Search results for " Large"

Conceptual design of the International Axion Observatory (IAXO)

2014

The International Axion Observatory (IAXO) will be a forth generation axion helioscope. As its primary physics goal, IAXO will look for axions or axion-like particles (ALPs) originating in the Sun via the Primakoff conversion of the solar plasma photons. In terms of signal-to-noise ratio, IAXO will be about 4-5 orders of magnitude more sensitive than CAST, currently the most powerful axion helioscope, reaching sensitivity to axion-photon couplings down to a few $\times 10^{-12}$ GeV$^{-1}$ and thus probing a large fraction of the currently unexplored axion and ALP parameter space. IAXO will also be sensitive to solar axions produced by mechanisms mediated by the axion-electron coupling $g_{…

Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma

2021

Abstract Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded accor…

The relationship between Polypharmacy and Trajectories of Cognitive Decline in People with Dementia: a large representative cohort study

2019

Polypharmacy, defined through the number of medications prescribed, has been linked to a range of adverse health outcomes in people with dementia. It is however unclear whether a numerical threshold of concurrently prescribed drugs is a suitable predictor for cognitive decline. We aimed to test associations between polypharmacy and both short-term (six months) and long-term (three years) cognitive trajectories in patients with incident dementia. Using data from a large mental health and dementia care database in South London, a cohort of 12,148 patients (mean age = 80.7 years, 61.1% female, mean MMSE = 18.6) clinically diagnosed with dementia was identified. We determined the number of medi…

A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome

2010

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047).…

TGF-β Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD

2017

Background: The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD. Methods: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis. Results: TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium…

Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

2011

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through w…

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

2015

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cance…

Uncommon Presentations of Non-Hodgkin’s Lymphoma

2003

Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation

2006

International audience; Objective: Autism is a complex, largely genetic psychiatric disorder. In the majority of cases, the cause of autism is not known, but there is strong evidence for a genetic etiology. To identify candidate genes, the physical mapping of balanced chromosomal aberrations is a powerful strategy, since several genes have been characterized in numerous disorders. In this study, the authors analyzed a balanced reciprocal translocation arising de novo in a subject with autism and mental retardation. Method: The authors performed the physical mapping of the balanced 9q23/ 10q22 translocation by fluorescent in situ hybridization experiments using bacterial artificial chromosom…

Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium

2010

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-…