A histological study of the spinal cord and peripheral nervous system in scrapie disease of sheep

This work records the results of a study of the spinal cords, spinal sensory ganglia, sympathetic ganglia, Gasserian ganglia and neurones in the adrenal glands of sheep affected with scrapie disease.It was suggested that many minor changes in sympathetic ganglia may be of a non -specific nature and it was concluded that there was no significant morphological difference, including vacuolation of neurones, between the gelglia of clinically healthy sheep and those with scrapie disease

Chromatin Profiles of Chromosomally Integrated Human Herpesvirus-6A

Human herpesvirus-6A (HHV-6A) and 6B (HHV-6B) are two closely related betaherpesviruses that are associated with various diseases including seizures and encephalitis. The HHV-6A/B genomes have been shown to be present in an integrated state in the telomeres of latently infected cells. In addition, integration of HHV-6A/B in germ cells has resulted in individuals harboring this inherited chromosomally integrated HHV-6A/B (iciHHV-6) in every cell of their body. Until now, the viral transcriptome and the epigenetic modifications that contribute to the silencing of the integrated virus genome remain elusive. In the current study, we used a patient-derived iciHHV-6A cell line to assess the global viral gene expression profile by RNA-seq, and the chromatin profiles by MNase-seq and ChIP-seq analyses. In addition, we investigated an in vitro generated cell line (293-HHV-6A) that expresses GFP upon the addition of agents commonly used to induce herpesvirus reactivation such as TPA. No viral gene expression including miRNAs was detected from the HHV-6A genomes, indicating that the integrated virus is transcriptionally silent. Intriguingly, upon stimulation of the 293-HHV-6A cell line with TPA, only foreign promoters in the virus genome were activated, while all HHV-6A promoters remained completely silenced. The transcriptional silencing of latent HHV-6A was further supported by MNase-seq results, which demonstrate that the latent viral genome resides in a highly condensed nucleosome-associated state. We further explored the enrichment profiles of histone modifications via ChIP-seq analysis. Our results indicated that the HHV-6 genome is modestly enriched with the repressive histone marks H3K9me3/H3K27me3 and does not possess the active histone modifications H3K27ac/H3K4me3. Overall, these results indicate that HHV-6 genomes reside in a condensed chromatin state, providing insight into the epigenetic mechanisms associated with the silencing of the integrated HHV-6A genome

The Wicked Machinery of Government: Malta and the Problems of Continuity under the New Model Administration

This is a study focused on the early years of British rule in Malta (1800-1813). It explores the application to the island of the “new model” of colonial government, one based on direct rule from London mediated by the continuation of existing laws and institutions. Systemic deficiencies are identified. These tended to undermine the effectiveness of direct British rule. This study also reveals, in the context of legal and constitutional continuity, unresolved tensions between modernity and tradition. The political stability of the island was damaged and the possibility of continued British possession was threatened

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

Evolutionary history of endogenous Human Herpesvirus 6 reflects human migration out of Africa

Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result, ∼70 million people harbor the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if 1) these integrations are ancient, 2) if they still occur, and 3) whether circulating virus strains differ from integrated ones. Here, we used next-generation sequencing and mining of public human genome data sets to generate the largest and most diverse collection of circulating and integrated HHV-6 genomes studied to date. In genomes of geographically dispersed, only distantly related people, we identified clades of integrated viruses that originated from a single ancestral event, confirming this with fluorescent in situ hybridization to directly observe the integration locus. In contrast to HHV-6B, circulating and integrated HHV-6A sequences form distinct clades, arguing against ongoing integration of circulating HHV-6A or “reactivation” of integrated HHV-6A. Taken together, our study provides the first comprehensive picture of the evolution of HHV-6, and reveals that integration of heritable HHV-6 has occurred since the time of, if not before, human migrations out of Africa

The Current State of Performance Appraisal Research and Practice: Concerns, Directions, and Implications

On the surface, it is not readily apparent how some performance appraisal research issues inform performance appraisal practice. Because performance appraisal is an applied topic, it is useful to periodically consider the current state of performance research and its relation to performance appraisal practice. This review examines the performance appraisal literature published in both academic and practitioner outlets between 1985 and 1990, briefly discusses the current state of performance appraisal practice, highlights the juxtaposition of research and practice, and suggests directions for further research

Retaining young people in a longitudinal sexual health survey: a trial of strategies to maintain participation

<p>BACKGROUND:There is an increasing trend towards lower participation in questionnaire surveys. This reduces representativeness, increases costs and introduces particular challenges to longitudinal surveys, as researchers have to use complex statistical techniques which attempt to address attrition. This paper describes a trial of incentives to retain longitudinal survey cohorts from ages 16 to 20, to question them on the sensitive topic of sexual health.</p> <p>METHODS: A longitudinal survey was conducted with 8,430 eligible pupils from two sequential year groups from 25 Scottish schools. Wave 1 (14 years) and Wave 2 (16 years) were conducted largely within schools. For Wave 3 (18 years), when everyone had left school, the sample was split into 4 groups that were balanced across predictors of survey participation: 1) no incentive; 2) chance of winning one of twenty-five vouchers worth 20 pounds; 3) chance of winning one 500 pounds voucher; 4) a definite reward of a 10 pounds voucher sent on receipt of their completed questionnaire. Outcomes were participation at Wave 3 and two years later at Wave 4. Analysis used logistic regression and adjusted for clustering at school level.</p> <p>RESULTS: The only condition that had a significant and beneficial impact for pupils was to offer a definite reward for participation (Group 4). Forty-one percent of Group 4 participated in Wave 3 versus 27% or less for Groups 1 to 3. At Wave 4, 35% of Group 4 took part versus 25% or less for the other groups. Similarly, 22% of Group 4 participated in all four Waves of the longitudinal study, whereas for the other three groups it was 16% or less that participated in full.</p> <p>CONCLUSIONS: The best strategy for retaining all groups of pupils and one that improved retention at both age 18 and age 20 was to offer a definite reward for participation. This is expensive, however, given the many benefits of retaining a longitudinal sample, we recommend inclusion of this as a research cost for cohort and other repeat-contact studies.</p&gt

Factors determining social participation in the first year after kidney transplantation: a prospective study

BACKGROUND: This study describes changes in social participation in the first year after kidney transplantation and examines the influence of clinical factors, health status, transplantation-related symptoms, and psychological characteristics on change in social participation. METHODS: A prospective study was performed on a cohort of primary kidney transplant recipients, transplanted between March 2002 and March 2003. Data on participation in obligatory activities (i.e., employment, education, household tasks) and leisure activities (i.e., volunteer work, assisting others, sports, clubs/associations, recreation, socializing, going out) were collected by in-home interviews (n=61) at 3 months (T1) and 1 year posttransplantation (T2). Analysis of covariance was performed. RESULTS: Data showed an increase in participation in obligatory activities and diversity of leisure participation between T1 and T2, although pre-end-stage renal disease level was not regained and differed from the general population. On T1, the majority of employed recipients were on sick leave, but returned to work on T2. Employment rate remained stable. An increase in obligatory participation was predicted by clinical factors (i.e., peritoneal dialysis, initial hospitalization), whereas change in leisure participation was related to serum albumin and cognitive capacity. No effects were found for type of donation, comorbidity, and renal function. CONCLUSIONS: We found that mainly clinical factors were associated with an increase in participation in society. Although health-status related factors and the psychological attribute self-efficacy may be related to recovery of social participation, their effect was outweighed by the strength of clinical predictors in multivariate analysis