Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed

RELICS: The Reionization Lensing Cluster Survey and the Brightest High-z Galaxies

Massive foreground galaxy clusters magnify and distort the light of objects behind them, permitting a view into both the extremely distant and intrinsically faint galaxy populations. We present here the z ~ 6-8 candidate high-redshift galaxies from the Reionization Lensing Cluster Survey (RELICS), a Hubble and Spitzer Space Telescope survey of 41 massive galaxy clusters spanning an area of ≈200 arcmin². These clusters were selected to be excellent lenses, and we find similar high-redshift sample sizes and magnitude distributions as the Cluster Lensing And Supernova survey with Hubble (CLASH). We discover 257, 57, and eight candidate galaxies at z ~ 6, 7, and 8 respectively, (322 in total). The observed (lensed) magnitudes of the z ~ 6 candidates are as bright as AB mag ~23, making them among the brightest known at these redshifts, comparable with discoveries from much wider, blank-field surveys. RELICS demonstrates the efficiency of using strong gravitational lenses to produce high-redshift samples in the epoch of reionization. These brightly observed galaxies are excellent targets for follow-up study with current and future observatories, including the James Webb Space Telescope

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Cerebrospinal fluid in the diagnosis of spinal schistosomiasis

Cerebrospinal fluid (CSF) changes in spinal shistosomiasis have been described. Its characteristic features are mild to moderate pleocytosis, presence of eosinophils, slight to moderate protein increase, elevated gamma globulin concentration and a positive immune assay. Nevertheless, these abnormalities are not always present together and therefore difficulties may arise in the assessment of the diagnosis. The purpose of this paper is to evaluate the importance of each CSF alteration concerning the diagnosis in 22 cases of spinal shistosomiasis. According to the results, only 20% of the cases had all the five feature that are considered to be characteristic of spinal shistomiasis. Abnormal cell count was present in 86%, protein increase in 77.3%, immunoglobulin G increase in 60,8%, eosinophils were present in 36.8% and indirect fluorescent antibody test was positive in 68.2%. In three cases all CSF parameters studied were within the normal limits. As the most specific test among those described was the indirect fluorescent antibody test, it should be regarded for the diagnosis.As três espécies de esquistossoma podem comprometer o sistema nervoso. O S. mansoni é responsável pela esquistossomose no Brasil, sendo a mielopatia uma forma grave desta helmintose. O propósito deste trabalho é analisar as alterações do líquido cefalorraquidiano (LCR) para dar mais subsídios para o diagnóstico da esquistossomose raquimedular. Fizeram parte deste estudo 22 amostras de LCR de pacientes com esquistossomose espinal. Os resultados das análises destas amostras mostraram que a associação de alterações do LCR com quadro inflamatório e RIFI-IgM positiva ocorreu em 88% dos pacientes, que o eosinófilo esteve presente em apenas 7 amostras (36,8%), e que 3 dos 22 pacientes estudados apresentaram LCR normal. Conclui-se que o exame de LCR é coadjuvante muito útil para o diagnóstico da neuroesquistossomose.Universidade Estadual de Londrina Centro de Ciências da SaúdeUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Faculdade de Ciências Farmacêuticas Departamento de Análises ClínicasUNIFESPSciEL

Screening of antioxidant properties of the apple juice using the front-face synchronous fluorescence and chemometrics

Fluorescence spectroscopy is gaining increasing attention in food analysis due to its higher sensitivity and selectivity as compared to other spectroscopic techniques. Synchronous scanning fluorescence technique is particularly useful in studies of multi-fluorophoric food samples, providing a further improvement of selectivity by reduction in the spectral overlapping and suppressing light-scattering interferences. Presently, we study the feasibility of the prediction of the total phenolics, flavonoids, and antioxidant capacity using front-face synchronous fluorescence spectra of apple juices. Commercial apple juices from different product ranges were studied. Principal component analysis (PCA) applied to the unfolded synchronous fluorescence spectra was used to compare the fluorescence of the entire sample set. The regression analysis was performed using partial least squares (PLS1 and PLS2) methods on the unfolded total synchronous and on the single-offset synchronous fluorescence spectra. The best calibration models for all of the studied parameters were obtained using the PLS1 method for the single-offset synchronous spectra. The models for the prediction of the total flavonoid content had the best performance; the optimal model was obtained for the analysis of the synchronous fluorescence spectra at Delta lambda = 110 nm (R (2) = 0.870, residual predictive deviation (RPD) = 2.7). The optimal calibration models for the prediction of the total phenolic content (Delta lambda = 80 nm, R (2) = 0.766, RPD = 2.0) and the total antioxidant capacity (Delta lambda = 70 nm, R (2) = 0.787, RPD = 2.1) had only an approximate predictive ability. These results demonstrate that synchronous fluorescence could be a useful tool in fast semi-quantitative screening for the antioxidant properties of the apple juices.info:eu-repo/semantics/publishedVersio

Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis

BACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. AIMS: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. METHODS: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. RESULTS: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. CONCLUSIONS: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

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