| 1. |
- Hjort, Rebecka, et al.
(författare)
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Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)
- 2017
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Ingår i: Diabetes & Metabolism. - : Elsevier BV. - 1262-3636 .- 1878-1780. ; 43:6, s. 536-542
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Tidskriftsartikel (refereegranskat)abstract
- Background: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age. <. 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.
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| 4. |
- Ahlberg, Ernst, et al.
(författare)
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Using conformal prediction to prioritize compound synthesis in drug discovery
- 2017
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Ingår i: Proceedings of Machine Learning Research. - Stockholm : Machine Learning Research. ; , s. 174-184
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Konferensbidrag (refereegranskat)abstract
- The choice of how much money and resources to spend to understand certain problems is of high interest in many areas. This work illustrates how computational models can be more tightly coupled with experiments to generate decision data at lower cost without reducing the quality of the decision. Several different strategies are explored to illustrate the trade off between lowering costs and quality in decisions.AUC is used as a performance metric and the number of objects that can be learnt from is constrained. Some of the strategies described reach AUC values over 0.9 and outperforms strategies that are more random. The strategies that use conformal predictor p-values show varying results, although some are top performing.The application studied is taken from the drug discovery process. In the early stages of this process compounds, that potentially could become marketed drugs, are being routinely tested in experimental assays to understand the distribution and interactions in humans.
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| 5. |
- Arvidsson, Staffan, et al.
(författare)
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Prediction of Metabolic Transformations using Cross Venn-ABERS Predictors
- 2017
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Ingår i: Conformal and Probabilistic Prediction with Applications (COPA) 2017. ; , s. 118-131
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Konferensbidrag (refereegranskat)abstract
- Prediction of drug metabolism is an important topic in the drug discovery process, and we here present a study using probabilistic predictions applying Cross Venn-ABERS Predictors (CVAPs) on data for site-of-metabolism. We used a dataset of 73599 biotransformations, applied SMIRKS to define biotransformations of interest and constructed five datasets where chemical structures were represented using signatures descriptors. The results show that CVAP produces well-calibrated predictions for all datasets with good predictive capability, making CVAP an interesting method for further exploration in drug discovery applications.
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| 6. |
- Asan, Noor Badariah, 1984-, et al.
(författare)
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Intra-body microwave communication through adipose tissue
- 2017
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Ingår i: Healthcare technology letters. - : The Institution of Engineering and Technology. - 2053-3713. ; 4:4, s. 115-121
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Tidskriftsartikel (refereegranskat)abstract
- The human body can act as a medium for the transmission of electromagnetic waves in the wireless body sensor networks context. However, there are transmission losses in biological tissues due to the presence of water and salts. This Letter focuses on lateral intra-body microwave communication through different biological tissue layers and demonstrates the effect of the tissue thicknesses by comparing signal coupling in the channel. For this work, the authors utilise the R-band frequencies since it overlaps the industrial, scientific and medical radio (ISM) band. The channel model in human tissues is proposed based on electromagnetic simulations, validated using equivalent phantom and ex-vivo measurements. The phantom and ex-vivo measurements are compared with simulation modelling. The results show that electromagnetic communication is feasible in the adipose tissue layer with a low attenuation of approximate to 2 dB per 20 mm for phantom measurements and 4 dB per 20 mm for ex-vivo measurements at 2 GHz. Since the dielectric losses of human adipose tissues are almost half of ex-vivo tissue, an attenuation of around 3 dB per 20 mm is expected. The results show that human adipose tissue can be used as an intra-body communication channel.
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| 7. |
- Bjurman, Christian, 1983, et al.
(författare)
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Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
- 2017
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Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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| 8. |
- Broman, M., et al.
(författare)
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Trace elements in patients on continuous renal replacement therapy
- 2017
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 61:6, s. 650-659
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Intensive care patients with acute kidney injury (AKI), treated with continuous renal replacement therapy (CRRT) are at great risk for disturbances in plasma levels of trace elements due to the underlying illness, AKI, and dialysis. This study was performed to increase our knowledge regarding eight different trace elements during CRRT. Methods: Thirty one stable patients with AKI, treated with CRRT, were included in the study. Blood, plasma and effluent samples were taken at the start of the study and 36 ± 12 h later. A group of 48 healthy volunteers were included as controls and exposed to one fasting blood sample. Samples were analysed for trace elements (Cr, Cu, Mn, Co, Zn, Rb, Mo, Se) and standard blood chemistry. Results: Blood and plasma levels of selenium and rubidium were significantly reduced while the levels of chromium, cobalt, and molybdenum were significantly increased in the study group vs. healthy volunteers. There was an uptake of chromium, manganese, and zinc. Molybdenum mass balance was around zero. For selenium, copper, and rubidium there were a marked loss. Conclusions: The low levels of selenium and rubidium in blood and plasma from CRRT patients, together with the loss via CRRT effluent, raises the possibility of the need for selenium supplementation in this group of patients, despite the unchanged levels during the short study period. Further investigations on the effect of additional administration of trace elements to CRRT patients would be of interest.
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| 9. |
- Carlbom, Lina, et al.
(författare)
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[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:5, s. 1286-1292
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Tidskriftsartikel (refereegranskat)abstract
- [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.
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| 10. |
- Carlsson, Axel C., et al.
(författare)
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High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction
- 2017
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 228, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.
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