Assessing behavioural changes in ALS: cross-validation of ALS-specific measures

Objective: The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Methods: 60 ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity and overall accuracy of the BBI, when compared to the ALS-FTD-Q, were obtained. Results: The mean score of the whole sample on the BBI was 11.45±13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6±14.64, 9.62±11.38; p<.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r=.807, p<.0001), and no significant correlations between the BBI and other clinical/demographic characteristics, indicating good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Discussion: Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Prevention and management of excessive gestational weight gain: a survey of overweight and obese pregnant women

Background - Excessive gestational weight gain is associated with adverse infant, childhood and maternal outcomes and research to develop interventions to address this issue is ongoing. The views of women on gestational weight gain and the resources they would consider helpful in addressing this are however largely unknown. This survey aimed to determine the views of newly pregnant women, living in areas of social disadvantage, on 1) their current body weight and potential gestational weight gain and 2) the resources or interventions they would consider helpful in preventing excessive gestational weight gain. Methods - A convenience sample of overweight and obese pregnant women living in Fife, UK, were invited to complete a short anonymised questionnaire at their 12 week booking visit. Results - 428 women, BMI&#62;25 kg/m2, completed the questionnaire. Fifty-four per cent of respondents were obese (231) and 62% were living in areas of mild to moderate deprivation. Over three-quarters of participants felt dissatisfied with their current weight (81%). The majority of women (60%) expressed some concern about potential weight gain. Thirty-nine percent were unconcerned about weight gain during their pregnancy, including 34 women (19%) who reported having retained weight gained in earlier pregnancies. Amongst those concerned about weight gain advice on physical activity (41%) and access to sports/leisure facilities were favoured resources (36%). Fewer women (12%) felt that group sessions on healthy eating or attending a clinic for individualised advice (14%) would be helpful. "Getting time off work" was the most frequently cited barrier (48%) to uptake of resources other than leaflets. Conclusions- These data suggest a lack of awareness amongst overweight and obese women regarding excessive gestational weight gain. Monitoring of gestational weight gain, and approaches for its management, should be formally integrated into routine antenatal care. Barriers to the uptake of resources to address weight gain are numerous and must be considered in the design of future interventions and services

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

High-throughput gene and SNP discovery in Eucalyptus grandis, an uncharacterized genome

<p>Abstract</p> <p>Background</p> <p>Benefits from high-throughput sequencing using 454 pyrosequencing technology may be most apparent for species with high societal or economic value but few genomic resources. Rapid means of gene sequence and SNP discovery using this novel sequencing technology provide a set of baseline tools for genome-level research. However, it is questionable how effective the sequencing of large numbers of short reads for species with essentially no prior gene sequence information will support contig assemblies and sequence annotation.</p> <p>Results</p> <p>With the purpose of generating the first broad survey of gene sequences in <it>Eucalyptus grandis</it>, the most widely planted hardwood tree species, we used 454 technology to sequence and assemble 148 Mbp of expressed sequences (EST). EST sequences were generated from a normalized cDNA pool comprised of multiple tissues and genotypes, promoting discovery of homologues to almost half of <it>Arabidopsis</it> genes, and a comprehensive survey of allelic variation in the transcriptome. By aligning the sequencing reads from multiple genotypes we detected 23,742 SNPs, 83% of which were validated in a sample. Genome-wide nucleotide diversity was estimated for 2,392 contigs using a modified theta (θ) parameter, adapted for measuring genetic diversity from polymorphisms detected by randomly sequencing a multi-genotype cDNA pool. Diversity estimates in non-synonymous nucleotides were on average 4x smaller than in synonymous, suggesting purifying selection. Non-synonymous to synonymous substitutions (Ka/Ks) among 2,001 contigs averaged 0.30 and was skewed to the right, further supporting that most genes are under purifying selection. Comparison of these estimates among contigs identified major functional classes of genes under purifying and diversifying selection in agreement with previous researches.</p> <p>Conclusion</p> <p>In providing an abundance of foundational transcript sequences where limited prior genomic information existed, this work created part of the foundation for the annotation of the <it>E. grandis </it>genome that is being sequenced by the US Department of Energy. In addition we demonstrated that SNPs sampled in large-scale with 454 pyrosequencing can be used to detect evolutionary signatures among genes, providing one of the first genome-wide assessments of nucleotide diversity and Ka/Ks for a non-model plant species.</p

Successful establishment of primary small airway cell cultures in human lung transplantation

Background: The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway function either physiologically or directly. Our aims were to develop robust methods for sampling small airway epithelial cells (SAEC) and to establish submerged SAEC cultures for downstream experimentation

Multiplex Detection and SNP Genotyping in a Single Fluorescence Channel

Probe-based PCR is widely used for SNP (single nucleotide polymorphism) genotyping and pathogen nucleic acid detection due to its simplicity, sensitivity and cost-effectiveness. However, the multiplex capability of hydrolysis probe-based PCR is normally limited to one target (pathogen or allele) per fluorescence channel. Current fluorescence PCR machines typically have 4–6 channels. We present a strategy permitting the multiplex detection of multiple targets in a single detection channel. The technique is named Multiplex Probe Amplification (MPA). Polymorphisms of the CYP2C9 gene (cytochrome P450, family 2, subfamily C, polypeptide 9, CYP2C9*2) and human papillomavirus sequences HPV16, 18, 31, 52 and 59 were chosen as model targets for testing MPA. The allele status of the CYP2C9*2 determined by MPA was entirely concordant with the reference TaqMan® SNP Genotyping Assays. The four HPV strain sequences could be independently detected in a single fluorescence detection channel. The results validate the multiplex capacity, the simplicity and accuracy of MPA for SNP genotyping and multiplex detection using different probes labeled with the same fluorophore. The technique offers a new way to multiplex in a single detection channel of a closed-tube PCR