Attraction of Culex mosquitoes to aldehydes from human emanations.

Anecdotes related to preferential mosquito bites are very common, but to date there is no complete explanation as to why one out of two people systematically receives more mosquito bites than the other when both are equally accessible. Here we tested the hypothesis that two constituents of skin emanations, 6-methyl-5-heptan-2-one (6-MHO) and geranylacetone (GA), are natural repellents and may account for differential attraction in different ratios. We studied skin emanations from two human subjects, confirmed in behavioral assays that female southern house mosquitoes are significantly more attracted to subject A (attractant) than to subject N (non-attractant), and tested their 6-MHO/GA ratios in a dual-choice olfactometer. Although repelling at high doses, 6-MHO/GA mixtures were not active at the levels emitted by human skin. We found, however, differential attraction elicited by the aldehydes in the ratios produced by subjects A and N. When tested in a dose commensurate with the level released from human skin and in the ratio produced by subject A, the aldehyde mixture significantly attracted mosquitoes. By contrast, an aldehyde mixture at the same ratio released by subject N did not attract mosquitoes. We, therefore, hypothesized that aldehydes may play a role in the commonly observed differential attraction

Modelling long-memory volatilities with leverage effect: A-LMSV versus FIEGARCH

A new stochastic volatility model, called A-LMSV, is proposed to cope simultaneously with leverage effect and long-memory in volatility. Its statistical properties are derived and compared with the properties of the FIEGARCH model. It is shown that the dependence of the autocorrelations of squares on the parameters measuring the asymmetry and the persistence is different in both models. The kurtosis and autocorrelations of squares do not depend on the asymmetry in the A-LMSV model while they increase with the asymmetry in the FIEGARCH model. Furthermore, the autocorrelations of squares increase with the persistence in the A-LMSV model and decrease in the FIEGARCH model. On the other hand, if the correlation between returns and future volatilities is negative, the autocorrelations of absolute returns increase with the magnitude of the asymmetry in the FIEGARCH model while they decrease in the A-LMSV model. Finally, the cross-correlations between squares and original observations are, in general, larger in absolute value in the FIEGARCH model than in the A-LMSV model. The results are illustrated by fitting both models to represent the dynamic evolution of volatilities of daily returns of the S&P500 and DAX indexes.Publicad

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses

Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium

Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of immunohistochemistry (IHC)-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared to the clinical record and RNA-based intrinsic (PAM50) subtypes

Post-operative exercises after breast cancer surgery: results of a RCT evaluating standard care versus standard care plus additional yoga exercise

Introduction: There is a lack of standardisation in the guidelines for post-operative exercises following breast cancer surgery. Adherence to exercise programmes is low, and complementary therapies such as yoga often appeal to patients and may encourage practise. A step-by-step guide to yoga DVD was evaluated in addition to the standard care exercises (SC) compared to SC alone. Methods: Women with early-stage breast cancer were randomised to SC plus or minus a yoga DVD for 10-weeks. Patient-reported outcomes were collected at baseline, 10 weeks and 6 months. The primary study-endpoint was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Treatment-Breast; a recognised quality of life (QoL) tool with an arm morbidity subscale (FACT-B+4). Results: 92/103 (89%) women were randomised to the study. The SC group reported practising post-operative exercises more often than the yoga DVD group. There was a 69% improvement from baseline in FACT-B+4 TOI, which included an arm subscale, at 10 weeks and 6 months in the SC group. This was 62% and 81% respectively for the yoga DVD group. Numbness in the affected arm was greater in the SC group (OR= 2.5, 95% CI: 1.1, 5.6) and in patients receiving chemotherapy (OR=2.17, 95% CI: 1, 4.6). Despite no group differences, 74% of women would definitely recommend following the yoga DVD after surgery. Conclusions: Practising post-operative exercises does improve arm and shoulder morbidity following breast cancer surgery. The addition of a self-practise general yoga programme was well received and appeared to improve QoL at 6 months

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Dietary Intakes of Total and Specific Lignans Are Associated with Clinical Breast Tumor Characteristics 1-3

. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER 2 cancer in premenopausal women. J. Nutr. 142: 91-98, 2012

Decline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes.

The humoral Idiotypic Network consisting of antibodies and their anti-idiotypic antibodies (anti-Id) can be temporarily upset by antigen exposure. In the healthy immune response the original equilibrium is eventually restored through counter-regulatory mechanisms. In certain autoimmune diseases however, autoantibody levels exceed those of their respective anti-Id, indicating a permanent disturbance in the respective humoral Idiotypic Network. We investigated anti-Id directed to a major Type 1 diabetes (T1D)-associated autoantibody (GAD65Ab) in two independent cohorts during progression to disease. Samples taken from participants of the Natural History Study showed significantly lower anti-Id levels in individuals that later progressed to T1D compared to non-progressors (anti-Id antibody index of 0.06 vs. 0.08, respectively, p = 0.02). We also observed a significant inverse correlation between anti-Id levels and age at sampling, but only in progressors (p = 0.014). Finally, anti-Id levels in progressors showed a significant decline during progression as compared to longitudinal anti-Id levels in non-progressors (median rate of change: -0.0004 vs. +0.0004, respectively, p = 0.003), suggesting a loss of anti-Id during progression. Our analysis of the Diabetes Prediction in Skåne cohort showed that early in life (age 2) individuals at risk have anti-Id levels indistinguishable from those in healthy controls, indicating that low anti-Id levels are not an innate characteristic of the immune response in individuals at risk. Notably, anti-Id levels declined significantly in individuals that later developed GAD65Ab suggesting that the decline in anti-Id levels precedes the emergence of GAD65Ab (median rate of change: -0.005) compared to matched controls (median rate of change: +0.001) (p = 0.0016). We conclude that while anti-Id are present early in life, their levels decrease prior to the appearance of GAD65Ab and to the development of T1D

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization’s World Mental Health Survey Initiative

Background:There is a substantial proportion of patients who drop out of treatment beforethey receive minimally adequate care. They tend to have worse health outcomes than thosewho complete treatment. Our main goal is to describe the frequency and determinants ofdropout from treatment for mental disorders in low-, middle-, and high-income countries.Methods: Respondents from 13 low- or middle-income countries (N= 60 224) and 15 in high-income countries (N= 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for thosewho screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. Results: Dropout rates are high, both in high-income (30%) and low/middle-income (45%)countries. Dropout mostly occurs during the first two visits. It is higher in general medicalrather than in specialist settings (nearly 60%v.20% in lower income settings). It is also higherfor mild and moderate than for severe presentations. The lack of financial protection for men-tal health services is associated with overall increased dropout from care.Conclusions:Extending financial protection and coverage for mental disorders may reducedropout. Efficiency can be improved by managing the milder clinical presentations at theentry point to the mental health system, providing adequate training, support and specialistsupervision for non-specialists, and streamlining referral to psychiatrists for more severe casesPeer ReviewedPostprint (author's final draft