Ajuste e interpretacion de datos demograficos

Documento presentado a la Conferencia del UIECP en 1969Incluye Bibliografí

Comentarios sobre estrategias de comparacion para la evaluacion del impacto de la planificacion de la familia

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Impaired muscle oxygen use at onset of exercise in peripheral arterial disease

ObjectivesIn patients with peripheral arterial disease (PAD), abnormal muscle metabolism and impaired oxygen delivery distal to the arterial occlusions may contribute to the exercise limitation observed in this population. Muscle tissue hemoglobin saturation (StO2), measured with near-infrared spectroscopy, reflects the relative contributions of oxygen delivery and oxygen use. Thus differences in the kinetics of StO2 in response to exercise may yield important insight into the potential mechanisms associated with the PAD exercise impairment. The purposes of this study were to characterize the muscle oxygenation responses in patients with PAD and in healthy control subjects at the onset of exercise, and to compare the kinetics of StO2 desaturation. We hypothesized that at the onset of exercise the kinetics of StO2 desaturation would be slowed in PAD compared with control responses.Material and methodsSix patients with PAD and 6 healthy control subjects from a university center were examined in a prospective cross-sectional analysis that evaluated the desaturation kinetics of StO2 at the onset of walking exercise. On separate visits subjects performed graded treadmill exercise and 3 constant work rate treadmill tests equivalent to ∼60% (low), ∼80% (medium), and 100% (peak) of their peak exercise work rate. Gastrocnemious muscle StO2 response profiles (InSpectra tissue spectrometer) were measured at rest and across the rest to exercise transition. Muscle StO2 responses were characterized by an exponential mathematical model. The end point value was taken as the time constant of StO2 desaturation after onset of exercise (ie, equivalent to time to reach approximately 63% of StO2 decrease).ResultsThe patients with PAD and the control subjects were of similar age and activity level. The qualitative patterns of StO2 responses at onset of exercise were also similar between patients and control subjects at all work rates. However, the kinetic time constants of StO2 desaturation were prolonged in patients with PAD versus control subjects (averaged time constant across all work rates, 21.9 ± 9.4 seconds vs 4.9 ± 2.2 seconds; P < .01).ConclusionsThe slowed muscle StO2 kinetics in PAD are consistent with an impairment in muscle oxygen use at the onset of walking exercise. Impaired muscle metabolism may contribute to the altered physiologic responses to exercise and to exercise impairment in patients with PAD

Estimación de la mortalidad adulta a partir de información sobre orfandad

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Evaluación del trabajo de campo del método de la sobrevivencia de hermanas para medir la mortalidad materna

Incluye BibliografíaBase teórica y descripción del método de sobrevivencia de hermanas para estimar la mortalidad materna; trabajo de campo realizado en Gambia y Per

Triangle-free intersection graphs of line segments with large chromatic number

In the 1970s, Erdos asked whether the chromatic number of intersection graphs of line segments in the plane is bounded by a function of their clique number. We show the answer is no. Specifically, for each positive integer $k$, we construct a triangle-free family of line segments in the plane with chromatic number greater than $k$. Our construction disproves a conjecture of Scott that graphs excluding induced subdivisions of any fixed graph have chromatic number bounded by a function of their clique number.Comment: Small corrections, bibliography updat

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication

Background: Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. Methods: The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. Results: When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population

Trust, guilds and kinship in London, 1330-1680

How was trust created and reinforced between the inhabitants of medieval and early modern cities? And how did the social foundations of trusting relationships change over time? Current research highlights the role of kinship, neighbourhood and associations, particularly guilds, in creating ‘relationships of trust’ and social capital in the face of high levels of migration, mortality and economic volatility, but tells us little about their relative importance or how they developed. We uncover a profound shift in the contribution of family and guilds to trust networks among the middling and elite of one of Europe’s major cities, London, over three centuries, from the 1330s to the 1680s. We examine the networks of sureties created to secure the inheritances of children whose fathers died while they were minors, surviving in the records of London’s Orphans Court. Our analysis of almost fifteen thousand networks evaluates the presence of trusting relationships connected with guild membership, family and place over several centuries. We show a profound increase in the role of kinship – a re-embedding of trust within the family - and a decline of the importance of shared guild membership in connecting Londoner’s who secured orphans’ inheritances together. We suggest these developments are best explained as a result of the impact of the Reformation on the form and intensity of sociability fostered by guilds and the enormous growth of the metropolis