Level set clustering in a flow cytometry dataset

Pro Gradu -työn tarkoituksena oli testata kuinka hyvin tasopuumenetelmä soveltuu virtaussytometria-aineiston klusterointiin, ja verrata sitä k-lähimmän naapurin menetelmään. Tasopuumenetelmää myös parannettiin lisäämällä Nelder-Mead (NM) -optimointimenetelmä yhteen työvaiheeseen, jotta laskenta-ajat pysyisivät hallinnassa. Virtaussytometriassa mitataan yksittäisia soluja ja niiden ominaisuuksia, kun ne kulkevat laserin läpi. Ennen mittausta näyte on käsitelty fluerosoivalla aineella, jolloin solu hohtaa valon aallonpituuksia kulkiessaan laserin läpi. Nykyaikaiset laitteet pystyvät mittaamaan satoja tuhansia soluja ja kymmeniä aallonpituuksia kerralla. Tälläisen aineiston käsittely perinteisillä menetelmillä on erittäin raskasta. FlowCAP-konsortio perustettiin testaamaan kuinka hyvin erilaiset klusterointi- ja luokittelumenetelmät soveltuvat sytometria-aineiston käsittelyyn. Tässä gradussa käytetään FlowCAP II -kisasta “akuutti myelooinen leukemia” -aineistoa, joka sisältää 43 sairastunutta ja 359 tervettä verrokkia. Henkilön luokitteleminen terveisiin ja sairaisiin tehtiin tukivektorikoneella tasopuumenetelmästä tai k-lähimmän naapurin menetelmästä saatuja klustereita hyödyntäen. NM-menetelmällä saatiin selvä ajallinen hyöty ilman suurempaa menetystä tarkkuudessa, koska NM-menetelmä pääsi aina hyvin lähelle alkuperäisen algoritmin tulosta. Tasopuumenetelmä itsessään ei ollut k-lähimmän naapurin menetelmää parempi. Tämä johtui osaksi siitä, että variaatio tasopuumenetelmän tuloksien välillä oli hyvin suuri. Ero tasopuumenetelmän ja k-lähimmän naapurin menetelmän välillä oli kuitenkin pieni

Effect of physical activity on pulse wave velocity in elderly subjects with normal glucose, prediabetes or Type 2 Diabetes

AbstractCarotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P Abstract Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not. The 2 h glucose, heart rate and alcohol consumption in T2D subjects had independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were significantly associated to (cf)PWV. Interestingly, lipids did not have an additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had 0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of T2D, elevated heart rate and alcohol consumption in males were associated with increased aortic stiffening in elderly subjects

The Long-Term Footprint of Endometriosis : Population-Based Cohort Analysis Reveals Increased Pain Symptoms and Decreased Pain Tolerance at Age 46 Years

Previous studies have shown increased pain sensitivity in fertile-aged women with endometriosis in response to mechanical stimuli. As yet, population-based studies on the association of endometriosis with pain sensation and pain symptoms in late fertile age are lacking. The main objective of this population-based cohort study was to investigate whether a history of endometriosis is associated with altered pain sensation and musculoskeletal pain symptoms at age 46 years. Our data are derived from the Northern Finland Birth Cohort 1966, which contains postal questionnaire data (72% response rate) as well as clinical data assessing pressure-pain threshold and maximal pain tolerance. The study population consisted of 284 women with endometriosis and 3,390 controls. Our results showed that at age 46 women with a history of endometriosis had a 5.3% lower pressure-pain threshold and 5.1% lower maximal pain tolerance compared with controls. The most significant contributors besides endometriosis were anxiety, depression, and current smoking status. Women with endometriosis also reported an increased number of pain sites (0 pain sites, 9.6 vs 17.9%; 5-8 pain sites, 24.8 vs 19.1%, endometriosis vs controls respectively; P Perspective: This population-based cohort study showed decreased pain threshold and maximal pain tolerance in women with endometriosis in the late fertile age of 46 years. The pain was also found to be more bothersome and intense compared with controls. (C) 2018 by the American Pain SocietyPeer reviewe

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Peer reviewe

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants

Background: Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories. Methods: We used data from 1108 population-representative studies with 141 million participants aged 18 years and older with measurements of fasting glucose and glycated haemoglobin (HbA1c), and information on diabetes treatment. We defined diabetes as having a fasting plasma glucose (FPG) of 7·0 mmol/L or higher, having an HbA1c of 6·5% or higher, or taking medication for diabetes. We defined diabetes treatment as the proportion of people with diabetes who were taking medication for diabetes. We analysed the data in a Bayesian hierarchical meta-regression model to estimate diabetes prevalence and treatment. Findings: In 2022, an estimated 828 million (95% credible interval [CrI] 757-908) adults (those aged 18 years and older) had diabetes, an increase of 630 million (554-713) from 1990. From 1990 to 2022, the age-standardised prevalence of diabetes increased in 131 countries for women and in 155 countries for men with a posterior probability of more than 0·80. The largest increases were in low-income and middle-income countries in southeast Asia (eg, Malaysia), south Asia (eg, Pakistan), the Middle East and north Africa (eg, Egypt), and Latin America and the Caribbean (eg, Jamaica, Trinidad and Tobago, and Costa Rica). Age-standardised prevalence neither increased nor decreased with a posterior probability of more than 0·80 in some countries in western and central Europe, sub-Saharan Africa, east Asia and the Pacific, Canada, and some Pacific island nations where prevalence was already high in 1990; it decreased with a posterior probability of more than 0·80 in women in Japan, Spain, and France, and in men in Nauru. The lowest prevalence in the world in 2022 was in western Europe and east Africa for both sexes, and in Japan and Canada for women, and the highest prevalence in the world in 2022 was in countries in Polynesia and Micronesia, some countries in the Caribbean and the Middle East and north Africa, as well as Pakistan and Malaysia. In 2022, 445 million (95% CrI 401-496) adults aged 30 years or older with diabetes did not receive treatment (59% of adults aged 30 years or older with diabetes), 3·5 times the number in 1990. From 1990 to 2022, diabetes treatment coverage increased in 118 countries for women and 98 countries for men with a posterior probability of more than 0·80. The largest improvement in treatment coverage was in some countries from central and western Europe and Latin America (Mexico, Colombia, Chile, and Costa Rica), Canada, South Korea, Russia, Seychelles, and Jordan. There was no increase in treatment coverage in most countries in sub-Saharan Africa; the Caribbean; Pacific island nations; and south, southeast, and central Asia. In 2022, age-standardised treatment coverage was lowest in countries in sub-Saharan Africa and south Asia, and treatment coverage was less than 10% in some African countries. Treatment coverage was 55% or higher in South Korea, many high-income western countries, and some countries in central and eastern Europe (eg, Poland, Czechia, and Russia), Latin America (eg, Costa Rica, Chile, and Mexico), and the Middle East and north Africa (eg, Jordan, Qatar, and Kuwait). Interpretation: In most countries, especially in low-income and middle-income countries, diabetes treatment has not increased at all or has not increased sufficiently in comparison with the rise in prevalence. The burden of diabetes and untreated diabetes is increasingly borne by low-income and middle-income countries. The expansion of health insurance and primary health care should be accompanied with diabetes programmes that realign and resource health services to enhance the early detection and effective treatment of diabetes

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe