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Protons from the Los Alamos Neutron Science Center have been used for pulsed radiography in dynamic experiments for the past 25 years. Pulses of protons are imaged on a scintillator, and the light from these images is captured by fast gated cameras. The need for fast, bright scintillators has led to some compromises in image quality due to tiling the scintillators and backgrounds with totally internally reflected light. We show how large-grain scintillator screens, made using a thin plastic binder, solve these problems.
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Conventional continuum solvation models are ubiquitous in computational catalysis, including for describing metal/water interfaces, which are relevant to both solution-phase heterogeneous catalysis and electrocatalysis. Nonetheless, we find that such continuum models qualitatively fail to describe both the adsorption free energy and conformational preference for many organic molecules at such interfaces, largely due to the failure of continuum models to incorporate the role of competitive water adsorption. We develop a simple phenomenological model that accounts for competitive water adsorption and show that the model, when used in conjunction with continuum solvation, provides a dramatic improvement in the description of both adsorption and conformational preference. The model is also extended to additionally incorporate the influence of applied potential at the electrode surface, thus facilitating computationally efficient applications to scenarios including electrocatalysis.
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Epitaxial crystallization of complex oxides provides the means to create materials with precisely selected composition, strain, and orientation, thereby controlling their functionalities. Extending this control to nanoscale three-dimensional geometries can be accomplished via a three-dimensional analog of oxide solid-phase epitaxy, lateral epitaxial crystallization. The orientation of crystals within laterally crystallized SrTiO3 systematically changes from the orientation of the SrTiO3 substrate. This evolution occurs as a function of lateral crystallization distance, with a rate of approximately 50° µm-1. The mechanism of the rotation is consistent with a steady-state stress of tens of megapascal over a 100-nanometer scale region near the moving amorphous/crystalline interface arising from the amorphous-crystalline density difference. Second harmonic generation and piezoelectric force microscopy reveal that the laterally crystallized SrTiO3 is noncentrosymmetric and develops a switchable piezoelectric response at room temperature, illustrating the potential to use lateral crystallization to control the functionality of complex oxides.
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Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.
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Anticoagulantes , Neoplasias , Recidiva , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/tratamento farmacológico , Neoplasias/complicações , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , França/epidemiologiaRESUMO
Electrosynthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction (2e- ORR) is promising for various practical applications, such as wastewater treatment. However, few electrocatalysts are active and selective for 2e- ORR yet are also resistant to catalyst leaching under realistic operating conditions. Here, a joint experimental and computational study reveals active and stable 2e- ORR catalysis in neutral media over layered PdSe2 with a unique pentagonal puckered ring structure type. Computations predict active and selective 2e- ORR on the basal plane and edge of PdSe2, but with distinct kinetic behaviors. Electrochemical measurements of hydrothermally synthesized PdSe2 nanoplates show a higher 2e- ORR activity than other Pd-Se compounds (Pd4Se and Pd17Se15). PdSe2 on a gas diffusion electrode can rapidly accumulate H2O2 in buffered neutral solution under a high current density. The electrochemical stability of PdSe2 is further confirmed by long device operational stability, elemental analysis of the catalyst and electrolyte, and synchrotron X-ray absorption spectroscopy. This work establishes a new efficient and stable 2e- ORR catalyst at practical current densities and opens catalyst designs utilizing the unique layered pentagonal structure motif.
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The hydrogenolysis or hydrodeoxygenation of a carbonyl group, where the CâO group is converted to a CH2 group, is of significant interest in a variety of fields. A challenge in electrochemically achieving hydrogenolysis of a carbonyl group with high selectivity is that electrochemical hydrogenation of a carbonyl group, which converts the CâO group to an alcohol group (CH-OH), is demonstrated not to be the initial step of hydrogenolysis. Instead, hydrogenation and hydrogenolysis occur in parallel, and they are competing reactions. This means that although both hydrogenolysis and hydrogenation require adding H atoms to the carbonyl group, they involve different intermediates formed on the electrode surface. Thus, revealing the difference in intermediates, transition states, and kinetic barriers for hydrogenolysis and hydrogenation pathways is the key to understanding and controlling hydrogenolysis/hydrogenation selectivity of carbonyl compounds. In this study, we aimed to identify features of reactant molecules that can affect their hydrogenolysis/hydrogenation selectivity on a Zn electrode that was previously shown to promote hydrogenolysis over hydrogenation. In particular, we examined the electrochemical reduction of para-substituted benzaldehyde compounds with substituent groups having different electron donating/withdrawing abilities. Our results show a strikingly systematic impact of the substituent group where a stronger electron-donating group promotes hydrogenolysis and a stronger electron-withdrawing group promotes hydrogenation. These experimental results are presented with computational results explaining the substituent effects on the thermodynamics and kinetics of electrochemical hydrogenolysis and hydrogenation pathways, which also provide critically needed information and insights into the transition states involved with these pathways.
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We report a deep learning-based approach to accurately predict the emission spectra of phosphorescent heteroleptic [Ir( C ⧠N ${{\rm{C}}^\wedge {\rm{N}}}$ )2( N ⧠N ${{\rm{N}}^\wedge {\rm{N}}}$ )]+ complexes, enabling the rapid discovery of novel Ir(III) chromophores for diverse applications including organic light-emitting diodes and solar fuel cells. The deep learning models utilize graph neural networks and other chemical features in architectures that reflect the inherent structure of the heteroleptic complexes, composed of C ⧠N ${{\rm{C}}^\wedge {\rm{N}}}$ and N ⧠N ${{\rm{N}}^\wedge {\rm{N}}}$ ligands, and are thus geared towards efficient training over the dataset. By leveraging experimental emission data, our models reliably predict the full emission spectra of these complexes across various emission profiles, surpassing the accuracy of conventional DFT and correlated wavefunction methods, while simultaneously achieving robustness to the presence of imperfect (noisy, low-quality) training spectra. We showcase the potential applications for these and related models for in silico prediction of complexes with tailored emission properties, as well as in "design of experiment" contexts to reduce the synthetic burden of high-throughput screening. In the latter case, we demonstrate that the models allow us to exploit a limited amount of experimental data to explore a wide range of chemical space, thus leveraging a modest synthetic effort.
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Rivers and streams contribute to global carbon cycling by decomposing immense quantities of terrestrial plant matter. However, decomposition rates are highly variable and large-scale patterns and drivers of this process remain poorly understood. Using a cellulose-based assay to reflect the primary constituent of plant detritus, we generated a predictive model (81% variance explained) for cellulose decomposition rates across 514 globally distributed streams. A large number of variables were important for predicting decomposition, highlighting the complexity of this process at the global scale. Predicted cellulose decomposition rates, when combined with genus-level litter quality attributes, explain published leaf litter decomposition rates with high accuracy (70% variance explained). Our global map provides estimates of rates across vast understudied areas of Earth and reveals rapid decomposition across continental-scale areas dominated by human activities.
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Ciclo do Carbono , Celulose , Atividades Humanas , Plantas , Rios , Humanos , Celulose/metabolismo , Folhas de Planta/metabolismo , Plantas/metabolismo , Rios/químicaRESUMO
BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.
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Ciclofosfamida , Hemofilia A , Rituximab , Humanos , Rituximab/uso terapêutico , Hemofilia A/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Imunossupressores/uso terapêutico , Adulto , Fator VIII/uso terapêutico , Fator VIII/imunologia , Idoso de 80 Anos ou maisRESUMO
We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.
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GOAL: Rising incidents of violence and mistreatment of healthcare workers by patients and visitors have been reported. U.S. healthcare workers are five times more likely to experience nonfatal workplace violence (WPV) than workers in any other profession. However, less is known about the national trends in the incidence of violence and mistreatment in healthcare. The specific organizational and individual-level factors that relate to stress arising from these occurrences specifically by patients and family members are also not fully understood. The goals of this study were to examine national trends of violence toward healthcare workers, understand which populations are most vulnerable to stress from violence and mistreatment, and explore organizational factors that are related to these occurrences. METHODS: Data were collected from three sources: (1) The Bureau of Labor Statistics Intentional Injury by Another Person data for the period 2011-2020, (2) data from a large national workers' compensation claim services provider for the period 2018-2022, and (3) results from a survey distributed at a large medical center in June and July 2022. Data were represented graphically and analyzed using multivariate regression and dominance analysis to identify specific predictors of WPV and mistreatment among healthcare workers. PRINCIPAL FINDINGS: Of the total surveyed sample, 23.7% of participants reported mistreatment from patients or visitors as a major stressor and 14.6% reported WPV from patients or visitors as a major stressor. Stress from mistreatment and WPV was most frequently reported by nurses, employees aged 18 to 24 years other than nurses, those who identified as White, and those who identified as female or a gender minority. The emergency room (ER) showed the highest percentages of stress from mistreatment (61.8%) and violence (55.9%) from patients or visitors. The top predictors of stress from WPV and mistreatment by patients or visitors among healthcare workers ranked high to low were working in the ER, working as a nurse, a lack of necessary supplies or equipment, patient or visitor attitudes or beliefs about COVID-19, and working in a hospital-based unit. PRACTICAL APPLICATIONS: In addition to protecting employees as a moral imperative, preventing WPV is critical for organizational performance. Employee productivity is estimated to decrease up to 50% in the 6 to 18 weeks following an incident of violence, while turnover can increase 30% to 40%. An effective WPV prevention plan and a proactive approach to supporting the physical and mental health conditions that may result from WPV can mitigate the potential costs and exposures from these incidents. Organizations must also set clear expectations of behavior with patients and visitors by refusing to tolerate violence and mistreatment of caregivers. The impact of WPV can remain present and active for up to 8 years following an incident. Policy-level interventions are also needed. Currently, there are no federal protections for healthcare workers related to violence, though some states have made it a felony to abuse healthcare workers.
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Pessoal de Saúde , Violência no Trabalho , Humanos , Feminino , Violência no Trabalho/psicologia , Pacientes , Hospitais , Serviço Hospitalar de Emergência , Inquéritos e Questionários , Local de Trabalho/psicologiaRESUMO
AIM: This systematic review and network meta-analysis (NMA) aimed to establish a clinically relevant hierarchy of the different adhesive and/or restorative approaches to restore cavitated root caries lesions through the synthesis of available evidence. MATERIALS AND METHODS: A systematic search was conducted in Medline/Web of Science/Embase/ Cochrane Library/Scopus/grey literature. RCTs investigating ≥2 restorative strategies (restorative /adhesive materials) for root caries lesions in adult patients were included. Risk of bias within studies was assessed (Cochrane_RoB-2) and the primary outcome was survival rate of restorations at different follow-up times (6-/12-/24-months). Network meta-analyses were conducted using a random effects model stratified by follow-up times. I2-statistics assessed the ratio of true to total variance in the observed effects. All available combinations of adhesives (1-SE: one-step self-etch; 2-3ER: two-/three-step etch-and-rinse) and restorative materials (conventional composite (CC) as well as conventional and resin-modified glass ionomer cements (GIC, RMGIC)) were included. Risk of bias across studies and confidence in NMA (CINeMA) were assessed. RESULTS: 547 studies were identified and nine were eligible for the NMA. In total, 1263 root caries lesions have been restored in 473 patients in the included clinical trials. Patients involved were either healthy (n = 6 trials), living in nursing homes (n = 1 trial) or received head-and-neck radiotherapy (n = 2 trials). There was statistically weak evidence to favour either of material/material combination regarding the survival rate. A tendency for higher survival rate (24-months) was observed for 2-3ER/CC (OR24mths 2.65; 95%CI=1.45/4.84) as well as RMGIC (OR24mths 2.05; 95%CI=1.17/3.61) compared to GIC. These findings were though not statistically significant and confidence of the NMA was low. CONCLUSION: An evidence-based choice of restorative strategy for managing cavitated root caries lesions is currently impossible. There is a clear need for more standardised, well-designed RCTs evaluating the retention rate of root caries restoration approaches.
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Cárie Dentária , Cárie Radicular , Adulto , Humanos , Cárie Radicular/tratamento farmacológico , Cimentos Dentários/uso terapêutico , Metanálise em Rede , Restauração Dentária Permanente , Materiais Dentários , Cárie Dentária/tratamento farmacológico , Cimentos de Ionômeros de Vidro/uso terapêutico , Resinas Compostas/uso terapêuticoRESUMO
Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A or the lipid transfer protein ATG2 leads to the accumulation of phosphorylated p62 aggregates in the context of basal autophagy. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Lastly, we present evidence that poly-ubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.
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INTRODUCTION: PET/CT is regularly used to investigate inflammatory syndrome of unknown origin (IUO), but hypermetabolisms found are not always consistent with the final diagnosis. The objective of the study was to assess the cost attributed to the diagnostic work-up for these false positives. MATERIALS AND METHODS: We conducted an ancillary study on a previous retrospective cohort from the internal medicine department at Amiens university hospital in patients who had a PET/CT scan between October 2004 and April 2017. Patients were included if PET/CT had been prescribed to investigate IUO. Among the 763 PET/CT performed, 144 met the inclusion criteria and a false-positive rate of 17.4% (n=25) was reported. RESULTS: Among these 25 patients, 21 underwent further investigations. The most frequently found hypermetabolic territories were digestive (n=12, mean SUVmax 8 [±4.33]) and osteoarticular (n=11, mean SUVmax 4.33 [±1.15]). The total cost of the 13 prescribed consultations was 390, the total cost of the 40 additional tests was 4,476 (mainly digestive endoscopies and radiological tests) and the total cost of medical transport was 572. The total cost of the 35 days of hospitalization specifically required to investigate these false positives was 22,952. In 23.8% (n=5), these investigations led to the incidental discovery of tumor lesions. CONCLUSION: The economic impact of false-positive PET/CT results does not appear to be negligible and merits a genuine prospective medico-economic study.
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Reductive upgrading of 5-hydroxymethylfurfural (HMF), a biomass-derived platform molecule, to 2,5-dimethylfuran (DMF), a biofuel with an energy density 40% greater than that of ethanol, involves hydrogenolysis of both the aldehyde (CâO) and the alcohol (C-OH) groups of HMF. It is known that when hydrogenation of the aldehyde occurs to form 2,5-bis(hydroxymethyl)furan (BHMF), BHMF cannot be further reduced to DMF. Thus, aldehyde hydrogenation must be suppressed to increase the selectivity for DMF production. Previously, it was shown that on a Cu electrode hydrogenolysis occurs mainly through proton-coupled electron transfer (PCET), where a proton from the solution and an electron from the electrode are transferred to the organic species. In contrast, hydrogenation occurs not only through PCET but also through hydrogen atom transfer (HAT), where a surface-adsorbed hydrogen atom (H*) is transferred to the organic species. This study shows that halide adsorption on Cu can effectively suppress HAT by decreasing the steady-state H* coverage on Cu during HMF reduction. As HAT enables only aldehyde hydrogenation, a striking suppression of BHMF is observed, thereby enhancing DMF production. We discuss how the identity and concentration of the halide, along with the reduction conditions (i.e., potential and pH), affect halide adsorption on Cu and identify when optimal halide coverages are achieved to maximize DMF selectivity. Our experimental results are presented alongside computational results that elucidate how halide adsorption affects the adsorption energy of hydrogen and the steady-state H* coverage on Cu, which provide an atomic-level understanding of all experimentally observed effects.
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Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases.