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Background: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain. Methods: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71–1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66–0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival. Conclusion: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies of genetic predisposition to renal cell carcinoma (RCC) have been highly variable in design and have reported similarly highly variable rates of cases identified as carrying pathogenic variants in cancer susceptibility genes (4–26%). The aim of our study was to conduct a population-based study of genetic predisposition to RCC. We conducted a 21-gene panel sequencing study and identified that 18/1029 participants (1.7%) carried a pathogenic or likely pathogenic (PLP) variant. Genes with PLP variants included BAP1, FH, FLCN, MITF, MSH6, SDHB, TSC1, and VHL. This study provides further evidence that family history alone may not be sufficient for identifying all individuals who are at increased genetic risk of renal cell carcinoma, and further research is urgently needed to understand how to target genetic testing to identify those at high genetic risk of kidney cancer. Renal cell carcinoma (RCC) has been associated with germline pathogenic or likely pathogenic (PLP) variants in recognised cancer susceptibility genes. Studies of RCC using gene panel sequencing have been highly variable in terms of study design, genes included, and reported prevalence of PLP variant carriers (4–26%). Studies that restricted their analysis to established RCC predisposition genes identified variants in 1–6% of cases. This work assessed the prevalence of clinically actionable PLP variants in renal cancer predisposition genes in an Australian population-based sample of RCC cases. Germline DNA from 1029 individuals diagnosed with RCC who were recruited through the Victoria and Queensland cancer registries were screened using a custom amplicon-based panel of 21 genes. Mean age at cancer diagnosis was 60 ± 10 years, and two-thirds (690, 67%) of the participants were men. Eighteen participants (1.7%) were found to carry a PLP variant. Genes with PLP variants included BAP1, FH, FLCN, MITF, MSH6, SDHB, TSC1, and VHL. Most carriers of PLP variants did not report a family history of the disease. Further exploration of the clinical utility of gene panel susceptibility testing for all RCCs is warranted. [ABSTRACT FROM AUTHOR]

Self-rated health (SRH) is a subjective indicator of overall health based on a single questionnaire item. Previous evidence found that it is a strong predictor of mortality, although the underlying mechanism is poorly understood. Epigenetic age is an objective, emerging biomarker of health, estimated using DNA methylation data at hundreds of sites across the genome. This study aimed to assess the overlap and interaction between SRH and epigenetic ageing in predicting mortality risk. We used DNA methylation data from 1059 participants in the Melbourne Collaborative Cohort Study (mean age: 69 years) to calculate three age-adjusted measures of epigenetic ageing: GrimAge, PhenoAge, and DunedinPACE. SRH was assessed using a five-category questionnaire item ("excellent, very good, good, fair, poor"). Cox models were used to assess the associations of SRH, epigenetic ageing, and their interaction, with all-cause mortality over up to 17 years of follow-up (Ndeaths = 345). The association of SRH with mortality per category increase was HR = 1.29; 95%CI: 1.14–1.46. The association was slightly attenuated after adjusting for all three epigenetic ageing measures (HR = 1.25, 95%CI: 1.10–1.41). A strong gradient was observed in the association of GrimAge (Pinteraction = 0.006) and DunedinPACE (Pinteraction = 0.002) with mortality across worsening SRH strata. For example, the association between DunedinPACE and mortality in participants with "excellent" SRH was HR = 1.02, 95%CI: 0.73–1.43 and for "fair/poor" HR = 1.72, 95%CI: 1.35–2.20. SRH and epigenetic ageing were synergistic risk factors of mortality in our study. These findings suggest that consideration of subjective and objective factors may improve general health assessment, which has implications for the ongoing development of molecular markers of ageing. [ABSTRACT FROM AUTHOR]

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008—0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring. [ABSTRACT FROM AUTHOR]

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests. [ABSTRACT FROM AUTHOR]

Research into relationships between victim-generated content, abuse received, and observer characteristics when considering Twitter abuse has been limited to male victims. We evaluated participant perceptions of female celebrity victims and abuse received on Twitter. We used a 3 (Initial Tweet Valence; negative, neutral, positive) × 2 (Abuse Volume; low, high) repeated measures design and online survey method. Participants were shown tweets generated by six female celebrities, counterbalanced such that each participant saw each celebrity in one Valence-Volume condition. Stimuli were presented across six ‘lists’ such that celebrity ‘victims’ could be rotated across Valence-Volume pairings. Participants rated—per target stimulus—the level of blame attributable to the victim and the perceived severity of the incident. Furthermore, participants were asked to complete a Dark Tetrad scale—measuring their Machiavellianism, Narcissism, Psychopathy, and Sadism. Analyses determined that victim-blaming was influenced by victim Initial Tweet Valence (greater victim-blaming associated with more-negative content) and observer Machiavellianism. Perceived severity was influenced by victim Initial Tweet Valence, Volume of Abuse received, and observer Machiavellianism. Results were consistent with previous research involving male celebrity victims. Further research is needed to understand the contributions of participants’ hostile and benevolent sexism, as well as the role of victim attractiveness. [ABSTRACT FROM AUTHOR]

Epigenetic age is an emerging marker of health that is highly predictive of disease and mortality risk. There is a lack of evidence on whether lifestyle changes are associated with changes in epigenetic aging. We used data from 1 041 participants in the Melbourne Collaborative Cohort Study with blood DNA methylation measures at baseline (1990–1994, mean age: 57.4 years) and follow-up (2003–2007, mean age: 68.8 years). The Alternative Healthy Eating Index-2010 (AHEI-2010), the Mediterranean Dietary Score, and the Dietary Inflammatory Index were used as measures of diet quality, and weight, waist circumference, and waist-to-hip ratio as measures of body size. Five age-adjusted epigenetic aging measures were considered: GrimAge , PhenoAge , PCGrimAge, PCPhenoAge, and DunedinPACE. Multivariable linear regression models including restricted cubic splines were used to assess the cross-sectional and longitudinal associations of body size and diet quality with epigenetic aging. Associations between weight and epigenetic aging cross-sectionally at both time points were positive and appeared greater for DunedinPACE (per SD : β ~0.24) than for GrimAge and PhenoAge (β ~0.10). The longitudinal associations with weight change were markedly nonlinear (U-shaped) with stable weight being associated with the lowest epigenetic aging at follow-up, except for DunedinPACE , for which only weight gain showed a positive association. We found negative, linear associations for AHEI-2010 both cross-sectionally and longitudinally. Other adiposity measures and dietary scores showed similar results. In middle-aged to older adults, declining diet quality and weight gain may increase epigenetic age, while the association for weight loss may require further investigation. Our study sheds light on the potential of weight management and dietary improvement in slowing aging processes. [ABSTRACT FROM AUTHOR]

"The Partisan Republic" explores the transition from the republic established by the Constitution of 1787 to a democracy by the 1830s. The authors argue that this democracy explicitly excluded non-white men from civic participation. They examine the tensions within the Democratic Party of Andrew Jackson and Martin Van Buren, which aimed to be anti-hierarchical but maintained an all-white, all-male definition of citizenship. The book highlights the contradictions and limitations of early American democracy, which expanded political participation while constricting the rights of marginalized groups. The authors also discuss battles over constitutional interpretation and the role of the Supreme Court in shaping democracy. [Extracted from the article]

Objectives: The use of silver fluoride followed by stannous fluoride was designed for the treatment of open carious lesions in primary molars in dental outreach programs. However, during the COVID‐19 pandemic when aerosol‐producing procedures were inadvisable, one dental location started using it as the first stage in a two‐visit restorative procedure for carious primary molars. If the gap between the fluoride application and the restoration placement stages was around 3–5 weeks it was noticed that a black friable crust appeared on the caries surface. To investigate further a normally discarded crust from one patient was retrieved and sent for analysis. Materials and Methods: Two techniques suitable for identification and preliminary analysis of material of unknown composition, scanning electron microscopy and energy dispersive spectroscopy (EDS) were used. The only preparation was that the specimen was dried and coated beforehand. Results and Conclusions: This preliminary examination showed two unexpected findings. The first was that the crust surface indicated a possible dentine derivation as it was covered with reasonably evenly spaced holes. In addition, the EDS spectrum showed it to be, at least, partially mineralized. The second unexpected finding was that the surface was coated with electron‐dense particles. The size of the particles and the EDS spectrum pointed to the likelihood of the majority of them being nanosilver. These unexpected findings suggest a possible new direction for research. [ABSTRACT FROM AUTHOR]

Ever since its discovery1, the notion of the Berry phase has permeated all branches of physics and plays an important part in a variety of quantum phenomena2. However, so far all its realizations have been based on a continuous evolution of the quantum state, following a cyclic path. Here we introduce and demonstrate a conceptually new manifestation of the Berry phase in light-driven crystals, in which the electronic wavefunction accumulates a geometric phase during a discrete evolution between different bands, while preserving the coherence of the process. We experimentally reveal this phase by using a strong laser field to engineer an internal interferometer, induced during less than one cycle of the driving field, which maps the phase onto the emission of higher-order harmonics. Our work provides an opportunity for the study of geometric phases, leading to a variety of observations in light-driven topological phenomena and attosecond solid-state physics.The Berry phase is resolved in light-driven crystals, via attosecond interferometry, in which the electronic wavefunction accumulates a geometric phase as it interacts with the laser field, mapping its coherence into the emission of high-order harmonics. [ABSTRACT FROM AUTHOR]

Background The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. Methods Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. Results During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10–11 years; HR, 1.28; 95% CI, 1.00–1.64), younger (<40; HR, 1.31; 95% CI, 1.05–1.62) and older (≥55; HR, 1.33; 95% CI, 1.05–1.68) ages at menopause (vs 40–44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02–1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13–1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00–1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76–0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70–0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. Conclusions Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight. [ABSTRACT FROM AUTHOR]

Context: The Western Australian Environmental Protection Authority's (EPA's) terrestrial fauna survey guidelines for detailed surveys recommends a two-season survey with a minimum of one, or a few survey sites, for each fauna habitat. Aims: This study demonstrates that in two common fauna habitat types and probably most others, this survey effort is unlikely to provide an indication of species richness and abundance. Methods: A pit and funnel trapping program targeting small ground dwelling mammals and reptiles was replicated in 20 trapping sites over two survey periods in two different fauna habitat types. Results: For most project areas, compliance with the EPA's guidelines is unlikely to provide better quality data on species richness than publicly available from a desktop assessment. Conclusion: It is difficult to provide an adequate scientific justification for undertaking low intensity surveys when desktop surveys will mostly provide better quality information for an environmental impact assessment (EIA), and these surveys probably should not be approved by an animal ethics committee. Implications: When preparing for and undertaking vertebrate fauna surveys for an EIA, environmental practitioners should place greater emphasis on the scientific validity and robustness of the proposed surveys rather than just complying with an EPA technical guidance. The EPA's technical vertebrate fauna survey guidance should be completely rewritten. Here, we analysed the data from two terrestrial fauna surveys undertaken in different fauna habitats that are common in Western Australia. Although environmental practitioners comply with the Western Australian Environmental Protection Authority's (EPA's) terrestrial fauna survey guidelines when surveying one site in each fauna habitat type, these surveys typically collect insufficient data to record more than 60% of the terrestrial species present. They are also unlikely to provide better quality data on species richness than publicly available from a desktop assessment. In addition, it is difficult to provide a scientific justification to an animal ethics committee for undertaking low intensity surveys when desktop surveys may provide adequate information for an environmental impact assessment. Therefore, these surveys probably should not be approved. We argue that the EPA should rewrite its existing guidelines. [ABSTRACT FROM AUTHOR]

Independent living skills (ILS) are crucial for the post-school success of students with disabilities. In this systematic literature review, we examined ILS interventions for secondary and postsecondary education students with intellectual disability or autism ranging from ages 13–24 years. Forty-two articles met the inclusion criteria and were examined. Findings indicated the most frequent intervention method used was prompting followed by video modeling/prompting. Technology was the most frequent modality used to deliver interventions. The most common types of ILS taught to students were cooking and cleaning. Implications for policy and practice include educators evaluating the range of ILS taught to students. Implications for future research include an emphasis on further developing technological interventions that expand to a wider variety of skills. [ABSTRACT FROM AUTHOR]

In this preregistered study, we confirmed a transition-planning construct and determined its relationship with an established economic-hardship construct using parent- and youth-reported data from the National Longitudinal Transition Study 2012 and following established quality indicators of preregistered secondary data analyses studies. Transition planning was made up of seven items relevant to individualized education program (IEP) meeting participation. We examined measurement invariance on the basis of disability category and race/ethnicity as well as the intersection of these student characteristics in order to make unbiased group comparisons on key latent parameters. Contrary to our hypotheses, there was no meaningful correlation between transition planning and economic hardship. Moreover, we were unable to establish measurement invariance of transition planning because the item "youth's role in IEP meeting" functioned differently on the basis of disability category. Implications for practice are discussed regarding how decisions about IEP meeting participation are made, by whom and why, and whether evidence-based practices are effectively disseminated. Future research should ensure adequate sampling plans for national survey attempts in order to conduct an in-depth examination based on intersectional student characteristics. [ABSTRACT FROM AUTHOR]

Objectives: Incorporating the perspectives of patients and public into the conduct of research has the potential to make scientific research more democratic. This paper explores how being a patient partner on an arthritis patient advisory board shapes the patienthood of a person living with arthritis. Methods: An analysis was undertaken of the narratives of 22 patient research partners interviewed about their experiences on the Arthritis Patient Advisory Board (APAB), based in Vancouver, Canada. Results: Participants' motivations to become involved in APAB stemmed largely from their desire to change their relationship with their condition. APAB was a living collective project in which participants invested their hope, both for their own lives as patients and for others with the disease. Conclusions: Our findings highlight how the journeys of patient partners connect and integrate seemingly disparate conceptions of what it means to be a patient. One's experience as a clinical 'patient' transforms into the broader notion of civic patienthood. [ABSTRACT FROM AUTHOR]

319‐44 is a human monoclonal antibody capable of passively protecting mice against tick‐mediated infection with Borreliella burgdorferi, the bacterial genospecies responsible for Lyme disease in North America. In vitro, 319‐44 has complement‐dependent borreliacidal activity and spirochete agglutinating properties. Here, we report the 2.2 Å‐resolution crystal structure of 319‐44 Fab fragments in complex with Outer surface protein A (OspA), the ~30 kDa lipoprotein that was the basis of the first‐generation Lyme disease vaccine approved in the United States. The 319‐44 epitope is focused on OspA β‐strands 19, 20, and 21, and the loops between β‐strands 16‐17, 18‐19, and 20‐21. Contact with loop 20‐21 explains competition with LA‐2, the murine monoclonal antibody used to estimate serum borreliacidal activities in the first‐generation Lyme disease vaccine clinical trials. A high‐resolution B‐cell epitope map of OspA will accelerate structure‐based design of second generation OspA‐based vaccines. [ABSTRACT FROM AUTHOR]

Background: Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology. Methods: We used digitised mammograms for 371 monozygotic twin pairs, aged 40–70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method. Results: The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22–0.81; all P < 0.005). We estimated that 28–92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively). Conclusions: In a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways. [ABSTRACT FROM AUTHOR]

Background The extent to which known and unknown factors explain how much people of the same age differ in disease risk is fundamental to epidemiology. Risk factors can be correlated in relatives, so familial aspects of risk (genetic and non-genetic) must be considered. Development We present a unifying model (VALID) for variance in risk, with risk defined as log(incidence) or logit(cumulative incidence). Consider a normally distributed risk score with incidence increasing exponentially as the risk increases. VALID's building block is variance in risk, Δ2, where Δ = log(OPERA) is the difference in mean between cases and controls and OPERA is the odds ratio per standard deviation. A risk score correlated r between a pair of relatives generates a familial odds ratio of exp(r Δ2). Familial risk ratios, therefore, can be converted into variance components of risk, extending Fisher's classic decomposition of familial variation to binary traits. Under VALID, there is a natural upper limit to variance in risk caused by genetic factors, determined by the familial odds ratio for genetically identical twin pairs, but not to variation caused by non-genetic factors. Application For female breast cancer, VALID quantified how much variance in risk is explained—at different ages—by known and unknown major genes and polygenes, non-genomic risk factors correlated in relatives, and known individual-specific factors. Conclusion VALID has shown that, while substantial genetic risk factors have been discovered, much is unknown about genetic and familial aspects of breast cancer risk especially for young women, and little is known about individual-specific variance in risk. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to conceptually replicate a multi-indicator construct of economic hardship in a national sample of adolescents with and without disabilities (N = 9,230). Using data from the National Longitudinal Transition Study 2012 (NLTS2012), the latent construct economic hardship was confirmed from six theoretically relevant indicators: household income, parent education level, parent employment status, one- or two-parent household, household internet access, and participation in government-assisted social programs (e.g., Supplemental Security Income benefits, Supplemental Nutrition Assistance Program, Temporary Assistance for Needy Families). In addition, we examined group differences on the latent mean of economic hardship based on disability category, race and ethnicity, and school and family factors. Mean differences showed significantly lower economic hardship for youth on 504 plans, youth with autism, and for White non-Hispanic youth; whereas there was significantly greater hardship for youth with intellectual disability and youth with emotional disturbance and among youth of color. The implications of the replicated and expanded findings for adolescents with and without disabilities are discussed. [ABSTRACT FROM AUTHOR]

Background: Cereal‐derived polyphenols have demonstrated protective mechanisms in colorectal cancer (CRC) models; however, confirmation in human studies is lacking. Therefore, this study examined the association between cereal polyphenol intakes and CRC risk in the Melbourne Collaborative Cohort Study (MCCS), a prospective cohort study in Melbourne, Australia that recruited participants between 1990 and 1994 to investigate diet–disease relationships. Methods: Using food frequency questionnaire diet data matched to polyphenol data, dietary intakes of alkylresorcinols, phenolic acids, lignans, and total polyphenols from cereals were estimated. Hazard ratios (HRs) and 95% confidence intervals for CRC risk were estimated for quintiles of intake with the lowest quintile as the comparison category, using multivariable adjusted Cox proportional hazards models with age as the time axis adjusted for sex, socio‐economic status, alcohol consumption, fibre intake, country of birth, total energy intake, physical activity and smoking status. Results: From 35,245 eligible adults, mean (SD) age 54.7 (8.6) years, mostly female (61%) and Australian‐born (69%), there were 1394 incident cases of CRC (946 colon cancers and 448 rectal cancers). Results for total cereal polyphenol intake showed reduced HRs in Q2 (HR: 0.80; 95% CI, 0.68–0.95) and Q4 (HR: 0.75; 95% CI, 0.62–0.90), and similar for phenolic acids. Alkylresorcinol intake showed reduced HR in Q3 (HR: 0.80; 95% CI, 0.67–0.95) and Q4 (HR: 0.79; 95% CI, 0.66–0.95). Conclusions: Overall, the present study showed little evidence of association between intakes of cereal polyphenols and CRC risk. Future investigations may be useful to understand associations between cereal‐derived polyphenols and additional cancers in different populations. [ABSTRACT FROM AUTHOR]

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case‐control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B‐cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health‐related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5‐1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2‐1.3) with urothelial cancer risk for smoking MS and with mature B‐cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1‐1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B‐cell neoplasms: +8%). Methylation scores for smoking, BMI and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction. What's new? Data from large, population‐based studies have long indicated that lifestyle factors are associated with increased cancer risk. But molecular markers might provide more accurate exposure data than questionnaires, and may also reveal variations in individual responses. In this study, the authors found that DNA methylation scores may provide such a biomarker. They found that changes in methylation associated with smoking, alcohol consumption and obesity are also associated with an increased risk of several types of cancer. These lifestyle methylation scores may thus provide improved risk prediction for these cancers. [ABSTRACT FROM AUTHOR]

In this study, we estimated the cost of implementing the Self-Determined Learning Model of Instruction (SDLMI), an evidence-based practice in secondary transition, at scale in 17 U.S. school districts to enhance self-determination and transition goal attainment outcomes among 340 transition-age adolescents with intellectual disability. An advantage of the SDLMI is that it can be overlaid upon any curriculum and, therefore, can minimize opportunity costs for self-determination instruction. Using the ingredients method, the current study: (a) identified and described the essential ingredients of SDLMI implementation in typical high school settings, (b) assigned and described the cost of needed ingredients, and (c) calculated a generalizable estimate of the average cost of using the SDLMI with 340 students for one school year across 17 school districts to be $40,221.26 (or $118.30 per student). We discuss how decision-makers considering using the SDLMI in their context can minimize costs while maximizing effects on transition goal attainment outcomes. Several implications of these findings for the field of transition are also described. [ABSTRACT FROM AUTHOR]

Secondary data analyses occur when new analyses are proposed for existing data. Although they are prevalent in special education research, there is little guidance on how to prepare secondary data analyses studies. Preregistration of secondary data analyses studies provides a nice opportunity and structure for fellow researchers to share innovative questions and analytic approaches to existing data sets as well as increase transparency. In this manuscript, we (a) describe quality indicators of secondary data analyses consistent with open science practices and (b) provide applied examples of these indicators from a sampling of published studies based on two iterations of data from the National Longitudinal Transition Study (NLTS2 and NLTS2012) with the overall goals to provide guidance to authors and peer reviewers and promote collaboration among fellow researchers engaged in secondary analyses for a range of purposes. [ABSTRACT FROM AUTHOR]

DNA methylation marks that are inherited from parents to offspring are known to play a role in cancer risk and could explain part of the familial risk for cancer. We therefore conducted a genome-wide search for heritable methylation marks associated with prostate cancer risk. Peripheral blood DNA methylation was measured for 133 of the 469 members of 25 multiple-case prostate cancer families, using the EPIC array. We used these families to systematically search the genome for methylation marks with Mendelian patterns of inheritance, then we tested the 1,000 most heritable marks for association with prostate cancer risk. After correcting for multiple testing, 41 heritable methylation marks were associated with prostate cancer risk. Separate analyses, based on 869 incident cases and 869 controls from a prospective cohort study, showed that 9 of these marks near the metastable epiallele VTRNA2-1 were also nominally associated with aggressive prostate cancer risk in the population. [ABSTRACT FROM AUTHOR]

Purpose: Women with preeclampsia are more likely to deliver preterm. Reports of inverse associations between preeclampsia and breast cancer risk, and positive associations between preterm birth and breast cancer risk are difficult to reconcile. We investigated the co-occurrence of preeclampsia/gestational hypertension with preterm birth and breast cancer risk using data from the Premenopausal Breast Cancer Collaborative Group. Methods: Across 6 cohorts, 3096 premenopausal breast cancers were diagnosed among 184,866 parous women. We estimated multivariable hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal breast cancer risk using Cox proportional hazards regression. Results: Overall, preterm birth was not associated (HR 1.02, 95% CI 0.92, 1.14), and preeclampsia was inversely associated (HR 0.86, 95% CI 0.76, 0.99), with premenopausal breast cancer risk. In stratified analyses using data from 3 cohorts, preterm birth associations with breast cancer risk were modified by hypertensive conditions in first pregnancies (P-interaction = 0.09). Preterm birth was positively associated with premenopausal breast cancer in strata of women with preeclampsia or gestational hypertension (HR 1.52, 95% CI: 1.06, 2.18), but not among women with normotensive pregnancy (HR = 1.09, 95% CI: 0.93, 1.28). When stratified by preterm birth, the inverse association with preeclampsia was more apparent, but not statistically different (P-interaction = 0.2), among women who did not deliver preterm (HR = 0.82, 95% CI 0.68, 1.00) than those who did (HR = 1.07, 95% CI 0.73, 1.56). Conclusion: Findings support an overall inverse association of preeclampsia history with premenopausal breast cancer risk. Estimates for preterm birth and breast cancer may vary according to other conditions of pregnancy. [ABSTRACT FROM AUTHOR]

Understanding the effects of harvest on wildlife populations is fundamental to theoretical wildlife science and applied wildlife management. Demographic compensation plays a key role in models of wildlife population dynamics and in developing harvest strategies. The degree and form of compensation in a given population depend on its particular ecological and life‐history characteristics and the timing and magnitude of harvest. Consequently, substantial variation exists in compensatory potential among populations, and it cannot be assumed that a particular population is capable of compensating for harvest. This underscores the importance of population‐specific assessments of responses to harvest. We examined the hypothesis that concentrated hunting pressure in road‐accessible areas reduces subsequent breeding season densities of willow ptarmigan (Lagopus lagopus), in Alaska, USA, 2014–2015. We estimated breeding season densities of ptarmigan territories at sites within hunted access corridors and at remote sites with little or no hunting pressure. Estimated densities were substantially higher at remote sites (5.3–5.8 territories/km2) than at accessible sites (1.8–3.7 territories/km2). Two habitat‐proxy covariates, distance to water and elevation (modeled as smoothed effects), exhibited strong associations with the density of ptarmigan territories. These results suggest a possible additive effect of spatially concentrated harvest on local breeding densities. [ABSTRACT FROM AUTHOR]

Background: We quantified the individual and joint contribution of contemporaneous causal behavioural exposures on the future burden of oesophageal and stomach cancers and their subtypes and assessed whether these burdens differ between population groups in Australia, as such estimates are currently lacking. Methods: We combined hazard ratios from seven pooled Australian cohorts (N = 367,058) linked to national cancer and death registries with exposure prevalence from the 2017–2018 National Health Survey to estimate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death. Results: Current and past smoking explain 35.2% (95% CI = 11.7–52.4%), current alcohol consumption exceeding three drinks/day 15.7% (95% CI = 0.9–28.4%), and these exposures jointly 41.4% (95% CI = 19.8–57.3%) of oesophageal squamous cell carcinomas in Australia. Current and past smoking contribute 38.2% (95% CI = 9.4–57.9%), obesity 27.0% (95% CI = 0.6–46.4%), and these exposures jointly 54.4% (95% CI = 25.3–72.1%) of oesophageal adenocarcinomas. Overweight and obesity explain 36.1% (95% CI = 9.1–55.1%), current and past smoking 24.2% (95% CI = 4.2–40.0%), and these exposures jointly 51.2% (95% CI = 26.3–67.8%) of stomach cardia cancers. Several population groups had a significantly higher smoking-attributable oesophageal cancer burden, including men and those consuming excessive alcohol. Conclusions: Smoking is the leading preventable behavioural cause of oesophageal cancers and overweight/obesity of stomach cancers. [ABSTRACT FROM AUTHOR]

There is often considerable social media commentary on whether remnant kangaroo populations in urban areas should be euthanased or translocated. Here, we describe a translocation program in Western Australia where kangaroos were herded into a temporary enclosure, darted, sedated, and translocated to a site in the State Forest east of the Swan Coastal Plain where they were released after 24 h. Prior to darting and after being initially herded into a temporary holding enclosure, kangaroos were repeatedly released from the enclosure by members of the public. Sixty-three of 154 adult kangaroos and 20 of 52 pouched young (40.3%) died or were euthanased before being released from the translocation release enclosure. The total volume of the sedative Zoletil (mL kg−1) injected into kangaroos as a sedative was significantly higher in those that survived than those that died. The primary conclusion from this management program was that the western grey kangaroos were susceptible to capture myopathy and distressed animals are at a greater risk of not surviving a translocation program. In our professional judgement, from an animal welfare perspective, these kangaroos should have been euthanased and not translocated. Such scientific advice and professional experience should inform future decisions regarding management of remnant kangaroo populations. Western grey kangaroos distressed by members of the public that were translocate instead of being euthanased in response to social media pressure resulted in approximately 40% dying before being released at the translocation site. The primary conclusions from this investigation were that these kangaroos may be more susceptible to capture myopathy when they have been distressed by activities unrelated to translocation or capture, and that distressed animals may be at greater risk of not surviving a translocation program. [ABSTRACT FROM AUTHOR]

BACKGROUND: Proposed frameworks of college and career readiness include aspects of school climate perceptions and behavioral engagement. School climate initiatives emphasize the importance of healthy learning environments; while behavioral indicators tend to be used to identify students at-risk for disengagement, established early warning systems include few, if any, behavioral indicators. A promising and useful screening mechanism that combines behavioral indicators along with school climate perceptions may enhance identification of adolescents at risk for disengagement, academic failure, and dropout, and may ultimately improve college and career readiness. OBJECTIVE: The purpose of this study was to examine the relationship between self-reported adolescent perceptions of school climate and extant high school academic and behavioral data to create an index score which could be used as an early warning system for student disengagement. METHODS: To accomplish the stated objective, we employed structural equation modeling to estimate a multiple indicators multiple causes model using a sample of high school students (n = 5039) with and without disabilities. Extant school data included grade point average, attendance, tardies, and office discipline referrals, while school climate was measured using the Georgia Brief School Climate survey. RESULTS: Findings show evidence of a robust Adolescent Behavioral Index when controlled for disability status as those with disabilities are expected to have lower index scores indicating greater risk for school disengagement. CONCLUSION: Implications for research and practice are focused on the Adolescent Behavioral Index as a mechanism for systematic data collection that may underlie early warning systems in high schools specifically when designing college and career readiness interventions for adolescents and when identifying students who may be at risk for disengagement. [ABSTRACT FROM AUTHOR]

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis. [ABSTRACT FROM AUTHOR]

Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish construct validity of a college and career readiness measure using a sample of youth with (n = 356) and without (n = 1,599) disabilities from five high schools across three U.S. states. We established content validity through expert item review, structural validity through initial field-testing, and convergent validity by correlating domain scores with school academic and behavioral data. A four-factor measurement model emerged representing the domains Ownership of Learning, Academic Engagement and Processes, Interpersonal Engagement, and Career Development. Domain scores were significantly correlated with achievement, college admission exam scores, and attendance. Implications for research and practice with an emphasis on transition service delivery via multi-tiered systems of support are discussed. [ABSTRACT FROM AUTHOR]

Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan–NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation. [ABSTRACT FROM AUTHOR]

Limited evidence exists on the link between inflammation and epigenetic aging. We aimed to (a) assess the cross-sectional and prospective associations of 22 inflammation-related plasma markers and a signature of inflammaging with epigenetic aging and (b) determine whether epigenetic aging and inflammaging are independently associated with mortality. Blood samples from 940 participants in the Melbourne Collaborative Cohort Study collected at baseline (1990–1994) and follow-up (2003–2007) were assayed for DNA methylation and 22 inflammation-related markers, including well-established markers (eg, interleukins and C-reactive protein) and metabolites of the tryptophan–kynurenine pathway. Four measures of epigenetic aging (PhenoAge , GrimAge , DunedinPoAm , and Zhang) and a signature of inflammaging were considered, adjusted for age, and transformed to Z scores. Associations were assessed using linear regression, and mortality hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression. Cross-sectionally, most inflammation-related markers were associated with epigenetic aging measures, although with generally modest effect sizes (regression coefficients per SD ≤ 0.26) and explaining altogether between 1% and 11% of their variation. Prospectively, baseline inflammation-related markers were not, or only weakly, associated with epigenetic aging after 11 years of follow-up. Epigenetic aging and inflammaging were strongly and independently associated with mortality, for example, inflammaging: HR = 1.41, 95% CI = 1.27–1.56, p = 2 × 10−10, which was only slightly attenuated after adjustment for 4 epigenetic aging measures: HR = 1.35, 95% CI = 1.22–1.51, p = 7 × 10−9). Although cross-sectionally associated with epigenetic aging, inflammation-related markers accounted for a modest proportion of its variation. Inflammaging and epigenetic aging are essentially nonoverlapping markers of biological aging and may be used jointly to predict mortality. [ABSTRACT FROM AUTHOR]

Lifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N = 7,431) and validation (N = 4,307) samples. Using paired genetic-methylation data (N = 4,307), gene–environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), alcohol consumption (459 CpGs), and BMI (85 CpGs) and 2) two epigenetic ageing measures, PhenoAge and GrimAge. In the validation sample, PGS explained ~1.4% (P = 1 × 10−14), ~0.6% (P = 2 × 10−7), and ~8.7% (P = 7 × 10−87) of variance in smoking initiation, alcohol consumption, and BMI, respectively. Nominally significant interaction effects (P < 0.05) were found at 61, 14, and 7 CpGs for smoking, alcohol consumption, and BMI, respectively. There was strong evidence that all lifestyle-related phenotypes were positively associated with PhenoAge and GrimAge, except for alcohol consumption with PhenoAge. There was weak evidence that the association of smoking with GrimAge was attenuated in participants genetically predisposed to smoking (interaction term: −0.022, standard error [SE] = 0.012, P = 0.058) and that the association of alcohol consumption with PhenoAge was attenuated in those genetically predisposed to drink alcohol (interaction term: −0.030, SE = 0.015, P = 0.041). In conclusion, genetic susceptibility to unhealthy lifestyles did not strongly modify the association between observed lifestyle behaviour and blood DNA methylation. Potential associations were observed for epigenetic ageing measures, which should be replicated in additional studies. [ABSTRACT FROM AUTHOR]

Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.Results: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women. [ABSTRACT FROM AUTHOR]

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse‐variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08‐1.40). In blood‐based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02‐1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08‐1.34; blood‐based: 1.03, 1.01‐1.05) and early‐onset prostate cancer (MR: 1.37, 1.09‐1.73; blood‐based: 1.08, 0.98‐1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood‐based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups. [ABSTRACT FROM AUTHOR]

In this study, we examined college and career readiness (CCR) support for students with and without disabilities using data from the National Longitudinal Transition Study 2012. We selected variables relevant to CCR and focused on the interaction of disability, race and ethnicity, and household income across a range of disability categories, including those on individualized education programs and 504 plans, as well as for those without disabilities. Overall, we analyzed 19 groups of students representing these intersectional characteristics. Our findings show significant differences among the groups with regard to receiving the CCR supports: help with college applications, course-taking advice, interpretation of college admissions exam scores, and arranging college visits. Results show students of color without disabilities from low-income households were 2 times more likely to receive certain CCR supports. In contrast, across all study outcomes, students with disabilities showed different patterns than their counterparts without disabilities and were at a clear disadvantage with regard to access to CCR supports. Findings suggest disparities in schoolwide CCR supports for those with disabilities, which are more pronounced for students of color with disabilities. Implications for secondary transition educators and school counselors are discussed. [ABSTRACT FROM AUTHOR]

Background: DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer.Methods: Using data from four prospective case-control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage.Results: None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath 'age acceleration' (AA): OR per SD = 1.02, 95%CI: 0.95-1.10; AA-Hannum: OR = 1.03, 95%CI:0.95-1.12; PhenoAge: OR = 1.01, 95%CI: 0.94-1.09 and GrimAge: OR = 1.03, 95%CI: 0.94-1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01-1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics.Conclusion: We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer. [ABSTRACT FROM AUTHOR]

Objective: We aimed to broaden understanding of the perspectives of persons with arthritis on their use of wearables to self‐monitor physical activity, through a synthesis of evidence from qualitative studies. Methods: We conducted a systematic search of 5 databases (including Medline, CINAHL, and Embase) from inception to 2018. Eligible studies qualitatively examined the use of wearables from the perspectives of persons with arthritis. All relevant data were extracted and coded inductively in a thematic synthesis. Results: Of 4,358 records retrieved, 7 articles were included. Participants used a wearable during research participation in 3 studies and as part of usual self‐management in 2 studies. In remaining studies, participants were shown a prototype they did not use. Themes identified were: 1) the potential to change dynamics in patient–health professional communication: articles reported a common opinion that sharing wearable data could possibly enable patients to improve communication with health professionals; 2) wearable‐enabled self‐awareness, whether a benefit or downside: there was agreement that wearables could increase self‐awareness of physical activity levels, but perspectives were mixed on whether this increased self‐awareness motivated more physical activity; 3) designing a wearable for everyday life: participants generally felt that the technology was not obtrusive in their everyday lives, but certain prototypes may possibly embarrass or stigmatize persons with arthritis. Conclusion: Themes hint toward an ethical dimension, as participants perceive that their use of wearables may positively or negatively influence their capacity to shape their everyday self‐management. We suggest ethical questions pertinent to the use of wearables in arthritis self‐management for further exploration. [ABSTRACT FROM AUTHOR]

Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer‐free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF‐mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36‐2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF‐mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19‐1.48). In the case only analysis, BRAF‐mutation was differentially associated with diabetes (Pdifference =.03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF‐mutated tumors. [ABSTRACT FROM AUTHOR]