A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

A review of the mesotheliogenic potency of cleavage fragments found in talc.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Assessment of worst-case potential airborne asbestos exposure associated with the use of cosmetic talc: application of an exponential decay model.

Talc is used in cosmetic products to confer desirable properties, such as moisture absorption and smooth texture, to the finished products. Concerns have been raised about the potential presence of asbestos in products containing cosmetic talc. Reconstruction of potential asbestos exposure from the use of cosmetic talc products (assuming a trace level of asbestos) requires consideration of consumer use patterns. Although application generally only lasts seconds, exposure theoretically may continue if the consumer remains in the immediate vicinity. Most published exposure measurements have not adequately characterized the potential for continued exposure. In this analysis, estimates and measurements of airborne asbestos fiber concentrations associated with cosmetic talc use from 10 published studies were used as inputs to an exponential decay model to estimate "worst-case" exposure during and following application. The resulting geometric mean 30-min time-weighted average (TWA) concentrations were 0.006 f/cc for both puff and shaker application, for diapering, 0.0001 f/cc (adult applying baby powder) and 0.0002 f/cc (infant), and for makeup application, 0.0005 f/cc. Application of an exponential decay model to measured or estimated asbestos concentrations associated with the use of cosmetic talc products yields a conservative means to comprehensively reconstruct such exposures. Moreover, our results support that, if a cosmetic talc powder product contained a trace level of asbestos fibers, the "worst-case" airborne asbestos exposure associated with its application is low.

Ultrabright Electron Bunch Injection in a Plasma Wakefield Driven by a Superluminal Flying Focus Electron Beam.

We propose a new method for self-injection of high-quality electron bunches in the plasma wakefield structure in the blowout regime utilizing a "flying focus" produced by a drive beam with an energy chirp. In a flying focus the speed of the density centroid of the drive bunch can be superluminal or subluminal by utilizing the chromatic dependence of the focusing optics. We first derive the focal velocity and the characteristic length of the focal spot in terms of the focal length and an energy chirp. We then demonstrate using multidimensional particle-in-cell simulations that a wake driven by a superluminally propagating flying focus of an electron beam can generate GeV-level electron bunches with ultralow normalized slice emittance (∼30 nm rad), high current (∼17 kA), low slice energy spread (∼0.1%), and therefore high normalized brightness (>10^{19} A/m^{2}/rad^{2}) in a plasma of density ∼10^{19} cm^{-3}. The injection process is highly controllable and tunable by changing the focal velocity and shaping the drive beam current. Near-term experiments at FACET II where the capabilities to generate tens of kA, <10 fs drivers are planned, could potentially produce beams with brightness near 10^{20} A/m^{2}/rad^{2}.

Improved Limit on Tensor Currents in the Weak Interaction from

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the ß-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a_{ßν}=-0.3325±0.0013_{stat}±0.0019_{syst} at 1σ for the case of coupling to right-handed neutrinos (C_{T}=-C_{T}^{'}), which is consistent with the standard model prediction.

Carbon footprint of inhalational and total intravenous anaesthesia for paediatric anaesthesia: a modelling study.

BACKGROUND: Tackling the climate emergency is now a key target for the healthcare sector. Avoiding inhalational anaesthesia is often cited as an important element of reducing anaesthesia-related emissions. However, evidence supporting this is based on adult practice. The aim of this study was to identify the difference in carbon footprint of inhalational and i.v. anaesthesia when used in children. METHODS: We used mathematical simulation models to compare general anaesthetic techniques in children weighing 5-50 kg for TIVA, i.v. induction then inhalational maintenance, inhalational induction then i.v. maintenance, and inhalational induction and maintenance. We simulated inhalational induction with sevoflurane alone, and co-induction with sevoflurane and nitrous oxide, and both remifentanil-propofol and propofol-only i.v. anaesthesia. For each technique, we drew on previously published life-cycle data to calculate carbon dioxide equivalents for anaesthetic durations up to 480 min. RESULTS: TIVA with propofol and remifentanil had a smaller carbon footprint over a typical anaesthetic duration of 60 min (1.26 kg carbon dioxide equivalents [CO2e] for a 20 kg child) than i.v. induction followed by inhalational maintenance (2.58 kg CO2e) or inhalational induction and maintenance (2.98 kg CO2e). Inhalational induction followed by i.v. maintenance only had a lower carbon footprint than inhalational induction and maintenance when used in longer procedures (>77 min for children 5-20 kg; >105 min for children 30-50 kg). CONCLUSIONS: In a simulation study, i.v. anaesthesia had climate benefits in paediatric anaesthesia. However, when used after inhalational induction, benefits were only achieved in longer procedures. These findings provide evidence-based guidance for reducing the environmental impact of paediatric anaesthesia, but these will require confirmation using real-world data.

Genetic Determinants of Salmonella Resistance to the Biofilm-Inhibitory Effects of a Synthetic 4-Oxazolidinone Analog.

Biofilms formed by Salmonella enterica are a frequent source of food supply contamination. Since biofilms are inherently resistant to disinfection, new agents capable of preventing biofilm formation are needed. Synthetic analogs of 4-oxazolidinone containing natural products have shown promise as antibiofilm compounds against Gram-positive bacteria. The purpose of our study was 2-fold: to establish the antibiofilm effects and mechanism of action of a synthetic 4-oxazolidinone analog (JJM-ox-3-70) and to establish mechanisms of resistance to this compound in Salmonella enterica serovar Typhimurium (S Typhimurium). JJM-ox-3-70 inhibited biofilm formation but had no effect on cell growth. The antibiofilm effects were linked to disruption of curli fimbriae and flagellar gene expression and alteration in swimming motility, suggesting an effect on multiple cellular processes. Using a 2-step screening approach of defined multigene and single-gene deletion mutant libraries, we identified 3 mutants that produced less biofilm in the presence of JJM-ox-3-70 than the isogenic WT, with phenotypes reversed by complementation in trans Genes responsible for S Typhimurium resistance to the compound included acrB, a component of the major drug efflux pump AcrAB-TolC, and two genes of unknown function (STM0437 and STM1292). The results of this study suggest that JJM-ox-3-70 inhibits biofilm formation by indirect inhibition of extracellular matrix production that may be linked to disruption of flagellar motility. Further work is needed to establish the role of the newly characterized genes as potential mechanisms of biofilm intrinsic antimicrobial resistance.IMPORTANCE Biofilms are resistant to killing by disinfectants and antimicrobials. S. enterica biofilms facilitate long-term host colonization and persistence in food processing environments. Synthetic analogs of 4-oxazolidinone natural products show promise as antibiofilm agents. Here, we show that a synthetic 4-oxazolidinone analog inhibits Salmonella biofilm through effects on both motility and biofilm matrix gene expression. Furthermore, we identify three genes that promote Salmonella resistance to the antibiofilm effects of the compound. This work provides insight into the mechanism of antibiofilm effects of a synthetic 4-oxazolidinone analog in Gram-negative bacteria and demonstrates new mechanisms of intrinsic antimicrobial resistance in Salmonella biofilms.

Imaging Fluorescence of He_{2}

We show unequivocal evidence for formation of He_{2}^{*} excimers in liquid He II created by ionizing radiation produced through neutron capture. Laser beams induce fluorescence of the excimers. The fluorescence is recorded at a rate of 55.6 Hz by a camera. The location of the fluorescence is determined with an uncertainty of 5 µm. The technique provides an opportunity to record the flow of He_{2}^{*} excimers in a medium with very small viscosity and enables measurement of turbulence around macroscopic liter size objects or vortex matter in three dimensions.

Factors that influence magnetic orientation in Caenorhabditis elegans.

Magnetoreceptive animals orient to the earth's magnetic field at angles that change depending on temporal, spatial, and environmental factors such as season, climate, and position within the geomagnetic field. How magnetic migratory preference changes in response to internal or external stimuli is not understood. We previously found that Caenorhabditis elegans orients to magnetic fields favoring migrations in one of two opposite directions. Here we present new data from our labs together with replication by an independent lab to test how temporal, spatial, and environmental factors influence the unique spatiotemporal trajectory that worms make during magnetotaxis. We found that worms gradually change their average preferred angle of orientation by ~ 180° to the magnetic field during the course of a 90-min assay. Moreover, we found that the wild-type N2 strain prefers to orient towards the left side of a north-facing up, disc-shaped magnet. Lastly, similar to some other behaviors in C. elegans, we found that magnetic orientation may be more robust in dry conditions (< 50% RH). Our findings help explain why C. elegans accumulates with distinct patterns during different periods and in differently shaped magnetic fields. These results provide a tractable system to investigate the behavioral genetic basis of state-dependent magnetic orientation.

Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial.

BACKGROUND: The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. PATIENTS AND METHODS: Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. RESULTS: CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. CONCLUSION: We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00433563.

Large contribution of natural aerosols to uncertainty in indirect forcing.

The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.

Outcomes of Patients Hospitalized for Severe Acute Alcoholic Hepatitis.

OBJECTIVES: Severe acute alcoholic hepatitis is a serious condition in individuals who consume significant quantities of alcohol. We aimed to identify risk factors for short-term mortality with this illness. METHODS: Patients with severe acute alcoholic hepatitis admitted to our academic medical center from 2010 to 2012 were identified. Demographic features, laboratory values, and patient outcomes were recorded. In-hospital mortality and transfer to inpatient hospice were combined to calculate overall inpatient mortality. RESULTS: A total of 251 hospitalizations of 191 patients were identified. The average age was 43.1 years (standard deviation 9.55). Most patients were men (80.6%). Compared with all adult patients admitted to internal medicine services during the same period, patients self-reporting Native American and Hispanic race/ethnicity were overrepresented (11.1% vs 34.0% and 14.8% vs 27.7%, χ2 P < 0.0001). In-hospital mortality was 20.3%. Another 10% of patients were transferred to inpatient hospice facilities. In the multivariate analysis, higher overall inpatient mortality was associated with an admission bilirubin >20 mg/dL (odds ratio 4.59). Of the patients, 11.9% were readmitted with a complication within 30 days-most commonly septic shock. Of the readmitted patients, the overall inpatient mortality was 86.2%. CONCLUSIONS: This study confirms the severity of illness among patients with severe acute alcoholic hepatitis. Patients with the highest total bilirubin levels on admission had the highest overall inpatient mortality. Readmission was a strong predictor of overall in-hospital mortality.

Peer Observation of Rounds Leads to Collegial Discussion of Teaching.

PROBLEM: Faculty in the Division of Hospital Medicine provide most of the clinical teaching for learners at our institution. The majority of these faculty are Assistant Professors with limited formal instruction in clinical teaching. Previous Divisional strategies to improve clinical teaching ability included discussion of effective teaching behaviors, developing written expectations for teaching faculty, and instituting seminars on effective clinical teaching. Heretofore, the Division had not utilized a direct observation exercise. INTERVENTION: We developed a direct observation exercise to encourage discussion of teaching techniques and contemplation of change. Using a social learning model, we developed a peer-to-peer observation followed by a nonevaluative discussion. We created a tool for describing teaching behaviors in 5 domains that were similar to or different from the usual behavior of the observing peer: learner presentations, team leadership, bedside teaching, professionalism, and other. After the observation, the observing and observed faculty met to discuss observed teaching behaviors. Both faculty members discussed and then recorded any teaching behaviors that they planned to adopt or change. CONTEXT: We implemented this intervention in a 22-member Academic Division of Hospital Medicine at a tertiary care medical center in the United States. A high proportion were junior faculty and graduates of our residency program. OUTCOME: We reviewed records of 28 of 31 observations that were completed during the initial 9-month period of implementation and later surveyed faculty. The exercise resulted in planned changes in teaching behaviors that included instituting new methods to improve teaching team leadership, triaging of patients seen on rounds, faculty behaviors during oral presentations, giving real-time feedback, use of technology and humor, demonstrating physical examination findings, and modeling professional behaviors. Faculty later reported adoption of new teaching behaviors that were important to them. LESSONS LEARNED: This exercise was easily implemented, resulted in planned changes by both observed and observing peers, and resulted in widespread adoption of some specific teaching behaviors. The most commonly planned change dealt with team leadership or organizational issues. When given the freedom to choose, junior faculty were more likely to observe senior faculty.