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The reaction of a Ni 0.9 Pt 0.1 7 nm-thick thin film with the underlying Si(001) substrate as a function of the annealing temperature was studied using in situ XRD techniques as well as ex situ advanced XRD and TEM imaging on quenched samples. It was found that the Ni 0.9 Pt 0.1 /Si system initially evolves accordingly to diffusion controlled reactions via the development of nano-crystalline Ni-rich Ni 1 − x (Pt) Si x phases that combine the ability of fast kinetic growth and texture inheritance. The system remains then stable over some tens of degrees before Ni(Pt)Si nucleation occurs, once the related energetic barrier is overcome. It was additionally found that this newly observed phase sequence remains valid up to Ni 0.9 Pt 0.1 deposited layer thicknesses of about 16 nm, which is remarkable for such systems. [ABSTRACT FROM AUTHOR]

Abstract Metastatic urothelial carcinoma (mUC) is a lethal cancer, with limited therapeutic options. Large-scale studies in early settings provided critical insights into the genomic and transcriptomic characteristics of non-metastatic UC. The genomic landscape of mUC remains however unclear. Using Whole Exome (WES) and mRNA sequencing (RNA-seq) performed on metastatic biopsies from 111 patients, we show that driver genomic alterations from mUC were comparable to primary UC (TCGA data). APOBEC, platin, and HRD mutational signatures are the most prevalent in mUC, identified in 56%, 14%, and 9% of mUC samples, respectively. Molecular subtyping using consensus transcriptomic classification in mUC shows enrichment in neuroendocrine subtype. Paired samples analysis reveals subtype heterogeneity and temporal evolution. We identify potential therapeutic targets in 73% of mUC patients, of which FGFR3 (26%), ERBB2 (7%), TSC1 (7%), and PIK3CA (13%) are the most common. NECTIN4 and TACSTD2 are highly expressed regardless of molecular subtypes, FGFR3 alterations and sites of metastases.

The formation of Ti based contacts in new image sensor complementary metal–oxide–semiconductor technologies is limited by the requirement of a low thermal budget. The objectives of these new 3D-technologies are to promote ohmic, low resistance, repeatable, and reliable contacts by keeping the process temperature as low as possible. In this work, ultraviolet-nanosecond laser annealing was performed before classical rapid thermal annealing (RTA) to promote the formation at lower RTA temperatures of the low resistivity C54-TiSi2 phase. The laser energy density was varied from 0.30 to 1.00 J/cm² with three pulses in order to form the C40-TiSi2 phase and finally to obtain the C54-TiSi2 phase by a subsequent RTA at low temperatures. The formed Ti-silicides were characterized by four-point probe measurements, x-ray diffraction, transmission electron microscopy, and atom probe tomography. A threshold in the laser energy density for the formation of the C40-TiSi2 is observed at an energy density of 0.85 J/cm² for the targeted TiN/Ti stack on blanket wafers. The C40-TiSi2 formation by laser annealing prior to RTA enables to reduce the formation temperature of the C54-TiSi2 phase by 150 °C in comparison to a single RTA applied after the Ti/TiN deposition. This specific phase sequence is only observed for a laser energy density close to 0.85 J/cm². At higher energy densities, the presence of C49-TiSi2 or a mixture of C49-TiSi2 and C54-TiSi2 is observed. The underlying mechanisms of the phase sequence and formation are discussed in detail. [ABSTRACT FROM AUTHOR]

Abstract In a four-dimensional quantum field theory that flows between two fixed points under the renormalization group, the change in the conformal anomaly ∆a has been related to the average null energy. We extend this result to derive a sum rule for the other anomaly coefficient, ∆c, in terms of the stress tensor three-point function. While the sum rule for ∆a is an expectation value of the averaged null energy operator, and therefore positive, the result for ∆c involves the off-diagonal matrix elements, so it does not have a fixed sign.

Abstract Background Practice-based research is one of the levers identified by the World Health Organization (WHO) to strengthen primary health care. The scaling of health and social care innovations has the potential to reduce inequities in health and to expand the benefits of effective innovations. It is now rapidly gaining the attention of decision-makers in health and social care, particularly in high-income countries. To meet the challenge of declining numbers of primary care physicians in France, Multi-professional Healthcare Centers (MHC) were created to bring together medical and paramedical professionals. They are a source of innovation in meeting the health challenges facing our populations. Specific methodology exists to identify health innovations and assess their scalability. A working group, including end-users and specialists, has adapted this methodology to the French context and the University department of general practice of Montpellier-Nîmes (France) launched a pilot study in Occitanie, a French region. Objective To identify and evaluate the scalability of innovations produced in pluri-professional healthcare centers in the Occitanie region. Methods A pilot, observational, cross-sectional study was carried out. The SPRINT Occitanie study was based on a questionnaire with two sections: MHC information and the modified Innovation Scalability Self-Administered Questionnaire (ISSaQ), version 2020. The study population was all 279 MHC in the Occitanie region. Results 19.3% (54) of MHC in the Occitanie region, responded fully or incompletely to the questionnaire. Four out of 5 U-MHCs were represented. Five MHC presented multiple innovations. The average per MHC was 1.94 (± 2.4) innovations. 26% of them (n = 9) had high scalability, 34% (n = 12) medium scalability and 40% (n = 14) low scalability. The main innovation represented (86%) were healthcare program, service, and tool. Conclusions In our cross-sectional study, a quarter of the innovations were highly scalable. We were able to demonstrate the importance of MHC teams in working on primary care research through the prism of innovations. Primary-care innovations must be detected, evaluated, and extracted to improve their impact on their healthcare system.

Abstract Introduction Long-term oxygen therapy (LTOT) is reported to improve survival in patients with chronic respiratory failure. We aimed to describe effectiveness, burden, and cost of illness of patients treated with portable oxygen concentrators (POC) compared to other LTOT options. Methods This retrospective comparative analysis included adult patients with chronic respiratory insufficiency and failure (CRF) upon a first delivery of LTOT between 2014 and 2019 and followed until December 2020, based on the French national healthcare database SNDS. Patients using POC, alone or in combination, were compared with patients using stationary concentrators alone (aSC), or compressed tanks (CTC) or liquid oxygen (LO2), matched on the basis of age, gender, comorbidities, and stationary concentrator use. Results Among 244,719 LTOT patients (mean age 75 ± 12, 48% women) included, 38% used aSC, 46% mobile oxygen in the form of LO2 (29%) and POC (18%), whereas 9% used CTC. The risk of death over the 72-month follow-up was estimated to be 13%, 15%, and 12% lower for patients in the POC group compared to aSC, CTC, and LO2, respectively. In the POC group yearly mean total costs per patient were 5% higher and 4% lower compared to aSC and CTC groups, respectively, and comparable in the LO2 group. The incremental cost-effectiveness ratio (ICER) of POC was €8895, €6288, and €13,152 per year of life gained compared to aSC, CTC, and LO2, respectively. Conclusion Within the POC group, we detected an association between higher mobility (POCs autonomy higher than 5 h), improved survival, lower costs, and ICER − €6 238, compared to lower mobility POCs users.

Abstract Background The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities. Results Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements. Conclusion The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.

Summary: Background: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. Methods: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. Findings: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8–5.1) per 100 person-years to 103.9 (95% CI 103.2–104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3–1.9) to 14.3 (95% CI 14.1–14.6)), abdominal pain (from 0.3 (95% CI 0.1–0.5) to 9.9 (95% CI 9.7–10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4–0.9) to 13.3 (95% CI 13.1–13.6)), cough (from 0.3 (95% CI 0.2–0.5) to 9.1 (95% CI 8.9–9.3)), and anxiety (from 0.8 (95% CI 0.6–1.2) to 11.4 (95% CI 11.2–11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008–0.2) to 1.7 (95% CI 1.6–1.8)), pins and needles (from 0.05 (95% CI 0.03–0.0.9) to 1.5 (95% CI 1.4–1.6)), memory issues (from 0.03 (95% CI 0.02–0.06) to 0.8 (95% CI 0.7–0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004–0.01) to 0.6 (95% CI 0.4–0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03–0.04) to 0.7 (95% CI 0.6–0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1–2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7–3.9); anxiety, 2.3 (1.4–3.8); allergy, 2.1 (1.7–2.8) and sleep disorders, 2.1 (1.5–2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3–2.8). Interpretation: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. Funding: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

Rational Studies are needed to determine if multimorbidity screening and management reduce the rate of multimorbidity accumulation in patients with chronic inflammatory rheumatic diseases (IRD).Objectives This study evaluates the impact of systematic screening programme on patient care and hospitalisation rates.Methods Patients with IRD who participated in the screening programme (exposed patients) were identified within the French national health database and matched with controls. Two sets of analysis were performed: one with multivariate analysis and a second using a propensity score matching to ensure comparability between exposed patients and controls. The primary endpoint (PE) was a composite score assessing the dispensation of multimorbidity-preventing drugs, including vaccines, lipid-lowering agents, antiosteoporotic medications and antiplatelet drugs, during the year following the index date.Results The first analysis included 286 exposed patients and 858 controls, demonstrating a higher rate of meeting the PE in exposed patients (adjusted OR=1.6 (1.2–2.2), p

Abstract Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of male and female mice treated with or without an estrogen agonist by integrating liver multi-omics data. We found that selective ER activation recovers HFD-induced molecular and physiological liver phenotypes. HFD and systemic ER activation altered core liver pathways, beyond lipid metabolism, that are consistent between mice and primates. By including patient cohort data, we uncovered that ER-regulated enhancers govern central regulatory and metabolic genes with clinical significance in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, including the transcription factor TEAD1. TEAD1 expression increased in MASLD patients, and its downregulation by short interfering RNA reduced intracellular lipid content. Subsequent TEAD small molecule inhibition improved steatosis in primary human hepatocyte spheroids by suppressing lipogenic pathways. Thus, TEAD1 emerged as a new therapeutic candidate whose inhibition ameliorates hepatic steatosis.