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Background: In November 2020, bamlanivimab received emergency use authorization (EUA) to treat patients with early, mild-to-moderate COVID-19 who are at high risk of progression. Montefiore Medical Center serves an economically underserved community of >1.4 million residents in the Bronx, New York. Montefiore’s antimicrobial stewardship team (AST) developed a multidisciplinary treatment pathway for patients meeting EUA criteria: (1) outpatients and hospital associates and (2) acute-care patients (EDs or inpatient). Methods: The Montefiore AST established a centralized process for screening high-risk COVID-19 patients 7 days a week. Referrals were sent by e-mail from occupational health, primary care practices, specialty practices, emergency departments, and urgent care centers. Patients were screened in real time and were treated in the ED or a newly established infusion center within 24 hours. After infusion, all patients received phone calls from nurses and had an infectious diseases televisit. Demographics, clinical symptoms, subsequent ED visit or hospital admission, and timing from infusion to ED or hospitalization were obtained from the electronic health record. Results: In total, 281 high-risk patients (median age, 62 years; 57% female) received bamlanivimab at the infusion center or in the acute-care setting between December 2, 2020, and January 27, 2021 (Table 1). The number of treated patients increased weekly (Figure 1). Also, 62% were Hispanic or black, and 96% met EUA criteria. Furthermore, 51 (18%) were referred from occupational health, 205 (73%) were referred from the community, and 25 (9%) were inpatients (https://www.fda.gov/media/143605/download). All patients were successfully infused without adverse reactions. In addition, 23 patients (8.2%) were hospitalized and 6 (2.1%) visited EDs within 30 days of treatment. The average number of days between symptom onset and infusion was 4.9. The median age of admitted versus nonadmitted patients was 68 years versus 61.5 years (P = .07). Conclusions: An AST-coordinated bamlanivimab treatment program successfully treated multiple high-risk COVID-19 patients and potentially reduced hospitalizations. However, the effort, personnel, and resources required are significant. Dedicated hospital investment is necessary for maximal success.
The influence of surface melt on the flow of Greenland's largest outlet glaciers remains poorly known and in situ observations are few. We use field observations to link surface meltwater forcing to glacier-wide diurnal velocity variations on East Greenland's Helheim Glacier over two summer melt seasons. We observe diurnal variations in glacier speed that peak ~6.5 h after daily maximum insolation and extend from the terminus region to the equilibrium line. Both the amplitude of the diurnal speed variation and its sensitivity to daily melt are largest at the glacier terminus and decrease up-glacier, suggesting that the magnitude of the response is controlled not only by melt input volume and temporal variability, but also by background effective pressure, which approaches zero at the terminus. Our results provide evidence that basal lubrication by meltwater drives diurnal velocity variations at Greenland's marine-terminating glaciers in a similar manner to alpine glaciers and Greenland's land-terminating outlet glaciers.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
ABSTRACT IMPACT: Current practice guidelines offer a variety of treatment options for sternal reconstruction but complications and infections remain a serious surgical problem. This work seeks to provide a comprehensive picture of the com-morbidities and reconstructive methods that lead to success and improve patient outcomes. OBJECTIVES/GOALS: Patients that undergo cardiac surgery via the median sternotomy approach are at risk of wound complications that require repair. We seek to evaluate how outcomes of sternal reconstruction are influenced by patient comorbidities, flap usage and internal mammary artery grafts and methods of sternal closure. METHODS/STUDY POPULATION: We identified patients between 2005 and 2020 who underwent sternotomy followed by debridement and flap coverage at our institution. Comorbidities, method of reconstruction, demographic data, surgical history, and other factors pertaining to mortality and morbidity were collected. The data will then be analyzed to identify population characteristics using logistic regression variables to determine univariate and adjusted multivariable measures of association with mortality. We present the pre-liminary data analyzed using chi-square and one-way anova in R. RESULTS/ANTICIPATED RESULTS: In this study we present a preliminary characterization of one institution’s sternal reconstruction patient outcomes with a variety of reconstruction methods including pectoralis advancement flaps, omental flaps and latissumus dorsi flaps. Notable preoperative comorbidities include 50% of patients > age 60, 18% with diabetes mellitus, 18 % with diagnosed hypertension, 18% with COPD, and 9% with a smoking history DISCUSSION/SIGNIFICANCE OF FINDINGS: In an evolving cardiothoracic landscape, clinical characteristics of patients being treated for sternal reconstructive surgery present a moving target. Understanding current risk factors, preoperative management and timing for aggressive surgical treatment offers an opportunity to update treatment protocol and maximize successful outcomes.
This study aimed to investigate the relationships between diet quality, the relative abundance of butyrate-producing bacteria of the gut microbiome and muscle mass, strength and function. In this cross-sectional study, n = 490 men (64.4 ± 13.5 years) from the Geelong Osteoporosis Study provided food frequency questionnaire data, from which the Australian Recommended Food Score (ARFS) and Dietary Inflammatory Index (DII) score were calculated. Muscle mass (skeletal muscle index from DXA-derived lean mass), muscle strength (handgrip strength) and muscle function (Timed Up-and-Go test) were measured. Participants provided stool samples for 16S rRNA gene sequencing. There was no evidence of associations between alpha or beta diversity and muscle health measures. A healthier ARFS score was positively associated with the relative abundance of butyrate-producing bacteria (β 0.09, 95%CI 0.03, 0.15) and a higher (pro-inflammatory) DII score was associated with lower relative abundance of butyrate-producing bacteria (β −0.60, 95%CI −1.06, −0.15). The relative abundance of butyrate-producing bacteria was positively associated with healthier muscle mass, strength and function; however, these relationships were attenuated in multivariable models. These findings support the role of diet quality in achieving a healthier gut microbiome, however, further evidence is required for a gut-muscle axis in humans.
Subglacial sediments have the potential to reveal information about the controls on glacier flow, changes in ice-sheet history and characterise life in those environments. Retrieving sediments from beneath the ice, through hot water drilled access holes at remote field locations, present many challenges. Motivated by the need to minimise weight, corer diameter and simplify assembly and operation, British Antarctic Survey, in collaboration with UWITEC, developed a simple mechanical percussion corer. At depths over 1000 m however, manual operation of the percussion hammer is compromised by the lack of clear operator feedback at the surface. To address this, we present a new auto-release-recovery percussion hammer mechanism that makes coring operations depth independent and improves hammer efficiency. Using a single rope tether for both the corer and hammer operation, this modified percussion corer is relatively simple to operate, easy to maintain, and has successfully operated at a depth of >2130 m.
To examine children’s sugar-sweetened beverage (SSB) and water intakes in relation to implemented intervention activities across the social ecological model (SEM) during a multilevel community trial.
Children’s Healthy Living was a multilevel, multicomponent community trial that reduced young child obesity (2013–2015). Baseline and 24-month cross-sectional data were analysed from nine intervention arm communities. Implemented intervention activities targeting reduced SSB and increased water consumption were coded by SEM level (child, caregiver, organisation, community and policy). Child SSB and water intakes were assessed by caregiver-completed 2-day dietary records. Multilevel linear regression models examined associations of changes in beverage intakes with activity frequencies at each SEM level.
US-Affiliated Pacific region.
Children aged 2–8 years (baseline: n 1343; 24 months: n 1158).
On average (± sd), communities implemented 74 ± 39 SSB and 72 ± 40 water activities. More than 90 % of activities targeted both beverages together. Community-level activities (e.g. social marketing campaign) were most common (61 % of total activities), and child-level activities (e.g. sugar counting game) were least common (4 %). SSB activities across SEM levels were not associated with SSB intake changes. Additional community-level water activities were associated with increased water intake (0·62 ml/d/activity; 95 % CI: 0·09, 1·15) and water-for-SSB substitution (operationalised as SSB minus water: –0·88 ml/d/activity; 95 % CI: –1·72, –0·03). Activities implemented at the organization level (e.g. strengthening preschool wellness guidelines) and policy level (e.g. SSB tax advocacy) also suggested greater water-for-SSB substitution (P < 0·10).
Community-level intervention activities were associated with increased water intake, alone and relative to SSB intake, among young children in the Pacific region.
Originally developed by applying models from cognitive psychology to the study of foreign policy decision making, the field of behavioral IR is undergoing important transformations. Building on a broader range of models, methods, and data from the fields of neuroscience, biology, and genetics, behavioral IR has moved beyond the staid debate between rational choice and psychology and instead investigates the plethora of mechanisms selected by evolution for solving adaptive problems. This opens new opportunities for collaboration between scholars informed by rational choice and behavioral insights. Examining the interactions between the individual's genetic inheritance, social environment, and downstream behavior of individuals and groups, the emerging field of behavioral epigenetics offers novel insights into the methodological problem of aggregation that has confounded efforts to apply behavioral findings to IR. In the first instance empirical, behavioral IR raises numerous normative and philosophical questions best answered in dialogue with political and legal theorists.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.
This chapter examines the regulatory framework governing the use of human embryos and gametes in treatment and research in the United Kingdom. This framework, overseen by the Human Fertilisation and Embryology Authority (HFEA), permits the use of germline genome modification in human embryos for specific research purposes, but it does not currently allow such modified embryos to be used in treatment. The chapter goes on to consider how germline genome modification may become a licensable treatment in the future, building on the recent experience of regulating research into mitochondrial donation and its clinical application in the United Kingdom. The legal and ethical challenges raised against the use of mitochondrial donation (and likely to be raised against the clinical use of germline genome modification) are also considered, including concerns arising out of EU legislation.
Light and intermittent smokers (LITS) represent almost 50% of all current smokers. Research is needed to understand smoking motives among adult light smokers.
To explore smoking cues and motivators among a racially diverse sample of adult LITS (≤10 CPD). In addition, we explored differences between native (always smoked ≤10), and converted (former heavier) LITS.
We used purposive sampling to recruit participants who were native and converted LITS and to include equal numbers of African Americans, Whites and Latinos. We coded and analyzed transcripts using a stage approach to identify themes.
Four main themes emerged that may be unique to light smokers and suggests potential strategies for intervention: (1) smoking in response to cues and control, (2) identifying as a smoker, (3) concern about health consequences, and (4) other priorities influencing smoking. There were some differences among smoking cues and motivators by race and ethnicity, and differences between native and converted LITS.
Overall, LITS reported drivers of smoking that were unrelated to symptoms of nicotine withdrawal. Even when experiencing salient cues, our LITS cohort expressed the ability to assert control over smoking by abstaining when situational contexts made smoking inconvenient.
Community advisory boards (CABs) are a valuable strategy for engaging and partnering with communities in research. Eighty-nine percent of Clinical and Translational Science Awardees (CTSA) responding to a 2011 survey reported having a CAB. CTSAs’ experiences with CABs are valuable for informing future practice. This study was conducted to describe common CAB implementation practices among CTSAs; document perceived benefits, challenges, and contributions; and examine their progress toward desirable outcomes. A cross-CTSA collaborative team collected survey data from respondents representing academic and/or community members affiliated with CTSAs with CABs. Data representing 44 CTSAs with CABs were analyzed using descriptive statistics. A majority of respondents reported practices reflecting respect for CAB members’ expertise and input such as compensation (75%), advisory purview beyond their CTSA’s Community Engagement program (88%), and influence over CAB operations. Three-quarters provide members with orientation and training on roles and responsibilities and 89% reported evaluating their CAB. Almost all respondents indicated their CTSA incorporates the feedback of their CABs to some degree; over half do so a lot or completely. This study profiles practices that inform CTSAs implementing a CAB and provide an evaluative benchmark for those with existing CABs.
On the threshold of our modernity, on 29 March 1901, Lionel Mapleson made two artful cylinder phonautogramsof the air. It was no ordinary air. His wax tracings captured for posterity the legendary vocal tones of the fifty-year-old Jean de Reszke and the chorus of the old Metropolitan Opera House in Richard Wagner’s Lohengrin. The atmosphere was thick with anticipation for this final gala performance of the first twentieth-century season, an event that had been offered as an extra night to subscribers, and the last time that Reszke would appear in New York in a complete opera. The newspapers reported a crush as never before in the lobby and outside on the street for ‘the strongest cast which can be brought together’, including Jean’s younger brother Édouard, David Bispham, Adolph Mühlmann, soprano Milka Ternina and Bohemian–German contralto Ernestine Schumann-Heink.
Withdrawal reactions when coming off antidepressants have long been neglected or minimised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs) entered the market for the first systematic review to be published. More reviews have followed, demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the sparse but growing evidence base. What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe. These findings are now increasingly acknowledged by official professional bodies and societies.
Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, and modulate the host immune system, which may aid worm infection establishment, maintenance and survival in the host. Here we have identified and characterized a σ class glycosylated GST (OoGST1), from the cattle-infective filarial nematode Onchocerca ochengi, which is homologous (99% amino acid identity) with an immunodominant GST and potential vaccine candidate from the human parasite, O. volvulus, (OvGST1b). Onchocerca ochengi native GSTs were purified using a two-step affinity chromatography approach, resolved by 2D and 1D SDS-PAGE and subjected to enzymic deglycosylation revealing the existence of at least four glycoforms. A combination of lectin-blotting and mass spectrometry (MS) analyses of the released N-glycans indicated that OoGST1 contained mainly oligomannose Man5GlcNAc2 structure, but also hybrid- and larger oligommanose-type glycans in a lower proportion. Furthermore, purified OoGST1 showed prostaglandin synthase activity as confirmed by Liquid Chromatography (LC)/MS following a coupled-enzyme assay. This is only the second reported and characterized glycosylated GST and our study highlights its potential role in host-parasite interactions and use in the study of human onchocerciasis.
Excavations by Chichester and District Archaeology Society on the site of a Roman villa at Warblington, near Emsworth, Hampshire, revealed a small stone cist containing two lead packages. While interpretation as a burial is explored, it appears more likely that the cist and its contents represent a ritual deposit within a domestic structure.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.