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- Amgad, M, et al.
(författare)
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
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- Veronese, N., et al.
(författare)
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Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects
- 2015
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015
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Forskningsöversikt (refereegranskat)abstract
- Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, 30kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI=1.26-1.58) for underweight, 0.85 (95% CI=0.73-0.99) for overweight and 0.74 (95% CI=0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR=1.65 [95% CI=1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
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- Home, P.D., et al.
(författare)
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Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial
- 2009
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Ingår i: The Lancet. - : Elsevier: Lancet. - 0140-6736 .- 1474-547X. ; 373:9681, s. 2125-2135
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. Methods: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A 1c (HbA 1c) of 7·9% were randomly assigned to addition of rosiglitazone (n=2220) or to a combination of metformin and sulfonylurea (active control group, n=2227). The primary endpoint was cardiovascular hospitalisation or cardiovascular death, with a hazard ratio (HR) non-inferiority margin of 1·20. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00379769. Findings: 321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 5·5-year follow-up, meeting the criterion of non-inferiority (HR 0·99, 95% CI 0·85-1·16). HR was 0·84 (0·59-1·18) for cardiovascular death, 1·14 (0·80-1·63) for myocardial infarction, and 0·72 (0·49-1·06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2·10, 1·35-3·27, risk difference per 1000 person-years 2·6, 1·1-4·1). Upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean HbA 1c was lower in the rosiglitazone group than in the control group at 5 years. Interpretation: Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs. Funding: GlaxoSmithKline plc, UK. © 2009 Elsevier Ltd. All rights reserved.
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- Beck, Dani, et al.
(författare)
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Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults
- 2022
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Ingår i: NeuroImage. - : Elsevier Science Ltd. - 2213-1582. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropometric features fail to describe regional differences in body fat distribution and composition. The sample consisted of baseline brain magnetic resonance imaging (MRI) acquired from 790 healthy participants aged 18-94 years (mean +/- standard deviation (SD) at baseline: 46.8 +/- 16.3), and follow-up brain MRI collected from 272 of those individuals (two time-points with 19.7 months interval, on average (min = 9.8, max = 35.6). Of the 790 included participants, cross-sectional body MRI data was available from a subgroup of 286 participants, with age range 19-86 (mean = 57.6, SD = 15.6). Adopting a mixed cross-sectional and longitudinal design, we investigated cross-sectional body magnetic resonance imaging measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry (T1) and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) - the difference between actual age and the prediction of the brains biological age - at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.
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- Brommesson, Peter, et al.
(författare)
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Assessing intrastate shipments from interstate data and expert opinion
- 2021
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Ingår i: Royal Society Open Science. - : Royal Society of Open Science. - 2054-5703. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Live animal shipments are a potential route for transmitting animal diseases between holdings and are crucial when modelling spread of infectious diseases. Yet, complete contact networks are not available in all countries, including the USA. Here, we considered a 10% sample of Interstate Certificate of Veterinary Inspections from 1 year (2009). We focused on distance dependence in contacts and investigated how different functional forms affect estimates of unobserved intrastate shipments. To further enhance our predictions, we included responses from an expert elicitation survey about the proportion of shipments moving intrastate. We used hierarchical Bayesian modelling to estimate parameters describing the kernel and effects of expert data. We considered three functional forms of spatial kernels and the inclusion or exclusion of expert data. The resulting six models were ranked by widely applicable information criterion (WAIC) and deviance information criterion (DIC) and evaluated through within- and out-of-sample validation. We showed that predictions of intrastate shipments were mildly influenced by the functional form of the spatial kernel but kernel shapes that permitted a fat tail at large distances while maintaining a plateau-shaped behaviour at short distances better were preferred. Furthermore, our study showed that expert data may not guarantee enhanced predictions when expert estimates are disparate.
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- Fugelstad, A, et al.
(författare)
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Use of morphine and 6-monoacetylmorphine in blood for the evaluation of possible risk factors for sudden death in 192 heroin users
- 2003
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 98:4, s. 463-470
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To detect risk factors for sudden death from heroin injection. Design: Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Setting: Stockholm, Sweden. Measurements: Autopsy investigation and toxicological analysis of blood and urine: and police reports. Findings: In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. Conclusions: We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.
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