Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

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

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness

Background: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and$31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was$2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority

Using a Non-Image-Based Medium-Throughput Assay for Screening Compounds Targeting N-myristoylation in Intracellular Leishmania Amastigotes

We have refined a medium-throughput assay to screen hit compounds for activity against N-myristoylation in intracellular amastigotes of Leishmania donovani. Using clinically-relevant stages of wild type parasites and an Alamar blue-based detection method, parasite survival following drug treatment of infected macrophages is monitored after macrophage lysis and transformation of freed amastigotes into replicative extracellular promastigotes. The latter transformation step is essential to amplify the signal for determination of parasite burden, a factor dependent on equivalent proliferation rate between samples. Validation of the assay has been achieved using the anti-leishmanial gold standard drugs, amphotericin B and miltefosine, with EC50 values correlating well with published values. This assay has been used, in parallel with enzyme activity data and direct assay on isolated extracellular amastigotes, to test lead-like and hit-like inhibitors of Leishmania Nmyristoyl transferase (NMT). These were derived both from validated in vivo inhibitors of Trypanosoma brucei NMT and a recent high-throughput screen against L. donovani NMT. Despite being a potent inhibitor of L. donovani NMT, the activity of the lead T. brucei NMT inhibitor (DDD85646) against L. donovani amastigotes is relatively poor. Encouragingly, analogues of DDD85646 show improved translation of enzyme to cellular activity. In testing the high-throughput L. donovani hits, we observed macrophage cytotoxicity with compounds from two of the four NMT-selective series identified, while all four series displayed low enzyme to cellular translation, also seen here with the T. brucei NMT inhibitors. Improvements in potency and physicochemical properties will be required to deliver attractive lead-like Leishmania NMT inhibitors

Temporal estimation with two moving objects: overt and covert pursuit

The current study examined temporal estimation in a prediction motion task where participants were cued to overtly pursue one of two moving objects, which could either arrive first, i.e., shortest [time to contact (TTC)] or second (i.e., longest TTC) after a period of occlusion. Participants were instructed to estimate TTC of the first-arriving object only, thus making it necessary to overtly pursue the cued object while at the same time covertly pursuing the other (non-cued) object. A control (baseline) condition was also included in which participants had to estimate TTC of a single, overtly pursued object. Results showed that participants were able to estimate the arrival order of the two objects with very high accuracy irrespective of whether they had overtly or covertly pursued the first-arriving object. However, compared to the single-object baseline, participants’ temporal estimation of the covert object was impaired when it arrived 500 ms before the overtly pursued object. In terms of eye movements, participants exhibited significantly more switches in gaze location during occlusion from the cued to the non-cued object but only when the latter arrived first. Still, comparison of trials with and without a switch in gaze location when the non-cued object arrived first indicated no advantage for temporal estimation. Taken together, our results indicate that overt pursuit is sufficient but not necessary for accurate temporal estimation. Covert pursuit can enable representation of a moving object’s trajectory and thereby accurate temporal estimation providing the object moves close to the overt attentional focus

Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)

Expression profile of human Fc receptors in mucosal tissue: implications for antibody-dependent cellular effector functions targeting HIV-1 transmission

The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies

Eccentric Viewing Training for Age-Related Macular Disease: Results of a Randomized Controlled Trial (the EFFECT Study)

PURPOSE: Eccentric viewing training for macular disease has been performed for > 40 years, but no large studies including control groups have assessed the benefits of this training. The EFFECT (Eccentric Fixation From Enhanced Clinical Training) study is a large randomized controlled trial of 2 types of eccentric viewing training. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred adults with age-related macular disease. METHODS: Participants were randomized to either of the following: (1) a control group; (2) a group receiving supervised reading support; (3) a group receiving 3 sessions of training to optimize the use of their own preferred retinal locus; or (4) a group receiving 3 sessions of biofeedback training of a theoretically optimal trained retinal locus. All participants received standard low-vision rehabilitation. MAIN OUTCOME MEASURES: The primary outcome was patient-reported visual task ability measured on the Activity Inventory instrument at goal level. Secondary outcomes included reading performance and fixation stability. RESULTS: There was no difference between groups on change in task ability (F(3,174) = 1.48, P = 0.22) or on any of the secondary outcome measures. Visual acuity and contrast sensitivity fell in all groups, suggesting that disease progression outweighed any benefit of training. CONCLUSIONS: Eccentric viewing training did not systematically improve task ability, reading performance, or fixation stability in this study. Our results do not support the routine use of eccentric viewing training for people with progressing age-related macular disease, although this training may help people with end-stage disease. Rehabilitation of an inherently progressive condition is challenging. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article