Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities

General Approach for Combining Diverse Rare Variant Association Tests Provides Improved Robustness Across a Wider Range of Genetic Architectures

The widespread availability of genome sequencing data made possible by way of next-generation technologies has yielded a flood of different gene-based rare variant association tests. Most of these tests have been published because they have superior power for particular genetic architectures. However, for applied researchers it is challenging to know which test to choose in practice when little is known a priori about genetic architecture. Recently, tests have been proposed which combine two particular individual tests (one burden and one variance components) to minimize power loss while improving robustness to a wider range of genetic architectures. In our analysis we propose an expansion of these approaches, yielding a general method that works for combining any number of individual tests. We demonstrate that running multiple different tests on the same dataset and using a Bonferroni correction for multiple testing is never better than combining tests using our general method. We also find that using a test statistic that is highly robust to the inclusion of non-causal variants (Joint-infinity) together with a previously published combined test (SKAT-O) provides improved robustness to a wide range of genetic architectures and should be considered for use in practice. Software for this approach is supplied. We support the increased use of combined tests in practice-- as well as further exploration of novel combined testing approaches using the general framework provided here--to maximize robustness of rare-variant testing strategies against a wide range of genetic architectures

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Design and Operationalization of Connectivist Activities: an Approach through Business Process Management

International audienceThe work presented in this paper focuses on massive open online course (MOOC) environments, and more specifically on the activity of designing and implementing pedagogical scenarios for a connectivist MOOC (cMOOC). This paper presents a research work, which aims to propose a model and tool to support the design of connectivist MOOC scenarios. The major contribution of this work is a visual authoring tool that is intended for the design and deployment of cMOOC-oriented scenarios. The tool is based on the BPMN notation that we have extended to suit our objectives. The tool was evaluated primarily from the point of view of utility and usability. The findings confirm that the tool can be used to design connectivist pedagogical scenarios and can provide all the necessary elements to operationalize such courses

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Effect of Ambrotose AO® on resting and exercise-induced antioxidant capacity and oxidative stress in healthy adults

<p>Abstract</p> <p>Background</p> <p>The purpose of this investigation was to determine the effects of a dietary supplement (Ambrotose AO^®) on resting and exercise-induced blood antioxidant capacity and oxidative stress in exercise-trained and untrained men and women.</p> <p>Methods</p> <p>25 individuals (7 trained and 5 untrained men; 7 trained and 6 untrained women) received Ambrotose AO^®(4 capsules per day = 2 grams per day) or a placebo for 3 weeks in a random order, double blind cross-over design (with a 3 week washout period). Blood samples were collected at rest, and at 0 and 30 minutes following a graded exercise treadmill test (GXT) performed to exhaustion, both before and after each 3 week supplementation period. Samples were analyzed for Trolox Equivalent Antioxidant Capacity (TEAC), Oxygen Radical Absorbance Capacity (ORAC), malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and nitrate/nitrite (NOx). Quality of life was assessed using the SF-12 form and exercise time to exhaustion was recorded. Resting blood samples were analyzed for complete blood count (CBC), metabolic panel, and lipid panel before and after each 3 week supplementation period. Dietary intake during the week before each exercise test was recorded.</p> <p>Results</p> <p>No condition effects were noted for SF-12 data, for GXT time to exhaustion, or for any variable within the CBC, metabolic panel, or lipid panel (p > 0.05). Treatment with Ambrotose AO^®resulted in an increase in resting levels of TEAC (p = 0.02) and ORAC (p < 0.0001). No significant change was noted in resting levels of MDA, H₂O₂, or NOx (p > 0.05). Exercise resulted in an acute increase in TEAC, MDA, and H₂O₂(p < 0.05), all which were higher at 0 minutes post exercise compared to pre exercise (p < 0.05). No condition effects were noted for exercise related data (p > 0.05), with the exception of ORAC (p = 0.0005) which was greater at 30 minutes post exercise for Ambrotose AO^®compared to placebo.</p> <p>Conclusion</p> <p>Ambrotose AO^®at a daily dosage of 4 capsules per day increases resting blood antioxidant capacity and may enhance post exercise antioxidant capacity. However, no statistically detected difference is observed in resting or exercise-induced oxidative stress biomarkers, in quality of life, or in GXT time to exhaustion.</p

Background risk of breast cancer and the association between physical activity and mammographic density

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Postprandial Oxidative Stress in Exercise Trained and Sedentary Cigarette Smokers

Cigarette smokers experience an exaggerated triglyceride (TAG) and oxidative stress response to high fat feeding. Exercise training may serve to attenuate the rise in these variables, by improving TAG clearance and antioxidant defense. We compared blood TAG, antioxidant capacity, and oxidative stress biomarkers in exercise trained (>2 hrs per wk) and untrained smokers matched for age, in response to a high fat test meal. We report here that low volume exercise training can attenuate postprandial lipid peroxidation, but has little impact on blood TAG and other markers of oxidative stress. Higher volumes of exercise may be needed to allow for clinically meaningful adaptations in postprandial lipemia and oxidative stress

A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25–65 when interviewed in 1990–92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93–1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02–1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86–1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09–1.64) compared with never users (SIR = 1.07, 95% CI 0.96–1.19). Breast cancer increased with increasing duration of use and for 48–120 months use the SIR was 1.92 (95% CI 1.32–2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use. © 2001 Cancer Research Campaign http://www.bjcancer.co