714 research outputs found

    Development of a Personalized Decision Aid for Breast Cancer Risk Reduction and Management

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    Background: Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Methods: Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Results: Overall, the evaluations were favorable. The patient focus group evaluations and usability testing (N = 34) provided qualitative feedback about format and design; 88% of these participants found the tool useful and 94% found it easy to use. 91% of the providers (N = 23) indicated that they would use the tool in their clinical setting. Conclusion: BreastHealthDecisions.org represents a new approach to breast cancer prevention care and a framework for high quality preventive healthcare. The ability to integrate risk assessment and decision support in real time will allow for informed, value-driven, and patient-centered breast cancer prevention decisions. The tool is being further evaluated in the clinical setting

    Maximal supergravity in D=10: forms, Borcherds algebras and superspace cohomology

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    We give a very simple derivation of the forms of N=2,D=10N=2,D=10 supergravity from supersymmetry and SL(2,\bbR) (for IIB). Using superspace cohomology we show that, if the Bianchi identities for the physical fields are satisfied, the (consistent) Bianchi identities for all of the higher-rank forms must be identically satisfied, and that there are no possible gauge-trivial Bianchi identities (dF=0dF=0) except for exact eleven-forms. We also show that the degrees of the forms can be extended beyond the spacetime limit, and that the representations they fall into agree with those predicted from Borcherds algebras. In IIA there are even-rank RR forms, including a non-zero twelve-form, while in IIB there are non-trivial Bianchi identities for thirteen-forms even though these forms are identically zero in supergravity. It is speculated that these higher-rank forms could be non-zero when higher-order string corrections are included.Comment: 15 pages. Published version. Some clarification of the tex

    IIA/IIB Supergravity and Ten-forms

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    We perform a careful investigation of which p-form fields can be introduced consistently with the supersymmetry algebra of IIA and/or IIB ten-dimensional supergravity. In particular the ten-forms, also known as "top-forms", require a careful analysis since in this case, as we will show, closure of the supersymmetry algebra at the linear level does not imply closure at the non-linear level. Consequently, some of the (IIA and IIB) ten-form potentials introduced in earlier work of some of us are discarded. At the same time we show that new ten-form potentials, consistent with the full non-linear supersymmetry algebra can be introduced. We give a superspace explanation of our work. All of our results are precisely in line with the predictions of the E(11) algebra.Comment: 17 page

    Polygenic risk scores for coronary artery disease and subsequent event risk amongst established cases

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    BACKGROUND: There is growing evidence that polygenic risk scores (PRS) can identify individuals with elevated lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify risk of subsequent events among those surviving a first CAD event remains uncertain, with possible biological differences between CAD onset and progression, and the potential for index event bias. METHODS: Using two baseline subsamples of UK Biobank; prevalent CAD cases (N = 10 287) and individuals without CAD (N = 393 108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes. RESULTS: A 1 S.D. higher PRS was associated with increased risk of incident MI in participants without CAD (OR 1.33; 95% C.I. 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% C.I. 1.06, 1.25); heterogeneity P = 0.0012. Additionally, among prevalent CAD cases, we found evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% C.I. 0.85, 0.98) compared to those without CAD (OR 1.01; 95% C.I. 0.99, 1.03); heterogeneity P = 0.0041. A similar inverse association was found for ischaemic stroke (Prevalent CAD (OR 0.78; 95% C.I. 0.67, 0.90); without CAD (OR 1.09; 95% C.I. 1.04, 1.15), heterogeneity P < 0.001). CONCLUSIONS: Bias induced by case stratification and survival into UK Biobank may distort associations of polygenic risk scores derived from case-control studies or populations initially free of disease. Differentiating between effects of possible biases and genuine biological heterogeneity is a major challenge in disease progression research

    Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents

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    Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment

    Facial Genetics: A Brief Overview

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    Historically, craniofacial genetic research has understandably focused on identifying the causes of craniofacial anomalies and it has only been within the last 10 years, that there has been a drive to detail the biological basis of normal-range facial variation. This initiative has been facilitated by the availability of low-cost hi-resolution three-dimensional systems which have the ability to capture the facial details of thousands of individuals quickly and accurately. Simultaneous advances in genotyping technology have enabled the exploration of genetic influences on facial phenotypes, both in the present day and across human history. There are several important reasons for exploring the genetics of normal-range variation in facial morphology.     - Disentangling the environmental factors and relative parental biological contributions to heritable traits can help to answer the age-old question "why we look the way that we do?"     - Understanding the etiology of craniofacial anomalies; e.g., unaffected family members of individuals with non-syndromic cleft lip/palate (nsCL/P) have been shown to differ in terms of normal-range facial variation to the general population suggesting an etiological link between facial morphology and nsCL/P.     - Many factors such as ancestry, sex, eye/hair color as well as distinctive facial features (such as, shape of the chin, cheeks, eyes, forehead, lips, and nose) can be identified or estimated using an individual's genetic data, with potential applications in healthcare and forensics.     - Improved understanding of historical selection and adaptation relating to facial phenotypes, for example, skin pigmentation and geographical latitude.     - Highlighting what is known about shared facial traits, medical conditions and genes

    Limits of minimal models and continuous orbifolds

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    The lambda=0 't Hooft limit of the 2d W_N minimal models is shown to be equivalent to the singlet sector of a free boson theory, thus paralleling exactly the structure of the free theory in the Klebanov-Polyakov proposal. In 2d, the singlet sector does not describe a consistent theory by itself since the corresponding partition function is not modular invariant. However, it can be interpreted as the untwisted sector of a continuous orbifold, and this point of view suggests that it can be made consistent by adding in the appropriate twisted sectors. We show that these twisted sectors account for the `light states' that were not included in the original 't Hooft limit. We also show that, for the Virasoro minimal models (N=2), the twisted sector of our orbifold agrees precisely with the limit theory of Runkel & Watts. In particular, this implies that our construction satisfies crossing symmetry.Comment: 33 pages; v2: minor improvements and references added, published versio

    Body mass index, body dissatisfaction and adolescent smoking initiation

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    BACKGROUND: Smoking influences body weight, but there is little evidence as to whether body mass index (BMI) and body dissatisfaction increase smoking initiation in adolescents. METHODS: We evaluated the association between measured BMI, body dissatisfaction and latent classes of smoking initiation (never smokers, experimenters, late onset regular smokers, early onset regular smokers) in the Avon Longitudinal Study of Parents and Children. In observational analyses we used BMI (N=3754) and body dissatisfaction at age 10.5 years (N=3349). In Mendelian randomisation (MR) analysis, we used a BMI genetic risk score of 76 single nucleotide polymorphisms (N=4017). RESULTS: In females, higher BMI was associated with increased odds of early onset regular smoking (OR: 1.11, 95% CI: 1.04, 1.18) compared to being a never smoker, but not clearly associated with experimenting with smoking (OR: 1.04, 95% CI: 0.99, 1.10) or late onset regular smoking (OR: 1.01, 95% CI: 0.94, 1.09). No clear evidence was found for associations between BMI and smoking initiation classes in males (p-value for sex interaction≤0.001). Body dissatisfaction was associated with increased odds of late-onset regular smoking (OR: 1.71, 95% CI: 1.32, 1.99) in males and females combined (P-value for sex interaction=0.32). There was no clear evidence for an association between the BMI genetic risk score and smoking latent classes in males or females but estimates were imprecise. CONCLUSIONS: BMI in females and body dissatisfaction in males and females are associated with increased odds of smoking initiation, highlighting these as potentially important factors for consideration in smoking prevention strategies

    Trends in Students Media Usage

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    Trends in media usage by students can affect the way they learn. Students demand the use of technology, thus institutions and instructors should meet students’ requests. This paper describes the results of a survey where drivers in the use of media show continuously increasing or decreasing values from the first to the fourth year of study experience at the Western University, Canada, highlighting trends in the usage of new and traditional media in higher education by students. The survey was used to gather data on students’ media usage habits and user satisfaction from first to fourth year of study and found that media usage increases over the years from first to fourth. The presentation of data using bar charts reveals a slight increase over the years in students owning notebooks or laptops off-campus and a significant increase from first to fourth year of students accessing online academic periodicals and journals. Another noteworthy finding relates to fourth year students being more conscious of the quality of information that they read on the Internet in comparison to students in first year, even though this is a slight year on year increase
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