bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidisciplinary analysis of invasive meningococcal disease as a framework for continuous quality and safety improvement in regional Australia
Authors: Taylor Kathryn A , Durrheim David N , Merritt Tony , Massey Peter , Ferguson John , Ryan Nick , Hullick Carolyn 
Published: February 2018

BackgroundSystem factors in a regional Australian health district contributed to avoidable care deviations from invasive meningococcal disease (IMD) management guidelines. Traditional root cause analysis (RCA) is not well-suited to IMD, focusing on individual cases rather than system improvements. As IMD requires complex care across healthcare silos, it presents an opportunity to explore and address system-based patient safety issues.ContextBaseline assessment of IMD cases (2005–2006) identified inadequate triage, lack of senior clinician review, inconsistent vital sign recording and laboratory delays as common issues, resulting in antibiotic administration delays and inappropriate or premature discharge.MethodsClinical governance, in partnership with clinical and public health services, established a multidisciplinary Meningococcal Reference Group (MRG) to routinely review management of all IMD cases. The MRG comprised representatives from primary care, acute care, public health, laboratory medicine and clinical governance. Baseline data were compared with two subsequent evaluation points (2011–2012 and 2013–2015).InterventionsPhase I involved multidisciplinary process mapping and development of a standardised audit tool from national IMD management guidelines. Phase II involved formalisation of group processes and advocacy for operational change. Phase III focused on dissemination of findings to clinicians and managers.ResultsGreatest care improvements were observed in the final evaluation. Median antibiotic delay decreased from 72 to 42 min and proportion of cases triaged appropriately improved from 38% to 75% between 2013 and 2015. Increasing fatal outcomes were attributed to the emergence of more virulent meningococcal serotypes.ConclusionsThe MRG was a key mechanism for identifying system gaps, advocating for change and enhancing communication and coordination across services. Employing IMD case review as a focus for district-level process reflection presents an innovative patient safety approach, combining the strengths of prospective hazard analysis with more traditional RCA methodologies.
Career specialty choices of UK medical graduates of 2015 compared with earlier cohorts: questionnaire surveys
Authors: Lambert Trevor William , Smith Fay , Goldacre Michael J 
Published: February 2018

AbstractObjectiveTo report the career specialty choices of UK medical graduates of 2015 one year after graduation and to compare these with the choices made at the same postgraduate stage by previous cohorts.DesignNational survey using online and postal questionnaires.SettingUK.ParticipantsUK-trained medical graduates.Main outcome measuresGrouped and individual specialty choices.ResultsThe response rate was 41.3% (3040/7095). Among the graduates of 2015, general practice (27.8% of first choices) and hospital medical specialties (26.5%) were the most frequent first choices of long-term career. First choices for general practice declined among women from 36.1% for the 2005–2009 cohorts to 33.3% for the 2015 cohort, and among men from 22.4% for the 2005–2009 cohorts to 19.3% for the 2015 cohort. First choices for surgery declined among men (from 29.5% for the 2005–2009 cohorts to 21.7% for the 2015 cohort), but not among women (12.3% for the 2005–2009 cohorts and 12.5% for the 2015 cohort). There was an increase in the percentage of first choices for anaesthesia, psychiatry, radiology and careers outside medicine. Anaesthesia, oncology, paediatrics and radiology increased in popularity over time among men, but not among women.ConclusionsCareer choices for general practice remain low. Other current shortage specialties, apart from radiology and psychiatry, are not showing an increase in the number of doctors who choose them. Large gender differences remain in the choices for some specialties. Further work is needed into the determinants of junior doctors’ choices for shortage specialties and those with large gender imbalances.
Surrogate and Intermediate Endpoints in Randomized Trials: What's the Goal?
Authors: Korn Edward L. , Freidlin Boris 
Published: February 2018

Abstract
Establishing trial-level surrogacy of an intermediate endpoint for predicting survival benefit in future trials is extremely challenging because of the extrapolations required, but there are other useful drug development and patient management applications of intermediate endpoints. Clin Cancer Res; 24(10); 2239–40. ©2018 AACR.
See related article by Mushti et al., p. 2268
Rhotics and Palatalization: An Acoustic Examination of Upper and Lower Sorbian
Authors: Howson Phil 
Published: February 2018

AbstractTwo of the major problems with rhotics are: (1) rhotics, unlike most other classes, are highly resistant to secondary palatalization, and (2) acoustic cues for rhotics as a class have been elusive. This study examines the acoustics of Upper and Lower Sorbian rhotics. Dynamic measures of the F1-F3 and F2-F1 were recorded and compared using SSANOVAs. The results indicate there is a striking delay in achievement of F2 for both the palatalized rhotics, while F2, F1, and F2-F1 are similar for all the rhotics tested here. The results suggest an inherent articulatory conflict between rhotics and secondary palatalization. The delay in the F2 increase indicates a delay in the palatalization gesture. This is likely due to conflicting constraints on the tongue dorsum. There was also an overlap in the F2 and F2-F1 for both the uvular and alveolar rhotics. This suggests a strong acoustic cue to rhotic classhood is found in the F2 signal. The overall formant similarities in frequency and trajectory also suggest a strong similarity in the vocal tract shapes between uvular and alveolar rhotics.
Different Weight Histories and Risk of Incident Coronary Heart Disease and Stroke: Tehran Lipid and Glucose Study
Authors: Kabootari Maryam , Asgari Samaneh , Mansournia Mohammad Ali , Khalili Davood , Valizadeh Majid , Azizi Fereidoun , Hadaegh Farzad 
Published: February 2018

Background

This study aimed to determine the association between different weight histories, including cumulative excess weight, cumulative excess waist circumference (
WC
), duration of general and central adiposity, current and maximum body mass index, and current and maximum WC, and incident coronary heart disease (
CHD
) and stroke.

Methods and Results

The study population consisted of 4398 adults aged ≥40 years without
CHD
or stroke at baseline. Associations between different weight histories and
CHD
and stroke were determined by multivariable time‐varying Cox regression models after adjustment for age, sex, and time‐varying confounders. Further adjustment was also done for mediators (eg, diabetes mellitus, hypercholesterolemia, and hypertension). During median follow‐up of 13.9 years, 718 incident
CHD
and 158 stroke events were documented. Multivariable adjusted hazard ratios (HRs) were calculated in the sex and confounder adjusted model for CHD per 1‐SD increase in cumulative excess weight (HR: 1.02; 95% confidence interval [
CI
], 0.96–1.07), cumulative excess WC (HR: 1.14; 95% CI, 1.04–1.24), duration of general adiposity (HR: 1.00; 95% CI, 0.92–1.08), duration of central adiposity (HR: 1.01; 95% CI, 0.93–1.09), current body mass index (HR: 1.03; 95% CI, 0.99–1.07), current WC (HR: 1.21; 95% CI, 1.11–1.32), maximum body mass index (HR: 1.01; 95% CI, 0.95–1.07), and maximum
WC
(HR: 1.17; 95% CI, 1.07–1.28). After further adjustment for mediators, current and maximum
WC
still showed a significant risk (HR: 1.13 [95% CI, 1.03–1.23] and 1.09 [95% CI, 1.00–1.20], respectively). Moreover, in the sex and confounder adjusted model, cumulative excess WC and maximum
WC
were associated with higher risk of stroke (hazard ratio: 1.21 [95% CI, 0.99–1.48] and 1.25 [95% CI, 1.02–1.55], respectively).

Conclusions

Exposure to cumulative excess weight and cumulative excess WC confers little additional risk beyond their current and maximum values. Even current and maximum
WC
were associated with incident
CHD
in the presence of obesity mediators, and the latter was a significant predictor of stroke in the presence of confounders.
U‐Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All‐Cause Mortality in the Elderly: The Role of Malnourishment
Authors: Tseng Wei‐Cheng , Chen Yung‐Tai , Ou Shuo‐Ming , Shih Chia‐Jen , Tarng Der‐Cherng , Tarng Der‐Cherng , Tseng Wei‐Cheng , Ou Shuo‐Ming , Yang Chih‐Yu , Lin Yao‐Ping , Chuang Yi‐Fang , Chen Liang‐Kung , Wang Kwua‐Yun , Chen Yu‐Hsin , Tsai Ming‐Tsun , Shih Chia‐Jen , Chen Yung‐Tai , Lin Yi‐Sheng , Hung Szu‐Chun , Kuo Ko‐Lin , Hung Tung‐Po , Hu Fen‐Hsiang , Chen Nien‐Jung , Chen Yu‐Chi , Lin Chi‐Hung , Tsai Tung‐Hu , Hsieh Shie‐Liang , Wei Yau‐Huei , Hsu Chih‐Cheng , Liu Jia‐Sin , Chang Yu‐Kang , Chiang Ming‐Han 
Published: February 2018

Background

The link between elevated serum uric acid (
SUA
) levels and cardiovascular disease (
CVD
)–related mortality in the elderly population remains inconclusive. Nutritional status influences both
SUA
and
CVD
outcomes. Therefore, we investigated whether
SUA
‐predicted mortality and the effect‐modifying roles of malnourishment in older people.

Methods and Results

A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of
SUA
. Low
SUA
(<4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index <98, serum albumin <38 g/L, or body mass index <22 kg/m
2
. Study outcomes were all‐cause and
CVD
‐related mortality. Cox models were used to estimate hazard ratios (
HRs
) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877
CVD
‐related deaths. Compared with the reference
SUA
strata of 4 to <5 mg/dL, all‐cause mortality was significantly higher at
SUA
<4 mg/dL (
HR
, 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL (
HR
, 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher
CVD
‐related mortality was found at the SUA level <4 mg/dL (
HR
, 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL (
HR
, 1.17; confidence interval, 1.04–1.32). Remarkably, among the low
SUA
(<4 mg/dL) strata, only malnourished participants had greater all‐cause and
CVD
‐related mortality. This modifying effect of malnourishment remained consistent across subgroups.

Conclusions

SUA
≥8 or <4 mg/dL independently predicts higher all‐cause and
CVD
‐related mortality in the elderly, particularly in those with malnourishment.
The Behavior of Squall Lines in Horizontally Heterogeneous Coastal Environments
Authors: Lombardo Kelly , Kading Tristan 
Published: February 2018

Abstract
Inland squall lines respond to the stable marine atmospheric boundary layer (MABL) as they move toward a coastline and offshore. As a storm’s cold pool collides with the marine layer, characteristics of both determine the resulting convective forcing mechanism over the stable layer and storm characteristics. Idealized numerical experiments exploring a parameter space of MABL characteristics show that the postcollision forcing mechanism is determined by the buoyancy of the cold pool relative to the MABL. When the outflow is less buoyant, storms are forced by a cold pool within the marine environment. When the buoyancies are equivalent, a hybrid cold pool–internal gravity wave develops after the collision. The collision between a cold pool and less buoyant MABL initiates internal waves along the stable layer, regardless of MABL depth. These waves are inefficient at lifting air into the storm, and ascent from the trailing cold pool is needed to support deep convection. Storm intensity decreases with deeper and less buoyant MABLs, in part due to the reduction in elevated instability. Precipitation is enhanced just prior to the collision between a storm and the deepest marine layers. Storms modify their environment downstream, leading to the development of a moist adiabatic unstable layer and a lowering of the level of free convection (LFC) to below the top of the deepest marine layer. An MABL moving as a sea breeze into the storm-modified air successfully lifts parcels to the new LFC, generating convective towers ahead of the squall line. This mechanism may contribute to increased coastal flash flooding risks during observed events.
What unites Europe and what divides it? Solidarity and the European heritage reconsidered
Authors: Delanty Gerard 
Published: February 2018

AbstractDespite the on-set on new divisions, there is a strong case to be made for the view that ultimately Europe is more united than divided. There is still significant continuity with the post-war project of reconstruction and peace and that this common ground that constitutes the European heritage needs to be given greater recognition. One of the defining features of European self-understanding is opposition to war.
GTL1 and DF1 regulate root hair growth through transcriptional repression of ROOT HAIR DEFECTIVE 6-LIKE 4 in Arabidopsis
Authors: Shibata Michitaro , Breuer Christian , Kawamura Ayako , Clark Natalie M. , Rymen Bart , Braidwood Luke , Morohashi Kengo , Busch Wolfgang , Benfey Philip N. , Sozzani Rosangela , Sugimoto Keiko 
Published: February 2018

ABSTRACT
How plants determine the final size of growing cells is an important, yet unresolved, issue. Root hairs provide an excellent model system with which to study this as their final cell size is remarkably constant under constant environmental conditions. Previous studies have demonstrated that a basic helix-loop helix transcription factor ROOT HAIR DEFECTIVE 6-LIKE 4 (RSL4) promotes root hair growth, but how hair growth is terminated is not known. In this study, we demonstrate that a trihelix transcription factor GT-2-LIKE1 (GTL1) and its homolog DF1 repress root hair growth in Arabidopsis. Our transcriptional data, combined with genome-wide chromatin-binding data, show that GTL1 and DF1 directly bind the RSL4 promoter and regulate its expression to repress root hair growth. Our data further show that GTL1 and RSL4 regulate each other, as well as a set of common downstream genes, many of which have previously been implicated in root hair growth. This study therefore uncovers a core regulatory module that fine-tunes the extent of root hair growth by the orchestrated actions of opposing transcription factors.
The developmental and genetic basis of ‘clubfoot’ in the peroneal muscular atrophy mutant mouse
Authors: Collinson J. Martin , Lindström Nils O. , Neves Carlos , Wallace Karen , Meharg Caroline , Charles Rebecca H. , Ross Zoe K. , Fraser Amy M. , Mbogo Ivan , Oras Kadri , Nakamoto Masaru , Barker Simon , Duce Suzanne , Miedzybrodzka Zosia , Vargesson Neil 
Published: February 2018

ABSTRACTGenetic factors underlying the human limb abnormality congenital talipes equinovarus (‘clubfoot’) remain incompletely understood. The spontaneous autosomal recessive mouse ‘peroneal muscular atrophy’ mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The pma mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (Limk1) identified, which is upregulated in mutant lateral LMC motor neurons. Genetic and molecular analyses showed that the mutation acts in the EphA4–Limk1–Cfl1/cofilin–actin pathway to modulate growth cone extension/collapse. In the chicken, both experimental upregulation of Limk1 by electroporation and pharmacological inhibition of actin turnover led to defects in hindlimb spinal motor neuron growth and pathfinding, and mimicked the clubfoot phenotype. The data support a neuromuscular aetiology for clubfoot and provide a mechanistic framework to understand clubfoot in humans.
EFA6 proteins regulate lumen formation through α-actinin 1
Authors: Milanini Julie , Fayad Racha , Partisani Mariagrazia , Lecine Patrick , Borg Jean-Paul , Franco Michel , Luton Frédéric 
Published: February 2018

ABSTRACT
A key step of epithelial morphogenesis is the creation of the lumen. Luminogenesis by hollowing proceeds through the fusion of apical vesicles at cell–cell contacts. The small nascent lumens grow through extension, coalescence and enlargement, coordinated with cell division, to give rise to a single central lumen. Here, by using MDCK cells grown in 3D-culture, we show that EFA6A (also known as PSD) participates in luminogenesis. EFA6A recruits α-actinin 1 (ACTN1) through direct binding. In polarized cells, ACTN1 was found to be enriched at the tight junction where it acts as a primary effector of EFA6A for normal luminogenesis. Both proteins are essential for the lumen extension and enlargement, where they mediate their effect by regulating the cortical acto-myosin contractility. Finally, ACTN1 was also found to act as an effector for the isoform EFA6B (also known as PSD4) in the human mammary tumoral MCF7 cell line. EFA6B restored the glandular morphology of this tumoral cell line in an ACTN1-dependent manner. Thus, we identified new regulators of cyst luminogenesis essential for the proper maturation of a newly-formed lumen into a single central lumen.
Image co-localization – co-occurrence versus correlation
Authors: Aaron Jesse S. , Taylor Aaron B. , Chew Teng-Leong 
Published: February 2018

ABSTRACT
Fluorescence image co-localization analysis is widely utilized to suggest biomolecular interaction. However, there exists some confusion as to its correct implementation and interpretation. In reality, co-localization analysis consists of at least two distinct sets of methods, termed co-occurrence and correlation. Each approach has inherent and often contrasting strengths and weaknesses. Yet, neither one can be considered to always be preferable for any given application. Rather, each method is most appropriate for answering different types of biological question. This Review discusses the main factors affecting multicolor image co-occurrence and correlation analysis, while giving insight into the types of biological behavior that are better suited to one approach or the other. Further, the limits of pixel-based co-localization analysis are discussed in the context of increasingly popular super-resolution imaging techniques.
Evolution of neuropeptide signalling systems
Authors: Elphick Maurice R. , Mirabeau Olivier , Larhammar Dan 
Published: February 2018

ABSTRACT
Neuropeptides are a diverse class of neuronal signalling molecules that regulate physiological processes and behaviour in animals. However, determining the relationships and evolutionary origins of the heterogeneous assemblage of neuropeptides identified in a range of phyla has presented a huge challenge for comparative physiologists. Here, we review revolutionary insights into the evolution of neuropeptide signalling that have been obtained recently through comparative analysis of genome/transcriptome sequence data and by ‘deorphanisation’ of neuropeptide receptors. The evolutionary origins of at least 30 neuropeptide signalling systems have been traced to the common ancestor of protostomes and deuterostomes. Furthermore, two rounds of genome duplication gave rise to an expanded repertoire of neuropeptide signalling systems in the vertebrate lineage, enabling neofunctionalisation and/or subfunctionalisation, but with lineage-specific gene loss and/or additional gene or genome duplications generating complex patterns in the phylogenetic distribution of paralogous neuropeptide signalling systems. We are entering a new era in neuropeptide research where it has become feasible to compare the physiological roles of orthologous and paralogous neuropeptides in a wide range of phyla. Moreover, the ambitious mission to reconstruct the evolution of neuropeptide function in the animal kingdom now represents a tangible challenge for the future.
Provision of mental health care within primary care in Peru: A qualitative study exploring the perspectives of psychologists, primary health care providers, and patients
Authors: Cavero Victoria , Diez-Canseco Francisco , Toyama Mauricio , Flórez Salcedo Gustavo , Ipince Alessandra , Araya Ricardo , Miranda J. Jaime 
Published: February 2018

Background: This study aimed to understand the offer of mental health care at the primary care level, collecting the views of psychologists, primary health care providers (PHCPs), and patients, with a focus on health services in which patients attend regularly and who present a higher prevalence of mental disorders. Methods: A qualitative study was conducted in antenatal care, tuberculosis, HIV/AIDS, and chronic diseases services from six primary health care centers. Semi-structured interviews were conducted with psychologists, PHCPs, and patients working in or attending the selected facilities. Results: A total of 4 psychologists, 22 PHCPs, and 37 patients were interviewed. A high perceived need for mental health care was noted. PHCPs acknowledged the emotional impact physical health conditions have on their patients and mentioned that referral to psychologists was reserved only for serious problems. Their approach to emotional problems was providing emotional support (includes listening, talk about their patients’ feelings, provide advice). PHCPs identified system-level barriers about the specialized mental health care, including a shortage of psychologists and an overwhelming demand, which results in brief consultations and lack in continuity of care. Psychologists focus their work on individual consultations; however, consultations were brief, did not follow a standardized model of care, and most patients attend only once. Psychologists also mentioned the lack of collaborative work among other healthcare providers. Despite these limitations, interviewed patients declared that they were willing to seek specialized care if advised and considered the psychologist's care provided as helpful; however, they recognized the stigmatization related to seeking mental health care. Conclusions: There is a perceived need of mental health care for primary care patients. To attend these needs, PHCPs provide emotional support and refer to psychology the most severe cases, while psychologists provide one-to-one consultations. Significant limitations in the care provided are discussed.