Continuous testing for Poisson process intensities: A new perspective on scanning statistics

We propose a novel continuous testing framework to test the intensities of Poisson Processes. This framework allows a rigorous definition of the complete testing procedure, from an infinite number of hypothesis to joint error rates. Our work extends traditional procedures based on scanning windows, by controlling the family-wise error rate and the false discovery rate in a non-asymptotic manner and in a continuous way. The decision rule is based on a \pvalue process that can be estimated by a Monte-Carlo procedure. We also propose new test statistics based on kernels. Our method is applied in Neurosciences and Genomics through the standard test of homogeneity, and the two-sample test

In-vitro testing of stent retrievers for cerebral thrombi removal

International audienceRecent articles appeared in literature demonstrated that early mechanical thrombectomy offered to patients presenting with acute ischemic stroke is related to improved functional outcome. Stent retrievers (STR) are recognized as the most effective devices for intracranial thrombectomy. In the present study we experimentally analyzed devices mechanical properties, behavior during retrieval and their interaction with clots of different features. The aim of this study was to identify any device feature that was functional to the thrombus removal

DELIVERING EARLY, CONTEXTUALIZED GUIDANCE REGARDING CLOUD CARBON FOOTPRINT

Across multiple industry segments, organizations that are deploying systems to the cloud are increasingly concerned with the carbon footprint of their activities. However, once a system has progressed through design and development and it is in production, its fundamental energy consumption profile is set. Consequently, a need exists for a way to deliver energy consumption awareness to engineers during the development process so that a lower carbon footprint may be established within a system, at the earliest possible stage. To address that need, techniques are presented herein that support a system for delivering such awareness to engineers during the development process. Aspects of the presented techniques encompass integrating with integrated development environments (IDEs) using industry-standard technology, interfacing with energy monitoring technology, and carrying out a statistical analysis involving correlation and regression between tokenized source code and granular workload-oriented carbon impact assessments

Arrest of mammalian fibroblasts in G1 in response to actin inhibition is dependent on retinoblastoma pocket proteins but not on p53

p53 and the retinoblastoma (RB) pocket proteins are central to the control of progression through the G1 phase of the cell cycle. The RB pocket protein family is downstream of p53 and controls S-phase entry. Disruption of actin assembly arrests nontransformed mammalian fibroblasts in G1. We show that this arrest requires intact RB pocket protein function, but surprisingly does not require p53. Thus, mammalian fibroblasts with normal pocket protein function reversibly arrest in G1 on exposure to actin inhibitors regardless of their p53 status. By contrast, pocket protein triple knockout mouse embryo fibroblasts and T antigen–transformed rat embryo fibroblasts lacking both p53 and RB pocket protein function do not arrest in G1. Fibroblasts are very sensitive to actin inhibition in G1 and arrest at drug concentrations that do not affect cell adhesion or cell cleavage. Interestingly, G1 arrest is accompanied by inhibition of surface ruffling and by induction of NF2/merlin. The combination of failure of G1 control and of tetraploid checkpoint control can cause RB pocket protein–suppressed cells to rapidly become aneuploid and die after exposure to actin inhibitors, whereas pocket protein–competent cells are spared. Our results thus establish that RB pocket proteins can be uniquely targeted for tumor chemotherapy

Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups

Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-Cre$^{ERT2}$::Smarcb1$^{flox/flox}$ model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway

Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma

Background: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. Methods We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). Results We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively;P-value < 5x10(-8)) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84x10(-8)). Conclusions: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. Impact Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci

Terrestrial Very-Long-Baseline Atom Interferometry:Workshop Summary

This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Goodness-of-Fit Tests and Nonparametric Adaptive Estimation for Spike Train Analysis

International audienceWhen dealing with classical spike train analysis, the practitioner often per-forms goodness-of-fit tests to test whether the observed process is a Poisson process, for instance, or if it obeys another type of probabilistic model (Yana et al. in Bio-phys.. In doing so, there is a fundamental plug-in step, where the parameters of the supposed underlying model are estimated. The aim of this article is to show that plug-in has sometimes very un-desirable effects. We propose a new method based on subsampling to deal with those plug-in issues in the case of the Kolmogorov–Smirnov test of uniformity. The method relies on the plug-in of good estimates of the underlying model that have to be consis-tent with a controlled rate of convergence. Some nonparametric estimates satisfying those constraints in the Poisson or in the Hawkes framework are highlighted. More-over, they share adaptive properties that are useful from a practical point of view. We show the performance of those methods on simulated data. We also provide a com-plete analysis with these tools on single unit activity recorded on a monkey during a sensory-motor task. Electronic supplementary material The online version of this article (doi:10.1186/2190-8567-4-3) contains supplementary material

Assessing the Macroeconomic Effects of Water Scarcity in South Africa using a CGE Model

National audienceWe develop a dynamic computable general equilibrium (CGE) model to assess the macroeconomic impacts of water scarcity and water (in)security in South Africa. The CGE model which includes a detailed representation of water resources (surface water, groundwater, wastewater, and seawater) has been calibrated with an updated social accounting matrix enabling to conduct policy simulations up to 2030. With the 17% expected increase of water scarcity (population growth, climate change, and poor management of water resources), the CGE model predicts a decrease of South African GDP by −0.44% in 2030. The long-term impact of water scarcity varies from one sector to another, the most negatively impacted sectors being those related to water. Due to water scarcity, unemployment will increase in the short term by 0.76%. In the long term (2030), unemployment is however expected to recover its baseline level. The increase in water scarcity is also predicted to have a negative impact on household welfare, household consumption being reduced by −0.47% in 2030. A particular concern for policy-makers might be that low-income households are expected to be more impacted by water scarcity than high-income households. Some policies may mitigate the negative impacts of water scarcity, the most promising ones being to promote water saving and to decrease non-revenue water