bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing the Budget: Stock‐Flow Reasoning and the CO2 Accumulation Problem
Authors: Newell Ben R. , Kary Arthur , Moore Chris , Gonzalez Cleotilde 
Published: December 2015

AbstractThe majority of people show persistent poor performance in reasoning about “stock‐flow problems” in the laboratory. An important example is the failure to understand the relationship between the “stock” of CO2 in the atmosphere, the “inflow” via anthropogenic CO2 emissions, and the “outflow” via natural CO2 absorption. This study addresses potential causes of reasoning failures in the CO2 accumulation problem and reports two experiments involving a simple re‐framing of the task as managing an analogous financial (rather than CO2) budget. In Experiment 1 a financial version of the task that required participants to think in terms of controlling debt demonstrated significant improvements compared to a standard CO2 accumulation problem. Experiment 2, in which participants were invited to think about managing savings, suggested that this improvement was fortuitous and coincidental rather than due to a fundamental change in understanding the stock‐flow relationships. The role of graphical information in aiding or abetting stock‐flow reasoning was also explored in both experiments, with the results suggesting that graphs do not always assist understanding. The potential for leveraging the kind of reasoning exhibited in such tasks in an effort to change people's willingness to reduce CO2 emissions is briefly discussed.
Capnocytophaga canimorsus Meningitis: Three Cases and a Review of the Literature
Authors: van Samkar A. , Brouwer M. C. , Schultsz C. , van der Ende A. , van de Beek D. 
Published: December 2015

SummaryBacterial meningitis is a disease with a high morbidity and mortality. It may be caused by the zoonotic pathogen Capnocytophaga canimorsus, which is part of the commensal oral flora in dogs and cats. We report three cases of C. canimorsus meningitis in a nationwide cohort study of bacterial meningitis patients and performed a review of the literature. Three episodes of C. canimorsus meningitis were identified in three patients included in a nationwide cohort study from 2006 through 2014. The calculated annual incidence was 0.03 per million adults. When combined with the literature, 33 patients were identified of which 28 were male (85%). The median age was 63 years, and 13 (42%) were immunocompromised, which consisted of alcoholism in 7 (21%). Animal contact could be established in 29 of 30 patients (93%) and consisted of dog bites in 22 of 29 (76%). One patient died (3%) and 8 had neurological sequelae upon discharge (25%), most often hearing loss (n = 6, 19%). Capnocytophaga canimorsus meningitis is associated with dog bites. Although mortality is relatively low, survivors often have neurological sequelae.
STAT-5 Regulates Transcription of the Topoisomerase IIβ-Binding Protein 1 (TopBP1) Gene To Activate the ATR Pathway and Promote Human Papillomavirus Replication
Authors: Hong Shiyuan , Cheng Shouqiang , Iovane Andre , Laimins Laimonis A. 
Published: December 2015

ABSTRACT
The life cycle of high-risk human papillomaviruses (HPVs) is dependent upon epithelial differentiation. Following infection of basal cells, HPV genomes are stably maintained at low copy numbers, and productive replication or amplification is restricted to highly differentiated suprabasal cells. In high-risk HPV infections, the ATM pathway is constitutively activated in the absence of external DNA-damaging agents and is required for productive viral replication. The ataxia telangiectasia (ATM) pathway repairs double-strand breaks in DNA, while the ataxia telangiectasia and Rad3-related (ATR) pathway targets single-strand breaks. Our studies show that the ATR pathway, like the ATM pathway, is activated in HPV-positive cells and that inhibitors of ATR or CHK1 phosphorylation block both amplification and late viral gene expression in differentiated cells while moderately reducing stable copy numbers in undifferentiated cells. TopBP1 is a critical upstream activator of the ATR pathway and is expressed at elevated levels in HPV-positive cells. This increased expression of TopBP1 is necessary for ATR/CHK1 activation in HPV-positive cells, and knockdown blocks amplification. Furthermore, TopBP1 activation is shown to be regulated at the level of transcription initiation by the innate immune regulator STAT-5, which is activated by HPV proteins. STAT-5 has also been shown to be a regulator of the ATM response, demonstrating that these two pathways are coordinately regulated in HPV-positive cells. These findings identify a novel link between the innate immune response and activation of the ATR DNA damage response in regulating the life cycle of high-risk HPVs.

IMPORTANCE
High-risk human papillomaviruses (HPVs) are the causative agents of cervical and other anogenital cancers, as well as many oral cancers. HPVs infect epithelial cells and restrict productive viral replication or amplification and virion production to differentiated cells. Our studies demonstrate that HPVs activate the ATR single-strand DNA repair pathway and this activation is necessary for HPV genome amplification. The innate immune regulator STAT-5 is shown to regulate transcription of the ATR binding factor TopBP1, and this is critical for the induction of the ATR pathway. Our study identifies important links between innate immune signaling, the ATR DNA damage pathway, and productive HPV replication that may lead to the characterization of new targets for the development of therapeutics to treat HPV-induced infections.
Policy change eliminating body checking in non-elite ice hockey leads to a threefold reduction in injury and concussion risk in 11- and 12-year-old players
Authors: Black Amanda M , Macpherson Alison K , Hagel Brent E , Romiti Maria A , Palacios-Derflingher Luz , Kang Jian , Meeuwisse Willem H , Emery Carolyn A 
Published: December 2015

BackgroundIn ice hockey, body checking is associated with an increased risk of injury. In 2011, provincial policy change disallowed body checking in non-elite Pee Wee (ages 11–12 years) leagues.ObjectiveTo compare the risk of injury and concussion between non-elite Pee Wee ice hockey players in leagues where body checking is permitted (2011–12 Alberta, Canada) and leagues where policy change disallowed body checking (2011–12 Ontario, Canada).MethodNon-elite Pee Wee players (lower 70%) from Alberta (n=590) and Ontario (n=281) and elite Pee Wee players (upper 30%) from Alberta (n=294) and Ontario (n=166) were recruited to participate in a cohort study. Baseline information, injury and exposure data was collected using validated injury surveillance.ResultsBased on multiple Poisson regression analyses (adjusted for clustering by team, exposure hours, year of play, history of injury/concussion, level of play, position and body checking attitude), the incidence rate ratio (IRR) associated with policy allowing body checking was 2.97 (95% CI 1.33 to 6.61) for all game injury and 2.83 (95% CI 1.09 to 7.31) for concussion. There were no differences between provinces in concussion [IRR=1.50 (95% CI 0.84 to 2.68)] or injury risk [IRR=1.22 (95% CI 0.69 to 2.16)] in elite levels of play where both provinces allowed body checking.ConclusionsThe rate of injury and concussion were threefold greater in non-elite Pee Wee ice hockey players in leagues where body checking was permitted. The rate of injury and concussion did not differ between provinces in elite levels, where body checking was allowed.
Sidecut radius and kinetic energy: equipment designed to reduce risk of severe traumatic knee injuries in alpine giant slalom ski racing
Authors: Kröll Josef , Spörri Jörg , Gilgien Matthias , Schwameder Hermann , Müller Erich 
Published: December 2015

BackgroundKinetic energy (Ekin) increases with speed by the power of 2 and is considered a major risk factor for injuries in alpine ski racing. There is no empirical knowledge about the effect of ski geometry on Ekin. Consequently, the aim of this study was to investigate the influence of sidecut radius on the progress of Ekinwhile skiing through a multigate section in giant slalom (GS).Methods5 European-Cup level athletes skied on three different pairs of GS skis varying in sidecut radii (30, 35 and 40 m). Each athlete's position over time within a six gate section (including flat and steep terrain) was captured by the use of a differential Global Navigational Satellite System. Ekin, speed, time and path length were analysed for each pair of skis used.ResultsWhen using skis with greater sidecut radius, average Ekinwas significantly lower over the entire six gate section, but not locally at every turn cycle. Particular decreases of Ekinwere observed for both turns on the flat terrain, as well as for the turn at the terrain transition and the first turn on the steep terrain. The observed decreases in Ekinwere found to be primarily explainable by increases in turn time.ConclusionsWith respect to typical sport mechanisms that cause severe knee injuries, using skis with greater sidecut radius potentially provides additional injury preventative gain, particularly in specific areas within a run. However, this injury preventative gain during falls in GS should not be overestimated.
Conformal Region Classification with Instance-Transfer Boosting
Authors: Zhou Shuang , Smirnov Evgueni Nikolaevich , Peeters Ralf 
Published: December 2015

Conformal region classification focuses on developing region classifiers; i.e., classifiers that output regions (sets) of classes for new test instances.2,13,16 Conformal region classifiers have been proven to be valid for any significance level [Formula: see text] in the sense that the probability the class regions do not contain the true instances' classes does not exceed [Formula: see text]. In practice, however, conformal region classifiers need to be also efficient; i.e., they have to output non-empty and relatively small class regions. In this paper we show that conformal region classification can benefit from instance transfer learning. Our new approach consists of the basic conformal region classifier with a nonconformity function that implements instance transfer. We propose to learn such a function using a new multi-class Transfer AdaBoost.M1 algorithm. The function and its relation to the conformal region classification are theoretically justified. The experiments showed that our approach is valid for any significance level [Formula: see text] and its efficiency can be improved with instance transfer.
Injury-Mediated Vascular Regeneration Requires Endothelial ER71/ETV2
Authors: Park Changwon , Lee Tae-Jin , Bhang Suk Ho , Liu Fang , Nakamura Rei , Oladipupo Sunday S. , Pitha-Rowe Ian , Capoccia Benjamin , Choi Hong Seo , Kim Tae Min , Urao Norifumi , Ushio-Fukai Masuko , Lee Dongjun , Miyoshi Hiroyuki , Kim Byung-Soo , Lim Dae-Sik , Apte Rajendra S. , Ornitz David M. , Choi Kyunghee 
Published: December 2015

Objective—
Comprehensive understanding of the mechanisms regulating angiogenesis might provide new strategies for angiogenic therapies for treating diverse physiological and pathological ischemic conditions. The E-twenty six (ETS) factor Ets variant 2 (ETV2; aka Ets-related protein 71) is essential for the formation of hematopoietic and vascular systems. Despite its indispensable function in vessel development, ETV2 role in adult angiogenesis has not yet been addressed. We have therefore investigated the role of ETV2 in vascular regeneration.

Approach and Results—

We used endothelial
Etv2
conditional knockout mice and ischemic injury models to assess the role of ETV2 in vascular regeneration. Although
Etv2
expression was not detectable under steady-state conditions, its expression was readily observed in endothelial cells after injury. Mice lacking endothelial
Etv2
displayed impaired neovascularization in response to eye injury, wounding, or hindlimb ischemic injury. Lentiviral
Etv2
expression in ischemic hindlimbs led to improved recovery of blood perfusion with enhanced vessel formation. After injury, fetal liver kinase 1 (
Flk1
), aka VEGFR2, expression and neovascularization were significantly upregulated by
Etv2
, whereas
Flk1
expression and vascular endothelial growth factor response were significantly blunted in
Etv2
-deficient endothelial cells. Conversely, enforced
Etv2
expression enhanced vascular endothelial growth factor–mediated endothelial sprouting from embryoid bodies. Lentiviral
Flk1
expression rescued angiogenesis defects in endothelial
Etv2
conditional knockout mice after hindlimb ischemic injury. Furthermore,
Etv2
+/−
;
Flk1
+/−
double heterozygous mice displayed a more severe hindlimb ischemic injury response compared with
Etv2

+/
−

or
Flk1

+/
−

heterozygous mice, revealing an epistatic interaction between ETV2 and FLK1 in vascular regeneration.

Conclusions—
Our study demonstrates a novel obligatory role for the ETV2 in postnatal vascular repair and regeneration.
Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia
Authors: Wolters Frank J. , de Bruijn Renée F.A.G. , Hofman Albert , Koudstaal Peter J. , Ikram M. Arfan 
Published: December 2015

Objective—
Cerebral vasoreactivity (CVR) is a key factor in maintenance of continuous cerebral perfusion and a marker of (micro)vascular damage. We aimed to determine the longitudinal relation between CVR and the risk of dementia in the general population.

Approach and Results—

We determined CVR in nondemented participants who underwent transcranial Doppler with induced hypercapnia from 1997 to 1999, as part of the ongoing population-based Rotterdam Study. We used a Cox model to determine the risk of dementia in relation to CVR, adjusted for age, sex, cardiovascular risk factors, and carotid intima-media thickness. We furthermore determined decline on a cognitive test battery in relation to CVR, using linear mixed models. Among 1629 participants (mean±SD age 70.6±6.2 years, 46.2% female) with a mean follow-up of 11.5 years, 209 were diagnosed with dementia, of whom 171 had Alzheimer disease. Higher CVR at baseline was associated with lower risk of dementia (adjusted hazard ratio, 95% confidence interval, per SD increase: 0.87, 0.75–1.00) and Alzheimer disease (adjusted hazard ratio, 0.84; 0.71–0.99). This association was more profound in
APOE
ε4 carriers than in noncarriers (adjusted hazard ratio for all dementia: 0.77, 0.60–0.98 versus 0.89, 0.73–1.07). Performance on cognitive tests at baseline was better with higher CVR (g-factor:
P
=0.02), but during 3 cognitive assessments over 11 years of follow-up, higher CVR at baseline was associated with less decline in test scores on the Stroop reading and interference tasks in
APOE
ε4 carriers only (
P
=0.01 and 0.02, respectively).

Conclusions—
Impaired CVR is associated with an increased risk of dementia in the general population.
Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease
Authors: Gurbel Paul A. , Bliden Kevin P. , Turner Susan E. , Tantry Udaya S. , Gesheff Martin G. , Barr Travis P. , Covic Lidija , Kuliopulos Athan 
Published: December 2015

Objective—
Pepducins are membrane-tethered, cell-penetrating lipopeptides that target the cytoplasmic surface of their cognate receptor. Here, we report the first human use of a protease-activated receptor-1–based pepducin, which is intended as an antiplatelet agent to prevent ischemic complications of percutaneous coronary interventions.

Approach and Results—
PZ-128 was administered by 1 to 2 hours continuous intravenous infusion (0.01–2 mg/kg) to 31 subjects with coronary artery disease or multiple coronary artery disease risk factors. Safety, antiplatelet efficacy, and pharmacokinetics were assessed at baseline and 0.5, 1, 2, 6, 24 hours, and 7 to 10 days postdosing. The inhibitory effects of PZ-128 on platelet aggregation stimulated by the protease-activated receptor-1 agonist SFLLRN (8 μmol/L) at 30 minutes to 6 hours were dose dependent with 20% to 40% inhibition at 0.3 mg/kg, 40% to 60% at 0.5 mg/kg, and ≥80% to 100% at 1 to 2 mg/kg. The subgroup receiving aspirin in the 0.5 and 1-mg/kg dose cohorts had 65% to 100% inhibition of final aggregation to SFLLRN at 30 minutes to 2 hours and 95% to 100% inhibition by 6 hours. The inhibitory effects of 0.5 mg/kg PZ-128 were reversible with 50% recovery of aggregation to SFLLRN by 24 hours. There were no significant effects of PZ-128 on aggregation induced by AYPGKF, ADP, or collagen, indicating that the observed effects were specific to protease-activated receptor-1. The plasma half-life was 1.3 to 1.8 hours, and PZ-128 was nondetectable in urine. There were no effects on bleeding, coagulation, clinical chemistry, or ECG parameters.

Conclusions—
PZ-128 is a promising antiplatelet agent that provides rapid, specific, dose dependent, and reversible inhibition of platelet protease-activated receptor-1 through a novel intracellular mechanism.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01806077.
Use of Warfarin at Discharge Among Acute Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation in China
Authors: Yang Xiaomeng , Li Zixiao , Zhao Xingquan , Wang Chunjuan , Liu Liping , Wang Chunxue , Pan Yuesong , Li Hao , Wang David , Hart Robert G. , Wang Yilong , Wang Yongjun 
Published: December 2015

Background and Purpose—
Guidelines recommend oral anticoagulation for ischemic stroke patients with atrial fibrillation, and previous studies have shown the underuse of anticoagulation for these patients in China. We sought to explore the underlying reasons and factors that currently affect the use of warfarin in China.

Methods—
From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals voluntarily participating in the China National Stroke Registry II. Multivariable logistic regression models using the generalized estimating equation method were used to identify patient/hospital factors independently associated with warfarin use at discharge.

Results—
Among the 952 acute ischemic stroke patients with nonvalvular atrial fibrillation, 19.4% were discharged on warfarin. The risk of bleeding (52.8%) and patient refusal (31.9%) were the main reasons for not prescribing anticoagulation. Larger/teaching hospitals were more likely to prescribe warfarin. Older patients, heavy drinkers, patients with higher National Institutes of Health Stroke Scale score on admission were less likely to be given warfarin, whereas patients with history of heart failure and an international normalized ratio between 2.0 and 3.0 during hospitalization were significantly associated with warfarin use at discharge.

Conclusions—
The rate of warfarin use remains low among patients with ischemic stroke and known nonvalvular atrial fibrillation in China. Hospital size and academic status together with patient age, heart failure, heavy alcohol drinking, international normalized ratio in hospital, and stroke severity on admission were each independently associated with the use of warfarin at discharge. There is much room for improvement for secondary stroke prevention in nonvalvular atrial fibrillation patients in China.
Attentional Selection Can Be Predicted by Reinforcement Learning of Task-relevant Stimulus Features Weighted by Value-independent Stickiness
Authors: Balcarras Matthew , Ardid Salva , Kaping Daniel , Everling Stefan , Womelsdorf Thilo 
Published: December 2015

AbstractAttention includes processes that evaluate stimuli relevance, select the most relevant stimulus against less relevant stimuli, and bias choice behavior toward the selected information. It is not clear how these processes interact. Here, we captured these processes in a reinforcement learning framework applied to a feature-based attention task that required macaques to learn and update the value of stimulus features while ignoring nonrelevant sensory features, locations, and action plans. We found that value-based reinforcement learning mechanisms could account for feature-based attentional selection and choice behavior but required a value-independent stickiness selection process to explain selection errors while at asymptotic behavior. By comparing different reinforcement learning schemes, we found that trial-by-trial selections were best predicted by a model that only represents expected values for the task-relevant feature dimension, with nonrelevant stimulus features and action plans having only a marginal influence on covert selections. These findings show that attentional control subprocesses can be described by (1) the reinforcement learning of feature values within a restricted feature space that excludes irrelevant feature dimensions, (2) a stochastic selection process on feature-specific value representations, and (3) value-independent stickiness toward previous feature selections akin to perseveration in the motor domain. We speculate that these three mechanisms are implemented by distinct but interacting brain circuits and that the proposed formal account of feature-based stimulus selection will be important to understand how attentional subprocesses are implemented in primate brain networks.
A Neural Correlate of Strategic Exploration at the Onset of Adolescence
Authors: Kayser Andrew S. , Op de Macks Zdeňa , Dahl Ronald E. , Frank Michael J. 
Published: December 2015

Abstract
The onset of adolescence is associated with an increase in the behavioral tendency to explore and seek novel experiences. However, this exploration has rarely been quantified, and its neural correlates during this period remain unclear. Previously, activity within specific regions of the rostrolateral PFC (rlPFC) in adults has been shown to correlate with the tendency for exploration. Here we investigate a recently developed task to assess individual differences in strategic exploration, defined as the degree to which the relative uncertainty of rewards directs responding toward less well-evaluated choices, in 62 girls aged 11–13 years from whom resting state fMRI data were obtained in a separate session. Behaviorally, this task divided our participants into groups of explorers (n = 41) and nonexplorers (n = 21). When seed ROIs within the rlPFC were used to interrogate resting state fMRI data, we identified a lateralized connection between the rlPFC and posterior putamen/insula whose strength differentiated explorers from nonexplorers. On the basis of Granger causality analyses, the preponderant direction of influence may proceed from posterior to anterior. Together, these data provide initial evidence concerning the neural basis of exploratory tendencies at the onset of adolescence.