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

Chronic Oedema and the older person: The effects of ageing upon treatment outcomes

Chronic oedema (CO) and lymphoedema (LO) are long-term conditions that can become more complicated or are more likely to develop with age. The ageing process can involve alterations in the structures that support the normal function of the lymphatic system or put it at greater risk of damage. The main three components (skin care, exercise and compression therapy) within the management of CO/LO can become more difficult to apply with age. This is because of reduced healing rates, decreased cardiovascular capacity and deterioration in vascular and arterial structures. The impact of ageing and how this can affect patients and treatment outcomes requires careful consideration

Skeletal Muscle-Specific Ablation of γcyto-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γcyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γcyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γcyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γcyto-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests γcyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a γcyto-actin-utrophin interaction

Recruiting to a large-scale physical activity randomised controlled trial – experiences with the gift of hindsight

Background: Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to support researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this paper is to build on the knowledge available to researchers on recruiting to community based trials. Methods: A critical commentary of the recruitment challenges encountered during the ‘Booster’ Study, a randomised controlled trial which investigated the effectiveness of a Motivational Interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Results: Two hundred and eighty two people, 47% of the original target, were recruited through mail-outs with secondary recruitment pathways yielding no additional participants. The research team encountered problems re-contacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study compared to the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the RCT. Conclusion: Despite utilising widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the ‘Booster’ study failed to randomise a sufficient number of participants. Recruitment to community based, behavioural interventions may face different challenges than trials based in clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design is facilitative to recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible the impact of new strategies should be measured, and recruitment successes and challenges shared with those planning similar studies. The study was a registered controlled trial (ISRCTN56495859 12 Feb 2009; NCT00836459 03 Feb 2009) KEYWORDS: Recruitment, Physical Activity, mail-outs, BOOSTER, behaviour maintenance

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Implementing GDPR in the Charity Sector: A Case Study

Due to their organisational characteristics, many charities are poorly prepared for the General Data Protection Regulation (GDPR). We present an exemplar process for implementing GDPR and the DPIA Data Wheel, a DPIA framework devised as part of the case study, that accounts for these characteristics. We validate this process and framework by conducting a GDPR implementation with a charity that works with vulnerable adults. This charity processes both special category (sensitive) and personally identifiable data. This GDPR implementation was conducted and devised for the charity sector, but can be equally applied in any organisation that needs to implement GDPR or conduct DPIAs

Comparison of Human Memory CD8 T Cell Responses to Adenoviral Early and Late Proteins in Peripheral Blood and Lymphoid Tissue

Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16–24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients