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This paper applies a child-centric approach to examine the relationship between poverty, deprivation and well-being among children aged between 11 and 16 attending government high schools in New South Wales, Australia. Poverty is measured using children’s perceptions of the ability of their family to ‘get by’ while the consensual approach is used to identify as deprived children who do not have but want items that are regarded by a majority as essential for all children. A survey was developed after conducing focus groups with children and was completed by 2672 children attending one of 52 schools in mid-2016. The survey data were used to estimate the incidence of poverty and deprivation and the severity of both conditions was compared with a range of indicators of subjective well-being that cover overall life satisfaction, happiness, connectedness and contentment with aspects of schooling. The results show that children who perceive themselves as either poor or deprived (or both) have lower levels of well-being in all four dimensions compared with children to who are neither poor nor deprived. The associations between well-being and both poverty and deprivation are similar, which suggests that both have a role to play and that some form of composite (overlap) measure should be included in future studies of child poverty and disadvantage.

Background: Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles. Methods: We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls. Results: Truncating variants in these genes were rare, and were not associated with breast cancer risk. Burden testing of rare missense variants highlighted 5 genes with some suggestion of an association with breast cancer, although none met the multiple testing thresholds: MKL1, FTO, NEK10, MDM4, and COX11. Six common alleles in COX11, MAP3K1 (two), and NEK10 (three) were associated at the P < 0.0001 significance level, but these likely reflect linkage disequilibrium with causal regulatory variants. Conclusions: There was no evidence that rare coding variants in these genes confer substantial breast cancer risks. However, more modest effect sizes could not be ruled out. Impact: We tested the hypothesis that rare variants in 38 genes near breast cancer GWAS loci may mediate risk. These variants do not appear to play a major role in breast cancer heritability.

Using nationally representative Time Use Surveys from Australia, Korea, and Finland (n = 19,127 diaries) we examine how parenthood and the age of the youngest child are associated with the recuperative activities of leisure and sleep, the productive activities of market and nonmarket work, and with subjective time stress. Time stress differences by fatherhood are greatest for Finns and least for Koreans; time stress differences by motherhood are absent for Finns and high for Australians and Koreans. Results of the comparative analysis suggest that social policy and average national working hours produce different gendered gaps in both objective and subjective time stress among parents.

Motherhood brings significant change in the way women spend and experience their time. Having children is an intensely personal experience. Yet, much of the practical impact upon mothers’ time is shaped by the social organisation of work and care, which means the daily demands of parenting and child-raising vary over time and place. This chapter uses nationally representative time use surveys from four countries (Australia, Finland, Korea and Spain) to compare parents’ overall workloads when paid and unpaid work is scheduled over the day and week, gender divisions of work and care and the subjective time pressure associated with transitions to parenthood. It discusses how the findings relate to family policy, national work time regimes and social attitudes towards gender roles, mothering and fatherhood.

The authors investigated gender differences in couple parents' subjective time pressure, using detailed Australian time use data (n=756 couples with minor children). They examined how family demand, employment hours, and nonstandard work schedules of both partners relate to each spouse's non-employment time quality (“pure” leisure, “contaminated” leisure, multitasking housework, and child care) and subjective feelings of being rushed or pressed for time. Mothers averaged more contaminated leisure and less pure leisure and did much more unpaid work multitasking than fathers. These results suggest that these differences in time quality do partially account for mothers feeling more rushed than fathers. Weekend work was associated with mothers having less pure leisure, but not contaminated leisure. The opposite was found for fathers. Spousal work characteristics also related to time use and feeling rushed in gendered ways, with male long work hours positively associated with higher time pressure for mothers as well as the fathers who worked them.

Few studies of media use and adiposity explore the influence of parenting on children's lifestyle behaviors. Screen media access, bedroom television, lack of physical activity, and snacking on energy-dense foods have long been implicated in child overweight. This research used data from the first three waves of the Longitudinal Study of Australian Children to investigate, prospectively, the associations between parental practices in early to middle childhood and children's behaviors and weight in late childhood. A path model was used to investigate whether consistent parenting predicted setting of boundaries for access to and use of media, and was indirectly associated with children's lifestyle behaviors that increase the likelihood of healthy weight maintenance. The findings demonstrated that children's lifestyles pertinent to weight maintenance and media use cluster together and involve both old and newer screen media, but are also predicted by parenting practices and the family environment.

Gender equality in time spent in market work and in housework and family care is widely seen as desirable, potentially enhancing women’s financial security and allowing men to participate more fully in family life, but does gendered time equality engender higher subjective time stress than gender specialization? This chapter uses time use data from Australia, Finland, and Korea to compare the reported time stress of men and women in time use equality households versus those in more gender specialized households. The findings provide evidence of a complex interplay among social norms, policy regimes, average weekly employment hours, and time stress from equality of time use. Time stress of equality is lowest in Finland where average hours of employment are low for men.

In most Western countries, a growing proportion ofemployeesworknonstandardhours(Rapoport & Le Bourdais, 2008). A body of research suggests that nonstandard hours have detrimen- tal effects on employees' health and well-being, on their job satisfaction, and on their work-life balance (Bardasi & Francesconi, 2000; Benach, Gimeno, Benavides, Martinez, & Torne, 2004; Presser, 2003; Shields, 2002; Tausig & Fenwick, 2001). The negative outcomes of nonstandard work schedules are thought to arise at least in part from the constraints they place on how employees can spend their nonwork time. All paid work limits the opportunity to spend time in other activities, but some scholars have argued that a particular feature of nonstandard hours is that they put people out of sync with their family, friends, and community, making it difficult to coordinate time with others (La Valle, Arthur, Millward, & Scott, 2002).Nonstandard work schedules include work- ing evenings, nights, and weekends. All deviate from standard patterns, but weekend work has particular implications for shared activities, in particular shared leisure and relaxation. Research indicates that, compared to other forms of nonstandard work, including night and evening shifts, weekend employment is associated with the most interference between work and family activities (Almeida, 2004; Demerouti, Geurts, Bakker, & Euwema, 2004; Martin, Wittmer, & Lelchook, 2011; Presser, 2003). This interference encompasses joint leisure activities, because weekends are when most sports and recreation activities are scheduled, church attendance and civic partic- ipation take place, and people meet together socially (Presser, Gornick, & Parashar, 2008). Spending leisure and recreation time with family and friends is important for rest and recuperation and for cementing social ties (Iwasaki & Smale, 1998; Shaw & Dawson, 2001). If these activities are diminished, work- ers are likely to feel more isolated, to be less integrated into their communities, and to have poorer mental health than others (Han & Miller, 2009; Presser, 2000; Strazdins, Clements, Korda, Broom, & D'Souza, 2006).Family psychologists have noted the advan- tages of couples and families spending leisure time together. Shared couple leisure time is thought to be particularly important for mar- riage quality and cementing the relationship, and it is a predictor of relationship satisfaction (Shaw & Dawson, 2001; Shepanski & Diamond, 2007; Smith, Snyder, Trull, & Monsma, 1988; Strazdins et al., 2006). Time use studies con- firm that nonstandard work leads to desynchro- nization in couple time on work days (Lesnard, 2008; Wight, Raley, & Bianchi, 2008), but to date none have explored connections between weekend work and leisure time shared with a spouse.Weekend work is also likely to affect parents' leisure time with children. Parents' schedules determine when they are available to their children and, conversely, children's schedules determine when they are available to their parents (Fagan, 2001; Maher, Lindsay, & Bardoel, 2010; Wight et al., 2008). For many working parents weekends are the main opportu- nity to share leisure time with children because both parties are available. Because their working hours are typically longer than mothers', fathers in particular use the weekends to spend time with children (Hook, 2012; Maume, 2011). Although there is some evidence that evening and night shifts may allow parents, again espe- cially fathers, to spend more time with children on the days they work (Wight et al., 2008), this is less possible for weekend workers (La Valle et al., 2002).Weekend workers potentially could make up on other days for the activities forgone on the days they work. Indeed, research has suggested that some employed parents choose weekend shifts expressly to maximize the time that chil- dren can be cared for by one or the other parent (Mills & Taht, 2010). …

Most research on gender divisions of housework focuses on couple and family households. This article extends this literature to examine gender differences in domestic labour across living arrangements, with particular focus on young adults. Using time-diary data from the nationally representative Australian Bureau of Statistics (ABS) Time Use Survey (2006) it examines the amount and composition of domestic work performed by 20–34-year-olds ( n = 889) living with parents, in a share household, alone, or in a couple, differentiating between routine and non-routine housework tasks, and between housework done for oneself only or for the household. It finds gender differences are strongest in couple households, but pertain across living arrangements, including share houses. Also, women’s domestic labour varies more by household characteristics than men’s. However, there is some evidence of non-conformity to gender stereotypes, with young men living in couple relationships contributing more time on activities for the household than young men in other households.

The transition from having no children to starting a family brings substantial changes in time use (Craig and Bittman 2008; Kotila, Schoppe-Sullivan, and Kamp Dush 2013). The increase in household workload is large and, although it varies somewhat across different social and policy contexts, it is present cross-nationally (Dribe and Stanfors 2009; Craig and Mullan 2010; Gauthier and DeGusti 2012). Parenthood also changes the composition of time use, adding requirements to perform not only child care but additional domestic work as well (Craig and Bittman 2008). Households meet this additional unpaid time demand in a variety of ways, including redirecting time to child care that nonparents can allocate to other things, such as leisure, sleep, and market work (Bianchi 2005). Other forms of adaptation include time compression—by doing more within the same period of time (Robinson and Godbey 1997).

The advent of the Global Financial Crisis reminds us that modern epidemiological research has consistently demonstrated links between the socio‑economic circumstances of families and children's health and development. Drawing on data from the Longitudinal Study of Australian Children, this article firstly examines the evidence for intergenerational transmission of socio-economic disadvantage from parents to young children. It then examines parents' jobs as another source of social inequality. Results confirm that children's healthy development is affected by family income, by parents' hours of work and by the quality of parents' jobs. Job combinations that include long work hours of mothers and fathers and poorer quality jobs are associated with elevated rates of parental mental health problems, less time spent in developmentally important activities with children, and socio-emotional developmental difficulties for children. The evidence suggests that these effects are greater within low income families. These findings highlight the need for social and economic policies to move beyond simplistic notions of promoting parental workforce participation as a way of reducing the adverse effects of social disadvantage. A more nuanced approach is required that considers the additional impacts of the quality and characteristics of jobs, especially for the parents of young children.

Background: Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors. Methods: Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density). We tested for associations between hormone levels and density measures and estimated the genetic and environmental correlations between pairs of traits using variance and covariance components models and pedigree-based maximum likelihood methods. Results: We found no significant associations between estradiol, testosterone, or SHBG levels and any of the three density measures, after adjusting for body mass index (BMI). The estimated heritabilities were 63%, 66%, and 65% for square root–transformed adjusted percentage density, dense area, and nondense area, respectively, and 40%, 25%, and 58% for log-transformed–adjusted estradiol, testosterone, and SHBG. We found no evidence of a shared genetic basis between any hormone levels and any measure of density, after adjusting for BMI. The negative genetic correlation between dense and nondense areas remained significant even after adjustment for BMI and other covariates (ρ = −0.34; SE = 0.08; P = 0.0005). Conclusions: Breast density and sex hormones can be considered as independent sets of traits. Impact: Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci. Cancer Epidemiol Biomarkers Prev; 21(12); 2167–75. ©2012 AACR.

Covalent modifications of titanium with small molecules known to promote human osteoblast maturation are especially attractive in developing superior biomaterials. An important step in securing competent bone formation at implant sites is promoting the formation of mature osteoblasts, either from committed pre-osteoblasts or from their mesenchymal progenitors. To this end our research has focussed on identifying molecules that enhance human osteoblast formation and maturation and to develop ways of covalently attaching these molecules to implant surfaces so that they are more likely to withstand the rigors of the implantation process whilst still retaining their bioactivity. Herein we report the novel production of lipid-functionalised titanium using lysophosphatidic acid or a related compound, (3S) 1-fluoro-3-hydroxy-4-butyl- 1-phosphonate. Both lipids were especially effective at co-operating with calcitriol to promote human osteoblast maturation at these modified Ti surfaces in vitro. The novel findings presented offer enticing new developments towards the fabrication of next-generation implant devices with the potential to significantly enhance the osseointegration process and with it improvements in future prosthesis performance and longevity.

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of single-nucleotide polymorphisms (SNP) were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case–control status as the outcome. This analysis was repeated using 10 different cutoff points for the most significant density SNPs (1%–10% representing 5,222–50,899 SNPs). Permutation analysis was also conducted across all 10 cutoff points. The association between risk score and breast cancer was significant for all cutoff points from 3% to 10% of top density SNPs, being most significant for the 6% (2-sided P = 0.002) to 10% (P = 0.001) cutoff points (overall permutation P = 0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR = 1.31; 95% confidence interval (CI), 1.08–1.59] compared with women in the bottom 10%. Together, our results show that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants. Cancer Res; 72(6); 1478–84. ©2012 AACR.

Time use data (TUD) are distinctive, being episodic in nature and consisting of both continuous and discrete (exact zeros) values. TUD is non-negative and generally right skewed. To analyze such data, the Tobit, and to a lesser extent, linear regression models are often used. Tobit models assume the zeros represent censored values of an underlying normally distributed latent variable that theoretically includes negative values. Both the linear regression and Tobit models have normality as a key assumption. The Poisson-gamma distribution is a distribution with both a point mass at zero (corresponding to zero time spent on a given activity) and a continuous component. Using generalized linear models, TUD can be modeled utilizing the Poisson-gamma distribution. Using TUD, Tobit and linear regression models are compared to the Poisson-gamma with respect to the interpretation of the model, the model fit (analysis of residuals), and model performance through the use of a simulated data experiment. The Poisson-gamma is found to be theoretically and empirically more sound in many circumstances.

Alarm about the increasing prevalence of childhood obesity has focussed attention on individual lifestyle behaviours that may contribute to unhealthy weight. Television viewing is often a focus of the obesity debate. Not only is it sedentary, it also has the potential to influence other lifestyle behaviours either by displacing physical activities or through the consumption of high energy snack foods while watching TV. The research reported here uses data from 2,143 Australian 6–7 year children to examine the lifestyle behaviours associated with excess weight. These children spent 90 min each day watching television, 100 min each day in physical activity, and 39% consumed high levels of snack foods. Nearly one in five (18%) were overweight or obese. After adjustment for family and child characteristics, more time spent watching television was associated with more snacking and less physical activity. However, television viewing was associated with children’s weight status, but snacking and physical activities were not. These findings confirm the existence from a young age, of a cluster of lifestyle behaviours that are associated with unhealthy weight status.

Mobile phone services are now universally diffused, creating the possibility of perpetual contact, regardless of time and location. Many think the impossibility of being ‘out of touch’ leads to increased time pressure. In addition to claims that the mobile phone has led to harried leisure, others have argued that perpetual contact extends work into the home or intensifies work in other ways. In this article, these issues are explored using survey data employing some novel methodologies — combining a questionnaire with logs of phone traffic recovered from respondents’ handsets and a purpose-designed time-diary of technology use. Overall, results show that mobile phone use is not associated with more harried leisure. Fears of work intruding into home life appear to be exaggerated. However, there is some evidence that frequent use of mobiles during working hours is associated with work intensification, at least among men.

Major recent advances in the field of POM-surfactant ISA complexes are the extension of the studies into both thermo- and lyotropic phase behaviour, and the use of the vesicle motif for the production of novel hybrid vesicle structures. The use of metal-coordinating functional surfactants has led to the expression of synergistic functionality in POM-based materials.

There can be little doubt that the cell phone is one of the most rapidly diffused devices in the history of technological innovation. Worldwide there are now over 1.7 billion cell phone accounts, 600 million more cell phones services than fixed lines (Castells et al. 2007). Many contemporary social scientists have seen the social effects of diffusion of portable information and communication technologies (ICTs) as signaling a historical watershed. For example, Virilio (2000) has asserted that ICTs, including the cell phone have transformed proximity, so that it is now based on time rather than place. The capacity of cell phones to operate regardless of location gives rise to new patterns of continuous mediated interactions (Agar 2003; Katz and Aakhus 2002; Licoppe and Smoreda 2006). While Nicola Green (2002) argues that mobile technologies afford novel opportunities for intensifying strong ties, others presume these technologies encourage work problems to * spillover' and colonize the social spaces and times once reserved for family life (Fligstein and Sharone 2002; Chesley 2005; Duxbury et al. 2006). Many writers have linked the 'always on' character of mobile technology with an increase in the pace of daily life (Wajcman 2008). The accelerated change popularly ascribed to ICTs is neatly captured in the title of journalist and science writer James Gleick's (1999) book, Faster: The Acceleration of Just About Everything. Cell phones are said to eliminate 'down time', presumably increasing the sensation that there is never a moment to spare. Although they do not connect their observations to the use of ICTs, Robinson and Godbey (1997) have suggested that the fragmentation of leisure explains the rising proportion of Americans who felt increasingly 'rushed or pressed for time' between 1965 and 1995 (even though the average leisure time of Americans had increased over this period).

Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P < 10−5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk. Cancer Res; 75(12); 2457–67. ©2015 AACR.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending familial cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p < 0.001) and 4 months post-notification of result (t = -3.22; p = 0.002). For non-carriers, significant decreases in mean scores for intrusive and avoidant thoughts about colorectal cancer were observed at all follow-up assessment time points relative to baseline. Non-carriers also showed significant decreases from baseline in mean depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.

For AIDS prevention programmes, finding the right time and the right place in which to impart the right message is critical. This ethnographic study asks if the traditional seclusion period following male circumcision among the Meru in Kenya may be a “moment to seize.” Interviews were conducted with boys undergoing circumcision, adult Meru men, traditional circumcisers, and hospital staff carrying out circumcision. Traditionally, during the seclusion period following the circumcision, cut boys, already physically “made into men,” were taught how to behave, feel, and function as men. Ingrained in Meru culture is not only an expectation of social, psychological, sexual, and behavioural change but teaching/social mechanisms to facilitate change. A pilot health education programme, held during circumcision seclusion, appears to be an acceptable and effective means of modifying risk-taking behaviour, though further rigorous evaluation is required. The Meru imperative for circumcised youth to “learn the ways of men” presents an opportunity to reach young men with health messages.

Psychological adjustment in 90 women (30 carriers and 60 non-carriers) who had undergone genetic testing for mutations in BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes was compared with that of 53 women who were not offered genetic testing. Women were assessed prior to genetic testing and 7–10 days, 4 and 12 months after carrier status disclosure using self-administered questionnaires. Compared with women not offered testing, mutation carriers had significantly higher breast cancer distress 7–10 days ( t =2.80, P =0.005) and 12 months ( t =2.01, P =0.045) post-notification. Non-carriers showed a significant decrease in state anxiety 7–10 days post-notification ( t =2.27, P =0.024) and in depression 4 months post-notification ( t =2.26, P =0.024), compared with women not offered testing. These data show that non-carriers derive psychological benefits from genetic testing. Women testing positive may anticipate a sustained increase in breast cancer distress following disclosure, although no other adverse psychological outcomes were observed in this group.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology. ispartof: Nature communications vol:5 pages:4999- ispartof: location:England status: published

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49–2.19); P for trend=1.90 × 10−9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities., Studies have shown that breast cancer prognosis is hereditary. Here the authors show that a genetic variant in CCL20, a chemokine ligand involved in immune response, is significantly associated with breast cancer survival and may therefore represent an important therapeutic or prognostic target.

Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P

SUMMARY Research interest in psychosocial predictors of the onset and course of cancer has been active since the 1950s. However, results have been contradictory and the literature is noted for methodological weaknesses. In this prospective study we aimed to systematically obtain data on psychosocial factors thought to be associated with cancer outcome in early-stage breast cancer. Consecutive patients with early-stage breast cancer seen for the first time for ongoing treatment at a major teaching hospital in Sydney participated in the study. Exclusion criteria included inability to speak English and co-existing psychiatric illness. Participants completed a series of questionnaires every 3 months for up to 2 years following their diagnosis. Domains measured included cognitive appraisal of threat, coping, psychological adjustment, social support, quality of life and perceived aim of treatment. Disease and demographic data were obtained from medical records, including age, marital status, education and occupational status, treatment received, menopausal status, tumour size and grade. 233 patients agreed to participate in the study and 211 (88%) had sufficient data for analysis. Patients were a mean age of 51 years; 84% of the sample were Australian-born; 25% of the sample had a University education and 39% were in managerial or professional occupations. 59% had chemotherapy following surgery and 54% were taking tamoxifen. Women entered the study a median of 91 days since diagnosis. 30 (14%) of the 211 women died within the study period and 36 (17%) relapsed. Multivariate analysis of baseline measures only, used the Cox proportional hazards model. Two psychosocial factors independently predicted both survival and time to relapse. Apart from disease variables, three non-medical factors remained in both of the final models: appetite, concern about dependence and concern about the disease. Patients who had high levels of concern about the disease and low levels of concern about dependence survived for a significantly shorter time (Hazard Ratio (HR) = 1.04, 95% CI = 1.01–1.06; HR = 0.96, 95% CI = 0.94–0.99) and relapsed quicker (HR = 1.03, 95% CI = 1.01–1.06; HR = 0.96, 95% CI = 0.93–0.98). Concern about the disease was also predictive of outcome in primary melanoma patients, but the directional effect was opposite; that is, patients with a higher concern about their disease did better. Perhaps patients with early melanoma are mobilized by their concern to take active self-protective measures which can have a real impact on their disease (such as staying out of the sun), whereas similar self-protective strategies are not available to patients with early breast cancer. Alternatively, concern about the disease may reflect medical factors in breast cancer which we did not record. Interestingly, the coping response of minimization, which was significantly predictive of outcome in our metastatic breast cancer sample, was not significant in this population. It is likely that different coping styles are salient and predictive of outcome at different stages of disease. There is still much to learn about the potential relationships between psychological wellbeing, human behaviours and cancer outcome. Research in this area needs to clarify the psychological processes themselves as well as understand the biological and/or behavioural mechanisms that may link them to outcome.

To examine whether maternal caffeine consumption is associated with the risk of spontaneous abortion, we analyzed data from a population-based prospective study. The study population comprised 575 women delivering singleton livebirths and 75 women who had spontaneous abortions. The subjects were predominantly white, middle-class women enrolled before pregnancy. Study participants were traced to delivery of a liveborn, singleton infant or a spontaneous abortion. Of the 71 women who did not experience nausea, 29.6% had a spontaneous abortion, compared with 7.2% of 514 women who did experience nausea. Maternal caffeine consumption before pregnancy, or in women without nausea, did not increase the risk of spontaneous abortion, whereas maternal caffeine consumption during the first trimester after nausea started might increase risk of spontaneous abortion (risk ratio = 5.4, 95% confidence interval = 2.0-14.6 for caffeine consumption > or = 300 mg per day compared with < 20 mg per day). These results suggest that maternal caffeine consumption during pregnancy may influence fetal viability in women with nausea.

This study evaluates the reliability and validity of parental measurements of infant size, using illustrated instructions and simple measuring tools. Following pilot tests, final methods were evaluated on a sample of 28 parents (26 mothers and 2 fathers) of infants from 1 to 6 weeks of age. Parents independently measured twice the infant's head circumference (HC), mid-upper arm circumference (MUAC), abdominal circumference (AC), and recumbent length (RL). Infants were also measured twice by a trained observer. Mean parental measures were correlated (intraclass R) with the observer criterion measures at the levels of 0.81 for RL, 0.70 for AC, 0.80 for MUAC, and 0.94 for HC. Relative differences in the means for measurements obtained by parents and the trained observer were small, ranging from 0.3% for HC and RL, to 3.8% for AC. Intraclass correlations of reliability between the two parental measurements ranged from R = 0.84 for MUAC to 0.96 for RL. Given the reliability and validity of the results, the methods tested yield measurements that are suitable for ranking individuals and for use in group-level analyses, and at least in the case of head circumference, for individual-level analyses. Am. J. Hum. Biol. 13:275–279, 2001. © 2001 Wiley-Liss, Inc.

This study explored psychosocial predictors of relapse and survival in early stage melanoma patients. Patients with locoregional melanoma whose tumour thickness exceeded 0.69 mm, seen at the Sydney Melanoma Unit between 1991 and 1996 participated in the study. Questionnaires were sent to participating patients every 3 months for 2 years. Domains measured included cognitive appraisal of threat, coping, psychological adjustment, quality of life and perceived aim of treatment. Disease and demographic data were obtained from medical records. Multivariate analyses from baseline data used the Cox proportional hazards model. Of the 682 patients invited to participate 426 (62%) agreed. 91 (21%) relapsed and 60 (14%) died within the follow-up period, that ended in October 1997. After controlling for known prognostic indicators, several psychosocial variables predicted time to relapse and/or survival duration. Patients who perceived their aim of treatment to be cured, who did not use avoidance as a coping strategy or who were concerned about their disease experienced longer periods without relapse. Shorter survival duration was associated with a positive mood, the use of avoidance as a coping strategy, not being concerned with their disease and concern about the impact of the disease on family. There is still much to learn about the potential relationships between psychological well being, human behaviours and cancer outcome. Research in this area needs to clarify the psychological processes, as well as understand the biological and/or behavioural mechanisms that may link them to outcome. © 2000 Cancer Research Campaign http://www.bjcancer.com

Background: Quality of life (QOL) assessment is an important component within cancer research. There is often variability in QOL scores both between patients and across time. Understanding this variability in terms of personal characteristics and psychosocial factors would be useful but is often obstructed by the types of analyses that are applied to longitudinal data sets. Improved understanding can be gained with the application of multi-level or hierarchical models that allow for greater flexibility for modelling individual patterns of change over time. Methods and patients: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months for up to 2 years. The data reported here are from a sub-sample of 44 patients who each completed between 3 and 8 questionnaires. Three aspects of QOL were measured (effort to cope, mood and physical well-being), each with a single LASA line. Multilevel techniques were used to model the patterns of QOL over time. Covariates were added to explain variation between patients in their average QOL and change in QOL over time. Results: The scores of each of the three QOL measures showed marked fluctuations over time. However, there was little systematic change during the study in either effort to cope ( p = 0.32) or mood ( p = 0.06). In contrast, the physical well-being scores of some patients improved while others deteriorated ( p < 0.001). On average, physical well-being deteriorated ( p < 0.001). Variability between patients accounted for 60% (effort to cope), 45% (mood) and 44% (physical well-being) of the total variance of each scale. A range of psycho-social factors including active and avoidant coping styles and psychological adjustment accounted for significant amounts of the variability between patients in each QOL measure. Conclusion: Individual coping and psychological adjustment are related to individual changes in QOL and to differences among patients' QOL. The study illustrates the use of multi-level techniques to further our understanding of differences between patients in their QOL and how it changes over time.

Associations between maternal cigarette smoking and accelerated placental maturation measured as tissue calcification have been reported. The authors sought to address whether intakes of the dietary antioxidants, vitamin C, alpha-tocopherol, and beta-carotene, were related to placental calcification of the maternal surface and villi in a cohort of smokers and nonsmokers at risk for delivering small-for-gestational age infants. Gross and histologic examination of placentas were used to determine calcification at the surface (n = 1,213) and villus sites (n = 730), respectively, in a prospective study of black and white women who delivered singleton births between December 1985 and October 1988 at the University of Alabama at Birmingham Hospital in Birmingham, Alabama. Controlling for race and gestational age, likelihood of surface and villus calcification increased as smoking levels increased. Significant reductions in villus calcification were related to alpha-tocopherol intake after controlling for smoking and gestation while intakes of beta-carotene and vitamin C were related to significant reductions in calcification for black but not white women. Surface calcification was not found to be related to antioxidant intake. The authors' findings confirm a pathologic relation between smoking and placental calcification and suggest that dietary antioxidants may reduce villus calcification.

Major advances in research related to maternal nutrition and the outcome of pregnancy have been achieved in the past decade. This article highlights these recent advances, summarizes nutritional recommendations for practice, and overviews the body of evidence that implicates aspects of maternal nutrition in the development of hypertension, heart disease, diabetes, and other disorders in offspring.

Objective To provide accurate population normative data documenting cross-sectional, age-specific sleep patterns in Australian children aged 0–9 years. Design and setting The first three waves of the nationally representative Longitudinal Study of Australian Children, comprising two cohorts recruited in 2004 at ages 0–1 years (n=5107) and 4–5 years (n=4983), and assessed biennially. Participants Children with analysable sleep data for at least one wave. Measures At every wave, parents prospectively completed 24-h time-use diaries for a randomly selected week or weekend day. ‘Sleeping, napping’ was one of the 26 precoded activities recorded in 15-min time intervals. Results From 0 to 9 years of age, 24-h sleep duration fell from a mean peak of 14 (SD 2.2) h at 4–6 months to 10 (SD 1.9) h at 9 years, mainly due to progressively later mean sleep onset time from 20:00 (SD 75 min) to 21:00 (SD 60 min) and declining length of day sleep from 3.0 (SD 1.7) h to 0.03 (SD 0.2) h. Number and duration of night wakings also fell. By primary school, wake and sleep onset times were markedly later on weekend days. The most striking feature of the centile charts is the huge variation at all ages in sleep duration, sleep onset time and, especially, wake time in this normal population. Conclusions Parents and professionals can use these new centile charts to judge normalcy of children’s sleep. In future research, these population parameters will now be used to empirically determine optimal child sleep patterns for child and parent outcomes like mental and physical health.

Objective To investigate characteristics associated with wearing an accelerometer for the required and requested time among 8-year-old to 10-year-old children. Design Cross-sectional. Setting 60 Bristol and North Somerset primary schools taking part in the ‘Active for Life Year 5’ randomised controlled trial (RCT) in 2011. Participants 2048 children, aged 8–10 years, invited to wear an accelerometer for 5 days of recording. Primary outcome measure Numbers meeting required wear-time for inclusion in main RCT analysis (≥8 h/day ≥3 days) and numbers meeting requested wear-time (≥8 h/day for all 5 days). Results 817 (40%) of the children wore the accelerometer for the requested time and 1629 (80%) for the required time. In adjusted multivariable analyses the odds of wearing the accelerometer for the required time were greater in females as compared with males (OR 1.76 (1.42–2.18)), those with higher scores for reporting their mother restricted time on sedentary behaviours (1.26 (1.04–1.52) per increase of 1 on a 1–4 scale) and in children from schools with larger year group sizes (1.01 (1.00–1.02) per additional child). Living in a neighbourhood with higher levels of deprivation (0.49 (0.33–0.72) comparing highest to lowest third of the deprivation score) or reporting higher levels of weekday outdoor play (0.97 (0.94, 1.00) per 30 min more) were associated with reduced odds of meeting required time. Results were essentially the same for requested wear-time. Other characteristics, including child body mass index, were not associated with required or requested wear-time. Conclusions Only 40% of children wore the accelerometer for the requested time but 80% fulfilled the required criteria to be included in the main study analyses. Knowing which characteristics are associated with accelerometer wear could help target interventions to increase wear-time.

Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10!-14), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10!-15) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10!-12) and BRCA1 mutation carrier (P = 1.6 × 10!-14) breast and invasive ovarian (P = 1.3 × 10!-11) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant. European Commission Seventh Framework Programme (agreement 223175-HEALTH-F2-2009-223175); Cancer Research UK (C1287/A10118 and C1287/A12014) peer-reviewed