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  1. Article ; Online: Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank

    David A. Kolin / Scott Kulm / Olivier Elemento

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Abstract Both clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown. Using Cox ... ...

    Abstract Abstract Both clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown. Using Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We then created a polygenic risk score of 36 single nucleotide polymorphisms and a clinical score determined by age, sex, body mass index, previous cancer diagnosis, smoking status, and fracture in the last 5 years. Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (subhazard ratio, 4.37 [95% CI, 3.85–4.97]) or high genetic risk (subhazard ratio, 3.02 [95% CI, 2.63–3.47]) relative to participants at low clinical or genetic risk, respectively. The combined model, consisting of clinical and genetic components, was significantly better than either the clinical or the genetic model alone (P < 0.001). Participants at high risk in the combined score had nearly an eightfold increased risk of venous thromboembolism relative to participants at low risk (subhazard ratio, 7.51 [95% CI, 6.28–8.98]). This risk score can be used to guide decisions regarding venous thromboembolism prophylaxis, although external validation is needed.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Publisher Correction

    David A. Kolin / Scott Kulm / Olivier Elemento

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank

    2021  Volume 4

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    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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  3. Article ; Online: Clinical and Genetic Characteristics of Covid-19 Patients from UK Biobank

    David A Kolin / Scott Kulm / Olivier Elemento

    Abstract: We conducted an analysis of 669 Covid-19 positive patients within the UK Biobank cohort, a prospective cohort including over 500,000 participants. Our analyses led to several findings. We found that black participants in the cohort were over four times ... ...

    Abstract We conducted an analysis of 669 Covid-19 positive patients within the UK Biobank cohort, a prospective cohort including over 500,000 participants. Our analyses led to several findings. We found that black participants in the cohort were over four times more likely to be diagnosed with Covid-19 than white participants. In order to assess for confounding, we produced - to our knowledge - the first multivariable adjusted estimate of the association of racial characteristics with Covid-19. Our adjusted estimates indicated that black participants remained at over threefold increased risk of Covid-19 relative to white participants. Exploratory analyses identified that 22.9% of Covid-19 positive black patients were using either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, relative to just 6.7% of all black participants. Our genetic analyses confirmed the finding of a previous report noting an association of blood type A with Covid-19, and we discovered a novel genetic association with HLA DQA1_509 that remained significant even after Bonferroni correction.
    Keywords covid19
    Publisher medrxiv
    Document type Article ; Online
    DOI 10.1101/2020.05.05.20075507
    Database COVID19

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  4. Article ; Online: Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank.

    David A Kolin / Scott Kulm / Paul J Christos / Olivier Elemento

    PLoS ONE, Vol 15, Iss 11, p e

    2020  Volume 0241264

    Abstract: Background Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people worldwide. Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19. In this study, we analyzed the effects of ... ...

    Abstract Background Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people worldwide. Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19. In this study, we analyzed the effects of clinical, regional, and genetic factors on Covid-19 positive status. Methods The UK Biobank is a longitudinal cohort study that recruited participants from 2006 to 2010 from throughout the United Kingdom. Covid-19 test results were provided to UK Biobank starting on March 16, 2020. The main outcome measure in this study was Covid-19 positive status, determined by the presence of any positive test for a single individual. Clinical risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed using census features local to each participant's home zone. We used robust adjusted Poisson regression with clustering by testing laboratory to estimate relative risk. Blood types were derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association were conducted using logistic-Firth hybrid regression. Results This prospective cohort study included 397,064 UK Biobank participants, of whom 968 tested positive for Covid-19. The unadjusted relative risk of Covid-19 for Black participants was 3.66 (95% CI 2.83-4.74), compared to White participants. Adjusting for Townsend deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86-3.20). Comorbidities that significantly increased Covid-19 risk included chronic obstructive pulmonary disease (adjusted relative risk [ARR] 1.64, 95% CI 1.18-2.27), ischemic heart disease (ARR 1.48, 95% CI 1.16-1.89), and depression (ARR 1.32, 95% CI 1.03-1.70). There was some evidence that angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13-1.93) were associated with increased risk of Covid-19. Each standard deviation increase in the number of total individuals living in a participant's locality was associated with increased risk of Covid-19 (ARR 1.14, 95% CI 1.08-1.20). ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Risk factors for blood transfusion in traumatic and postpartum hemorrhage patients

    David A Kolin / Haleema Shakur-Still / Adenike Bello / Rizwana Chaudhri / Imelda Bates / Ian Roberts

    PLoS ONE, Vol 15, Iss 6, p e

    Analysis of the CRASH-2 and WOMAN trials.

    2020  Volume 0233274

    Abstract: BACKGROUND:Hemorrhage is a leading cause of death after trauma and childbirth. In response to severe hemorrhage, bleeding patients often receive transfusions of red blood cells, plasma, platelets, or other blood components. We examined risk factors for ... ...

    Abstract BACKGROUND:Hemorrhage is a leading cause of death after trauma and childbirth. In response to severe hemorrhage, bleeding patients often receive transfusions of red blood cells, plasma, platelets, or other blood components. We examined risk factors for transfusion in acute severe bleeding in two trials of over 20,000 patients to better understand factors associated with transfusion likelihood. STUDY DESIGN AND METHODS:We conducted a cohort analysis of data from the CRASH-2 and WOMAN trials, two multinational trials that recruited patients with traumatic and postpartum hemorrhage, respectively. For each trial, we examined the effect of 10 factors on blood transfusion likelihood. Univariate and multivariate Poisson regressions were used to analyze the relationship between risk factors and blood transfusion. RESULTS:Of the 20,207 traumatic hemorrhage patients, 10,232 (51%) received blood components. Of the 20,060 women with postpartum hemorrhage, 10,958 (55%) received blood components. For patients who suffered from traumatic hemorrhage, those greater than three hours from injury to hospitalization were more likely to be transfused (ARR 1.37; 95% CI, 1.20-1.56). Postpartum hemorrhage patients had an increased likelihood of transfusion if they gave birth outside the hospital (ARR 1.30; 95% CI 1.22-1.39), gave birth more than three hours before hospitalization (ARR 1.09; 95% CI 1.01-1.17), had a Caesarean section (ARR 1.16; 95% CI 1.08-1.25), and if they had any identifiable causes of hemorrhage other than uterine atony. CONCLUSION:Several risk factors are associated with an increased likelihood of transfusion in traumatic and postpartum hemorrhage patients. Altering modifiable factors, by reducing time from injury or childbirth to hospitalization, for example, might be able to reduce transfusions and their complications. TRIAL REGISTRATION:CRASH-2 is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. WOMAN is registered as ISRCTN76912190, ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  6. Article ; Online: Reversible association with motor proteins (RAMP)

    Carlos M Guardia / Raffaella De Pace / Aritra Sen / Amra Saric / Michal Jarnik / David A Kolin / Ambarish Kunwar / Juan S Bonifacino

    PLoS Biology, Vol 17, Iss 5, p e

    A streptavidin-based method to manipulate organelle positioning.

    2019  Volume 3000279

    Abstract: We report the development and characterization of a method, named reversible association with motor proteins (RAMP), for manipulation of organelle positioning within the cytoplasm. RAMP consists of coexpressing in cultured cells (i) an organellar protein ...

    Abstract We report the development and characterization of a method, named reversible association with motor proteins (RAMP), for manipulation of organelle positioning within the cytoplasm. RAMP consists of coexpressing in cultured cells (i) an organellar protein fused to the streptavidin-binding peptide (SBP) and (ii) motor, neck, and coiled-coil domains from a plus-end-directed or minus-end-directed kinesin fused to streptavidin. The SBP-streptavidin interaction drives accumulation of organelles at the plus or minus end of microtubules, respectively. Importantly, competition of the streptavidin-SBP interaction by the addition of biotin to the culture medium rapidly dissociates the motor construct from the organelle, allowing restoration of normal patterns of organelle transport and distribution. A distinctive feature of this method is that organelles initially accumulate at either end of the microtubule network in the initial state and are subsequently released from this accumulation, allowing analyses of the movement of a synchronized population of organelles by endogenous motors.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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