The genetic basis of thoracic aortic aneurysms and dissections: Genetic heterogeneity and mapping of TAAD1 and TAAD2 loci

Thoracic aortic aneurysms leading to aortic dissections (TAAD) are a major cause of morbidity and mortality in the United States. TAAD is a complication of some known genetic disorders, such as Marfan syndrome and Turner syndrome, but the majority of familial cases are not due to a known genetic syndrome. Previous studies by our group have established that nonsyndromic, familial TAAD is inherited in an autosomal dominant manner with decreased penetrance and variable expression. Using one large family with multiple members with TAAD for the genome wide scan, a major locus for familial TAAD was mapped to 5q13–14 (TAAD1). Nine out of 15 families studied were linked to this locus, establishing that TAAD1 was a major locus, and that there was genetic heterogeneity for the condition. Mapping of TAAD2 locus was accomplished using a single large family with multiple members with TAAD not linked to known loci of aneurysm formation. This established a second novel locus for familial TAAD on 3p24–25 (LOD score of 4.3), termed the TAAD2 locus. Two putative loci with suggestive LOD scores were mapped on 4q and 12q through a genome scan carried out using three families. TAAD phenotype in 12 families did not segregate with known loci, indicating further genetic heterogeneity. An STS-tagged BAC based contig was constructed for 7.8Mb and 25Mb critical interval of TAAD1 and TAAD2 respectively and characterized to identify the defective gene. The hypothesis that the defective genes responsible for the TAAD1 and TAAD2 encoded extracellular matrix (ECM) proteins, the major components of the elastic fiber system in the aortic media was tested. Four genes encoding ECM proteins, versican, thrombospondin-3, CRTL1, on TAAD1 and FBLN2 at TAAD2 were sequenced, but no disease-causing mutations were identified. Studies to identify the defective gene are initiated through the positional candidate gene approach using combination of bioinformatics and expression studies. The identification of the TAAD susceptibility genes will allow for presymptomatic diagnosis of individuals at risk for this life threatening disease. The identification of the molecular defects that contribute to TAAD will also further our understanding of the proteins that provide structural integrity to the aortic wall. ^

Is Our Business Family-Centered?

Human Services agencies often claim to be family-centered, but continue to implement “Service Integration” in a way that supports their mission rather than supporting families. David Berns, guest editor for this issue of the Journal of Family Strengths, presents a framework for redefining the role of governmental agencies beyond their day-to-day delivery of services to one that prevents the need for more intrusive and more costly interventions. Under this philosophy, agencies must consider how families functioned before they requested assistance, and how they will function if services are not successful. By taking the time to truly understand a family’s needs, caseworkers often discover that they may need a service for which they are not eligible and may be eligible for services that they don’t want or need. Instead of focusing entirely on what their agency can do for the family, caseworkers should consider all types of support that might produce better results. Families often need support from friends and communities rather than, or in addition to, a formalized service. Facilitating natural supports in the community may prevent the need for a governmental program. It is only when basic supports break down that families must use ever more intensive and costly programs. The author gives examples of how this framework is guiding the redesign of the TANF Program in Washington, D.C.

Family Stability and Childhood Behavioral Outcomes: A Critical Review of the Literature

As the definition of what is considered a family changes in our society, the family unit itself continues to undergo changes. These changes can sometimes lead to decreased stability within the family unit. One of the greatest challenges facing those researching this phenomenon is the lack of consistency within the existing body of research surrounding what familial instability actually is (the definition). This critical review of the literature examines the current body of literature in order to identify what is known about family stability and its impact on adolescent behavior, as well as what gaps currently exist. This review focuses on definitions of family stability, current factors surrounding the stability of the family unit, and addresses the implications that the current body of literature presents.

Improving Family Functioning Through Family Preservation Services: Results of the Los Angeles Experiment

This article describes a study of the outcomes of home-based family preservation services for abusive and neglectful families in Los Angeles County. It focuses on changes in family functioning during the 3 month service period and one year after case closing. Families known to the public child welfare agency were referred to the project based on caseworker judgement of the need for services rather than on the criteria of imminent risk of placement. Two hundred forty families were randomly assigned to either the service group receiving family preservation services from two non-profit agencies or to the comparison group receiving regular public agency services. Both caseworkers and families reported small but significant improvements in family functioning for the service group families, but not for the comparison group families. Study findings also suggest the aspects of family functioning most changed by services, the characteristics of families most affected by services, and variables which predicted service success.

Intensive Family Preservation Services: Do They Have Any Impact on Family Functioning?

Tills article presents a review of the intensive family preservation evaluation literature, the prepost test rnethology employed to evaluate three models in one state and the findings which have informed policymakers and program designers as the service expands. After intensive family preservation services, significant changes were found in parent-centered risk, parental disposition, and child-centered and child performance. No changes were found in economic risk and household adequacy.

Intensive Family Reunification Services: A Conceptual Framework and Case Example

Recent federal mandates require child welfare agencies to make reasonable efforts to reunify families after out-of-home placement. Consistent with those mandates, agencies are increasingly employing techniques from family preservation services intended initially to prevent out-of-home placement. The purpose of this article is to articulate a conceptual framework and practice guidelines for family reunification services and to describe an experimental reunification program based on a family preservation model. A case example illustrates the way in which the services affected one family that participated in the experiment.

A Multi- Faceted, Intensive Family Preservation Program Evaluation

This evaluation of a county intensive family preservation services (ifps) program makes several important methodological contributions to assessing post-treatment placement patterns of ifps clients. It is the first published ifps evaluation that utilizes an interval-level, overall measure of restrictiveness of placement, and one of the few that has followed placement patterns for a full two-years after treatment. The study is also a good example of complementing placement data with measures of family health and stability, and with qualitative feedback from former ifps clients. Finally, this study demonstrates the potential for doing methodologically sound evaluations of local ifps programs.

The Role of Consistency and Diversity in Building Knowledge in Family Preservation

Family preservation has been criticized for implementing programs that are not theoretically founded. One result of this circumstance is a lack of information regarding processes and outcomes of family preservation services. The knowledge base of family preservation is thus rather limited at present and will remain limited unless theory is consistently integrated within individual programs. A model for conceptualizing how theoretical consistency may be implemented within programs is presented and applied to family preservation. It is also necessary for programs to establish theoretical consistency before theoretical diversity, both within individual and across multiple programs, in order to advance the field in meaningful ways. A developmental cycle of knowledge generation is presented and applied to family preservation.

Coordination of Family Preservation Services in a Rural Community: A Case Study

Family preservation programs designed to prevent the out-of-home placement of children depend on the coordination of services from multiple agencies. Little is known regarding how coordination occurs. This case study examined this issue. Information was sought from all workers who provided services to each of five families and 'from families' case records. Thirty-one workers were interviewed with a semi-structured interview schedule containing rating scales and questions with open-ended response formats. Case records were reviewed with a case record review form. Analyses of data revealed the following. Services were coordinated to a moderate degree but that coordination deteriorated over time. Workers elaborated how aspects of communities, human service agencies, workers, and families affected coordination. Implications of findings for future research were drawn.

What is Family Preservation and Why Does it Matter?

This paper describes competing ideas about family preservation, defined both as a defined program of social services and a philosophical approach to helping troubled families. A straightforward definition has become almost impossible because the phrase has taken on so many different meanings, provoking controversy about its "real" meaning and value. Indeed, "family preservation" has become the proverbial elephant whose splendors and horrors are described with great certainty by those impressed by only one of its aspects. While skirmishes between "child savers" and "family preservers" have been part of the child welfare field since its beginning at the turn of the last century, recent debates over family preservation have been especially heated, generating more confusion and animosity than might be expected from the ranks of the small and usually mild-mannered social work profession. The debate is so heated that the director of one of the nation's largest child welfare agencies said recently that he is afraid to "even use the two words on the same page." <1> While the debate about the value of family preservation is unresolved, experimentation with different approaches to service delivery over the last two decades has helped to lay the groundwork for a resurgence of interest in family and community-centered reforms. Better understanding of the family preservation "debates" may be helpful if these reforms are to be successful over the long term. The paper discusses the competing ideas, values, and perceptions that have led observers to their different understandings of family preservation. It briefly chronicles the history of child welfare and examines key theories that have helped lay the groundwork for the resurgence of interest in family-centered services. It concludes with observations about how the competing values at stake in family preservation may affect the next generation of reforms.

The illness experiences of patients and their family members living with congestive heart failure

Purpose. To investigate and understand the illness experiences of patients and their family members living with congestive heart failure (CHF). ^ Design. Focused ethnographic design. ^ Setting. One outpatient cardiology clinic, two outpatient heart failure clinics, and informants' homes in a large metropolitan city located in southeast Texas. ^ Sample. A purposeful sampling technique was used to select a sample of 28 informants. The following somewhat overlapping, sampling strategies were used to implement the purposeful method: criterion; typical case; operational construct; maximum variation; atypical case; opportunistic; and confirming and disconfirming case sampling. ^ Methods. Naturalistic inquiry consisted of data collected from observations, participant observations, and interviews. Open-ended semi-structured illness narrative interviews included questions designed to elicit informant's explanatory models of the illness, which served as a synthesizing framework for the analysis. A thematic analysis process was conducted through domain analysis and construction of data into themes and sub-themes. Credibility was enhanced through informant verification and a process of peer debriefing. ^ Findings. Thematic analysis revealed that patients and their family members living with CHF experience a process of disruption, incoherence, and reconciling. Reconciling emerged as the salient experience described by informants. Sub-themes of reconciling that emerged from the analysis included: struggling; participating in partnerships; finding purpose and meaning in the illness experience; and surrendering. ^ Conclusions. Understanding the experiences described in this study allows for a better understanding of living with CHF in everyday life. Findings from this study suggest that the experience of living with CHF entails more than the medical story can tell. It is important for nurses and other providers to understand the experiences of this population in order to develop appropriate treatment plans in a successful practitioner-patient partnership. ^

The influence of ideological interest groups on congressional financial support of international family planning

The World Health Organization estimates there are about 585,000 maternal deaths each year, with 98% of the maternal deaths in developing countries. Access to family planning methods is one method to decrease maternal mortality and morbidity. ^ The U.S. was the leader in providing financial and technical assistance to developing countries to enable women to have this access. The election of Ronald Regan changed the course of U.S. support; abortion became a central factor in the political decision-making with regards to the financial support of international family planning. ^ One factor that may sway policy-makers' decisions is the influence of ideological interest groups, Political Action Committees funding of candidates in relation to votes on bills that impacted on financial support of international family planning and the amount spent by these groups on lobbyist was reviewed. Pro-choice funding of candidates was greater for the four of the fives votes supporting family planning. Pro-Choice lobbyist spending was $185,000 vs. $8,184,000 spent by Pro-Life ideological groups. ^

Development and preliminary validation of the cancer family impact scale for colorectal cancer

This study aimed to develop and validate The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and colorectal cancer (CRC) screening when family history is a risk factor. We used existing data to develop the measure from 1,285 participants (637 families) across the United States who were in the Johns Hopkins Colon Cancer Genetic Testing study. Participants were 94% white with an average age of 50.1 years, and 60% were women. None had a personal CRC history, and eighty percent had 1 FDR with CRC and 20% had more than one FDR with CRC. The study had three aims: (1) to identify the latent factors underlying the CFIS via exploratory factor analysis (EFA); (2) to confirm the findings of the EFA via confirmatory factor analysis (CFA); and (3) to assess the reliability of the scale via Cronbach's alpha. Exploratory analyses were performed on a split half of the sample, and the final model was confirmed on the other half. The EFA suggested the CFIS was an 18-item measure with 5 latent constructs: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. CFA on the holdout sample showed the CFIS to have a reasonably good fit (Chi-square = 389.977, df = 122, RMSEA= 0.058 (.052-.065), CFI=.902, TLI=.877, GF1=.939). The overall reliability of the scale was α=0.65. The reliability of the subscales was: (1) NEGATIVE α = 0.682; (2) POSITIVE α = 0.686; (3) COMMUNICATE α = 0.723; (4) FLOW α = 0.467; and (5) NORM α = 0.732. ^ We concluded the CFIS to be a good measure with most fit levels over 0.90. The CFIS could be used to compare theoretically driven hypotheses about the pathways through which family factors could influence health behavior among unaffected individuals at risk due to family history, and also aid in the development and evaluation of cancer prevention interventions including a family component. ^

Characterization of glucocorticoid receptor (NR3C1) gene polymorphisms and a family-based association study with hypertension

Hypertension is usually defined as having values of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg. Hypertension is one of the main adverse effects of glucocorticoid on the cardiovascular system. Glucocorticoids are essential hormones, secreted from adrenal glands in circadian fashion. Glucocorticoid's effect on blood pressure is conveyed by the glucocorticoid receptor (NR3C1), an omnipresent nuclear transcription factor. Although polymorphisms in this gene have long been implicated to be a causal factor for cardiovascular diseases such as hypertension, no study has yet thoroughly interrogated the gene's polymorphisms for their effect on blood pressure levels. Therefore, I have first resequenced ∼30 kb of the gene, encompassing all exons, promoter regions, 5'/3' UTRs as well as at least 1.5 kb of the gene's flanking regions from 114 chromosome 5 monosomic cell lines, comprised of three major American ethnic groups—European American, African American and Mexican American. I observed 115 polymorphisms and 14 common molecularly phased haplotypes. A subset of markers was chosen for genotyping study populations of GENOA (Genetic Epidemiology Network of Atherosclerosis; 1022 non-Hispanic whites, 1228 African Americans and 954 Mexican Americans). Since these study populations include sibships, the family-based association test was performed on 4 blood pressure-related quantitative variables—pulse, systolic blood pressure, diastolic blood pressure and mean arterial pressure. Using these analyses, multiple correlated SNPs are significantly protective against high systolic blood pressure in non-Hispanic whites, which includes rsb198, a SNP formerly associated with beneficial body compositions. Haplotype association analysis also supports this finding and all p-values remained significant after permutation tests. I therefore conclude that multiple correlated SNPs on the gene may confer protection against high blood pressure in non-Hispanic whites. ^

Sibling relationships in the family of a child with a burn injury

Purpose. Understanding siblings' experiences after a major childhood burn injury was the purpose of this mixed method, qualitative dominant study. The following research questions guided this project: How do siblings describe the impact of a major childhood burn injury experience? How do sibling relationship factors of warmth/closeness, relative status/power, conflict, and rivalry further clarify their relationship and their experience after a major burn injury? ^ Methods. A mixed method, qualitative dominant, design was implemented to understand the sibling experiences in a family with a child suffering from a major burn injury. Informants were selected from patients with childhood burn injuries attending the reconstructive clinic at a Gulf coast children's specialty hospital. The qualitative portion used the life story method, a narrative process, to portray the long-term impact on sibling relationships. A "case" represents a family unit and could be composed of one or multiple family members. Participants from 22 cases (N = 40 participants) were interviewed. Interviews were conducted in person and via telephone. The quantitative portion, or the embedded part of this mixed method design, used the Sibling Relationship Questionnaire Revised (SRQ-R) to conduct an additional structured interview and acquire scoring data. It was postulated that the SRQ-R would provide another perspective on the sibling experience and expand the qualitative data analysis. Thematic analysis was implemented on the qualitative interview data including the qualitative data from the interviews structured on the SRQ-R. Additionally, scores on the SRQ-R were tabulated to further describe the cases. ^ Results. The overall thematic pattern for the sibling relationship in families having a child with a major burn injury was that of normalization. Areas of normalization as well as the process of adjustment were the major themes. Areas of normalization were found in play and other activities, in school and work, and in family relations with their siblings and their parents. The process of adjustment in the sibling relationship was described as varied, involved school and work re-entry, and might even change their life perspective. Further analysis included an examination of the cases in which more than one person were interviewed and completed the SRQ-R. Participants from five ( n = 11) of six cases (n = 14), scored above 3.0 on the five-point scale on the Warmth/Closeness construct, indicating they perceived the sibling relationship as close. Five participants scored high on the Conflict construct and four participants scored high on the Rivalry construct. Finally, Relative Status/Power was low or negative in the six cases (n = 13). ^ Conclusions/implications. These findings suggest the importance of returning to normalcy for many of the families and the significance of sibling relationships on the process. Some of these families were able to use this major life event in a positive way to promote normalization. ^