Assistive robotic device: evaluation of intelligent algorithms

Assistive robotic devices can be used to help people with upper body disabilities gaining more autonomy in their daily life. Although basic motions such as positioning and orienting an assistive robot gripper in space allow performance of many tasks, it might be time consuming and tedious to perform more complex tasks. To overcome these difficulties, improvements can be implemented at different levels, such as mechanical design, control interfaces and intelligent control algorithms. In order to guide the design of solutions, it is important to assess the impact and potential of different innovations. This paper thus presents the evaluation of three intelligent algorithms aiming to improve the performance of the JACO robotic arm (Kinova Robotics). The evaluated algorithms are 'preset position', 'fluidity filter' and 'drinking mode'. The algorithm evaluation was performed with 14 motorized wheelchair's users and showed a statistically significant improvement of the robot's performance.Comment: 4 page

Analyse de la variation intra- et inter-populationnelle : application de deux méthodes craniométriques sur des collections amérindiennes-canadiennes

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon

BACKGROUND: Genetic variation at loci influencing adult levels of HbF have been shown to modify the clinical course of sickle cell disease (SCD). Data on this important aspect of SCD have not yet been reported from West Africa. We investigated the relationship between HbF levels and the relevant genetic loci in 610 patients with SCD (98% HbSS homozygotes) from Cameroon, and compared the results to a well-characterized African-American cohort. Methods and FINDINGS: Socio-demographic and clinical features were collected and medical records reviewed. Only patients >5 years old, who had not received a blood transfusion or treatment with hydroxyurea were included. Hemoglobin electrophoresis and a full blood count were conducted upon arrival at the hospital. RFLP-PCR was used to describe the HBB gene haplotypes. SNaPshot PCR, Capillary electrophoresis and cycle sequencing were used for the genotyping of 10 selected SNPs. Genetic analysis was performed with PLINK software and statistical models in the statistical package R. Allele frequencies of relevant variants at BCL11A were similar to those detected in African Americans; although the relationships with Hb F were significant (p <.001), they explained substantially less of the variance in HbF than was observed among African Americans (∼ 2% vs 10%). SNPs in HBS1L-MYB region ( HMIP ) likewise had a significant impact on HbF, however, we did not find an association between HbF and the variations in HBB cluster and OR51B5/6 locus on chromosome 11p, due in part to the virtual absence of the Senegal and Indian Arab haplotypes. We also found evidence that selected SNPs in HBS1L-MYB region ( HMIP ) and BCL11A affect both other hematological indices and rates of hospitalization. CONCLUSIONS: This study has confirmed the associations of SNPs in BCL11A and HBS1L-MYB and fetal haemoglobin in Cameroonian SCA patients; hematological indices and hospitalization rates were also associated with specific allelic variants

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 108) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 106). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure

Rare Variants of Putative Candidate Genes Associated With Sporadic Meniere&apos;s Disease in East Asian Population

Objectives: The cause of Meniere&apos;s disease (MD) is unclear but likely involves genetic and environmental factors. The aim of this study was to investigate the genetic basis underlying MD by screening putative candidate genes for MD. Methods: Sixty-eight patients who met the diagnostic criteria for MD of the Barany Society were included. We performed targeted gene sequencing using next generation sequencing (NGS) panel composed of 45 MD-associated genes. We identified the rare variants causing non-synonymous amino acid changes, stop codons, and insertions/deletions in the coding regions, and excluded the common variants with minor allele frequency &gt;0.01 in public databases. The pathogenicity of the identified variants was analyzed by various predictive tools and protein structural modeling. Results: The average read depth for the targeted regions was 1446.3-fold, and 99.4% of the targeted regions were covered by 20 or more reads, achieving the high quality of the sequencing. After variant filtering, annotation, and interpretation, we identified a total of 15 rare heterozygous variants in 12 (17.6%) sporadic patients. Among them, four variants were detected in familial MD genes (DTNA, FAM136A, DPT), and the remaining 11 in MD-associated genes (PTPN22, NFKB1, CXCL10, TLR2, MTHFR, SLC44A2, NOS3, NOTCH2). Three patients had the variants in two or more genes. All variants were not detected in our healthy controls (n = 100). No significant differences were observed between patients with and without a genetic variant in terms of sex, mean age of onset, bilaterality, the type of MD, and hearing threshold at diagnosis. Conclusions: Our study identified rare variants of putative candidate genes in some of MD patients. The genes were related to the formation of inner ear structures, the immune-associated process, or systemic hemostasis derangement, suggesting the multiple genetic predispositions in the development of MD

Strategies to fine-map genetic associations with lipid levels by combining epigenomic annotations and liver-specific transcription profiles

Characterization of the epigenome promises to yield the functional elements buried in the human genome sequence, thus helping to annotate non-coding DNA polymorphisms with regulatory functions. Here, we develop two novel strategies to combine epigenomic data with transcriptomic profiles in humans or mice to prioritize potential candidate SNPs associated with lipid levels by genome-wide association study (GWAS). First, after confirming that lipid-associated loci that are also expression quantitative trait loci (eQTL) in human livers are enriched for ENCODE regulatory marks in the human hepatocellular HepG2 cell line, we prioritize candidate SNPs based on the number of these marks that overlap the variant position. This method recognized the known SORT1 rs12740374 regulatory SNP associated with LDL-cholesterol, and highlighted candidate functional SNPs at 15 additional lipid loci. In the second strategy, we combine ENCODE chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) data and liver expression datasets from knockout mice lacking specific transcription factors. This approach identified SNPs in specific transcription factor binding sites that are located near target genes of these transcription factors. We show that FOXA2 transcription factor binding sites are enriched at lipid-associated loci and experimentally validate that alleles of one such proxy SNP located near the FOXA2 target gene BIRC5 show allelic differences in FOXA2-DNA binding and enhancer activity. These methods can be used to generate testable hypotheses for many non-coding SNPs associated with complex diseases or traits

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

Low Digit Ratio Predicts Early Age at Menarche in Colombian Schoolgirls

Background:  The ratio between the lengths of the second and fourth fingers (digit ratio: 2D : 4D), a purported negative correlate of prenatal androgen exposure, has been inversely related to age at menarche. However, a recent study found high digit ratios in carriers of a single variant in the LIN28B gene, which has been linked to delayed menarche. Methods:  We investigated the association of digit ratio and age at menarche in 299 pre‐menarcheal girls aged 5–12 years who participated in a longitudinal cohort study in Bogotá, Colombia. Finger lengths were measured at baseline and the occurrence of menarche was periodically ascertained over a median 32 months of follow‐up. We used time‐to‐event analysis to estimate median ages at menarche as well as hazard ratios for menarche according to tertiles of the digit ratio for each hand. Results:  Estimated median age at menarche was lower for girls in the lowest digit ratio tertile of the right hand compared with those in the highest (12.0 vs. 12.3 years; P ‐value = 0.04). After adjustment for baseline age, height‐ and body mass index‐for‐age z ‐scores, the hazard of menarche was 86% higher in girls of the lowest digit ratio tertile (hazard ratio 1.9 [95% confidence interval 1.2, 2.9]) compared with those in the highest digit ratio tertile of the right hand. No significant associations were found with the left hand. Conclusions:  Digit ratio was positively associated with age at menarche in this longitudinal investigation, consistent with results from a recent gene‐linkage study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93549/1/j.1365-3016.2012.01310.x.pd

Extended Haplotypes in the Growth Hormone Releasing Hormone Receptor Gene (GHRHR) Are Associated with Normal Variation in Height

Mutations in the gene for growth hormone releasing hormone receptor (GHRHR) cause isolated growth hormone deficiency (IGHD) but this gene has not been found to affect normal variation in height. We performed a whole genome linkage analysis for height in a population from northern Sweden and identified a region on chromosome 7 with a lod-score of 4.7. The GHRHR gene is located in this region and typing of tagSNPs identified a haplotype that is associated with height (p = 0.00077) in the original study population. Analysis of a sample from an independent population from the most northern part of Sweden also showed an association with height (p = 0.0039) but with another haplotype in the GHRHR gene. Both haplotypes span the 3′ part of the GHRHR gene, including the region in which most of the mutations in IGHD have been located. The effect size of these haplotypes are larger than that of any gene previously associated with height, which indicates that GHRHR might be one of the most important genes so far identified affecting normal variation in human height