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Abstract Background Anti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC. Methods We retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI. Results The DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI. Conclusion The 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted.

Background People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons. Aims To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services. Method This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001–2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database – Cymru with primary and secondary healthcare records. We present results of conditional logistic regression. Results We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1–2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4–1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6–0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2–0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5–4.5) v. 2.6 (95% CI 2.1–3.1)). Conclusions We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.

Objective In many countries, before COVID-19 vaccines became available, reluctance to get vaccinated was particularly prevalent among women, the most disadvantaged social groups and ethnoracial minorities, known to be at higher risk for the virus. Using a longitudinal perspective, we analyse the social determinants that are associated with the transition from attitudes towards vaccination to actual vaccination practices.Design Representative population-based prospective cohort.Settings From November 2020 to July 2021.Participants Adults included in the Epidemiology and Living Conditions (EpiCoV) cohort (n=86 701).Main outcome measures Attitudes towards vaccination in November 2020 before COVID-19 vaccines were available in France (in January 2021) and vaccination practices in July 2021.Results Among those who were initially reluctant in November 2020, the youngest, the poorest 10% (OR=0.68, 0.59–0.77), non-European immigrants (OR=0.72, 0.59–0.88) and descendants of non-European immigrants (OR=0.72, 0.61–0.86) were less likely to be vaccinated in July 2021, irrespective of trust in government and scientists. The same social factors were associated with non-vaccination among those who initially were undecided or who favoured vaccination.Conclusion Despite the fact that COVID-19 vaccines were relatively available and free of charge in France in July 2021, social inequalities in vaccination against the virus remained the same than those observed in vaccination reluctance in November 2020, before vaccines were available. While adjusting for trust, migration background, younger age and lower income were associated with lower vaccination uptake irrespective of initial intention. By neglecting to genuinely target specific groups that were initially reluctant to be vaccinated, vaccination policies contributed to strengthening pre-existing social inequalities around COVID-19 burden.

Long-term climate change and periodic environmental extremes threaten food and fuel security1 and global crop productivity2-4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6-knowledge that has been limited to a small number of well-studied model systems. Here we present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum). Analysis of biomass and survival among 732 resequenced genotypes, which were grown across 10 common gardens that span 1,800 km of latitude, jointly revealed extensive genomic evidence of climate adaptation. Climate-gene-biomass associations were abundant but varied considerably among deeply diverged gene pools. Furthermore, we found that gene flow accelerated climate adaptation during the postglacial colonization of northern habitats through introgression of alleles from a pre-adapted northern gene pool. The polyploid nature of switchgrass also enhanced adaptive potential through the fractionation of gene function, as there was an increased level of heritable genetic diversity on the nondominant subgenome. In addition to investigating patterns of climate adaptation, the genome resources and gene-trait associations developed here provide breeders with the necessary tools to increase switchgrass yield for the sustainable production of bioenergy.

Abstract Background CIC‐rearranged sarcomas (CIC‐RS) represent the most frequent subset of “Ewing‐like” undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC‐RS included in the French NETSARC+ database. Methods Pediatric and adult patients from 13 French centers with a diagnosis of CIC‐RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC‐RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high‐grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan–Meier method and the log‐rank test was used to compare survival. Results Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2–87). With a median follow‐up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission. Conclusion FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen.

Which communication channels should be prioritized to make populations aware of local volcanic risks? In the internet age, is it still necessary to privilege the classic channels (radio, television, posters), or are the new communication channels (websites, social media) sufficient? Using an interview-based survey of a population in Peru (n = 76) who have been the object of several volcanic risk communication campaigns using posters, websites, social media and traditional media, we compare the recall (memorization) and perception of these previous campaigns. Two main empirical results emerge from the interviews: 1) Web- sites are proving to be particularly effective communication channels in this context, in stark contrast to the low impact of the printed press; 2) We find that the the same communication campaigns are perceived differently by residents depending on the neighborhood in which they live. This second empirical result advocates for a much more territory-based and localized strategy, where the district by district socio-cultural and geological environment form the foundations for communication strategies.

Future long-duration human spaceflights require developments to limit biocontamination of surface habitats. The three MATISS (Microbial Aerosol Tethering on Innovative Surfaces in the International Space Station) campaigns exposed surface treatments over several months in the ISS. To this end, eight sample holders designed were mounted with lamella-bearing FDTS ((1H, 1H, 2H, 2H)-perfluorodecyltrichlorosilane), SiOCH, and parylene hydrophobic coatings, at two different locations, for several months, during three distinct periods from 2016 to 2020. Tile scanning optical microscopy (×3 and ×30 magnifications) detected several thousand particles, indicating a relatively clean environment (a few particles per mm2). In previous studies, exposure rates were analyzed for all the coarse and fine particles detected on the largest total area of the integrated FDTS area exposed in the ISS (several cm2). Here, the contamination rates observed for a smaller constant area unit (the 0.66-cm2 window area of the holder) were statistically analyzed. Therefore, a statistical difference in rate distributions between RGSH (Return Grid Sensor House) and EDR (European Drawer Rack) and between FDTS and either SiOCH or parylene was shown for the coarse particles but not for the fine particles. The contamination rates were found to be low, confirming the efficiency of the long-term air purification system. The rates tend to vary with the astronaut occupancy rates. Surfaces of spacecraft for long-duration exploration left unmanned during dormancy periods can be considered safe from biocontamination.

Local adaptation is the process by which natural selection drives adaptive phenotypic divergence across environmental gradients. Theory suggests that local adaptation results from genetic trade-offs at individual genetic loci, where adaptation to one set of environmental conditions results in a cost to fitness in alternative environments. However, the degree to which there are costs associated with local adaptation is poorly understood because most of these experiments rely on two-site reciprocal transplant experiments. Here, we quantify the benefits and costs of locally adaptive loci across 17° of latitude in a four-grandparent outbred mapping population in outcrossing switchgrass (Panicum virgatum L.), an emerging biofuel crop and dominant tallgrass species. We conducted quantitative trait locus (QTL) mapping across 10 sites, ranging from Texas to South Dakota. This analysis revealed that beneficial biomass (fitness) QTL generally incur minimal costs when transplanted to other field sites distributed over a large climatic gradient over the 2 y of our study. Therefore, locally advantageous alleles could potentially be combined across multiple loci through breeding to create high-yielding regionally adapted cultivars.

Abstract Background Improving eHealth literacy (eHL) is one of the biggest challenges currently facing the global healthcare community. Indeed the use of digital services has the potential to engage patients in care as well as improve the effectiveness of chronic disease self-management, it remains highly dependent on a patient’s specific skills and experiences in the health care systems. Although eHealth literacy has gained momentum in the past decade, it remains an underresearched area, particularly eHealth literacy measurement. The aim of the review is to identify patient-reported outcome measures (PROMs) of eHealth literacy for adult populations and to summarize the evidence on their psychometric properties. Methods We will conduct a systematic literature review of the tools used to measure eHealth literacy for adult population. The search strategy aims to find published studies. A three-step search strategy will be used in this review. Published studies will be searched in CINAHL, PubMed, PsycINFO, and Web of Science from inception until end. Grey literature will be searched to find theses. Database search strategies will be formulated and tested with the assistance of an expert Health Sciences Librarian. The selection of studies will be done by two independent reviewers. Disagreements will be resolved through consensus, and a third reviewer will solve discrepancies. Furthermore, two reviewers will independently evaluate the methodological rigor of the instruments development and testing and assign a grade using the standardized Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. Disagreements will be discussed with a third reviewer, expert in psychometrics. Extracted data will be aggregated and analyzed to produce a set of synthesized findings that will be used to develop evidence-informed recommendations in regard of eHL instruments. We will present a synthesis of all instruments, their psychometric properties, and make recommendations for eHL instrument selection in practice. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and a PRISMA flow diagram. Discussion This systematic review will summarize the evidence on the psychometric properties of PROMs instruments used to measure eHL and will help clinicians, managers, and policy-makers to select an appropriate instrument. Systematic review registration PROSPERO CRD42021232765

BackgroundThe development of telehealth and telemedicine, in the form of increased teleconsultation and medical telemonitoring, accelerated during the COVID-19 health crisis in France to ensure continued access to care for the population. Since these new information and communication technologies (ICTs) are diverse and likely to transform how the health care system is organized, there is a need better to understand public attitudes toward them and their relationship with peoples’ current experience of health care. ObjectiveThis study aimed to determine the French general population’s perception of the usefulness of video recording/broadcasting (VRB) and mobile Health (mHealth) apps for medical consultations in France during the COVID-19 health crisis and the factors associated with this perception. MethodsData were collected for 2003 people in 2 waves of an online survey alongside the Health Literacy Survey 2019 (1003 in May 2020 and 1000 in January 2021) based on quota sampling. The survey collected sociodemographic characteristics, health literacy levels, trust in political representatives, and perceived health status. The perceived usefulness of VRB in medical consultations was measured by combining 2 responses concerning this technology for consultations. The perceived usefulness of mHealth apps was measured by combining 2 responses concerning their usefulness for booking doctor appointments and for communicating patient-reported outcomes to doctors. ResultsThe majority (1239/2003, 62%) of respondents considered the use of mHealth apps useful, while only 27.6% (551/2003) declared VRB useful. The factors associated with the perceived usefulness of both technologies were younger age (≤ 55 years), trust in political representatives (VRB: adjusted odds ratio [aOR] 1.68, 95% CI 1.31-2.17; mHealth apps: aOR 1.88, 95% CI 1.42-2.48), and higher (sufficient and excellent) health literacy. The period of the beginning of the COVID-19 epidemic, living in an urban area, and being limited in daily activities were also associated with perceiving VRB positively. The perceived usefulness of mHealth apps increased with the level of education. It was also higher in people who had 3 or more consultations with a medical specialist. ConclusionsThere are important differences in attitudes toward new ICTs. Perceived usefulness was lower for VRB than for mHealth apps. Moreover, it decreased after the initial months of the COVID-19 pandemic. There is also the possibility of new inequalities. Hence, despite the potential benefits of VRB and mHealth apps, people with low health literacy considered them to be of little use for their health care, possibly increasing their difficulties in accessing health care in the future. As such, health care providers and policy makers need to consider those perceptions to guarantee that new ICTs are accessible and beneficial to all.

Abstract Future long-duration human spaceflight will require developments to limit biocontamination of surface habitats. The MATISS (Microbial Aerosol Tethering on Innovative Surfaces in the international Space Station) experiments allowed for exposing surface treatments in the ISS (International Space Station) using a sample-holder developed to this end. Three campaigns of FDTS (perFluoroDecylTrichloroSilane) surface exposures were performed over monthly durations during distinct periods. Tile scanning optical microscopy (×3 and ×30 magnifications) showed a relatively clean environment with a few particles on the surface (0.8 to 7 particles per mm2). The varied densities and shapes in the coarse area fraction (50–1500 µm2) indicated different sources of contamination in the long term, while the bacteriomorph shapes of the fine area fraction (0.5–15 µm2) were consistent with microbial contamination. The surface contamination rates correlate to astronauts’ occupancy rates on board. Asymmetric particles density profiles formed throughout time along the air-flow. The higher density values were located near the flow entry for the coarse particles, while the opposite was the case for the fine particles, probably indicating the hydrophobic interaction of particles with the FDTS surface.