Postcraniometric sex and ancestry estimation in South Africa: a validation study.

With the acceptance of the Daubert criteria as the standards for best practice in forensic anthropological research, more emphasis is being placed on the validation of published methods. Methods, both traditional and novel, need to be validated, adjusted, and refined for optimal performance within forensic anthropological analyses. Recently, a custom postcranial database of modern South Africans was created for use in Fordisc 3.1. Classification accuracies of up to 85% for ancestry estimation and 98% for sex estimation were achieved using a multivariate approach. To measure the external validity and report more realistic performance statistics, an independent sample was tested. The postcrania from 180 black, white, and colored South Africans were measured and classified using the custom postcranial database. A decrease in accuracy was observed for both ancestry estimation (79%) and sex estimation (95%) of the validation sample. When incorporating both sex and ancestry simultaneously, the method achieved 70% accuracy, and 79% accuracy when sex-specific ancestry analyses were run. Classification matrices revealed that postcrania were more likely to misclassify as a result of ancestry rather than sex. While both sex and ancestry influence the size of an individual, sex differences are more marked in the postcranial skeleton and are therefore easier to identify. The external validity of the postcranial database was verified and therefore shown to be a useful tool for forensic casework in South Africa. While the classification rates were slightly lower than the original method, this is expected when a method is generalized.

Sex estimation from the long bones of modern South Africans.

Best scientific practice for sex estimation incorporates accurate techniques that employ appropriate standards and population- and period-specific data. Single measurements provide accurate sex estimations, but multiple measurements and multivariate techniques offer greater validity to biological profile assessments. Appropriate, modern standards for sex estimation are limited to the cranium in South Africans (SA), which warrants the examination of the potential for sex estimation using the postcrania of socially defined SA blacks, whites and coloureds through multivariate models and advanced statistical techniques. A total of 39 standard osteometric measurements were taken from the postcrania of 360 socially defined SA blacks, whites and coloureds (equal sex and ancestry). Univariate and multivariate models were evaluated. Multivariate models, with cross-validation and equal priors, were explored with linear and flexible discriminant analysis (LDA and FDA, respectively). Classification accuracies associated with univariate models ranged from 56 to 89%, whereas multivariate classification accuracies using bone models (i.e. all measurements from one element) ranged from 75 to 91%. The highest correct classifications were achieved with multivariate subsets (i.e. combinations of measurements from different bones) and ranged from 90 to 98%. Overall, FDA and LDA yielded similar accuracy rates. Postcranial bones achieve comparable classification accuracies to the pelvis and higher accuracies than metric or morphological techniques using the cranium. While LDA is the most commonly used classification statistic in biological anthropology, FDA provides a good alternative for classification.

Sexual dimorphism in cranial morphology among modern South Africans.

Pattern expressions of morphoscopic cranial traits vary across populations with classification accuracies being highly dependent on the reference collection to which unknown skulls are compared. Despite recent developments in population-specific standards for South Africans, researchers have not addressed the accuracy of morphological methods. Several studies demonstrate differences in sexual dimorphism between South Africans and North Americans, warranting a need to re-evaluate sex estimation methods in South Africa. The purposes of this study were to test the reliability and accuracy of the Walker (2008) method and to examine patterns of sexual dimorphism among South Africans. A total of 245 modern Black and White South African male and female crania from the Pretoria Bone Collection, University of Pretoria, were scored using the Walker (2008) methodology. Cohen's kappa was used to evaluate reliability of the method, and percent correct assessed validity of the method. Logistic regression was utilised to create modified population-specific formulae. Inter- and intra-observer agreement was moderate to excellent (0.60-0.90), except for the mental eminence (0.40). The percent correct results for sex were 80% or higher for combinations of glabella, mastoid and menton and between 68% and 73% for menton, mastoid, orbital and nuchal margin using logistic equations of Walker (2008). White males had the highest (94-97%) and White females had the lowest (31-62%) percent correct. The low accuracies obtained when using Walker's (2008) equations emphasised the need for population-specific sex estimation models. Modified formulae for South Africans were created, yielding higher classification rates (84-93%) than when North American standards were employed.

Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome.

BACKGROUND: Floating-Harbor syndrome is a rare autosomal dominant short stature syndrome with retarded speech development, intellectual disability and dysmorphic facial features. Recently dominant mutations almost exclusively located in exon 34 of the Snf2-related CREBBP activator protein gene were identified to cause FHS. METHODS: Here we report the genetic analysis of 5 patients fulfilling the diagnostic criteria of FHS obtained by Sanger sequencing. All of them presented with short stature, speech delay as well as psychomotor delay and typical facial dysmorphism. Three patients showed a good response to growth hormone treatment. RESULTS: Two patients demonstrate novel, heterozygous de novo frameshift mutations in exon 34 (c.7396delA and c.7218dupT) leading to premature stop mutations in SRCAP (p.Val2466Tyrfs*9 and p.Gln2407Serfs*36, respectively). In two further patients we found already known SRCAP mutations in exon 34, c.7330C > T and c.7303C > T, respectively, which also lead to premature stop codons: p.Arg2444* and p.Arg2435*. In one patient, we identified a novel de novo stop mutation in exon 33 (c.6985C > T, p.Arg2329*) demonstrating that not all FHS cases are caused by mutations in exon 34 of SRCAP. CONCLUSIONS: Our data confirm a mutational hot spot in the final exon of SRCAP in the majority of FHS patients but also show that exon 33 of this gene can be affected.

Deletion and point mutations of PTHLH cause brachydactyly type E.

Autosomal-dominant brachydactyly type E (BDE) is a congenital limb malformation characterized by small hands and feet predominantly as a result of shortened metacarpals and metatarsals. In a large pedigree with BDE, short stature, and learning disabilities, we detected a microdeletion of approximately 900 kb encompassing PTHLH, the gene coding for parathyroid hormone related protein (PTHRP). PTHRP is known to regulate the balance between chondrocyte proliferation and the onset of hypertrophic differentiation during endochondral bone development. Inactivation of Pthrp in mice results in short-limbed dwarfism because of premature differentiation of chondrocyte. On the basis of our initial finding, we tested further individuals with BDE and short stature for mutations in PTHLH. We identified two missense (L44P and L60P), a nonstop (X178WextX( *)54), and a nonsense (K120X) mutation. The missense mutation L60P was tested in chicken micromass culture with the replication-competent avian sarcoma leukosis virus retroviral expression system and was shown to result in a loss of function. Thus, loss-of-function mutations in PTHLH cause BDE with short stature.

Veldt fires in South Africa: Implications on osteometry and the biological profile.

Standard operating procedures for forensic anthropological analyses dictate that thermally altered remains should not be measured, hindering the creation of a biological profile. Few studies have addressed estimating biological parameters from burned remains, with the greatest focus of this research area being on cremated remains. However, veldt fires are more common than cremation in the South African forensic context. The aim of this study was to explore the degree of structural changes observed in domestic pig (Sus scrofa) bones associated with thermal destruction and the potential impact on the estimation of a biological profile using standard osteometric methods. A total of 96 pig femora were divided equally into two categories: fresh and dry. Within each category, equal samples were exposed to different durations of burning, namely, 5, 10, and 20 min. Ten standard femoral anthropological measurements were collected before and after burning. Technical error of measurement and Wilcoxon signed-rank tests were used to assess changes in the femoral dimensions before and after burning. Most measurements were significantly different after burning, with the fresh bones decreasing in size by up to 7.8% and the dry bones decreasing in size by up to 4.0%. The magnitude of post-burning measurement changes for both burn conditions was similar to, or smaller than has previously been reported for observer measurement errors of commonly used variables investigated for standard osteometric studies. Veldt fires are less intense than cremation, thus causing less shrinkage.

Standardization and quality assurance in skeletal landmark placement and osteometry.

Studies revising methodology are essential to the development and standardization of the field of anthropology, especially as the ultimate goal is improved forensic analyses. A series of revisions were made to the Standards for Data Collection Procedures reference manual. This includes changes made to the definitions of several standard measurements ranging from modified landmark placement to variation in the proper orientation of the caliper. The aim of this paper was to compare measurements collected using the different sets of definitions to determine if the measurements would differ significantly. Fifteen measurements were collected from 30 crania and postcrania, first using the original definitions, and then using the modified definitions and/or landmarks. The measurement differences for the 2 sets of definitions were assessed using technical error of measurement and a Kruskal-Wallis test. Results indicate that 8 of the 15 measurements differed significantly when the modified definitions were employed. Therefore, data collected using the different sets of definitions should not be used interchangeably. Forensic practitioners and laboratories making use of the updated reference manual must take into consideration how the current results might influence their standard operating procedures. Furthermore, all databases that currently make use of the original measurements, such as the South African-specific databases used in Fordisc, must be updated to include the modified measurements to stay on par with international data collection standards.

Kinetic parameters during land and water walking performed by individuals with Down Syndrome.

BACKGROUND: Down Syndrome (DS) is a genetic condition presenting delay in acquisition of main motor milestones, such as walking. Although studies have been investigating the biomechanical parameters during land walking performed by individual with DS, the literature is scarce regarding kinetic parameters analysis in this population, specially during water walking. RESEARCH QUESTION: This study sought to assess the vertical ground reaction force (Fz) of walking performed in water and on land at different speeds by individuals with DS. METHODS: Fourteen adults with DS (age: 27.9 ± 7.9 years; body mass: 58.4 ± 12.9 kg; height: 1.4 ± 0.1 m, body mass index: 29.2 ± 5.4 kg.m-2) completed two sessions of data collection, one on land and another in aquatic environment. The protocol consisted of walking performed at three self-selected speeds (slow, comfortable and fast) in randomized order. The Fz was assessed with a waterproof force plate in each condition. Two-way repeated-measures ANOVA (environment and speed), with Bonferroni's post hoc tests, were used for analysis. A significance level was set as α = 0.05. RESULTS: Significant differences were observed between environments (p < 0.001), with reduced first peak of Fz (68-73%), second peak of Fz (66-70%), loading rate (75-78%) and impulse (40-41%) in the water walking for all speeds analyzed. In the aquatic environment, no significant difference was observed for the first and second Fz peaks with the increasing speed of walking. Moreover, the loading rate significantly increased (p = 0.019) as the impulse significantly reduced (p < 0.001) in the higher speeds. SIGNIFICANCE: Individuals with DS present reduced Fz outcomes during water walking in comparison to land. Therefore, water walking may be performed by individuals with DS with safe vertical loads on lower limbs regardless the self-selected speed for rehabilitation, correction of gait and training purposes.

Intronic mutations in the L1CAM gene may cause X-linked hydrocephalus by aberrant splicing.

L1 disease is a clinically heterogeneous X-chromosomal neurodevelopmental disorder that is frequently associated with mental retardation and congenital hydrocephalus in males. It is caused by mutations in L1CAM that encodes a multifunctional transmembrane neuronal cell adhesion molecule. We report our findings on 6 novel intronic L1CAM sequence variants (c.523+5G>A, c.1123+1G>A, c.1547-13delC, c.3323-17dupG, c.3457+3A>T, and c.3457+18C>T), and a recurrent one (c.523+12C>T). While the pathogenic potential of nucleotide changes within the evolutionarily well-conserved splice consensus sequence (c.523+5G>A, c.1123+1G>A, and c.3457+3A>T) is widely accepted, it is not always straight forward to assess the disease relevance of intronic mutations, if they lie outside the consensus. The c.523+12C>T variant co-segregated with X-linked hydrocephalus in two unrelated families. In the mutated allele, a preferentially used novel splice donor site is generated that results in a frame shift due to insertion of the first 10 bp of intron 5 in the mature mRNA, a largely truncated protein, and most likely a functional null allele. The c.1547-13delC mutation creates a new acceptor site resulting in the insertion of 4 additional amino acids at the end of the immunoglobulin like domain 5. In contrast, c.3323-17dupG and c.3457+18C>T seem to be non-pathogenic L1CAM variants.

Características das instalações e equipamentos para a prática de atividade física em escolas da zona rural de Pelotas, Rio Grande do Sul / Facilities and equipments for physical activity practice in rural schools of Pelotas, Rio Grande do Sul

O objetivo do estudo foi descrever as instalações e equipamentos para atividade física nas escolas da zona rural de Pelotas, Rio Grande do Sul. Trata-se de um estudo transversal, de base escolar, realizado no ano de 2014, em todas as 26 escolas localizadas na zona rural da cidade de Pelotas. Foi utilizado um instrumento com questões relacionadas às políticas de Educação Física e avaliação das estruturas e materiais para a prática de atividade física, elaborado a partir do Physical Activity Resource Assessment (PARA), adaptado para o ambiente escolar. Observou-se que o professor e a disciplina de Educação Física estiveram presentes em todas as escolas. Mesmo com a maior frequência de estruturas como quadras esportivas (34,6% a 65,4%), pracinha/parquinhos (76,9%) e materiais como bolas (50,0% a 84,6%), cones (80,8%), cordas (88,5%), colchonetes (80,8%) e arcos (76,9%), as condições dos atributos foram regulares (7,7% a 46,2%) e ruins (11,5% a 50,0%). Poucas instituições ofereceram instalações e equipamentos em condições adequadas para a prática de atividade física. A ausência de ginásios, quadras cobertas e materiais em melhores condições chama a atenção para a necessidade de investimentos e intervenções nesses espaços

The aim of the study was to describe the facilities and equipment for physical activity practice in rural area schools of Pelotas, Rio Grande do Sul. The design was cross-sectional, school-based, carried out in all the 26 schools located in rural areas of Pelotas Southern, Brazil. We used a survey tool to assess the policies for Physical Education and evaluate the facilities and equipment/materials for physical activity. The instrument was based on the Physical Activity Resource Assessment (PARA), adapted for the school environment. We observed that curricular Physical Education and specific teachers were present in all schools. Despite the high number of facilities, such as courts and fields (34.6% to 65.4%), playgrounds (76.9%) and materials such as balls (50.0% to 84.6%), hoops (88.5%), exercise cones (80.8%) and mats (76.9%), the condition of the facilities and apparatus/equipment were fair (7.7% to 46.2%) or poor (11.5% to 50.0%). Few institutions have provided suitable facilities and equipment for physical activity. The absence of gymnasiums, covered courts and materials in better conditions draws attention to the need for investments and interventions in these spaces

Motor skills of children with autism spectrum disorder / Habilidades motoras de crianças com transtorno do espectro autista

Abstract The objective of this study is to describe variables of life habits associated with motor skills of children with autism spectrum disorder aged 8-10 years living in the city of Pelotas / RS. A questionnaire about lifestyle was applied and the Test of Gross Motor Development-2 (TGMD-2) was applied to assess motor skills. Independent T-test, ANOVA and Wilcoxon test were used to compare means. The study consisted of 49 individuals (42 males). The results indicate that the higher the level of ASD, the better the motor skills. Children making use of medications have greater deficits in motor skills. Higher scores on motor skills are associated with greater participation in physical education classes. Motor skills are strongly associated with independence in activities of the daily living, food, personal hygiene, dressing and bathing. The importance of the creation of PA programs aiming at improving the motor skills of this population was highlighted.

Resumo O objetivo deste estudo é descrever as variáveis de hábitos de vida associadas as habilidades motoras de crianças com transtorno do espectro autista de oito a 10 anos residentes na cidade de Pelotas/RS. Foi respondido um questionário sobre o estilo de vida e aplicado o Test of Gross Motor Development-2 (TGMD-2) para avaliação das habilidades motoras. Foi utilizado o teste T independente, ANOVA e teste de Wilcoxon para comparação de médias. Fizeram parte do estudo 49 indivíduos (42 do sexo masculino). Os resultados indicam que quando maior o grau de TEA, melhor são as habilidades motoras. As crianças que tomam medicamento apresentam maiores déficits nas habilidade motoras. Maiores escores nas habilidades motoras, estão associados a maior participação nas aulas de educação física. As habilidades motoras estão fortemente associadas a independência nas atividades de vida diária, alimentar-se, higiene pessoal, arrumar-se e banhar-se. Pode-se perceber a importância da criação de programas de AF visando a melhora nas habilidades motoras dessa população.

O efeito de um programa de atividades rítmicas na interação social e na coordenação motora em crianças com transtorno do espectro autista / The effect of a program of rhythmic activities on social interaction and motor coordination in children with autism spectrum disorder

Este estudo tem como objetivo verificar o efeito de um programa de atividades rítmicas na interação social e coordenação motora de crianças com transtorno do espectro autista (TEA). Realizou-se um delineamento experimental com nove crianças com TEA, entre cinco e 10 anos (cinco no grupo intervenção e quatro no grupo controle). Os dados foram obtidos por meio de três instrumentos aplicados antes e após intervenção. Os pais reportaram informações sobre o estilo de vida e interação social das crianças (CARS) e um teste de desenvolvimento motor grosso (TGMD-2) foi aplicado com as crianças. O grupo intervenção realizou 14 semanas, duas sessões por semana de 50 minutos cada, de atividades de dança. O grupo controle foi apenas acompanhado nas atividades diárias. Os dados foram comparados por meio da estatística não-paramétrica, com p < 0,05. O grupo interven-ção apresentou melhora nas habilidades motoras após as 14 semanas (p = 0,042; tamanho do efeito de 1,86). Em relação a interação social não foram observadas melhoras significativas em nenhum dos grupos. Conclui-se que 14 semanas de atividades rítmicas pode ser uma ferramenta eficaz para desenvolver as habilidades motoras de crianças com transtorno do espectro autista

The aim of the present study is to examine the effect of an intervention with rhythmic activities on the motor coordination and social interaction of children with autism spectrum disorder (ASD). The research is an experimental study. The sample consisted of children with ASD between the ages of five and 10 years. The data were obtained through three instruments applied before and after the intervention: two questionnaires, answered by parents or guardians: one about lifestyle and one about social interaction (CARS) and a gross motor development test (TGMD-2) performed with the children. No significant differences were found between groups after 14 weeks of activities. However, only the intervention group presented improvements from the first evaluation for the second evaluation (pre and post) (p = 0,042; effect size of 1.86) in motor skills. Regarding social interaction, no significant improvements were observed in either group. We conclude that 14 weeks of rhythmic activities can be an interesting tool to develop the motor skills of children with autism spectrum disorder

Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST).

Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.

Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome.

Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. The NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. In a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects.