Association between work-related factors and health behaviour clusters among Finnish private-sector service workers.

PURPOSE: We examined how work-related factors associate with several health behaviours that appear together among the large, but less-studied, blue- and pink-collar worker group, which is characterized by low education and income levels. METHODS: In 2019, we conducted a cross-sectional survey among private sector service workers (n = 5256) in Finland. We applied two-step cluster analysis to identify groups on the basis of leisure-time physical activity, sleep adequacy, frequency of heavy drinking, smoking status, and frequency of fruit, vegetable and berry consumption. We examined the associations with work-related factors, using multinomial regression analyses and adjusting for confounding factors. RESULTS: We identified six clusters labelled as Moderately Healthy (28% of the participants), Healthy - Vigorous Exercise (19%), Sedentary Lifestyle (16%), Inadequate Sleep (15%), Mixed Health Behaviours (15%), and Multiple Risk Behaviours (8%). Those who perceived their work to be mentally or physically strenuous more commonly belonged to the Inadequate Sleep and Multiple Risk Behaviours clusters. Time pressure made belonging to the Inadequate Sleep, Mixed Health Behaviours, and Multiple Risk Behaviours clusters more likely. Those who were dissatisfied with their work more often belonged to the Healthy - Vigorous Exercise, Inadequate Sleep, and Multiple Risk Behaviours clusters. CONCLUSION: In addition of finding several considerably differing health behaviour clusters, we also found that adverse working conditions were associated with clusters characterized by multiple risk behaviours, especially inadequate sleep. Private-sector service workers' working conditions should be improved so that they support sufficient recovery, and occupational health services should better identify co-occurring multiple risk behaviours.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial.

INTRODUCTION: Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening. METHODS: The trial aims to recruit at least 111 000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray's test using intention-to-screen analysis of randomised men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening. ETHICS AND DISSEMINATION: The trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (2910/2017). Results will be disseminated through publications in international peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03423303.

Impact of Timing of Surgery and Adjuvant Treatment on Survival of Adult IDH-wild-type Glioblastoma: A Single-center Study of 392 Patients.

BACKGROUND: The purpose of our study was to analyze the impact of time interval from referral to surgery and from surgery to adjuvant treatment on survival of adult isocitrate dehydrogenase-wild-type (IDH-wt) glioblastomas. METHODS: Data on 392 IDH-wt glioblastomas diagnosed at the Tampere University Hospital in 2004-2016 were obtained from the electronic patient record system. Piecewise Cox regression was used to calculate hazard ratios for different time intervals between referral and surgery, as well as between surgery and adjuvant treatments. RESULTS: The median survival time from primary surgery was 9.5 months (interquartile range: 3.8-16.0). Survival among patients with an interval exceeding 4 weeks from referral to surgery was no worse compared to <2 weeks (hazard ratio: 0.78, 95% confidence interval: 0.54-1.14). We found indications of poorer outcome when the interval from surgery to radiotherapy exceeded 30 days (hazard ratio: 1.42, 95% confidence interval: 0.91-2.21 for 31-44 days; and 1.59, 0.94-2.67 for over 45 days). CONCLUSIONS: Interval from referral to surgery in the range of 4-10 weeks was not associated with decreased survivals in IDH-wt glioblastomas. In contrast, delay exceeding 30 days from surgery to adjuvant treatment may decrease long-term survival.

Lung cancer incidence attributable to residential radon exposure in Finland.

This study aimed to estimate (1) the number of avoidable lung cancer cases attributable to residential radon in Finland in 2017, separately by age, sex, dwelling type and smoking status, (2) the impact of residential radon alone and the joint effect of residential radon and smoking on the number of lung cancers and (3) the potential decrease in the number of radon-attributable lung cancers if radon concentrations exceeding specified action levels (100, 200 and 300 Bq m-3) would have been mitigated to those levels. Population-based surveys of radon concentrations and smoking patterns were used. Observed radon levels were contrasted with 25 Bq m-3 representing a realistic minimum level of exposure. Lung cancer risk estimates for radon and smoking were derived from literature. Lastly, the uncertainty due to the estimation of exposure and risk was quantified using a computationally derived uncertainty interval. At least 3% and at most 8% of all lung cancers were estimated as being attributable to residential radon. For small cell carcinoma, the proportion of cases attributable to radon was 8-13%. Among smokers, the majority of the radon-related cases were attributable to the joint effect of radon and smoking. Reduction of radon exposure to 100 Bq m-3 action level would eliminate approximately 30% of radon-attributable cases. Estimates were low compared with the literature, given the (relatively high) radon levels in Finland. This was mainly due to the lower radon levels and higher smoking prevalence in flats than in houses and a more realistic point of comparison, factors which have been ignored in previous studies. The results can guide actions in radon protection and in prevention of lung cancers.

Sustainability analysis of Finnish pre-schoolers' diet based on targets of the EAT-Lancet reference diet.

PURPOSE: The EAT-Lancet reference diet is a healthy plant-based diet produced within planetary boundaries. To inform the food system transformation, we compared Finnish pre-schoolers' food consumption with the reference diet's food group targets. METHODS: Food record data for 3- to 6-year-old pre-schoolers were collected in the cross-sectional DAGIS survey. Ingredients of composite dishes were available in the data. In addition, we manually decomposed industrial products such as sausages and biscuits by estimating the shares of ingredients. We also estimated the consumption of added sugars and converted the consumption of dairy products into milk equivalents. We used usual intake modelling to estimate the mean consumption and the proportion of children who met the reference diet's targets. We set the target amounts separately for 3- to 4-year-olds and 5- to 6-year-olds in grams by proportioning the published target amounts (assuming a 2500 kcal diet) to the children's mean reported energy intake. RESULTS: For both age groups (3- to 4-year-olds, n = 460; 5- to 6-year-olds, n = 402), the daily mean consumption of whole grains, vegetables, legumes, nuts, and unsaturated oils was below targets, whereas the consumption of red meat, dairy foods, tubers, and added sugars was above targets. The consumption of fruit and fish was in line with targets. CONCLUSION: To comply with the reference diet's targets, major changes in the diets of Finnish children are needed. The key food groups targeted for higher consumption are whole grains and legumes and targeted for lower consumption red meat and dairy products.

Cancer screening simulation models: a state of the art review.

BACKGROUND: Nowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies. METHODS: A systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999-2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study. RESULTS: Currently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time. CONCLUSIONS: Our findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.

Comparability and validity of cancer registry data in the northwest of Russia.

BACKGROUND: Despite the elaborate history of statistical reporting in the USSR, Russia established modern population-based cancer registries (PBCR) only in the 1990s. The quality of PBCRs data has not been thoroughly analyzed. This study aims at assessing the comparability and validity of cancer statistics in regions of the Northwestern Federal District (NWFD) of Russia. MATERIAL AND METHODS: Data from ten Russian regional PBCRs covering ∼13 million (∼5 million in St. Petersburg) were processed in line with IARC/IACR and ENCR recommendations. We extracted and analyzed all registered cases but focused on cases diagnosed between 2008 and 2017. For comparability and validity assessment, we applied established qualitative and quantitative methods. RESULTS: Data collection in NWFD is in line with international standards. Distributions of diagnosis dates revealed higher variation in several regions, but overall, distributions are relatively uniform. The proportion of multiple primaries between 2008 and 2017 ranged from 6.7% in Vologda Oblast to 12.4% in Saint-Petersburg. We observed substantial regional heterogeneity for most indicators of validity. In 2013-2017, proportions of morphologically verified cases ranged between 61.7 and 89%. Death certificates only (DCO) cases proportion was in the range of 1-14% for all regions, except for Saint-Petersburg (up to 23%). The proportion of cases with a primary site unknown was between 1 and 3%. Certain cancer types (e.g., pancreas, liver, hematological malignancies, and CNS tumors) and cancers in older age groups showed lower validity. CONCLUSION: While the overall level of comparability and validity of PBCRs data of four out of ten regions of NWFD of Russia meets the international standards, differences between the regions are substantial. The local instructions for cancer registration need to be updated and implemented. The data validity assessment also reflects pitfalls in the quality of diagnosis of certain cancer types and patient groups.

Prognostic Index for Predicting Prostate Cancer Survival in a Randomized Screening Trial: Development and Validation.

We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0-3, 3-9 and 9-20 years) for development and two corresponding validation periods (3-6 and 9-15 years). A multivariable complementary log-log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3-6 year and 9-15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making.

Number of screening rounds attended and incidence of high-risk prostate cancer in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer has shown a 20% reduction in prostate cancer (PC) mortality by prostate-specific antigen-based screening. In addition, screening has been shown to reduce the risk of advanced PC. The objective of the current study was to analyze the impact of screening participation on the incidence of PC by risk group. METHODS: The participants in the screening arm of the Finnish trial (31,867 men) were classified according to screening attendance in a time-dependent fashion. Initially, all men in the screening arm were regarded as nonattenders until the first screening attendance; they then remained in the once-screened group until the second screen and similarly for the possible third round. The control arm formed the reference group. Follow-up started at randomization and ended at the time of diagnosis of PC, emigration, or the end of 2015. PC cases were divided into risk groups according to European Association of Urology definitions. RESULTS: The incidence of low-risk PC increased with the number of screens, whereas no clear relation with participation was noted in the intermediate-risk and high-risk cases. For patients with advanced PC, attending screening at least twice was associated with a lower risk. CONCLUSIONS: Screening reduces the risk of advanced PC after only 2 screening cycles. A single screen demonstrated no benefit in terms of PC incidence. Repeated screening is necessary to achieve screening advantages.

Childhood risk factors and carotid atherosclerotic plaque in adulthood: The Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. METHODS: The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3-18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6-18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. RESULTS: Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen >50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76-5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99-2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26-2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. CONCLUSIONS: Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

Examining retail purchases of cigarettes and nicotine replacement therapy in Finland.

INTRODUCTION: Finland's success in achieving the goal of its tobacco endgame largely depends on rectifying deficiencies in the delivery of smoking cessation services. One such weakness, which has not been documented with empirical data, is misuse of nicotine replacement therapy (NRT). This study's objective was to examine purchase patterns of NRT for estimating improper use of the medication. The study was based on the assumption that duration of a purchase episode is indicative of either proper use or misuse of NRT. METHODS: The participants (n=728), who purchased at least one NRT product in 2016 (mostly gum/lozenge), were selected through enrollment in a large customer loyalty program in Finland (LoCard). Participants were categorized into one of five groups according to their longest purchase episode of NRT, defined by purchases made in consecutive, 4-week intervals. RESULTS: Most participants, who did not adhere to NRT guidelines, either purchased the medication for too short (≤4 weeks, 63.5%) or too long (>24 weeks, 13.2%) of a purchase episode. Median purchases of NRT in the first month of use were one and four in the former and latter, respectively. In contrast to other groups, persistent users (>24 weeks) did not curtail purchases of NRT across several 4-week intervals, suggesting potential for dependence on NRT. CONCLUSIONS: The observation that most purchase episodes were terminated prematurely is consistent with surveys reporting widespread NRT misuse. Given uncertainty of greater regulation of NRT sales through legislation, it would be prudent for Finnish retailers to promote proper use of the therapy.

Alcohol expenditure in grocery stores and their associations with tobacco and food expenditures.

BACKGROUND: Alcohol consumption is a significant cause of disease, death and social harm, and it clusters with smoking tobacco and an unhealthy diet. Using automatically registered retail data for research purposes is a novel approach, which is not subject to underreporting bias. Based on loyalty card data (LoCard) obtained by a major Finnish retailer holding a market share of 47%, we examined alcohol expenditure and their associations with food and tobacco expenditures. METHODS: The data consisted of 1,527,217 shopping events in 2016 among 13,274 loyalty card holders from southern Finland. A K-means cluster analysis was applied to group the shopping baskets according to their content of alcoholic beverages. The differences in the absolute and relative means of food and tobacco between the clusters were tested by linear mixed models with the loyalty card holder as the random factor. RESULTS: By far, the most common basket type contained no alcoholic beverages, followed by baskets containing a small number of beers or ciders. The expenditure on food increased along with the expenditure on alcoholic beverages. The foods most consistently associated with alcohol purchases were sausages, soft drinks and snacks. The expenditure on cigarettes relative to total basket price peaked in the mid-price alcohol baskets. CONCLUSION: Clustering of unhealthy choices occurred on the level of individual shopping events. People who bought many alcoholic beverages did not trim their food budget. Automatically registered purchase data provide valuable insight into the health behaviours of individuals and the population.

Trends in occupational diseases in Finland, 1975-2013: a register study.

OBJECTIVES: The objective was to investigate trends in the incidence of recognized and suspected cases of occupational diseases in Finland from 1975 to 2013, including variations by industry - and describe and recognize factors affecting variations in incidence. DESIGN: A register study. SETTING: The data consisted of recognized and suspected cases of occupational diseases recorded in the Finnish Registry of Occupational Diseases (FROD) in 1975-2013. PARTICIPANTS: Altogether 240 000 cases of suspected and recognized ODs were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: From the annual workforce statistics and FROD data, we calculated the incidence of ODs and suspected ODs per 10 000 employees. For time trends by industrial sector, we used a 5-year moving average and a Poisson regression analysis. RESULTS: Annual average rates of ODs have varied from year to year. The total number was 25.0/10 000 employees in 1975 and 20.1/10 000 employees in 2013. Screening campaigns and legislative changes have caused temporary increases. When the financial sector was the reference (1.0), the highest incidence rates according to industrial sector were in mining and quarrying (9.87; 95% CI 8.65 to 11.30), construction (9.11; 95% CI 9.98 to 10.43), manufacturing (9.04; 95% CI 7.93 to 10.36) and agriculture (8.78; 95% CI 7.69 to 10.06). There is a distinct decreasing trend from 2005 onwards: the average annual change in incidence was, for example, -9.2% in agriculture, -10.3% in transportation and -4.7% in construction. The average annual decline was greatest in upper limb strain injuries (-11.1%). CONCLUSION: This study provides a useful overview of the status of ODs in Finland over several decades. These data are a valuable resource for determining which occupations are at an increased risk and where preventive actions should be targeted. It is important to study long-term trends in the statistics of ODs to see beyond the year-to-year fluctuations.

The Number of Screening Cycles Needed to Reduce Prostate Cancer Mortality in the Finnish Section of the European Randomized Study of Prostate Cancer (ERSPC).

PURPOSE: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer mortality by PSA-based screening. The aim of the study is to evaluate screening effect on prostate cancer incidence and mortality in relation to number of screening rounds attended.Experimental Design: The participants in the screening arm of the Finnish trial (31,867 men) were classified according to screening attendance in a time-dependent fashion. Initially, all men in the screening arm were regarded as nonattenders until the first screening attendance, then remained among the once-screened until the second screen and similarly for the possible third round. The control arm was the reference. Follow-up started at randomization and ended at death, emigration, or end of 2013. Prostate cancer incidence and mortality, as well lung cancer and overall mortality were evaluated. RESULTS: Prostate cancer incidence was increased among screened men, but was not directly related to the number of screening rounds. Prostate cancer mortality was decreased in men screened twice or three times, but did not materially differ in those who did not attend the screening, and in men screened once compared with the control arm. The largest mortality reduction was in men screened three times [HR 0.17; 95% confidence interval (CI), 0.09-0.33]. However, a reduction was also seen in lung cancer (HR 0.59; 95% CI, 0.47-0.73) and overall mortality (HR 0.56; 95% CI, 0.52-0.60). CONCLUSIONS: Assuming a similar relative reduction being due to selection bias and screening in prostate cancer as other causes of death (40% reduction), approximately half of the observed prostate cancer mortality reduction by repeated screening is likely to be noncausal and a real screening effect may account for up to 40% reduction in men screened three times. Prostate cancer mortality reduction can only be achieved by repeated screening cycles.

Incorporating interaction networks into the determination of functionally related hit genes in genomic experiments with Markov random fields.

MOTIVATION: Incorporating gene interaction data into the identification of 'hit' genes in genomic experiments is a well-established approach leveraging the 'guilt by association' assumption to obtain a network based hit list of functionally related genes. We aim to develop a method to allow for multivariate gene scores and multiple hit labels in order to extend the analysis of genomic screening data within such an approach. RESULTS: We propose a Markov random field-based method to achieve our aim and show that the particular advantages of our method compared with those currently used lead to new insights in previously analysed data as well as for our own motivating data. Our method additionally achieves the best performance in an independent simulation experiment. The real data applications we consider comprise of a survival analysis and differential expression experiment and a cell-based RNA interference functional screen. AVAILABILITY AND IMPLEMENTATION: We provide all of the data and code related to the results in the paper. CONTACT: sean.j.robinson@utu.fi or laurent.guyon@cea.fr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cardiovascular Risk Factors From Childhood and Midlife Cognitive Performance: The Young Finns Study.

BACKGROUND: In adults, high blood pressure (BP), adverse serum lipids, and smoking associate with cognitive deficits. The effects of these risk factors from childhood on midlife cognitive performance are unknown. OBJECTIVES: This study sought to investigate the associations between childhood/adolescence cardiovascular risk factors and midlife cognitive performance. METHODS: From 1980, a population-based cohort of 3,596 children (baseline age: 3 to 18 years) have been followed for 31 years in 3- to 9-year intervals. BP, serum lipids, body mass index, and smoking were assessed in all follow-ups. Cumulative exposure as the area under the curve for each risk factor was determined in childhood (6 to 12 years), adolescence (12 to 18 years), and young adulthood (18 to 24 years). In 2011, cognitive testing was performed in 2,026 participants aged 34 to 49 years. RESULTS: High systolic BP, elevated serum total-cholesterol, and smoking from childhood were independently associated with worse midlife cognitive performance, especially memory and learning. The number of early life risk factors, including high levels (extreme 75th percentile for cumulative risk exposure between ages 6 and 24 years) of systolic BP, total-cholesterol, and smoking associated inversely with midlife visual and episodic memory and visuospatial associative learning (-0.140 standard deviations per risk factor, p < 0.0001) and remained significant after adjustment for contemporaneous risk factors. Individuals with all risk factors within recommended levels between ages 6 and 24 years performed 0.29 standard deviations better (p = 0.006) on this cognitive domain than those exceeding all risk factor guidelines at least twice. This difference corresponds to the effect of 6 years aging on this cognitive domain. CONCLUSIONS: Cumulative burden of cardiovascular risk factors from childhood/adolescence associate with worse midlife cognitive performance independent of adulthood exposure.

Global tests for novelty.

Outlier detection covers the wide range of methods aiming at identifying observations that are considered unusual. Novelty detection, on the other hand, seeks observations among newly generated test data that are exceptional compared with previously observed training data. In many applications, the general existence of novelty is of more interest than identifying the individual novel observations. For instance, in high-throughput cancer treatment screening experiments, it is meaningful to test whether any new treatment effects are seen compared with existing compounds. Here, we present hypothesis tests for such global level novelty. The problem is approached through a set of very general assumptions, making it innovative in relation to the current literature. We introduce test statistics capable of detecting novelty. They operate on local neighborhoods and their null distribution is obtained by the permutation principle. We show that they are valid and able to find different types of novelty, e.g. location and scale alternatives. The performance of the methods is assessed with simulations and with applications to real data sets.

What explains the differences between centres in the European screening trial? A simulation study.

BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) is a multicentre, randomised screening trial on men aged 55-69 years at baseline without known prostate cancer (PrCa) at randomisation to an intervention arm invited to screening or to a control arm. The ERSPC has shown a significant 21% reduction in PrCa mortality at 13 years of follow-up. The effect of screening appears to vary across centres, for which several explanations are possible. We set to assess if the apparent differences in PrCa mortality reduction between the centres can be explained by differences in screening protocols. METHODS: We examined the centre differences by developing a simulation model and estimated how alternative screening protocols would have affected PrCa mortality. RESULTS: Our results showed outcomes similar to those observed, when the results by centres were reproduced by simulating the screening regimens with PSA threshold of 3 versus 4ng/ml, or screening interval of two versus four years. The findings suggest that the differences are only marginally attributable to the different screening protocols. CONCLUSION: The small screening impact in Finland was not explained by the differences in the screening protocols. A possible reason for it was the contamination of and the unexpectedly low PrCa mortality in the Finnish control arm.

Segmentation of Image Data from Complex Organotypic 3D Models of Cancer Tissues with Markov Random Fields.

Organotypic, three dimensional (3D) cell culture models of epithelial tumour types such as prostate cancer recapitulate key aspects of the architecture and histology of solid cancers. Morphometric analysis of multicellular 3D organoids is particularly important when additional components such as the extracellular matrix and tumour microenvironment are included in the model. The complexity of such models has so far limited their successful implementation. There is a great need for automatic, accurate and robust image segmentation tools to facilitate the analysis of such biologically relevant 3D cell culture models. We present a segmentation method based on Markov random fields (MRFs) and illustrate our method using 3D stack image data from an organotypic 3D model of prostate cancer cells co-cultured with cancer-associated fibroblasts (CAFs). The 3D segmentation output suggests that these cell types are in physical contact with each other within the model, which has important implications for tumour biology. Segmentation performance is quantified using ground truth labels and we show how each step of our method increases segmentation accuracy. We provide the ground truth labels along with the image data and code. Using independent image data we show that our segmentation method is also more generally applicable to other types of cellular microscopy and not only limited to fluorescence microscopy.