Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015

The third International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California in February 2015 with a panel of 17 international experts. The delegates represented 4 countries and 9 medical and scientific sub-specialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism, and body fluid homeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the second International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance. The following statement is a summary of the data synthesized by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarize the most current information on the prevalence, etiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers, and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed upon, did not agree upon, and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to both: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document as well as areas of controversy that remain in this topic. [excerpt

Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies

Background: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. Methods and Findings: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively. Conclusions: These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races. Please see later in the article for the Editors' Summar

Hyponatremia and Congestive Heart Failure: A Marker of Increased Mortality and a Target for Therapy

Heart failure is one of the most common chronic medical conditions in the developed world. It is characterized by neurohormonal activation of multiple systems that can lead to clinical deterioration and significant morbidity and mortality. In this regard, hyponatremia is due to inappropriate and continued vasopressin activity despite hypoosmolality and volume overload. Hyponatremia is also due to diuretic use in an attempt to manage volume overload. When hyponatremia occurs, it is a marker of heart failure severity and identifies patients with increased mortality. The recent introduction of specific vasopressin-receptor antagonists offers a targeted pharmacological approach to these pathophysiological derangements. Thus far, clinical trials with vasopressin-receptor antagonists have demonstrated an increase in free-water excretion, improvement in serum sodium, modest improvements in dyspnea but no improvement in mortality. Continued clinical trials with these agents are needed to determine their specific role in the treatment of both chronic and decompensated heart failure

Numerical simulation of electrocardiograms for full cardiac cycles in healthy and pathological conditions

This work is dedicated to the simulation of full cycles of the electrical activity of the heart and the corresponding body surface potential. The model is based on a realistic torso and heart anatomy, including ventricles and atria. One of the specificities of our approach is to model the atria as a surface, which is the kind of data typically provided by medical imaging for thin volumes. The bidomain equations are considered in their usual formulation in the ventricles, and in a surface formulation on the atria. Two ionic models are used: the Courtemanche-Ramirez-Nattel model on the atria, and the "Minimal model for human Ventricular action potentials" (MV) by Bueno-Orovio, Cherry and Fenton in the ventricles. The heart is weakly coupled to the torso by a Robin boundary condition based on a resistor- capacitor transmission condition. Various ECGs are simulated in healthy and pathological conditions (left and right bundle branch blocks, Bachmann's bundle block, Wolff-Parkinson-White syndrome). To assess the numerical ECGs, we use several qualitative and quantitative criteria found in the medical literature. Our simulator can also be used to generate the signals measured by a vest of electrodes. This capability is illustrated at the end of the article

Search for rare and forbidden decays of charm and charmed-strange mesons to final states h^+- e^-+ e^+

We have searched for flavor-changing neutral current decays and lepton-number-violating decays of D^+ and D^+_s mesons to final states of the form h^+- e^-+ e^+, where h is either \pi or K. We use the complete samples of CLEO-c open-charm data, corresponding to integrated luminosities of 818 pb^-1 at the center-of-mass energy E_CM = 3.774 GeV containing 2.4 x 10^6 D^+D^- pairs and 602 pb^-1 at E_CM = 4.170 GeV containing 0.6 x 10^6 D^*+-_s D^-+_s pairs. No signal is observed in any channel, and we obtain 90% confidence level upper limits on branching fractions B(D^+ --> \pi^+ e^+ e^-) < 5.9 x 10^-6, B(D^+ --> \pi^- e^+ e^+) K^+ e^+ e^-) < 3.0 x 10^-6, B(D^+ --> K^- e^+ e^+) \pi^+ e^+ e^-) < 2.2 x 10^-5, B(D^+_s --> \pi^- e^+ e^+) K^+ e^+ e^-) < 5.2 x 10^-5, and B(D^+_s --> K^- e^+ e^+) < 1.7 x 10^-5.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS

Determination of the D0 -> K+pi- Relative Strong Phase Using Quantum-Correlated Measurements in e+e- -> D0 D0bar at CLEO

We exploit the quantum coherence between pair-produced D0 and D0bar in psi(3770) decays to study charm mixing, which is characterized by the parameters x and y, and to make a first determination of the relative strong phase \delta between doubly Cabibbo-suppressed D0 -> K+pi- and Cabibbo-favored D0bar -> K+pi-. We analyze a sample of 1.0 million D0D0bar pairs from 281 pb^-1 of e+e- collision data collected with the CLEO-c detector at E_cm = 3.77 GeV. By combining CLEO-c measurements with branching fraction input and time-integrated measurements of R_M = (x^2+y^2)/2 and R_{WS} = Gamma(D0 -> K+pi-)/Gamma(D0bar -> K+pi-) from other experiments, we find \cos\delta = 1.03 +0.31-0.17 +- 0.06, where the uncertainties are statistical and systematic, respectively. In addition, by further including external measurements of charm mixing parameters, we obtain an alternate measurement of \cos\delta = 1.10 +- 0.35 +- 0.07, as well as x\sin\delta = (4.4 +2.7-1.8 +- 2.9) x 10^-3 and \delta = 22 +11-12 +9-11 degrees.Comment: 37 pages, also available through http://www.lns.cornell.edu/public/CLNS/2007/. Incorporated referee's comment

A Study of Exclusive Charmless Semileptonic B Decays and Extraction of |V_{ub}| at CLEO

We have studied semileptonic B decay to the exclusive charmless states pi, rho/omega, eta and eta' using the full 15.5 fb^-1 CLEO Upsilon(4S) sample, with measurements performed in subregions of phase space to minimize dependence on a priori knowledge of the form factors involved. We find total branching fractions B(B^0 -> pi^-l^+nu) = (1.37 +- 0.15_stat +- 0.11_sys) x 10^-4 and B(B^0 -> rho^- l^+ nu) = (2.93 +- 0.37_stat +- 0.37_sys) x 10^-4. We find evidence for B^+ -> eta' l^+ nu, with B(B^+ -> eta' l^+ nu) = (2.66 +- 0.80_stat +- 0.56_sys) x 10^-4 and 1.20 x 10^-4 eta' l^+ nu) < 4.46 x 10^-4 (90% CL). We also limit B(B^+ -> eta l^+ nu) < 1.01 x 10^-4 (90% CL). By combining our B -> pi l nu information with unquenched lattice calculations, we find |V_ub| = (3.6 +- 0.4 +- 0.2 +0.6 -0.4) x 10^-3, where the errors are statistical, experimental systematic, and theoretical systematic, respectively.Comment: 35 pages, 15 figures; revise

Measurement of the Decay Constant fDS+f_D{_S^+} using $D_S^+ --> ell^+ nu

We measure the decay constant fDs using the Ds -> l+ nu channel, where the l+ designates either a mu+ or a tau+, when the tau+ -> pi+ nu. Using both measurements we find fDs = 274 +-13 +- 7 MeV. Combining with our previous determination of fD+, we compute the ratio fDs/fD+ = 1.23 +- 0.11 +- 0.04. We compare with theoretical estimates.Comment: 6 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2007