Publications by authors named "Langan C"

Field experiments were performed to evaluate the deposition velocity of tritium oxide within a forest environment at the Savannah River Site near Aiken, SC. Field releases were designed to guide selection of deposition velocity values for use in safety-basis modeling. Six releases of deuterium oxide were conducted in 2020 and 2021 with corresponding air samples during and following each release.

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Conditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh.

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Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR-Cas9 loss-of-function screens across 851 human cancer cell lines and found that frequent overexpression of SLC34A2-encoding a phosphate importer-is correlated with sensitivity to loss of the phosphate exporter XPR1, both in vitro and in vivo. In patient-derived tumor samples, we observed frequent PAX8-dependent overexpression of SLC34A2, XPR1 copy number amplifications and XPR1 messenger RNA overexpression.

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Objective: To investigate the presence, degree, predictors, and trajectory of dysphagia, dysphonia, and dysarthria among adults hospitalized with COVID-19 across the Republic of Ireland (ROI) during the first wave of the pandemic.

Study Design: Prospective observational cohort study.

Methods: Adults with confirmed COVID-19 who were admitted into 14 participating acute hospitals across ROI and referred to speech and language therapy between March 1st and June 30th 2020 were recruited.

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The opioid epidemic led to an increase in the number of neonatal opioid withdrawal syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS.

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Objectives: This study aims to (i) investigate post-extubation dysphagia and dysphonia amongst adults intubated with SARS-COV-2 (COVID-19) and referred to speech and language therapy (SLT) in acute hospitals across the Republic of Ireland (ROI) between March and June 2020; (ii) identify variables predictive of post-extubation oral intake status and dysphonia and (iii) establish SLT rehabilitation needs and services provided to this cohort.

Design: A multi-site prospective observational cohort study.

Participants: One hundred adults with confirmed COVID-19 who were intubated across eleven acute hospital sites in ROI and who were referred to SLT services between March and June 2020 inclusive.

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T lymphoma cells may constitutively express PD-1 and PD-L1. The relative role of PD-1 and PD-L1 in T lymphoma is incompletely understood. We report here that PD-1 PDL-1 human T lymphoma cells exhibit constitutive hyperactivation of the TCR signaling and do not respond to PD-L1-mediated suppression in vitro.

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Rationale: Methamphetamine (MA) addiction is a major public health issue in the USA, with a poorly understood genetic component. We previously identified heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1; H1) as a quantitative trait gene underlying sensitivity to MA-induced behavioral sensitivity. Mice heterozygous for a frameshift deletion in the first coding exon of H1 (H1) showed reduced MA phenotypes including oral self-administration, locomotor activity, dopamine release, and dose-dependent differences in MA conditioned place preference.

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Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB.

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Background: Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the 'rich-club', represents an important network for integration of brain functioning.

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Delirium is an acute and usually transient severe neuropsychiatric syndrome associated with significant long-term physical morbidity. However, its chronic psychiatric sequelae remain poorly characterized. To investigate the prevalence of psychiatric symptoms, namely anxiety, depressive, and post-traumatic stress disorder (PTSD) symptoms after delirium, a systematic literature search of MEDLINE, EMBASE and PsycINFO databases was performed independently by two authors in March 2016.

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Retinal image analysis is emerging as a key source of biomarkers of chronic systemic conditions affecting the cardiovascular system and brain. The rapid development and increasing diversity of commercial retinal imaging systems present a challenge to image analysis software providers. In addition, clinicians are looking to extract maximum value from the clinical imaging taking place.

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Previous structural magnetic resonance imaging (S-MRI) studies of bipolar disorder have reported variable morphological changes in subcortical brain structures and ventricles. This study aimed to establish trait-related subcortical volumetric and shape abnormalities in a large, homogeneous sample of prospectively confirmed euthymic bipolar I disorder (BD-I) patients (n=60), compared with healthy volunteers (n=60). Participants were individually matched for age and gender.

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Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively.

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Objective: The study sought to assess opinions and attitudes of general practitioners (GPs) in Ireland towards fitness to drive (FTD) assessment in people older than 65 years old as well as to gather information on current assessment practices.

Method: A postal-based cross-sectional survey was carried out with 603 GP practices randomly selected using the Irish College of General Practitioners database.

Results: Response rate was 42.

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Load theory (Lavie, N., Hirst, A., De Fockert, J.

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Objectives: A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients.

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Background: White matter microstructural changes detected using diffusion tensor imaging have been reported in bipolar disorder. However, findings are heterogeneous, which may be related to the use of analysis techniques that cannot adequately model crossing fibers in the brain. We therefore sought to identify altered diffusion anisotropy and diffusivity changes using an improved high angular resolution fiber-tracking technique.

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Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies.

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Dissecting trait neurobiological abnormalities in bipolar disorder (BD) from those characterizing episodes of mood disturbance will help elucidate the aetiopathogenesis of the illness. This selective review highlights the immunological, neuroendocrinological, molecular biological and neuroimaging abnormalities characteristic of BD, with a focus on those likely to reflect trait abnormalities by virtue of their presence in euthymic patients or in unaffected relatives of patients at high genetic liability for illness. Trait neurobiological abnormalities of BD include heightened pro-inflammatory function and hypothalamic-pituitary-adrenal axis dysfunction.

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Objective: Psychiatric illness and the use of psychotropic medication are recognised as factors that may impair driving ability. Clinicians in the UK have a legal duty to advise patients on the effects of illness and prescribed medication on driving ability. Although clinicians in Ireland have no equivalent legal obligations, good medical practice suggests that doctors should be aware of whether patients are active drivers, and issue appropriate advice, supported by adequate documentation in clinical notes.

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Pulmonary embolism is one of the greatest diagnostic challenges in emergency medicine. New techniques and strategies constantly arise for the diagnosis and treatment of this disease. A review of the new diagnostic and treatment modalities for pulmonary embolism (PE) suggests that it should be suspected in any patient with unexplained dyspnea, tachypnea, or chest pain.

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In a randomized, open-label, controlled, multicentre study, the clinical and bacteriological efficacy, safety and tolerability of oral gemifloxacin (320 mg once daily, 5 days) was compared with sequential intravenous (i.v.) ceftriaxone (1 g once daily, maximum 3 days) followed by oral cefuroxime axetil (500 mg twice daily, maximum 7 days) in adult hospitalized patients with acute exacerbations of chronic bronchitis (AECB) (n = 274).

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There is little published information on the measurement of health status or quality of life in acute exacerbations of chronic bronchitis. The measure yourself medical outcome profile (MYMOP), the medical outcomes study 6-item general health survey (MOS-6A), and EuroQoL (EQ-5D) were evaluated in 81 patients with acute exacerbations of Type-1 chronic bronchitis presenting at a single general practice centre in Glasgow. The questionnaires were administered at the first clinic visit and at a second visit within 1 week of treatment completion.

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Objectives: To assess the efficacy and tolerability of three antibiotic regimens in patients with acute exacerbation of chronic bronchitis.

Methods: In this double-blind, randomized, multicentered, parallel-group study, patients received once-daily cefdinir 600 mg, twice-daily cefdinir 300 mg, or twice-daily cefuroxime axetil 250 mg for 10 days. Primary efficacy measures were microbiologic eradication rate, by pathogen and by patient, and clinical response rate, by patient.

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