Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence, the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association (STREGA) studies initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Eyes With Previous Myopic Laser Refractive Surgery

Purpose: To calculate theoretically the errors in the estimation of corneal power when using the keratometric index (nk) in eyes that underwent laser refractive surgery for the correction of myopia and to define and validate clinically an algorithm for minimizing such errors. Methods: Differences between corneal power estimation by using the classical nk and by using the Gaussian equation in eyes that underwent laser myopic refractive surgery were simulated and evaluated theoretically. Additionally, an adjusted keratometric index (nkadj) model dependent on r1c was developed for minimizing these differences. The model was validated clinically by retrospectively using the data from 32 myopic eyes [range, −1.00 to −6.00 diopters (D)] that had undergone laser in situ keratomileusis using a solid-state laser platform. The agreement between Gaussian (PGaussc) and adjusted keratometric (Pkadj) corneal powers in such eyes was evaluated. Results: It was found that overestimations of corneal power up to 3.5 D were possible for nk = 1.3375 according to our simulations. The nk value to avoid the keratometric error ranged between 1.2984 and 1.3297. The following nkadj models were obtained: nkadj= −0.0064286r1c + 1.37688 (Gullstrand eye model) and nkadj = −0.0063804r1c + 1.37806 (Le Grand). The mean difference between Pkadj and PGaussc was 0.00 D, with limits of agreement of −0.45 and +0.46 D. This difference correlated significantly with the posterior corneal radius (r = −0.94, P < 0.01). Conclusions: The use of a single nk for estimating the corneal power in eyes that underwent a laser myopic refractive surgery can lead to significant errors. These errors can be minimized by using a variable nk dependent on r1c.

Operator-induced errors in Hartmann-Shack wavefront sensing:model eye study

Purpose: To evaluate the effects of instrument realignment and angular misalignment during the clinical determination of wavefront aberrations by simulation in model eyes. Setting: Aston Academy of Life Sciences, Aston University, Birmingham, United Kingdom. Methods: Six model eyes were examined with wavefront-aberration-supported cornea ablation (WASCA) (Carl Zeiss Meditec) in 4 sessions of 10 measurements each: sessions 1 and 2, consecutive repeated measures without realignment; session 3, realignment of the instrument between readings; session 4, measurements without realignment but with the model eye shifted 6 degrees angularly. Intersession repeatability and the effects of realignment and misalignment were obtained by comparing the measurements in the various sessions for coma, spherical aberration, and higher-order aberrations (HOAs). Results: The mean differences between the 2 sessions without realignment of the instrument were 0.020 μm ± 0.076 (SD) for Z3 - 1(P = .551), 0.009 ± 0.139 μm for Z3 1(P = .877), 0.004 ± 0.037 μm for Z4 0 (P = .820), and 0.005 ± 0.01 μm for HO root mean square (RMS) (P = .301). Differences between the nonrealigned and realigned instruments were -0.017 ± 0.026 μm for Z3 - 1(P = .159), 0.009 ± 0.028 μm for Z3 1 (P = .475), 0.007 ± 0.014 μm for Z4 0(P = .296), and 0.002 ± 0.007 μm for HO RMS (P = 0.529; differences between centered and misaligned instruments were -0.355 ± 0.149 μm for Z3 - 1 (P = .002), 0.007 ± 0.034 μm for Z3 1(P = .620), -0.005 ± 0.081 μm for Z4 0(P = .885), and 0.012 ± 0.020 μm for HO RMS (P = .195). Realignment increased the standard deviation by a factor of 3 compared with the first session without realignment. Conclusions: Repeatability of the WASCA was excellent in all situations tested. Realignment substantially increased the variance of the measurements. Angular misalignment can result in significant errors, particularly in the determination of coma. These findings are important when assessing highly aberrated eyes during follow-up or before surgery. © 2007 ASCRS and ESCRS.

Visual acuity measures do not reliably detect childhood refractive error - an epidemiological study

Purpose To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. Methods The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. Results Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. Conclusions Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver.

Epidemiology of myopia in a United Kingdom urban child population

The Aston Eye Study (AES) was instigated in October 2005 to determine the distribution of refractive error and associated ocular biometry in a sample of UK urban school children. The AES is the first study to compare outcome measures separately in White, South Asian and Black children. Children were selected from two age groups (Year 2 children aged 6/7 years, Year8 children aged 12/13 years of age) using random cluster sampling of schools in Birmingham, West Midlands UK. To date, the AES has examined 598 children (302 Year 2,296 Year 8). Using open-field cycloplegic autorefraction, the overall prevalence of myopia (=-0.50D SER in either eye) determined was 19.6%, with a higher prevalence in older (29.4%) compared to younger (9.9%) children (p<0.001). Using multiple logistic regression models, the risk of myopia was higher in Year 8 South Asian compared to White children and higher in children attending grammar schools relative to comprehensive schools. In addition, the prevalence of uncorrected ametropia was found to be high (Year 8: 12.84%, Year 2: 15.23%), which will be of concern to bodies responsible for the implementation of school vision screening strategies. Biometric data using non-contact partial coherence interferometry revealed a contributory effect of axial length (AL) and central corneal radius (CR) on myopic refraction, resulting in a strong coefficient of determination of the AL/CR ratio on refractive error. Ocular biometric measures did not vary significantly as a function of ethnicity, suggesting a greater miscorrelation of components in susceptible ethnic groups to account for their higher myopia prevalence. Corneal radius was found to be steeper in myopes in both age groups, but was found to flatten with increasing axial length. Due to the inextricable link between myopia and axial elongation, the paradoxical finding of the cornea demands further longitudinal investigation, particularly in relation to myopia onset. Questionnaire analysis revealed a history of myopia in parents and siblings to be significantly associated with myopia in Year 8 children, with a dose-dependent rise in the odds ratio of myopia evident with increasing number of myopic parents. By classifying socioeconomic status (SES) using Index of Multiple Deprivation values, it was found that Year 8 children from moderately deprived backgrounds were more at risk of myopia compared with children located at both extremities of the deprivation spectrum. However, the main effect of SES weakened following multivariate analysis, with South Asian ethnicity and grammar schooling remaining associated with Year 8 myopia after adjustment.

Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.

Cytogenetic And Morphologic Approaches Of Hybrids From Experimental Crosses Between Triatoma Lenti Sherlock & Serafim, 1967 And T. Sherlocki Papa Et Al., 2002 (hemiptera: Reduviidae).

The reproductive capacity between Triatoma lenti and Triatoma sherlocki was observed in order to verify the fertility and viability of the offspring. Cytogenetic, morphological and morphometric approaches were used to analyze the differences that were inherited. Experimental crosses were performed in both directions. The fertility rate of the eggs in crosses involving T. sherlocki females was 65% and 90% in F1 and F2 offspring, respectively. In reciprocal crosses, it was 7% and 25% in F1 and F2 offspring, respectively. The cytogenetic analyses of the male meiotic process of the hybrids were performed using lacto-acetic orcein, C-banding and Feulgen techniques. The male F1 offspring presented normal chromosome behavior, a finding that was similar to those reported in parental species. However, cytogenetic analysis of F2 offspring showed errors in chromosome pairing. This post-zygotic isolation, which prevents hybrids in nature, may represent the collapse of the hybrid. This phenomenon is due to a genetic dysregulation that occurs in the chromosomes of F1. The results were similar in the hybrids from both crosses. Morphological features, such as color and size of connexive and the presence of red-orange rings on the femora, were similar to T. sherlocki, while wins size was similar to T. lenti in F1 offspring. The eggshells showed characteristics that were similar to species of origin, whereas the median process of the pygophore resulted in intermediate characteristics in the F1 and a segregating pattern in F2 offspring. Geometric morphometric techniques used on the wings showed that both F1 and F2 offspring were similar to T. lenti. These studies on the reproductive capacity between T. lenti and T. sherlocki confirm that both species are evolutionarily closed; hence, they are included in the brasiliensis subcomplex. The extremely reduced fertility observed in the F2 hybrids confirmed the specific status of the species that were analyzed.

Refractive Error In School Children In Campinas, Brazil.

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Medidas de associação em estudo transversal com delineamento complexo: razão de chances e razão de prevalência

O objetivo deste estudo foi apresentar e discutir a utilização das medidas de associação: razão de chances e razão de prevalências, em dados obtidos de estudo transversal realizado em 2001-2002, utilizando-se amostra estratificada por conglomerados em dois estágios (n=1.958). As razões de chances e razões de prevalências foram estimadas por meio de regressão logística não condicional e regressão de Poisson, respectivamente, utilizando-se o pacote estatístico Stata 7.0. Intervalos de confiança e efeitos do desenho foram considerados na avaliação da precisão das estimativas. Dois desfechos do estudo transversal com diferentes níveis de prevalência foram avaliados: vacinação contra influenza (66,1%) e doença pulmonar referida (6,9%). Na situação em que a prevalência foi alta, as estimativas das razões de prevalência foram mais conservadoras com intervalos de confiança menores. Na avaliação do desfecho de baixa prevalência, não se observaram grandes diferenças numéricas entre as estimações das razões de chances e razões de prevalência e erros-padrão obtidos por uma ou outra técnica. O efeito do desenho maior que a unidade indicou que a amostragem complexa, em ambos os casos, aumentou da variância das estimativas. Cabe ao pesquisador a escolha da técnica e do estimador mais adequado ao seu objeto de estudo, permanecendo a escolha no âmbito epidemiológico.

Species determination of Brazilian mammals implicated in the epidemiology of rabies based on the control region of mitochondrial DNA

Identification of animals that are decomposing or have been run over or burnt and cannot be visually identified is a problem in the surveillance and control of infectious diseases. Many of these animals are wild and represent a valuable source of information for epidemiologic research as they may be carriers of an infectious agent. This article discusses the results obtained using a method for identifying mammals genetically by sequencing their mitochondrial DNA control region. Fourteen species were analyzed and identified. These included the main reservoirs and transmitters of rabies virus, namely, canids, chiroptera and primates. The results prove that this method of genetic identification is both efficient and simple and that it can be used in the surveillance of infectious diseases which includes mammals in their epidemiologic cycle, such as rabies.

Epidemiology of leisure, transportation, occupational, and household physical activity: prevalence and associated factors

Background: To estimate the prevalence of and identify factors associated with physical activity in leisure, transportation, occupational, and household settings. Methods: This was a cross-sectional study aimed at investigating living and health conditions among the population of São Paulo, Brazil. Data on 1318 adults aged 18 to 65 years were used. To assess physical activity, the long version of the International Physical Activity Questionnaire was applied. Multivariate analysis was conducted using a hierarchical model. Results: The greatest prevalence of insufficient activity related to transportation (91.7%), followed by leisure (77.5%), occupational (68.9%), and household settings (56.7%). The variables associated with insufficient levels of physical activity in leisure were female sex, older age, low education level, nonwhite skin color, smoking, and self-reported poor health; in occupational settings were female sex, white skin color, high education level, self-reported poor health, nonsmoking, and obesity; in transportation settings were female sex; and in household settings, with male sex, separated, or widowed status and high education level. Conclusion: Physical activity in transportation and leisure settings should be encouraged. This study will serve as a reference point in monitoring different types of physical activities and implementing public physical activity policies in developing countries

Epidemiology of Leisure, Transportation, Occupational, and Household Physical Activity: Prevalence and Associated Factors

Background: To estimate the prevalence of and identify factors associated with physical activity in leisure, transportation, occupational, and household settings. Methods: This was a cross-sectional study aimed at investigating living and health conditions among the population of So Paulo, Brazil. Data on 1318 adults aged 18 to 65 years were used. To assess physical activity, the long version of the International Physical Activity Questionnaire was applied. Multivariate analysis was conducted using a hierarchical model. Results: The greatest prevalence of insufficient activity related to transportation (91.7%), followed by leisure (77.5%), occupational (68.9%), and household settings (56.7%). The variables associated with insufficient levels of physical activity in leisure were female sex, older age, low education level, nonwhite skin color, smoking, and self-reported poor health; in occupational settings were female sex, white skin color, high education level, self-reported poor health, nonsmoking, and obesity; in transportation settings were female sex; and in household settings, with male sex, separated, or widowed status and high education level. Conclusion: Physical activity in transportation and leisure settings should be encouraged. This study will serve as a reference point in monitoring different types of physical activities and implementing public physical activity policies in developing countries.

A spatial approach for the epidemiology of antibiotic use and resistance in community-based studies: the emergence of urban clusters of Escherichia coli quinolone resistance in Sao Paulo, Brasil

Background: Population antimicrobial use may influence resistance emergence. Resistance is an ecological phenomenon due to potential transmissibility. We investigated spatial and temporal patterns of ciprofloxacin (CIP) population consumption related to E. coli resistance emergence and dissemination in a major Brazilian city. A total of 4,372 urinary tract infection E. coli cases, with 723 CIP resistant, were identified in 2002 from two outpatient centres. Cases were address geocoded in a digital map. Raw CIP consumption data was transformed into usage density in DDDs by CIP selling points influence zones determination. A stochastic model coupled with a Geographical Information System was applied for relating resistance and usage density and for detecting city areas of high/low resistance risk. Results: E. coli CIP resistant cluster emergence was detected and significantly related to usage density at a level of 5 to 9 CIP DDDs. There were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density. Conclusions: There were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density. The usage density of 5-9 CIP DDDs per 1,000 inhabitants within the same influence zone was the resistance triggering level. This level led to E. coli resistance clustering, proving that individual resistance emergence and dissemination was affected by antimicrobial population consumption.

Cross-national epidemiology of DSM-IV major depressive episode

Background: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low-to middle-income countries in the World Mental Health Survey Initiative. Methods: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2: 1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low-to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.

Knowledge acquisition by networks of interacting agents in the presence of observation errors

In this work we investigate knowledge acquisition as performed by multiple agents interacting as they infer, under the presence of observation errors, respective models of a complex system. We focus the specific case in which, at each time step, each agent takes into account its current observation as well as the average of the models of its neighbors. The agents are connected by a network of interaction of Erdos-Renyi or Barabasi-Albert type. First, we investigate situations in which one of the agents has a different probability of observation error (higher or lower). It is shown that the influence of this special agent over the quality of the models inferred by the rest of the network can be substantial, varying linearly with the respective degree of the agent with different estimation error. In case the degree of this agent is taken as a respective fitness parameter, the effect of the different estimation error is even more pronounced, becoming superlinear. To complement our analysis, we provide the analytical solution of the overall performance of the system. We also investigate the knowledge acquisition dynamic when the agents are grouped into communities. We verify that the inclusion of edges between agents (within a community) having higher probability of observation error promotes the loss of quality in the estimation of the agents in the other communities.