and ice algae, which are the critical players and the dominant primary colonisers and net producers during the melt season. Here for the first time we have evaluated the role of these algae in association with the full microbial community composition (i.e., algae, bacteria, archaea) in distinct surface habitats and on 12 glaciers and permanent snow fields in Svalbard and Arctic Sweden. We cross‐correlated these data with the analyses of specific metabolites such as fatty acids and pigments, and a full suite of potential critical physico‐chemical parameters including major and minor nutrients, and trace metals. It has been shown that correlations between single algal species, metabolites, and specific geochemical parameters can be used to unravel mixed metabolic signals in complex communities, further assign them to single species and infer their functionality. The data also clearly show that the production of metabolites in snow and ice algae is driven mainly by nitrogen and less so by phosphorus limitation. This is especially important for the synthesis of secondary carotenoids, which cause a darkening of glacial surfaces leading to a decrease in surface albedo and eventually higher melting rates.
Enhanced ferrihydrite dissolution by a unicellular, planktonic cyanobacterium: a biological contribution to particulate iron bioavailability
Authors: Kranzler Chana , Kessler Nivi , Keren Nir , Shaked Yeala 
Published: August 2016

SummaryIron (Fe) bioavailability, as determined by its sources, sinks, solubility and speciation, places severe environmental constraints on microorganisms in aquatic environments. Cyanobacteria are a widespread group of aquatic, photosynthetic microorganisms with especially high iron requirements. While iron exists predominantly in particulate form, little is known about its bioavailability to cyanobacteria. Some cyanobacteria secrete iron solubilizing ligands called siderophores, yet many environmentally relevant strains do not have this ability. This work explores the bioavailability of amorphous synthetic Fe‐oxides (ferrihydrite) to the non‐siderophore producing, unicellular cyanobacterium, Synechocystis sp PCC 6803. Iron uptake assays with 55ferrihydrite established dissolution as a critical prerequisite for iron transport. Dissolution assays with the iron binding ligand, desferrioxamine B, demonstrated that Synechocystis 6803 enhances ferrihydrite dissolution, exerting siderophore‐independent biological influence on ferrihydrite bioavailability. Dissolution mechanisms were studied using a range of experimental conditions; both cell‐particle physical proximity and cellular electron flow were shown to be important determinants of bio‐dissolution by Synechocystis 6803. Finally, the effects of ferrihydrite stability on bio‐dissolution rates and cell physiology were measured, integrating biological and chemical aspects of ferrihydrite bioavailability. Collectively, these findings demonstrate that Synechocystis 6803 actively dissolves ferrihydrite, highlighting a significant biological component to mineral phase iron bioavailability in aquatic environments.
China's Growing Government Debt in a Computable Overlapping Generations Model
Authors: Li Shiyu , Lin Shuanglin , Wang Yan , Zhai Fan 
Published: August 2016

AbstractThis paper simulates the effects of China's growing government debt in a computable equilibrium model of overlapping generations. Our model assumes that the government increases debt to finance its spending in the short run, and then increases taxes or cuts spending to keep the debt–GDP ratio constant. The spending‐driven government debt increases public capital and output in the short run, but decreases private investment, total capital stock, output, and net exports in the long run, and makes the future generations worse off. Among various means of debt control, a decrease in government spending seems to be the least harmful to private investment, capital stock, and output while an increase in capital taxation is most detrimental.
Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010
Authors: Lavery JA , Friedman AM , Keyes KM , Wright JD , Ananth CV 
Published: August 2016

ObjectiveTo examine age–period–cohort effects on trends in gestational diabetes mellitus (GDM) prevalence in the US, and to evaluate how these trends have affected the rates of stillbirth and large for gestational age (LGA)/macrosomia.DesignRetrospective cohort study.SettingUSA, 1979–2010.PopulationOver 125 million pregnancies (3 337 284 GDM cases) associated with hospitalisations.MethodsTrends in GDM prevalence were examined via weighted Poisson models to parse out the extent to which GDM trends can be attributed to maternal age, period of delivery, and maternal birth cohort. Multilevel models were used to assess the contribution of population effects to the rate of GDM. Log‐linear Poisson regression models were used to estimate the contributions of the increasing GDM rates to changes in the rates of LGA and stillbirth between 1979–81 and 2008–10.Main outcome measuresRates and rate ratios (RRs).ResultsCompared with 1979–1980 (0.3%), the rate of GDM has increased to 5.8% in 2008–10, indicating a strong period effect. Substantial age and modest cohort effects were evident. The period effect is partly explained by period trends in body mass index (BMI), race, and maternal smoking. The increasing prevalence of GDM is associated with a 184% (95% CI 180–188%) decline in the rate of LGA/macrosomia and a 0.75% (95% CI 0.74–0.76) increase in the rate of stillbirths for 2008–10, compared with 1979–81.ConclusionsThe temporal increase in GDM can be attributed to period of pregnancy and age. Increasing BMI appears to partially contribute to the GDM increase in the US.Tweetable abstractThe increasing prevalence of GDM can be attributed to period of delivery and increasing maternal age.