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Prognostic index for predicting prostate cancer survival in a randomized screening trial: Development and validation
Full text linkWe 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
Legal enclaves as a test environment for innovative products: Toward legally resilient experimentation policies1
Full text linkMany countries adhere to the Organisation for Economic Co-operation and Development creed that innovation is good for the economy. Experiments are often used to intentionally create space for innovation. Decisions allowing experiments result in temporary legal enclaves for a few, excluding many others. Therefore, they come with risks. The aim of this article is to provide a set of guidelines that help improve the legal resilience of experimentation policies, so they are better able to withstand legal attacks when they occur. To do so, we first arranged the existing diversity of legal experiments in a theoretical model. Special attention was paid to two archetypes of legal experiments: statutory experiments and regulatory sandboxes. Second, we analyzed the impact of both types of experiments on four core legal principles: legality, certainty, equality, and public accountability. From this assessment, we eventually formulated a set of guidelines to secure or improve legal resilience
Phytochemical characterization of turnip greens (Brassica rapa ssp. rapa): A systematic review
Full text linkObjective The Turnip (Brassica rapa L. ssp. rapa) is a leaf and root vegetable grown and consumed worldwide. The consumption of Turnip has been associated with beneficial effects on human health due to their phytochemicals that may control a variety of physiological functions, including antioxidant activity, enzyme regulation, and apoptotic control and the cell cycle. The current systematic review of the literature aims to evaluate both the profile and quantity of phytochemicals commonly found in Turnip greens and to provide perspectives for further investigation. Methods This review was conducted following the PRISMA guidelines. Four bibliographic databases (PubMed, Embase, Web-of-Science and Cochrane Central Register of Controlled Trials) were searched to identify published studies until April 8th, 2020 (date last searched) without data and language restriction. Studies were included if they used samples of Turnip greens (the leaves), and evaluated its phytochemical content. Two reviewers independently evaluated the titles and abstracts according to the selection criteria. For each potentially eligible study, two reviewers assessed the full-texts and independently extracted the data using a predesigned data extraction form. Results Based on the search strategy 5,077 potentially relevant citations were identified and full texts of 37 studies were evaluated, among which 18 studies were eligible to be included in the current review. The majority of included studies were focused on identification of glucosinolates and isothiocyanates (n = 14, 82%), four studies focused on organic acids, and five studies reported phenolic component profile in Turnip greens. Among included studies nine studies (50%) provided information on phytochemical’s content. We found 129 phytochemicals (19 glucosinolates, 33 glucosinolate-breakdown products, 10 organic acids and 59 polyphenolic compounds) reported in Turnip greens. Flavonoids were mainly present as quercetin, kaempferol and isorhamnetin derivatives; while aliphatic forms were the predominant glucosinolate (gluconapin was the most common across five studies, followed by glucobrassicanapin). In general, the phytochemical content varied among the leaves, tops and Turnip roots. Conclusions Emerging evidence suggests the Turnip as a substantial source of diverse bioactive compounds. However, detailed investigation on the pure compounds derived from Turnip green, their bioavailability, transport and metabolism after consumption is further needed. Additional studies on their biological activity are crucial to develop dietary recommendations on the effective dosage and dietary recommendation of Turnip greens for nutrition and health
Heritability of sleep duration and quality: A systematic review and meta-analysis
Full text linkEpidemiological and interventional research has highlighted sleep as a potentially modifiable risk factor associated with poor physical and mental health. Emerging evidence from (behavioral) genetic research also shows that sleep characteristics are under strong genetic control. With this study we aimed to meta-analyze the literature in this area to quantify the heritability of sleep duration and sleep quality in the general population. We conducted a systematic literature search in five online databases on January 24th 2020. Two authors independently screened 5644 abstracts, and 160 complete articles for the inclusion criteria of twin studies from the general population reporting heritability statistics on sleep duration and/or quality, and written in English. We ultimately included 23 papers (19 independent samples: 45,328 twins between 6 mo and 88 y) for sleep duration, and 13 papers (10 independent samples: 39,020 twins between 16 and 95 y) for sleep quality. Collectively, we showed that 46% of the variability in sleep duration and 44% of the variability in sleep quality is genetically determined. The remaining variation in the sleep characteristics can mostly be attributed to the unique environment the twins experience, although the shared environment seemed to play a role for the variability of childhood sleep duration. Meta-analyzed heritability estimates for sleep duration, however, varied substantially with age (17% infancy, 20–52% childhood, 69% adolescence and 42–45% adulthood) and reporter (8% parent-report, 38–52% self-report). Heritability estimates for actigraphic and Polysomnography (PSG)-estimated sleep were based on few small samples, warranting more research. Our findings highlight the importance of considering genetic influences when aiming to understand the underlying mechanisms contributing to the trajectories of sleep patterns across the lifespan
Social media use and the not-so-imaginary audience: Behavioral and neural mechanisms underlying the influence on self-concept
Full text linkWe investigated behavioral and neural mechanisms in the relation between social media use (SMU) and self-concept, as well as longitudinal developmental outcomes. Adolescents and young adults (N = 150, 11–21 years old at T1) rated themselves on 60 traits in the academic, physical and prosocial domain, and also indicated how they thought peers would judge them (reflected-peer-judgements). Longitudinal questionnaires (1- and 2-year follow-up) were collected to assess positive (prosocial behavior, self-concept clarity) and negative (clinical symptoms) long-term outcomes. Results indicated that heavier self-reported SMU was linked with lower difference scores between self-judgements and reflected-peer-judgements. Lower SMU was related to more positive ratings from self-judgements vs. reflected-peer-judgements. SMU was also associated with less positive self-concept, particularly in the academic domain (boys and girls) and physical domain (girls). Neurally, increased SMU was linked to heightened mPFC-activity during self-judgements compared to reflected-peer-judgements, and increased activity during physical compared to academic and prosocial self-judgements. Longitudinal analyses indicated no evidence for long-term effects of social media use, self/reflected-peer-difference scores and mPFC-activity on clinical symptoms, prosocial behavior or self-concept clarity. This study highlights the complex relationship between social media use and wellbeing and future research is needed to confirm the lack of long-term effects
Investigating the decrease in participation in the Dutch cervical cancer screening programme: The role of personal and organisational characteristics
Full text linkDeclining attendance in the Dutch cervical cancer screening programme was recently observed, coinciding with preparations for implementing primary hrHPV-based screening, which was implemented in January 2017. We aimed to investigate which factors were related to decreased attendance. We conducted a population-based cohort study including all women aged 30 to 60 years who were eligible for screening between 2014 and 2018. Attendance was defined as participation in the screening programme within 15 months of the start of the invitation-eligible year. We used data from the Dutch pathology archive (PALGA) linked with data from Statistics Netherlands to investigate population characteristics (position in the household, household income, socio-economic status, number of people in the household, migration background, age) and data from the five Dutch screening organisations (SO) to investigate the effect of cessing self-inviting GP's (‘inviting organisation’). SO's were termed SO 1 to 5. Higher attendance rates were observed in women who were employed (60.8%), married (62.9%), Dutch (61.2%), in the highest income bracket (63.4%), living in households with four persons (65.3%) and women who were invited by their GP (69.8%). Differences in personal characteristics did not explain the decline in attendance rates. By adjusting for whether the GP or the SO sent the invitation, the differences in attendance rates between 2014 and 2015 and 2016 and between 2014 and 2015 and 2017–2018 were explained in some screening organisations. Removing the possibility for GPs to send invitations explains some of the decline in participation, although this did not account for the total change in attendance
Effects of Family Literacy Programs on the Emergent Literacy Skills of Children From Low-SES Families: A Meta-Analysis
Full text linkThe aim of this meta-analysis was to investigate effects of family literacy programs on the emergent literacy skills of children from low socioeconomic
status families (0–6) and to establish which program, sample, study, and measurement characteristics moderate program effects. Outcomes of 48 (quasi-)
experimental studies covering 42 different programs revealed a medium average effect of Cohen’s d = 0.50 on immediate posttests and a marginal average
effect of Cohen’s d = 0.16 on follow-up measures. Together, effects of different
moderator variables indicate that children benefit from targeted programs
that focus on a limited set of activities and skills and that are restricted to one
(training) context. Additionally, we found larger effects in experimental studies and when researcher-developed tests were used. Our outcomes not only
provide guidelines for program developers but also call for more longitudinal
research that examines how positive short-term changes as a consequence of
program participation can be sustained over time
DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan
Full text linkDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits
Circulating cell-free nucleosomes as biomarker for kidney transplant rejection: a pilot study
Full text linkBackground: There is an unmet need for noninvasive markers specific for kidney transplant rejection. Such a marker may eventually overcome the need for a transplant biopsy. In this pilot study, the potential of circulating cell-free nucleosomes (CCFN) to serve as a biomarker for kidney transplant rejection was evaluated. Methods: Forty de novo kidney transplant recipients were prospectively followed as part of a randomized, controlled clinical trial. Total CCFN (H3) and CCFN with the histone modifications H3K36me3 and H3 citrulline were measured in patients at four fixed time points: before transplantation and on days 3–6, 30 and 180 after kidney transplantation. In addition, serum collected at times of transplant rejection (n = 14) was analyzed. CCFN were measured with a Nu.Q™ Assay kit (VolitionRx), an ELISA-based assay using antibodies directed against nucleosomes. Results: For total CCFN (H3), H3K36me3, and H3 citrulline, the same pattern was seen over time: Concentrations were elevated shortly after transplantation (day 3–6) followed by a decline reaching baseline (pre-transplantation) values at days 30 and 180. At times of acute rejection, the median concentration of total CCFN (H3) was significantly higher compared to the stable situation (day 30): 4309 (3435–5285) versus 2885 (1668–3923) ng/mL, p < 0.05, respectively. Total CCFN (H3) had an acceptable ability to discriminate rejection from no rejection (AUC-ROC = 0.73) with a negative predictive value of 92.9%. For both histone modifications (H3K36me3 and H3 citrulline), there was no significant difference between episodes of acute rejection and the stable situation (day 30). Conclusion: In this pilot study, total CCFN (H3) concentrations are increased at times of acute kidney transplant rejection. The high negative predictive value implies that whenever a patient experiences loss of renal transplant function and the total CCFN (H3) is not increased, causes other than acute rejection should be considered. Clinical implementation of total CCFN (H3) measurement may avoid unnecessary and potentially harmful kidney transplant biopsies
The longitudinal association of actigraphy-estimated sleep with grief in middle-aged and elderly persons
Full text linkMost people experience grief after a loss, about 10% develop complicated grief, often accompanied by sleep complaints. Yet, the role of objectively estimated poor sleep remains unclear. Therefore, we assessed the cross-sectional and longitudinal association of actigraphy-estimated sleep with grief. We included 1,776 participants (mean age: 61.8 ± 8.9 years, 55% women) of a prospective population-based cohort. Of 1,471 participants (83%) repeated measures of grief were available (median follow-up 6 years, inter quartile range 5.6–6.3). At baseline, sleep was objectively estimated using actigraphy (mean duration 6.0 ± 0.8days). At baseline and follow-up, participants were asked about significant losses and completed the Dutch Inventory of Complicated Grief (17 items, cut-off ≥22). At baseline 1,521 (86%) participants experienced no grief, 44 (2%) acute grief (<6 months, any grief score), 158 (9%) non-complicated grief (≥6 months, grief score<22), and 53 (3%) complicated grief (≥6 months, grief score≥22). In those indicating any grief (n = 255), low sleep efficiency (B = −0.16, 95%CI = −0.30;-0.02), long sleep onset latency (B = 0.07, 95%CI = 0.01; 0.14), and long wake after sleep onset (B = 0.06, 95%CI = 0.01; 0.10) were cross-sectionally associated with more grief symptoms. Over time, those with a short total sleep time (OR = 0.59, 95%CI = 0.39; 0.91), low sleep efficiency (OR = 0.95, 95%CI = 0.91; 0.99), long sleep onset latency (OR = 1.02, 95%CI = 1.00; 1.04), and long wake after sleep onset (OR = 1.02, 95%CI = 1.00; 1.03) at baseline more often experienced complicated grief than non-complicated grief at follow-up. This study suggests that objectively estimated poor sleep is associated with grief over time. Poor sleep might not only accompany grief, but also be a risk factor for developing complicated grief after a loss