Sulfidation of metallic nanoparticles such as silver nanoparticles (AgNPs) released to the environment may be an important detoxification mechanism. Two types of AgNPsan engineered polydisperse and ...aggregated AgNP powder, and a laboratory-synthesized, relatively monodisperse AgNP aqueous dispersionwere studied. The particles were sulfidized to varying degrees and characterized to determine the effect of initial AgNP polydispersity and aggregation state on AgNP sulfidation, and then exposed to Escherichia coli to determine if the degree of sulfidation of pristine AgNPs affects growth inhibition of bacteria. The extent of sulfidation was found to depend on the HS–/Ag ratio. However, for the same reaction times, the more monodisperse particles were fully transformed to Ag2S, and the polydisperse, aggregated particles were not fully sulfidized, thus preserving the toxic potential of Ag0 in the aggregates. A higher Ag2S:Ag0 ratio in the sulfidized nanoparticles resulted in less growth inhibition of E. coli over 6 h of exposure. These results suggest that the initial properties of AgNPs can affect sulfidation products, which in turn affect microbial growth inhibition, and that these properties should be considered in assessing the environmental impact of AgNPs.
The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over ...previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200<E_{ν}^{QE}<1250 MeV. Combining these data with the νover ¯_{e} appearance data from 11.27×10^{20} protons on target in antineutrino mode, a total ν_{e} plus νover ¯_{e} charged-current quasielastic event excess of 460.5±99.0 events (4.7σ) is observed. If interpreted in a two-neutrino oscillation model, ν_{μ}→ν_{e}, the best oscillation fit to the excess has a probability of 21.1%, while the background-only fit has a χ^{2} probability of 6×10^{-7} relative to the best fit. The MiniBooNE data are consistent in energy and magnitude with the excess of events reported by the Liquid Scintillator Neutrino Detector (LSND), and the significance of the combined LSND and MiniBooNE excesses is 6.0σ. A two-neutrino oscillation interpretation of the data would require at least four neutrino types and indicate physics beyond the three neutrino paradigm. Although the data are fit with a two-neutrino oscillation model, other models may provide better fits to the data.
The MiniBooNE experiment at Fermilab reports a total excess of 638.0 ± 52.1 (stat .) ± 122.2 (syst.) electronlike events from a data sample corresponding to 18.75 × 10 20 protons-on-target in ...neutrino mode, which is a 46% increase in the data sample with respect to previously published results and 11.27 × 10 20 protons-on-target in antineutrino mode. The overall significance of the excess, 4.8σ, is limited by systematic uncertainties, assumed to be Gaussian, as the statistical significance of the excess is 12.2σ. The additional statistics allow several studies to address questions on the source of the excess. First, we provide two-dimensional plots in visible energy and the cosine of the angle of the outgoing lepton, which can provide valuable input to models for the event excess. Second, we test whether the excess may arise from photons that enter the detector from external events or photons exiting the detector from π 0 decays in two model independent ways. Beam timing information shows that almost all of the excess is in time with neutrinos that interact in the detector. The radius distribution shows that the excess is distributed throughout the volume, while tighter cuts on the fiducial volume increase the significance of the excess. The data likelihood ratio disfavors models that explain the event excess due to entering or exiting photons.
Objectives
There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may ...individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia.
Design, Setting and Participants
This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English.
Results
The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone).
Conclusion
This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.
ABSTRACT
We present an improved measurement of the Hubble constant (H0) using the ‘inverse distance ladder’ method, which adds the information from 207 Type Ia supernovae (SNe Ia) from the Dark ...Energy Survey (DES) at redshift 0.018 < z < 0.85 to existing distance measurements of 122 low-redshift (z < 0.07) SNe Ia (Low-z) and measurements of Baryon Acoustic Oscillations (BAOs). Whereas traditional measurements of H0 with SNe Ia use a distance ladder of parallax and Cepheid variable stars, the inverse distance ladder relies on absolute distance measurements from the BAOs to calibrate the intrinsic magnitude of the SNe Ia. We find H0 = 67.8 ± 1.3 km s−1 Mpc−1 (statistical and systematic uncertainties, 68 per cent confidence). Our measurement makes minimal assumptions about the underlying cosmological model, and our analysis was blinded to reduce confirmation bias. We examine possible systematic uncertainties and all are below the statistical uncertainties. Our H0 value is consistent with estimates derived from the Cosmic Microwave Background assuming a ΛCDM universe.
A search for sub-GeV dark matter produced from collisions of the Fermilab 8 GeV Booster protons with a steel beam dump was performed by the MiniBooNE-DM Collaboration using data from 1.86 × 1020 ...protons on target in a dedicated run. The MiniBooNE detector, consisting of 818 tons of mineral oil and located 490 meters downstream of the beam dump, is sensitive to a variety of dark matter initiated scattering reactions. Three dark matter interactions are considered for this analysis: elastic scattering off nucleons, inelastic neutral pion production, and elastic scattering off electrons. Multiple data sets were used to constrain flux and systematic errors, and time-of-flight information was employed to increase sensitivity to higher dark matter masses. No excess from the background predictions was observed, and 90% confidence level limits were set on the vector portal and leptophobic dark matter models. New parameter space is excluded in the vector portal dark matter model with a dark matter mass between 5 and 50 MeV c−2 . The reduced neutrino flux allowed to test if the MiniBooNE neutrino excess scales with the production of neutrinos. No excess of neutrino oscillation events were measured ruling out models that scale solely by number of protons on target independent of beam configuration at 4.6σ.
Currently, the concept of engineered tissues depends on the ability of cultured cells to fabricate new tissue around a scaffold. This is inherently slow and expensive and has had limited success so ...far. We report here a new process for the cell‐independent, controlled engineering of biomimetic scaffolds by rapid removal of fluid from hyperhydrated collagen gel (or other) constructs, using plastic compression (PC). PC fabrication produces dense, cellular, mechanically strong native collagen structures with controllable nano‐ and microscale biomimetic structures. The huge‐scale shrinkage (> 100‐fold) provides the ability to introduce controllable mechanical properties, microlayering, and embossed interface topography without cell participation, but with high cell viability. Critically, this takes minutes rather than the conventional days and weeks. The rapidity and biomimetic potential of the PC fabrication process at the mesoscale opens a new route for the production of biomaterials and patient‐customized tissues. It also represents a new concept in ‘engineering’ tissues.
Cell‐independent, controlled engineering of biomimetic scaffolds can be achieved by rapid fluid removal from hyperhydrated collagen gel via plastic compression. Mechanically strong native collagen with controllable nano‐ and microscale biomimetic structures (see Figure) can be produced over a timescale of minutes rather than the conventional days and weeks, providing promise for rapid production of biomaterials and patient‐customized tissues.
A repeat expansion mutation in the C9orf72 gene is the leading known genetic cause of FTD and ALS. The C9orf72-ALS/FTD field has been plagued by a lack of reliable tools to monitor this genomic locus ...and its RNA and protein products. We have validated assays that quantify C9orf72 pathobiology at the DNA, RNA and protein levels using knock-out human iPSC lines as controls. Here we show that single-molecule sequencing can accurately measure the repeat expansion and faithfully report on changes to the C9orf72 locus in what has been a traditionally hard to sequence genomic region. This is of particular value to sizing and phasing the repeat expansion and determining changes to the gene locus after gene editing. We developed ddPCR assays to quantify two major C9orf72 transcript variants, which we validated by selective excision of their distinct transcriptional start sites. Using validated knock-out human iPSC lines, we validated 4 commercially available antibodies (of 9 tested) that were specific for C9orf72 protein quantification by Western blot, but none were specific for immunocytochemistry. We tested 15 combinations of antibodies against dipeptide repeat proteins (DPRs) across 66 concentrations using MSD immunoassay, and found two (against poly-GA and poly-GP) that yielded a 1.5-fold or greater signal increase in patient iPSC-motor neurons compared to knock-out control, and validated them in human postmortem and transgenic mouse brain tissue. Our validated DNA, RNA and protein assays are applicable to discovery research as well as clinical trials.
Airborne and ground‐based measurements during the CalNex (California Research at the Nexus of Air Quality and Climate Change) field study in May/June 2010 show a weekend effect in ozone in the South ...Coast Air Basin (SoCAB) consistent with previous observations. The well‐known and much‐studied weekend ozone effect has been attributed to weekend reductions in nitrogen oxide (NOx = NO + NO2) emissions, which affect ozone levels via two processes: (1) reduced ozone loss by titration and (2) enhanced photochemical production of ozone due to an increased ratio of non‐methane volatile organic compounds (VOCs) to NOx. In accord with previous assessments, the 2010 airborne and ground‐based data show an average decrease in NOx of 46 ± 11% and 34 ± 4%, respectively, and an average increase in VOC/NOxratio of 48 ± 8% and 43 ± 22%, respectively, on weekends. This work extends current understanding of the weekend ozone effect in the SoCAB by identifying its major causes and quantifying their relative importance from the available CalNex data. Increased weekend production of a VOC‐NOxoxidation product, peroxyacetyl nitrate, compared to a radical termination product, nitric acid, indicates a significant contribution from increased photochemical production on weekends. Weekday‐to‐weekend differences in the products of NOx oxidation show 45 ± 13% and 42 ± 12% more extensive photochemical processing and, when compared with odd oxygen (Ox = O3 + NO2), 51 ± 14% and 22 ± 17% greater ozone production efficiency on weekends in the airborne and ground‐based data, respectively, indicating that both contribute to higher weekend ozone levels in the SoCAB.
Key Points
A weekend ozone effect is observed in the South Coast Air Basin
Reductions in NOx emissions drive weekday and weekend differences in ozone
Photochemical ozone production contributes to observed weekend ozone levels
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