bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in workplace car parking and commute mode: a natural experimental study
Authors: Knott Craig S , Sharp Stephen J , Mytton Oliver T , Ogilvie David , Panter Jenna 
Published: October 2018

BackgroundThe use of private motor vehicles places a considerable burden on public health. Changes in workplace car parking policies may be effective in shifting behaviour. We use a natural experimental design to assess whether changes in policy were associated with differences in commute mode.MethodsWe used cohort data from participants working in Cambridge (2009–2012). Commuters reported their trips and travel modes to work over the last week, workplace car parking policy and socioeconomic, environmental and health characteristics. Changes in policy were defined between phases (1608 transition periods; 884 participants). Using generalised estimating equations, we estimated associations between changes in parking policy and the proportion of trips that (i) were exclusively by motor vehicle, (ii) involved walking or cycling and (iii) involved public transport at follow-up.Results25.1% of trips were made by motor vehicle, 54.6% involved walking or cycling and 11.7% involved public transport. The introduction of free or paid workplace parking was associated with higher proportions of motor vehicle trips (11.4%, 95% CI (6.4 to 16.3)) and lower proportions involving walking or cycling (−13.3%, 95% CI (−20.2 to –6.4)) and public transport (−5.8%, 95% CI (−10.6 to –0.9)) compared with those with no workplace parking. Restrictive changes in policy were associated with shifts in the expected direction but these were not statistically significant.ConclusionRelaxation of parking policy was associated with higher proportions of trips made by motor vehicle. Further longitudinal and intervention research is required to assess generalisability of these findings.
Information Processing and Security Analysis of Shared System Resource Based Architectures
Authors: Anjaria Kushal , Mishra Arun 
Published: September 2018

Background: Nowadays, service-oriented architectures and cloud-based infrastructures are widely used in manufacturing industries and IT organizations. These architectures and infrastructures are based on shared system resources. In some organizations, system resources like a printer, photocopy machines, and scanners are also shared among the members of the organization. The purpose of the proposed work is to model various types of shared system resources, shared system resources based architecture/infrastructure and analyze the model to identify the possible security risk associated with shared system resources and shared system resources based architecture/infrastructure. Design Approach: To model shared system resources and shared system resources based architecture/Infrastructure, Petri net and its variations are used. For security analysis of the Petri net based model of the shared system resource, Petri net algebra based concepts are applied. Results: The present paper successfully demonstrates that the proposed Petri net based modeling approach can be used for quantitative and qualitative security analysis of shared system resources and shared system resources based architecture/infrastructure. For quantitative analysis of security risk associated with shared system resources, information theoretic concepts are used. To demonstrate the effectiveness of the proposed method, case studies are also incorporated in the present paper. The proposed approach can take various security risk factors like timing analysis attack, information leakage due to confidentiality policy violation and power analysis attack into the consideration while analyzing the security of shared system resources in the industrial environment.
Anticipatory postural adjustments and spatial organization of motor cortex: evidence of adaptive compensations in healthy older adults
Authors: Smith Jo Armour , Fisher Beth E. 
Published: October 2018

During anticipated postural perturbations induced by limb movement, the central nervous system generates anticipatory postural adjustments (APAs) in the trunk and hip musculature to minimize disturbances to equilibrium. Age-related changes in functional organization of the nervous system may contribute to changes in APAs in healthy older adults. Here we examined if altered APAs of trunk/hip musculature in older adults are accompanied by changes in the representation of these muscles in motor cortex. Twelve healthy older adults, 5 with a history of falls and 7 nonfallers, were compared with 13 young adults. APAs were assessed during a mediolateral arm raise task in standing. Temporal organization of postural adjustments was quantified as latency of APAs in the contralateral external oblique, lumbar paraspinals, and gluteus medius relative to activation of the deltoid. Spatial organization was quantified as extent of synergistic coactivation between muscles. Volume and location of the muscle representations in motor cortex were mapped using transcranial magnetic stimulation. We found that older adults demonstrated significantly delayed APAs in the gluteus medius muscle. Spatial organization of the three muscles in motor cortex differed between groups, with the older adults demonstrating more lateral external oblique representation than the other two muscles. Separate comparisons of the faller and nonfaller subgroups with young adults indicated that nonfallers had the greatest delay in gluteus medius APAs and a reduced distance between the representational areas of the lumbar paraspinals and gluteus medius. This study indicates that altered spatial organization of motor cortex accompanies altered temporal organization of APA synergies in older adults. NEW & NOTEWORTHY Anticipatory postural adjustments are a critical component of postural control. Here we demonstrate that, in healthy older adults with and without a history of falls, delayed anticipatory postural adjustments in the hip musculature during mediolateral perturbations are accompanied by altered organization of trunk/hip muscle representation in motor cortex. The largest adaptations are evident in older adults with no history of falls.
Effects of bilateral priming on motor cortex function in healthy adults
Authors: Jordan Harry T. , Stinear Cathy M. 
Published: October 2018

Bilateral priming is a rehabilitation adjuvant that can improve upper limb motor recovery poststroke. It uses a table-top device to couple the upper limbs together such that active flexion and extension of one wrist leads to passive movement of the opposite wrist in a mirror symmetric pattern. Bilateral priming increases corticomotor excitability (CME) in the primary motor cortex (M1) of the passively driven wrist; however, the neurophysiological mechanisms underlying this increase remain unclear. This study explored these mechanisms by using transcranial magnetic stimulation over the right M1 and recording motor-evoked potentials from the passively driven left extensor carpi radialis of healthy adults. Intracortical measures were recorded before and 5 and 35 min after a single 15-min session of priming. One-millisecond short-interval intracortical inhibition, long-interval intracortical inhibition, late cortical disinhibition (LCD), and intracortical facilitation were recorded with a posterior-anterior (PA) intracortical current, whereas CME and short-interval intracortical facilitation (SICF) were recorded with both PA and anterior-posterior (AP) currents. CME with PA stimulation was also recorded ~1 h postpriming. PA CME was elevated 35 min postpriming and remained elevated ~1 h postpriming. LCD decreased, and AP SICF increased at both 5 and 35 min postpriming. However, these changes in LCD and AP SICF are unlikely to be the cause of the increased PA CME because of the differing timelines of their effects and AP and PA currents activating separate interneuron circuits. These results suggest that bilateral priming does not increase CME through alterations of the intracortical circuits investigated here. NEW & NOTEWORTHY This is the first study to measure how bilateral priming modulates corticomotor excitability with posterior-anterior and anterior-posterior intracortical currents, 1-ms short-interval intracortical inhibition, late cortical disinhibition, intracortical facilitation, and short-interval intracortical facilitation. We found corticomotor excitability with a posterior-anterior current increased by 35 min until ~1 h postpriming. Short-interval intracortical facilitation with an anterior-posterior current was greater for at least 35 min postpriming. This provides further insight into the neurophysiological mechanisms underlying bilateral priming.
PD-L1 Mediates Dysfunction in Activated PD-1+ NK Cells in Head and Neck Cancer Patients
Authors: Concha-Benavente Fernando , Kansy Benjamin , Moskovitz Jessica , Moy Jennifer , Chandran Uma , Ferris Robert L. 
Published: October 2018

Abstract
Inhibitory immune-checkpoint receptors (ICRs), including programmed death 1 (PD-1), have been characterized as exhaustion markers on T cells that infiltrate the tumor microenvironment (TME) of many cancer types, including head and neck cancer (HNC). However, expression and function of ICRs, including PD-1, on natural killer (NK) cells remains less defined. NK cells are innate immune effector cells that lyse epidermal growth factor receptor–overexpressing HNC cells via cetuximab-mediated antibody-dependent cytotoxicity. Cetuximab is clinically effective but only in 10% to 15% of patients. Therefore, it is necessary to investigate how immunomodulation with cetuximab or PD-1 blockade might enhance NK cell responses in the TME and improve monoclonal antibody therapeutic efficacy. We observed that expression of PD-1 on NK cells marks an activated phenotype, which was suppressed only after binding programmed death ligand-1 (PD-L1). HNC patients who exhibit higher circulating PD-1+ NK cells associate with better clinical outcome, and these cells are enriched in the TME. Cetuximab-mediated NK cell activation increased PD-1 expression on NK cells in vitro, which was confirmed in vivo in a prospective neoadjuvant cetuximab trial. In contrast, PD-L1 ligation of PD-1+ NK cells diminished their activation status, whereas PD-1 blockade increased cetuximab-mediated NK cell activation and cytotoxicity, but only against HNC targets with high PD-L1 expression. Therefore, blocking the PD-1–PD-L1 axis may be a useful strategy to reverse immune evasion of HNC tumors with high PD-L1 expression during cetuximab therapy by reversing NK cell dysfunction.
Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure
Authors: Sabbah Hani N. , Gupta Ramesh C. , Kohli Smita , Wang Mengjun , Hachem Souheila , Zhang Kefei 
Published: September 2018

Background—
Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial function in dogs with heart failure (HF).

Methods and Results—

Fourteen dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (control, HF-CON, n=7). LV ejection fraction, plasma n-terminal pro-brain natriuretic peptide, tumor necrosis factor-α, and C-reactive protein were measured before (pretreatment) and 3 months after initiating therapy (post-treatment). Mitochondrial respiration, membrane potential (Δψm), maximum rate of ATP synthesis, and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, ejection fraction decreased at post-treatment compared with pretreatment (29±1% versus 31±2%), whereas in HF+ELA dogs, ejection fraction significantly increased at post-treatment compared with pretreatment (36±2% versus 30±2%;
P
<0.05). In HF-CON, n-terminal pro-brain natriuretic peptide increased by 88±120 pg/mL during follow-up but decreased significantly by 774±85 pg/mL in HF+ELA dogs (
P
<0.001). Treatment with elamipretide also normalized plasma tumor necrosis factor-α and C-reactive protein and restored mitochondrial state-3 respiration, Δψm, rate of ATP synthesis, and ATP/ADP ratio (ATP/ADP: 0.38±0.04 HF-CON versus 1.16±0.15 HF+ELA;
P
<0.001).

Conclusions—
Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF.
Induction Therapy With Antithymocyte Globulin in Patients Undergoing Cardiac Transplantation Is Associated With Decreased Coronary Plaque Progression as Assessed by Intravascular Ultrasound
Authors: Azarbal Babak , Cheng Richard , Vanichsarn Christopher , Patel Jignesh K. , Czer Lawrence S. , Chang David H. , Kittleson Michelle M. , Kobashigawa Jon A. 
Published: September 2018

Background—
Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS).

Methods and Results—

Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8±12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0±1.2 versus 2.3±2.6 mm
2
;
P
=0.001), maximal percent stenosis (6.3±7.9 versus 12.8±12.3%; =0.003), maximal intimal thickness (0.2±0.2 versus 0.3±0.3 mm;
P
=0.035), and plaque volume (0.5±0.7 versus 1.0±1.3 mm
3
/mm;
P
=0.016). Rapid plaque progression by maximal percent stenosis (≥20%) occurred less frequently in the ATG arm (4.3% versus 26.3;
P
=0.003). Survival (
P
=0.242) and any treated rejection (
P
=0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection (
P
=0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection (
P
=0.073).

Conclusions—
Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection.
Clinical and Echocardiographic Outcomes After Bariatric Surgery in Obese Patients With Left Ventricular Systolic Dysfunction
Authors: Vest Amanda R. , Patel Parag , Schauer Philip R. , Satava Mary Ellen , Cavalcante João L. , Brethauer Stacy , Young James B. 
Published: September 2018

Background—
Obesity is a risk factor for development of left ventricular systolic dysfunction (LVSD) and can complicate LVSD management, especially for individuals in whom cardiac transplantation is indicated. Bariatric surgery is increasingly recognized as a safe and effective intervention to achieve marked weight loss, but experience is limited in the LVSD population.

Methods and Results—

We retrospectively reviewed patients with obesity and left ventricular ejection fraction (LVEF) <50% who underwent bariatric surgery at a tertiary center 2004 to 2013. An analysis of outcomes and efficacy compared 42 surgical patients with LVSD to 2588 without known LVSD. The LVSD group had greater baseline prevalence of comorbidities and showed a slight excess of early postoperative heart failure and myocardial infarction. However, patients with LVSD achieved good weight loss efficacy (mean decrease 22.6%) and no excess in mortality at 1 year. An overlapping cohort of 38 patients with LVSD had both pre- and postoperative echocardiographic images available for review by 2 blinded readers. Obese nonsurgical controls were matched on age, sex, initial LVEF, and interval between echocardiograms. There was a mean pre- to postoperative LVEF improvement of +5.1% ±8.3 (
P
=0.0005) for surgical subjects, but not for controls (+3.4%±10.5,
P
=0.056). Among surgical subjects, 11 patients had an LVEF improvement of >10%, whereas only 6 improved by >10% among nonsurgical controls.

Conclusions—
At experienced centers, bariatric surgery may be a safe and effective intervention for obese patients with LVSD. Bariatric surgery was associated with an improvement in LVEF, although the magnitude of change was on the cusp of clinical significance.
Relation of QRS Duration to Clinical Benefit of Cardiac Resynchronization Therapy in Mild Heart Failure Patients Without Left Bundle Branch Block
Authors: Biton Yitschak , Kutyifa Valentina , Cygankiewicz Iwona , Goldenberg Ilan , Klein Helmut , McNitt Scott , Polonsky Bronislava , Ruwald Anne Christine , Ruwald Martin H. , Moss Arthur J. , Zareba Wojciech 
Published: September 2018

Background—
There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block.

Methods and Results—

We evaluated the long-term clinical outcomes of 537 non–left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter–defibrillator and CRT with defibrillator (CRT-D), respectively (
P
=0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (≤134 ms) experienced 2.4-fold (
P
=0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter–defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97,
P
=0.86;
P
value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31,
P
=0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (≤230 ms;, HR=1.19,
P
=0.386;
P
value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01,
P
=0.975), and intraventricular conduction delay (HR=1.31,
P
=0.172).

Conclusions—
Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter–defibrillator -only.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.
Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices
Authors: Nassif Michael E. , LaRue Shane J. , Raymer David S. , Novak Eric , Vader Justin M. , Ewald Gregory A. , Gage Brian F. 
Published: September 2018

Background—
We evaluated thrombotic and bleeding outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values <2.5 (range, 2–3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant.

Methods and Results—

We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between January 2005 and August 2013. Using Poisson models, we analyzed their 10 927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6±13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of <1.5, but INR values of 1.5 to 1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (hazard ratio, 0.40; 95% confidence interval, 0.22–0.72;
P
=0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6.

Conclusions—
INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values <2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.
Left Ventricular Thrombus Formation After ST-Segment–Elevation Myocardial Infarction
Authors: Pöss Janine , Desch Steffen , Eitel Charlotte , de Waha Suzanne , Thiele Holger , Eitel Ingo 
Published: September 2018

Background—
Data on left ventricular (LV) thrombus formation after primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction (STEMI) are scarce. The aims of this study were to assess the (1) incidence of LV thrombi using cardiac magnetic resonance in a multicenter cohort of STEMI patients and (2) prognostic relevance of LV thrombi at 1-year follow-up.

Methods and Results—

In total, 738 STEMI patients reperfused by primary angioplasty were enrolled in 8 centers. Cardiac magnetic resonance was completed within 1 week after infarction. Central core laboratory-masked analyses for the presence of LV thrombi were performed. The primary clinical end point was the occurrence of major adverse cardiac events within 1 year. LV thrombi were detected in 26 patients (3.5%) in the overall cohort and in 7.1% in anterior STEMI patients. The presence of thrombi was associated with larger infarcts (
P
<0.001), less myocardial salvage (
P
<0.01), impaired LV ejection fraction (
P
<0.001), and more pronounced late microvascular obstruction (
P
=0.002). The presence of thrombi was independently associated with the incidence of major adverse cardiac events at 12 months (hazard ratio, 2.73; 95% confidence interval, 1.11–6.73;
P
=0.03).

Conclusions—
In this multicenter cohort of patients with STEMI, thrombus prevalence assessed by cardiac magnetic resonance was 3.5% and associated with decreased myocardial salvage, larger infarcts, and more pronounced reperfusion injury. Importantly, LV thrombus was independently associated with major adverse cardiac events at 1-year follow-up.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00712101.