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The use of technology to automate clinical workflows at The Chester County Hospital in West Chester, Pa., has resulted in the following benefits: An 82 percent reduction in hospital-acquired MRSA infections. A significant reduction in catheter-associated urinary tract infections. Enhanced documentation of pre-existing pressure ulcers (The Centers for Medicare & Medicaid Services classifies pressure ulcers that develop during a hospital stay as \"never events\").

This dissertation focuses on some of the factors affecting defect formation and the characterization of these defects in aluminum lost foam castings. Several statistically designed experiments were used to evaluate the effects of various gating designs, aluminum alloy compositions, foam pattern properties, and coating properties. Metal velocity measurements, along with the number, type, and size of defects, were used as response variables. Foam properties of interest in this dissertation included foam density, fusion level, and bead chemistry. Decreasing the nominal density of the pattern was found to decrease the total amount of defects. The same was true when a high fusion level was used. It was determined that the current qualitative measure of fusion level is not adequate; a quantitative measure needs to be developed. This research also revealed that the use of beads containing a bromide additive significantly reduced the amount of defects found in the castings, particularly for conditions where the metal temperature is low or solidification times are short. Coating properties of interest were permeability and thickness. Both of these properties can be controlled via the viscosity of the coating slurry applied to the pattern. It was found that decreasing the permeability and increasing the thickness of the coating decreased the total amount of defects in the casting. Defect characterization was done using Auger spectroscopy, scanning electron microscopy (SEM), and optical metallography. Auger results revealed that the color of the defect changed with carbon layer thickness. SEM imaging showed the presence of wrinkles on fold surfaces while no wrinkles were found on the surface of pores.

Work in our laboratory has centered on the development of the glow discharge as an ionization source for solids elemental mass spectrometry. The electrical discharge produced by applying a large potential between a cathode, formed from the analytical sample, and an anode in the presence of a low pressure inert gas is known to generate ion signals and mass spectra representative of the sample composition. The acquisition of a tunable dye laser has allowed studies of various laser/discharge interactions to be performed. These include investigations into the laser opto-galvanic effect, resonance ionization, and laser ablation. The opto-galvanic effect, which involves monitoring changes in discharge resistance during the time period of laser interaction, was employed in conjunction with atomic absorption and mass spectrometric studies to determine the major mechanisms of ionization in our discharge configuration. Laser depopulation of the rare gas metastable states was observed to decrease the ionization rate of the discharge, indicating a dependence on the metastable state in the ionization mechanisms. This is consistent with a Penning ionization process, where the potential energy of a metastable rare gas atom is collisionally transferred to a second atom, resulting in ionization. Although the discharge produces a large ion population, less than 1% of the total atomic density is ionized in the discharge. Therefore, a large neutral atomic population remains for interaction with the laser output. Resonant two photon absorption of the laser light can result in a wavelength selective enhancement of the ionization rate in the discharge source, with the enhancements occurring only at wavelengths corresponding to atomic transitions. This results in a technique that is both wavelength and mass selective, commonly termed resonance ionization mass spectrometery (RIMS). The laser can also serve to enhance the atomization of the discharge through laser ablation. In this case, the beam is focused onto the sample surface causing the ejection of an atomic population into the discharge for subsequent ionization. The results of these investigations will also be presented.

Combinations of nontrivial band topology and long-range magnetic order hold promise for realizations of novel spintronic phenomena, such as the quantum anomalous Hall effect and the topological magnetoelectric effect. Following theoretical advances, material candidates are emerging. Yet, so far a compound that combines a band-inverted electronic structure with an intrinsic net magnetization remains unrealized.MnBi2Te4has been established as the first antiferromagnetic topological insulator and constitutes the progenitor of a modular(Bi2Te3)n(MnBi2Te4)series. Here, forn=1, we confirm a nonstoichiometric composition proximate toMnBi4Te7. We establish an antiferromagnetic state below 13 K followed by a state with a net magnetization and ferromagnetic-like hysteresis below 5 K. Angle-resolved photoemission experiments and density-functional calculations reveal a topologically nontrivial surface state on theMnBi4Te7(0001)surface, analogous to the nonmagnetic parent compoundBi2Te3. Our results establishMnBi4Te7as the first band-inverted compound with intrinsic net magnetization providing a versatile platform for the realization of magnetic topological states of matter.

Io's interaction with the Jovian magnetosphere generates a power of about 1012 W which propagates as Alfvén waves along the magnetic field lines and is partly transferred to electrons, resulting in intense auroral emissions. A recent study of the power transmission along the Io flux tube and of the electron acceleration at high latitudes showed that the power of the observed emissions is well explained by assuming filamentation of the Alfvén waves in the torus and the acceleration of the electrons at high latitude. At Jupiter, UV footprints related to Europa and Ganymede have also been observed. At Saturn recent observations revealed a weak UV footprint of Enceladus. We apply the Io interaction model to the Europa and Enceladus interactions. We show that the Alfvén wave filamentation leads to a precipitating electron power consistent with the power of the observed UV footprints.

Emergency departments (EDs) frequently care for individuals with opioid use disorder (OUD). Buprenorphine (BUP) is an effective treatment option for patients with OUD that can safely be initiated in the ED. At present, BUP is rarely initiated as a part of routine ED care. Clinical decision support (CDS) could accelerate adoption of ED-initiated BUP into routine emergency care. This study aimed to design and formatively evaluate a user-centered decision support tool for ED initiation of BUP for patients with OUD. User-centered design with iterative prototype development was used. Initial observations and interviews identified workflows and information needs. The design team and key stakeholders reviewed prototype designs to ensure accuracy. A total of 5 prototypes were evaluated and iteratively refined based on input from 26 attending and resident physicians. Early feedback identified concerns with the initial CDS design: an alert with several screens. The timing of the alert led to quick dismissal without using the tool. User feedback on subsequent iterations informed the development of a flexible tool to support clinicians with varied levels of experience with the intervention by providing both one-click options for direct activation of care pathways and user-activated support for critical decision points. The final design resolved challenging navigation issues through targeted placement, color, and design of the decision support modules and care pathways. In final testing, users expressed that the tool could be easily learned without training and was reasonable for use during routine emergency care. A user-centered design process helped designers to better understand users' needs for a Web-based clinical decision tool to support ED initiation of BUP for OUD. The process identified varying needs across user experience and familiarity with the protocol, leading to a flexible design supporting both direct care pathways and user-initiated decision support.

Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis . The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis , by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis . Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis , describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors of M. tuberculosis CoaB, which we show to bind to a cryptic allosteric site within CoaB. The bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioesters and forms a dodecamer and by performing a high-throughput screen they identify selective inhibitors of M. tuberculosis CoaB that bind to an allosteric site within CoaB.

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66–0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Eisai.