Re-estimation of argon isotope ratios leading to a revised estimate of the Boltzmann constant

In 2013, NPL, SUERC and Cranfield University published an estimate for the Boltzmann constant [1] based on a measurement of the limiting low-pressure speed of sound in argon gas. Subsequently, an extensive investigation by Yang et al [2] revealed that there was likely to have been an error in the estimate of the molar mass of the argon used in the experiment. Responding to [2], de Podesta et al revised their estimate of the molar mass [3]. The shift in the estimated molar mass, and of the estimate of kB, was large: -2.7 parts in 106, nearly four times the original uncertainty estimate. The work described here was undertaken to understand the cause of this shift and our conclusion is that the original samples were probably contaminated with argon from atmospheric air.
 In this work we have repeated the measurement reported in [1] on the same gas sample that was examined in [2, 3]. However in this work we have used a different technique for sampling the gas that has allowed us to eliminate the possibility of contamination of the argon samples. We have repeated the sampling procedure three times, and examined samples on two mass spectrometers. This procedure confirms the isotopic ratio estimates of Yang et al [2] but with lower uncertainty, particularly in the relative abundance ratio R38:36.
 Our new estimate of the molar mass of the argon used in Isotherm 5 in [1] is 39.947 727(15) g mol-1 which differs by +0.50 parts in 106 from the estimate 39.947 707(28) g mol-1 made in [3]. This new estimate of the molar mass leads to a revised estimate of the Boltzmann constant of kB = 1.380 648 60 (97) × 10−23 J K−1 which differs from the 2014 CODATA value by +0.05 parts in 106.&#13

Microbiological assessment of aerosol generated during debond of fixed orthodontic appliances

Introduction The aims of this study were to describe bacterial load and diversity of the aerosol created during enamel cleanup after the removal of fixed orthodontic appliances and to assess the effect of a preprocedural mouth rinse. Methods The study involved the sampling of ambient air adjacent to the patient's mouth during adhesive removal using a slow-speed handpiece and a spiral fluted tungsten carbide bur without water irrigation. Sampling was carried out during enamel cleanup with or without a preprocedural mouth rinse of either sterile water or chlorhexidine. Airborne particles were collected using a viable inertial impactor simulating the human respiratory tree. The bacteria collected were analyzed using both culture and molecular techniques. Results Bacteria produced during debond and enamel cleanup can reach all levels of the respiratory tree. The use of a preprocedural mouth rinse, either sterile water or chlorhexidine, increased the numbers and diversity of the bacteria in the air. Conclusions When using a slow-speed handpiece and a spiral fluted tungsten carbide bur for enamel cleanup after orthodontic treatment, the bacterial load and diversity of the aerosol produced are lower when a preprocedural mouth rinse is not used.</p

Microbiological assessment of aerosol generated during debond of fixed orthodontic appliances

Introduction The aims of this study were to describe bacterial load and diversity of the aerosol created during enamel cleanup after the removal of fixed orthodontic appliances and to assess the effect of a preprocedural mouth rinse. Methods The study involved the sampling of ambient air adjacent to the patient's mouth during adhesive removal using a slow-speed handpiece and a spiral fluted tungsten carbide bur without water irrigation. Sampling was carried out during enamel cleanup with or without a preprocedural mouth rinse of either sterile water or chlorhexidine. Airborne particles were collected using a viable inertial impactor simulating the human respiratory tree. The bacteria collected were analyzed using both culture and molecular techniques. Results Bacteria produced during debond and enamel cleanup can reach all levels of the respiratory tree. The use of a preprocedural mouth rinse, either sterile water or chlorhexidine, increased the numbers and diversity of the bacteria in the air. Conclusions When using a slow-speed handpiece and a spiral fluted tungsten carbide bur for enamel cleanup after orthodontic treatment, the bacterial load and diversity of the aerosol produced are lower when a preprocedural mouth rinse is not used.</p

Genome-Wide Transcriptional Response of Silurana (Xenopus) tropicalis to Infection with the Deadly Chytrid Fungus

Emerging infectious diseases are of great concern for both wildlife and humans. Several highly virulent fungal pathogens have recently been discovered in natural populations, highlighting the need for a better understanding of fungal-vertebrate host-pathogen interactions. Because most fungal pathogens are not fatal in the absence of other predisposing conditions, host-pathogen dynamics for deadly fungal pathogens are of particular interest. The chytrid fungus Batrachochytrium dendrobatidis (hereafter Bd) infects hundreds of species of frogs in the wild. It is found worldwide and is a significant contributor to the current global amphibian decline. However, the mechanism by which Bd causes death in amphibians, and the response of the host to Bd infection, remain largely unknown. Here we use whole-genome microarrays to monitor the transcriptional responses to Bd infection in the model frog species, Silurana (Xenopus) tropicalis, which is susceptible to chytridiomycosis. To elucidate the immune response to Bd and evaluate the physiological effects of chytridiomycosis, we measured gene expression changes in several tissues (liver, skin, spleen) following exposure to Bd. We detected a strong transcriptional response for genes involved in physiological processes that can help explain some clinical symptoms of chytridiomycosis at the organismal level. However, we detected surprisingly little evidence of an immune response to Bd exposure, suggesting that this susceptible species may not be mounting efficient innate and adaptive immune responses against Bd. The weak immune response may be partially explained by the thermal conditions of the experiment, which were optimal for Bd growth. However, many immune genes exhibited decreased expression in Bd-exposed frogs compared to control frogs, suggesting a more complex effect of Bd on the immune system than simple temperature-mediated immune suppression. This study generates important baseline data for ongoing efforts to understand differences in response to Bd between susceptible and resistant frog species and the effects of chytridiomycosis in natural populations

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Centrifugation does not remove bacteria from the fat fraction of human milk

Abstract Analysis of the human milk microbiome is complicated by the presence of a variable quantity of fat. The fat fraction of human milk is typically discarded prior to analysis. It is assumed that all cells are pelleted out of human milk by high speed centrifugation; however, studies of bovine milk have reported that bacteria may remain trapped within the fat fraction. Here, the bacterial DNA profiles of the fat fraction and cell pellet of human milk (n = 10) were analysed. Human and bacterial DNA was consistently recovered from the fat fraction of human milk (average of 12.4% and 32.7%, respectively). Staphylococcus epidermidis was significantly more abundant in the cell pellet compared to the fat fraction (P = 0.038), and three low-abundance species (< 5% relative abundance) were recovered from one fraction only. However, inclusion of fat reduced the efficiency of DNA extraction by 39%. Culture-based methods were used to quantify the distribution of an exogenously added strain of Staphylococcus aureus in human milk fractions. S. aureus was consistently recovered from the fat fraction (average 28.9%). Bacterial DNA profiles generated from skim milk or cell pellets are not representative of the entire human milk microbiome. These data have critical implications for the design of future work in this field

Dietary pattern trajectories across adolescence and early adulthood and their associations with childhood and parental factors

Background: Although adolescent dietary patterns tend to be of poor quality, it is unclear whether dietary patterns established in adolescence persist into adulthood. Objectives: We examined trajectories across adolescence and early adulthood for 2 major dietary patterns and their associations with childhood and parental factors. Methods: Using data from the Western Australian Pregnancy Cohort (Raine Study), intakes of 38 food groups were estimated at ages 14, 17, 20 and 22 y in 1414 participants using evaluated FFQs. Using factor analysis, 2 major dietary patterns (healthy and Western) were consistently identified across follow-ups. Sex-specific group-based modeling assessed the variation in individual dietary pattern z scores to identify group trajectories for each pattern between ages 14 and 22 y and to assess their associations with childhood and parental factors. Results: Two major trajectory groups were identified for each pattern. Between ages 14 and 22 y, a majority of the cohort (70% males, 73% females) formed a trajectory group with consistently low z scores for the healthy dietary pattern. The remainder had trajectories showing either declining (27% females) or reasonably consistent healthy dietary pattern z scores (30% males). For the Western dietary pattern, the majority formed trajectories with reasonably consistent average scores (79% males, 81% females) or low scores that declined over time. However, 21% of males had a trajectory of steady, marked increases in Western dietary pattern scores over time. A lower maternal education and higher BMI (in kg/m2) were positively associated with consistently lower scores of the healthy dietary pattern. Lower family income, family functioning score, maternal age, and being in a single-parent family were positively related to higher scores of the Western dietary pattern. Conclusions: Poor dietary patterns established in adolescence are likely to track into early adulthood, particularly in males. This study highlights the transition between adolescence and early adulthood as a critical period and the populations that could benefit from dietary interventions

A blueprint for a multi-disease, multi-domain Bayesian adaptive platform trial incorporating adult and paediatric subgroups: the Staphylococcus aureus Network Adaptive Platform trial.

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registration NCT05137119 . Registered on 30 November 2021