The lattice of the CERN Large Hadron Collider

The lattice of the CERN Large Hadron Collider is designed with 23 regular cells per arc, each containing 6 tightly packed 14.2 m long dipoles. This allows to reach 7 TeV per beam with a dipole field of 8.4 Tesla. There are four experimental insertions, two of which are devoted to high luminosity experiments with ± 23 m of free space for the detector. The other two experimental insertions are combined with injection. The value of ß* at the interaction points is tunable from 6 m at injection to 0.5 m in collision. The energy deposition in the inner triplets is carefully reduced to sustain the nominal luminosity of 1034 cm-2s-1. Two insertions are devoted to collect the halo particles with large emittance and momentum spread surrounding the beam core: escaping rates of the protons are estimated to be less than 4·106 sec-1m-1. Finally, one insertion is used to extract the particles in the vertical direction with a minimized deflecting strength

Performance of the TOTEM Detectors at the LHC

The TOTEM Experiment is designed to measure the total proton-proton cross-section with the luminosity-independent method and to study elastic and diffractive pp scattering at the LHC. To achieve optimum forward coverage for charged particles emitted by the pp collisions in the interaction point IP5, two tracking telescopes, T1 and T2, are installed on each side of the IP in the pseudorapidity region 3.1 < = |eta | < = 6.5, and special movable beam-pipe insertions - called Roman Pots (RP) - are placed at distances of +- 147 m and +- 220 m from IP5. This article describes in detail the working of the TOTEM detector to produce physics results in the first three years of operation and data taking at the LHC.Comment: 40 pages, 31 figures, submitted to Int. J. Mod. Phys.

Bovine Tuberculosis Prevalence Survey on Cattle in the Rural Livestock System of Torodi (Niger)

BACKGROUND: Bovine tuberculosis (BTB) is a widespread zoonosis in developing countries but has received little attention in sub-Saharan Africa, especially in Niger. Recent investigations confirmed the high incidence of the disease in cattle slaughtered in an abattoir in Niamey. The fact that most of the animals in which M. bovis has been identified were from the rural area of Torodi implied the existence of a probable source of BTB in this region. This study aimed to determine the prevalence of BTB infection in cattle and to identify risk factors for infection in human and cattle populations in Torodi. METHODS AND PRINCIPAL FINDINGS: A survey was carried out at the level of households keeping livestock (n = 51). The questionnaire was related to the potential risk factors and the presence of clinical signs of TB both in animals and humans. Comparative Intradermal Tuberculin Test was conducted to determine the TB status in cattle (n = 393). The overall apparent individual animal prevalence of tuberculin reactors was 3.6% (CI: 95%, 1.9-5.9), whereas the individual true prevalence was estimated at 0.8% (CI: 95%, 0.0-5.0). Using a multivariate logistic regression analysis and a classification tree analysis, the only household level risk factor that significantly influenced the presence of BTB in cattle was the presence of animals coughing in the herd (OR = 4.7, 95% CI: 1.12-19.71, p-value = 0.034). The lack of the practice of quarantine was borderline significant (OR = 4.2, 95% CI: 0.96-18.40, p-value = 0.056). CONCLUSION/SIGNIFICANCE: The study confirmed that BTB is endemic in cattle in Torodi and the risk of the transmission of the disease to humans is potentially high. For the control of the disease in livestock, slaughtering of infected animals and the compensation of the owners is needed. Collaboration between the veterinary and the medical sectors, in the diagnosis, monitoring, prevention and control of BTB is strongly encouraged

Animal influence on water, sanitation and hygiene measures for zoonosis control at the household level: A systematic literature review

Neglected zoonotic diseases (NZDs) have a significant impact on the livelihoods of the world’s poorest populations, which often lack access to basic services. Water, sanitation and hygiene (WASH) programmes are included among the key strategies for achieving the World Health Organization’s 2020 Roadmap for Implementation for control of Neglected Tropical Diseases (NTDs). There exists a lack of knowledge regarding the effect of animals on the effectiveness of WASH measures. This review looked to identify how animal presence in the household influences the effectiveness of water, hygiene and sanitation measures for zoonotic disease control in low and middle income countries; to identify gaps of knowledge regarding this topic based on the amount and type of studies looking at this particular interaction

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MKs). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping, and similarity regression. We describe 2 unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was linked to reduced proplatelet formation from cultured MKs, cell clustering, and abnormal cortical filamentous actin. Similarly, in platelets, there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Overexpression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insight into the autoregulation of DIAPH1 activity.The NIHR BioResource- Rare Diseases and the associated BRIDGE genome sequencing projects are supported by the National Institute for Health Research (NIHR; http://www.nihr.ac.uk). B.N. was supported by the Deutsche Forschungsgemeinschaft (SFB 688). S.S. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg. ET, DG, JCS, SP, IS, CJP, RM, SAsh, ST and KS are supported by the NIHR BioResource - Rare Diseases. KF, CT, and CVG are supported by the Fund for Scientific Research-Flanders (FWO-Vlaanderen, Belgium, G.0B17.13N) and by the Research Council of the University of Leuven (BOF KU Leuven‚ Belgium, OT/14/098). WNE is supported by the Cancer Council Western Australia. Research in the Ouwehand laboratory is supported by program grants from the European Commission, NIHR to WJA, SM, MK, RP, SBJ and WHO under numbers RP-PG-0310-1002; the laboratory also receives funding from NHS Blood and Transplant; CL and SKW are supported by Medical Research Council (MRC) Clinical Training Fellowships (number MR/K023489/1) and TKB by a British Society of Haematology/NHS Blood and Transplant grant. MAL and CL are supported by the Imperial College London Biomedical Research Centre; JRB acknowledges support by the NIHR Cambridge Biomedical Research Centre and SR by the Medical Research Council and Cambridge Biomedical Research Centre. CVG is holder of the Bayer and Norbert Heimburger (CSL Behring) Chairs. ADM is supported by the NIHR Bristol Cardiovascular Biomedical Research Unit

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Cross-Location Analysis of the Impact of Household Socioeconomic Status on Participation in Urban and Peri-Urban Agriculture in West Africa

This study explores the relation between household socioeconomic status (SES) and participation in urban and periurban agriculture (UPA) in three West African cities. We used a structured questionnaire to survey 700 randomly selected households: 250 in Kano, Nigeria, 250 in Bobo Dioulasso, Burkina Faso, and 200 in Sikasso, Mali. Multiple correspondence analysis was applied on household asset variables to create an index of assets which was used as a proxy for household SES. The results showed no significant differences in households’ rate of participation in UPA across socioeconomic groups. Participation in UPA was rather significantly (P < 0.001) and positively related to household size. Interestingly, the analysis revealed that field crop cultivation and gardening were more common among households in the low and medium SES groups while those in the high SES group were more likely to keep livestock