Hospital-acquired infections are emerging major concurrent conditions during the coronavirus disease (COVID-19) pandemic. We conducted a retrospective review of hospitalizations during March‒October ...2020 of adults tested by reverse transcription PCR for severe acute respiratory syndrome coronavirus 2. We evaluated associations of COVID-19 diagnosis with risk for laboratory-confirmed bloodstream infections (LCBIs, primary outcome), time to LCBI, and risk for death by using logistic and competing risks regression with adjustment for relevant covariates. A total of 10,848 patients were included in the analysis: 918 (8.5%) were given a diagnosis of COVID-19, and 232 (2.1%) had LCBIs during their hospitalization. Of these patients, 58 (25%) were classified as having central line‒associated bloodstream infections. After adjusting for covariates, COVID-19‒positive status was associated with higher risk for LCBI and death. Reinforcement of infection control practices should be implemented in COVID-19 wards, and review of superiority and inferiority ranking methods by National Healthcare Safety Network criteria might be needed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Offshore platforms, subsea pipelines, wells and related fixed structures supporting the oil and gas (O&G) industry are prevalent in oceans across the globe, with many approaching the end of their ...operational life and requiring decommissioning. Although structures can possess high ecological diversity and productivity, information on how they interact with broader ecological processes remains unclear. Here, we review the current state of knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological connectivity with natural marine habitats. There is a paucity of studies on the subject with only 33 papers specifically targeting connectivity and O&G structures, although other studies provide important related information. Evidence for O&G structures facilitating vertical and horizontal seascape connectivity exists for larvae and mobile adult invertebrates, fish and megafauna; including threatened and commercially important species. The degree to which these structures represent a beneficial or detrimental net impact remains unclear, is complex and ultimately needs more research to determine the extent to which natural connectivity networks are conserved, enhanced or disrupted. We discuss the potential impacts of different decommissioning approaches on seascape connectivity and identify, through expert elicitation, critical knowledge gaps that, if addressed, may further inform decision making for the life cycle of O&G infrastructure, with relevance for other industries (e.g. renewables). The most highly ranked critical knowledge gap was a need to understand how O&G structures modify and influence the movement patterns of mobile species and dispersal stages of sessile marine species. Understanding how different decommissioning options affect species survival and movement was also highly ranked, as was understanding the extent to which O&G structures contribute to extending species distributions by providing rest stops, foraging habitat, and stepping stones. These questions could be addressed with further dedicated studies of animal movement in relation to structures using telemetry, molecular techniques and movement models. Our review and these priority questions provide a roadmap for advancing research needed to support evidence‐based decision making for decommissioning O&G infrastructure.
Offshore platforms and related fixed structures supporting the oil and gas (O&G) industry are prevalent in all oceans. We review current knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological seascape connectivity. There is a paucity of studies assessing connectivity and O&G structures. We discuss existing knowledge and identify critical knowledge gaps for decision‐making, such as the need to understand how O&G structures modify and influence movement patterns of mobile species and dispersal. Our review and priority questions provide a roadmap for advancing research needed to support evidence‐based decision‐making for decommissioning O&G infrastructure.
Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA ...were identified in a genome-wide association study and meta-analysis.
We sought to investigate genetic susceptibility to PA.
Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations.
An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10−8), whereas SNPs associated with Src kinase–associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase–activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10−6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10−6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10−11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10−6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30.
This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.
Donepezil is an approved therapy for the treatment of Alzheimer's disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the ...pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes.
From the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6-12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison.
Donepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response.
Our data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment.
ClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.
Cancer immunotherapy has markedly improved the prognosis of patients with a broad variety of malignancies. However, benefits are weighed against unique toxicities, with immune-related adverse events ...(irAE) that are frequent and potentially life-threatening. The diagnosis and management of these events are challenging due to heterogeneity of timing onset, multiplicity of affected organs, and lack of non-invasive monitoring techniques. We demonstrate the use of a granzyme B-targeted PET imaging agent (GZP) for irAE identification in a murine model.
We generated a model of immunotherapy-induced adverse events in Foxp3-DTR-GFP mice bearing MC38 tumors. GZP PET imaging was performed to evaluate organs non-invasively. We validated imaging with ex vivo analysis, correlating the establishment of these events with the presence of immune infiltrates and granzyme B upregulation in tissue. To demonstrate the clinical relevance of our findings, the presence of granzyme B was identified through immunofluorescence staining in tissue samples of patients with confirmed checkpoint inhibitor-associated adverse events.
GZP PET imaging revealed differential uptake in organs affected by irAEs, such as colon, spleen, and kidney, which significantly diminished after administration of the immunosuppressor dexamethasone. The presence of granzyme B and immune infiltrates were confirmed histologically and correlated with significantly higher uptake in PET imaging. The presence of granzyme B was also confirmed in samples from patients that presented with clinical irAEs.
We demonstrate an interconnection between the establishment of irAEs and granzyme B presence and, for the first time, the visualization of those events through PET imaging.
Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis ...has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion.
Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day.
All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable.
The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
ClinicalTrials.gov identifier: NCT01163825 . Registered on 14 Jul 2010.
Elucidating compensatory mechanisms underpinning phonemic fluency (PF) may help to minimize its decline due to normal aging or neurodegenerative diseases. We investigated cortical brain networks ...potentially underpinning compensation of age-related differences in PF. Using graph theory, we constructed networks from measures of thickness for PF, semantic, and executive-visuospatial cortical networks. A total of 267 cognitively healthy individuals were divided into younger age (YA, 38-58 years) and older age (OA, 59-79 years) groups with low performance (LP) and high performance (HP) in PF: YA-LP, YA-HP, OA-LP, OA-HP. We found that the same pattern of reduced efficiency and increased transitivity was associated with both HP (compensation) and OA (aberrant network organization) in the PF and semantic cortical networks. When compared with the OA-LP group, the higher PF performance in the OA-HP group was associated with more segregated PF and semantic cortical networks, greater participation of frontal nodes, and stronger correlations within the PF cortical network. We conclude that more segregated cortical networks with strong involvement of frontal nodes seemed to allow older adults to maintain their high PF performance. Nodal analyses and measures of strength were helpful to disentangle compensation from the aberrant network organization associated with OA.
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