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[Role models of residents graduating in family medicine and in different specialties in Quebec].

OBJECTIVE: To describe and compare the role models of Quebec residents graduating from French-language faculties of family medicine and from medical specialities. DESIGN: Survey by mail. PARTICIPANTS: Quebec residents graduating in family medicine (189), medical specialities (147), and surgical specialities (64) in 1990. MAIN OUTCOME MEASURES: Number of models chosen, social, demographic, professional, and personal characteristics of primary role models, role models' influence on students. RESULTS: Role models chosen by family medicine graduates more closely resemble those of their medical speciality colleagues than those of their surgical speciality colleagues. Family medicine graduates, particularly female graduates, have more difficulty choosing models. Their choices are based mainly on qualities that reflect a biopsychosocial approach to care and concern with the community aspects of medical practice. CONCLUSION: Choosing role models is a complex process. Medical faculty in residency programs play an important role in the professional identity of future physicians.

Adult↗

Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction.

OBJECTIVES: Recently, anecdotal reports via the FDA's MedWatch reporting system have documented rare but serious hyperglycaemia in elderly patients receiving gatifloxacin. One possible factor contributing to these events may be gatifloxacin overexposure, resulting from age-related decreases in renal function in elderly patients predisposed to glycaemic alterations. These analyses examine gatifloxacin exposure in 10 patients with severe hyperglycaemia, provide a pharmacokinetic-pharmacodynamic (PK-PD) rationale for a potential age-related dose reduction to avoid high exposures, and evaluate the likely impact of such a dose reduction on clinical efficacy in this specific patient population. METHODS: First, a previously derived population pharmacokinetic model, with patient demographics, was used to estimate gatifloxacin AUC0-24 following a dosage regimen of 400 mg/24 h in 10 index patients with severe hyperglycaemia. Second, the population pharmacokinetic model and patient demographic data from 2696 patients aged > or =65 years from two New Drug Application (NDA) databases were used to estimate AUC0-24 following dosage regimens for gatifloxacin of 200 and 400 mg/24 h. Finally, Monte Carlo simulation was utilized to assess the probability of achieving PK-PD target exposures against Streptococcus pneumoniae in elderly patients using these regimens. RESULTS: The mean estimated AUC0-24 among severe hyperglycaemia cases was 74 mg.h/L (range 57-100). Gatifloxacin AUC0-24 exposures for the 400 mg regimen were predicted to be higher in patients aged > or =65 years and similar to the severe hyperglycaemia cases. The probability of AUC0-24 > or =60 and > or =70 in patients aged > or =65 years for the 200 mg regimen was 0.03 and <0.01, respectively, versus 0.51 and 0.35 for the 400 mg regimen, respectively. The probability of achieving PK-PD target exposures against S. pneumoniae in patients aged > or =65 years receiving the 200 mg regimen was 0.99. CONCLUSIONS: The probability of a patient aged > or =65 years having an AUC0-24 > or =60-70 mg.h/L is markedly lower following a 200 mg regimen relative to a 400 mg regimen, suggesting a decreased risk of severe hyperglycaemia in a predisposed patient. Moreover, a dose reduction does not appear to significantly modify the likelihood of achieving the PK-PD target of gatifloxacin against S. pneumoniae.

Aged↗

Parameterized multistate population dynamics and projections.

"This article reports progress on the development of a population projection process that emphasizes model selection over demographic accounting. Transparent multiregional/multistate population projections that rely on parameterized model schedules are illustrated [using data primarily from a number of developed countries, particularly Sweden], together with simple techniques that extrapolate the recent trends exhibited by the parameters of such schedules." The author notes that "the parameterized schedules condense the amount of demographic information, expressing it in a language and variables that are more readily understood by the users of the projections. In addition, they permit a concise specification of the expected temporal patterns of variation among these variables, and they allow a disaggregated focus on demographic change that otherwise would not be feasible."

Demography↗

Risk factor analysis of hypersensitivity reactions to abacavir.

BACKGROUND: A hypersensitivity reaction to abacavir has been known to occur in approximately 4% of patients treated with the drug. OBJECTIVE: The goal of this study was to determine risk factors associated with the development of hypersensitivity reactions to abacavir. METHODS: We constructed an analysis population from all protocols conducted by GlaxoSmithKline that involved at least 24 weeks of abacavir exposure with a quality-assured or validated clinical database by June 30, 2000. Demographic, clinical, and laboratory characteristics of patients who developed a hypersensitivity reaction to abacavir were compared with those of patients who did not. Univariate and multivariate logistic regression models were fit to understand the predictive ability of each potential risk factor. Odds ratios (ORs) and 95% Wald CIs were computed. RESULTS: A total of 5332 patients exposed to abacavir were included in this analysis; 197 cases of hypersensitivity reaction were reported (3.7%). In univariate models, several associations were noted, but most subgroups produced rates within the expected range of 3% to 6%. The multivariate model using all demographic data available (Model 1) indicated that the risk of hypersensitivity reaction among black patients (3% hypersensitivity reaction) was lower (OR = 0.59; 95% CI, 0.38-0.91) compared with other ethnic groups. In addition, a lower rate of hypersensitivity reaction was observed in patients who received previous therapy for HIV-1 infection with other antiretroviral agents (3% hypersensitivity reaction) compared with those receiving therapy for the first time (OR = 0.58; 95% CI, 0.44-0.78). CONCLUSIONS: The only characteristics identified as prognostic factors for hypersensitivity reaction to abacavir were antiretroviral treatment status (ie, treatment experience) and black race, each resulting in a lower rate compared with the expected incidence.

Adult↗

Stochastic analogues of deterministic single-species population models.

Although single-species deterministic difference equations have long been used in modeling the dynamics of animal populations, little attention has been paid to how stochasticity should be incorporated into these models. By deriving stochastic analogues to difference equations from first principles, we show that the form of these models depends on whether noise in the population process is demographic or environmental. When noise is demographic, we argue that variance around the expectation is proportional to the expectation. When noise is environmental the variance depends in a non-trivial way on how variation enters into model parameters, but we argue that if the environment affects the population multiplicatively then variance is proportional to the square of the expectation. We compare various stochastic analogues of the Ricker map model by fitting them, using maximum likelihood estimation, to data generated from an individual-based model and the weevil data of Utida. Our demographic models are significantly better than our environmental models at fitting noise generated by population processes where noise is mainly demographic. However, the traditionally chosen stochastic analogues to deterministic models--additive normally distributed noise and multiplicative lognormally distributed noise--generally fit all data sets well. Thus, the form of the variance does play a role in the fitting of models to ecological time series, but may not be important in practice as first supposed.

Animals↗

An analysis of life history evolution in terms of the density-dependent Lefkovitch matrix model.

The evolution of demographic characteristics is considered in terms of the density-dependent Lefkovitch matrix model, which describes a species' population dynamics with a stage-specific pattern of reproduction and mortality. We obtain the invadability condition of a mutant-type into the wild-type population at the equilibrium state. The condition depends on the left and right eigenvectors at the equilibrium state. The condition depends on the left and right eigenvectors at the equilibrium state and the difference, between wild-type and mutant-type populations, of the values of elements in the Lefkovitch matrix at the equilibrium state. It is also shown that if elements of the density-dependent Lefkovitch matrix are decreasing functions of population density, then the equilibrium population density increases in the process of natural selection; that is, K-selection acts even on the stage-structured population. The evolution of life history in perennial plants is discussed through two models as an application of the above results. The evolution of perennial plants with no vegetative reproduction is analyzed in the first example. It is shown that whether monocarpic perennials (which reproduce once and die) or polycarpic perennial plants (which reproduce more than once) are favored depends on the cost of a produced seed. The second example concerns perennial plants that reproduce vegetatively. It is shown that whether monocarpic or polycarpic perennial plants are favored depends on the cost of a seed and that where vegetative reproduction is common, polycarpic perennials with no seed reproduction are favored.

Mathematics↗

Allee effect and self-fertilization in hermaphrodites: reproductive assurance in demographically stable populations.

The fact that selfing increases seed set (reproductive assurance) has often been put forward as an important selective force for the evolution of selfing. However, the role of reproductive assurance in hermaphroditic populations is far from being clear because of a lack of theoretical work. Here, I propose a theoretical model that analyzes self-fertilization in the presence of reproductive assurance. Because reproductive assurance directly influences the per capita growth rate, I developed an explicit demographic model for partial selfers in the presence of reproductive assurance, specifically when outcrossing is limited by the possibility of pollen transfer (Allee effect). Mating system parameters are derived as a function of the underlying demographical parameters. The functional link between population demography and mating system parameters (reproductive assurance, selfing rate) can be characterized. The demographic model permits the analysis of the evolution of self-fertilization in stable populations when reproductive assurance occurs. The model reveals some counterintuitive results such as the fact that increasing the fraction of selfed ovules can, in certain circumstances, increase the fraction of outcrossed ovules. Moreover, I demonstrate that reproductive assurance per se cannot account for the evolution of stable mixed selfing rates. Also, the model reveals that the extinction of outcrossing populations depends on small changes in population density (ecological perturbations), while the transition from outcrossing to selfing can, in certain cases, lead the population to extinction (evolutionary suicide). More generally, this paper highlights the fact that self-fertilization affects both the dynamics of individuals and the dynamics of selfing genes in hermaphroditic populations.

Biological Evolution↗

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans↗

[Model calculations of the effect of demographic changes on the incidence of cancer in Saarland].

Resulting from the population structure and current fertility and mortality rates, a rapid aging of the West German society is to be expected. The impact of these demographic changes on numbers of cancer cases and incidence rates is quantitatively assessed for the Saarland, which is the only state with reliable population-based cancer registration in the FRG. Despite a projected decrease in population size during the next decades, numbers of incident cases are expected to rise substantially in males and to remain almost constant in females for all of the most common forms of cancer. The projected changes have model character for other parts of the FRG.

Cohort Studies↗

Macro-effects of changes in household preferences for children: simulated history and future time paths.

The basic ideas underlying the analysis in this paper are that family size can be viewed as an economic life cycle decision and that there are decision trade-offs among fertility, consumption, and leisure. A micro-model of life cycle choice is developed and embedded in an economic-demographic macro-model. The macro-model is then used in a series of computer experiments to assess the effects on the population and the economy of changes in household preferences for children. The experiments include factual and counterfactual simulations of Canadian historical demographic experience and simulations of alternative future scenarios. The analysis and conclusions have general relevance for countries that have been through a fertility boom-and-bust sequence.

Americas↗

Variation of female and male lineages in sub-Saharan populations: the importance of sociocultural factors.

In this paper, we present a study of genetic variation in sub-Saharan Africa, which is based on published and unpublished data on fast-evolving (hypervariable region 1 of mitochondrial DNA and six microsatellites of Y chromosome) and slow-evolving (haplogroup frequencies) polymorphisms of mtDNA and Y chromosome. Our study reveals a striking difference in the genetic structure of food-producer (Bantu and Sudanic speakers) and hunter-gatherer populations (Pygmies, Kung, and Hadza). In fact, the ratio of mtDNA to Y-chromosome Nupsilon is substantially higher in food producers than in hunter-gatherers as determined by fast-evolving polymorphisms (1.76 versus 0.11). This finding indicates that the two population groups differ substantially in female and male migration rate and/or effective size. The difference also persists when linguistically homogeneous populations are used and outlier populations are eliminated (1.78 vs 0.19) or when the jacknife procedure is applied to a paired population data set (1.32 to 7.84 versus 0.14 to 0.66). The higher ratio of mtDNA to Y-chromosome Nnu in food producers than in hunter-gatherers is further confirmed by the use of slow-evolving polymorphisms (1.59 to 7.91 versus 0.12 to 0.35). To explain these results, we propose a model that integrates demographic and genetic aspects and incorporates ethnographic knowledge. In such a model, the asymmetric gene flow, polyginy, and patrilocality play an important role in differentiating the genetic structure of sub-Saharan populations. The existence of an asymmetric gene flow is supported by the phylogeographic features of mtDNA and Y-chromosome haplogroups found in the two population groups. The role of polyginy and patrilocality is sustained by the evidence of a differential pressure of genetic drift and gene flow on maternal and paternal lineages of food producers and hunter-gatherers that is revealed through the analysis of mitochondrial and Y-chromosomal intrapopulational variation.

Africa South of the Sahara↗

[Integrating demographic and socioeconomic policies].

"The article offers a theoretical model of integration between demographic and socioeconomic policy [in Bulgaria].... The author examines the changes in the population's demographic structures: changes in the sex ratio; ageing; [and] family nuclearisation.... The conclusion is drawn that in order to boost the effectiveness of the demographic policy, social practice and its scientific back-up should be even more fully integrated." (SUMMARY IN ENG)

Bulgaria↗

The demographic impact of AIDS in sub-Saharan Africa: short- and long-term projections.

"This paper describes the methodology used to incorporate AIDS mortality in recently revised World Bank population projections.... The paper first reviews different approaches for projecting AIDS and its demographic consequences. This is followed by a summary of an epidemiological model that simulates the spread of HIV used in this analysis, and a demographic model that translates mortality from AIDS into population outcomes. These models are then used in a set of simulations, from which the effect of current HIV prevalence on projected future mortality is extracted. Finally, the extracted equations linking current HIV prevalence with future mortality indicators are applied to sub-Saharan countries with a measurable level of current HIV prevalence."

Acquired Immunodeficiency Syndrome↗

Sexual reproduction and population dynamics: the role of polygyny and demographic sex differences.

Most models of population dynamics do not take sexual reproduction into account (i.e., they do not consider the role of males). However, assumptions behind this practice--that no demographic sex differences exist and males are always abundant enough to fertilize all the females--are usually not justified in natural populations. On the contrary, demographic sex differences are common, especially in polygynous species. Previous models that consider sexual reproduction report a stabilizing effect through mixing of different genotypes, thus suggesting a decrease in the propensity for complex of dynamics in sexually reproducing populations. Here we show that considering the direct role of males in reproduction and density dependence leads to the conclusion that a two-sex model is not necessarily more stable compared with the corresponding one-sex model. Although solutions exist where sexual reproduction has a stabilizing effect even when no genotypic variability is included (primarily when associated with monogamy), factors like polygyny, sex differences in survival or density dependence, and possible alterations of the primary sex ratio (the Trivers-Willard mechanism), may enlarge the parametric region of complex dynamics. Sexual reproduction therefore does not necessarily increase the stability of population dynamics and can have destabilizing effects, at least in species with complicated mating systems and sexual dimorphism.

Animals↗

Predicting "charge outliers" after spinal cord injury: a multicenter analysis of demographics, injury characteristics, outcomes, and rehabilitation charges.

OBJECTIVE: To describe the distribution of charges, to distinguish between "charge outliers" and nonoutliers, and to identify a model that uses demographics and injury characteristics to predict charge outlier status in individuals with spinal cord injury (SCI). DESIGN: Retrospective data analysis of patients admitted to 24 acute inpatient rehabilitation national Spinal Cord Injury Model Systems centers. Statistical analysis, including proportions, means, and standard deviations (SDs), were compiled for the following variables: demographic and injury information, rehabilitation charges, medical complications, associated injuries, and surgical procedures. SETTING: Tertiary, university medical centers participating in the National Institute on Disability and Rehabilitation Research's SCI Model Systems project. PARTICIPANTS: A total of 13,392 patients who were admitted to 24 acute, intensive, interdisciplinary rehabilitation settings after traumatic SCI between November 1972 and August 1996. MAIN OUTCOME MEASURES: Statistical data analysis was used to determine significance between charge outliers and nonoutliers on the basis of demographic, injury characteristics, and clinical factors. Outliers, under the current diagnostic-related group system, are defined as cases in which lengths of stay exceed the mean by the lesser of 20 days or 1.94 SDs. RESULTS: Statistically significant differences were found between SCI charge outliers and nonoutliers based on ethnicity, education, employment, level of injury, American Spinal Injury Association impairment classification, and sponsor of hospitalization. On average, outliers were 4 years older than nonoutliers, and tended to have more associated injuries, pressure ulcers, surgical procedures, and medical complications. A forward-conditional stepwise multiple logistic regression analysis was used to confirm univariate analysis and to predict the presence or absence of outliers based on the predictor variables. A model for the prediction of SCI charge outlier status was defined. CONCLUSIONS: SCI charge outliers are most likely to be retired, insured, have high cervical level injuries, and be educated beyond high school. Improved treatment efficiency serves as a means of cost reduction and is a reason to identify outlier characteristics.

Adolescent↗