The influence of clan structure on the genetic variation in a single Ghanaian village

Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure. To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations. In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana. We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village. We also observed a deep male substructure within one of the clans in this village. Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a*-M2, E1b1a7a*-U174 and E1b1a8a*-U209, P277, P278. In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans. On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure. If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale. Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large.     

Morphometrics and inertial properties in the body segments of chimpanzees (Pan troglodytes)

Inertial characteristics and dimensions of the body and body segments form an integral part of a biomechanical analysis of motion. In primate studies, however, segment inertial parameters of non-human hominoids are scarce and often obtained using varying techniques. Therefore, the principal aim of this study was to expand the existing chimpanzee inertial property data set using a non-invasive measuring technique. We also considered age- and sex-related differences within our sample. By means of a geometric model based on Crompton et al. (1996; Am J Phys Anthropol 99, 547-570) we generated inertial properties using external segment length and diameter measurements of 53 anaesthetized chimpanzees (Pan troglodytes). We report absolute inertial parameters for immature and mature subjects and for males and females separately. Proportional data were computed to allow the comparison between age classes and sex classes. In addition, we calculated whole limb inertial properties and we discuss their potential biomechanical consequences. We found no significant differences between the age classes in the proportional data except for hand and foot measures where juveniles exhibit relatively longer and heavier distal segments than adults. Furthermore, most sex-related differences can be directly attributed to the higher absolute segment masses in male chimpanzees resulting in higher moments of inertia. Additionally, males tend to have longer upper limbs than females. However, regarding proportional data we discuss the general inertial properties of the chimpanzee. The described segment inertial parameters of males and females, and of the two age classes, represent a valuable data set ready for use in a range of biomechanical locomotor models. These models offer great potential for improving our understanding of early hominin locomotor patterns.     

Photoaligned Liquid Crystal Devices with Switchable Hexagonal Diffraction Patterns

Highly efficient optical diffraction can be realized with the help of micrometer-thin liquid crystal (LC) layers with a periodic modulation of the director orientation. Electrical tunability is easily accessible due to the strong stimuli-responsiveness in the LC phase. By using well-designed photoalignment patterns at the surfaces, we experimentally stabilize two dimensional periodic LC configurations with switchable hexagonal diffraction patterns. The alignment direction follows a one-dimensional periodic rotation at both substrates, but with a 60° or 120° rotation between both grating vectors. The resulting LC configuration is studied with the help of polarizing optical microscopy images and the diffraction properties are measured as a function of the voltage. The intricate bulk director configuration is revealed with the help of finite element Q-tensor simulations. Twist conflicts induced by the surface anchoring are resolved by introducing regions with an out-of-plane tilt in the bulk. This avoids the need for singular disclinations in the structures and gives rise to voltage induced tuning without hysteretic behavior.     

Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia

OBJECTIVE: To investigate the effect of melatonin treatment on sleep, behavior, cognition, and quality of life in children with attention-deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia. METHOD: A total of 105 medication-free children, ages 6 to 12 years, with rigorously diagnosed ADHD and chronic sleep onset insomnia participated in a randomized, double-blind, placebo-controlled trial using 3 or 6 mg melatonin (depending on body weight), or placebo for 4 weeks. Primary outcome parameters were actigraphy-derived sleep onset, total time asleep, and salivary dim light melatonin onset. RESULTS: Sleep onset advanced by 26.9 +/- 47.8 minutes with melatonin and delayed by 10.5 +/- 37.4 minutes with placebo (p < .0001). There was an advance in dim light melatonin onset of 44.4 +/- 67.9 minutes in melatonin and a delay of 12.8 +/- 60.0 minutes in placebo (p < .0001). Total time asleep increased with melatonin (19.8 +/- 61.9 minutes) as compared to placebo (-13.6 +/- 50.6 minutes; p = .01). There was no significant effect on behavior, cognition, and quality of life, and significant adverse events did not occur. CONCLUSION: Melatonin advanced circadian rhythms of sleep-wake and endogenous melatonin and enhanced total time asleep in children with ADHD and chronic sleep onset insomnia; however, no effect was found on problem behavior, cognitive performance, or quality of life.     

Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice.

Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.     

Support vector methods for survival analysis: a comparison between ranking and regression approaches

Objective

To compare and evaluate ranking, regression and combined machine learning approaches for the analysis of survival data.

Methods

The literature describes two approaches based on support vector machines to deal with censored observations. In the first approach the key idea is to rephrase the task as a ranking problem via the concordance index, a problem which can be solved efficiently in a context of structural risk minimization and convex optimization techniques. In a second approach, one uses a regression approach, dealing with censoring by means of inequality constraints. The goal of this paper is then twofold: (i) introducing a new model combining the ranking and regression strategy, which retains the link with existing survival models such as the proportional hazards model via transformation models; and (ii) comparison of the three techniques on 6 clinical and 3 high-dimensional datasets and discussing the relevance of these techniques over classical approaches fur survival data.

Results

We compare svm-based survival models based on ranking constraints, based on regression constraints and models based on both ranking and regression constraints. The performance of the models is compared by means of three different measures: (i) the concordance index, measuring the model’s discriminating ability; (ii) the logrank test statistic, indicating whether patients with a prognostic index lower than the median prognostic index have a significant different survival than patients with a prognostic index higher than the median; and (iii) the hazard ratio after normalization to restrict the prognostic index between 0 and 1. Our results indicate a significantly better performance for models including regression constraints above models only based on ranking constraints.

Conclusions

This work gives empirical evidence that svm-based models using regression constraints perform significantly better than svm-based models based on ranking constraints. Our experiments show a comparable performance for methods including only regression or both regression and ranking constraints on clinical data. On high dimensional data, the former model performs better. However, this approach does not have a theoretical link with standard statistical models for survival data. This link can be made by means of transformation models when ranking constraints are included.     

Technology for Hospital Management of Diabetes: Statistical Approach of Assessing the Reliability of Glucose Sensors: The GLYCENSIT Procedure

Background

In healthcare, patients with diabetes are instructed on how to apply intensified insulin therapy in an optimal manner. Tight blood glucose control is also performed on patients treated in the intensive care unit (ICU). Different blood glucose meters and glucose monitoring systems (GMSs) are used to achieve this goal, and some may lack reliability.

Methods

The GLYCENSIT procedure is a statistical assessment tool we are proposing for evaluating the significant difference of paired glucose measurements. The performance of the GlucoDay^® system in the ICU is analyzed with GLYCENSIT.

Results

The GLYCENSIT analysis comprises three phases: testing possible persistent measurement behavior as a function of the glycemic range, testing the number of measurement errors with respect to a standard criterion for binary assessment of glucose sensors, and computing the tolerance intervals that indicate possible test sensor deviations for new observations. The probability of the tolerance intervals directly reflects the number of samples and additionally improves current assessment techniques. The method can be tuned according to the clinician''s preferences regarding significance level, tolerance level, and glycemic range cutoff values. The measurement behavior of the GlucoDay sensor is found to be persistent but inaccurate and returns wide tolerance intervals, suggesting that the GlucoDay sensor may not be sufficiently reliable for glycemia control in the ICU.

Conclusions

The GLYCENSIT procedure aims to serve as statistical guide for clinicians in the assessment of glucose sensor devices.