Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as -23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.Peer reviewe

Measuring neutron yield and ρR anisotropies with activation foils at the National Ignition Facility

Neutron yields at the National Ignition Facility (NIF) are measured with a suite of diagnostics, including activation of ∼20–200 g samples of materials undergoing a variety of energy-dependent neutron reactions. Indium samples were mounted on the end of a Diagnostic Instrument Manipulator (DIM), 25–50 cm from the implosion, to measure 2.45 MeV D-D fusion neutron yield. The 336.2 keV gamma rays from the 4.5 hour isomer of 115mIn produced by (n,n′) reactions are counted in high-purity germanium detectors. For capsules producing D-T fusion reactions, zirconium and copper are activated via (n,2n) reactions at various locations around the target chamber and bay, measuring the 14 MeV neutron yield to accuracies on order of 7%. By mounting zirconium samples on ports at nine locations around the NIF chamber, anisotropies in the primary neutron emission due to fuel areal density asymmetries can be measured to a relative precision of 3%

The neutron imaging system fielded at the National Ignition Facility

We have fielded a neutron imaging system at the National Ignition Facility to collect images of fusion neutrons produced in the implosion of inertial confinement fusion experiments and scattered neutrons from (n, n′) reactions of the source neutrons in the surrounding dense material. A description of the neutron imaging system is presented, including the pinhole array aperture, the line-of-sight collimation, the scintillator-based detection system and the alignment systems and methods. Discussion of the alignment and resolution of the system is presented. We also discuss future improvements to the system hardware

Comparing neutron and X-ray images from NIF implosions

Directly laser driven and X-radiation driven DT filled capsules differ in the relationship between neutron and X-ray images. Shot N110217, a directly driven DT-filled glass micro-balloon provided the first neutron images at the National Ignition Facility. As seen in implosions on the Omega laser, the neutron image can be enclosed inside time integrated X-ray images. HYDRA simulations show the X-ray image is dominated by emission from the hot glass shell while the neutron image arises from the DT fuel it encloses. In the absence of mix or jetting, X-ray images of a cryogenically layered THD fuel capsule should be dominated by emission from the hydrogen rather than the cooler plastic shell that is separated from the hot core by cold DT fuel. This cool, dense DT, invisible in X-ray emission, shows itself by scattering hot core neutrons. Germanium X-ray emission spectra and Ross pair filtered X-ray energy resolved images suggest that germanium doped plastic emits in the torus shaped hot spot, probably reducing the neutron yield

Comparing neutron and X-ray images from NIF implosions

Directly laser driven and X-radiation driven DT filled capsules differ in the relationship between neutron and X-ray images. Shot N110217, a directly driven DT-filled glass micro-balloon provided the first neutron images at the National Ignition Facility. As seen in implosions on the Omega laser, the neutron image can be enclosed inside time integrated X-ray images. HYDRA simulations show the X-ray image is dominated by emission from the hot glass shell while the neutron image arises from the DT fuel it encloses. In the absence of mix or jetting, X-ray images of a cryogenically layered THD fuel capsule should be dominated by emission from the hydrogen rather than the cooler plastic shell that is separated from the hot core by cold DT fuel. This cool, dense DT, invisible in X-ray emission, shows itself by scattering hot core neutrons. Germanium X-ray emission spectra and Ross pair filtered X-ray energy resolved images suggest that germanium doped plastic emits in the torus shaped hot spot, probably reducing the neutron yield

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P < 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients