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Various nanostructured sensor designs currently aim to achieve or claim single molecular detection by a reduction of the active sensor size. However, a reduction of the sensor size has the negative effect of reducing the capture probability considering the diffusion-based analyte transport commonly used. Here we introduce and apply a localized programmable electrodynamic precipitation concept as an alternative to diffusion. The process provides higher collection rates of airborne species and detection at lower concentration. As an example, we compare an identical nanostructured surfaced-enhanced Raman spectroscopy sensor with and without localized delivery and find that the sensitivity and detection time is improved by at least two orders of magnitudes. Localized collection in an active-matrix array-like fashion is also tested, yielding hybrid molecular arrays on a single chip over a broad range of molecular weights, including small benzenethiol (110.18 Da) and 4-fluorobenzenethiol (128.17 Da), or large macromolecules such as anti-mouse IgG (~150 kDa). Effective collection of molecules on a small sensing area is not possible based on diffusion alone and the employment of a directed force is required. The authors report a localized electrodynamic precipitation concept to collect, spot and detect airborne species in an active-matrix array-like fashion.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium–tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules—several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics. A statistical approach to designing and predicting the fusion yield of cryogenic deuterium–tritium implosions leads to tripled yield in direct-drive laser fusion of deuterium–tritium layered targets.

Opioid misuse and deaths are increasing in the United States. In 2017, Ohio had the second highest overdose rates in the US, with the city of Cincinnati experiencing a 50% rise in opioid overdoses since 2015. Understanding the temporal and geographic variation in overdose emergencies may help guide public policy responses to the opioid epidemic. We used a publicly available data set of suspected heroin-related emergency calls (n = 6,246) to map overdose incidents to 280 census block groups in Cincinnati between August 1, 2015, and January 30, 2019. We used a Bayesian space-time Poisson regression model to examine the relationship between demographic and environmental characteristics and the number of calls within block groups. Higher numbers of heroin-related incidents were found to be associated with features of the built environment, including the proportion of parks (relative risk [RR] = 2.233; 95% credible interval [CI]: [1.075-4.643]), commercial (RR = 13.200; 95% CI: [4.584-38.169]), manufacturing (RR = 4.775; 95% CI: [1.958-11.683]), and downtown development zones (RR = 11.362; 95% CI: [3.796-34.015]). The number of suspected heroin-related emergency calls was also positively associated with the proportion of male population, the population aged 35-49 years, and distance to pharmacies and was negatively associated with the proportion aged 18-24 years, the proportion of the population with a bachelor's degree or higher, median household income, the number of fast food restaurants, distance to hospitals, and distance to opioid treatment programs. Significant spatial and temporal heterogeneity in the risks of incidents remained after adjusting for covariates. Limitations of this study include lack of information about the nature of incidents after dispatch, which may differ from the initial classification of being related to heroin, and lack of information on local policy changes and interventions. We identified areas with high numbers of reported heroin-related incidents and features of the built environment and demographic characteristics that are associated with these events in the city of Cincinnati. Publicly available information about opiate overdoses, combined with data on spatiotemporal risk factors, may help municipalities plan, implement, and target harm-reduction measures. In the US, more work is necessary to improve data availability in other cities and states and the compatibility of data from different sources in order to adequately measure and monitor the risk of overdose and inform health policies.

To assess the utility of cost-effective dried blood spot (DBS) field sampling for incidence and drug resistance surveillance of persons at high risk for HIV infection. We evaluated DBS collected in 2007-2010 in non-clinical settings by finger-stick from HIV-positive heterosexuals at increased risk of HIV infection (n = 124), men who have sex with men (MSM, n = 110), and persons who inject drugs (PWID, n = 58). Relative proportions of recent-infection findings among risk groups were assessed at avidity index (AI) cutoffs of ≤25%, ≤30%, and ≤35%, corresponding to an infection mean duration of recency (MDR) of 220.6, 250.4, and 278.3 days, respectively. Drug resistance mutation prevalence was compared among the risk groups and avidity indices. HIV antibody avidity testing of all self-reported ARV-naïve persons (n = 186) resulted in 9.7%, 11.3% and 14.0% with findings within the 221, 250, and 278-day MDRs, respectively. The proportion of ARV-naïve MSM, heterosexuals, and PWID reporting only one risk category who had findings below the suggested 30% AI was 23.1%, 6.9% and 3.6% (p<0.001), respectively. MSM had the highest prevalence of drug resistance and the only cases of transmitted multi-class resistance. Among the ARV-experienced, MSM had disproportionately more recent-infection results than did heterosexuals and PWID. The disproportionately higher recent-infection findings for MSM as compared to PWID and heterosexuals increased as the MDR window increased. Unreported ARV use might explain greater recent-infection findings and drug resistance in this MSM population. DBS demonstrated utility in expanded HIV testing; however, optimal field handling is key to accurate recent-infection estimates.

Focussing laser light onto the surface of a small target filled with deuterium and tritium implodes it and leads to the creation of a hot and dense plasma, in which thermonuclear fusion reactions occur. In order for the plasma to become self-sustaining, the heating of the plasma must be dominated by the energy provided by the fusion reactions—a condition known as a burning plasma. A metric for this is the generalized Lawson parameter, where values above around 0.8 imply a burning plasma. Here, we report on hydro-equivalent scaling of experimental results on the OMEGA laser system and show that these have achieved core conditions that reach a burning plasma when the central part of the plasma, the hotspot, is scaled in size by at least a factor of 3.9 ± 0.10, which would require a driver laser energy of at least 1.7 ± 0.13 MJ. In addition, we hydro-equivalently scale the results to the 2.15 MJ of laser energy available at the National Ignition Facility and find that these implosions reach 86% of the Lawson parameter required for ignition. Our results support direct-drive inertial confinement fusion as a credible approach for achieving thermonuclear ignition and net energy in laser fusion. Hydro-equivalent scaling of recent direct-drive inertial confinement fusion implosions shows that a burning plasma can be achieved with a higher laser energy.

Irradiating a small capsule containing deuterium and tritium fuel directly with intense laser light causes it to implode, which creates a plasma hot enough to initiate fusion reactions between the fuel nuclei. Here we report on such laser direct-drive experiments and observe that the fusion reactions produce more energy than the amount of energy in the central so-called hot-spot plasma. This condition is identified as having a hot-spot fuel gain greater than unity. A hot-spot fuel gain of around four was previously accomplished at the National Ignition Facility in indirect-drive inertial confinement fusion experiments where the capsule is irradiated by X-rays. In that case, up to 1.9 MJ of laser energy was used, but in contrast, our experiments on the OMEGA laser system require as little as 28 kJ. As the hot-spot fuel gain is predicted to grow with laser energy and target size, our work establishes the direct-drive approach to inertial fusion as a promising path towards burning and ignited plasmas in the laboratory. Additionally, we report a record (direct-drive) fusion yield of 0.9 kJ on OMEGA, which we achieved with thin-ice deuterium–tritium liner targets. Inertial confinement fusion experiments in a direct-drive configuration report more energy produced in deuterium–tritium fusion reactions than the amount of energy in the central part of the plasma created by laser irradiation of the fuel capsule.

Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, infection, and patient-important bleeding. A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Abstract Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433–0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457–0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37–0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341–0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534–0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii .