bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital dystrophic epidermolysis bullosa (DEB) in Sprague Dawley rats: a case series
Authors: Eden Kristin B. , Peterson Ashley , Payne Harold R. , Corapi Wayne V. , Mansell Joanne , Hoffman Aline Rodrigues 
Published: February 2016

BackgroundEpidermolysis bullosa is a rare skin disease caused by defects in the basement membrane and/or other dermoepidermal junction components.Hypothesis/ObjectivesWe describe a series of spontaneous cases of dystrophic epidermolysis bullosa (DEB) in a colony of Sprague Dawley rats investigated with histopathology, transmission electron microscopy (TEM) and inheritance pattern.AnimalsFour, 4‐day‐old pups from a litter of Sprague Dawley rats developed blistering, haemorrhagic skin lesions and were euthanized. Age‐matched controls from the same litter were normal. Several months later two more litters presented with identical findings. All three litters had the same sire, suggesting a genetic component.MethodsSkin from affected and control animals was evaluated histologically and with TEM. Unaffected sibling pairs from affected litters were bred in order to potentially reproduce the disease and determine the mode of inheritance.ResultsHistologically, there was significant dermoepidermal clefting below the basement membrane with variable amounts of haemorrhage and cellular debris within the clefts. Ultrastructurally, clefting occurred below the basement membrane with an intact lamina densa and normal hemidesmosomes. Anchoring filaments were strikingly absent. Litters produced from phenotypically unaffected sibling pairs resulted in a total of four more litters with approximately a quarter of pups affected.Conclusions and clinical importanceBased on the gross lesions, histopathological features and TEM determination of separation below the lamina densa and lack of normal anchoring fibrils, these cases are most consistent with DEB. This is the first report of naturally occurring, localized and reproducible recessive DEB in Sprague Dawley rats.
Intracellular soluble α‐synuclein oligomers reduce pyramidal cell excitability
Authors: Kaufmann Timothy J. , Harrison Paul M. , Richardson Magnus J. E. , Pinheiro Teresa J. T. , Wall Mark J. 
Published: February 2016

Key points
The presynaptic protein α‐synuclein forms aggregates during Parkinson's disease.
Accumulating evidence suggests that the small soluble oligomers of α‐synuclein are more toxic than the larger aggregates appearing later in the disease.
The link between oligomer toxicity and structure still remains unclear.
In the present study, we have produced two structurally‐defined oligomers that have a similar morphology but differ in secondary structure.
These oligomers were introduced into neocortical pyramidal cells during whole‐cell recording and, using a combination of experimentation and modelling, electrophysiological parameters were extracted.
Both oligomeric species had similar effects on neuronal properties reducing input resistance, time constant and increasing capacitance. The net effect was a marked reduction in neuronal excitability that could impact on network activity.
AbstractThe presynaptic protein α‐synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore‐forming complexes that permeabilize membranes. In the present study, two well‐defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole‐cell patch clamp recording. Using a combined experimental and modelling approach, neuronal parameters were extracted to measure, for the first time in the neocortex, specific changes in neuronal electrophysiology. Both species of oligomer had similar effects: (i) a significant reduction in input resistance and the membrane time constant and (ii) an increase in the current required to trigger an action potential with a resultant reduction in the firing rate. Differences in oligomer secondary structure appeared to produce only subtle differences in the activity of the oligomers. Monomeric αSyn had no effect on neuronal parameters, even at high concentrations. The oligomer‐induced fall in neuronal excitability has the potential to impact both network activity and cognitive processing.
Quantification of Seasonal-Long Physical Load in Soccer Players With Different Starting Status From the English Premier League: Implications for Maintaining Squad Physical Fitness
Authors: Anderson Liam , Orme Patrick , Michele Rocco Di , Close Graeme L. , Milsom Jordan , Morgans Ryland , Drust Barry , Morton James P. 
Published: February 2016

Purpose:To quantify the accumulative training and match load during an annual season in English Premier League soccer players classified as starters (n = 8, started ≥60% of games), fringe players (n = 7, started 30–60% of games) and nonstarters (n = 4, started <30% of games).
MethodsPlayers were monitored during all training sessions and games completed in the 2013–14 season with load quantified using global positioning system and Prozone technology, respectively.
Results:When including both training and matches, total duration of activity (10,678 ± 916, 9955 ± 947, 10,136 ± 847 min; P = .50) and distance covered (816.2 ± 92.5, 733.8 ± 99.4, 691.2 ± 71.5 km; P = .16) were not different between starters, fringe players, and nonstarters, respectively. However, starters completed more (all P < .01) distance running at 14.4–19.8 km/h (91.8 ± 16.3 vs 58.0 ± 3.9 km; effect size [ES] = 2.5), high-speed running at 19.9–25.1 km/h (35.0 ± 8.2 vs 18.6 ± 4.3 km; ES = 2.3), and sprinting at >25.2 km/h (11.2 ± 4.2 vs 2.9 ± 1.2 km; ES = 2.3) than nonstarters. In addition, starters also completed more sprinting (P < .01, ES = 2.0) than fringe players, who accumulated 4.5 ± 1.8 km. Such differences in total high-intensity physical work done were reflective of differences in actual game time between playing groups as opposed to differences in high-intensity loading patterns during training sessions.
ConclusionsUnlike total seasonal volume of training (ie, total distance and duration), seasonal high-intensity loading patterns are dependent on players’ match starting status, thereby having potential implications for training program design.
Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review
Authors: Wexler Nancy S , Collett Laura , Wexler Alice R , Rawlins Michael D , Tabrizi Sarah J , Douglas Ian , Smeeth Liam , Evans Stephen J 
Published: February 2016

ObjectivesThe prevalence of Huntington's disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD.SettingIncident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations.ParticipantsA total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9 282 126 persons.Primary and secondary outcome measuresThe incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I2statistic.ResultsThe data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some—though not all—those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods.ConclusionsThe rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele.
How smoking affects the proportion of deaths attributable to obesity: assessing the role of relative risks and weight distributions
Authors: Stokes Andrew , Preston Samuel H 
Published: February 2016

ObjectiveAlthough ever-smokers make up the majority of the older adult population in the USA, they are often excluded from studies examining the impact of obesity on mortality. Understanding how smoking and obesity interact is critical to assessing the proportion of deaths attributable to obesity.SettingNationally representative sample of the non-institutionalised population of the USA. Baseline data were drawn from the National Health and Nutrition Examination Survey, 1988–1994 and 1999–2004.ParticipantsUS adults aged 50–74 (n=9835).Primary outcome measureWe used Cox models to estimate the mortality risks of obesity by smoking status. All-cause mortality was assessed prospectively through 31 December 2006 (n=1243 deaths). Maximum body mass index (BMI) was specified as the key exposure variable. We also calculated population attributable fractions (PAFs) by smoking status and investigated differences in PAFs in a decomposition analysis.ResultsThe HR associated with a one-unit increment in BMI beyond 25.0 kg/m2was 1.057 for never-smokers (95% CI 1.033 to 1.082; p<0.001), 1.036 for former smokers (95% CI 1.015 to 1.059; p<0.01) and 1.024 for current smokers (95% CI 0.997 to 1.052).We estimated that 19.8% of deaths were attributable to excess weight. The PAFs were 31.9, 20.4 and 11.3 for never-smokers, former and current smokers, respectively. The difference in PAFs between never-smokers and current smokers was almost entirely explained by the difference in HRs.ConclusionsThe proportion of deaths attributable to obesity is nearly 3 times as high among never-smokers compared with current smokers. This finding is consistent with the fact that smokers are subject to significant competing risks. Analyses that exclude smokers are likely to substantially overestimate the proportion of deaths attributable to obesity in the USA.
A prospective surveillance of paediatric head injuries in Singapore: a dual-centre study
Authors: Chong Shu-Ling , Chew Su Yah , Feng Jasmine Xun Yi , Teo Penny Yun Lin , Chin Sock Teng , Liu Nan , Ong Marcus Eng Hock 
Published: February 2016

ObjectiveTo study the causes of head injuries among the paediatric population in Singapore, and the association between causes and mortality, as well as the need for airway or neurosurgical intervention.DesignThis is a prospective observational study utilising data from the trauma surveillance system from January 2011 to March 2015.SettingPaediatric emergency departments (EDs) of KK Women's and Children's Hospital and the National University Health System.ParticipantsWe included children aged <16 years presenting to the paediatric EDs with head injuries who required a CT scan, admission for monitoring of persistent symptoms, or who died from the head injury. We excluded children who presented with minor mechanisms and those whose symptoms had spontaneously resolved.Primary and secondary outcome measuresPrimary composite outcome was defined as death or the need for intubation or neurosurgical intervention. Secondary outcomes included length of hospital stay and type of neurosurgical intervention.ResultsWe analysed 1049 children who met the inclusion criteria. The mean age was 6.7 (SD 5.2) years. 260 (24.8%) had a positive finding on CT. 17 (1.6%) children died, 52 (5.0%) required emergency intubation in the ED and 58 (5.5%) underwent neurosurgery. The main causes associated with severe outcomes were motor vehicle crashes (OR 7.2, 95% CI 4.3 to 12.0) and non-accidental trauma (OR 5.8, 95% CI 1.8 to 18.6). This remained statistically significant when we stratified to children aged <2 years and performed a multivariable analysis adjusting for age and location of injury. For motor vehicle crashes, less than half of the children were using restraints.ConclusionsMotor vehicle crashes and non-accidental trauma causes are particularly associated with poor outcomes among children with paediatric head injury. Continued vigilance and compliance with injury prevention initiatives and legislature are vital.
Improving the Physical Health Monitoring of City & Hackney Assertive Outreach Service Patients
Authors: Akyuz Elvan , jain amit , phelan declan , Gupta Susham 
Published: February 2016

AbstractImproving physical healthcare to reduce premature mortality in people with SMI (Serious Mental Illness) is a priority for ELFT (East London NHS Foundation Trust) and NHS England. It is well know that people with schizophrenia have a life expectancy which is approximately 20% shorter than that of the general population and a substantial mortality difference exists between people with schizophrenia and the general community.[1-2] Among other risk factors, such as poor diet, physical inactivity, and high rates of smoking, the iatrogenic effects of anti-psychotic medications have been found to increase the risk of metabolic syndrome. This can easily be detected through regular monitoring.Through this project, it was our aim to improve the physical health monitoring of City & Hackney Assertive Outreach Service (AOS) patients with a view to decrease mortality rate, increase life expectancy, increase the quality of life, and reduce harm from medication. This was done using quality improvement methods, including several change ideas, each of which started sequentially over the course of a nine month period from November 2014. Following QI methodology, this utilised cycles of iterative learning using PDSA methods and was supported by the Trust’s extensive programme of quality improvement, including training provided by the Institute for Healthcare Improvement.The project involved setting a specific aim which was improving the physical health monitoring of AOS patients to 80% by July 2015 and for our patients to have physical health checks (blood tests, weight, ECG, BP) as a minimum annually. From baseline measurements of between 50-75%, we reached our target of 80% for weight, BP and blood tests monitoring, with 89%, 91%, and 84% achieved respectively by July 2015. Further progress still needs to be made on ECGs, with 77% achieved by July 2015, although the monitoring of ECG nearly doubled from 39% in November 2014 to 77% in July 2015.This project demonstrated that effective leadership, collaborative team work, embedding the project in our daily practice, generating local solutions, and improved communication between primary and secondary care can increase the physical health monitoring of this complex and challenging patient group. The team continues to identify other areas for change that may lead to further improvement in the physical health monitoring of AOS patients while making sure that the improvement is sustained.
Dynamic cycling in atrial size and flow during obstructive apnoea
Authors: Pressman Gregg S , Cepeda-Valery Beatriz , Codolosa Nicolas , Orban Marek , Samuel Solomon P , Somers Virend K 
Published: February 2016

ObjectiveObstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease. However, acute cardiovascular effects of repetitive airway obstruction are poorly understood. While past research used a sustained Mueller manoeuver to simulate OSA we employed a series of gasping efforts to better simulate true obstructive apnoeas. This report describes acute changes in cardiac anatomy and flow related to sudden changes in intrathoracic pressure.Methods and results26 healthy, normal weight participants performed 5–6 gasping efforts (target intrathoracic pressure −40 mm Hg) while undergoing Doppler echocardiography. 14 participants had sufficient echocardiographic images to allow comparison of atrial areasduringthe manoeuver with baseline measurements. Mitral and tricuspid E-wave and A-wave velocitiespostmanoeuver were compared with baseline in all participants. Average atrial areas changed little during the manoeuver, but variance in both atrial areas was significantly greater than baseline. Further, an inverse relationship was noted with left atrial collapse and right atrial enlargement at onset of inspiratory effort. Significant inverse changes were noted in Doppler flow when comparing the first beat postmanoeuver (pMM1) with baseline. Mitral E-wave velocity increased 9.1 cm/s while tricuspid E-wave velocity decreased 7.0 cm/s; by the eighth beat postmanoeuver (pMM8) values were not different from baseline. Mitral and tricuspid A-wave velocities were not different from baseline at pMM1, but both were significantly higher by pMM8.ConclusionsRepetitive obstructive apnoeas produce dynamic, inverse changes in atrial size and Doppler flow across the atrioventricular valves. These observations have important implications for understanding the pathophysiology of OSA.
Comparison of cushioned centrifugation and SpermFilter filtration on longevity and morphology of cooled‐stored equine semen
Authors: Roach J. , Schnobrich M. , Ellerbrock R. , Feijo L. , Bradecamp E. , Alvarenga M. A. , Kline K. , Canisso I. 
Published: February 2016

This study compares two methods for seminal plasma removal by evaluating sperm recovery rates, and motility and morphology of cooled‐stored semen. Ejaculates were divided into three groups: control, filtration and cushioned centrifugation. Semen was extended to 25 million sperm/ml using a skim‐milk‐based extender and stored at 5°C for all groups. Sperm motility (total motility (%TM) and progressive motility (%PM)) was determined at 0, 24, 48 and 72 hours by a computer‐assisted sperm analyser. Sperm morphology was assessed using differential interference microscopy. Overall, %TM of the centrifugation group was significantly higher than the filter group, but not significantly different than the control. No significant difference in %TM or %PM was detected for the control group and filter. Cushioned centrifugation was a superior method to obtain progressively motile sperm compared with control (P=0.03) and filter groups (P<0.001). No significant difference was found for the per cent of normal sperm cells and detached heads between the groups. This study demonstrated that cushioned centrifugation was a superior method to remove seminal plasma while preserving %TM and enhancing %PM for stallions under cooled storage over three days. However, as the differences appear to be negligible, the SpermFilter may represent an alternative for farms lacking a centrifuge.
Measurement of junction temperature and thermal resistance in InGaAlAs/AlGaAs quantum-well superluminescent diodes (SLDs)
Authors: Zhou Shuai , Zhang Jing , Duan Li-Hua , Tang Zu-Rong , Deng Guang-Hua 
Published: February 2016

This paper reports on the experimental method of the determination of junction temperature and thermal resistance in 840 nm InGaAlAs/AlGaAs compressive strained single quantum well (SQW) superluminescent diodes (SLDs). The linear relation between forward voltage and junction temperature clearly occurs by utilizing the forward voltage–temperature ([Formula: see text]–[Formula: see text]) method. The temperature coefficient [Formula: see text] has been determined. Under 100 mA continuous-wave (CW) operation condition, the thermal resistance is measured to be 81.6[Formula: see text]C/W, which is not significantly different with the theoretical calculation result.
Performance Challenges, Current Bad Practices, and Hints in PaaS Cloud Application Design
Authors: Gesvindr David , Buhnova Barbora 
Published: February 2016

Cloud computing is becoming a popular approach to software application operation, utilizing on-demand network access to a pool of shared computing resources, and associated with many benefits including low-effort provisioning, rapid elasticity, maintenance cost reduction and pay-as-yougo billing model. However, application deployment in the cloud is not itself a guarantee of high performance, scalability, and related quality attributes, which may come as a surprise to many software engineers who detract from the importance of proper design of a cloud application, expecting that the cloud itself is the solution.
In this paper we analyze the issues and challenges associated with the design of a cloud application that has to be in compliance with given performance criteria, such as the throughput and response time. We also analyze the concerns related to other relevant quality criteria, including scalability, elasticity and availability. To support our findings, we demonstrate the identified performance effects of the examined design decisions on two case studies.
Performance Monitoring in SAP HANA's Continuous Integration Process
Authors: Rehmann Kim-Thomas , Seo Changyun , Hwang Dongwon , Truong Binh Than , Boehm Alexander , Lee Dong Hun 
Published: February 2016

Development principles such as continuous integration and continuous delivery become increasingly popular in the software industry. They allow for the quick and automated build, test, and delivery of software, thereby significantly improving the overall quality assurance and release processes.
In this paper, we show how to apply the ideas of continuous delivery to complex system software, as exemplified by the SAP HANA database platform. We discuss the integration of performance testing early in the delivery process and the construction of services to detect and report performance anomalies in a continuous integration process.