bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates and aetiological factors associated with hedonic well-being among an ageing population of US men and women: secondary data analysis of a national survey
Authors: Odlum Michelle , Davis Nicole , Owens Otis , Preston Michael , Brewer Russell , Black Danielle 
Published: November 2018

ObjectiveTo understand the gender-specific factors that uniquely contribute to successful ageing in a US population of men and women, 57–85 years of age. This was achieved through the examination of the correlates of subjective well-being defined by health-related quality of life (HRQoL), across several biological and psychosocial determinants of health.DesignCross-sectional study.SettingThe National Social Life, Health and Ageing Project (NSHAP), 2010–2011 a representative sample of the US population.Participants3377 adults aged 57–85 (1538 men, 1839 women) from the NSHAP.Main outcome measuresThe biopsychosocial factors of biological/physiological function, symptom status, functional status, general health perceptions and HRQoL happiness.MethodHRQoL was measured using the NSHAP wave 2 multistage, stratified area probability sample of US households (n=3377). Variable selection was guided by the Wilson and Cleary model (WCM) that classifies health outcomes at five main levels and characteristics.ResultsOur findings indicate differences in biopsychosocial factors comprised in the WCM and their relative importance and unique impact on HRQoL by gender. Women reported significantly lower HRQoL than men (t=3.5, df=3366). The most significant contributors to HRQoL in women were mental health (B=0.31; 0.22, 0.39), loneliness (B=−0.26; −0.35, –0.17), urinary incontinence (B=−0.22; −0.40, –0.05) and support from spouse/partner (B=0.27; 0.10, 0.43) and family B=0.12; 0.03, 0.20). Men indicated mental health (B=0.21; 0.14, 0.29), physical health (B=0.17; 0.10, 0.23), functional difficulties (B=0.38; 0.10, 0.65), loneliness (B=−0.20; −0.26, –0.12), depression (B=−0.36; −0.58, –0.15) and support from friends (B=0.06; 0.10, 0.11) as significant contributors. Those with greater social support had better HRQoL (F=4.22, df=4). Lack of companionship and reliance on spouse/partner were significant HRQoL contributors in both groups.ConclusionOur findings offer insight into ageing, gender and subjective well-being. The results provide an opportunity to identify biopsychosocial factors to inform interventions to support successful ageing.
Quality of life, loneliness and health-related characteristics among older people in Liaoning province, China: a cross-sectional study
Authors: Zhu Yaxin , Liu Jie , Qu Bo , Yi Zhe 
Published: November 2018

ObjectivesThe aim of the study was to examine the relations among quality of life (QOL), loneliness and health-related characteristics in a sample of Chinese older people.DesignCross-sectional study.SettingCommunities in Dandong city, Liaoning province, China.ParticipantsSample of 732 older people aged 60 and older who were living in Dandong, Liaoning province, China.MethodsA questionnaire was administered to the participants face-to-face. The questionnaire contained four sections: demographic characteristics, health-related characteristics, the EQ-5D Scale and the UCLA Loneliness Scale. The t-test, F-test and multivariable linear regression analyses were performed to individually test associations between the demographic data, health-related characteristics, loneliness and QOL.ResultsChronic diseases, loneliness, age and smoking status were negatively associated with QOL (p<0.05). Satisfaction with health services, income and physical activity were positively associated with QOL (p<0.05).ConclusionsLoneliness, chronic diseases and health service satisfaction were important factors related to low QOL among older people in China. The findings indicate that reducing loneliness, managing chronic diseases and improving the health service may help to improve the QOL for older people.
Is the Rule of Halves framework relevant for diabetes care in Copenhagen today? A register-based cross-sectional study
Authors: Holm Astrid Ledgaard , Andersen Gregers Stig , Jørgensen Marit E , Diderichsen Finn 
Published: November 2018

ObjectiveThe study aimed at analysing whether the ‘Rule of Halves’ framework applies for diabetes care in the Danish healthcare system with high levels of accessibility and equity. The Rule of Halves states that only one-half of people with a particular chronic condition are diagnosed; one-half of those diagnosed get treatment, and one-half of treated achieve desired therapeutic goals.DesignThe analysis is cross sectional based on available surveys, register data and clinical databases covering the adult population in Copenhagen. We analysed five levels of prevention and care including behavioural risk factors and biomarkers, prevalence of diagnosed and undiagnosed diabetes as well as how many received care according to guidelines and achieved relevant outcomes.SettingThe study population is Copenhagen City with a population of 550 000 with 21 500 prevalent cases of diabetes. While the registers used cover the whole population, the surveys include 750 cases and the biobank data 365 cases.Outcome measuresOutcome measures are for each level of analysis: the prevalence of high-risk individuals, prevalence of undiagnosed and diagnosed diabetes, proportion receiving treatment and proportion achieving quality and treatment targets.ResultsWe found that the ‘Rule of Halves’ framework raises relevant questions on how diabetes care works in a specific population, but the actual proportions found in Copenhagen are far from halves. Our analyses showed that 74% are diagnosed and among those who are 90% are receiving care. 40%–60% have achieved target levels of treatment in terms of HbA1c level and lipid levels. 80% have received eye and foot examinations in the last 2 years. 11% have retinopathy and 25% have macrovascular complications.ConclusionCopenhagen is doing much better than halves, when it comes to diagnosis and providing treatment, whereas the Rule of Halves still prevails when it comes to treatment targets. There is thus still room for improvement.
Retrospective analysis of alcohol testing in trauma team activation patients at a Canadian tertiary trauma centre
Authors: Erdogan Mete , Kureshi Nelofar , Karim Saleema A , Tallon John M , Asbridge Mark , Green Robert S 
Published: November 2018

ObjectivesAlthough alcohol screening is an essential requirement of level I trauma centre accreditation, actual rates of compliance with mandatory alcohol testing in trauma patients are seldom reported. Our objective was to determine the prevalence of blood alcohol concentration (BAC) testing in patients requiring trauma team activation (TTA) for whom blood alcohol testing was mandatory, and to elucidate patient-level, injury-level and system-level factors associated with BAC testing.DesignRetrospective cohort study.SettingTertiary trauma centre in Halifax, Canada.Participants2306 trauma patients who required activation of the trauma team.Primary outcome measureThe primary outcome was the rate of BAC testing among TTA patients. Trends in BAC testing over time and across patient and injury characteristics were described. Multivariable logistic regression examined patient-level, injury-level and system-level factors associated with testing.ResultsOverall, 61% of TTA patients received BAC testing despite existence of a mandatory testing protocol. Rates of BAC testing rose steadily over the study period from 33% in 2000 to 85% in 2010. Testing varied considerably across patient-level, injury-level and system-level characteristics. Key factors associated with testing were male gender, younger age, lower Injury Severity Score, scene Glasgow Coma Scale score <9, direct transport to hospital and presentation between midnight and 09:00 hours, or on the weekend.ConclusionsAt this tertiary trauma centre with a policy of empirical alcohol testing for TTA patients, BAC testing rates varied significantly over the 11-year study period and distinct factors were associated with alcohol testing in TTA patients.
Compliance with pathology testing guidelines in Australian general practice: protocol for a secondary analysis of electronic health record data
Authors: Sezgin Gorkem , Georgiou Andrew , Hardie Rae-Anne , Li Ling , Pont Lisa G , Badrick Tony , Franco Guilherme S , Westbrook Johanna I , Rinehart Natalie , McLeod Adam , Pearce Christopher , Shearer Marianne , Whyte Robin , Deveny Elizabeth 
Published: November 2018

IntroductionIn Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key part of diagnosis and monitoring. However overutilisationand underutilisation of pathology tests have been reported across several tests and conditions, despite evidence-based guidelines outlining best practice in pathology testing. There are a limited number of studies evaluating the impact of these guidelines on pathology testing in general practice. The aim of our quantitative observational study is to define how pathology tests are used in general practice and investigate how test ordering practices align with evidence-based pathology guidelines.Methods and analysisAccess to non-identifiable patient data will be obtained through electronic health records from general practices across three primary health networks in Victoria, Australia. Numbers and characteristics of patients, general practices, encounters, pathology tests and problems managed over time will be described. Overall rates of encounters and tests, alongside more detailed investigation between subcategories (encounter year, patient’s age, gender, and location and general practice size), will also be undertaken. To evaluate how general practitioner test ordering coincides with evidence-based guidelines, five key candidate indicators will be investigated: full blood counts for patients on clozapine medication; international normalised ratio measurements for patients on warfarin medication; glycated haemoglobin testing for monitoring patients with diabetes; vitamin D testing; and thyroid function testing.Ethics and disseminationEthics clearance to collect data from general practice facilities has been obtained by the data provider from the RACGP National Research and Evaluation Ethics Committee (NREEC 17–008). Approval for the research group to use these data has been obtained from Macquarie University (5201700872). This study is funded by the Australian Government Department of Health Quality Use of Pathology Program (Agreement ID: 4-2QFVW4M). Findings will be reported to the Department of Health and disseminated in peer-reviewed academic journals and presentations (national and international conferences, industry forums).
Effect of beta-blocker therapy on clinical outcomes, safety, health-related quality of life and functional capacity in patients with chronic obstructive pulmonary disease (COPD): a protocol for a systematic literature review and meta-analysis with multiple treatment comparison
Authors: Gulea Claudia , Zakeri Rosita , Quint Jennifer K 
Published: November 2018

IntroductionPatients with chronic obstructive pulmonary disease (COPD) who have a clinical indication for beta-blocker therapy, are often not prescribed such medication, despite evidence suggesting that beta-blockers are not associated with adverse respiratory outcomes. The primary objective of this systematic review and meta-analysis is to examine the class effect of beta-blocker use in patients with COPD. We will focus on a broad range of endpoints including, clinical, safety, and patient-centric outcomes such as health related quality of life (HRQoL) and functional capacity. A secondary objective is to explore potential within-class variation in the effects of beta-blockers among patients with COPD, and rank individual agents according to their relative benefit(s).Methods and analysisMEDLINE, Embase, The Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases will be systematically searched, from inception to present, to identify randomised controlled trials (RCTs) and other prospective and interventional studies of beta-blocker use in patients with COPD which report on the outcomes of interest. Relative treatment effects with respect to mortality, COPD exacerbations, all-cause hospitalisation, lung function, HRQoL and exercise capacity will be summarised by meta-analysis. Individual treatments (agents) will be compared in a Bayesian network meta-analysis including RCT and observational data, if feasible.Ethics and disseminationThe results of the study will be submitted for publication in a peer-reviewed journal. Only previously published aggregate data will be used for the purpose of this review.PROSPERO registration numberCRD42018098983.
Comparison of two gap-filling techniques for nitrous oxide fluxes from agricultural soil
Authors: Taki Rezvan , Wagner-Riddle Claudia , Parkin Gary , Gordon Rob , VanderZaag Andrew 
Published: November 2018

Micrometeorological methods are ideally suited for continuous measurements of N2O fluxes, but gaps in the time series occur due to low-turbulence conditions, power failures, and adverse weather conditions. Two gap-filling methods including linear interpolation and artificial neural networks (ANN) were utilized to reconstruct missing N2O flux data from a corn–soybean–wheat rotation and evaluate the impact on annual N2O emissions from 2001 to 2006 at the Elora Research Station, ON, Canada. The single-year ANN method is recommended because this method captured flux variability better than the linear interpolation method (average R2 of 0.41 vs. 0.34). Annual N2O emission and annual bias resulting from linear and single-year ANN were compatible with each other when there were few and short gaps (i.e., percentage of missing values <30%). However, with longer gaps (>20 d), the bias error in annual fluxes varied between 0.082 and 0.344 kg N2O-N ha−1 for linear and 0.069 and 0.109 kg N2O-N ha−1 for single-year ANN. Hence, the single-year ANN with lower annual bias and stable approach over various years is recommended, if the appropriate driving inputs (i.e., soil temperature, soil water content, precipitation, N mineral content, and snow depth) needed for the ANN model are available.
Model-independent measures of gravity at large scales
Authors: Amendola Luca , Pinho Ana Marta , Casas Santiago 
Published: November 2018

This paper aims at showing how to probe gravity in a model independent way using observable quantities which can be measured with the minimum number of assumptions. We find that it is possible to estimate the gravitational slip, defined as the ratio of the gravitational potentials, independently of assumptions concerning initial conditions, bias, and other cosmological parameters. Analyzing all the data currently available, we find [Formula: see text] in the redshift range [Formula: see text]. Future datasets, like those provided by the Euclid satellite, will tighten this constraint by more than an order of magnitude.
Search for heavy neutral leptons at the NA62 experiment at CERN
Authors: Zamkovsky Michal 
Published: November 2018

Search for heavy neutral lepton (HNL) production in charged kaon decays using the data collected by kaon experiments NA48/2 and NA62 at CERN are reported. Upper limits are established on the elements of the extended neutrino mixing matrix for heavy neutral lepton mass in the range 130–450 MeV, improving on the results from previous HNL production search.
Functional and anatomical relationships between the medial precentral cortex, dorsal striatum, and head direction cell circuitry. I. Recording studies
Authors: Mehlman Max L. , Winter Shawn S. , Valerio Stephane , Taube Jeffrey S. 
Published: November 2018

Head direction (HD) cells fire as a function of the animal’s directional heading and provide the animal with a sense of direction. In rodents, these neurons are located primarily within the limbic system, but small populations of HD cells are found in two extralimbic areas: the medial precentral cortex (PrCM) and dorsal striatum (DS). HD cell activity in these structures could be driven by output from the limbic HD circuit or generated intrinsically. We examined these possibilities by recording the activity of PrCM and DS neurons in control rats and in rats with anterodorsal thalamic nucleus (ADN) lesions, a manipulation that disrupts the limbic HD signal. HD cells in the PrCM and DS of control animals displayed characteristics similar to those of limbic HD cells, and these extralimbic HD signals were eliminated in animals with complete ADN lesions, suggesting that the PrCM and DS HD signals are conveyed from the limbic HD circuit. Angular head velocity cells recorded in the PrCM and DS were unaffected by ADN lesions. Next, we determined if the PrCM and DS convey necessary self-motion signals to the limbic HD circuit. Limbic HD cell activity recorded in the ADN remained intact following combined lesions of the PrCM and DS. Collectively, these experiments reveal a unidirectional functional relationship between the limbic HD circuit and the PrCM and DS; the limbic system generates the HD signal and transmits it to the PrCM and DS, but these extralimbic areas do not provide critical input or feedback to limbic HD cells.NEW & NOTEWORTHY Head direction (HD) cells have been extensively studied within the limbic system. The lesion and recording experiments reported here examined two relatively understudied populations of HD cells located outside of the canonical limbic HD circuit in the medial precentral cortex and dorsal striatum. We found that HD cell activity in these two extralimbic areas is driven by output from the limbic HD circuit, revealing that HD cell circuitry functionally extends beyond the limbic system.
Agmatine preferentially antagonizes GluN2B-containingN-methyl-d-aspartate receptors in spinal cord
Authors: Waataja Jonathan J. , Peterson Cristina D. , Verma Harsha , Goracke-Postle Cory J. , Séguéla Philippe , Delpire Eric , Wilcox George L. , Fairbanks Carolyn A. 
Published: November 2018

The role of the N-methyl-d-aspartate receptor (NMDAr) as a contributor to maladaptive neuroplasticity underlying the maintenance of chronic pain is well established. Agmatine, an NMDAr antagonist, has been shown to reverse tactile hypersensitivity in rodent models of neuropathic pain while lacking the side effects characteristic of global NMDAr antagonism, including sedation and motor impairment, indicating a likely subunit specificity of agmatine’s NMDAr inhibition. The present study assessed whether agmatine inhibits subunit-specific NMDAr-mediated current in the dorsal horn of mouse spinal cord slices. We isolated NMDAr-mediated excitatory postsynaptic currents (EPSCs) in small lamina II dorsal horn neurons evoked by optogenetic stimulation of Nav1.8-containing nociceptive afferents. We determined that agmatine abbreviated the amplitude, duration, and decay constant of NMDAr-mediated EPSCs similarly to the application of the GluN2B antagonist ifenprodil. In addition, we developed a site-specific knockdown of the GluN2B subunit of the NMDAr. We assessed whether agmatine and ifenprodil were able to inhibit NMDAr-mediated current in the spinal cord dorsal horn of mice lacking the GluN2B subunit of the NMDAr by analysis of electrically evoked EPSCs. In control mouse spinal cord, agmatine and ifenprodil both inhibited amplitude and accelerated the decay kinetics. However, agmatine and ifenprodil failed to attenuate the decay kinetics of NMDAr-mediated EPSCs in the GluN2B-knockdown mouse spinal cord. The present study indicates that agmatine preferentially antagonizes GluN2B-containing NMDArs in mouse dorsal horn neurons.NEW & NOTEWORTHY Our study is the first to report that agmatine preferentially antagonizes the GluN2B receptor subunit of the N-methyl-d-aspartate (NMDA) receptor in spinal cord. The preferential targeting of GluN2B receptor is consistent with the pharmacological profile of agmatine in that it reduces chronic pain without the motor side effects commonly seen with non-subunit-selective NMDA receptor antagonists.
A rapid visuomotor response on the human upper limb is selectively influenced by implicit motor learning
Authors: Gu Chao , Pruszynski J. Andrew , Gribble Paul L. , Corneil Brian D. 
Published: November 2018

How do humans learn to adapt their motor actions to achieve task success? Recent behavioral and patient studies have challenged the classic notion that motor learning arises solely from the errors produced during a task, suggesting instead that explicit cognitive strategies can act in concert with the implicit, error-based, motor learning component. In this study, we show that the earliest wave of directionally tuned neuromuscular activity that begins within ~100 ms of peripheral visual stimulus onset is selectively influenced by the implicit component of motor learning. In contrast, the voluntary neuromuscular activity associated with reach initiation, which evolves ~100–200 ms later, is influenced by both the implicit and explicit components of motor learning. The selective influence of the implicit, but not explicit, component of motor learning on the directional tuning of the earliest cascade of neuromuscular activity supports the notion that these components of motor learning can differentially influence descending motor pathways. NEW & NOTEWORTHY Motor learning can be driven both by an implicit error-based component and an explicit strategic component, but the influence of these components on the descending pathways that contribute to motor control is unknown. In this study, we show that the implicit component selectively influences a reflexive circuit that rapidly generates a visuomotor response on the human upper limb. Our results show that the substrates mediating implicit and explicit motor learning exert distinct influences on descending motor pathways.
PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow
Authors: Hopkins Todd A. , Ainsworth William B. , Ellis Paul A. , Donawho Cherrie K. , DiGiammarino Enrico L. , Panchal Sanjay C. , Abraham Vivek C. , Algire Mikkel A. , Shi Yan , Olson Amanda M. , Johnson Eric F. , Wilsbacher Julie L. , Maag David 
Published: November 2018

Abstract

PARP inhibitors have recently been approved as monotherapies for the treatment of recurrent ovarian cancer and metastatic BRCA-associated breast cancer, and ongoing studies are exploring additional indications and combinations with other agents. PARP inhibitors trap PARP onto damaged chromatin when combined with temozolomide and methyl methanesulfonate, but the clinical relevance of these findings remains unknown. PARP trapping has thus far been undetectable in cancer cells treated with PARP inhibitors alone. Here, we evaluate the contribution of PARP trapping to the tolerability and efficacy of PARP inhibitors in the monotherapy setting. We developed a novel implementation of the proximity ligation assay to detect chromatin-trapped PARP1 at single-cell resolution with higher sensitivity and throughput than previously reported methods. We further demonstrate that the PARP inhibitor–induced trapping appears to drive single-agent cytotoxicity in healthy human bone marrow, indicating that the toxicity of trapped PARP complexes is not restricted to cancer cells with homologous recombination deficiency. Finally, we show that PARP inhibitors with dramatically different trapping potencies exhibit comparable tumor growth inhibition at MTDs in a xenograft model of BRCA1-mutant triple-negative breast cancer. These results are consistent with emerging clinical data and suggest that the inverse relationship between trapping potency and tolerability may limit the potential therapeutic advantage of potent trapping activity.

Implications:
PARP trapping contributes to single-agent cytotoxicity of PARP inhibitors in both cancer cells and healthy bone marrow, and the therapeutic advantage of potent trapping activity appears to be limited.