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Objectives: Fetuses with late‐onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late‐onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. Methods: This was a prospective observational study that included fetuses with late‐onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto‐occipital (POF) and calcarine (CF) fissures, were compared between late‐onset FGR, small‐for‐gestational‐age (SGA) and appropriate‐for‐gestational‐age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data. Results: A total of 52 late‐onset FGR fetuses with normal Doppler findings, 60 late‐onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late‐onset FGR fetuses with normal Doppler findings and late‐onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9–56.1) mm vs 41.9 (27.8–51.8) mm vs 38.5 (29.1–50.5) mm vs 31.7 (23.8–40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7–16.8) mm vs 12.7 (9.8–15.1) mm vs 11.9 (9.1–13.4) mm vs 8.3 (6.7–10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3–11.1) mm vs 8.1 (5.6–10.4) mm vs 7.8 (6.1–9.3) mm vs 6.6 (4.2–8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7–11.5) mm vs 8.2 (5.7–10.7) mm vs 7.7 (5.2–9.4) mm vs 6.3 (4.5–7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6–29.2) mm vs 21.6 (15.2–26.1) mm vs 19.1 (13.8–25.9) mm vs 21.0 (13.5–25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late‐onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses. Conclusions: Fetuses with late‐onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late‐onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription‐factor‐related forms, and syndromic forms. The widespread use of next‐generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic‐specific role of the SEC23B loss‐of‐function in iron metabolism dysregulation in CDA II, deepening CDIN1 dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with RACGAP1 variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics. [ABSTRACT FROM AUTHOR]

Probabilities of coastal extreme water levels (EWLs) are increasing as sea levels rise. Using a time‐dependent statistical model on tide gauge data along U.S. and Pacific Basin coastlines, we show that EWL probability distributions also shift on an annual basis from climate forcing and long‐period tidal cycles. In some regions, combined variability (>15 cm) can be as large or larger than the amount of sea level rise (SLR) experienced over the past 30 years and projected over the next 30 years. Considering SLR and variability by 2050 at a location like La Jolla, California suggests a moderate‐level (damaging) flood today with a 50‐year return level (2% annual chance) would occur about 3–4 times a year during an El Nino nearing the peak of the nodal tide cycle. If interannual variability is overlooked, SLR related impacts could be more severe than anticipated based solely upon decadal‐scale projections. Plain Language Summary: Coastal communities are flooding more often due to sea level rise (SLR), but some years are worse than others. We use a statistical model to show how the probabilities of coastal high waters, often referred to as extreme water levels—a combination of above average tides and storm surge—have shifted higher or lower every year with SLR and from changes in the tides and climatic (persistent weather and ocean) patterns. There are many U.S. and Pacific coastal regions where year‐to‐year variability is 15 cm or more, which is as large as the last 30 years of SLR and this pattern is projected to continue over the next 30 years. Considering additional SLR over the next 30 years could help compensate for year‐to‐year variability. Key Points: Probability distributions of coastal extreme water levels shift higher and lower with tide cycles, climatic patterns and sea level rise (SLR)Annual shifts of >15 cm from variability along Pacific coasts exceed SLR over the last 30 years and projected over the next 30 yearsAnnual‐scale variability envelopes are envisioned to assist in decadal‐scale SLR and flood frequency assessments [ABSTRACT FROM AUTHOR]

We herein report that the highly hydrophobic ether 4‐MeTHP constitutes a promising resource for the development of sustainable synthetic methodologies grounded on the use of organometallic reagents. The beneficial effects of 4‐MeTHP as reaction medium are illustrated in the organolithium‐promoted anionic ortho‐Fries rearrangement of 1,1'‐bi‐2‐naphthol (BINOL)‐based carbamates under bench‐type conditions. The use of 4‐MeTHP induces a remarkable and unexpected stability of the organolithiums species, enabling the efficient preparation of chiral (bis)carboxamide catalysts. Furthermore, superior performances of 4‐MeTHP than other environmentally responsible solvents are observed using the synthesized BINOL catalysts in the asymmetric addition of organozinc reagents to aldehydes. Spectroscopic studies in solution suggest that 4‐MeTHP plays a key role in these reactions by inducing the preferential formation of a reactive monomeric dinuclear complex. This methodology allows for the asymmetric assembly of enantioenriched secondary alcohols in good yields and high stereoselectivity, working at 0 °C and under air. [ABSTRACT FROM AUTHOR]

We study germs of real‐analytic Levi‐flat hypersurfaces with singularities on a boundary manifold. We prove the existence of a normal form for a real‐analytic Levi‐flat hypersurface which is defined by the vanishing of the real part of Bk$B_k$, Ck$C_k$, and F4$F_4$ singularities. Finally, we prove a version of Morse–Vey's lemma for a real‐analytic Levi‐flat hypersurface with singularities on the boundary. [ABSTRACT FROM AUTHOR]

Vertebrate populations are often monitored as part of broader assessments of ecosystem status, where they are expected to provide information on the ability of the ecosystem to support higher‐level predators. However, because many vertebrates are long‐lived and often only subsets of their populations can be monitored, abundance may not be sufficiently responsive to ecosystem status to provide early warnings of impending changes. Marine birds are often used as indicators of ecosystem status but, due to their long lifespan and delayed recruitment to the breeding population, changes in abundance are generally slow and often difficult to interpret. Their breeding productivity is, however, also widely monitored and much more responsive to ecosystem status, but the relevance of variation in productivity may be difficult to assess. We propose a model‐based indicator that integrates monitoring of abundance and breeding productivity through demographic matrix models. The metric of the proposed indicator is the expected population growth rate, given the observed level of breeding productivity. This expected growth rate is then compared with a threshold derived from the criteria employed for red‐listing of threatened species by the International Union for the Conservation of Nature. We demonstrate the suggested approach using data from Black‐legged Kittiwakes Rissa tridactyla in the Greater North Sea region, Northwest Europe. The proposed indicator shows that the current level of breeding productivity is expected to lead to a population decline of 3–4% per year, which is equivalent to a red‐list status as Endangered for the species in this region. Our indicator approach is used in OSPAR's Quality Status Report 2023 and is expected to be used by European Union member states for reporting under the Marine Strategy Framework Directive in 2024. Our approach represents a major step forward in assessing the status of marine bird populations; the ideal next step would be to develop a coherent Integrated Population Modelling (IPM) framework that would allow inclusion of all data on population abundance and demography collected across the large and diverse marine ecosystems involved. [ABSTRACT FROM AUTHOR]

In the last decades, the development of high‐throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker‐driven oncology trials. In this review, strengths and limitations of various state‐of‐the‐art sequencing technologies, including gene panel sequencing (DNA and RNA), whole‐exome/whole‐genome sequencing and whole‐transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial. [ABSTRACT FROM AUTHOR]

Empirical research on poverty today often goes beyond a focus on income to consider other dimensions of well‐being. However, relatively few multidimensional poverty measures explicitly consider time‐use, despite its particular relevance to women's double burden of paid and unpaid work. We construct a bivariate relative poverty line between income and leisure, based on their joint distribution in the population. Because the strength of the dependence between income and leisure influences the vulnerability to poverty, we incorporate distributional regression into copula models. Utilizing the 2018 Mexican National Survey of Households, Income and Expenses, we investigate differences in bidimensional poverty with respect to gender and ethnicity. We find that the fraction defined as bidimensional poor is 18 percent points higher than the poverty rate computed from separate time and income measures. Those below the relative but above the absolute poverty line are primarily non‐indigenous women whose poverty is made visible by our approach. [ABSTRACT FROM AUTHOR]

Introduction: Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short‐mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizumab or lenvatinib as first‐line treatment. Methods and Material: The cohort included consecutive patients affected by BCLC‐c and BCLC‐B HCC patients from a multicenter international study group who received atezolizumab plus bevacizumab or lenvatinib as first‐line therapy. Population was stratified according to the BMI in under‐, over‐ and normal‐weight according to the conventional thresholds. The primary objective of the study was to evaluate the prognostic and predictive impact of BMI in patients affected by advanced or intermediate HCC. Survival curves were estimated using the product‐limit method of Kaplan–Meier. The role of stratification factors was analysed with log‐rank tests. Results: 1292 consecutive patients with HCC were analysed. 466 (36%) patients were treated with lenvatinib and 826 (64%) patients were treated with atezolizumab plus bevacizumab. In the atezolizumab plus bevacizumab arm, 510 (62%) patients were normal‐weight, 52 (6%) underweight and 264 (32%) overweight. At the univariate analysis for OS, underweight patients had significantly shorter OS compared to normal‐weight patients, whereas no differences were found between normal‐weight versus overweight. Multivariate analysis confirmed that underweight patients had significantly shorter OS compared to normal‐weight patients (HR: 1.7; 95% CI: 1.0–2.8; p =.0323). In the lenvatinib arm, 26 patients (5.6%) were categorized as underweight, 256 (54.9%) as normal‐weight, and 184 (39.5%) as overweight. At the univariate analysis for OS, no significant differences were found between normal‐weight versus underweight and between normal‐weight versus overweight, which was confirmed at multivariate analysis. Conclusion: Our analysis highlighted a prognostic role of BMI in a cohort of patients with advanced HCC who received atezolizumab plus bevacizumab, while no prognostic role for low BMI was apparent in patients who received lenvatinib. [ABSTRACT FROM AUTHOR]

Reliable projections of extreme future precipitation are fundamental for risk management and adaptation strategies. Convection‐permitting models (CPMs) explicitly resolve large convective systems and represent sub‐daily extremes more realistically than coarser resolution models, but present short records due to the high computational costs. Here, we evaluate the potential of a non‐asymptotic approach, the Simplified Metastatistical Extreme Value (SMEV) to provide information on the future change of extreme sub‐daily return levels based on CPM simulations. We focus on a complex‐orography area in the North Eastern Italy and use three 10‐year time periods COSMO‐crCLIM simulations (2.2 km resolution) under RCP8.5 scenario. When compared to a block r‐maxima approach currently used in similar applications, the proposed approach shows reduced uncertainty in rare return level estimates (about 5%–10% smaller confidence interval) and can improve the quantification of future changes from CPM simulations. We evaluate these changes and their statistical significance in return levels for 1–24 hr durations. The changes show an interesting spatial organization associated with orography, with significant positive changes located at high elevations. These positive changes tend to increase with increasing return period and decreasing duration. Because SMEV can separate the roles of event intensity and occurrence, it allows for physical interpretations of these changes. We suggest that non‐asymptotic approaches permit the quantification of change in rare extremes within available CPM runs. Plain Language Summary: Short duration heavy rainfall may lead to various natural hazards like floods and landslides. Expected change in extreme precipitation due to global warming is a major concern. However, we still cannot quantify these changes because typical climate models cannot reproduce extreme precipitation accurately. The few models that can are very computationally expensive so that we have too few simulations for properly quantifying changes in extremes using traditional statistical methods. Here, we show how to use a new statistical method to quantify extremes from short model simulations. This method is more accurate than currently used methods and may help provide additional insights on the reasons underlying the observed changes. This method could represent a new tool in the hands of the climate research community. Examining the simulations of one model over North‐Eastern Italy, we report an increase in extreme precipitation in mountainous areas and a non‐significant decrease in the low elevation areas. Key Points: Future changes in extreme precipitation are estimated from a convection‐permitting climate model using a non‐asymptotic statistical approachThe method allows to evaluate the significance of the future changes in return levels and to link them to the changing processesSignificant increase in return levels is generally found in the mountains, higher at the short durations (1–3 hr) and for rarer return levels [ABSTRACT FROM AUTHOR]

Digital health technologies (DHTs) can enable more patient‐centric therapeutic development by generating evidence that captures how patients feel and function, enabling decentralized trial designs that increase participant inclusivity and convenience, and collecting and structuring patient‐generated data for regulators to use in approval decisions alongside traditional clinical outcomes. Although a growing body of evidence has documented increasing use of DHTs in clinical trials overall, the use of DHTs in clinical trials supporting medical product development is unclear; here, we quantify the use of DHTs in clinical trials sponsored by pharmaceutical and medical device firms. Despite interest from pharmaceutical and medical device manufacturers in DHTs, we find tepid uptake of DHTs in trials by these sponsor types over time. Further, to date, these sponsors have most frequently used conventional, hardware‐based technologies that have been available for many years (e.g., Holter monitors and glucose meters) rather than newer activity monitors, mobile apps, and other online‐based tools that are frequently used by non‐industry sponsors. Considering the recent and evolving nature of regulatory guidance around DHT use in clinical trials, our findings suggest that organizations pursuing product development still appear hesitant to incorporate DHTs in trials that provide the most critical evidence for regulatory review and impact how new products are used. This suggests there are likely additional opportunities for sponsors of regulated trials to incorporate (more) DHTs and patient‐centric endpoints into product development clinical trials. However, additional regulatory clarity and efforts to reduce operational barriers may be needed in order to more fully capture these opportunities. [ABSTRACT FROM AUTHOR]

Aims: To assess the extent of off‐label drug use and the occurrence of suspected adverse drug reactions (ADRs) among paediatric patients in Italian hospitals. Methods: We conducted a 2‐year prospective cohort study across 22 Italian hospital wards from September 2020 to September 2022. As part of the surveillance project, we performed a 6‐month retrieval of all reported ADRs and evaluated all drug prescriptions for their possible off‐label use. Following an educational project on pharmacovigilance addressed to healthcare professionals in participating wards, the same data collection was performed. Results: Among the 892 patients included in the study, 64% were admitted to paediatric wards and 36% to neonatal wards. Fifty per cent of all drugs prescribed were used off‐label and mainly concerned the administration of a different dose from the one authorized. In neonatal wards, off‐label prescriptions occurred slightly more often, with antibacterials being the most frequently used off‐label drugs. A total of 35 reports of suspected ADRs were collected, five before the educational project and 30 afterwards. Based on product licence, 10 of the total 35 reports concerned at least one off‐label drug use. Conclusions: The off‐label use of drugs in treating paediatric patients was extensive in Italian hospitals. Regulatory interventions are needed to promote the use of drugs based on the latest available literature and improve ADR reporting on children. Paediatric indications and dosages of the drugs most commonly used in children should be supported by appropriate ad hoc studies. [ABSTRACT FROM AUTHOR]

The ongoing Congo Basin drying is linked to decreasing atmospheric water vapour. To comprehend the processes reducing precipitation, we analysed water and Moist Static Energy components, associated with heating sources using ERA5 reanalysis data over the period 1981–2022. The findings reveal that the precipitation deficit in the Congo Basin during March–April–May and September–October–November is primarily attributed to a decreasing trend in the vertical moisture advection anomaly induced by vertical velocity anomalies. Following this, a horizontal moisture advection anomaly induced by specific humidity anomalies plays a significant role. However, evaporation, horizontal moisture advection anomalies induced by wind anomalies, and vertical moisture advection anomalies induced by specific humidity anomalies do not appear to contribute significantly to the drying trend in the region. The horizontal propagation of MSE advection anomalies exhibits a similar pattern to that of moisture flux advection anomalies, both at different boundaries and within the basin itself. Conversely, the contribution of vertical advection of MSE anomalies remains weak. By integrating moisture and MSE budgets, we interpret the declining precipitation trend as a consequence of uplift driven by horizontal MSE advection. Furthermore, our analysis indicates a decreasing trend in the atmospheric heating source within the basin in association with reduced precipitation. This reduction could signify a decrease in moisture influx into the basin, thereby providing more explanations for the observed drying. [ABSTRACT FROM AUTHOR]

While there is intense interest in the production of allogeneic CAR‐T cells from umbilical cord units, little is known about the reactivity and persistence of CAR‐T cells of umbilical origin. We report the case of a patient at our hematological center with multiple relapsing Ph+ B‐ALL, notably a Blinatunomab non‐responder, who underwent therapy with Brexucabtagene Autoleucel following relapse on Ponatinib post‐allogeneic hematopoietic stem cell transplantation. The patient achieved a rapid CAR‐T expansion and durable remission presenting in good clinical conditions 6 months post‐CAR‐T infusion, without manifestations of graft‐versus‐host disease. The case report provides insight into the reactivity and persistence of CAR‐T cells of umbilical origin, confirming the potential promise of allogeneic umbilical cord‐derived CAR‐T cells. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prove the direct correlation of a successions of gravel‐clay beds recovered in borehole with the melt‐water pulses associated with the sea‐level oscillations indicated in the δ18O record in the time‐span preceding the 100‐kyr glacial cycles. Aimed at this scope, we provide combined 40Ar/39Ar and paleomagnetic constraints to a set of seven aggradational successions recovered from a 120 m deep borehole drilled in the buried Paleo‐Tiber delta in Rome (central Italy). The geochronologic constraints enable the correlation of each aggradational succession, characterized by a sudden transition from coarse gravel at the base to sandy clay sediments, with periods of sea‐level rise indicated by the δ18O curve encompassing MIS 37 through MIS 19, from 1250 to 780 ka. This stratigraphy, provides a unique and unprecedented well‐dated evidence of glacial/deglacial events, matching the global benthic δ18O stack during this time frame. Furthermore, this study validates the hypothesis that gravel deposition in the catchment basin and the delta of the main rivers in central Italy is triggered by the melting of glaciers in the Apennines Mountain range. It demonstrates the significant potential of these deglaciation proxies to be used worldwide to unravel the chronology of glacio‐eustatic events. Plain Language Summary: In this study, we used a combination of dating techniques and paleomagnetic data to examine a series of sediment layers found in a buried ancient river delta in Rome, Italy. These sediment layers were collected from a 120 m deep borehole. By analyzing the age of these sediment layers, we were able to link them to a period in the past when sea level was rising. This sea‐level rise occurred between 1250 and 780 ka, covering a range of time from MIS 37 to MIS 19. These sediment layers show a distinct change from coarse gravel to sandy clay, which provides valuable information about glacial and deglacial events. These findings support the idea that the deposition of gravel in river catchment areas and deltas in central Italy is linked to the melting of glaciers in the Apennines Mountain range. This research not only validates this hypothesis but also highlights the potential for using similar techniques globally to better understand the timing of glacio‐eustatic events. Key Points: We provide 40Ar/39Ar and paleomagnetic constraints to seven aggradational successions recovered from a 120 m deep borehole in RomeEach aggradational succession is correlated with a period of sea‐level rise encompassing MIS 37 through MIS 19, 1250 to 780 kaThis study shows that gravel deposition in the catchment basin of the main rivers in central Italy is a direct proxy of deglacial events [ABSTRACT FROM AUTHOR]

In temperate regions, the annual pattern of spring onset can be envisioned as a 'green wave' of emerging vegetation that moves across continents from low to high latitudes, signifying increasing food availability for consumers.Many herbivorous migrants 'surf' such resource waves, timing their movements to exploit peak vegetation resources in early spring. Although less well studied at the individual level, secondary consumers such as insectivorous songbirds can track vegetation phenology during migration as well.We hypothesized that four species of ground‐foraging songbirds in eastern North America—two warblers and two thrushes—time their spring migrations to coincide with later phases of vegetation phenology, corresponding to increased arthropod prey, and predicted they would match their migration rate to the green wave but trail behind it rather than surfing its leading edge.We further hypothesized that the rate at which spring onset progresses across the continent influences bird migration rates, such that individuals adjust migration timing within North America to phenological conditions they experience en route.To test our hypotheses, we used a continent‐wide automated radio telemetry network to track individual songbirds on spring migration between the U.S. Gulf Coast region and northern locations closer to their breeding grounds.We measured vegetation phenology using two metrics of spring onset, the spring index first leaf date and the normalized difference vegetation index (NDVI), then calculated the rate and timing of spring onset relative to bird detections.All individuals arrived in the southeastern United States well after local spring onset. Counter to our expectations, we found that songbirds exhibited a 'catching up' pattern: Individuals migrated faster than the green wave of spring onset, effectively closing in on the start of spring as they approached breeding areas.While surfing of resource waves is a well‐documented migration strategy for herbivorous waterfowl and ungulates, individual songbirds in our study migrated faster than the green wave and increasingly caught up to its leading edge en route.Consequently, songbirds experience a range of vegetation phenophases while migrating through North America, suggesting flexibility in their capacity to exploit variable resources in spring. [ABSTRACT FROM AUTHOR]

The combination of amoxicillin (AMX) and clavulanic acid (CLA) is one of the most widely used antibiotic medicines in the world. This paper describes a novel electrochemical method for the fast sequential determination of AMX and CLA using batch injection analysis with amperometric detection (BIA‐AD) and boron‐doped diamond (BDD) as the working electrode. In the proposed strategy, AMX was selectively detected at +1.3 V and both compounds (AMX+CLA) at +1.8 V. The oxidation current from CLA was accessed by subtracting the currents detected at both potential pulses (i+1.8 V–i+1.3V) and using a simple correction factor. The developed method proved to be simple, cost‐effective, precise (RSD<1.3 %, n=10), rapid (>200 injection h−1), required simple sample preparation steps (dissolution and dilution only) and can be used in laboratories with minimal infrastructure (portable characteristics). The limits of detection were 0.31 (0.13) and 1.99 (0.47) μmol L−1 (mg L−1) for AMX and CLA, respectively. The results obtained by the proposed BIA‐AD method were comparable to those obtained by capillary electrophorese (95 % confidence level). [ABSTRACT FROM AUTHOR]

Summary: The present literature points to an alteration of the human K‐complex during non‐rapid eye movement sleep in Alzheimer's disease. Nevertheless, the few findings on the K‐complex changes in mild cognitive impairment and their possible predictive role on the Alzheimer's disease conversion show mixed findings, lack of replication, and a main interest for the frontal region. The aim of the present study was to assess K‐complex measures in amnesic mild cognitive impairment subsequently converted in Alzheimer's disease over different cortical regions, comparing them with healthy controls and stable amnesic mild cognitive impairment. We assessed baseline K‐complex density, amplitude, area under the curve and overnight changes in frontal, central and parietal midline derivations of 12 amnesic mild cognitive impairment subsequently converted in Alzheimer's disease, 12 stable amnesic mild cognitive impairment and 12 healthy controls. We also assessed delta electroencephalogram power, to determine if K‐complex alterations in amnesic mild cognitive impairment occur with modification of the electroencephalogram power in the frequency range of the slow‐wave activity. We found a reduced parietal K‐complex density in amnesic mild cognitive impairment subsequently converted in Alzheimer's disease compared with stable amnesic mild cognitive impairment and healthy controls, without changes in K‐complex morphology and overnight modulation. Both amnesic mild cognitive impairment groups showed decreased slow‐wave sleep percentage compared with healthy controls. No differences between groups were observed in slow‐wave activity power. Our findings suggest that K‐complex alterations in mild cognitive impairment may be observed earlier in parietal regions, likely mirroring the topographical progression of Alzheimer's disease‐related brain pathology, and express a frontal predominance only in a full‐blown phase of Alzheimer's disease. Consistently with previous results, such K‐complex modification occurs in the absence of significant electroencephalogram power changes in the slow oscillations range. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. METHODS: We looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG‐PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An algorithm based on FDG‐PET hypometabolism classified each subject into subtypes, then compared biomarker measures and clinical progression. RESULTS: Three subtypes emerged: hippocampal sparing–cortical hypometabolism, associated with younger age and the highest level of Alzheimer's disease (AD)‐CSF pathology; hippocampal/cortical hypometabolism, associated with a high percentage of APOE ε3/ε4 or ε4/ε4 carriers; medial–temporal hypometabolism, characterized by older age, the lowest AD‐CSF pathology, the most severe hippocampal atrophy, and a benign course. Within the whole cohort, the severity of temporo‐parietal hypometabolism, correlated with AD‐CSF pathology and marked the rate of progression of cognitive decline. DISCUSSION: FDG‐PET can distinguish clinically comparable aMCI at single‐subject level with different risk of progression to AD dementia or stability. The obtained results can be useful for the optimization of pharmacological trials and automated‐classification models. Highlights: Algorithm based on FDG‐PET hypometabolism demonstrates distinct subtypes across aMCI;Three different subtypes show heterogeneous biological profiles and risk of progression;The cortical hypometabolism is associated with AD pathology and cognitive decline;MTL hypometabolism is associated with the lowest conversion rate and CSF‐AD pathology. [ABSTRACT FROM AUTHOR]

This paper explores connections between Francis Ford Coppola's biography and recurrent themes in the choice and assemblage of The Conversation and Apocalypse Now. Framed broadly by the psychobiography tradition, the paper deploys key concepts from the independent school (Bollas, Winnicott and Phillips), coupled with textual analysis so as to expand the meaning‐making opportunities available to the two films and Coppola's psychobiography. With such partnering, the paper explores Coppola's autobiographical renderings as a projective feature in the assemblage and production of the films, with dedicated attention to evolving under‐standings of agony and horror as a unified affective state. [ABSTRACT FROM AUTHOR]

Background and purpose: After successful mechanical thrombectomy for middle cerebral artery occlusion, basal ganglia infarction is commonly detectable. Whilst the functional outcome of these patients is often good, less knowledge is available about the cognitive outcome. The aim of our study was to assess the presence of cognitive impairment within 1 week after thrombectomy. Methods: In all, 43 subjects underwent a general cognitive assessment using the Montreal Cognitive Assessment and an extensive battery of tests. Patients were classified as cognitively impaired (CImp) or not (noCImp) according to a Montreal Cognitive Assessment score below 18. Results: Cognitively impaired and noCImp subjects did not differ either in their National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admittance, or in their Fazekas score and Alberta Stroke Program Early Computed Tomography Score. At discharge, CImp subjects showed higher scores than noCImp subjects on NIHSS (p = 0.002) and mRS (p < 0.001). The percentage of pathological performances on each neuropsychological test in the whole sample and in CImp and noCImp patients shows a similar cognitive profile between the groups. Conclusions: Some patients who underwent thrombectomy experienced a detectable cognitive impairment that probably led to worse NIHSS and mRS. The neuropsychological profile of such cognitive impairment at the acute stage consists of wide deficits in numerous cognitive domains, suggesting that basal ganglia damage may lead to complex functional impairments. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis (OA) negatively impacts the health outcomes and equity, social and employment participation, and socio‐economic wellbeing of those affected. Little community‐based support is offered to people with knee OA in Aotearoa New Zealand. Identifying Māori and non‐Māori with knee OA in community pharmacy and providing co‐ordinated, evidence‐ and community‐based care may be a scalable, sustainable, equitable, effective and cost‐effective approach to improve health and wellbeing. Aim: Assess whether the Knee Care for Arthritis through Pharmacy Service (KneeCAPS) intervention improves knee‐related physical function and pain (co‐primary outcomes). Secondary aims assess impacts on health‐related quality of life, employment participation, medication use, secondary health care utilisation, and relative effectiveness for Māori. Methods and analysis: A pragmatic randomised controlled trial will compare the KneeCAPS intervention to the Pharmaceutical Society of New Zealand Arthritis Fact Sheet and usual care (active control) at 12 months for Māori and non‐Māori who have knee OA. Participants will be recruited in community pharmacies. Knee‐related physical function will be measured using the function subscale of the Short Form of the Western Ontario and McMaster Universities Osteoarthritis Index. Knee‐related pain will be measured using an 11‐point numeric pain rating scale. Primary outcome analyses will be conducted on an intention‐to‐treat basis using linear mixed models. Parallel within‐trial health economic analysis and process evaluation will also be conducted. Ethics and trial dissemination: Ethical approval was obtained from the Central Health and Ethics Committee (2022‐EXP‐11725). The trial is registered with ANZCTR (ACTRN12622000469718). Findings will be submitted for publication and shared with participants. [ABSTRACT FROM AUTHOR]

The article focuses on the evolving roles of genetic counselors, emphasizing the need for ongoing training and education in response to the dynamic field of applied genetics and genomics. It explores the desire for additional training among genetic counselors, particularly in emerging subspecialties, and discusses fellowships as an emerging model to address these training needs beyond the existing continuing education unit (CEU) model.

Objective: Develop charts for cavum septum pellucidi (CSP) following a standardized methodology and using quantile regression. The secondary objective was to assess the influence of fetal gender on the generated reference curves. Methods: In a cross‐sectional prospective study 453 low‐risk singleton pregnancies were evaluated at a gestational age interval between 18 and 34 weeks. The width of CSP were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). Differences between sex were evaluated. Results: The measurement of CSP significantly increased with gestation and HC. Linear models better described the changes of CSP with GA and HC. The fits of CSP width with GA and HC were not significantly different. Male fetuses showed significantly higher CSP width when compared to female fetuses (u = 2.973; p = 0.005). Conclusions: We generated prospective nomograms of fetal CSP development using quantile regression and following a strict standardized methodology. These new charts may be useful to better identify abnormal cases at higher risk of associated anomalies. Further our findings underline the potential effect of gender in developing fetal brain. [ABSTRACT FROM AUTHOR]

River floods are generated by various processes that, if disregarded, may induce errors in flood hazard assessment. This is particularly relevant where events extraordinarily larger than the typical floods have been observed, that is, for rivers with a flood divide in their flood‐frequency curves. We identify 11 such cases in a large set of German catchments and test a statistical approach that accounts for different runoff‐generation processes to predict the magnitude and frequency of extraordinarily high floods. We observe that in catchments with a flood divide, ordinary peaks are generated by different runoff‐generation processes and the distribution of at least one process is heavy‐tailed. By accounting for the different tail behaviors of multiple processes, we can reproduce flood‐frequency curves in these catchments. Our findings shed light on the origin of flood divides and set a method to improve the estimation of high flood quantiles in these high‐risk cases. Plain Language Summary: River floods can be caused by many different processes. Neglecting this fact may impair our capability to predict the probability of occurrence of the most extreme floods. In this study, we combine knowledge of runoff‐generation mechanisms across different events with a statistical method which uses information on these ordinary events to infer the magnitude and frequency of floods. We apply the method to 11 rivers in Germany where extraordinarily high floods have been observed. By accounting for ordinary runoff events and their diverse runoff‐generation processes we obtain accurate estimates of the magnitude of rare and extreme floods, substantially improving results provided by traditional methods. Key Points: We develop a statistical model to predict extraordinarily high floods occurring in river basins with variable flood extremesThe approach leverages knowledge of various hydrologic processes generating runoff events to estimate the magnitude of extreme floodsBy accounting for multiple processes in flood magnitude‐frequency analysis, we improve the estimation of extraordinarily high floods [ABSTRACT FROM AUTHOR]

Understanding the geographic linkages among populations across the annual cycle is an essential component for understanding the ecology and evolution of migratory species and for facilitating their effective conservation. While genetic markers have been widely applied to describe migratory connections, the rapid development of new sequencing methods, such as low‐coverage whole genome sequencing (lcWGS), provides new opportunities for improved estimates of migratory connectivity. Here, we use lcWGS to identify fine‐scale population structure in a widespread songbird, the American Redstart (Setophaga ruticilla), and accurately assign individuals to genetically distinct breeding populations. Assignment of individuals from the nonbreeding range reveals population‐specific patterns of varying migratory connectivity. By combining migratory connectivity results with demographic analysis of population abundance and trends, we consider full annual cycle conservation strategies for preserving numbers of individuals and genetic diversity. Notably, we highlight the importance of the Northern Temperate‐Greater Antilles migratory population as containing the largest proportion of individuals in the species. Finally, we highlight valuable considerations for other population assignment studies aimed at using lcWGS. Our results have broad implications for improving our understanding of the ecology and evolution of migratory species through conservation genomics approaches. [ABSTRACT FROM AUTHOR]

The impact of climate on topography, which is a theme in landscape evolution studies, has been demonstrated, mostly, at mountain range scales and across climate zones. However, in drylands, spatiotemporal discontinuities of rainfall and the crucial role of extreme rainstorms raise questions and challenges in identifying climate properties that govern surface processes. Here, we combine methods to examine hyperarid escarpment sensitivity to storm‐scale forcing. Using a high‐resolution DEM and field measurements, we analyzed the topography of a 40‐km‐long escarpment in the Negev desert (Israel). We also used rainfall intensity data from a convection‐permitting numerical weather model for storm‐scale statistical analysis. We conducted hydrological simulations of synthetic rainstorms, revealing the frequency of sediment mobilization along the sub‐cliff slopes. Results show that cliff gradients along the hyperarid escarpment increase systematically from the wetter (90 mm yr−1) southwestern to the drier (45 mm yr−1) northeastern sides. Also, sub‐cliff slopes at the southwestern study site are longer and associated with milder gradients and coarser sediments. Storm‐scale statistical analysis reveals a trend of increasing extreme (>10 years return‐period) intensities toward the northeast site, opposite to the trend in mean annual rainfall. Hydrological simulations based on these statistics indicate a higher frequency of sediment mobilization in the northeast, which can explain the pronounced topographic differences between the sites. The variations in landscape and rainstorm properties across a relatively short distance highlight the sensitivity of arid landforms to extreme events. Plain Language Summary: Identifying the link between climatic properties and topography helps to elucidate key controlling processes affecting Earth's landscape evolution. In drylands, however, it is harder to associate topography with average climate as surface processes are significantly affected by spatially disconnected, discrete and short‐duration rainstorms. In this study, we investigate whether variations in rainstorm properties can account for topographic differences along a 40‐km‐long hyperarid escarpment. Results indicate that in the drier parts of the escarpment, cliffs are steeper, and slopes are covered by finer sediment. Rainstorm statistical analysis indicates that the drier part of the escarpment is associated with extreme rainstorms characterized by higher rainfall intensities. We demonstrate that these storms mobilize sediment more frequently in the drier part of the escarpment, which can explain the pronounced topographic differences along the escarpment. This study presents a rarely‐recognized link between small‐scale variations in arid rainstorm properties and topography and highlights the susceptibility of arid landscapes to extreme rainstorms. Key Points: The morphology of cliffs and sub‐cliff slopes varies significantly with rainfall along a 40‐km hyperarid escarpmentThe observed morphologic variability is triggered primarily by differences in sediment mobilization frequencies on sub‐cliff slopesRainstorm properties in arid landscapes could change over relatively short distances and leave a significant geomorphic imprint [ABSTRACT FROM AUTHOR]

Steel seven‐wire strands are highly vulnerable to corrosion phenomena, which can strongly reduce their strength and ductility capacities. Following several parametric studies already conducted on corroded wires and strands, which allowed to identify the key parameters that govern their mechanical behavior, this paper presents a new resistance model for corroded seven‐wire strands. The model introduces a new coefficient that takes into account the variability of the corrosion in the seven wires that constitute the strand, with the purpose of representing the dispersion in the peak strength often emerged from tensile tests available in the literature. The lower bound of this coefficient is estimated analytically considering a brittle behavior for the wires. The ductile behavior is then taken into account by means of several Monte‐Carlo simulations of corroded strands. Finally, the resistance model allows to define strength reduction curves that allow to estimate the strength of corroded strands taking into account both the geometry of the corrosion and the steel material parameters. They represent simple engineering tools that are of great interest from both a design and safety assessment point of view. [ABSTRACT FROM AUTHOR]

The exponential growth of e‐commerce in the last decade boosts the need of large logistic centers. Steel rack supported warehouses (SRSWs) are one of the most competitive solutions for such infrastructures. The execution phase of SRSWs is challenging, as the stability of the structure has to be ensured throughout the different erection stages. The wind action is here particular important. The density of structural elements and the incompleteness of the SRSWs structure, is a vulnerable condition under wind loads. The determination of wind forces during execution according to the EN 1991‐1‐4 is very limited when dealing with open frame structures, and in particular, with structural systems such as SRSWs. In order to overcome this lack, the wind action on SRSWs during execution has been subject of a recent concluded RFCS research project "STEELWAR". This paper presents the proposal of a method to determine the wind forces on SRSWs under construction. The method is derived from a series of wind tunnel tests. Subsequently, given the inherent limitation of such experimental program, the extension of the method to a range of practical cases is proposed. Finally, an application to a real case study is used to assess the vulnerability of the SRSWs during the execution. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to test the agreement between a manual and an automatic technique in measuring fetal brain volume (FBV) from three‐dimensional (3D) fetal head datasets. Methods: FBV were acquired independently by two operators from low risk singleton pregnancies at a gestational age between 19 and 34 weeks. FBV measurements were obtained using an automatic software (Smart ICV™) and manually by Virtual Organ Computer‐aided AnaLysis (VOCAL™). Intraclass correlation coefficient (ICC) were calculated to assess reliability, while bias and agreement were evaluate by examining Bland–Altman plots. The time spent in measuring volumes was calculated and values obtained compared. Results: Sixty‐three volumes were considered for the study. In all the included volumes successful volume analysis were obtained with both techniques. Smart ICV™ showed a high intra‐observer (0.996; 95% CI 0.994–0.998) and inter‐observer (ICC 0.995; 95% CI 0.991–0.997). An excellent degree of reliability was found when the two techniques were compared (ICC 0.995; 95% CI 0.987–0.998). The time required to perform FBV was significantly lower for Smart ICV™ than VOCAL™ (8.2 ± 4.5 vs. 121.3 ± 19.0 s; p < 0.0001). Conclusions: The measurement of FBV is feasible with both manual and automatic techniques. Smart ICV™ showed an excellent intra‐ and inter‐observer reliability associated with a valuable agreement with volume measurements obtained manually with VOCAL™. Volumes may be measured significantly faster with smart ICV™ than manually and this automatic software has the potential to become the preferred methods for the assessment of FBV. [ABSTRACT FROM AUTHOR]

We integrate 10 new with five published 40Ar/39Ar age determinations, both on primary volcanic deposits and on detrital sanidine, which provide precise geochronologic control on the Marine Isotope Stage (MIS) 5.5 and MIS 5.3 sea‐level indicators that occur at three coastal caves in a tectonically stable region of the central Tyrrhenian Sea of Italy. The age of a Strombus‐bearing bioclastic conglomerate, associated with a tidal notch occurring at 9.5 m a.s.l. at Cape Circeo, is constrained to between 121.5 ± 5.8 and 116.2 ± 1.2 ka. Moreover, backbeach deposits intercalated in the sedimentary filling of Guattari and Capre coastal caves are directly correlated with a tidal notch at ∼2.5 m associated with another bioclastic conglomerate at Cape Circeo and dated to 110.4 ± 1.4–104.9 ± 0.9 ka. The latter deposit is also correlated with the adjacent marine terrace, occurring at 3–5 m on the coast between Capes Circeo and Anzio, for which a maximum age of 100.7 ± 6.6 ka was previously reported. These data provide evidence for a maximum sea level around 9.5 m above the present sea level and a duration of MIS 5.5 highstand until 116 ka, in agreement with estimates from other regions in the world. In contrast, they suggest a maximum sea level during MIS 5.3 highstand that is similar to the present level, and only ∼7 m lower than the MIS 5.5 highstand, challenging the reconstructions of the MIS 5 ice‐sheet volumes and derived global sea levels that are based on benthic oxygen isotope records. Key Points: We present 10 40Ar/39Ar ages on the Marine Isotope Stage (MIS) 5.5 and MIS 5.3 sea‐level indicators on the Tyrrhenian Sea coastMIS 5.5 paleo‐sea level at ∼9.5 m a.s.l. is dated 121.5 ± 5.8 through 116.2 ± 1.2 kaWe find a MIS 5.3 sea level ca. 20 m higher than the δ18O‐derived values [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, structurally characterized by progressive fibro‐fatty replacement of the normal myocardium and clinically by ventricular arrhythmias (VAs). Predominantly thanks to the use of cardiac magnetic resonance, we have learnt that the spectrum of the disease encompasses not only the classical right ventricular phenotype, but also biventricular and left dominant variants. Sport activity contributes to the phenotypic expression and progression of ACM and may trigger life‐threatening VAs and sudden cardiac death (SCD). We conducted a review of the literature about ACM and its implications in Sport Cardiology and summarized the main findings in this topic. Early identification of affected athletes through preparticipation screening (PPS) is fundamental but, while classical right‐ventricular or biventricular phenotypes are usually suspected because of electrocardiogram (ECG) and echocardiographic abnormalities, variants with predominant left ventricular involvement are often characterized by normal ECG and unremarkable echocardiography. Usually the only manifestations of such variants are exercise‐induced VAs and for this reason exercise testing may empower the diagnostic yield of the PPS. Patients with ACM are not eligible to competitive sports activity, but low‐to‐moderate intensity physical activity under medical supervision is possible in most cases. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to explore machine learning (ML) methods for early prediction of Alzheimer's disease (AD) and related dementias (ADRD) using the real‐world electronic health records (EHRs). Methods: A total of 23,835 ADRD and 1,038,643 control patients were identified from the OneFlorida+ Research Consortium. Two ML methods were used to develop the prediction models. Both knowledge‐driven and data‐driven approaches were explored. Four computable phenotyping algorithms were tested. Results: The gradient boosting tree (GBT) models trained with the data‐driven approach achieved the best area under the curve (AUC) scores of 0.939, 0.906, 0.884, and 0.854 for early prediction of ADRD 0, 1, 3, or 5 years before diagnosis, respectively. A number of important clinical and sociodemographic factors were identified. Discussion: We tested various settings and showed the predictive ability of using ML approaches for early prediction of ADRD with EHRs. The models can help identify high‐risk individuals for early informed preventive or prognostic clinical decisions. [ABSTRACT FROM AUTHOR]

Background: Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end‐to‐side triangular venous anastomosis. Methods: We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end‐to‐side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. Results: VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p =.04), re‐transplantation (p =.008), and presence of two hepatic veins (p <.0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p =.87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22–8.46; p =.01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. Conclusion: VOO after LLS split LT with end‐to‐side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re‐transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases. [ABSTRACT FROM AUTHOR]

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This article, titled "EP05.05: Adherence to the Mediterranean diet during pregnancy: effects on fetal cortical development," explores the relationship between a mother's adherence to the Mediterranean diet (MD) during pregnancy and fetal cortical development. The study involved a cohort of 214 women, and cortical development variables were compared based on their adherence to the MD using the Mediterranean Diet Adherence Screener (MEDAS) score. The results showed that fetuses from pregnancies with medium or low adherence to the MD had significant differences in cortical development compared to those from pregnancies with high adherence, with reduced depths in certain cortical areas. These findings suggest a link between maternal nutrition and fetal brain development in uncomplicated pregnancies. [Extracted from the article]

This article, published in the Australasian Journal of Dermatology, examines the quality of TikTok videos related to psoriasis. The study analyzed 209 videos under the hashtag "#psoriasis" and found that over 50% of the videos were of low quality. Laypeople uploaded the majority of the videos, which received more views compared to uploads by physicians. The study also found that videos discussing home remedies and anecdotes had the lowest quality scores. The authors suggest that healthcare providers should address patient concerns and engage in conversations about the safe use of alternative treatments for psoriasis. They also recommend increasing the presence of dermatologists on TikTok to limit the spread of inaccurate information. [Extracted from the article]

Changes in the frequency of temperature extremes are often attributed to global warming. The recent availability of near‐surface temperature data records from reference networks, such as the U.S. Climate Reference Network (USCRN), enables the quantification of measurement uncertainties. Within an activity of the Copernicus Climate Change Service, the estimation of the measurement uncertainty has been provided for USCRN temperature data, using metadata made available by the National Oceanic and Atmospheric Administration (NOAA). In this paper, four climate extreme indices (Frost Days, Summer Days, Ice Days, Tropical Nights) and the related uncertainties are calculated for the period 2006–2020 from the USCRN data set and compared with traditional indices. Moreover, the asymmetric USCRN measurement uncertainties are propagated to estimate the uncertainties of climate indices. The comparison shows expanded uncertainties homogeneously distributed with the latitude and typically within 15 days per year for Frost Days and within 10 days for Ice Days, while smaller uncertainties are estimated for Summer Days and Tropical Nights, with values typically within six to seven days per year. Positive uncertainties are typically larger than negative ones for all the indices. The values of Frost and Ice Days with the related uncertainties for USCRN have also been compared with the corresponding values calculated from reanalyses data, showing differences typically within 60 days for median values, quite often smaller than USCRN and inconsistent within the related uncertainties, Overall, the results show that USCRN measurement uncertainties increase confidence in the estimation of climate extreme indices and decisions for adaptation. Plain Language Summary: The relationship between the intensity and frequency of extremes and climate change as well as their attribution to human activities is fundamental for improving the assessment of risk and the elaboration of adaptation strategies. Temperature extremes are often reported and estimated using observations or model data using indices, which are widely adopted in the research community and by decision‐makers. However, the number of temperature extremes is quantified assuming input observations as perfect, whereas these are always affected by uncertainties due to instrumental noise and systematic effects that cannot be always properly accounted for. This also implies that climate extreme indices may under or over‐represent the number of temperature extremes. The advent of reference measurement networks, as well as the overall increase in observational data quality due to recent technological improvements, allows us to quantify measurement uncertainties in detail. In this paper, temperature extremes over the US are estimated from near‐surface temperature measurements provided by the USCRN network in the period 2006–2020 with related uncertainties. The use of uncertainty illustrates the range of values that climate extreme indices may assume. Possible sources of uncertainties and comparisons with data from atmospheric reanalysis are also discussed. Key Points: An extensive assessment of uncertainties for four climate extreme indices is provided using reference near‐surface temperaturesEstimate uncertainties of climate indices for reanalysis validation and quantification of extremes by propagating measurement uncertaintiesUSCRN traceable measurements with quantified uncertainties increase confidence in estimating extreme indices and decisions for adaptation [ABSTRACT FROM AUTHOR]

The estimation of extreme flood frequency for ungauged or poorly gauged catchments is a longstanding problem of great practical importance. Simulated streamflow derived from distributed hydrological models can be used to address this issue, but their representation of extreme flood peaks is often prone to large biases. This study evaluates the potential of a nonasymptotic statistical approach able to consider all the independent flood peaks instead of extremes only, the Simplified Metastatistical Extreme Value (SMEV), for the estimation of extreme flood frequency from time series of simulated streamflow. We examined 28 years of simulated daily streamflow across the contiguous United States and compared SMEV to traditional statistical models based on annual maxima. Our results suggest that when its assumptions are met SMEV can moderate the impact of hydrological model biases in the quantification of extreme flood frequency. SMEV exhibits a lower relative difference between quantiles derived from observations and simulations for all return periods and forcing dataset. Quantiles estimated from simulated streamflow time series (28‐year records) using SMEV are usually in better agreement with the estimates based on 70‐year‐long observations. Geographical variations in the results of SMEV are noticed, with a better performance of SMEV in the east and west coasts (California, New England, and Mid‐Atlantic) and in the southwestern regions (Texas‐Gulf). These results indicate that the potential of SMEV for flood frequency analyses in ungauged and poorly gauged basins deserves further investigations. [ABSTRACT FROM AUTHOR]

We develop a flexible two‐equation copula model to address endogeneity of medical expenditures in a distribution regression for health. The expenditure margin uses the compound gamma distribution, a special case of the Tweedie family of distributions, to account for a spike at zero and a highly skewed continuous part. An efficient estimation algorithm offers flexible choices of copulae and link functions, including logit, probit and cloglog for the health margin. Our empirical application revisits data from the Rand Health Insurance Experiment. In the joint model, using random insurance plan assignment as instrument for spending, a $1000 increase is estimated to reduce the probability of a low post‐program mental health index by 1.9 percentage points. The effect is not statistically significant. Ignoring endogeneity leads to a spurious positive effect estimate. [ABSTRACT FROM AUTHOR]

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in‐patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin‐converting‐enzyme‐inhibitor (ACE‐I) or an angiotensin‐receptor‐blocker (ARB) with a calcium‐channel‐blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE‐I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all‐cause death, cardiovascular (CV) hospitalization/death, CV death, non‐CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all‐cause death, all‐cause death/hospitalization, CV death, CV death/hospitalization and non‐CV death. Conclusions: Guidelines‐suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients. [ABSTRACT FROM AUTHOR]