992 resultados para Case-parent trios


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Statistical approaches to evaluate higher order SNP-SNP and SNP-environment interactions are critical in genetic association studies, as susceptibility to complex disease is likely to be related to the interaction of multiple SNPs and environmental factors. Logic regression (Kooperberg et al., 2001; Ruczinski et al., 2003) is one such approach, where interactions between SNPs and environmental variables are assessed in a regression framework, and interactions become part of the model search space. In this manuscript we extend the logic regression methodology, originally developed for cohort and case-control studies, for studies of trios with affected probands. Trio logic regression accounts for the linkage disequilibrium (LD) structure in the genotype data, and accommodates missing genotypes via haplotype-based imputation. We also derive an efficient algorithm to simulate case-parent trios where genetic risk is determined via epistatic interactions.

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La leucémie lymphoblastique aigüe (LLA) est une maladie génétique complexe. Malgré que cette maladie hématologique soit le cancer pédiatrique le plus fréquent, ses causes demeurent inconnues. Des études antérieures ont démontrées que le risque à la LLA chez l’enfant pourrait être influencé par des gènes agissant dans le métabolisme des xénobiotiques, dans le maintient de l’intégrité génomique et dans la réponse au stress oxydatif, ainsi que par des facteurs environnementaux. Au cours de mes études doctorales, j’ai tenté de disséquer davantage les bases génétiques de la LLA de l’enfant en postulant que la susceptibilité à cette maladie serait modulée, au moins en partie, par des variants génétiques agissant dans deux voies biologiques fondamentales : le point de contrôle G1/S du cycle cellulaire et la réparation des cassures double-brin de l’ADN. En utilisant une approche unique reposant sur l’analyse d’une cohorte cas-contrôles jumelée à une cohorte de trios enfants-parents, j’ai effectué une étude d’association de type gènes/voies biologiques candidats. Ainsi, j’ai évaluer le rôle de variants provenant de la séquence promotrice de 12 gènes du cycle cellulaire et de 7 gènes de la voie de réparation de l’ADN, dans la susceptibilité à la LLA. De tels polymorphismes dans la région promotrice (pSNPs) pourraient perturber la liaison de facteurs de transcription et mener à des différences dans les niveaux d’expression des gènes pouvant influencer le risque à la maladie. En combinant différentes méthodes analytiques, j’ai évalué le rôle de différents mécanismes génétiques dans le développement de la LLA chez l’enfant. J’ai tout d’abord étudié les associations avec gènes/variants indépendants, et des essaies fonctionnels ont été effectués afin d’évaluer l’impact des pSNPs sur la liaison de facteurs de transcription et l’activité promotrice allèle-spécifique. Ces analyses ont mené à quatre publications. Il est peu probable que ces gènes de susceptibilité agissent seuls; j’ai donc utilisé une approche intégrative afin d’explorer la possibilité que plusieurs variants d’une même voie biologique ou de voies connexes puissent moduler le risque de la maladie; ces travaux ont été soumis pour publication. En outre, le développement précoce de la LLA, voir même in utero, suggère que les parents, et plus particulièrement la mère, pourraient jouer un rôle important dans le développement de cette maladie chez l’enfant. Dans une étude par simulations, j’ai évalué la performance des méthodes d’analyse existantes de détecter des effets fœto-maternels sous un design hybride trios/cas-contrôles. J’ai également investigué l’impact des effets génétiques agissant via la mère sur la susceptibilité à la LLA. Cette étude, récemment publiée, fût la première à démontrer que le risque de la leucémie chez l’enfant peut être modulé par le génotype de sa mère. En conclusions, mes études doctorales ont permis d’identifier des nouveaux gènes de susceptibilité pour la LLA pédiatrique et de mettre en évidence le rôle du cycle cellulaire et de la voie de la réparation de l’ADN dans la leucémogenèse. À terme, ces travaux permettront de mieux comprendre les bases génétiques de la LLA, et conduiront au développement d’outils cliniques qui amélioreront la détection, le diagnostique et le traitement de la leucémie chez l’enfant.

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Contexte - La prévalence de la maladie de Crohn (MC), une maladie inflammatoire chronique du tube digestif, chez les enfants canadiens se situe parmi les plus élevées au monde. Les interactions entre les réponses immunes innées et acquises aux microbes de l'hôte pourraient être à la base de la transition de l’inflammation physiologique à une inflammation pathologique. Le leucotriène B4 (LTB4) est un modulateur clé de l'inflammation et a été associé à la MC. Nous avons postulé que les principaux gènes impliqués dans la voie métabolique du LTB4 pourrait conférer une susceptibilité accrue à l'apparition précoce de la MC. Dans cette étude, nous avons exploré les associations potentielles entre les variantes de l'ADN des gènes ALOX5 et CYP4F2 et la survenue précoce de la MC. Nous avons également examiné si les gènes sélectionnés montraient des effets parent-d'origine, influençaient les phénotypes cliniques de la MC et s'il existait des interactions gène-gène qui modifieraient la susceptibilité à développer la MC chez l’enfant. Méthodes – Dans le cadre d’une étude de cas-parents et de cas-témoins, des cas confirmés, leurs parents et des contrôles ont été recrutés à partir de trois cliniques de gastro-entérologie à travers le Canada. Les associations entre les polymorphismes de remplacement d'un nucléotide simple (SNP) dans les gènes CYP4F2 et ALOX5 ont été examinées. Les associations allélique et génotypiques ont été examinées à partir d’une analyse du génotype conditionnel à la parenté (CPG) pour le résultats cas-parents et à l’aide de table de contingence et de régression logistique pour les données de cas-contrôles. Les interactions gène-gène ont été explorées à l'aide de méthodes de réduction multi-factorielles de dimensionnalité (MDR). Résultats – L’étude de cas-parents a été menée sur 160 trios. L’analyse CPG pour 14 tag-SNP (10 dans la CYP4F2 et 4 dans le gène ALOX5) a révélé la présence d’associations alléliques ou génotypique significatives entre 3 tag-SNP dans le gène CYP4F2 (rs1272, p = 0,04, rs3093158, p = 0.00003, et rs3093145, p = 0,02). Aucune association avec les SNPs de ALOX5 n’a pu être démontrée. L’analyse de l’haplotype de CYP4F2 a montré d'importantes associations avec la MC (test omnibus p = 0,035). Deux haplotypes (GAGTTCGTAA, p = 0,05; GGCCTCGTCG, p = 0,001) montraient des signes d'association avec la MC. Aucun effet parent-d'origine n’a été observé. Les tentatives de réplication pour trois SNPs du gene CYP4F2 dans l'étude cas-témoins comportant 225 cas de MC et 330 contrôles suggèrent l’association dans un de ceux-ci (rs3093158, valeur non-corrigée de p du test unilatéral = 0,03 ; valeur corrigée de p = 0.09). La combinaison des ces deux études a révélé des interactions significatives entre les gènes CYP4F2, ALOX et NOD2. Nous n’avons pu mettre en évidence aucune interaction gène-sexe, de même qu’aucun gène associé aux phénotypes cliniques de la MC n’a pu être identifié. Conclusions - Notre étude suggère que la CYP4F2, un membre clé de la voie métabolique LTB4 est un gène candidat potentiel pour MC. Nous avons également pu mettre en évidence que les interactions entre les gènes de l'immunité adaptative (CYP4F2 et ALOX5) et les gènes de l'immunité innée (NOD2) modifient les risques de MC chez les enfants. D'autres études sur des cohortes plus importantes sont nécessaires pour confirmer ces conclusions.

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BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.

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Towards the last decade of the last millennium, Indigenous knowledge has been central to scholarly debates relating to decolonising knowledge on a global level. Much of these debates were advanced by Indigenous scholars in colonised countries particularly Australia, New Zealand, Canada and the United States. Indigenous scholars argue for the location of Indigenous knowledge as the epistemological standpoint (Battiste, Bell and Findlay, 2002; Kai’a, 2005; Nakata 2002, 2007) for intellectual engagements and methodology for resisting colonial constructions of the colonised other (Rigney, 1997; Smith, 1999, 2005). However, the challenge to engage Indigenous knowledge to inform research and educational processes, in many respects, is still a contested debate in western-oriented universities and institutions of higher education. The place of Indigenous knowledge in Australian secondary and primary schools remains vague, while efforts to embed Indigenous perspectives in the curriculum continue to be made by both government and private educational providers. Educational funding for Indigenous education continues to operate from a ‘deficiency’ model, whereby educational outcomes are often measured against set criteria, reflecting a pass/fail structure, than a more comprehensive investigation of educational outcomes and quality of learning experiences. Teacher knowledge, effective parental and community engagement into students’ learning and students’ experiences of schooling continue to be secondary to students’ final results. This paper presents preliminary findings of Parent School Partnership Initiative (PSPI) project conducted by the Oodgeroo Unit at the Queensland University of Technology in partnerships with the Aboriginal and Torres Strait Islander Education Focus Group for the Caboolture Shire, in South East Queensland. The state government sponsored initiative was to examine factors that promote and enhance parent/school engagement with their students’ schooling, and to contribute to Aboriginal and Torres Strait Islander students’ learning and completion of secondary schooling within the participating schools in a more holistic way. We present four school case studies and discuss some of the early findings. We conclude by arguing the importance of the recognition of Indigenous knowledge and its place in enhancing parent – schools partnerships.

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This paper investigates a strategy for guiding school-based active travel intervention. School-based active travel programs address the travel behaviors and perceptions of small target populations (i.e., at individual schools) so they can encourage people to walk or bike. Thus, planners need to know as much as possible about the behaviors and perceptions of their target populations. However, existing strategies for modeling travel behavior and segmenting audiences typically work with larger populations and may not capture the attitudinal diversity of smaller groups. This case study used Q technique to identify salient travel-related attitude types among parents at an elementary school in Denver, Colorado; 161 parents presented their perspectives about school travel by rank-ordering 36 statements from strongly disagree to strongly agree in a normalized distribution, single centered around no opinion. Thirty-nine respondents' cases were selected for case-wise cluster analysis in SPSS according to criteria that made them most likely to walk: proximity to school, grade, and bus service. Analysis revealed five core perspectives that were then correlated with the larger respondent pool: optimistic walkers, fair-weather walkers, drivers of necessity, determined drivers, and fence sitters. Core perspectives are presented—characterized by parents' opinions, personal characteristics, and reported travel behaviors—and recommendations are made for possible intervention approaches. The study concludes that Q technique provides a fine-grained assessment of travel behavior for small populations, which would benefit small-scale behavioral interventions

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Parent-child sexual health communication can be beneficial. Many factors affect such communication in Chinese immigrant families. This qualitative study explored the influences of acculturation, parenting, and parental participation in the Raising Sexually Healthy Children Program (RSHC) on such communication. With a hermeneutic framework, the purpose was to develop understanding based on the topic, context, and researcher interpretations. Twelve interviews elicited data from six parent-child dyads, three from the RSHC. Analysis involved coding processes; data were compared repeatedly and organized into themes. Perceived personality differences between generations were confounded with cultural communicative differences. Parents used implicitness observed in Chinese culture to establish "open" communication; children expected explicitness observed in Western culture. Post- RSHC, parents perceived themselves as more open to talking about sex; children did not perceive such parental changes. Future research should include joint interviews and longitudinal program evaluation. Future practice should focus on cross-cultural communication and involving children in RSHC.

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International research has consistently found that good staff-parent relationships in early childhood centers benefit children, staff, and parents. Given these findings, the Australian federal government's Quality Improvement and Accreditation Scheme (QIAS) requires centers to involve parents in their programs. However, international research has also found that early childhood staff are anxious about their relationships with parents. This article describes a study in which early childhood staff in Australia were asked about their experiences with parent involvement. It draws on those interviews to consider communication strategies to create equitable relationships between staff and parents.

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Previous research has demonstrated the importance of the qualities of the teacher-child relationship on children’s development. Close teacher-child relationships are especially important for children at risk. Positive relationships have been shown to have beneficial effects on children’s social and academic development (Birch & Ladd, 1997; Pianta & Stuhlman, 2004). Children with language difficulties are likely to face increased risks with regard to long term social and academic outcomes. The purpose of the current research was to gain greater understanding of the qualities of teacher-child relationships for young children with parent reported language concerns. The research analyses completed for this thesis involved the use of data from the public-access database of Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC). LSAC is a longitudinal study involving a nationally representative sample of 10,000 Australian children. Data are being collected biennially from 2004 (Wave 1 data collection) until 2010 (Wave 4 data collection). LSAC has a cross-sequential research design involving two cohorts, an infant cohort (0-1 year at age of recruitment) and a kindergarten cohort (4-5 years at age of recruitment). Two studies are reported in this thesis using data for the LSAC Kindergarten Cohort which had 4983 child participants at recruitment. Study 1 used Wave 1 data to identify the differences between teacher-child relationship qualities for children with parent reported language concerns and their peers. Children identified by parents for whom concerns were held about their receptive and expressive language, as measured by items from the Parents’ Evaluation of Developmental Status (PEDS) (Glascoe, 2000) were the target (at risk) group in the study (n = 210). A matched case control group of peers (n = 210), matched on the child characteristics of sex, age, cultural and linguistic differences (CALD), and socio-economic positioning (SEP), were the comparison group for this analysis. Teacher-child relationship quality was measured by teacher reports on the Closeness and Conflict scales from the short version of the Student-Teacher Relationship Scale (STRS) (Pianta, 2001). There were statistically significant differences in the levels of closeness and conflict between the two groups. The target group had relationships with their teachers that had lower levels of closeness and higher levels of conflict than the control group. Study 2 reports analyses that examined the stability of the qualities of the teacher-child relationships at Wave 1 (4-5 years) and the qualities of the teacher-child relationships at Wave 2 (6-7 years). This time frame crosses the period of the children’s transition to school. The study examined whether early patterns in the qualities of the teacher-child relationship for children with parent reported language concerns at Wave 1 predicted the qualities of the teacher-child relationship outcomes in the early years of formal school. The sample for this study consisted of the group of children identified with PEDS language concerns at Wave 1 who also had teacher report data at Wave 2 (n = 145). Teacher-child relationship quality at Wave 1 and Wave 2 was again measured by the STRS scales of Closeness and Conflict. Results from multiple regression models indicated that teacher-child relationship quality at Wave 1 significantly contributed to the prediction of the quality of the teacher-child relationship at Wave 2, beyond other predictor variables included in the regression models. Specifically, Wave 1 STRS Closeness scores were the most significant predictor for STRS Closeness scores at Wave 2, while Wave 1 STRS Conflict scores were the only significant predictor for Wave 2 STRS Conflict outcomes. These results indicate that the qualities of the teacher-child relationship experienced prior to school by children with parent reported language concerns remained stable across transitions into formal schooling at which time the child had a different teacher. The results of these studies provide valuable insight into the nature of teacher-child relationship quality for young children with parent reported language concerns. These children experienced teacher-child relationships of a lower quality when compared with peers and, additionally, the qualities of these relationships prior to formal schooling were predictive of the qualities of the relationships in the early years of formal schooling. This raises concerns, given the increased risks of poorer social and academic outcomes already faced by children with language difficulties, that these early teacher-child relationships have an impact on future teacher-child relationships. Results of these studies are discussed with these considerations in mind and also discussed in terms of the implications for educational theory, policy and practice.

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Objective: The aim of the present study was to investigate whether parent report of family resilience predicted children’s disaster-induced post-traumatic stress disorder (PTSD) and general emotional symptoms, independent of a broad range of variables including event-related factors, previous child mental illness and social connectedness. ---------- Methods: A total of 568 children (mean age = 10.2 years, SD = 1.3) who attended public primary schools, were screened 3 months after Cyclone Larry devastated the Innisfail region of North Queensland. Measures included parent report on the Family Resilience Measure and Strengths and Difficulties Questionnaire (SDQ)–emotional subscale and child report on the PTSD Reaction Index, measures of event exposure and social connectedness. ---------- Results: Sixty-four students (11.3%) were in the severe–very severe PTSD category and 53 families (28.6%) scored in the poor family resilience range. A lower family resilience score was associated with child emotional problems on the SDQ and longer duration of previous child mental health difficulties, but not disaster-induced child PTSD or child threat perception on either bivariate analysis, or as a main or moderator variable on multivariate analysis (main effect: adjusted odds ratio (ORadj) = 0.57, 95% confidence interval (CI) = 0.13–2.44). Similarly, previous mental illness was not a significant predictor of child PTSD in the multivariate model (ORadj = 0.75, 95%CI = 0.16–3.61). ---------- Conclusion: In this post-disaster sample children with existing mental health problems and those of low-resilience families were not at elevated risk of PTSD. The possibility that the aetiological model of disaster-induced child PTSD may differ from usual child and adolescent conceptualizations is discussed.

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Over the past ten years, Queensland has experienced a period of significant education reform including the introduction in 2007 of a Preparatory Year of schooling for children aged five years. Recently, the development of a new Australian Curriculum represents a further curriculum reform impacting on Prep in Queensland, as Prep is, for the first time, part of the broader school curriculum and specific content is to be taught. The place of play as a context for learning is a current topic of interest during this period of change, and this thesis argues that consideration of parent views with regard to play and its place in Prep is timely and strategic. This thesis reports the findings of a research project that used case study to elicit and describe the ways in which eight parents viewed play in Prep. Analysis of parent interviews identified four themes: (1) parents interpreting play in Prep, (2) play and learning in Prep, (3) the Prep teacher's role in play and (4) parent tensions regarding play and learning in Prep. The results of the study suggest that variation exists in the ways in which parents may view and interpret play in Prep in Queensland. Analysis of the data further suggests that these interpretations may reflect parents' understanding of the Prep program and their attitudes to play and school generally. This thesis suggests that parents may spend limited time in Prep classrooms, which may impact on their understanding of play as a theoretical tenet in Prep and may highlight limitations in parent-teacher partnerships. The results of this study suggest that more attention be given to engaging parents in early childhood programs and eliciting their views on these programs. The results also suggest the importance of early childhood teachers advocating on behalf of play with their teaching colleagues, school leaders and policy makers.

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The accumulated evidence from more than four decades of education research strongly suggests that parent involvement in schools carries significant benefits for students as well as for the success of schools (e.g., Henderson & Mapp, 2002). Governments in Australia and overseas have supported parent involvement in schools with a range of initiatives while parent groups have indicated a strong desire for expanded school roles that include participation in formal educational processes namely curriculum, pedagogy, and assessment. Research has also signalled the need for teachers to engage parents rather than adopt traditional parent-school involvement practices so that parents can participate as joint educators in their children's schooling alongside teachers (Pushor, 2001). Actually improving the quality of contact and relationships between parents and teachers to enable engagement however remains problematic. Coteaching and cogenerative dialoguing originally emerged as an innovative approach in the context of teaching secondary school science. Coteaching brings together the collective expertise of several individuals to expand learning opportunities for students while cogenerative dialogues refer to sessions in which participants talk, listen, and learn from one another about the process (Roth & Tobin, 2002a). Coteaching and cogenerative dialoguing reportedly benefits students academically and socially while rewarding educators professionally and emotionally through the support and collaboration they receive from fellow coteachers. These benefits ensue because coteaching theoretically positions teachers at one another's elbows, providing new and different understandings about teaching based on first-hand perspectives and shared goals for assisting students to learn. This thesis proposes that coteaching and cogenerative dialoguing may provide a vehicle for improving quality of contact and relationships between parents and teachers. To investigate coteaching and cogenerative dialoguing as a parent-teacher engagement mechanism, interpretive ethnographic case study research was conducted involving two parents and a secondary school teacher. Sociological ideas, namely Bourdieu's (1977) fields, habitus, and capitals, together with multiple dialectical concepts such as agency|structure (Sewell, 1992) and agency|passivity (Roth, 2007b, 2010) were assembled into a conceptual framework to examine parent-teacher relationships by describing and explaining cultural production and identity construction throughout the case study. Video and audio recordings of cogenerative dialogues and cotaught lessons comprised the chief data sources. Data were analysed using qualitative techniques such as discourse and conversation analysis to identify patterns and contradictions (Roth & Tobin, 2002a). The use of quality criteria detailed by Guba and Lincoln (2005) gives credence to the way in which ethical considerations infused the planning and conduct of this research. From the processes of data collection and analyses, three broad assertions were proffered. The findings highlight the significance of using multiple coordinated dialectical concepts for analysing the affordances and challenges of coteaching and cogenerative dialogues that include parents and teachers. Adopting the principles and purposes of coteaching and cogenerative dialoguing promoted trusting respectful relationships that generated an equitable culture. The simultaneous processes and tensions between logistics and ethics (i.e., the logistics|ethics dialectic) were proposed as a new way to conceptualise how power was redistributed among the participants. Knowledge of positive emotional energy and ongoing capital exchange conceived dialectically as the reciprocal interaction among cultural, social, and symbolic capitals (i.e., the dialectical relationship of cultural|social|symbolic capital) showed how coteaching and cogenerative dialoguing facilitated mutual understandings, joint decision-making, and group solidarity. The notion of passivity as the dialectical partner of agency explained how traditional roles and responsibilities were reconfigured and individual and collective agency expanded. Complexities that surfaced when implementing the coteaching and cogenerative dialoguing approach were outweighed by the multiple benefits that accrued for all involved. These benefits included the development of community-relevant and culturally-significant curricula that increased student agency and learning outcomes, heightened parent self-efficacy for participating in and contributing to formal educational processes, and enhanced teacher professionalism. This case study contributes to existing theory, knowledge and practice, and methodology in the research areas of parent-teacher relationships, specifically in secondary schools, and coteaching and cogenerative dialoguing. The study is particularly relevant given the challenges schools and teachers increasingly face to meaningfully connect with parents to better meet the needs of educational stakeholders in times of continual, complex, and rapid societal change.

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A matched case-control study of mortality to children under age five was conducted to consider associations with parents' socio-economic status and social support in the Farafenni Demographic Surveillance Site (DSS). Cases and controls were selected from Farafenni DSS, matched on date of birth, and parents were interviewed about personal resources and social networks. Parents with the lowest personal socio-economic status and social support were identified. Multivariate multinomial regression was used to consider whether the children of these parents were at increased risk of either infant or 1-4 mortality, in separate models using either parents' characteristics. There was no benefit found for higher SES or better social support with respect to child mortality. Children of fathers who had the poorest social support had lower 1-4 mortality risk (OR=0.52, p=0.037). Given that socio-economic status was not associated with child mortality, it seems unlikely that the explanation for the link between father's social support and mortality is linked to resource availability. Explanations for the risk effect of father's social ties may lie in decision-making around health maintenance and health care for children.