811 research outputs found
Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women
IMPORTANCE: Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. OBJECTIVE: To determine whether rotating night shift work is associated with CHD risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). EXPOSURES: Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). MAIN OUTCOMES AND MEASURES: Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. RESULTS: During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] CONCLUSIONS AND RELEVANCE: Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics
The Bosnian version of the international self-report measure of posttraumatic stress disorder, the Posttraumatic Stress Diagnostic Scale, is reliable and valid in a variety of different adult samples affected by war
BACKGROUND: The aim of the present study was to assess the internal consistency and discriminant and convergent validity of the Bosnian version of a self-report measure of posttraumatic stress disorder (PTSD), the Posttraumatic Stress Diagnostic Scale (PTDS). The PTDS yields both a PTSD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders 4(th )edition (DSM-IV) and a measure of symptom severity. METHODS: 812 people living in Sarajevo or in Banja Luka in Bosnia-Herzegovina, of whom the majority had experienced a high number of traumatic war events, were administered the PTDS and other measures of trauma-related psychopathology. The psychometric properties of the instrument were assessed using Cronbach's alpha and principal components analysis, and its construct validity was assessed via Spearman correlation coefficients with the other instruments. RESULTS: The PTDS and its subscales demonstrated high internal consistency. The principal components revealed by an exploratory analysis are broadly consistent with the DSM-IV subscales except that they reproduce some previously reported difficulties with the "numbing" items from the avoidance subscale. The construct validity of the PTDS was supported by appropriate correlations with other relevant measures of trauma related psychopathology. CONCLUSION: The Bosnian version of the PTDS thus appears to be a time-economic and psychometrically sound measure for screening and assessing current PTSD. This self-report measure awaits further validation by interview methods
Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study
Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman\u27s individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model\u27s predictive power has not previously been evaluated. Methods Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses\u27 Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 (P \u3c 0.001) after the addition of imputed estradiol. Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman\u27s individual risk of breast cancer
Variability and Predictors of Urinary Bisphenol A Concentrations during Pregnancy
BackgroundPrenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy.ObjectiveOur goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy.MethodsWe measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models.ResultsGeometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations.ConclusionsThese results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures
Targeting targeted agents: open issues for clinical trial design
Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources
Building the process-drug–side effect network to discover the relationship between biological Processes and side effects
<p>Abstract</p> <p>Background</p> <p>Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.</p> <p>Methods</p> <p>We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.</p> <p>Results</p> <p>The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.</p> <p>Conclusions</p> <p>We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.</p
Higher-order multipole amplitudes in charmonium radiative transitions
Using 24 million decays in CLEO-c, we have searched
for higher multipole admixtures in electric-dipole-dominated radiative
transitions in charmonia. We find good agreement between our data and
theoretical predictions for magnetic quadrupole (M2) amplitudes in the
transitions and ,
in striking contrast to some previous measurements. Let and
denote the normalized M2 amplitudes in the respective aforementioned decays,
where the superscript refers to the angular momentum of the . By
performing unbinned maximum likelihood fits to full five-parameter angular
distributions, we determine the ratios and , where
the theoretical predictions are independent of the charmed quark magnetic
moment and are and .Comment: 32 pages, 7 figures, acceptance updat
Search for D0 to p e- and D0 to pbar e+
Using data recorded by CLEO-c detector at CESR, we search for simultaneous
baryon and lepton number violating decays of the D^0 meson, specifically, D^0
--> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We
set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar
--> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 *
10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/,
submitted to PRD. Comments: changed abstract, added reference for section 1,
vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo
Dalitz Plot Analysis of Ds to K+K-pi+
We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c
data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This
corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400
candidates with a background of roughly 15%. In contrast to previous
measurements we find good agreement with our data only by including an
additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit
fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+,
and f_0(1370)pi+ contributions and limit the possible contributions of other KK
and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/,
submitted to PR
Charmonium decays to gamma pi0, gamma eta, and gamma eta'
Using data acquired with the CLEO-c detector at the CESR e+e- collider, we
measure branching fractions for J/psi, psi(2S), and psi(3770) decays to gamma
pi0, gamma eta, and gamma eta'. Defining R_n = B[ psi(nS)-->gamma eta ]/B[
psi(nS)-->gamma eta' ], we obtain R_1 = (21.1 +- 0.9)% and, unexpectedly, an
order of magnitude smaller limit, R_2 < 1.8% at 90% C.L. We also use
J/psi-->gamma eta' events to determine branching fractions of improved
precision for the five most copious eta' decay modes.Comment: 14 pages, available through http://www.lns.cornell.edu/public/CLNS/,
published in Physical Review
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