Integrated chronological control on an archaeologically significant Pleistocene river terrace sequence: the Thames-Medway, eastern Essex, England

Late Middle Pleistocene Thames-Medway deposits in eastern Essex comprise both large expanses of Palaeolithic artefact-bearing river sands/gravels and deep channels infilled with thick sequences of fossiliferous fine-grained estuarine sediments that yield valuable palaeoenvironmental information. Until recently, chronological control on these deposits was limited to terrace stratigraphy and limited amino-acid racemisation (AAR) determinations. Recent developments in both this and optically stimulated luminescence (OSL) dating make them potentially powerful tools for improving the chronological control on such sequences. This paper reports new AAR analyses and initial OSL dating from the deposits in this region. These results will help with ongoing investigation of patterns of early human settlement. Using AAR, the attribution by previous workers of the interglacial channel deposits to both MIS 11 (Tillingham Clay) and MIS 9 (Rochford and Shoeburyness Clays) is reinforced. Where there are direct stratigraphic relationships between AAR and OSL as with the Cudmore Grove and Rochford Clays and associated gravels, they agree well. Where OSL dating is the only technique available, it seems to replicate well, but must be treated with caution since there are relatively few aliquots. It is suggested on the basis of this initial OSL dating that the gravel deposits date from MIS 8 (Rochford and Cudmore Grove Gravels) and potentially also MIS 6 (Dammer Wick and Barling Gravels). However, the archaeological evidence from the Barling Gravel and the suggested correlations between this sequence and upstream Thames terraces conflict with this latter age estimate and suggest that it may need more investigation

Exploration of the equilibrium operating space for NSTX-Upgrade

This paper explores a range of high-performance equilibrium scenarios available in the NSTX-Upgrade device [J.E. Menard, submitted for publication to Nuclear Fusion]. NSTX-Upgrade is a substantial upgrade to the existing NSTX device [M. Ono, et al., Nuclear Fusion 40, 557 (2000)], with significantly higher toroidal field and solenoid capabilities, and three additional neutral beam sources with significantly larger current drive efficiency. Equilibria are computed with freeboundary TRANSP, allowing a self consistent calculation of the non-inductive current drive sources, the plasma equilibrium, and poloidal field coil current, using the realistic device geometry. The thermal profiles are taken from a variety of existing NSTX discharges, and different assumptions for the thermal confinement scalings are utilized. The no-wall and idealwall n=1 stability limits are computed with the DCON code. The central and minimum safety factors are quite sensitive to many parameters: they generally increases with large outer plasmawall gaps and higher density, but can have either trend with the confinement enhancement factor. In scenarios with strong central beam current drive, the inclusion of non-classical fast ion diffusion raises qmin, decreases the pressure peaking, and generally improves the global stability, at the expense of a reduction in the non-inductive current drive fraction; cases with less beam current drive are largely insensitive to additional fast ion diffusion. The non-inductive current level is quite sensitive to the underlying confinement and profile assumptions. For instance, for BT=1.0 T and Pinj=12.6 MW, the non-inductive current level varies from 875 kA with ITER-98y,2 thermal confinement scaling and narrow thermal profiles to 1325 kA for an ST specific scaling expression and broad profiles. This sensitivity should facilitate the determination of the correct scaling of transport with current and field to use for future fully non-inductive ST devices. Scenarios are presented which can be sustained for 8-10 seconds, or (20-30)τCR, at βN=3.8-4.5, facilitating, for instance, the study of disruption avoidance for very long pulse. Scenarios have been documented which can operate with βT~25% and equilibrated qmin>1. The value of qmin can be controlled at either fixed non-inductive fraction of 100% or fixed plasma current, by varying which beam sources are used, opening the possibility for feedback qmin control. In terms of quantities like collisionality, neutron emission, non-inductive fraction, or stored energy, these scenarios represent a significant performance extension compared to NSTX and other present spherical torii

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health