The potential of trading activity income to fund third sector organisations operating in deprived areas

In the United Kingdom, as in other countries, Third Sector Organisations (TSOs) have been drawn towards income sources associated with trading activities (Teasdale, 2010), but many remain reliant on grant funding to support such activities (Chell, 2007). Using a multivariate analysis approach and data from the National Survey of Charities and Social Enterprises (NSCSE), it is found that trading activities are used relatively commonly in deprived areas. These organisations are also more likely to attempt to access public sector funds. This suggests policy-makers need to consider the impact of funding cuts on TSOs in the most deprived areas as TSOs are unlikely achieve their objectives without continuing support

Revision total hip arthroplasty using the Zweymuller femoral stem

Background: A variety of femoral stem designs have been reported to be successful in revision total hip arthroplasty without consensus as to optimal design. We evaluated the clinical and radiographic outcomes in a consecutive series of femoral revisions using a wedge-shape, tapered-stem design at medium and long-term follow-up. Materials and methods: We performed a retrospective review of clinical and radiographic outcomes of twenty-eight consecutive femoral revisions arthroplasties, which were done using the Zweymuller femoral stem. Results: The mean follow-up was 7.4 years (range 2-15 years). No stem re-revision was necessary. All stems were judged to be stable by radiographic criteria at the most recent follow-up. The final mean Harris hip score was 90. There was no difference in Harris hip scores, implant stability, or radiological appearance (distal cortical hypertrophy or proximal stress shielding) of the implants between medium-term (mean 5.7 years) and long-term (mean 12.4 years) follow-up. Conclusions: We found the Zweymuller femoral stem design to be durable for revision hip arthroplasty when there is an intact metaphyseal-diaphyseal junction for adequate press-fit stability at surgery. © Springer-Verlag 2008

Towards a national trauma registry for the United Arab Emirates

<p>Abstract</p> <p>Background</p> <p>Trauma is a major health problem in the United Arab Emirates (UAE) as well as worldwide. Trauma registries provide large longitudinal databases for analysis and policy improvement. We aim in this paper to report on the development and evolution of a national trauma registry using a staged approach by developing a single-center registry, a two-center registry, and then a multi-center registry. The three registries were established by developing suitable data collection forms, databases, and interfaces to these databases. The first two registries collected data for a finite period of time and the third is underway. The steps taken to establish these registries depend on whether the registry is intended as a single-center or multi-center registry.</p> <p>Findings</p> <p>Several issues arose and were resolved during the development of these registries such as the relational design of the database, whether to use a standalone database management system or a web-based system, and the usability and security of the system. The inclusion of preventive medicine data elements is important in a trauma registry and the focus on road traffic collision data elements is essential in a country such as the UAE. The first two registries provided valuable data which has been analyzed and published.</p> <p>Conclusions</p> <p>The main factors leading to the successful establishment of a multi-center trauma registry are the development of a concise data entry form, development of a user-friendly secure web-based database system, the availability of a computer and Internet connection in each data collection center, funded data entry personnel well trained in extracting medical data from the medical record and entering it into the computer, and experienced personnel in trauma injuries and data analysis to continuously maintain and analyze the registry.</p

Antibody-based protection against HIV infection by vectored immunoprophylaxis

Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV

Respiratory Virus Infection and Risk of Invasive Meningococcal Disease in Central Ontario, Canada

BACKGROUND: In temperate climates, invasive meningococcal disease (IMD) incidence tends to coincide with or closely follow peak incidence of influenza virus infection; at a seasonal level, increased influenza activity frequently correlates with increased seasonal risk of IMD. METHODS: We evaluated 240 cases of IMD reported in central Ontario, Canada, from 2000 to 2006. Associations between environmental and virological (influenza A, influenza B and respiratory syncytial virus (RSV)) exposures and IMD incidence were evaluated using negative binomial regression models controlling for seasonal oscillation. Acute effects of weekly respiratory virus activity on IMD risk were evaluated using a matched-period case-crossover design with random directionality of control selection. Effects were estimated using conditional logistic regression. RESULTS: Multivariable negative binomial regression identified elevated IMD risk with increasing influenza A activity (per 100 case increase, incidence rate ratio = 1.18, 95% confidence interval (CI): 1.06, 1.31). In case-crossover models, increasing weekly influenza A activity was associated with an acute increase in the risk of IMD (per 100 case increase, odds ratio (OR)  = 2.03, 95% CI: 1.28 to 3.23). Increasing weekly RSV activity was associated with increased risk of IMD after adjusting for RSV activity in the previous 3 weeks (per 100 case increase, OR = 4.31, 95% CI: 1.14, 16.32). No change in disease risk was seen with increasing influenza B activity. CONCLUSIONS: We have identified an acute effect of influenza A and RSV activity on IMD risk. If confirmed, these finding suggest that influenza vaccination may have the indirect benefit of reducing IMD risk

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways

One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization

Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies

To study how virus evolution affects neutralization sensitivity and to determine changes that occur in and around epitopes, we tested the ability of 13 anti-HIV-1 gp120 (anti-V2, anti-V3, anti-CD4bd and anti-carbohydrate) human monoclonal antibodies (mAbs) to neutralize sequential viruses obtained from five HIV-1 chronically infected drug naïve individuals. Overall, primary viruses collected from patients at first visit were resistant to neutralization by all anti-HIV-1 mAbs with the exception of one virus sensitive to IgG1b12. Four of the five patients' viruses evolved increased sensitivity to neutralization by anti-V3 mAbs. Virus collected from a patient obtained 31 months later, evolved increased sensitivity to anti-V2, anti-V3, and anti-CD4bd mAbs. Furthermore, the anti-V2 and anti-CD4bd mAbs also exhibited increased neutralization capacities against virus collected from a patient 29 months later. Of the seven anti-V3 mAbs, five showed increased potency to neutralize the evolved virus from a patient collected after 11 months, and three exhibited increased potency against viruses from two patients collected 29 and 36 months later. Anti-V3 mAbs exhibited the most breadth and potency in neutralizing the evolving viruses. Sequence analysis of the envelope regions revealed amino acid conservation within the V3 loop, while most of the changes identified occurred outside the core epitopes and in particular within the C3 region; these may account for increased neutralization sensitivity. These studies demonstrate that in vivo, HIV-1 can evolve increased neutralization sensitivity to mAbs and that the spectrum of neutralization capacities by mAbs can be broader when studied in longitudinal analysis

Surveys of rice sold in Canada for aflatoxins, ochratoxin A and fumonisins

Approximately 200 samples of rice (including white, brown, red, black, basmati and jasmine, as well as wild rice) from several different countries, including the United States, Canada, Pakistan, India and Thailand, were analysed for aflatoxins, ochratoxin A (OTA) and fumonisins by separate liquid Chromatographic methods in two different years. The mean concentrations for aflatoxin B1 (AFB1) were 0.19 and 0.17 ng g−1 with respective positive incidences of 56% and 43% (≥ the limit of detection (LOD) of 0.002 ng g−1). Twenty-three samples analysed in the second year also contained aflatoxin B2 (AFB2) at levels ≥LOD of 0.002 ng g−1 The five most contaminated samples in each year contained 1.44–7.14 ng AFB1 g−1 (year 1) and 1.45–3.48 ng AFB1 g−1 (year 2); they were mostly basmati rice from India and Pakistan and black and red rice from Thailand. The average concentrations of ochratoxin A (OTA) were 0.05 and 0.005 ng g−1 in year 1 and year 2, respectively; incidences of samples containing ≥LOD of 0.05 ng g−1 were 43% and 1%, respectively, in the 2 years. All positive OTA results were confirmed by LC-MS/MS. For fumonisins, concentrations of fumonisin B1 (FB1) averaged 4.5 ng g−1 in 15 positive samples (≥0.7 ng g−1) from year 1 (n = 99); fumonisin B2 (FB2) and fumonisin B3 (FB3) were also present (≥1 ng g−1). In the second year there was only one positive sample (14 ng g−1 FB1) out of 100 analysed. All positive FB1 results were confirmed by LC-MS/MS