bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Pacing Profiles of Olympic and IAAF World Championship Middle-Distance Runners Across Qualifying Rounds and Finals
Authors: Hanley Brian , Stellingwerff Trent , Hettinga Florentina J. 
Published: December 2018

Purpose: This was the first study to analyze high-resolution pacing data from multiple global championships, allowing for deeper and rigorous analysis of pacing and tactical profiles in elite-standard middle-distance racing. The aim of this study was to analyze successful and unsuccessful middle-distance pacing profiles and variability across qualifying rounds and finals. Methods: Finishing and 100-m-split speeds and season’s best times were collected for 265 men and 218 women competing in 800- and 1500-m races, with pace variability expressed using coefficient of variation. Results: In both events, successful athletes generally separated themselves from slower athletes in the final 200 m, not by speeding up but by avoiding slowing compared with competitors. This was despite different pacing profiles between events in the earlier part of the race preceding the end spurt. Approximately 10% of athletes ran season’s best times, showing a tactical approach to elite-standard middle-distance racing and possible fatigue across rounds. Men’s and women’s pacing profiles were remarkably similar within each event, but the previously undescribed seahorse-shaped profile in the 800-m (predominantly positive pacing) differed from the J-shaped negative pacing of the 1500-m. Pacing variability was high compared with world records, especially in the finals (coefficient of variation: 5.2–9.1%), showing that athletes need to be able to vary pace and cope with surges. Conclusions: The best athletes had the physiological capacity to vary pace and respond to surges through successive competition rounds. In competition-specific training, coaches should incorporate several sessions in which pace changes frequently and sometimes unexpectedly.
Age-related changes in baseline reading acuity and speed as measured using RADNER Reading Charts in healthy eyes with best corrected ETDRS distance acuity
Authors: Radner Wolfgang , Benesch Thomas 
Published: December 2018

PurposeTo assess age-related differences in baseline measures of reading performance obtained from the RADNER Reading Charts in healthy eyes with best corrected (ETDRS) distance acuity.MethodsCross-sectional study of participants (n=200) aged 25–74 years (n=20 per 5 years age group). Best corrected distance visual acuity was measured monocularly with ETDRS 2000 Charts. Reading performance was evaluated binocularly with the RADNER Reading Charts. Reading acuity (RA), reading acuity score (RA score), mean reading speed (MEAN-RS), maximum reading speed, reading speed with a long paragraph, critical print size (CPS) and the logMAR/logRAD ratio were analysed.ResultsRA, RA score, CPS-1 (last logRAD with normal reading speed) and ETDRS acuity did not change significantly between age 25 and 54 years. Overall, the mean RA was −0.091±0.07 logRAD, and the RA score was −0.069±0.07 logRAD. The mean difference between the RA and best ETDRS acuity was 0.0603±0.055 logMAR (r=0.62; p<0.05). The logMAR/logRAD ratio was 87.75%±11.23%. The MEAN-RS ranged from 189±21.9 words per minute (wpm) for the group aged 70–74 years to 236±22.5 wpm for the group aged 40–44 years and correlated well with the long paragraph results (r=0.87).ConclusionBest corrected RA, reading speed and ETDRS distance acuity were constant until the age of 54 years. An age-related break point was found between the groups aged 50–54 years and 55–59 years; for reading speed, the break point can be assumed to be within the age range of 50–54 years.
Management strategies for chronic rhinosinusitis: a qualitative study of GP and ENT specialist views of current practice in the UK
Authors: Vennik Jane , Eyles Caroline , Thomas Mike , Hopkins Claire , Little Paul , Blackshaw Helen , Schilder Anne , Boardman Jim , Philpott Carl M 
Published: December 2018

ObjectivesTo explore general practitioner (GP) and ears, nose and throat (ENT) specialist perspectives of current treatment strategies for chronic rhinosinusitis (CRS) and care pathways through primary and secondary care.DesignSemi-structured qualitative telephone interviews as part of the MACRO programme (Defining best Management for Adults with Chronic Rhinosinusitis)SettingPrimary care and secondary care ENT outpatient clinics in the UK.ParticipantsTwelve GPs and 9 ENT specialists consented to in-depth telephone interviews. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis.Main outcome measuresHealthcare professional views of management options and care pathways for CRS.ResultsGPs describe themselves as confident in recognising CRS, with the exception of assessing nasal polyps. In contrast, specialists report common missed diagnoses (eg, allergy; chronic headache) when patients are referred to ENT clinics, and attribute this to the limited ENT training of GPs. Steroid nasal sprays provide the foundation of treatment in primary care, although local prescribing restrictions can affect treatment choice and poor adherence is perceived to be the causes of inadequate symptom control. Symptom severity, poor response to medical treatment and patient pressure drive referral, although there is uncertainty about optimal timing. Treatment decisions in secondary care are based on disease severity, polyp status, prior medical treatment and patient choice, but there is major uncertainty about the place of longer courses of antibiotics and the use of oral steroids. Surgery is regarded as an important treatment option for patients with severe symptoms or with nasal polyps, although timing of surgery remains unclear, and the uncertainty about net long-term benefits of surgery makes balancing of benefits and risks more difficult.ConclusionsClinicians are uncertain about best management of patients with CRS in both primary and secondary care and practice is varied. An integrated care pathway for CRS is needed to improve patient management and timely referral.
Influenza-associated hospitalisation, vaccine uptake and socioeconomic deprivation in an English city region: an ecological study
Authors: Hungerford Daniel , Ibarz-Pavon Ana , Cleary Paul , French Neil 
Published: December 2018

ObjectivesEvery year, influenza poses a significant burden on the National Health Service in England. Influenza vaccination is an effective measure to prevent severe disease, hence, maximising vaccine coverage in the most vulnerable is a priority. We aimed to identify the extent to which socioeconomic status is associated with influenza-associated illness (IAI) and influenza vaccine coverage.DesignRetrospective observational study using hospital episode statistics.SettingMerseyside, North-West of England, including the city of Liverpool.ParticipantsResidents of Merseyside hospitalised with IAI between April 2004 and March 2016, and Merseyside general practice registered patients eligible for influenza vaccination in 2014/2015 and 2015/2016 influenza seasons.ExposuresSocioeconomic deprivation based on lower super output area English Indices of Deprivation scores.Primary and secondary outcome measuresIncidence and risk of IAI hospitalisation, and vaccine uptake.ResultsThere were 89 058 hospitalisations related to IAI among Merseyside residents (mean yearly rate=4.9 per 1000 population). Hospitalisations for IAI were more frequent in the most socioeconomically deprived areas compared with the least deprived in adults aged 15–39 years (incidence rate ratio (IRR) 2.08;95% CI 1.76 to 2.45; p<0.001), 60–64 years (IRR 2.65; 95% CI 2.35 to 2.99; p<0.001) and 65+ years (IRR 1.90; 95% CI 1.73 to 2.10; p<0.001), whereas rates in children were more homogeneous across deprivation strata. Vaccine uptake was lower than the nationally set targets in most neighbourhoods. The odds of vaccine uptake were 30% lower (OR 0.70; 95% CI 0.66 to 0.74; p<0.001) and 10% lower (OR 0.90; 95% CI 0.88 to 0.92; p<0.001) in the most socioeconomically deprived quintile compared with the least deprived, among children aged 24–59 months and 65+ years, respectively.ConclusionsHigher rates of IAI hospitalisations and lower vaccine uptake in the most socioeconomically deprived populations suggest that health promotion policies and interventions that target these populations should be a priority.
Real-world adherence to oral anticoagulants in atrial fibrillation patients: a study protocol for a systematic review and meta-analysis
Authors: Rodríguez-Bernal Clara L , García-Sempere Aníbal , Hurtado Isabel , Santa-Ana Yared , Peiró Salvador , Sanfélix-Gimeno Gabriel 
Published: December 2018

IntroductionAtrial fibrillation (AF) is one of the leading causes of cerebrovascular mortality and morbidity. Oral anticoagulants (OACs) have been shown to reduce the incidence of cardioembolic stroke in patients with AF, adherence to treatment being an essential element for their effectiveness. Since the release of the first non-vitamin K antagonist oral anticoagulant, several observational studies have been carried out to estimate OAC adherence in the real world using pharmacy claim databases or AF registers. This systematic review aims to describe secondary adherence to OACs, to compare adherence between OACs and to analyse potential biases in OAC secondary adherence studies using databases.Methods and analysisWe searched on PubMed, SCOPUS and Web of Science databases (completed in 26 September 2018) to identify longitudinal observational studies reporting days’ supply adherence measures with OAC in patients with AF from refill databases or AF registers. The main study endpoint will be the percentage of patients exceeding the 80% threshold in proportion of days covered or the medication possession ratio. Two reviewers will independently screen potential studies and will extract data in a structured format. A random-effects meta-analysis will be carried out to pool study estimates. The risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies and we will also assess some study characteristics that could affect days’ supply adherence estimates.Ethics and disseminationThis systematic review using published aggregated data does not require ethics approval according to Spanish law and international regulations. The final results will be published in a peer-review journal and different social stakeholders, non-academic audiences and patients will be incorporated into the diffusion activities.PROSPERO registration numberCRD42018095646.
Multicentre pilot study evaluation of lung ultrasound for the management of paediatric pneumonia in low-resource settings: a study protocol
Authors: Lenahan Jennifer L , Volpicelli Giovanni , Lamorte Alessandro , Jehan Fyezah , Bassat Quique , Ginsburg Amy Sarah 
Published: December 2018

IntroductionPneumonia is the leading infectious cause of death among children under 5 years of age worldwide. However, pneumonia is challenging to diagnose. Lung ultrasound (LUS) is a promising diagnostic technology. Further evidence is needed to better understand the role of LUS as a tool for the diagnosis of childhood pneumonia in low-resource settings.Methods and analysisThis study aims to pilot LUS in Mozambique and Pakistan and to generate evidence regarding the use of LUS as a diagnostic tool for childhood pneumonia. Children with cough <14 days with chest indrawing (n=230) and without chest indrawing (n=40) are enrolled. World Health Organization Integrated Management of Childhood Illness assessment is performed at enrolment, along with a chest radiograph and LUS examination. Respiratory and blood specimens are collected for viral and bacterial testing and biomarker assessment. Enrolled children are followed for 14 days (in person) and 30 days (phone call) post-enrolment with LUS examinations performed on Days 2, 6 and 14. Qualitative and quantitative data are also collected to assess feasibility, usability and acceptability of LUS among healthcare providers and caregivers. The primary outcome is LUS findings at enrolment with secondary outcomes including patient outcomes, repeat LUS findings, viral and bacterial test results, and patient status after 14 and 30 days of follow-up.Ethics and disseminationThis trial was approved by the Western Institutional Review Board as well as local ethics review committees at each site. We plan to disseminate study results in peer-reviewed journals and international conferences.Trial registration numberNCT03187067.
MYCNde novo gain-of-function mutation in a patient with a novel megalencephaly syndrome
Authors: Kato Kohji , Miya Fuyuki , Hamada Nanako , Negishi Yutaka , Narumi-Kishimoto Yoko , Ozawa Hiroshi , Ito Hidenori , Hori Ikumi , Hattori Ayako , Okamoto Nobuhiko , Kato Mitsuhiro , Tsunoda Tatsuhiko , Kanemura Yonehiro , Kosaki Kenjiro , Takahashi Yoshiyuki , Nagata Koh-ichi , Saitoh Shinji 
Published: December 2018

BackgroundIn this study, we aimed to identify the gene abnormality responsible for pathogenicity in an individual with an undiagnosed neurodevelopmental disorder with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly and neuroblastoma. We then explored the underlying molecular mechanism.MethodsTrio-based, whole-exome sequencing was performed to identify disease-causing gene mutation. Biochemical and cell biological analyses were carried out to elucidate the pathophysiological significance of the identified gene mutation.ResultsWe identified a heterozygous missense mutation (c.173C>T; p.Thr58Met) in theMYCNgene, at the Thr58 phosphorylation site essential for ubiquitination and subsequent MYCN degradation. The mutant MYCN (MYCN-T58M) was non-phosphorylatable at Thr58 and subsequently accumulated in cells and appeared to induce CCND1 and CCND2 expression in neuronal progenitor and stem cells in vitro. Overexpression of Mycn mimicking the p.Thr58Met mutation also promoted neuronal cell proliferation, and affected neuronal cell migration during corticogenesis in mouse embryos.ConclusionsWe identified a de novo c.173C>T mutation inMYCNwhich leads to stabilisation and accumulation of the MYCN protein, leading to prolonged CCND1 and CCND2 expression. This may promote neurogenesis in the developing cerebral cortex, leading to megalencephaly. While loss-of-function mutations inMYCNare known to cause Feingold syndrome, this is the first report of a germline gain-of-function mutation inMYCNidentified in a patient with a novel megalencephaly syndrome similar to, but distinct from, CCND2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. The data obtained here provide new insight into the critical role of MYCN in brain development, as well as the consequences of MYCN defects.
Incidence of acute respiratory distress syndrome and associated mortality in a polytrauma population
Authors: van Wessem Karlijn J P , Leenen Luke P H 
Published: December 2018

BackgroundThe incidence of acute respiratory distress syndrome (ARDS) has decreased in the last decade by improvement in trauma and critical care. However, it still remains a major cause of morbidity and mortality. This study investigated the current incidence and mortality of ARDS in polytrauma patients.MethodsA 4.5-year prospective study included consecutive trauma patients admitted to a level 1 trauma center intensive care unit (ICU). Isolated head injuries, drowning, asphyxiation, burns, and deaths <48 hours were excluded. Demographics, Injury Severity Score (ISS), physiologic parameters, resuscitation parameters, Denver Multiple Organ Failure scores, and ARDS data according to Berlin criteria were prospectively collected. Data are presented as median (IQR), and p<0.05 was considered significant.Results241 patients were included. The median age was 45 (27–59) years, 178 (74%) were male, the ISS was 29 (22–36), and 232 (96%) patients had blunt injuries. Thirty-one patients (13%) died. Fifteen patients (6%) developed ARDS. The median time to ARDS onset was 3 (2–5) days after injury. The median duration of ARDS was 2.5 (1–3.5) days. All patients with ARDS were male compared with 61% of non-ARDS patients (p=0.003). Patients who developed ARDS had higher ISS (30 vs. 25, p=0.01), lower Partial Pressure of Oxygen in arterial blood (PaO2) both in the emergency department and ICU, and higher Partial Pressure of Carbon Dioxide in arterial blood (PaCo2) in the ICU. Patients with ARDS needed more crystalloids <24 hours (8.7 vs. 6.8 L, p=0.03), received more fresh frozen plasma <24 hours (3 vs. 0 U, p=0.04), and more platelet <8 hours and <24 hours. Further, they stayed longer on the ventilator (11 vs. 2 days, p<0.001), longer in the ICU (12 vs. 3 days, p<0.001), and in the hospital (33 vs. 15 days, p=0.004). Patients with ARDS developed more often multiple organ dysfunction syndrome (40% vs. 3%, p<0.001) and died more often (20% vs. 3%, p=0.01). Only one patient with ARDS (7%) died of ARDS.DiscussionIn this polytrauma population mortality was predominantly caused by brain injury. The incidence of ARDS was low; its presentation was only early onset, during a short time period, and accompanied by low mortality.Level of evidenceLevel III.
Imperfect forward secrecy
Authors: Adrian David , Bhargavan Karthikeyan , Durumeric Zakir , Gaudry Pierrick , Green Matthew , Halderman J. Alex , Heninger Nadia , Springall Drew , Thomé Emmanuel , Valenta Luke , VanderSloot Benjamin , Wustrow Eric , Zanella-Béguelin Santiago , Zimmermann Paul 
Published: December 2018

We investigate the security of Diffie-Hellman key exchange as used in popular Internet protocols and find it to be less secure than widely believed. First, we present Logjam, a novel flaw in TLS that lets a man-in-the-middle downgrade connections to "export-grade" Diffie-Hellman. To carry out this attack, we implement the number field sieve discrete logarithm algorithm. After a week-long precomputation for a specified 512-bit group, we can compute arbitrary discrete logarithms in that group in about a minute. We find that 82% of vulnerable servers use a single 512-bit group, and that 8.4% of Alexa Top Million HTTPS sites are vulnerable to the attack. In response, major browsers have changed to reject short groups.
We go on to consider Diffie-Hellman with 768- and 1024-bit groups. We estimate that even in the 1024-bit case, the computations are plausible given nation-state resources. A small number of fixed or standardized groups are used by millions of servers; performing precomputation for a single 1024-bit group would allow passive eavesdropping on 18% of popular HTTPS sites, and a second group would allow decryption of traffic to 66% of IPsec VPNs and 26% of SSH servers. A close reading of published NSA leaks shows that the agency's attacks on VPNs are consistent with having achieved such a break. We conclude that moving to stronger key exchange methods should be a priority for the Internet community.
Voluntary wheel running prevents salt-induced endothelial dysfunction: role of oxidative stress
Authors: Guers John J. , Kasecky-Lardner Lauren , Farquhar William B. , Edwards David G. , Lennon Shannon L. 
Published: December 2018

Diets high in salt can lead to endothelial dysfunction, a nontraditional risk factor for cardiovascular disease (CVD). Exercise is known to reduce CVD risk; however, it remains unknown whether chronic physical activity can attenuate salt-induced endothelial dysfunction independent of blood pressure (BP) and whether these changes are due to an upregulation in endogenous antioxidants. Eight-week-old Sprague-Dawley rats were fed either a normal (NS; 0.49%)- or a high (HS; 4.0%)-salt diet and further divided into voluntary wheel running (NS-VWR, HS-VWR) and sedentary (NS, HS) groups for 6 wk. BP was measured weekly and remained unchanged within groups ( P = 0.373). Endothelium-dependent relaxation (EDR) was impaired in the femoral artery of HS compared with NS (38.6 ± 4.0% vs. 65.0 ± 3.6%; P = 0.013) animals, whereas it was not different between NS and HS-VWR (73.4 ± 6.4%; P = 0.273) animals. Incubation with the antioxidants TEMPOL ( P = 0.024) and apocynin ( P = 0.013) improved EDR in HS animals, indicating a role for reactive oxygen species (ROS). Wheel running upregulated the antioxidant superoxide dismutase-2 (SOD-2) ( P = 0.011) under HS conditions and lowered NOX4 and Gp91-phox, two subunits of NADPH oxidase. Wheel running elevated phosphorylated endothelial nitric oxide synthase (eNOS) ( P = 0.014) in HS-fed rats, demonstrating a role for physical activity and eNOS activity under HS conditions. Finally, there was a reduction in EDR ( P = 0.038) when femoral arteries from NS-VWR animals were incubated with TEMPOL or apocynin, suggesting there may be a critical level of ROS needed to maintain endothelial function. In summary, physical activity protected HS-fed rats from reductions in endothelial function, likely through increased SOD-2 levels and reduced oxidative stress. NEW & NOTEWORTHY Our data suggest that voluntary wheel running can prevent impairments in endothelium-dependent relaxation in the femoral artery of rats fed a high-salt diet. This appears to be independent of blood pressure and mediated through a decrease in expression of NADPH oxidases as a result of physical activity. These data suggest that increased chronic physical activity can protect the vasculature from a diet high in salt, likely through a reduction in oxidative stress.
Molecular adaptations in human subcutaneous adipose tissue after ten weeks of endurance exercise training in healthy males
Authors: Riis Simon , Christensen Britt , Nellemann Birgitte , Møller Andreas Buch , Husted Anna Sofie , Pedersen Steen B. , Schwartz Thue W. , Jørgensen Jens Otto Lunde , Jessen Niels 
Published: December 2018

Endurance exercise training induces adaptations in metabolically active organs, but adaptations in human subcutaneous adipose tissue (scAT) remains incompletely understood. On the basis of animal studies, we hypothesized that endurance exercise training would increase the expression of proteins involved in lipolysis and glucose uptake in scAT. To test these hypotheses, 19 young and healthy males were randomized to either endurance exercise training (TR; age 18–24 yr; BMI 19.0–25.4 kg/m2) or a nonexercising control group (CON; age 21–35 yr; BMI 20.5–28.8 kg/m2). Abdominal subcutaneous fat biopsies and blood were obtained at rest before and after intervention. By using Western blotting and PCR, we determined expression of lipid droplet-associated proteins, various proteins involved in substrate metabolism, and mRNA abundance of cell surface G protein-coupled receptors (GPCRs). Adipose tissue insulin sensitivity was determined from fasting plasma insulin and nonesterified fatty acids (adipose tissue insulin resistance index; Adipo-IR). Adipo-IR improved in TR compared with CON ( P = 0.03). This was accompanied by increased insulin receptor (IR) protein expression in scAT with a 1.54-fold (SD 0.79) change from baseline in TR vs. 0.85 (SD 0.30) in CON ( P = 0.007). Additionally, hexokinase II (HKII) and succinate dehydrogenase complex subunit A (SDHA) protein increased in TR compared with CON ( P = 0.006 and P = 0.04, respectively). We did not observe changes in lipid droplet-associated proteins or mRNA abundance of GPCRs. Collectively, 10 weeks of endurance exercise training improved adipose tissue insulin sensitivity, which was accompanied by increased IR, HKII, and SDHA protein expression in scAT. We suggest that these adaptations contribute to an improved metabolic flexibility. NEW & NOTEWORTHY This study is the first to investigate the molecular adaptations in human subcutaneous adipose tissue (scAT) after endurance exercise training compared with a nonexercising control group. We show that endurance exercise training improves insulin sensitivity in human scAT, and this is accompanied by increased expression of insulin receptor, hexokinase II, and succinate dehydrogenase complex subunit A. Collectively, our data suggest that endurance exercise training induces molecular adaptations in human scAT, which may contribute to an improved metabolic flexibility.