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.

Analysis of the mechanisms that maintain coordinate production of $\alpha$- and $\beta$-tubulin in mammalian cells

Alpha and beta tubulin are essential proteins in all eukaryotic cells. To study how cells maintain coordinate levels of these two interacting proteins, we have used PCR to add a 9 amino acid epitope from influenza hemagglutinin protein onto the carboxyl terminus of $\alpha$1 and $\beta$1-tubulin. The chimeric tubulin genes (HA$\alpha$1 and HA$\beta$1) were transfected into CHO cells and cell lines that stably express each gene were selected. Cells transfected with HA-tubulin do not exhibit any gross changes in growth or morphology. Immunofluorescence analysis demonstrated that HA-tubulins incorporate into both cytoplasmic and spindle microtubules. A quantitative biochemical assay was used to show that HA-tubulins incorporate into microtubules to a normal extent and do not alter the steady state distribution of endogenous tubulin between monomer and polymer pools. Two-dimensional gel analysis of pulse-labeled cells indicated that when HA$\beta$1-tubulin is expressed at high levels, it slightly represses the synthesis of the endogenous $\beta$-tubulin but produces a small increase in the synthesis of $\alpha$-tubulin. Analysis of cells labeled to steady state showed that HA$\beta$1-tubulin accumulates to a similar level as the wild-type gene product, but together these polypeptides produce only a small increase in total tubulin content consistent with the increased synthesis of $\alpha$-tubulin. It thus appears that HA$\beta$1-tubulin successfully competes with endogenous $\beta$-tubulin for heterodimer formation and that free $\beta$-tubulin subunits (endogenous and HA$\beta$1) are selectively degraded to maintain coordinate amounts of $\alpha$- and $\beta$-tubulin. In addition, the increased synthesis of $\alpha$-tubulin suggested the existence of a mechanism to ensure coordinate synthesis of $\alpha$- and $\beta$-tubulin subunits. To analyze whether reciprocal changes in endogenous tubulin synthesis occur when $\alpha$-tubulin is overexpressed, stably transfected CHO cell lines were isolated in which HA$\alpha$1-tubulin represents 50% of the total $\alpha$-tubulin, and its relative abundance can be further increased to 85-90% by treatment with sodium butyrate. In contrast with results obtained using HA$\beta$1-tubulin, transfection of HA$\alpha$1-tubulin decreased the synthesis of endogenous $\alpha$-tubulin to 60% of normal with little or no change in $\beta$-tubulin synthesis. When the transfected cells were treated with sodium butyrate to further increase HA$\beta$1-tubulin production, a larger decrease in the synthesis of endogenous $\alpha$-tubulin (to 30% of normal) was observed. The repression on the synthesis of endogenous $\alpha$-tubulin polypeptide was found to be directly proportional to the expression of HA$\alpha$1-tubulin indicating the existence of an autoregulatory loop, where $\alpha$-tubulin inhibits its own synthesis. To determine whether overproduction of HA$\alpha$1-tubulin affected the transcription, message stability or translation of endogenous $\alpha$-tubulin, the steady state levels of $\alpha$-tubulin mRNA were analyzed by ribonuclease protection assays. The results showed that the steady state level of $\alpha$-tubulin mRNA is not affected by the overexpression of HA$\alpha$1-tubulin, indicating that the repression is translational. The results are compatible with a model in which $\beta$-tubulin synthesis is largely unperturbed by overexpression of other tubulin subunits, and excess $\beta$-tubulin subunits are rapidly degraded to maintain coordinate $\alpha$- and $\beta$-tubulin levels at steady state. In contrast, free $\alpha$-tubulin represses its own synthesis at the translational level, suggesting that its level of production may be controlled by the amount of $\beta$-tubulin available for heterodimer formation. ^

An ecologic comparison study of the impact of economic disadvantage on Texas Assessment of Knowledge and Skills performance, graduation rates, and readiness for higher education for students attending public and charter schools in Texas from 2004 to 2006

Purpose. No Child Left Behind aimed to "improve the academic achievement of the disadvantaged." The primary research question considered how academic achievement of those from economic disadvantage compared to those not from disadvantage? ^ Economically disadvantaged students can potentially have added academic disadvantage. Research shows low academic achievement can potentially result in drug abuse, youth violence, and teen pregnancy. ^ Methods. To compare the student populations, measures included TAKS results and academic indicator data collected by the Texas Education Agency. ^ Results. T-test analyses showed a significant difference between the economically and non-economically disadvantaged student populations in meeting the TAKS passing standard, graduation, and preparation for higher education.^ Conclusions. The achievement gap between students remained as indicated by the Texas testing program. More research and time are needed to observe if the desired impact on those from economic disadvantage will be reflected by academic achievement data.^

AN ASSESSMENT OF KNOWLEDGE AND ATTITUDES OF GENETIC COUNSELING SERVICES IN U.S. HTCs

Hemophilia is a hereditary bleeding disorder which requires lifelong specialized care. A network of Hemophilia Treatment Centers (HTCs) exists to meet the medical needs of patients affected by hemophilia. Genetic counseling services are an integral part of the HTC model of care; however, many HTCs do not have genetic counselors on staff. As a result, the duty to provide these services must fall to other healthcare providers within the HTC. To assess the knowledge and attitudes of these providers we developed a 49 question survey that was distributed electronically to hematologists and nurses at U.S. HTCs. The survey consisted of a three sections: demographic information, knowledge of hemophilia genetics, and attitudes towards genetic services. A total of 111 complete responses were received and analyzed. The average knowledge score among all participants was 74.8% with a total of 81 participants receiving a passing score of 70% or above. Thirty participants scored below 70% in the knowledge section. In general, attitude scores were high indicating that the majority of hematologists and nurses in HTCs feel confident in their ability to provide genetic counseling services. Over 90% of participants reported that they have some form of access to genetic counseling services at their center. Hematologists and nurses practicing in U.S. HTCs demonstrate sufficient knowledge of the genetics of hemophilia, and they generally feel confident in their ability to provide genetic counseling services to their patients. While their knowledge is sufficient, the average knowledge score was lower than 75%. Certain questions covering new genetic technologies and testing practices were more commonly missed than questions asking about more basic aspects of hemophilia genetics, such as inheritance and carrier testing. Finally, many clinics report having access to a counselor, but it is oftentimes a hematologist or nurse who is providing genetic counseling services to patients. Given the inconsistency in knowledge among providers coupled with the high confidence in one’s ability to counsel patients, it leaves room to question whether information about the genetics of hemophilia is being communicated to patients in the most appropriate and accurate manner.

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

Role of FbpA and FbpB in the pathogenesis and mycolyltransferase activity of Mycobacterium tuberculosis

Mycobacterium tuberculosis infects more people worldwide each year than any other single organism. The Antigen 85 Complex, a family of fibronectin-binding proteins (Fbps) found in several species of mycobacteria and possibly involved in host interaction, is considered among the putative virulence factors of M. tuberculosis. These proteins are implicated in the production of trehalose dimycolate (TDM) and arabinogalactan-mycolate (AG-M), two prominent components of the mycobacterium cell wall and potent modulators of the immune system during infection. For these reasons, the principal members of the complex, FbpA and FbpB, were the focus of these studies. The genes encoding these proteins, fbpA and fbpB, were each disrupted by insertion of a kanamycin resistance cassette in a pathogenic strain of M. tuberculosis, H37Rv. Neither mutation affected growth in routine broth culture. Thin layer chromatography analysis of TDM and AG-M showed no difference in content between the parent strain H37Rv and the FbpA- and FbpB-deficient mutants grown under two different culture conditions. However, metabolic radiolabeling of the strains showed that the production of TDM (but not its precursor TMM) was delayed in the FbpA- and FbpB-deficient mutants compared to the parent H37Rv. During this same labeling period, FbpA-deficient mutant LAa1 failed to produce AG-M and in the FpbB-deficient mutant LAb1 production was decreased. In macrophage tissue culture assay, LAa1 failed to multiply when bacteria in early log phase were used to infect monolayers while LAb1 grew like the parent strain. The growth deficiency of LAa1 as well as the deficiencies in TDM and AG-M production were restored by complementing LAa1 with a functional fbpA gene. These results suggest that the FbpA and FbpB proteins are involved in synthesis of TDM (but not its precursor TMM) as well as AG-M. Other members of the complex appear to compensate for defects in synthesis caused by mutation of single genes in the complex over time. Mutation of the FbpA gene causes greater in vivo effect than mutation of the FbpB gene despite very similar deficiencies in the rate of production of mycolate containing molecules on the cell surface. ^

The construction of aging and health in older African American women

Persistence of racial and ethnic health disparities and governmental policies based on outdated ideas of aging call for inclusive approaches to the study of elder African Americans. The lived experiences of aging among urban, poor African American women, who comprise a vulnerable population, are not well known, as most studies focus on mainstream populations. Gerontological studies have tended to employ methods that collapse contextual information for ease of analysis, thus failing to capture nuanced information critically relevant to health of marginalized groups. Few researchers have been successful highlighting the importance of local knowledge, resilience, and resources for health by using participatory methods with older Black women. This study utilizes participatory principles to gather discursive data from nine older African American women, engaged in three generational cohorts: those born around World War II, women born after the great depression, and those born before the great depression. Videotaped and transcribed conversations of cohorts were analyzed in search of contextual factors that influence their experience of aging and health. As women responded to general themes that provoked their talk about their lives, they helped answer the study's questions: How do older African American women make sense of their aging experience? What are some of the important social and cultural influences that shape the construction of aging and health by these women? Are generational discourse groups an effective tool for exploring changes in the experiences of aging? A key finding demonstrated rich heterogeneity of experiences with strong generational influences on the construction of aging and health. The participants' moral orders comprised of traditional values of family, reinforced by personal experiences and the church, have guided their lives through oppression and stress but appear to be failing younger women who have greater exposure to new environmental pressures. Limited time and the size of the study were weaknesses although the women's interest in the study and their participation were gratifying. The participants served to highlight the importance of recognizing generational and other contextual factors in formation of ideas of aging and likelihood of additional challenges to the experience of old age among older, poorer, African Americans. ^

Stressful life events and their contributions to symptoms of anxiety and depression in adolescents

There are several innovative aspects to this thesis that extend our current knowledge of the relations between stress and psychiatric symptoms in adolescents. First, distal and proximal stressors are differentiated. This approach allows one to specifically examine the role of early childhood stressors as well as stressors experienced more recently as they impact the expression of depression and anxiety during adolescence. Second, a state-of-the-art assessment instrument was used to examine proximal stressors, helping to distinguish several aspects of stress, including objective stress and subjective stress. Third, the parent study from which these data were derived was designed to examine the role of familial risk for depression and related risk factors for the initial development of depression and alcohol use disorders. This allowed for a very thorough collection of demographic characteristics of the study population. Accordingly, this thesis examines the initial prodromal expression of anxiety and depressive symptoms as they are originally expressed prior to the development, if any, of a full-blown psychiatric disorder.^

Sociocultural context of knowledge and beliefs about cardiovascular disease among Latino women

We formed an academic-community partnership with the Salsa Caliente program to undertake a project to better understand how Latina women with cardiovascular disease (CVD) or at risk of CVD view and understand CVD. This study's research question examines the sociocultural factors that influence and inform Latino women's perceptions and beliefs about CVD. Seven out the eleven participants in the Salsa Caliente program consented to be interviewed. The data was collected through recorded interviews, which were transcribed and then analyzed for common themes found among all the participants' narratives. The content analysis looking into common themes yielded four: 1) increased awareness of CVD, 2) trust in doctor, 3) delay in doctor visits, and 4) awareness of health. Implications for interventions and further research are discussed.^