Machine learning, unsupervised learning and stain normalization in digital nephropathology

Chronic kidney disease is a serious health challenge and still, the field of study lacks awareness and funding. Improving the efficiency of diagnosing chronic disease is important. Machine learning can be used for various tasks in order to make CKD diagnosis more efficient. If the disease is discovered quickly it can be possible to reverse changes. In this project, we explore techniques that can improve clustering of glomeruli images. The current thesis evaluates the effects of applying stain normalization to nephropathological data in order to improve unsupervised learning cluster- ing. A unsupervised learning pipeline was implemented in order to evaluate the effects of using stain normalization techniques with different reference images. The stain normalization techniques that were implemented are: Reinhard stain normalization, Macenko stain normalization and Structure preserving color normalization. The evaluation of these methods was done by measuring clustering results from the unsupervised learning pipeline, using the Adjusted Rand Index metric. The results indicate that using these techniques will increase the cluster agreement between results and true labels for the data. Six reference images were used for each stain nor- malization technique. The average Adjusted Rand Index score for all ref- erence images was increased using all three stain normalization techniques. The best performing method overall was the Reinhard stain normalization technique. This method gave both the highest single experiment and aver- age score. The other normalization methods both have one score close to zero (unsuccessful clustering), and structure preserving color normalization would outperform the Reinhard method if this single clustering was more successful.Chronic kidney disease is a serious health challenge and still, the field of study lacks awareness and funding. Improving the efficiency of diagnosing chronic disease is important. Machine learning can be used for various tasks in order to make CKD diagnosis more efficient. If the disease is discovered quickly it can be possible to reverse changes. In this project, we explore techniques that can improve clustering of glomeruli images. The current thesis evaluates the effects of applying stain normalization to nephropathological data in order to improve unsupervised learning cluster- ing. A unsupervised learning pipeline was implemented in order to evaluate the effects of using stain normalization techniques with different reference images. The stain normalization techniques that were implemented are: Reinhard stain normalization, Macenko stain normalization and Structure preserving color normalization. The evaluation of these methods was done by measuring clustering results from the unsupervised learning pipeline, using the Adjusted Rand Index metric. The results indicate that using these techniques will increase the cluster agreement between results and true labels for the data. Six reference images were used for each stain nor- malization technique. The average Adjusted Rand Index score for all ref- erence images was increased using all three stain normalization techniques. The best performing method overall was the Reinhard stain normalization technique. This method gave both the highest single experiment and aver- age score. The other normalization methods both have one score close to zero (unsuccessful clustering), and structure preserving color normalization would outperform the Reinhard method if this single clustering was more successful

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Screening or constraining? The relationship between participation and target achievement in transboundary air pollution treaties

Enforcement and management scholars alike expect that countries participating in an international agreement will more likely achieve predetermined targets than nonparticipating countries will. The management school ascribes this expected association to a constraining effect of the treaty; the enforcement school ascribes it to a screening effect. If the latter conjecture is correct, the association between participation and target achievement should significantly weaken (or even vanish) when controlling for targets' ambition level and other confounding factors. We test this hypothesis on a new dataset comprising three protocols under the Convention on Long-Range Transboundary Air Pollution (CLRTAP). Our results suggest that the positive association between participation and target achievement is robust to controlling for confounding factors; hence, our data suggests that these CLRTAP protocols have indeed constrained participating states

Galectin-3, a marker of cardiac remodeling, is inversely related to serum Levels of marine omega-3 fatty acids. A cross-sectional study

Objective: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. Setting: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2–8 weeks after the index acute myocardial infarction. Results: Gal-3 was inversely correlated to eicosapentaenoic acid (r = −.120, p = .039) and docosahexaenoic acid (r = −.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). Conclusions: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction

Circumferential (360°) trabeculotomy in primary congenital glaucoma: 19–245 months of follow-up

Purpose: To evaluate the long-term efficacy and safety of circumferential trabeculotomy (CT) in the treatment of primary congenital glaucoma (PCG). Methods: Retrospective, single-institutional case series of CT performed for PCG in years 1997–2016. The surgery could be completed in 42 out of 65 eyes (65%) intended for CT, and 39 of them were included in the study. A follow-up examination was performed in 2017. Success was defined as intraocular pressure ≤ 16 mmHg without (complete) or with (qualified) glaucoma medication. Results: Complete success was obtained in 33/39 eyes (85%), qualified success in 34/39 eyes (87%). Of the 39 eyes with CT, 4 eyes (10%) needed additional surgery. Median follow-up time was 120 months (range, 19–245 months). Median pre- and postoperative IOP were 26.0 mmHg (range, 10–41 mmHg) and 11.0 mmHg (range, 8–19 mmHg), respectively (p < 0.001). Cup-disc ratio was ≥0.5 in 82% at baseline, at follow-up in 9%. The median distance corrected visual acuity at follow-up was logMAR 0.06 (range, −0.2 to 1.1). Median number of glaucoma medication at follow-up was 0 (range, 0–2), at baseline 1.0 (range, 0–2). No serious complications were noted. Conclusion: Circumferential trabeculotomy is an efficacious, safe and medication saving surgical treatment for PCG in the long term. After a median follow-up of 10 years (120 months), the morphological status of the optic nerve was either normalized or stabilized, and the visual acuity overall well preserved

Circumferential (360°) trabeculotomy in primary congenital glaucoma: 19–245 months of follow-up

Purpose: To evaluate the long-term efficacy and safety of circumferential trabeculotomy (CT) in the treatment of primary congenital glaucoma (PCG). Methods: Retrospective, single-institutional case series of CT performed for PCG in years 1997–2016. The surgery could be completed in 42 out of 65 eyes (65%) intended for CT, and 39 of them were included in the study. A follow-up examination was performed in 2017. Success was defined as intraocular pressure ≤ 16 mmHg without (complete) or with (qualified) glaucoma medication. Results: Complete success was obtained in 33/39 eyes (85%), qualified success in 34/39 eyes (87%). Of the 39 eyes with CT, 4 eyes (10%) needed additional surgery. Median follow-up time was 120 months (range, 19–245 months). Median pre- and postoperative IOP were 26.0 mmHg (range, 10–41 mmHg) and 11.0 mmHg (range, 8–19 mmHg), respectively (p < 0.001). Cup-disc ratio was ≥0.5 in 82% at baseline, at follow-up in 9%. The median distance corrected visual acuity at follow-up was logMAR 0.06 (range, −0.2 to 1.1). Median number of glaucoma medication at follow-up was 0 (range, 0–2), at baseline 1.0 (range, 0–2). No serious complications were noted. Conclusion: Circumferential trabeculotomy is an efficacious, safe and medication saving surgical treatment for PCG in the long term. After a median follow-up of 10 years (120 months), the morphological status of the optic nerve was either normalized or stabilized, and the visual acuity overall well preserved

Cardiac troponin I measured with a very high sensitivity assay predicts subclinical carotid atherosclerosis: The Akershus Cardiac Examination 1950 Study

Aims Concentrations of cardiac troponin I (cTnI) are associated with incident ischemic stroke and predict the presence and severity of coronary atherosclerosis. Accordingly, we hypothesized that concentrations of cTnI measured with a very high sensitivity (hs-) assay would be associated with subclinical stages of carotid atherosclerosis in the general population. Methods We measured hs-cTnI on the Singulex Clarity System in 1745 women and 1666 men participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including carotid ultrasound. We quantified carotid atherosclerosis by the carotid plaque score, carotid intima-media thickness (cIMT) and the presence of hypoechoic plaques. Results Concentrations of hs-cTnI were measurable in 99.8% of study participants and were significantly associated with increased carotid plaque score (odds ratio for quartile 4 of hs-cTnI 1.59, 95% CI 1.22 to 2.07, p for trend < 0.001) and cIMT (odds ratio for quartile 4 of hs-cTnI 1.57, 95% CI 1.02 to 2.42, p for trend = 0.036), but not with the presence of hypoechoic plaques. hs-cTnI concentrations significantly improved reclassification and discrimination models in predicting carotid plaques when added to cardiovascular risk factors, no improvements were evident in predicting cIMT or hypoechoic plaques. Conclusion Concentrations of cTnI measured with a very high sensitivity assay are predictive of carotid atherosclerotic burden, a phenomenon likely attributable to common risk factors of subclinical myocardial injury, coronary and carotid atherosclerosis