The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

Trachoma is an infectious disease of the eye that causes blindness in many of the poorest parts of the world. In this paper, we use a novel statistical approach to estimate the characteristics of this disease among people living in The Gambia who were examined every 2 weeks over a 6-month period. We found that the typical duration of infection with Chlamydia trachomatis and of clinically active disease were significantly longer than previously estimated. We tested different hypotheses about the natural history of trachoma that explain the relationship between infection and disease observed in the field. We also confirmed that disease lasts significantly longer among young children under 5 years old compared with older children and adults, even after accounting for high rates of re-infection in this age group, consistent with the development of immunity with age. The long duration of infection, especially among younger children, contributes to the persistence and gradual return of trachoma after community-wide treatment with azithromycin. This implies the need for high treatment coverage if infection is to be eliminated from a community, even where the return of infection after treatment is seen to be slow

Recent trends in cutaneous malignant melanoma in the Yorkshire region of England; incidence, mortality and survival in relation to stage of disease, 1993–2003

The aim of this study was to investigate recent trends in incidence, mortality and survival in patients diagnosed with malignant melanoma (MM) in relation to stage (Breslow thickness). Cases of primary invasive and in situ MM diagnosed between 1st January 1993 and 31st December 2003 in the former Yorkshire Health Authority were identified from cancer registry data. Over the study period, the incidence of invasive MM increased from 5.4 to 9.7 per 100 000 in male subjects and from 7.5 to 13.1 per 100 000 in female subjects. Most of this increase was seen in thin tumours (<1.5 mm). Thin tumours were more likely to be diagnosed in the younger age groups and be classified as superficial spreading melanoma. In situ melanoma rates increased only slightly. Over the same time period, mortality rates have been relatively constant in both male and female subjects. Five-year relative survival varied from 91.8% (95% CI 90.4–93.1) for patients with thin tumours to 41.5% (95% CI 36.7–46.3) for those with thick tumours. In multivariable analyses, Breslow thickness was the most important prognostic factor. Age, sex and level of deprivation were also identified as independent prognostic factors. The trends in incidence suggest that the increase is real, rather than an artefact of increased scrutiny, implying that primary prevention in the Yorkshire area of the UK has failed to control trends in incidence. Mortality, in contrast, appears to be levelling off, indicating that secondary prevention has been more effective

Activity Increase Despite Arthritis (AÏDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946]

<p>Abstract</p> <p>Background</p> <p>Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity.</p> <p>Methods/Design</p> <p>This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months.</p> <p>Discussion</p> <p>We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN24554946</p

Composition change-driven texturing and doping in solution-processed SnSe thermoelectric thin films

The discovery of SnSe single crystals with record high thermoelectric efficiency along the b-axis has led to the search for ways to synthesize polycrystalline SnSe with similar efficiencies. However, due to weak texturing and difficulties in doping, such high thermoelectric efficiencies have not been realized in polycrystals or thin films. Here, we show that highly textured and hole doped SnSe thin films with thermoelectric power factors at the single crystal level can be prepared by solution process. Purification step in the synthetic process produced a SnSe-based chalcogenidometallate precursor, which decomposes to form the SnSe2 phase. We show that the strong textures of the thin films in the b???c plane originate from the transition of two dimensional SnSe2 to SnSe. This composition change-driven transition offers wide control over composition and doping of the thin films. Our optimum SnSe thin films exhibit a thermoelectric power factor of 4.27 ??W cm???1 K???2

Rapid and Reversible Recruitment of Early Visual Cortex for Touch

The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex.We investigated the effect of sudden, complete and prolonged visual deprivation (five days) in normally sighted adult individuals while they were immersed in an intensive tactile training program. Following the five-day period, blindfolded subjects performed better on a Braille character discrimination task. In the blindfold group, serial fMRI scans revealed an increase in BOLD signal within the occipital cortex in response to tactile stimulation after five days of complete visual deprivation. This increase in signal was no longer present 24 hours after blindfold removal. Finally, reversible disruption of occipital cortex function on the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired Braille character recognition ability in the blindfold group but not in non-blindfolded controls. This disruptive effect was no longer evident once the blindfold had been removed for 24 hours.Overall, our findings suggest that sudden and complete visual deprivation in normally sighted individuals can lead to profound, but rapidly reversible, neuroplastic changes by which the occipital cortex becomes engaged in processing of non-visual information. The speed and dynamic nature of the observed changes suggests that normally inhibited or masked functions in the sighted are revealed by visual loss. The unmasking of pre-existing connections and shifts in connectivity represent rapid, early plastic changes, which presumably can lead, if sustained and reinforced, to slower developing, but more permanent structural changes, such as the establishment of new neural connections in the blind

Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

BACKGROUND: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. METHODS: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. RESULTS: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. CONCLUSION: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma

Rabies-Specific Antibodies: Measuring Surrogates of Protection against a Fatal Disease

Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization—the ability of antibody to inactivate virus infectivity, often measured in vitro—is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the “gold standard” assay to measure rabies virus–neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations—but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection

Study protocol: healthy urban living and ageing in place (HULAP): an international, mixed methods study examining the associations between physical activity, built and social environments for older adults the UK and Brazil

Abstract Background The ability to ‘age in place’ is dependent on a range of inter-personal, social and built environment attributes, with the latter being a key area for potential intervention. There is an emerging body of evidence that indicates the type of built environment features that may best support age friendly communities, but there is a need to expand and consolidate this, while generating a better understanding of how on how research findings can be most effectively be translated in to policy and practice. Methods The study is based on two case study cities, Curtiba (Brazil) and Belfast (UK), which have highly contrasting physical, social and policy environments. The study deploys a mix methods approach, mirrored in each city. This includes the recruitment of 300 participants in each city to wear GPS and accelerometers, a survey capturing physical functioning and other personal attributes, as well as their perception of their local environment using NEWS-A. The study will also measure the built environments of the cities using GIS and develop a tool for auditing the routes used by participants around their neighbourhoods. The study seeks to comparatively map the policy actors and resources involved in healthy ageing in the two cities through interviews, focus groups and discourse analysis. Finally, the study has a significant knowledge exchange component, including the development of a tool to assess the capacities of both researchers and research users to maximise the impact of the research findings. Discussion The HULAP study has been designed and implemented by a multi-disciplinary team and integrates differing methodologies to purposefully impact on policy and practice on healthy ageing in high and low-middle income countries. It has particular strengths in its combination of objective and self-reported measures using validated tools and the integration of GPS, accelerometer and GIS data to provide a robust assessment of ‘spatial energetics’. The strong knowledge exchange strand means that the study is expected to also contribute to our understanding of how to maximise research impact in this field and create effective evidence for linking older adult’s physical activity with the social, built and policy environments

Does dietary tocopherol level affect fatty acid metabolism in fish?

Fish are a rich source of the n-3 polyunsaturated fatty acids (PUFA), particularly the highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids, which are vital constituents for cell membrane structure and function, but which are also highly susceptible to attack by oxygen and other organic radicals. Resultant damage to PUFA in membrane phospholipids can have serious consequences for cell membrane structure and function, with potential pathological effects on cells and tissues. Physiological antioxidant protection involves both endogenous components, such as free radical scavenging enzymes, and exogenous dietary micronutrients including tocopherols and tocotrienols, the vitamin E-type compounds, widely regarded as the primary lipid soluble antioxidants. The antioxidant activities of tocopherols are imparted by their ability to donate their phenolic hydrogen atoms to lipid (fatty acid) free radicals resulting in the stabilisation of the latter and the termination of the lipid peroxidation chain reaction. However, tocopherols can also prevent PUFA peroxidation by acting as quenchers of singlet oxygen. Recent studies on marine fish have shown correlations between dietary and tissue PUFA/tocopherol ratios and incidence of lipid peroxidation as indicated by the levels of TBARS and isoprostanes. These studies also showed that feeding diets containing oxidised oil significantly affected the activities of liver antioxidant defence enzymes and that dietary tocopherol partially attenuated these effects. However, there is evidence that dietary tocopherols can affect fatty acid metabolism in other ways. An increase in membrane PUFA was observed in rats deficient in vitamin E. This was suggested to be due to over production of PUFA arising from increased activity of the desaturation/elongation mechanisms responsible for the synthesis of PUFA. Consistent with this, increased desaturation of 18:3n-3 and 20:5n-3 in hepatocytes from salmon fed diets deficient in tocopherol and/or astaxanthin has been observed. Although the mechanism is unclear, tocopherols may influence biosynthesis of n-3PUFA through alteration of cellular oxidation potential or “peroxide tone”

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente