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ImportanceThe COVID-19 pandemic has affected youth mental health. Increases in site-specific eating disorder (ED) care have been documented; however, multisite studies demonstrating national trends are lacking.ObjectiveTo compare the number of adolescent/young adult patients seeking inpatient and outpatient ED care before and after onset of the COVID-19 pandemic.Design, Setting, and ParticipantsUsing an observational case series design, changes in volume in inpatient and outpatient ED-related care across 15 member sites (14 geographically diverse hospital-based adolescent medicine programs and 1 nonhospital-based ED program) of the US National Eating Disorder Quality Improvement Collaborative was examined. Sites reported monthly volumes of patients seeking inpatient and outpatient ED care between January 2018 and December 2021. Patient volumes pre- and postpandemic onset were compared separately for inpatient and outpatient settings. Demographic data such as race and ethnicity were not collected because this study used monthly summary data.ExposuresOnset of the COVID-19 pandemic.Main Outcomes and MeasuresMonthly number of patients seeking inpatient/outpatient ED-related care.ResultsAggregate total inpatient ED admissions were 81 in January 2018 and 109 in February 2020. Aggregate total new outpatient assessments were 195 in January 2018 and 254 in February 2020. Before the COVID-19 pandemic, the relative number of pooled inpatient ED admissions were increasing over time by 0.7% per month (95% CI, 0.2%-1.3%). After onset of the pandemic, there was a significant increase in admissions over time of 7.2% per month (95% CI, 4.8%-9.7%) through April 2021, then a decrease of 3.6% per month (95% CI, −6.0% to −1.1%) through December 2021. Prepandemic, pooled data showed relative outpatient ED assessment volume was stable over time, with an immediate 39.7% decline (95% CI, −50.4% to −26.7%) in April 2020. Subsequently, new assessments increased by 8.1% (95% CI, 5.3%-11.1%) per month through April 2021, then decreased by 1.5% per month (95% CI, −3.6% to 0.7%) through December 2021. The nonhospital-based ED program did not demonstrate a significant increase in the absolute number of admissions after onset of the pandemic but did see a significant increase of 8.2 (95% CI, 6.2-10.2) additional inquiries for care per month in the first year after onset of the pandemic.Conclusions and RelevanceIn this study, there was a significant COVID-19 pandemic-related increase in both inpatient and outpatient volume of patients with EDs across sites, particularly in the first year of the pandemic. Given inadequate ED care availability prior to the pandemic, the increased postpandemic demand will likely outstrip available resources. Results highlight the need to address ED workforce and program capacity issues as well as improve ED prevention strategies.

Synaptic inhibition plays a crucial role in regulating neuronal excitability, which is the foundation of nervous system function. This inhibition is largely mediated by the neurotransmitters GABA and glycine that activate Cl−-permeable ion channels, which means that the strength of inhibition depends on the Cl− gradient across the membrane. In neurons, the Cl− gradient is primarily mediated by two secondarily active cation-chloride cotransporters (CCCs), NKCC1 and KCC2. CCC-mediated regulation of the neuronal Cl− gradient is critical for healthy brain function, as dysregulation of CCCs has emerged as a key mechanism underlying neurological disorders including epilepsy, neuropathic pain, and autism spectrum disorder. This review begins with an overview of neuronal chloride transporters before explaining the dependent relationship between these CCCs, Cl− regulation, and inhibitory synaptic transmission. We then discuss the evidence for how CCCs can be regulated, including by activity and their protein interactions, which underlie inhibitory synaptic plasticity. For readers who may be interested in conducting experiments on CCCs and neuronal excitability, we have included a section on techniques for estimating and recording intracellular Cl−, including their advantages and limitations. Although the focus of this review is on neurons, we also examine how Cl− is regulated in glial cells, which in turn regulate neuronal excitability through the tight relationship between this nonneuronal cell type and synapses. Finally, we discuss the relatively extensive and growing literature on how CCC-mediated neuronal excitability contributes to neurological disorders.

Brand-name drug manufacturers can market or license authorized generics (AGs), which are the same product sold under a generic name. By contrast, independent generics (IGs) are made by other manufacturers. The brand-name manufacturer of entacapone, a treatment for Parkinson's disease, established 4 AGs before IGs emerged. We used this case study to understand how AGs can affect the length of brand-name exclusivity and robustness of generic competition.Using public Food and Drug Administration and court records, we identified the regulatory and legal history for generic entacapone products marketed through 2021. We used Medicare Part D data to estimate trends in use, prices, and spending on entacapone products from 2011 to 2020, comparing actual spending with projected spending if IG competition had begun after expiration of the key patent protecting entacapone (October 2013) and prices had fallen consistent with levels observed for other generic drugs.From 2012 to 2014, 3 potential entacapone IG manufacturers instead launched AG versions after settlement agreements with the brand-name manufacturer; the brand-name manufacturer additionally introduced its own AG. Four different IG versions were marketed beginning in 2015. From 2011 to 2020, average Medicare prices declined by 62%, less than the projected 74% to 92% price decline expected for a drug with 8 generics. Over this period, Medicare spent $1.1 billion on entacapone products, which could have been reduced by an estimated $137 to $449 million through typical IG competition.The case of entacapone demonstrates how licensing multiple AGs in place of IG competition can increase spending. Government regulators should more rigorously monitor AGs to prevent such strategies.

The Observing Air–Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air–sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our “Theory of Change” relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs’19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air–sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air–sea fluxes; and #3: improved representation of air–sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable–Accessible–Interoperable–Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.

The European Commission’s proposal to address antimicrobial resistance using transferable exclusivity vouchers (TEVs) is fundamentally flawed. European policymakers and regulators should consider alternatives, such as better funding for basic and clinical research, use of advance market commitments funded by a pay-or-play tax, or enacting an EU Fund for Antibiotic Development.

Background: Innovative shoe insoles, designed to enhance sensory information on the plantar surface of the feet, could help to improve walking in people with Multiple Sclerosis. Objective: To compare the effects of wearing textured versus smooth insoles, on measures of gait, foot sensation and patient-reported outcomes, in people with Multiple Sclerosis. Methods: A prospective, randomised controlled trial was conducted with concealed allocation, assessor blinding and intention-to-treat analysis. Thirty ambulant men and women with multiple sclerosis (MS) (Disease Steps rating 1–4) were randomly allocated to wear textured or smooth insoles for 12 weeks. Self-reported insole wear and falls diaries were completed over the intervention period. Laboratory assessments of spatiotemporal gait patterns, foot sensation and proprioception, and patient-reported outcomes, were performed at Weeks 0 (Baseline 1), 4 (Baseline 2) and 16 (Post-Intervention). The primary outcome was the size of the mediolateral base of support (stride/step width) when walking over even and uneven surfaces. Independent t-tests were performed on change from baseline (average of baseline measures) to post-intervention. Results: There were no differences in stride width between groups, when walking over the even or uneven surfaces (P ≥ 0.20) at post-intervention. There were no between-group differences for any secondary outcomes including gait (all P values > 0.23), foot sensory function (all P values ≥ 0.08) and patient-reported outcomes (all P values ≥ 0.23). Conclusions: In our small trial, prolonged wear of textured insoles did not appear to alter walking or foot sensation in people with MS who have limited foot sensory loss. Further investigation is needed to explore optimal insole design. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12615000421538).

Amidst the ongoing challenges of the COVID-19 pandemic and the collective social movements against systemic racism, an interesting opportunity presented itself for educators in family and consumer sciences (FCS). These two significant and complex scenarios have proven to be relevant avenues for understanding student experiences since the onset of the pandemic and for introducing and teaching the core concepts, integrative elements, and cross-cutting themes of the Family and Consumer Sciences Body of Knowledge (FCS-BOK). With these themes now connected to numerous societal occurrences—and with individual experiences still occurring in real-time—tying the FCS-BOK to the pandemic and social movement presents a significant opportunity for educators to gain insights into student experiences and connect them to the FCS-BOK.

Vascular patients, an inherently older, frail population, account for >80% of major lower extremity amputations (transtibial or transfemoral) in the United States. Retrospective data have shown that early physical therapy and discharge to an acute rehabilitation facility decreases the postoperative length of stay (LOS) and expedites ambulation. In the present study, we sought to determine whether patients treated with the lower extremity amputation protocol (LEAP) will have improved outcomes. We performed a nonrandomized prospective study of vascular patients undergoingan amputation from January 2019 to February 2020. Patients who were nonambulatory or had undergone a previous contralateral major amputation were excluded. LEAP is a multidisciplinary team approach to the perioperative care of amputees using an outlined protocol. The prospective patients were compared with historic controls treated before the initiation of LEAP (January 2016 to December 2018). The primary outcomes included the postoperative LOS, time to receipt of a prosthesis, and time to ambulation. Of the 141 included patients, 130 were in the retrospective group and 11 in the LEAP group. The demographics and comorbidities were similar. All 11 LEAP patients had undergone a below-the-knee amputation, with 1 requiring revision to an above-the-knee amputation. Of the 130 retrospective patients, 122 (94%) had undergone a below-the-knee amputation, with 1 requiring revision to an above-the-knee amputation. The LEAP patients were more likely to be discharged to acute rehabilitation (100% vs 27%; P&nbsp

After market exclusivity ends for biologic drugs, biosimilars-follow-on versions made by other manufacturers-can compete with lower prices. Biosimilars have modestly reduced prescription drug spending for US payers, but it is unclear whether patients have directly experienced any savings. In this study we assessed whether availability of biosimilar infliximab was associated with lower out-of-pocket (OOP) costs, using claims from a national data set of commercially insured patients from 2014 to 2018. We used two-part models, adjusting for patient demographics, clinical characteristics, insurance plan type, and calendar month. Compared with the reference biologic, there was no difference in the percentage of biosimilar claims with OOP costs (30.1% vs. 30.8%; adjusted odds ratio (aOR) 0.98, 95% confidence interval (CI), 0.84-1.15, P = 0.84) or the average nonzero OOP cost (median $378 vs. $538, adjusted mean ratio (aMR) 0.97, 95% CI, 0.80-1.18, P = 0.77). The percentage of claims with OOP costs was lower after biosimilar competition (30.7% vs. 35.0%, aOR 0.96, 95% CI, 0.94-0.99, P = 0.003), but average nonzero costs increased (median $534 vs. $520, aMR 1.04, 95% CI, 1.01-1.07, P = 0.004). Thus, early biosimilar infliximab competition did not improve affordability for patients. Policymakers need to better assure that competition in the biosimilar market translates to lower costs for patients using these medications.

We sought to characterize short- and long-term outcomes after superior cavopulmonary connection (SCPC) in children eligible for inclusion of antegrade pulmonary blood flow (APBF) in the SCPC circuit, exploring whether maintaining APBF was associated with outcomes.This was a retrospective cohort study of patients with single-ventricle heart disease and APBF who underwent SCPC at our center between January 1, 2000, and September 30, 2017. Patients were divided into 2 groups: APBF eliminated (APBF-), and APBF maintained (APBF+) at the time of SCPC.Of 149 patients, 108 (72.5%) were in APBF- and 41 (27.5%) were in APBF+. Of those in APBF+, 5 (12.2%) subsequently had APBF eliminated after SCPC. Patients in APBF+ had a higher prevalence of chest tube duration10 days and underwent more interventions during the post-SCPC hospitalization (1.9% vs 12%; P = .008 for both) but had shorter surgical support times at SCPC (P.0001). There were no differences in post-SCPC intensive care unit or hospital length of stay. During the study period, 82 patients (76%) in APBF- and 22 patients (54%) in APBF+ underwent Fontan completion. Patients in APBF+ had a greater weight gain from SCPC to Fontan (6.7 [1.8-22] kg vs 8.15 [4.4-20.6] kg; P = .012) and a shorter hospital length of stay after Fontan (9 [4-107] days vs 7.5 [4-14] days; P = .044).Short-term morbidity associated with maintaining APBF at the time of SCPC is modest, but longer term outcomes suggest potential benefits in those in whom APBF can be successfully maintained.

Background The Fontan circulation challenges the lymphatic system. Increasing production of lymphatic fluid and impeding lymphatic return, increased venous pressure may cause lymphatic dilatation and decrease lymphatic contractility. In-vitro studies have reported a lymphatic diameter-tension curve, with increasing passive stretch affecting the intrinsic contractile properties of each thoracic duct segment. We aimed to describe thoracic duct occlusion pressure and asses if thoracic duct dilation impairs contractility in individuals with a Fontan circulation and lymphatic failure. Methods Central venous pressure and thoracic duct measurements were retrospectively collected from 31 individuals with a Fontan circulation. Thoracic duct occlusion pressure was assessed during a period of external manual compression and used as an indicator of lymphatic vessel contractility. Measurements of pressure were correlated with measurements of the thoracic duct diameter in images obtained by dynamic contrast-enhanced MR lymphangiography. Results The average central venous pressure and average pressure of the thoracic duct were 17 mm Hg. During manual occlusion, the thoracic duct pressure significantly increased to 32 mm Hg. The average thoracic duct diameter was 3.3 mm. Thoracic duct diameter correlated closely with the central venous pressure. The rise in pressure following manual occlusion showed an inverse correlation with the diameter of the thoracic duct. Conclusion Higher central venous pressures are associated with increasing diameters of the thoracic duct. When challenged by manual occlusion, dilated thoracic ducts display a decreased ability to increase pressure. Dilatation and a resulting decreased contractility may partly explain the challenged lymphatic system in individuals with a Fontan circulation.

Substitution of brand-name drugs with less expensive, equally effective interchangeable generics is an important strategy for promoting adherence and controlling prescription drug spending. US state laws govern generic substitution, but there is variability among states in how these laws are designed. We aimed to determine how different features of state laws regulating generic substitution are associated with use of generic drugs.Using national claims databases, we studied individuals with commercial insurance or Medicare Advantage plans who newly initiated one of 34 prescription drugs during the year after new generic competition (2017-2018) to determine any association between generic use and 3 different features of state laws. We used multivariable logistic regression to adjust for demographic and clinical characteristics.Of 502 763 individuals who initiated one of the drugs, 409 856 (81.6%) received a generic version. Those in states requiring patient consent or notification had lower use of generics (81.1% vs 82.9%; adjusted odds ratio 0.89; 95% confidence interval 0.87-0.91; Plt; .001). By contrast, mandating versus permitting generic substitution and protecting pharmacists from liability did not appear to have significant effects.In this study of commercially insured and Medicare Advantage patients, patients in states requiring consent or notification for pharmacists to substitute Food and Drug Administration-certified interchangeable generics had lower use of generics. Laws in 39 states plus the District of Columbia could be amended to improve use of inexpensive and equally effective generic drugs.

Studies have been conducted on developing software programs and applications using C language to simulate drying methods particularly in paddy rice. However, these studies focused on the design and simulation of different drying parameters using specific drying methods. Therefore, this project developed a software program calculator as a simple tool on calculating the drying capacity using sun drying and flatbed drying methods. The study used four target moisture content to calculate the drying capacity based on different input parameters on each drying method. Results revealed that the higher the desired moisture content of paddy, the higher the drying capacity obtained in both sun drying and flatbed drying methods. In terms of drying time, result showed that the longer the drying time, the lower the drying capacity of paddy in both drying methods. Furthermore, it was concluded that the program calculator was able to calculate the final weight, drying weight loss, drying time and drying capacity of paddy in both sun drying and flatbed drying methods.

To investigate the immediate effects of wearing novel sensory-stimulating textured insoles on balance and gait in 41 people with multiple sclerosis (pwMS).Assessments of balance (firm/foam surface; eyes open/closed) and walking (when negotiating even/uneven surfaces) were performed wearing textured insoles, smooth insoles, shoes only, and barefoot. Outcome measures were centre of pressure (CoP) movement during standing (elliptical area, sway path velocity) and spatiotemporal gait patterns (stride/step width, stride time, double-limb support time, stride length, velocity).Wearing textured insoles led to reductions in CoP velocity measures when standing on foam with eyes open and closed when compared to barefoot (For pwMS, stimulating the foot with "texture" appears to provide enhanced sensory input with the capacity to improve CoP movement control during standing; offering a potential new treatment option for balance rehabilitation. Further research is needed to identify which individuals may benefit most from textured insoles.Implications for rehabilitationTextured shoe insoles, designed to stimulate plantar mechanoreceptors, are a novel approach to improve standing balance and walking patterns in people with multiple sclerosis (pwMS).Wearing textured insoles for the first time can lead to improvements in centre of pressure movement control when standing on an unstable compliant supporting surface.Textured insoles offer a potential new treatment technique for balance rehabilitation in pwMS who show early signs of diminished foot sensation.

This briefsummarizes policy-relevant insights and recommendations for the European Commission and EU member states from UNCHAIN project publications and research. As the impacts of climate change continue to intensify, the EU is transitioning to a more climate-resilient Europe. Four key policies drive this shift: the European Green Deal, the European Commission Adaptation Strategy launched in 2021, the 2022 Mission on Adaptation to Climate Change and the EU-wide Climate Risk Assessment (EUCRA) due in 2024. Against this background, the project Unpacking Climate Impact Chains (UNCHAIN) has been well placed to offer timely and relevant insights into the EU adaptation policy process. This brief summarizes the UNCHAIN approach and results from 11 European case studies. Key Messages Policymakers can make adaptation “smarter” by using the Impact Chain approach to analyse both conventional local climate risks and lesser well-known transboundary climate risks. Policymakers should embrace uncertainties by applying a reflect-then-act rather than the predict-then-act approach; by including socio-economic scenarios for a range of possible developments, from likely to unanticipated; and by ensuring transparency in communications. International actors can invest in method innovation, data collection and decision-support tools to identify and assess transboundary climate risks. They should also foster greater cooperation in adaptation planning and implementation across jurisdictions. Policymakers and relevant stakeholders should engage throughout the climate risk assessment process, to co-develop climate information and solutions that capture their needs, knowledge and perspectives and that account for social vulnerability and equitable adaptation.

International audience As the climate crisis continues to worsen, there is an increasing demand for scientific evidence from Climate Risk and Vulnerability Assessments (CRVA). We present 12 methodological advancements to the Impact Chain-based CRVA (IC-based CRVA) framework, which combines participatory and data-driven approaches to identify and measure climate risks in complex socio-ecological systems. The advancements improve the framework along five axes, including the existing workflow, stakeholder engagement, uncertainty management, socio-economic scenario modeling, and transboundary climate risk examination. Eleven case studies were conducted and evaluated to produce these advancements. Our paper addresses two key research questions: (a) How can the IC-based CRVA framework be methodologically advanced to produce more accurate and insightful results? and (b) How effectively can the framework be applied in research and policy domains that it was not initially designed for? We propose methodological advancements to capture dynamics between risk factors, to resolve contradictory worldviews, and to maintain consistency between Impact Chains across policy scales. We suggest using scenario-planning techniques and integrating uncertainties via Probability Density Functions and Reverse Geometric Aggregation. Our research examines the applicability of IC-based CRVAs to address transboundary climate risks and integrating macro-economic models to reflect possible future socio-economic exposure. Our findings demonstrate that the modular structure of IC-based CRVA allows for the integration of various methodological advancements, and further advancements are possible to better assess complex climate risks and improve adaptation decision-making.

Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation. In this work, we employed static and stable isotope tracing untargeted metabolomics methods along with gene expression and histone acetylation studies in an established BeWo cell culture model of trophoblast differentiation. Differentiation was associated with increased abundance of the TCA cycle intermediates citrate and α-ketoglutarate. Citrate was preferentially exported from mitochondria in the undifferentiated state but was retained to a larger extent within mitochondria upon differentiation. Correspondingly, differentiation was associated with decreased expression of the mitochondrial citrate transporter (CIC). CRISPR/Cas9 disruption of the mitochondrial citrate carrier showed that CIC is required for biochemical differentiation of trophoblasts. Loss of CIC resulted in broad alterations in gene expression and histone acetylation. These gene expression changes were partially rescued through acetate supplementation. Taken together, these results highlight a central role for mitochondrial citrate metabolism in orchestrating histone acetylation and gene expression during trophoblast differentiation.

Videoconference applications gained popularity when online learning became the new way of delivering instruction at all levels of education including graduate programs. However, excessive videoconferencing led to reports of fatigue among its users. Identifying the factors contributing to the videoconference exhaustion experience of graduate students is necessary. This study examined Zoom fatigue and selected associated factors among graduate students. An electronic one-shot survey using the Zoom Exhaustion and Fatigue scale was conducted among 109 graduate students of the College of Teacher Education in the Philippines. Correlation and predictive analysis were performed. Results of the study demonstrated a moderate level of Zoom fatigue with the highest level of fatigue in the general fatigue dimension. Pearson’s correlation analysis revealed a significant inverse correlation between attitude toward videoconferencing and Zoom fatigue. Non-verbal mechanisms of mirror anxiety, feeling physically trapped, hyper gaze, and cognitive load in producing non-verbal cues were significantly positively related to Zoom fatigue. Regression analysis revealed that the sense of being physically trapped and cognitive load in producing non-verbal cues remained significant predictors of Zoom fatigue. While videoconferencing supported educational activities and made schooling possible during the global disease outbreak, it is recommended to be mindful of the non-verbal factors contributing to Zoom fatigue.

Sex and gender differences exist with regard to the association between depression and cardiovascular disease (CVD). This narrative review describes the prevalence, mechanisms of action, and management of depression and CVD among women, with a particular focus on coronary heart disease (CHD).Women versus men with incident and established CHD have a greater prevalence of depression. Comorbid depression and CHD in women may be associated with greater mortality, and treatment inertia. Proposed mechanisms unique to the association among women of depression and CHD include psychosocial, cardiometabolic, behavioral, inflammatory, hormonal, and autonomic factors. The literature supports a stronger association between CHD and the prevalence of depression in women compared to men. It remains unclear whether depression treatment influences cardiovascular outcomes, or if treatment effects differ by sex and/or gender. Further research is needed to establish underlying mechanisms as diagnostic and therapeutic targets.

Within the very uniform series Laurifoliae, Passiflora acuminata (treated as a synonym of P. laurifolia in the Flora of China), P. tolimana, P. gleasonii and P. metae appear particularly similar. A review of their descriptions and the associated specimens confirms their lack of morphological differentiation and leads us to formally resurrect P. acuminata and place the three other taxa under its synonymy. This taxonomic move is also supported by a revision of 72 additional geolocalized specimens (for a grand total of 78) and an analysis of their distribution and habitats. In fact, the bioclimatic space corresponding to the specimens previously assigned to P. acuminata encompasses that of all specimens previously assigned to the three other taxa under study. The species range covers a wide region, comprising the lower Amazon and the north of its basin, mostly below 200 m, and, to the west, in the upper Amazon, the Orinoco basin, and along the Andean foothills and valleys, from Venezuela to Peru, at elevations between 100 and 2200 m. In the lowlands, the species appears associated with white sand savannas and water courses. A more complete description is proposed for the species, including its unusual fusiform and slightly ribbed fruit. Another rare trait in the series Laurifoliae is that the outer corona filaments tend to be longer than the corolla.

International audience; On the presence of Xylocopa (Koptortosoma) pubescens Spinola, 1838, in metropolitan France (Hymenoptera, Apidae). Xylocopa (Koptortosoma) pubescens Spinola, 1838, species native to Africa and the Middle East, is recorded for the first time in metropolitan France where it has been observed in an urban garden in Ronchin (Nord). To assess its ability to establish and expand, we developed a MAXENT climatic niche model. Ronchin is slightly above the threshold of suitability of X. pubescens. We assume that it should not expand in this unsuitable region. However, the species should be monitored.; Xylocopa (Koptortosoma) pubescens Spinola‚ 1838‚ espèce originaire d’Afrique et du Moyen-Orient‚ est signalée pour la première fois en France métropolitaine où elle a été observée dans un jardin urbain de Ronchin (Nord). Pour évaluer ses capacités d’installation et d’expansion‚ nous avons développé un modèle de niche climatique avec MAXENT. Ronchin est très légèrement au-dessus du seuil favorable à la survie de X. pubescens. Nous supposons qu’elle ne devrait pas se développer dans cette région peu favorable mais l’espèce est à surveiller.

An experimental test program and companion analytical study were designed and conducted to gain understanding of the tensile failure mechanisms in asymmetrical tapered sandwich core structures at cold temperatures. Representative test coupons were subjected to a tensile load in an environmental chamber to induce foam tensile failure in the core. Finite-element modeling with a proposed maximum principal stress criterion was used to predict the failure loads of the tapered test coupon design at the test temperatures. The predicted failure loads were in good agreement with test results. An important finding is that the cure stresses in the foam are significant and should not be ignored. Additionally, the analysis correctly predicted the failure initiation location, which was verified using high speed photography during the tensile test. The study identified the critical failure regions of asymmetrical tapered sandwich core designs and the failure load dependence on the temperature gradient in the structure.

Computational modeling of drug delivery is becoming an indispensable tool for advancing drug development pipeline, particularly in nanomedicine where a rational design strategy is ultimately sought. While numerous in silico models have been developed that can accurately describe nanoparticle interactions with the bioenvironment within prescribed length and time scales, predictive design of these drug carriers, dosages and treatment schemes will require advanced models that can simulate transport processes across multiple length and time scales from genomic to population levels. In order to address this problem, multiscale modeling efforts that integrate existing discrete and continuum modeling strategies have recently emerged. These multiscale approaches provide a promising direction for bottom-up in silico pipelines of drug design for delivery. However, there are remaining challenges in terms of model parametrization and validation in the presence of variability, introduced by multiple levels of heterogeneities in disease state. Parametrization based on physiologically relevant in vitro data from microphysiological systems as well as widespread adoption of uncertainty quantification and sensitivity analysis will help address these challenges.

Background Registry-derived stage (RD-Stage) provides a mechanism to capture cancer stage at diagnosis from routinely captured data available to population-based cancer registries (PBCRs). In 2021, a project was undertaken to develop business rules to capture RD-Stage for endometrial cancer, understand current capacity to capture this information at a national level, and assess how it compares with stage recorded in clinical notes at diagnosis by clinicians. Methodology Business rules for deriving RD-stage (Endometrial carcinoma) were developed using AJCC Cancer Staging Manual 8th edition and endorsed by a tumour-specific Expert Working group comprising cancer specialists responsible for delivering cancer care and PBCR epidemiologists and medical coders. Baseline completeness of data fields required to calculate RD-Stage, and an overall proportion of cases for whom an RD stage could be assigned was assessed across each Australian jurisdiction. A validation study was undertaken in one jurisdiction to compare RD-Stage (Endometrial cancer) calculated by the Victorian Cancer Registry (VCR) with clinical stage recorded in cases diagnosed in 2018-2020 in the National Gynae-Oncology Registry (NGOR). Results The level of completeness of data to enable RD-Stage (Endometrial carcinoma) to be calculated across jurisdictions ranged from 0 to 89%. Three jurisdictions captured degree of spread of cancer only (instead of TNM data) and therefore captured no data which would enable RD-Stage to be calculated. The RD-Stage (Endometrial carcinoma) validation study found that RD-Stage could not be derived for 64/485 (13%) cases in the VCR and was not captured for 44/485 (9%) cases in NGOR. There was concordance at stage level (I, II, III, IV) in 393/410 (96%) of cases (95.8%, Kendall’s coefficient=0.95). Conclusion A lack of consistency in data captured by, and data sources reporting to, PBCRs meant that it was not possible to provide an accurate national baseline of endometrial carcinoma stage at diagnosis. In a sample of Victorian cases, there was very good concordance between RD-Stage (Endometrial carcinoma) and that recorded by clinicians in medical records and captured by NGOR. However, for 10% of cases RD-Stage could not be calculated because data was not available. RD-Stage provides a useful tool to be used for population epidemiological purposes.

Background The impact of home monitoring on unanticipated interstage readmissions in infants with hypoplastic left heart syndrome has not been previously studied. We sought to examine the association of our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP) with readmission frequency, cumulative readmission days, and readmission illness severity and to identify patient‐level risk factors for readmission. Methods and Results We performed a retrospective single‐center cohort study comparing infants with hypoplastic left heart syndrome enrolled in ISVMP (December 2010–December 2019) to historical controls (January 2007–November 2010). The primary outcome was number of readmissions per interstage days. Secondary outcomes were cumulative interstage readmission days and occurrence of severe readmissions. Inverse probability weighted and multivariable generalized linear models were used to examine the association between ISVMP and the outcomes. We compared 198 infants in the ISVMP to 128 historical controls. Infants in the ISVMP had more than double the risk of interstage readmission compared with controls (adjusted incidence rate ratio, 2.38 [95% CI, 1.50–3.78]; P =0.0003). There was no difference in cumulative interstage readmission days (adjusted incidence rate ratio, 1.02 [95% CI, 0.69–1.50]; P =0.90); however, infants in the ISVMP were less likely to have severe readmissions (adjusted odds ratio, 0.28 [95% CI, 0.11–0.68]; P =0.005). Other factors independently associated with number of readmissions included residing closer to our center, younger gestational age, genetic syndrome, and discharge on exclusive enteral feeds. Conclusions Infants in the ISVMP had more frequent readmissions but comparable readmission days and fewer severe unanticipated readmissions. These findings suggest that home monitoring can reduce interstage morbidity without increasing readmission days.

HR pathway mutations

TP53 mutations

Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths.Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing.Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival.Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. Clin Cancer Res; 24(3); 569–80. ©2017 AACR.See related commentary by Peng and Mills, p. 508

Histotype classification

Revised Supplementary Data, containing Supplementary Methods, Supplementary Figures, Supplementary Tables Supplementary Figure S1. Outline of cohort selection and analyses. Supplementary Figure S2. Clinical response and therapy course of 96 patients with exceptional responses to chemotherapy. Supplementary Figure S3. Distribution and type of TP53 mutations. Supplementary Figure S4. RB1 protein expression altered by genomic inactivation. Supplementary Figure S5. Characterization of CD8 and Ki-67 in tumors according to homologous recombination mutation status. Supplementary Table S2 Immunohistochemical analysis: primary antibodies and staining conditions Supplementary Table S3 Homologous recombination and DNA repair panel Supplementary Table S6 Comparison of molecular alteration prevalence between clinical subgroups Supplementary Table S7 Patient characteristics of tissue microarray cohort

UNSTRUCTURED After the first COVID19 wave in New York City, we found marginally better quality metrics (blood pressure and depression screening) for in-person care vs video- and audio-based telemedicine visits in diverse, low socioeconomic status settings; de-adoption of telemedicine was marked within 2 years.

Le Projet sur la désinformation électorale au Québec visait à identifier et évaluer la propagation et les effets des fausses informations circulant durant l’élection provinciale québécoise de 2022. Le Projet visait également à examiner la couverture médiatique de la mésinformation, ainsi que les perceptions des citoyens sur ce phénomène. Pour ce faire, le Projet s’appuyait sur une veille humaine et informatisée des publications sur les médias sociaux en lien avec l’élection, de même que d’un sondage préélectoral et postélectoral représentatif de la population québécoise visant à évaluer l’exposition aux nouvelles vraies et fausses et les perceptions des citoyens sur l’environnement d’information et l’intégrité de l’élection. Les résultats montrent que la mésinformation est demeurée concentrée au sein de communautés spécifiques en ligne et a eu relativement peu d'influence sur l'élection. Les Québécois considèrent qu'il est difficile de distinguer l'information factuelle de la mésinformation et ont une compréhension différente du phénomène en fonction de leurs opinions politiques. Malgré la circulation de narratifs de fraude électorale, le niveau de confiance dans l'intégrité de l'élection est similaire à celui observé lors des élections précédentes. Le rapport offre des recommandations pour diminuer la propagation et l'influence de la mésinformation.

The case study focuses on economic effects of adapting critical infrastructure in the Mannheim metropolitan area. The case applied Impact Chain (IC) based Climate Risks and Vulnerability Assessment (CRVA) approach on a regional level. It starts from national Impact Chains and uses the regional results for further climate risk assessment for a single industrial stakeholder. This factsheet presents an evaluation of the outcome for key research innovation areas Impact Chain Modelling and co-production of knowledge.