Edwin E. Salpeter

SURFACE RECOMBINATION OF HYDROGEN MOLECULES.

Molecular hydrogen formation on dust grain surfaces, discussing recombination efficiency as function of surface temperature

Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women

Aim:  To quantify the effects of hormone‐replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women.

Electron Screening and Thermonuclear Reactions

In the interior of stars most atoms are ionized, but the electrostatic potential of a bare nucleus induces a spherically symmetric polarization of the surrounding electrons and nuclei. The effect of this screening charge cloud on the rate of thermonuclear reactions is investigated for the case of complete ionization of all atoms.

Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis.

AbstractOBJECTIVE: To assess the effect of hormone therapy (HT) on coronary heart disease (CHD) events in younger and older postmenopausal women. DESIGN: A comprehensive database search identified randomized-controlled trials of HT of at least 6 months’ duration that reported CHD events, defined as myocardial infarction or cardiac death. MEASUREMENTS: The pooled odds ratios (ORs) for CHD events were reported separately for younger and older women, defined as participants with mean time from menopause of less than or greater than 10 years, or mean age less than or greater than 60 years. MAIN RESULTS: Pooled data from 23 trials, with 39,049 participants followed for 191,340 patient-years, showed that HT significantly reduced CHD events in younger women (OR 0.68 [confidence interval (C I), 0.48 to 0.96]), but not in older women (OR 1.03 [CI, 0.91 to 1.16]). Hormone therapy reduced events in younger women compared with older women (OR 0.66 [CI, 0.46 to 0.95]). In older women, HT increased events in the first year (OR 1.47 [CI, 1.12 to 1.92]), then reduced events after 2 years (OR 0.79 [CI, 0.67 to 0.93]). CONCLUSIONS: Hormone therapy reduces the risk of CHD events in younger postmenopausal women. In older women, HT increases, then decreases risk over time.

Cardioselective β-Blockers in Patients with Reactive Airway Disease: A Meta-Analysis

Context Although -blockers improve clinical outcomes in many patients with cardiovascular disease, clinicians sometimes avoid these agents in patients with concomitant lung disease because they fear precipitation of acute bronchospasm. Contribution This meta-analysis of 29 randomized trials shows that cardioselective-blockers (1-blockers), given for a few days to a few weeks, do not significantly worsen pulmonary function or respiratory symptoms and do not lead to increased use of inhalers in patients with mild to moderate reactive (reversible) airway disease. Cautions The studies in this meta-analysis were short, evaluated only cardioselective -blockers, and did not include patients with severe or irreversible airway disease. The Editors -Adrenergic blocking agents, or -blockers, are indicated in the management of angina pectoris, myocardial infarction, hypertension, congestive heart failure, cardiac arrhythmia, and thyrotoxicosis and are given to reduce perioperative complications (1-13). Despite clear evidence of the effectiveness and mortality benefit of these drugs, clinicians are often hesitant to administer them in patients with some common conditions for fear of adverse reactions (14-17). Many patients with reactive airway disease, with or without a chronic obstructive component, have concomitant conditions such as hypertension or cardiac arrhythmias, which necessitate the use of -blockers. However, review articles and practice guidelines usually list asthma and chronic obstructive pulmonary disease (COPD) as contraindications to -blocker use, citing cases of acute bronchospasm during administration of noncardioselective -blockers (6, 10, 18-22). Cardioselective -blockers, or 1-blockers, have greater than 20 times more affinity for 1 receptors than for 2 receptors and in theory should pose much less risk for bronchoconstriction (23). We used data from randomized, blinded, placebo-controlled trials to evaluate the effect of cardioselective 1-blockers on respiratory function in patients with reactive airway disease (defined as asthma or COPD with a reversible obstructive component). We also sought to evaluate the respiratory response to 2-agonists administered after 1-blockers or after placebo in the same participants. This analysis has already been published as a review in the Cochrane Library (24). Methods Patients We chose to evaluate only patients with documented reactive airway disease because these patients are thought to be particularly susceptible to the adverse respiratory effects of -blockers. Patients with COPD are generally at greater risk for ischemic heart disease than are patients with asthma and thus may benefit more from the use of -blockers. This study evaluates a subgroup of patients with a documented chronic obstructive component of disease but was not designed to make recommendations about patients with COPD. A recent meta-analysis evaluated the use of cardioselective -blockers in patients with COPD, given as a single dose or as continued treatment (25). Pooled data from 19 trials demonstrated no adverse effect on FEV1 or respiratory symptoms for 1-blockers compared to placebo, even in patients with severe chronic airway obstruction. Search Strategy A search was performed to identify all relevant published clinical trials that addressed the effects of cardioselective -blockers on airway function in patients with reactive airway disease. Two investigators jointly developed strategies with the help of an information service librarian and the Cochrane Airways Group Trial Search Coordinator. The EMBASE, MEDLINE, and CINAHL databases were searched comprehensively to identify all relevant clinical trials in humans published between 1966 and May 2001. The search was performed by using the Cochrane Airways Group registry to identify randomized, blinded, placebo-controlled trials of reactive airways disease. Terms used in the search were asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* and obstructive airway disease*. Trials of -blockers were sought by using the terms adrenergic antagonist*, sympatholytic* and adrenergic receptor block*. Trials were not excluded on the basis of language. The search was further augmented by scanning references of identified articles, reviews, and abstracts at clinical symposia. Study Selection Two investigators independently evaluated studies for inclusion. In choosing articles, investigators were blinded to results but not to journal, author, or institution of studies. The observed interrater agreement for the assessment of inclusion was calculated as a percentage. For all clinical trials identified from the search, investigators determined whether the -blocker used was cardioselective and whether it was considered to have intrinsic sympathomimetic activity (1, 26-36). Studies were evaluated if intravenous or oral cardioselective -blockers were administered as a single dose or as continued treatment lasting 3 days or longer. Single-dose trials were included if 1) FEV1 at rest was reported, either as liters or as a percentage of the normal predicted value at baseline and at follow-up; 2) 2-agonists were withheld for at least 8 hours before initial FEV1 measurement; 3) patients were not selected on the basis of previous response to -blockers; 4) the study was randomized, placebo-controlled, and single- or double-blinded; and 5) only patients with documented reactive airway disease were included. Reactive airway disease was demonstrated by a mean increase of at least 15% in FEV1 in response to 2-agonist, response to methacholine challenge, or presence of asthma as defined by the American Thoracic Society (37). Crossover trials were included if different interventions were administered in random order. We decided a priori that inclusion criteria 3, 4, and 5 would be applied to trials of continued treatment. Studies of continued treatment were included if they did not report FEV1 but instead evaluated the amount of 2-agonist use and respiratory symptoms compared with placebo. Trials were also included if 2-agonists were not withheld during the trial. Assessment of Validity The methodologic quality of each trial was assessed according to the following factors: 1) Was the study randomized? If so, was the randomization procedure adequate, and was allocation concealed? 2) Were the patients and people administering the treatment blinded to the intervention? 3) Were withdrawals and dropouts described, and was the analysis performed on an intention-to-treat basis? On the basis of these criteria, studies were broadly subdivided as all quality criteria met (A), one or more quality criteria only partially met (B), or one or more criteria not met (C). Clinical trials that did not meet criteria for inclusion but gave information on FEV1 response to cardioselective -blockers in patients with reactive airway disease were analyzed separately and used in a sensitivity analysis. These included studies that were not placebo-controlled; did not document asthma criteria; did not give baseline FEV1 data; or, for single-dose studies, did not withhold 2-agonists for 8 hours before measurements. Study Characteristics The main intervention of interest was intravenous or oral cardioselective -blockers versus placebo, given as a single dose or as continued treatment. Administration of a 2-agonist, intravenously or by inhalation, after the study medication or after placebo was also studied. Each 1-blocker used was classified into one of two categories: 1-blockers without intrinsic sympathomimetic activity, and 1-blockers with intrinsic sympathomimetic activity. Data Extraction Two investigators independently extracted data on change in mean group FEV1 in response to placebo or study drug; response of FEV1 to 2-agonist administered after placebo or study drug; symptoms reported during the trial, such as wheezing, dyspnea, or exacerbation of asthma; and, for trials of continued treatment, weekly use of inhaled short-acting 2-agonists. Data Synthesis The ratio of the lowest group FEV1 value after administration of study drug to baseline FEV1 was measured for placebo and active treatment and was recorded as the percentage change from baseline. The placebo response was then subtracted from the treatment response to obtain the net treatment effect, reported as a percentage of the baseline FEV1 value. For response to 2-agonists given after treatment or placebo, the new baseline value was the mean group FEV1 value obtained after study drug but before 2-agonist administration. The net treatment effect was estimated by calculating the ratio of FEV1 measured after agonist administration to the new baseline value for both placebo and active treatment and then subtracting the placeboagonist response from the treatmentagonist response. Whenever possible, the SD for the net treatment effect was calculated from individual-patient data or P values and was then used to derive the SDs for the analysis. Some trials provided SDs for treatment response and placebo response separately. For trials that reported no information on SDs, the average SD was obtained from trials that provided such data, calculated separately for placebo, treatment, and -agonist responses. Sensitivity analyses were performed to evaluate the effect of including these trials by using the lowest and highest available SD in place of the pooled SD and also by excluding these trials from the analysis. The Appendix Table shows the method used to obtain SDs for each trial. The mean treatment effects were pooled to obtain a weighted average of the study means using the fixed-effects model for continuous outcomes (38, 39). Confidence intervals with 95% significance were obtained for the pooled study means. The analysis was performed by using Meta View 4.1 (Cochrane Library software [Update Software, Oxford, United Kingdom]). Results for respiratory symptoms were measured as a risk difference by subtractin

Mortality Associated with Hormone Replacement Therapy in Younger and Older Women: A Meta-analysis

OBJECTIVE: To assess mortality associated with hormone replacement in younger and older postmenopausal women.DESIGN: A comprehensive search of medline, cinahl, and embase databases was performed to identify randomized controlled trials of hormone replacement therapy from 1966 to September 2002. The search was augmented by scanning selected journals through April 2003 and references of identified articles. Randomized trials of greater than 6 months’ duration were included if they compared hormone replacement with placebo or no treatment, and reported at least 1 death.MEASUREMENTS: Outcomes measured were total deaths and deaths due to cardiovascular disease, cancer, or other causes. Odds ratios (OR) for total and cause-specific mortality were reported separately for trials with mean age of participants less than and greater than 60 years at baseline.MAIN RESULTS: Pooled data from 30 trials with 26,708 participants showed that the OR for total mortality associated with hormone replacement was 0.98 (95% confidence interval [CI], 0.87 to 1.12). Hormone replacement reduced mortality in the younger age group (OR, 0.61; CI, 0.39 to 0.95), but not in the older age group (OR, 1.03; CI, 0.90 to 1.18). For all ages combined, treatment did not significantly affect the risk for cardiovascular or cancer mortality, but reduced mortality from other causes (OR, 0.67; CI, 0.51 to 0.88).CONCLUSIONS: Hormone replacement therapy reduced total mortality in trials with mean age of participants under 60 years. No change in mortality was seen in trials with mean age over 60 years.

Meta-analysis: Metformin Treatment in Persons at Risk for Diabetes Mellitus

PURPOSE We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7--4.0), fasting glucose (-4.5%, CI, -6.0--3.0), fasting insulin (-14.4%, CI, -19.9--8.9), calculated insulin resistance (-22.6%, CI, -27.3--18.0), triglycerides (-5.3%, CI, -10.5--0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3--3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.

Monte Carlo simulation of miniature endplate current generation in the vertebrate neuromuscular junction

A Monte Carlo method for modeling the neuromuscular junction is described in which the three-dimensional structure of the synapse can be specified. Complexities can be introduced into the acetylcholine kinetic model used with only a small increase in computing time. The Monte Carlo technique is shown to be superior to differential equation modeling methods (although less accurate) if a three-dimensional representation of synaptic geometry is desired. The conceptual development of the model is presented and the accuracy estimated. The consequences of manipulations such as varying the spacing of secondary synaptic folds or that between the release of multiple quantal packets of acetylcholine, are also presented. Increasing the spacing between folds increases peak current. Decreased spacing of adjacent quantal release sites increases the potentiation of peak current.

Surface Adsorption of Light Gas Atoms

The adsorption on solid surfaces of very light gas atoms is reconsidered. A variational wavefunction is constructed for the quantum‐mechanical ground state of the adsorbed atom, and improved values of adsorption energies are calculated for a few cases. The surface mobility at low temperatures is determined quantum mechanically, by use of the variational ground‐state wavefunction. Simple analytic approximations are derived for the sticking coefficient S and the accommodation coefficient α for gas atoms impinging on a surface. A few previous accurate calculations and some experiments are used to derive some general analytic semiempirical formulas for S and α as a function of the gas temperature. Surface recombination of diatomic molecules from two adsorbed atoms is considered briefly.

The mass-radius relation for cold spheres of low mass

Mass and radius relations for zero temperature spheres of chemical elements, using equation of state and numerical integration