Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients

A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Càncer de mama; Genètica del càncerCáncer de mama; Genética del cáncerBreast cancer; Cancer geneticsYoung breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.This study received partial financial support by grants from the Italian Ministry of Health - 5 × 1000 funds 2017 (no grant number), the Italian Association for Cancer Research (AIRC; MFAG 2020 ID 24698), and “Les Amis de l’Institut Bordet” foundation (no grant number). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. M.L. acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium) at the time of study conduction. K.P. acknowledges the support from a predoctoral clinical ‘KOOR’ mandate from the University Hospitals Leuven (Leuven, Belgium). F.P.D. acknowledges the support for a postdoctoral clinical mandate (2017-034) from the not-for-profit organization ‘Foundation Against Cancer’ (Brussels, Belgium). A.H.P. acknowledges the support from Susan G. Komen and Breast Cancer Research Foundation (BCRF). J.H. acknowledges the support from the Carlos III National Health Institute funded by FEDER funds—a way to build Europe (PI16/11363). This research was presented in the Poster Spotlight session at the 2020 San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, United States of America, on 8–12 December 2020

Extragalactic Science, Cosmology and Galactic Archaeology with the Subaru Prime Focus Spectrograph (PFS)

The Subaru Prime Focus Spectrograph (PFS) is a massively-multiplexed fiber-fed optical and near-infrared 3-arm spectrograph (N_fiber=2400, 380<lambda<1260nm, 1.3 degree diameter FoV), offering unique opportunities in survey astronomy. Here we summarize the science case feasible for a survey of Subaru 300 nights. We describe plans to constrain the nature of dark energy via a survey of emission line galaxies spanning a comoving volume of 9.3 (Gpc/h)^3 in the redshift range 0.8<z<2.4. In each of 6 redshift bins, the cosmological distances will be measured to 3% precision via BAO, and redshift-space distortions will be used to constrain structure growth to 6% precision. In the GA program, radial velocities and chemical abundances of stars in the Milky Way and M31 will be used to infer the past assembly histories of spiral galaxies and the structure of their dark matter halos. Data will be secured for 10^6 stars in the Galactic thick-disk, halo and tidal streams as faint as V~22, including stars with V < 20 to complement the goals of the Gaia mission. A medium-resolution mode with R = 5000 to be implemented in the red arm will allow the measurement of multiple alpha-element abundances and more precise velocities for Galactic stars, elucidating the detailed chemo-dynamical structure and evolution of each of the main stellar components of the Milky Way Galaxy and of its dwarf spheroidal galaxies. For the extragalactic program, our simulations suggest the wide avelength range will be powerful in probing the galaxy population and its clustering over a wide redshift range. We propose to conduct a color-selected survey of 1<z<2 galaxies and AGN over 16 deg^2 to J~23.4, yielding a fair sample of galaxies with stellar masses above ~10^{10}Ms at z~2. A two-tiered survey of higher redshift LBGs and LAEs will quantify the properties of early systems close to the reionization epoch.Comment: This document describes the scientific program and requirements for the Subaru Prime Focus Spectrograph (PFS) project. Made significant revision based on studies for the Preliminary Design Review (PRD) held in Feb 2013. The higher-resolution paper file is available from http://member.ipmu.jp/masahiro.takada/pfs_astroph_rv.pd

Report on Innovative Financial Instruments for the Implementation of the SET Plan, First-Of-A-Kind projects

This report responds to the request of Commissioner Oettinger and the Cabinet of Commissioner Geoghegan-Quinn end of 2012, for an expert assessment and recommendations regarding the financing of first-of-a-kind commercial demonstration projects as prioritised in the roadmaps of the Strategic Energy Technology (SET) Plan. The expert group comprised representatives of financial organisations, i.e. the European Investment Bank, the European Venture Capital Association, the European Insurance and Re-insurance federation, the World Bank, and the Climate Change Capital. Six hearings with key stakeholders representing the SET Plan European Industrial Initiatives (EIIs), as well as the Fuel Cells and Hydrogen Joint Undertaking were held. These hearings provided information regarding their main barriers for implementation and the gaps as regards access to finance. Existing EU financial were evaluated too. The report concludes that a new financial instrument at EU level is not needed since existing financial instruments already provide equity, loans, or guarantees. However, until now, those instruments have not provided the financing required. As a response to this problem a set of changes to existing financial instruments and their utilisation were recommended.JRC.F.6-Energy systems evaluatio

Reliability of reporting of HIV status and antiretroviral therapy usage during verbal autopsies: a large prospective study in rural Malawi.

OBJECTIVE: Verbal autopsies (VAs) are interviews with a relative or friend of the deceased; VAs are a technique used in surveillance sites in many countries with incomplete death certification. The goal of this study was to assess the accuracy and validity of data on HIV status and antiretroviral therapy (ART) usage reported in VAs and their influence on physician attribution of cause of death. DESIGN: This was a prospective cohort study. METHODS: The Karonga Health and Demographic Surveillance Site monitors demographic events in a population in a rural area of northern Malawi; a VA is attempted on all deaths reported. VAs are reviewed by clinicians, who, with additional HIV test information collected pre-mortem, assign a cause of death. We linked HIV/ART information reported by respondents during adult VAs to database information on HIV testing and ART use and analysed agreement using chi-square and kappa statistics. We used multivariable logistic regression to analyse factors associated with agreement. RESULTS: From 2003 to 2014, out of a total of 1,952 VAs, 80% of respondents reported the HIV status of the deceased. In 2013-2014, this figure was 99%. Of those with an HIV status known to the study, there was 89% agreement on HIV status between the VA and pre-mortem data, higher for HIV-negative people (92%) than HIV-positive people (83%). There was 84% agreement on whether the deceased had started ART, and 72% of ART initiation dates matched within 1 year. CONCLUSIONS: In this population, HIV/ART information was often disclosed during a VA and matched well with other data sources. Reported HIV/ART status appears to be a reliable source of information to help classification of cause of death

Patterns and risk factors for deaths from external causes in rural Malawi over 10 years: a prospective population-based study.

BACKGROUND: Little is known about the pattern or risk factors for deaths from external causes in sub-Saharan Africa: there is a lack of reliable data, and public health priorities have been focussed on other causes. This study assessed the prevalence and risk factor for deaths from external causes in rural Malawi. METHODS: We analysed data from 2002-2012 from the Karonga demographic surveillance site which covers ~35,000 people in rural northern Malawi. Verbal autopsies with clinician coding are used to assign cause of death. Repeated annual surveys capture data on socio-economic factors. Using Poisson regression models we calculated age, sex and cause-specific rates and rate ratios of external deaths. We used a nested case-control study, matched on age, sex and time period, to investigate risk factors for these deaths, using conditional logistic regression. RESULTS: In 315,580 person years at risk (pyar) there were 2673 deaths, including 143 from external causes. The mortality rate from external causes was 47.1/100,000 pyar (95 % CI 32.5-68.2) among under-fives; 20.1/100,000 pyar (95 % CI 13.1-32.2) among 5-14 year olds; 46.3/100,000 pyar (95 % CI 35.8-59.9) among 15-44 year olds; and 98.7/100,000 pyar (95 % CI 71.8-135.7) among those aged ≥45 years. Drowning (including four deaths in people with epilepsy), road injury and suicide were the leading external causes. Adult males had the highest rates (100.7/100,000 pyar), compared to 21.8/100,000pyar in adult females, and the rate continued to increase with increasing age in men. Alcohol contributed to 21 deaths, all in adult males. Children had high rates of drowning (9.2/100,000 pyar, 95 % CI 5.5-15.6) but low rates of road injury (2.6/100,000 pyar, 95 % CI 1.0-7.0). Among 5-14 year olds, attending school was associated with fewer deaths from external causes than among those who had never attended school (adjusted OR 0.15, 95 % CI 0.08-0.81). Fishermen had increased risks of death from drowning and suicide compared to farmers. DISCUSSION: In this population the rate of deaths from external causes was lowest at age 5-14 years. Adult males had the highest rate of death from external causes, 5 times the rate in adult females. Drowning, road injury and suicide were the leading causes of death; alcohol consumption contributed to more than one quarter of the deaths in men CONCLUSIONS: The high proportion of alcohol-related deaths in men, the predominance of drowning, deaths linked to uncontrolled epilepsy, and the possible protective effect of school attendance suggest areas for intervention

Contributions of the Environmental Non Governmental Organisations and international law on climate change

This study aims at finding out how Non Governmental Organisations (NGOs) perceive this issue and what roles they play in the fight against this phenomenon and in its formation in order to contribute to this domain and analyse contributions of Non Governmental Organisations to the International law on climate change. Results show that consequences of climate changeare visible and real. Thus, NGOs such as Friends of the Earth, Greenpeace, World Wild Funds (WWF), World Watch Institute (WWI) and Sierra Club emerged in the mode of the International law, bringing an effective participation in International negotiations by cooperating with States and by sensitizing citizens and political decision-makers. For this purpose, the United Nations Framework Convention on Climate Change (UNFCCC) was adopted in 1992 and the Kyoto Protocol in 1997 as well as several other multilateral treaties during different Conventions of Parties (COP). However, this struggle is opposed by industrialists and other States that protect their short-term interests and support the idea that climate change mightnot exist or climatic change is not due to men, but rather to natural phenomena. That is why NGOs have to actively play their role of pressure to call out to decision makers and populations on consequences of the climate change so that we can attenuate this phenomenon because the more we are doing nothing today, the more difficult it will be to avoid the consequences tomorrow

X-ray Structures and Computational Studies of Two Bioactive 2-(Adamantane-1-carbonyl)-N-substituted Hydrazine-1-carbothioamides

Two biologically active adamantane-linked hydrazine-1-carbothioamide derivatives, namely 2-(adamantane-1-carbonyl)-N-(tert-butyl)hydrazine-1-carbothioamide) 1 and 2-(adamantane-1-carbonyl)-N-cyclohexylhydrazine-1-carbothioamide 2, have been synthesized. X-ray analysis was conducted to study the effect of the t-butyl and cyclohexyl moieties on the intermolecular interactions and conformation of the molecules in the solid state. X-ray analysis reveals that compound 1 exhibits folded conformation, whereas compound 2 adopts extended conformation. The Hirshfeld surface analysis indicates that the contributions of the major intercontacts involved in the stabilization of the crystal structures do not change much as a result of the t-butyl and cyclohexyl moieties. However, the presence and absence of these contacts is revealed by the 2D-fingerprint plots. The CLP–Pixel method was used to identify the energetically significant molecular dimers. These dimers are stabilized by different types of intermolecular interactions such as N–H···S, N–H···O, C–H···S, C–H···O, H–H bonding and C–H···π interactions. The strength of these interactions was quantified by using the QTAIM approach. The results suggest that N–H···O interaction is found to be stronger among other interactions. The in vitro assay suggests that both compounds 1 and 2 exhibit urease inhibition potential, and these compounds also display moderate antiproliferative activities. Molecular docking analysis shows the key interaction between urease enzyme and title compounds. Keywords: adamantane; hydrazine-1-carbothioamide; Hirshfeld surface; CLP–Pixel; QTAIM; molecular docking; urease inhibition; antiproliferative agents; H-H bondin