Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP diet and health study.

BACKGROUND: Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. METHODS: In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. RESULTS: In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. CONCLUSION: A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Measures of Parent-Infant Interaction

Increasingly, programs for handicapped infants and toddlers are including in their intervention activities objectives related to the quality of parent-child interaction. As a consequence, it has become necessary for programs to assess the impact of these intervention efforts on parent behaviors. This article considers tools available for assessing parent-child interaction for program planning and evaluation. Lastly, recommendations are offered to guide the selection of a measure of parent-child interactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69100/2/10.1177_027112148600600204.pd

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Relative risks (RR) and 95% confidence intervals for total mortality by categories of body mass index in non-Hispanic blacks.

a.<p>Subjects who did not have any prevalent cancer except non-melanoma skin cancer or heart disease at baseline.</p>b.<p>Per 100,000 person-years, directly standardized to the age distribution of the cohort according to sex.</p>c.<p>Adjusted for age, sex, education (less than high school, high school graduate, some college, and college graduate/postgraduate), marital status (married and not married), smoking status (never, former, current), time since quitting smoking (never, stopped ≥10 years ago, stopped 5–9 years ago, stopped 1–4 years ago, stopped <1 year ago, and currently smoking), number of cigarettes per day (0, 1–10, 11–20, 21–30, 31–40, 41–50, 51–60, and >60 cigarettes/day), physical activity (never/rare, ≤3 times/mo, and 1–2 and ≥3 times/wk), alcohol consumption (0, >0–<15, 15–<30, and ≥30 g/day) and menopausal hormone therapy use in women (never, ever). In analysis of men and women, sex was excluded from the list of covariates.</p>d.<p>Adjusted for same covariates as noted in footnote c, except smoking status, time since quitting, and number of cigarettes per day. In analysis of men and women separately, sex was excluded from the list of covariates.</p

Relative risk for total mortality per 5-unit increase in body mass index in non-Hispanic blacks, according to selected characteristics^{a, b, c}.

<p>a. Subjects who did not have any prevalent cancer except non-melanoma skin cancer or heart disease at baseline. b. Adjusted for following variables, except for the stratification variable in each analysis: age, sex, education, marital status, smoking status, time since quitting smoking, number of cigarettes per day, physical activity, alcohol consumption, and menopausal hormone therapy use in women. c. Markers indicate the relative risks and horizontal lines indicate 95% confidence intervals. d. Number of death; p value for interaction: 0.55 for sex, 0.50 for age at baseline, <0.001 for smoking, 0.75 for physical activity, 0.40 for education, and 0.13 for alcohol.</p

Relative risk for total mortality in non-Hispanic black men and women^{a, b, c}.

<p>a. Subjects who did not have any prevalent cancer except non-melanoma skin cancer or heart disease at baseline b. Adjusted for age, education, marital status, smoking status, time since quitting smoking, number of cigarettes per day, physical activity, alcohol consumption, and menopausal hormone therapy use in women. Analysis of never smokers with no history of diseases at baseline was adjusted for same covariates except smoking status, time since quitting smoking, number of cigarettes per day. c. Men, 1,347 deaths in subjects with no history of disease and 288 deaths in never smokers with no history of diseases: Women, 1,262 deaths in subjects with no history of disease and 425 deaths in never smokers with no history of diseases.</p

Relative risks (RR) and 95% confidence intervals for cause-specific deaths in non-Hispanic black never smokers ^a.

a.<p>Never smokers who did not have any prevalent cancer except non-melanoma skin cancer or heart disease at baseline.</p>b.<p>Adjusted for age, sex, education (less than high school, high school graduate, some college, and college graduate/postgraduate), marital status (married and not married), physical activity (never/rare, ≤3 times/mo, and 1–2 and ≥3 times/wk), alcohol consumption (0, >0–<15, 15–<30, and ≥30 g/day) and menopausal hormone therapy use in women (never, ever).</p