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Abstract Background The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. Methods We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. Results The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001). Conclusions This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

This study examines whether youth's goals for their future societal engagement affect their future political activities. We hypothesized, first, that youth's political interest would be a central predictor of their future political activities and, second, that their goals for future societal engagement would moderate their political interest. The greatest future political activity would be among youth who were both politically interested and had set high goals. A community sample of about 400 16-year-olds (M[subscript age]=16.62, SD=0.71, 50.8% females) was followed over four years. The theory of planned behavior was applied. Different types of political action were predicted: offline political activities, online political activities, membership of a political/civic organization, and taking a stance in public for a party pre and post voting in a national election. Age-16 political interest significantly predicted all age-20 political activities, except for being a member of political/civic organizations and actual voting. In line with the second hypothesis, significant interactions were found between political interest and setting societal goals for all the future political activities except voting. It was concluded that youth's early-developed agency in setting goals for their societal engagement has widespread predictive utility for their political activities over a lengthy period.

This study examines the idea that youth's perceptions of their political interactions with important others are influenced by their own political interest to a greater extent than the perceived political interactions that influence youth's political interest. Hence, it was proposed that youth's perceptions of important others' (parents', teachers', friends') political views, political interest, political influence, and support, as well as of being susceptible to others' political communication, are all affected by their own political interest. Community samples of 908 13-year-olds and 869 16-year-olds were followed over 1 year. Latent change models supported the idea that youth's political interest significantly affected their perceptions of important others' political views, influence, and support over time in both cohorts. In 11 out of 12 longitudinal analyses, youth's political interest strongly affected perceptions of their political interactions with others, but none of the 12 analyses showed that the perceptions of political interactions with others strongly predicted a change in youth's political interest. These results suggest that the political interest of young people is an input in their political development, making politically interested youth active agents in their political interactions with their important others.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

This study aimed to analyze affiliations with violent peers as an underlying mechanism that associates ethnic harassment with violent behaviors among immigrant youth (N = 365; M[subscript age] = 13.93, SD = 0.80), and also identify the risk factors in this relation. The results revealed that identification with an immigrant peer crowd at school made ethnically harassed immigrant adolescents more inclined to associate with violent peers and, in turn, engage in violent behaviors over time. Immigrant youth's orientation toward the mainstream culture was not found to either elevate or buffer the effect of ethnic harassment on youth's affiliation with violent peers. Yet, ethnically harassed immigrant adolescents were shown to be more prone to violent behaviors over time when they were less orientated toward Swedish culture. The findings suggest that preventing ethnicity-based harassment and diversifying adolescents' peer groups at schools may be a way to prevent immigrant adolescents' involvement in violent behaviors.

Background: Little is known about disease trajectories for men with castration-resistant prostate cancer (CRPC). Objective: To create a state transition model that estimates time spent in the CRPC state and its outcomes. Design, setting, and participants: The model was generated using population-based prostate-specific antigen data from 40% of the Swedish male population, which were linked to nationwide population-based databases. We compared the observed and predicted cumulative incidence of transitions to and from the CRPC state. Outcome measurements and statistical analysis: We measured time spent in the CRPC state and the proportion of men who died of prostate cancer during follow-up by CRPC risk category. Results and limitations: Time spent in the CRPC state varied from 1.1 yr for the highest risk category to 3.9 yr for the lowest risk category. The proportion of men who died from prostate cancer within 10 yr ranged from 93% for the highest risk category to 54% for the lowest. There was good agreement between the model estimates and observed data. Conclusions: There is large variation in the time spent in the CRPC state, varying from 1 yr to 4 yr according to risk category. Patient summary: It is possible to accurately estimate the disease trajectory and duration for men with castration-resistant prostate cancer.

Abstract Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.

The present study aims to investigate whether support from a friend protects against the negative effects of ethnic harassment on engagement in delinquent and violent behaviors among immigrant adolescents in Sweden (n = 365; X = 13.93, SD = 0.80). We found that when ethnically harassed immigrant adolescents received friend support, they were less likely to engage in problem behaviors concurrently. Yet, friend support did not moderate the longitudinal associations between ethnic harassment and problem behaviors. These findings highlight the important role of supportive friendship relations in counteracting the detrimental effects of ethnic harassment on externalizing problems, particularly in the short term.

Background: The implementation of preventive interventions is considered a crucial aspect of their success. However, few studies have investigated which components of implementation are most important. Objective: We aimed to understand whether the components of implementation integrity--adherence, quality of delivery, dose, and participants' involvement--influenced the effectiveness of four parenting programs. We also investigated factors associated with these components. Method: Data come from a national evaluation of parenting programs in Sweden. The study was a randomised controlled effectiveness trial, with a sample of 535 parents with 3-12-year-old children. Measures included parenting behaviors (angry outbursts, harsh parenting, attempts to understand, rewarding, and praising), child conduct problems (ECBI and SNAP-V), and measures tapping into the four components (adherence, quality of delivery, dose, and participant involvement). Results: We ran multilevel models and found that implementation quality (adherence and quality of delivery) did not influence the effects on parents and children. Conversely, participant involvement was associated with improvements in parenting and child conduct. Finally, parents' perceptions of their leaders as supportive and understanding were associated with parents' responsiveness and attendance. Conclusions: Our study highlights the importance of having actively engaged parents to maximise intervention effects.

BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

In Sweden, as in many other European countries, poor neighborhoods with ethnically diverse inhabitants and high crime rates have grown up around big cities in the last decades. We hypothesized that, compared with adolescents in advantaged neighborhoods, adolescents in disadvantaged neighborhoods would perceive their schools as relatively safe, due to their contrast with the more threatening and dangerous neighborhoods they lived in. Also, they would perceive their schools as relatively more open to their influence, due to the contrast with a lack of influence in their families. More broadly, they would experience their schools as supporting environments to a greater extent than adolescents in advantaged neighborhoods. We tested these ideas using a sample of 1390 adolescents (M[subscript age] = 14.34, SD = 1.01) in a Swedish city. The hypotheses were supported, and the findings were most salient for immigrant adolescents in disadvantaged neighborhoods. Thus, particularly for immigrant adolescents in disadvantaged neighborhoods, schools can be supporting environments, which should have implications for local policies regarding resource allocation to schools and student influence. Overall, schools seem to be able to play an important role in students' lives by functioning as a positive contrast to negative out-of-school experiences in disadvantaged neighborhoods.

This study examined age-related changes in friend similarity on delinquency to determine whether deviant behavior homophily peaks during mid-adolescence. A community sample of 1,663 male and 1,826 female Swedish youth from Grade 5 (M = 11.21 years) to Grade 10 (M = 16.25 years) provided self-reports of delinquency. Friendships were identified from nominations. Intraclass correlations revealed age group differences in friend delinquency similarity, independent of normative age-related changes in deviant behavior. Cross-sectional results indicated that similarity was greatest in the seventh grade (M = 13.21 years). Longitudinal results from a subsample of participants revealed an increase in friend similarity from ages 11 to 13 (Grades 5 to 7) and a decline in friend similarity from ages 14 to 16 (Grades 8 to 10). The findings demonstrate that similarity between friends in delinquent behavior peaks in mid-adolescence, independent of normative age-related changes in participation in deviant acts.

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

Abstract Background PREDICT Prostate is an endorsed prognostic model that provides individualised long-term prostate cancer-specific and overall survival estimates. The model, derived from UK data, estimates potential treatment benefit on overall survival. In this study, we externally validated the model in a large independent dataset and compared performance to existing models and within treatment groups. Methods Men with non-metastatic prostate cancer and prostate-specific antigen (PSA)