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  1. Article ; Online: The Role of Next-Generation Sequencing in Precision Medicine

    Margaret Morash / Hannah Mitchell / Himisha Beltran / Olivier Elemento / Jyotishman Pathak

    Journal of Personalized Medicine, Vol 8, Iss 3, p

    A Review of Outcomes in Oncology

    2018  Volume 30

    Abstract: Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming ...

    Abstract Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.
    Keywords precision medicine ; next generation sequencing ; oncology ; patient outcomes ; health insurance coverage ; Medicine ; R
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Applying clinical decision aids for the assessment and management of febrile infants presenting to emergency care in the UK and Ireland

    Kerry Woolfall / Mark D Lyttle / Damian Roland / Thomas Waterfield / Kathryn Wilson / Michael Barrett / Chris Watson / Hannah Mitchell / Etimbuk Umana / Steven Foster / Lisa McFetridge / Clare Mills / Hannah Norman-Bruce / Gareth McKeeman / Fiona A Lynn

    BMJ Open, Vol 13, Iss

    Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study protocol

    2023  Volume 9

    Abstract: Introduction Febrile infants 90 days and younger are at risk of invasive bacterial infections (bacteraemia and meningitis) and urinary tract infections. Together this is previously termed serious bacterial infection with an incidence of approximately 10– ... ...

    Abstract Introduction Febrile infants 90 days and younger are at risk of invasive bacterial infections (bacteraemia and meningitis) and urinary tract infections. Together this is previously termed serious bacterial infection with an incidence of approximately 10–20%. The National Institute for Health and Care Excellence guidance advocates a cautious approach with most infants requiring septic screening, parenteral broad-spectrum antibiotics and hospital admission. Internationally, variations exist in the approach to febrile infants, with European and North American guidance advocating a tailored approach based on clinical features and biomarker testing. None of the available international clinical decision aids (CDAs) has been validated in the UK and Irish cohorts. The aim of the Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study is to prospectively validate a range of CDAs in a UK and Irish population including CDAs that use procalcitonin testing.Methods and analysis The FIDO Study is a prospective multicentre mixed-methods cohort study conducted in UK and Irish hospitals. All infants aged 90 days and younger presenting with fever or history of fever (≥38°C) are eligible for inclusion. Infants will receive standard emergency clinical care without delay. Clinical data and blood samples will be collected, and consent will be obtained at the earliest appropriate opportunity using research without prior consent methodology. The performance and cost-effectiveness of CDAs will be assessed. An embedded qualitative study will explore clinician and caregiver views on different approaches to care and perceptions of risk.Ethics and dissemination This study was reviewed and approved by the Office for Research Ethics Committees Northern Ireland-Health and Social Care Research Ethics Committee B, Public Benefit and Privacy Panel for Health and Social Care Scotland, and Children’s Health Ireland Research and Ethics Committee Ireland. The results of this study will be presented at academic conferences and in peer-reviewed ...
    Keywords Medicine ; R
    Subject code 360
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Dynamic changes in cell size and corresponding cell fate after optic nerve injury

    Benjamin M. Davis / Li Guo / Nivedita Ravindran / Ehtesham Shamsher / Veerle Baekelandt / Hannah Mitchell / Anil A. Bharath / Lies De Groef / M. Francesca Cordeiro

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy ... ...

    Abstract Abstract Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Seroprevalence of SARS-CoV-2 antibodies in children of United Kingdom healthcare workers

    Mark David Lyttle / Derek Fairley / James McKenna / Claire Mcginn / Chris Watson / Hannah Mitchell / Jennifer Evans / Michael Corr / Rebecca Moore / Gala Rowe-Setz / Steven Foster / Lisa McFetridge / Julieann Maney / Michael David Shields / Tom Waterfield

    BMJ Open, Vol 10, Iss

    a prospective multicentre cohort study protocol

    2020  Volume 11

    Abstract: Background A novel coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Children typically have very mild, or no, symptoms of infection. This makes estimations of seroprevalence in children difficult. Research is therefore required to ... ...

    Abstract Background A novel coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Children typically have very mild, or no, symptoms of infection. This makes estimations of seroprevalence in children difficult. Research is therefore required to determine the seroprevalence of SARS-CoV-2 antibodies in children. The primary objective of this study is to report the seroprevalence of SARS-CoV-2 IgM and/or IgG antibodies in healthy children at baseline, 2 months and 6 months. This is the only longitudinal UK study of seroprevalence in an exclusively paediatric population. Determining the changing seroprevalence is of vital public health importance and can help inform decisions around the lifting of paediatric specific social distancing measures such as school closures and the cancellation of routine paediatric hospital services.Methods and analysis 1000 healthy children of healthcare workers aged between 2 and 15 years will be recruited from five UK sites (Belfast, Cardiff, Glasgow, London and Manchester). The children will undergo phlebotomy at baseline, 2 months and 6 months to measure IgM and/or IgG positivity to SARS-CoV-2. A sample size of 675 patients is required to detect a 5% change in seroprevalence at each time point assuming an alpha of 0.05 and a beta of 0.2. Adjusted probabilities for the presence of IgG and/or IgM antibodies and of SARS-CoV-2 infection will be reported using logistic regression models where appropriate.Ethics and dissemination Ethical approval was obtained from the London - Chelsea Research Ethics Committee (REC Reference—20/HRA/1731) and the Belfast Health & Social Care Trust Research Governance (Reference 19147TW-SW). Results of this study will be made available as preprints and submitted for publication in peer-reviewed journals.Trial registration number NCT0434740; Results
    Keywords Medicine ; R
    Subject code 360
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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