The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients

Type 1 diabetes (T1D) is a multifactorial autoimmune disease, with strong genetic component. Several susceptibility loci contribute to genetic predisposition to T1D. One of these loci have been mapped to chromosome 1q42 in UK and US joined affected family data sets but needs to be replicated in other populations. In this study, we evaluated sixteen microsatellites located on 1q42 for linkage with T1D in 97 Russian affected sibling pairs. A 2.7-cm region of suggestive linkage to T1D between markers D1S1644 and D1S225 was found by multipoint linkage analysis. The peak of linkage was shown for D1S2847 (P = 0.0005). Transmission disequilibrium test showed significant undertransmission of the 156-bp allele of D1S2847 from parents to diabetic children (28 transmissions vs. 68 nontransmissions, P = 0.043) in Russian affected families. A preferential transmission from parents to diabetic offspring was also shown for the T(-25) and T1362 alleles of the C/T(-25) and C/T1362 dimorphisms, both located at the TAF5L gene, which is situated 103 kb from D1S2847. Together with the A/C744 TAF5L SNP, these markers share common T(-25)/A744/T1362 and C(-25)/C744/T1362 haplotypes associated with higher and lower risk of diabetes (Odds Ratio = 2.15 and 0.62, respectively). Our results suggest that the TAF5L gene, encoding TAF5L-like RNA polymerase II p300/CBP associated factor (PCAF)-associated factor, could represent the susceptibility gene for T1D on chromosome 1q42 in Russian affected patients.

Adapting the 'family wellbeing' empowerment program to the needs of remote indigenous school children

Objective: To adapt the Family Wellbeing empowerment program, which was initially designed to support adults to take greater control and responsibility for their decisions and lives, to the needs of Indigenous school children living in remote communities. Method. At the request of two schools in remote Indigenous communities in far north Queensland, a pilot personal development and empowerment program based on the adult Family Wellbeing principles was developed, conducted and evaluated in the schools. The main aims of the program were to build personal identity and to encourage students to recognise their future potential and be more aware of their place in the community and wider society. Results: Participation in the program resulted in significant social and emotional growth for the students. Outcomes described by participating students and teachers included increased analytical and reflective skills, greater ability to think for oneself and set goals, less teasing and bullying in the school environment, and an enhanced sense of identity, friendship and,social relatedness'. Conclusion: This pilot implementation of the Family Wellbeing Program adapted for schools demonstrated the program's potential to enhance Indigenous young people's personal growth and development. Challenges remain in increasing parental/ family involvement and ensuring the program's sustainability and transferability. The team has been working with relevant stakeholders to further develop and package the School-based Family Wellbeing program for Education Queensland's New Basics curriculum framework.

Desperately seeking donors: The 'saviour siblings' decision in quintaville v human fertilisation embryology authority (UK)

The recent House of Lords decision in Quintavalle v Human Fertilisation and Embryology Authority has raised difficult and complex issues regarding the extent to which embryo selection and reproductive technology can be used as a means of rectifying genetic disorders and treating critically ill children. This comment outlines the facts of Quintavalle and explores how the House of Lords approached the legal, ethical and policy issues that arose out of the Human Fertilisation and Embryology Authority's (UK) decision to allow reproductive and embryo technology to be used to produce a 'saviour sibling' whose tissue could be used to save the life of a critically ill child. Particular attention will be given to the implications of the decision in Quintavalle for Australian family and medical law and policy. As part of this focus, the comment explores the current Australian legislative and policy framework regarding the use of genetic and reproductive technology as a mechanism through which to assist critically ill siblings. It is argued that the present Australian framework would appear to impose significant limits on the medical uses of genetic technology and, in this context, would seem to reflect many of the principles that were articulated by the House of Lords in Quintavalle.

Genomewide Linkage Scan of 409 European-ancestry and African American Families with Schizophrenia: Suggestive Evidence of Linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the Combined Sample

We report the clinical characteristics of a schizophrenia sample of 409 pedigrees-263 of European ancestry ( EA) and 146 of African American ancestry ( AA)-together with the results of a genome scan ( with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia ( SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs ( ASPs) ( 279 EA and 124 AA) and 100 all-possible half-sibling ASPs ( 15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 ( empirical Z likelihood-ratio score [ Z(lr)] threshold >= 2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z(lr) scores >= 2.0 in 8p were observed from 30.7 cM to 61.7 cM ( Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z(lr) of 3.25 ( equivalent Kong-Cox LOD of 2.30) near D8S1771 ( at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 ( NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families.

Response and function of cutaneous mucosal and serum antibodies in barramundi (Lates calcarifer) acclimated in seawater and freshwater

Mucosal and serum antibody responses were studied in sibling barramundi (Lates calcarifer) acclimated in either seawater or freshwater following vaccination by intraperitoneal injection or direct immersion in an inactivated Streptococcus iniae vaccine. As expected, route of vaccination had a marked effect on immune response, with direct immersion resulting in low serum antibody levels against S. iniae by ELISA detected 21 days post vaccination at 26 degrees C, whilst a significant response was detected in mucus. A strong specific antibody response was detected in both mucus and serum 21 days following intraperitoneal injection. Fish acclimated in seawater prior to vaccination showed a markedly higher specific mucosal antibody response than sibling fish acclimated in freshwater, regardless of the route of vaccination, whilst the serum antibody response was not affected by salinity. Both mucosal and serum antibodies from fish in seawater and freshwater were capable of binding antigen at salinities similar to full strength seawater in a modified ELISA assay. These results indicate that this euryhaline fish species is riot only able to mount significant specific antibody response in cutaneous mucus, but that these antibodies will function in the marine environment. (c) 2005 Elsevier Ltd. All rights reserved.

Mental playmates: Siblings, executive functioning and theory of mind

This study assessed the theory of mind (ToM) and executive functioning (EF) abilities of 124 typically developing preschool children aged 3 to 5 years in relation to whether or not they had a child-aged sibling (i.e. a child aged 1 to 12 years) at home with whom to play and converse. On a ToM battery that included tests of false belief, appearance-reality (AR) and pretend representation, children who had at least 1 child-aged sibling scored significantly higher than both only children and those whose only siblings were infants or adults. The numbers of child-aged siblings in preschoolers' families positively predicted their scores on both a ToM battery (4 tasks) and an EF battery (2 tasks), and these associations remained significant with language ability partialled out. Results of a hierarchical multiple regression analysis revealed that independent contributions to individual differences in ToM were made by language ability, EF skill and having a child-aged sibling. However, even though some conditions for mediation were met, there was no statistically reliable evidence that EF skills mediated the advantage of presence of child-aged siblings for ToM performance. While consistent with the theory that distinctively childish interaction among siblings accelerates the growth of both TOM and EF capacities, alternative evidence and alternative theoretical interpretations for the findings were also considered.

HLA and Genomewide Allele Sharing in Dizygotic Twins

Gametic selection during fertilization or the effects of specific genotypes on the viability of embryos may cause a skewed transmission of chromosomes to surviving offspring. A recent analysis of transmission distortion in humans reported significant excess sharing among full siblings. Dizygotic (DZ) twin pairs are a special case of the simultaneous survival of two genotypes, and there have been reports of DZ pairs with excess allele sharing around the HLA locus, a candidate locus for embryo survival. We performed an allele-sharing study of 1,592 DZ twin pairs from two independent Australian cohorts, of which 1,561 pairs were informative for linkage on chromosome 6. We also analyzed allele sharing in 336 DZ twin pairs from The Netherlands. We found no evidence of excess allele sharing, either at the HLA locus or in the rest of the genome. In contrast, we found evidence of a small but significant (P = .003 for the Australian sample) genomewide deficit in the proportion of two alleles shared identical by descent among DZ twin pairs. We reconciled conflicting evidence in the literature for excess genomewide allele sharing by performing a simulation study that shows how undetected genotyping errors can lead to an apparent deficit or excess of allele sharing among sibling pairs, dependent on whether parental genotypes are known. Our results imply that gene-mapping studies based on affected sibling pairs that include DZ pairs will not suffer from false-positive results due to loci involved in embryo survival.

Genetic and Cultural Transmission of Smoking Initiation: An Extended Twin Kinship Model

Background Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. Results Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype–environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age × gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. Conclusions This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.

RI MELHOR QUEM RI NA SALA DE AULA? UM ESTUDO SOBRE A PERCEPÇÃO DO RISO POR ALUNOS E PROFESSORES

Pouco discutido no âmbito pedagógico, o riso tem sido historicamente dissociado da escola, motivo pelo qual este trabalho tem como objetivo identificar como ele é percebido em sala de aula. A proposta é entender como o riso e sua função social são vistos por professores e alunos. Para isso, foi selecionada uma escola pública estadual na cidade de São Bernardo do Campo, SP. Lá são atendidos adolescentes que frequentam as aulas no Ensino Fundamental II e Médio. A pesquisa foi realizada com estudantes que estão terminando o Ensino Fundamental. Cem alunos responderam a questionários estruturados, compostos por itens de perfil e questões abertas. O mesmo foi feito com dezenove professores da referida escola, entretanto as questões para cada público sofreram variações. Como categoria analítica, foi utilizado o conceito de representação da Teoria de Representações Sociais, de forma instrumental. Os resultados obtidos indicam que os sujeitos observam um conceito híbrido presente na composição do objeto em análise, de forma que o avaliam ora como um elemento nocivo, ora como um recurso estimulante a aulas mais agradáveis. Foi constatado que os alunos riem na escola, mas é expressivo o fato de não associar essa ação ao contexto escolar. Os estudantes reforçam que o riso na sala de aula atrapalha a concentração, embora sejam conscientes de que essa constatação é circunstancial. Em contrapartida, mais de 60 alunos afirmaram já terem aprendido algo com a interferência do riso, sendo o professor o principal protagonista nesses momentos. Com relação aos docentes, a maioria afirmou que o riso pode ajudar o aluno a aprender algo, mas compreendem que a maior contribuição desse elemento na sala de aula é a de proporcionar um ambiente mais agradável. As duas desvantagens mais listadas pelos professores sobre o riso na sala de aula é a de que ele pode provocar a falta de atenção do aluno e também momentos de bullying entre os colegas de sala. Acredita-se que a associação do ambiente escolar com manifestações de seriedade justifique as frequentes referências feitas ao seu aspecto negativo, retratado na pesquisa pelos sujeitos. Mais da metade dos docentes analisa que o riso pode servir como instrumento pedagógico, entretanto os alunos afirmam que isso depende do professor e do momento. A pesquisa deixou evidente que o aspecto negativo do riso impede que este objeto seja mais bem aceito na escola, de forma que a percepção que os sujeitos fazem sobre o riso passa a interferir na relação que estabelecem com ele em sala de aula.

EXPERIÊNCIAS COM CÍRCULOS RESTAURATIVOS EM UMA ESCOLA PÚBLICA NO ESTADO DO AMAZONAS

Este estudo aborda o problema da violência na escola. A escolha do tema deveu-se ao fato de a violência nas escolas públicas brasileiras ter sido assunto diário na mídia nos últimos anos, com consequências devastadoras que afetam a formação da cidadania, principalmente quando crianças e adolescentes são envolvidos. Utilizou-se o método de pesquisa qualitativa por esperar compreender e descrever as experiências dos círculos restaurativos cujos objetivos são: 1) Avaliar a percepção de segurança de alunos e servidores de uma escola pública do estado do Amazonas e conhecer os tipos de violência com as quais se confrontam; 2) identificar e descrever o perfil socioeconômico das famílias dos participantes dos círculos restaurativos; e 3) descrever as experiências com os círculos restaurativos. Participaram da pesquisa 300 indivíduos de uma escola pública do Estado do Amazonas, distribuídos em 248 alunos, 49 servidores, sendo 148 do sexo masculino (49 por cento e 152 (51 por cento do sexo feminino, com idade média de (18,82) anos. Destes 210 (70 por cento ) solteiros, 33 (11 por cento ) casados, e mais 57 (19 por cento ) com outras situações conjugais. A escolaridade variava entre ensino fundamental incompleto (4 por cento ), ensino médio incompleto (83,9 por cento ) e mestrado completo (4 por cento ). Para coleta dos dados, utilizou-se um questionário com 11 itens, a escala sobre violência na escola com 8 itens e as técnicas dos círculos restaurativos. Trata-se, portanto, de uma pesquisa participante por ter utilizado, para coleta dados, as técnicas de observação participante e entrevista semiestruturada. Quanto aos resultados, observou-se uma correlação moderada e significativa entre as variáveis, percepção de segurança na sala de aula com a da escola (r=0,612; p<0,01). Conclui-se que existe evidência de violência nos diversos contextos estudados, sendo que a ocorrência de violência informada é maior nos arredores da escola: 127 (46,4 por cento ). Dos participantes, 160 (58 por cento ) sentem-se seguros. Entretanto, um percentual considerável, 94 (34,3 por cento ) responderam que não se sentem muito seguros. Quanto ao perfil socioeconômico, detectaram-se inúmeros problemas de natureza socioeconômicos e psicossociais, dentre os quais, os conflitos familiares, pobreza, ausência dos serviços públicos básicos ou dificuldades no acesso, o desemprego, analfabetismo, negligência contra crianças e adolescentes entre outros. Em relação às experiências com os círculos restaurativos, foram mediados quatro conflitos e instaurados os pré-círculos e os círculos: dois em decorrência do bullying praticado por meio de mensagens de celular, uma desavença entre dois alunos e um desentendimento entre professor e aluno. Todos os casos tiveram resultados satisfatórios.

Biochemical correlates of cognition: exploring the relationships between blood, brain and behaviour

This multi-modal investigation aimed to refine analytic tools including proton magnetic resonance spectroscopy (1H-MRS) and fatty acid gas chromatography-mass spectrometry (GC-MS) analysis, for use with adult and paediatric populations, to investigate potential biochemical underpinnings of cognition (Chapter 1). Essential fatty acids (EFAs) are vital for the normal development and function of neural cells. There is increasing evidence of behavioural impairments arising from dietary deprivation of EFAs and their long-chain fatty acid metabolites (Chapter 2). Paediatric liver disease was used as a deficiency model to examine the relationships between EFA status and cognitive outcomes. Age-appropriate Wechsler assessments measured Full-scale IQ (FSIQ) and Information Processing Speed (IPS) in clinical and healthy cohorts; GC-MS quantified surrogate markers of EFA status in erythrocyte membranes; and 1H-MRS quantified neurometabolite markers of neuronal viability and function in cortical tissue (Chapter 3). Post-transplant children with early-onset liver disease demonstrated specific deficits in IPS compared to age-matched acute liver failure transplant patients and sibling controls, suggesting that the time-course of the illness is a key factor (Chapter 4). No signs of EFA deficiency were observed in the clinical cohort, suggesting that EFA metabolism was not significantly impacted by liver disease. A strong, negative correlation was observed between omega-6 fatty acids and FSIQ, independent of disease diagnosis (Chapter 5). In a study of healthy adults, effect sizes for the relationship between 1H-MRS- detectable neurometabolites and cognition fell within the range of previous work, but were not statistically significant. Based on these findings, recommendations are made emphasising the need for hypothesis-driven enquiry and greater subtlety of data analysis (Chapter 6). Consistency of metabolite values between paediatric clinical cohorts and controls indicate normal neurodevelopment, but the lack of normative, age-matched data makes it difficult to assess the true strength of liver disease-associated metabolite changes (Chapter 7). Converging methods offer a challenging but promising and novel approach to exploring brain-behaviour relationships from micro- to macroscopic levels of analysis (Chapter 8).

Patients and doctors working together in partnership:Birch v UCL Hospital NHS Foundation Trust [2008] EWHC 2237 (QB)

Of the myriad of pressing topics current in medical law and ethics, the issue of informed consent appears to be the ‘plainer sibling’. The decision by Cranston J in Birch v UCL Hospital NHS Foundation Trust in 2008 has brought into sharp relief that which many commentators already held to be true. Far from being the ‘plainer sibling’ when weighed against other prominent issues in medical law and ethics, the doctrine of informed consent, is one of the most significant principles to emerge in recent years.

Impact of peanut allergy on quality of life, stress and anxiety in the family

Background: Peanut allergy (PA) is known to impact on quality of life (QoL) of the sufferer, but little research has focused on all family members. We therefore sought to establish the impact of PA on QoL and reported anxiety of children with clinically confirmed PA, their parents and older siblings. Methods: Forty-six families, who had a child with PA, completed QoL (PedsQLTM or WHOQOL-BREF), anxiety (SCAS or STAI) and perceived stress (PSS) scales. PA children completed a PA specific QoL questionnaire (Pediatr Allergy Immunol 2003;14:378). Parents and sibling also completed QoL proxy questionnaires for the PA child (PedsQLTM, Pediatr Allergy Immunol 2003;14:378). Results: Mothers rated their own psychological (P < 0.01) and physical (P < 0.05) QoL significantly worse than fathers rated theirs, and had higher scores than fathers for anxiety (P < 0.05) and stress (P < 0.001). Children with PA had significantly poorer physical health-related QoL (P < 0.05), QoL within school (P < 0.01) and general QoL (P < 0.05) than their siblings did, and greater separation anxiety (P < 0.05). The majority of differences were between girls with PA and female siblings. Mothers felt that there was a greater impact on QoL for their PA child, compared with that reported by siblings, fathers or the PA children themselves (P < 0.01). Conclusions: Mothers report that they have significantly poorer QoL and suffer more anxiety and stress than fathers do; this inter-parental difference may be an important feature of family stress caused by PA. Siblings have a similar view of how QoL affects the PA child as the PA child does, while mothers may possibly overestimate this impact.

Understanding the cycle of violence: An examination of bully and victim social roles in early childhood

The purpose of this study was to assess the prevalence of bullying and victimization in a metropolitan area. A cross-sectional study with kindergarten (n = 127) and first grade (n = 126) children was conducted in two Miami-Dade County Public Schools and three private schools in the same area. Bullying and victimization behavior and social acceptance were assessed through peer nomination and the mental health outcomes of depression and anxiety were assessed through children's self-report. Teachers and parents also completed a social behavior scale for each child. Three areas of analyses were conducted pertaining to membership classification of social roles and the social acceptance and mental health outcomes associated with those roles, reporter agreement within the social roles, and the psychometric properties of the Childhood Social Behavior Scale. Results showed an overall negative pattern of adjustment for children identified as a member of any of the negative social roles. Also, the results support a new analytic approach to the investigation of social roles. The implication of these findings for early identification, social policy, and effective prevention strategies are discussed. ^