Inertial confinement fusion seeks to create burning plasma conditions in a spherical capsule implosion, which requires efficiently absorbing the driver energy in the capsule, transferring that energy ...into kinetic energy of the imploding DT fuel and then into internal energy of the fuel at stagnation. We report new implosions conducted on the National Ignition Facility (NIF) with several improvements on recent work Phys. Rev. Lett. 120, 245003 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.245003; Phys. Rev. E 102, 023210 (2020)PRESCM2470-004510.1103/PhysRevE.102.023210: larger capsules, thicker fuel layers to mitigate fuel-ablator mix, and new symmetry control via cross-beam energy transfer; at modest velocities, these experiments achieve record values for the implosion energetics figures of merit as well as fusion yield for a NIF experiment.
Many studies have used retrospective reports to assess the long-term consequences of early life stress. However, current individual characteristics and experiences may bias the recall of these ...reports. In particular, depressed mood may increase the likelihood of recall of negative experiences. The aim of the study was to assess whether specific factors are associated with consistency in the reporting of childhood adverse experiences.
The sample comprised 7466 adults from Canada's National Population Health Survey who had reported on seven childhood adverse experiences in 1994/1995 and 2006/2007. Logistic regression was used to explore differences between those who consistently reported adverse experiences and those whose reports were inconsistent.
Among those retrospectively reporting on childhood traumatic experiences in 1994/1995 and 2006/2007, 39% were inconsistent in their reports of these experiences. The development of depression, increasing levels of psychological distress, as well as increasing work and chronic stress were associated with an increasing likelihood of reporting a childhood adverse experience in 2006/2007 that had not been previously reported. Increases in mastery were associated with reduced likelihood of new reporting of a childhood adverse experience in 2006/2007. The development of depression and increases in chronic stress and psychological distress were also associated with reduced likelihood of 'forgetting' a previously reported event.
Concurrent mental health factors may influence the reporting of traumatic childhood experiences. Studies that use retrospective reporting to estimate associations between childhood adversity and adult outcomes associated with mental health may be biased.
A series of cryogenic, layered deuterium-tritium (DT) implosions have produced, for the first time, fusion energy output twice the peak kinetic energy of the imploding shell. These experiments at the ...National Ignition Facility utilized high density carbon ablators with a three-shock laser pulse (1.5 MJ in 7.5 ns) to irradiate low gas-filled (0.3 mg/cc of helium) bare depleted uranium hohlraums, resulting in a peak hohlraum radiative temperature ∼290 eV. The imploding shell, composed of the nonablated high density carbon and the DT cryogenic layer, is, thus, driven to velocity on the order of 380 km/s resulting in a peak kinetic energy of ∼21 kJ, which once stagnated produced a total DT neutron yield of 1.9×10^{16} (shot N170827) corresponding to an output fusion energy of 54 kJ. Time dependent low mode asymmetries that limited further progress of implosions have now been controlled, leading to an increased compression of the hot spot. It resulted in hot spot areal density (ρr∼0.3 g/cm^{2}) and stagnation pressure (∼360 Gbar) never before achieved in a laboratory experiment.
Aflatoxins are fungal metabolites that frequently contaminate staple foods in much of sub-Saharan Africa, and are associated with increased risk of liver cancer and impaired growth in young children. ...We aimed to assess whether postharvest measures to restrict aflatoxin contamination of groundnut crops could reduce exposure in west African villages.
We undertook an intervention study at subsistence farms in the lower Kindia region of Guinea. Farms from 20 villages were included, ten of which implemented a package of postharvest measures to restrict aflatoxin contamination of the groundnut crop; ten controls followed usual postharvest practices. We measured the concentrations of blood aflatoxin–albumin adducts from 600 people immediately after harvest and at 3 months and 5 months postharvest to monitor the effectiveness of the intervention.
In control villages mean aflatoxin–albumin concentration increased postharvest (from 5·5 pg/mg 95% CI 4·7–6·1 immediately after harvest to 18·7 pg/mg 17·0–20·6 5 months later). By contrast, mean aflatoxin–albumin concentration in intervention villages after 5 months of groundnut storage was much the same as that immediately postharvest (7·2 pg/mg 6·2–8·4
vs 8·0 pg/mg 7·0–9·2). At 5 months, mean adduct concentration in intervention villages was less than 50% of that in control villages (8·0 pg/mg 7·2–9·2
vs 18·7 pg/mg 17·0–20·6, p<0·0001). About a third of the number of people had non-detectable aflatoxin–albumin concentrations at harvest. At 5 months, five (2%) people in the control villages had non-detectable adduct concentrations compared with 47 (20%) of those in the intervention group (p<0·0001). Mean concentrations of aflatoxin B1 in groundnuts in household stores in intervention and control villages were consistent with measurements of aflatoxin–albumin adducts.
Use of low-technology approaches at the subsistence-farm level in sub-Saharan Africa could substantially reduce the disease burden caused by aflatoxin exposure.
EXPOsOMICS is a European Union funded project that aims to develop a novel approach to the assessment of exposure to high priority environmental pollutants, by characterizing the external and the ...internal components of the exposome. It focuses on air and water contaminants during critical periods of life. To this end, the project centres on 1) exposure assessment at the personal and population levels within existing European short and long-term population studies, exploiting available tools and methods which have been developed for personal exposure monitoring (PEM); and 2) multiple “omic” technologies for the analysis of biological samples (internal markers of external exposures). The search for the relationships between external exposures and global profiles of molecular features in the same individuals constitutes a novel advancement towards the development of “next generation exposure assessment” for environmental chemicals and their mixtures. The linkage with disease risks opens the way to what are defined here as ‘exposome-wide association studies’ (EWAS).
Aflatoxins and fumonisins (FB) are mycotoxins contaminating a large fraction of the world's food, including maize, cereals, groundnuts and tree nuts. The toxins frequently co-occur in maize. Where ...these commodities are dietary staples, for example, in parts of Africa, Asia and Latin America, the contamination translates to high-level chronic exposure. This is particularly true in subsistence farming communities where regulations to control exposure are either non-existent or practically unenforceable. Aflatoxins are hepatocarcinogenic in humans, particularly in conjunction with chronic hepatitis B virus infection, and cause aflatoxicosis in episodic poisoning outbreaks. In animals, these toxins also impair growth and are immunosuppressive; the latter effects are of increasing interest in human populations. FB have been reported to induce liver and kidney tumours in rodents and are classified as Group 2B ‘possibly carcinogenic to humans’, with ecological studies implying a possible link to increased oesophageal cancer. Recent studies also suggest that the FB may cause neural tube defects in some maize-consuming populations. There is a plausible mechanism for this effect via a disruption of ceramide synthase and sphingolipid biosynthesis. Notwithstanding the need for a better evidence-base on mycotoxins and human health, supported by better biomarkers of exposure and effect in epidemiological studies, the existing data are sufficient to prioritize exposure reduction in vulnerable populations. For both toxins, there are a number of practical primary and secondary prevention strategies which could be beneficial if the political will and financial investment can be applied to what remains a largely and rather shamefully ignored global health issue.
Aflatoxins have been extensively studied with respect to their mechanisms of toxicity. An understanding of metabolism, DNA adduct induction, mutagenicity and carcinogenicity has been paralleled by ...the development of biomarkers of aflatoxin exposure and biological effects (e.g. mutations) applied to human populations. The improvements in exposure assessment and their application in prospective epidemiological studies and the demonstration of a specific mutation in the TP53 gene in hepatocellular carcinomas from areas of high aflatoxin exposure have contributed significantly to the classification of aflatoxins as human carcinogens. In addition to establishing the carcinogenicity of aflatoxins in humans, understanding molecular mechanisms of action has provided the scientific rationale for prevention strategies, including primary and chemoprevention approaches. Overall, integrated, multidisciplinary research on aflatoxins has provided the platform on which to base decisions regarding acceptable exposures and priorities for interventions to reduce human risk in a public health context.
Barrett's esophagus is associated with reflux disease and substantially increases the risk of esophageal adenocarcinoma. The authors undertook a systematic review and meta-analysis of the sex ratio ...for Barrett's esophagus, erosive reflux disease (ERD), and nonerosive reflux disease (non-ERD) to compare these results with the sex ratio for esophageal adenocarcinoma. MEDLINE (US National Library of Medicine, Bethesda, Maryland) (1966–2004) and EMBASE (Reed Elsevier PLC, Amsterdam, Netherlands) (1980–2004) were searched for relevant citations with a highly sensitive search strategy. Studies to be included required a sample size of 50 or more patients and consecutive recruitment at an institute accessible by all. Stata, version 8.2, software (StataCorp LP, College Station, Texas) was used to conduct random effects meta-analyses. Excess heterogeneity was investigated by meta-regression. The Barrett's esophagus meta-analysis gave an overall pooled male/female sex ratio of 1.96/1 (95% confidence interval (CI): 1.77, 2.17/1). For ERD, the pooled male/female sex ratio was 1.57/1 (95% CI: 1.40, 1.76/1) and, for non-ERD, 0.72/1 (95% CI: 0.62, 0.84/1). All of these estimates were associated with substantial heterogeneity (I2 = 81.1%, 92.7%, and 88.8%, respectively). The meta-analysis estimates for ERD and Barrett's esophagus, while showing an excess of males, are substantially lower than similar estimates for esophageal adenocarcinoma. It is important to establish why male Barrett's esophagus and ERD patients are at increased risk of malignancy compared with females.
Next-generation sequencing (NGS) technology has demonstrated that the cancer genomes are peppered with mutations. Although most somatic tumour mutations are unlikely to have any role in the cancer ...process per se, the spectra of DNA sequence changes in tumour mutation catalogues have the potential to identify the mutagens, and to reveal the mutagenic processes responsible for human cancer. Very recently, a novel approach for data mining of the vast compilations of tumour NGS data succeeded in separating and precisely defining at least 30 distinct patterns of sequence change hidden in mutation databases. At least half of these mutational signatures can be readily assigned to known human carcinogenic exposures or endogenous mechanisms of mutagenesis. A quantum leap in our knowledge of mutagenesis in human cancers has resulted, stimulating a flurry of research activity. We trace here the major findings leading first to the hypothesis that carcinogenic insults leave characteristic imprints on the DNA sequence of tumours, and culminating in empirical evidence from NGS data that well-defined carcinogen mutational signatures are indeed present in tumour genomic DNA from a variety of cancer types. The notion that tumour DNAs can divulge environmental sources of mutation is now a well-accepted fact. This approach to cancer aetiology has also incriminated various endogenous, enzyme-driven processes that increase the somatic mutation load in sporadic cancers. The tasks now confronting the field of molecular epidemiology are to assign mutagenic processes to orphan and newly discovered tumour mutation patterns, and to determine whether avoidable cancer risk factors influence signatures produced by endogenous enzymatic mechanisms. Innovative research with experimental models and exploitation of the geographical heterogeneity in cancer incidence can address these challenges.
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