Evaluation of the psychometric properties of the London Measure of Unplanned Pregnancy in Brazilian Portuguese

Background: Estimates of unplanned pregnancy worldwide are of concern, especially in low and middle-income countries, including Brazil. Although the contraceptive prevalence rate is high in Brazil, almost half of all pregnancies are reported as unintended. The only source of nationally representative data about pregnancy intention is the Demographic and Health Survey, as with many other countries. In more recent years, however, it has been realized that concept of unintended pregnancy is potentially more complex and requires more sophisticated measurement strategies, such as the London Measure of Unplanned Pregnancy (LMUP). The LMUP has been translated and validated in other languages, but not Portuguese yet. In this study, we evaluate the psychometric properties of the LMUP in the Portuguese language, Brazilian version. Methods: A Brazilian Portuguese version of the LMUP was produced via translation and back-translation. After piloting, the mode of administration was changed from self-completion to interviewer-administration. The measure was field tested with pregnant, postpartum, and postabortion women recruited at maternity and primary health care services in Sao Paulo city. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Construct validity was assessed using principal components analysis and hypothesis testing. Scaling was assessed with Mokken analysis. Results: 759 women aged 15–44 completed the Brazilian Portuguese LMUP. There were no missing data. The measure was acceptable and well targeted. Reliability testing demonstrated good internal consistency (alpha = 0.81, all item-rest correlations >0.2). Validity testing confirmed that the measure was unidimensional and that all hypotheses were met: there were lower LMUP median scores among women in the extreme age groups (p<0.001), among non-married women (p<0.001) and those with lower educational attainment (p<0.001). The Loevinger H coefficient was 0.60, indicating a strong scale. Conclusion: The Brazilian Portuguese LMUP is a valid and reliable measure of pregnancy planning/intention that is now available for use in Brazil. It represents a useful addition to the public health research and surveillance toolkit in Brazil

Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11–q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735–744, 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71371/1/21106_ftp.pd

Human bipedal instability in tree canopy environments is reduced by “light touch” fingertip support

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However “light touch”, a sensorimotor feedback strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor’s ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use

Vigilance of mustached tamarins in single-species and mixed-species groups—the influence of group composition

Species that participate in mixed-species groups (MSG) may have complementary roles in antipredator strategies. We studied vigilance in mustached tamarins (Saguinus mystax), small arboreal primates that form stable mixed-species groups with saddleback tamarins (Saguinus fuscicollis), in order to examine how the direction of vigilance changes with different species group compositions and whether the division of labor between the two species can be confirmed. We did so by comparing quantitative and qualitative differences in vigilance behavior between same individuals in and out of association (case A); MSG and single-species groups of the same total group size from two different populations (case B); and MSG of the same group size but with a different ratio of conspecifics to heterospecifics (case C). We predicted that individuals would increase downward scanning when heterospecifics are absent or their percentage is low, but total vigilance would increase only in case A due to the group size effect. However, mustached tamarins increased total vigilance due to horizontal scanning in cases A and C, and the predictions were confirmed only in small-sized groups in case B. Thus, we found indications that associating tamarin species in MSG might complement each other in the direction of vigilance, but the division of labor alone does not satisfactorily explain all the findings. There appear to be other mechanisms at work that define how direction of vigilance changes with group size and species composition. Complementarity of species probably occurs due to species vertical stratification rather than differences in the direction of vigilance

Seasonal variation and an “outbreak” of frog predation by tamarins

We report temporal variation and an “outbreak” of frog predation by moustached tamarins, Saguinus mystax, in north-eastern Peruvian Amazonia. Frog predation rates were generally very low, but strongly increased in October 2015. Other high rates, identified by outlier analyses, were also observed in September–November of other years. Over all study years, predation rates in this 3-month period were significantly higher than those in the remainder of the year, suggesting a seasonal pattern of frog predation by tamarins. Reduced fruit availability or increased frog abundance or a combination of both may be responsible for both the seasonal pattern and the specific “outbreak” of frog predation

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants.

The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10 -12 ) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. The area under the receiver operating characteristic curve (AUC) for REVEL was 0.046-0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants and 0.027-0.143 higher in an independent test set of 1,953 pathogenic and 2,406 benign variants recently reported in ClinVar than the AUCs for other ensemble methods. We provide pre-computed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale