Flyglow: Single-fly observations of simultaneous molecular and behavioural circadian oscillations in controls and an Alzheimer's model.

Circadian rhythms are essential for health and are frequently disturbed in disease. A full understanding of the causal relationships between behavioural and molecular circadian rhythms requires simultaneous longitudinal observations over time in individual organisms. Current experimental paradigms require the measurement of each rhythm separately across distinct populations of experimental organisms, rendering the comparability of the resulting datasets uncertain. We therefore developed FLYGLOW, an assay using clock gene controlled luciferase expression detected by exquisitely sensitive EM-CCD imaging, to enable simultaneous quantification of parameters including locomotor, sleep consolidation and molecular rhythms in single flies over days/weeks. FLYGLOW combines all the strengths of existing techniques, and also allows powerful multiparametric paired statistics. We found the age-related transition from rhythmicity to arrhythmicity for each parameter occurs unpredictably, with some flies showing loss of one or more rhythms during middle-age. Using single-fly correlation analysis of rhythm robustness and period we demonstrated the independence of the peripheral clock from circadian behaviours in wild type flies as well as in an Alzheimer's model. FLYGLOW is a useful tool for investigating the deterioration of behavioural and molecular rhythms in ageing and neurodegeneration. This approach may be applied more broadly within behavioural neurogenetics research

The epidemiology of patellar luxation in dogs attending primary-care veterinary practices in England

BACKGROUND: Canine patellar luxation is one of the most common orthopaedic disorders of dogs and is a potential welfare concern because it can lead to lameness, osteoarthritis and pain. However, there are limited epidemiological data on the disorder relating to the general population of dogs in England. This study aimed to investigate the VetCompass Programme database of dogs attending primary-care veterinary practices in England to report on the prevalence, risk factors and clinical management of diagnosed patellar luxation cases. RESULTS: The study included all dogs with at least one electronic patient record in the VetCompass database from September 1(st), 2009 to August 31(st), 2014. Candidate patellar luxation cases were identified using free-text word searching of the clinical notes and VeNom diagnosis term fields. Univariable and multivariable binary logistic regression modelling was used for risk factor analysis. The overall dataset comprised 210,824 dogs attending 119 clinics in England. The prevalence of patellar luxation diagnosis in dogs was 1.30 % (95 % confidence interval (CI) 1.21-1.39). Of the 751 incident cases, 293 (39.0 %) received medical management, 99 (13.2 %) received surgical intervention and 28 (3.7 %) were referred for further management. Multivariable modelling documented 11 breeds with increased odds of patellar luxation compared with crossbred dogs, including the Pomeranian (odds ratio [OR]: 6.5, 95 % CI 4.0-10.7, P < 0.001), Chihuahua (OR: 5.9, 95 % CI 4.4-7.9, P < 0.001), Yorkshire Terrier (OR: 5.5, 95 % CI 4.3-7.1, P < 0.001) and French Bulldog (OR: 5.4, 95 % CI 3.1-9.3, P < 0.001). Dogs with bodyweight below their mean for breed and sex had a 1.4 times odds of diagnosis (95 % CI 1.2-1.6, P < 0.001). Dogs aged ≥ 12.0 years showed 0.4 times the odds (95 % CI 0.3-0.5, P < 0.001) compared with dogs aged < 3.0 years. Females had 1.3 times the odds (95 % CI 1.1-1.5, P < 0.001), neutered dogs had 2.4 times the odds (95 % CI 1.8-3.2, P < 0.001) and insured dogs had 1.9 times the odds (95 % CI 1.6-2.3, P < 0.001). CONCLUSIONS: Patellar luxation warrants inclusion as a welfare priority in dogs and control strategies that include this disorder should be considered as worthwhile breeding goals, especially in predisposed breeds

On the Alexandrov Topology of sub-Lorentzian Manifolds

It is commonly known that in Riemannian and sub-Riemannian Geometry, the metric tensor on a manifold defines a distance function. In Lorentzian Geometry, instead of a distance function it provides causal relations and the Lorentzian time-separation function. Both lead to the definition of the Alexandrov topology, which is linked to the property of strong causality of a space-time. We studied three possible ways to define the Alexandrov topology on sub-Lorentzian manifolds, which usually give different topologies, but agree in the Lorentzian case. We investigated their relationships to each other and the manifold's original topology and their link to causality.Comment: 20 page

Health-related welfare prioritisation of canine disorders using electronic health records in primary care practice in the UK

Background: Evidence-based comparison of the disorder-specific welfare burdens of major canine conditions could better inform targeting of stakeholder resources, to maximise improvement of health-related welfare in UK dogs. Population-level disease related welfare impact offers a quantitative, welfare-centred framework for objective disorder prioritisation, but practical applications have been limited to date due to sparse reliable evidence on disorder-specific prevalence, severity and duration across the canine disease spectrum. The VetCompass™ Programme collects de-identified electronic health record data from dogs attending primary-care clinics UK-wide, and is well placed to fill these information gaps. Results: The eight common, breed-related conditions assessed were anal sac disorder, conjunctivitis, dental disease, dermatitis, overweight/obese, lipoma, osteoarthritis and otitis externa. Annual period prevalence estimates (based on confirming 250 cases from total potential cases identified from denominator population of 455, 557 dogs) were highest for dental disorder (9.6%), overweight/obese (5.7%) and anal sac disorder (4.5%). Dental disorder (76% of study year), osteoarthritis (82%), and overweight/obese (70%) had highest annual duration scores. Osteoarthritis (scoring 13/21), otitis externa (11/21) and dermatitis demonstrated (10/21) highest overall severity scores. Dental disorder (2.47/3.00 summative score), osteoarthritis (2.24/3.00) and overweight/obese (1.67/3.00) had highest VetCompass Welfare Impact scores overall. Discussion: Of the eight common, breed-related disorders assessed, dental disorder, osteoarthritis and overweight/obese demonstrated particular welfare impact, based on combinations of high prevalence, duration and severity. Future work could extend this methodology to cover a wider range of disorders. Conclusions: Dental disorders, osteoarthritis and overweight/obese have emerged as priority areas for health-related welfare improvement in the UK dog population. This study demonstrated applicability of a standardised methodology to assess the relative health-related welfare impact across a range of canine disorders using VetCompass clinical data

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.&lt;/p&gt

Hybrid management of a spontaneous ilio-iliac arteriovenous fistula: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous iliac arteriovenous fistulae are a rare clinical entity. Such localized fistulation is usually a result of penetrating traumatic or iatrogenic injury. Clinical presentation can vary greatly but commonly includes back pain, high-output congestive cardiac failure and the presence of an abdominal bruit. Diagnosis, therefore, is often incidental or delayed.</p> <p>Case presentation</p> <p>We report a case of a spontaneous ilio-iliac arteriovenous fistula in a 68-year-old Caucasian man detected following presentation with unilateral claudication and congestive cardiac failure. Following computed tomography evaluation, the fistula was successfully treated with a combined endovascular (aorto-uni-iliac device) and open (femoro-femoral crossover) approach.</p> <p>Conclusion</p> <p>Endovascular surgery has revolutionized the management of such fistulae and we report an interesting case of a high-output iliac arteriovenous fistulae successfully treated with a hybrid vascular approach.</p

Observational Evidence of For-Profit Delivery and Inferior Nursing Home Care: When Is There Enough Evidence for Policy Change?

This research was financially supported by the Social Sciences and Humanities Research Council

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Pressure pain sensitivity maps of the neck-shoulder and the low back regions in men and women

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal pain in the low back and neck-shoulder regions is a major problem among the working population all over the world. The prevalence of musculoskeletal pain is found to be higher among women. Women also have lower pressure pain thresholds (PPTs) than men. Pressure pain topography aims at mapping the spatial distribution of PPT within a muscle in an attempt to track changes in mechanical sensitivity. In order to assess gender differences in the pain topography, it is necessary to map the distribution in both healthy men and women. The aim of this study was to assess PPT maps from the cervico-thoracic and lumbar regions in men and women.</p> <p>Methods</p> <p>Eleven men and eleven women without any known musculoskeletal disorders participated in the study. PPT was measured twice at 36 points over the trapezius muscle of the dominant arm, at 36 points over the trapezius muscle on the contralateral side and at 12 points over the spine between the left and right trapezius. Further, 11 points were measured over the erector spinae muscle on the left side of the spine between the first and the fifth lumbar vertebrae, 11 on the right side and 5 points on the spine itself. The measurements on each trapezius muscle were divided according to anatomical subdivisions. Three-way and two-way ANOVAs were used to analyse the differences in PPTs with the following factors: gender, locations and sub-divisions (only for cervico-thoracic region).</p> <p>Results</p> <p>There were no differences between left and right side in neither the cervico-thoracic nor the lumbar region, but there were (large effect) differences between the subdivisions in the trapezius with the lowest values in the upper part (P < 0.001; partial η²= 0.19). Women had (small effect) lower PPT in both cervico-thoracic and lumbar regions (P ≤ 0.001; partial η²= 0.02 for both regions), but gender had no effect on neither location nor subdivisions.</p> <p>Conclusions</p> <p>The pain topography was not found to be different between genders in the cervico-thoracic and lumbar regions. This study can be used as basis for further clinical studies on musculoskeletal disorders.</p

Obesity prevalence estimates in a Canadian regional population of preschool children using variant growth references

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is a public health problem in Canada. Accurate measurement of a health problem is crucial in defining its burden. The objective of this study is to compare the prevalence estimates of overweight and obesity in preschool children using three growth references.</p> <p>Methods</p> <p>Weights and heights were measured on 1026 preschool children born in Newfoundland and Labrador (NL), Canada, and body mass index calculated. The prevalence of overweight and obesity was determined and statistical comparisons conducted among the three growth references; the Centres for Disease Control (CDC), the International Obesity Task Force (IOTF) and the World Health Organization (WHO).</p> <p>Results</p> <p>CDC and IOTF produced similar estimates of the prevalence of overweight, 19.1% versus 18.2% while the WHO reported a higher prevalence 26.7% (p < .001). The CDC classified twice as many children as obese compared to the IOTF 16.6% versus 8.3% (p < .001) and a third more than the WHO 16.6% versus 11.3% (p < .01). There was variable level of agreement between methods.</p> <p>Conclusions</p> <p>The CDC reported a much higher prevalence of obesity compared to the other references. The prevalence of childhood obesity is dependent on the growth reference used.</p