2,227 research outputs found
Higher order multi-point boundary value problems with sign-changing nonlinearities and nonhomogeneous boundary conditions
Collaborative Tagging of Phenotypic Data for Clinical and Translational Sciences
To fully understand results derived from genetic research, a patient’s genotype data must be integrated with other information about the individual (vital signs, height/weight, lab values, disease history – the phenotype of the patient) that can be obtained through clinical records. Within the clinical and translational sciences awards (CTSA), significant effort has been supported to expand translational research through the creation and mining of a phenotypic data warehouse (i2b2) that can be further linked to genotype data. However, this is just a first step towards meaningful use of the available information. Much of the information in electronic clinical records is trapped in unstructured free text, and inaccessible. Transforming this information into usable data has great potential to improve personalized healthcare and enhance the scientific enterprise. We are using “collaborative tagging,” a newer web 2.0 phenomenon used to structure information for accessibility online in which groups of individuals can add any word or phrase as a tag to identify an object (a weblog entry, a picture, etc.). Because taggers create whatever they deem as the most important tags, and are not required to select from a complex tree of predetermined tags, folksonomies can be a more palatable form of data entry than selected from a complex, predetermined list of tags. We will present our results on tagging of clinical notes by UMMS and community-based providers. This presentation was part of the retreat mini-symposium entitled: Data-Driven Approaches for Health Informatics
Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade
Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits
Berkeley Supernova Ia Program I: Observations, Data Reduction, and Spectroscopic Sample of 582 Low-Redshift Type Ia Supernovae
In this first paper in a series we present 1298 low-redshift (z\leq0.2)
optical spectra of 582 Type Ia supernovae (SNe Ia) observed from 1989 through
2008 as part of the Berkeley SN Ia Program (BSNIP). 584 spectra of 199 SNe Ia
have well-calibrated light curves with measured distance moduli, and many of
the spectra have been corrected for host-galaxy contamination. Most of the data
were obtained using the Kast double spectrograph mounted on the Shane 3 m
telescope at Lick Observatory and have a typical wavelength range of
3300-10,400 Ang., roughly twice as wide as spectra from most previously
published datasets. We present our observing and reduction procedures, and we
describe the resulting SN Database (SNDB), which will be an online, public,
searchable database containing all of our fully reduced spectra and companion
photometry. In addition, we discuss our spectral classification scheme (using
the SuperNova IDentification code, SNID; Blondin & Tonry 2007), utilising our
newly constructed set of SNID spectral templates. These templates allow us to
accurately classify our entire dataset, and by doing so we are able to
reclassify a handful of objects as bona fide SNe Ia and a few other objects as
members of some of the peculiar SN Ia subtypes. In fact, our dataset includes
spectra of nearly 90 spectroscopically peculiar SNe Ia. We also present
spectroscopic host-galaxy redshifts of some SNe Ia where these values were
previously unknown. [Abridged]Comment: 34 pages, 11 figures, 11 tables, revised version, re-submitted to
MNRAS. Spectra will be released in January 2013. The SN Database homepage
(http://hercules.berkeley.edu/database/index_public.html) contains the full
tables, plots of all spectra, and our new SNID template
An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration
Abstract Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive?compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA
RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord
ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients
Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice
The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans
Specialist Peri-Operative Allergy Clinic Services in the UK 2016: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6)
BACKGROUND: Guidelines for investigation of perioperative drug allergy exist, but the quality of services is unknown. Specialist perioperative anaphylaxis services were surveyed through the Royal College of Anaesthetists 6(th) National Audit Project. OBJECTIVES: We compare self-declared UK practice in specialist perioperative allergy services with national recommendations.
METHODS: A SurveyMonkey(™) questionnaire was distributed to providers of allergy services in the UK. Responses were assessed for adherence to the best practice recommendations of the British Society for Allergy and Clinical Immunology, the Association of Anaesthetists of Great Britain and Ireland and the National Institute for Health and Care Excellence (NICE) Guidance on Drug Allergy - CG183.
RESULTS: Over 1200 patients were evaluated in 44 centres annually. Variation in workload, waiting times, access, staffing and diagnostic approach was noted. Paediatric centres had the longest routine waiting times (most wait >13 weeks) in contrast to adult centres (most wait <12 weeks). Service leads are allergists/immunologists (91%) or anaesthetists (7%). Potentially important differences were seen in: testing repertoire [10/44 (23%) lacked BSACI compliant NMBA panels and 17/44 (39%) lacked a NAP6-defined extended panel; many failed to screen all cases for chlorhexidine 19/44 (43%) or latex 21/44 (48%)], staffing [only 26/44 (59%) had specialist nurses and 18/44 (41%) an anaesthetist], and provision of information [18/44 (41%) gave immediate information in clinic, and 5/44 (11%) on support groups]. Most centres were able to provide diagnostic challenges to antibiotics [40/44 (91%]) and local anaesthetics [41/44 (93%)].
CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic testing is not harmonised, with marked variability in the NMBA panels used to identify safe alternatives. Chlorhexidine and latex are not part of routine testing in many centres. Poor access to services and patient information provision require attention. Harmonisation of diagnostic approach is desirable, particularly with regard to a minimum NMBA panel for identification of safe alternatives. This article is protected by copyright. All rights reserved
ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors
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