44,820 research outputs found

    Performance of the local reconstruction algorithms for the CMS hadron calorimeter with Run 2 data

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    A description is presented of the algorithms used to reconstruct energy deposited in the CMS hadron calorimeter during Run 2 (2015‚Äď2018) of the LHC. During Run 2, the characteristic bunch-crossing spacing for proton-proton collisions was 25 ns, which resulted in overlapping signals from adjacent crossings. The energy corresponding to a particular bunch crossing of interest is estimated using the known pulse shapes of energy depositions in the calorimeter, which are measured as functions of both energy and time. A variety of algorithms were developed to mitigate the effects of adjacent bunch crossings on local energy reconstruction in the hadron calorimeter in Run 2, and their performance is compared

    Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J‚ÄĎAggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging

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    Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ‚ąľ40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ‚ąľ11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures

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

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    Background: Approximately 450‚ÄČ000 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‚ÄČ093 individuals in the FHSC registry, 11‚ÄČ848 (18¬∑8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50¬∑2%) of 11‚ÄČ476 included individuals were female and 5720 (49¬∑8%) were male. Sex data were missing for 372 (3¬∑1%) of 11‚ÄČ848 individuals. Median age at registry entry was 9¬∑6 years (IQR 5¬∑8-13¬∑2). 10‚ÄČ099 (89¬∑9%) of 11‚ÄČ235 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‚ÄČ848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92¬∑4%] of 10‚ÄČ202) than in children and adolescents from non-high-income countries (199 [48¬∑0%] of 415). 3414 (31¬∑6%) of 10‚ÄČ804 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‚ÄČ428 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

    Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC