313 research outputs found

    DoctorEye: A clinically driven multifunctional platform, for accurate processing of tumors in medical images

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    Copyright @ Skounakis et al.This paper presents a novel, open access interactive platform for 3D medical image analysis, simulation and visualization, focusing in oncology images. The platform was developed through constant interaction and feedback from expert clinicians integrating a thorough analysis of their requirements while having an ultimate goal of assisting in accurately delineating tumors. It allows clinicians not only to work with a large number of 3D tomographic datasets but also to efficiently annotate multiple regions of interest in the same session. Manual and semi-automatic segmentation techniques combined with integrated correction tools assist in the quick and refined delineation of tumors while different users can add different components related to oncology such as tumor growth and simulation algorithms for improving therapy planning. The platform has been tested by different users and over large number of heterogeneous tomographic datasets to ensure stability, usability, extensibility and robustness with promising results. AVAILABILITY: THE PLATFORM, A MANUAL AND TUTORIAL VIDEOS ARE AVAILABLE AT: http://biomodeling.ics.forth.gr. It is free to use under the GNU General Public License

    Risk of 16 cancers across the full glycemic spectrum: a population-based cohort study using the UK Biobank

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    INTRODUCTION: Diabetes is observed to increase cancer risk, leading to hypothesized direct effects of either hyperglycemia or medication. We investigated associations between glycosylated hemoglobin (HbA1c) across the whole glycemic spectrum and incidence of 16 cancers in a population sample with comprehensive adjustment for risk factors and medication. RESEARCH DESIGN AND METHODS: Linked data from the UK Biobank and UK cancer registry for all individuals with baseline HbA1c and no history of cancer at enrollment were used. Incident cancer was based on International Classification of Diseases - 10th Edition diagnostic codes. Age-standardized incidence rates were estimated by HbA1c category. Associations between HbA1c, modeled as a restricted cubic spline, and cancer risk were estimated using Cox proportional hazards models. RESULTS: Among 378 253 individuals with average follow-up of 7.1 years, 21 172 incident cancers occurred. While incidence for many of the 16 cancers was associated with hyperglycemia in crude analyses, these associations disappeared after multivariable adjustment, except for pancreatic cancer (HR 1.55, 95% CI 1.22 to 1.98 for 55 vs 35 mmol/mol), and a novel finding of an inverse association between HbA1c and premenopausal breast cancer (HR 1.27, 95% CI 1.00 to 1.60 for 25 vs 35 mmol/mol; HR 0.71, 95% CI 0.54 to 0.94 for 45 vs 35 mmol/mol), not observed for postmenopausal breast cancer. Adjustment for diabetes medications had no appreciable impact on HRs for cancer. CONCLUSIONS: Apart from pancreatic cancer, we did not demonstrate any independent positive association between HbA1c and cancer risk. These findings suggest that the potential for a cancer-inducing, direct effect of hyperglycemia may be misplaced

    Type 2 diabetes risks and determinants in 2nd generation migrants and mixed ethnicity people of South Asian and African Caribbean descent in the UK

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    Objectives: Excess risks of type 2 diabetes mellitus (T2DM) in UK South Asians (SA) and African Caribbeans (AC) compared to Europeans remain unexplained. We studied risks and determinants of T2DM in first- and second-generation (born in the UK) migrants, and in those of mixed ethnicity. / Design: Cross sectional analysis comparing T2DM in 2nd versus 1st generation migrants, and mixed ethnicity with non-mixed groups. Risks and explanations were analysed using logistic regression and mediation analysis, respectively. / Setting: UK Biobank, a population-based cohort of ~500k participants aged 40-69 at recruitment. / Participants: Ethnicity was both self-reported and genetically-assigned using admixture level scores. Europeans, mixed European/South Asians (MixESA), mixed European/African Caribbeans (MixEAC), SA and AC groups were analysed, matched for age and sex to enable comparison. / Main outcome measures: T2DM using self-report and glycated haemoglobin. / Results: T2DM prevalence was three to five times higher in SA and AC compared with Europeans [OR (95%CI): 4.80(3.60,6.40) and 3.30(2.70,4.10), respectively]. T2DM was 20-30% lower in second-versus first-generation SA and AC [0.78(0.60,1.01) and 0.71(0.57,0.87), respectively]. Favourable adiposity contributed to lower risk in 2nd generation migrants. T2DM in mixed populations was lower than comparator ethnic groups [MixESA versus SA 0.29(0.21,0.39), MixEAC versus AC 0.48(0.37,0.62)] and higher than Europeans, in MixESA 1.55(1.11, 2.17), and in MixEAC 2.06 (1.53, 2.78). Greater socioeconomic deprivation accounted for 17% and 42% of the excess T2DM risk in MixESA and MixEAC compared to Europeans, respectively. Replacing self-reported with genetically-assigned ethnicity corroborated the mixed population analysis. / Conclusions: T2DM risks in 2nd generation SA and AC migrants are a fifth lower than 1st generation migrants. Mixed ethnicity risks were markedly lower than SA and AC groups, though remaining higher than in Europeans. Distribution of environmental risk factors, largely obesity and socioeconomic status, play a key role in accounting for ethnic differences in T2DM risk

    The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomisation Study in the UK Biobank

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    We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from UK Biobank (n∼500,000). Our exposures were genetic instruments for type-2 diabetes (157 variants) and HbA1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal and white matter hyperintensity volumes, Alzheimer’s dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and, diabetes and HbA1c. We used conventional inverse-variance weighted (IVW) MR, alongside MR sensitivity analyses. Using IVW, genetic liability to type-2 diabetes was not associated with reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife

    Type 2 diabetes risks and determinants in second-generation migrants and mixed ethnicity people of South Asian and African Caribbean descent in the UK

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    AIMS/HYPOTHESIS: Excess risks of type 2 diabetes in UK South Asians (SA) and African Caribbeans (AC) compared with Europeans remain unexplained. We studied risks and determinants of type 2 diabetes in first- and second-generation (born in the UK) migrants, and in those of mixed ethnicity. METHODS: Data from the UK Biobank, a population-based cohort of ~500,000 participants aged 40-69 at recruitment, were used. Type 2 diabetes was assigned using self-report and HbA1c. Ethnicity was both self-reported and genetically assigned using admixture level scores. European, mixed European/South Asian (MixESA), mixed European/African Caribbean (MixEAC), SA and AC groups were analysed, matched for age and sex to enable comparison. In the frames of this cross-sectional study, we compared type 2 diabetes in second- vs first-generation migrants, and mixed ethnicity vs non-mixed groups. Risks and explanations were analysed using logistic regression and mediation analysis, respectively. RESULTS: Type 2 diabetes prevalence was markedly elevated in SA (599/3317 = 18%) and AC (534/4180 = 13%) compared with Europeans (140/3324 = 4%). Prevalence was lower in second- vs first-generation SA (124/1115 = 11% vs 155/1115 = 14%) and AC (163/2200 = 7% vs 227/2200 = 10%). Favourable adiposity (i.e. lower waist/hip ratio or BMI) contributed to lower risk in second-generation migrants. Type 2 diabetes in mixed populations (MixESA: 52/831 = 6%, MixEAC: 70/1045 = 7%) was lower than in comparator ethnic groups (SA: 18%, AC: 13%) and higher than in Europeans (4%). Greater socioeconomic deprivation accounted for 17% and 42% of the excess type 2 diabetes risk in MixESA and MixEAC compared with Europeans, respectively. Replacing self-reported with genetically assigned ethnicity corroborated the mixed ethnicity analysis. CONCLUSIONS/INTERPRETATION: Type 2 diabetes risks in second-generation SA and AC migrants are a fifth lower than in first-generation migrants. Mixed ethnicity risks were markedly lower than SA and AC groups, though remaining higher than in Europeans. Distribution of environmental risk factors, largely obesity and socioeconomic status, appears to play a key role in accounting for ethnic differences in type 2 diabetes risk

    The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis

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    Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped. Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively). Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM
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