Electrical conductivity in granular media and Branly's coherer: A simple experiment

accepted for publication in American Journal of Physics (to be published between February 2005 and June 2005)We show how a simple laboratory experiment can illustrate certain electrical transport properties of metallic granular media. At a low critical imposed voltage, a transition from an insulating to a conductive state is observed. This transition comes from an electro-thermal coupling in the vicinity of the microcontacts between grains where microwelding occurs. Our apparatus allows us to obtain an implicit determination of the microcontact temperature, which is analogous to the use of a resistive thermometer. The experiment also illustrates an old problem, the explanation of Branly's coherer effect - a radio wave detector used for the first wireless radio transmission, and based on the sensitivity of the metal fillings conductivity to an electromagnetic wave

Isoniazid Preventive Therapy Added to ART to Prevent TB: An Individual Participant Data Meta-Analysis

Background: Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. Methods: We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. Findings: Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49–0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43–1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. Interpretation: Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. Funding: National Institutes of Health and National Institute of Allergy and Infectious Diseases

Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT

International audienceBACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. METHODS: The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. RESULTS: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. CONCLUSIONS: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment

Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial

Background In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with high TB incidence rate (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). We will enrol 3780 children under 5 years presenting with WHO-defined severe pneumonia across 15 hospitals over 18 months. All hospitals will start managing children using the WHO SOC for severe pneumonia; one hospital will be randomly selected to switch to the intervention every 5 weeks. The intervention consists of the WHO SOC plus rapid TB detection on the day of admission using Ultra performed on 1 nasopharyngeal aspirate and 1 stool sample. All children will be followed for 3 months, with systematic trial visits at day 3, discharge, 2 weeks post-discharge, and week 12. The primary endpoint is all-cause mortality 12 weeks after inclusion. Qualitative and health economic evaluations are embedded in the trial. Discussion In addition to testing the main hypothesis that molecular detection and early treatment will reduce TB mortality in children, the strength of such pragmatic research is that it provides some evidence regarding the feasibility of the intervention as part of routine care. Should this intervention be successful, safe and well tolerated, it could be systematically implemented at district hospital level where children with severe pneumonia are referred. Trial registration ClinicalTrials.gov, NCT03831906. Registered 6 February 2019

The complete salmonid IGF-IR gene repertoire and its transcriptional response to disease

Acknowledgements This work was supported financially by the European Community’s Seventh Framework Program (FP7/2007-13) under Grant 442 Agreements 222719 (LIFECYCLE). AA was supported by a PhD studentship from Kuwait University. The authors thank Mr Anthony K. Redmond (University of Aberdeen) for assisting with gene prediction and phylogenetic analysis.Peer reviewedPublisher PD