A Modern Family: The Performance of "Family" and Familialism in Contemporary Television Series.

This dissertation addresses the complexities inherent in contemporary television articulations of family life and organization that construct the discourse on the American family since the mid-1990s. In addition to surveying the history of a number of television genres, such as father-centered series, teen-oriented programming, multigenerational family series, and reality TV, the dissertation uses textual analysis to examine how television frames and constructs “the family,” while also attempting to locate this construction within larger political, social, and cultural contexts. I argue that the socio-cultural evolution and construction of parenthood, marriage, and childhood have led to alternative definitions of “family” in contemporary television programming; however, specific case studies indicate a seemingly resilient commitment to, or performance of, a particular familial idealism. Each chapter concludes with notable case studies that offer an in-depth examination of various depictions of families, the kinds of “family values” they promote, and the way they continue to perform familialism even as they depict modern-day familial realities. The goal of this dissertation was to provide a better understanding as to both why a mythic “ideal” family has inhabited our cultural consciousness for so long, and how recent television series offer a space to question the appropriateness, authenticity, and usefulness of the dominant familial ideology to the twenty-first century family. In the end, what it found was that even amidst a multitude of diverse sentiments and structures of families on television, the most successful images of family continue to be bound to a performance of familialism that reaffirms the values deeply rooted in the nuclear family.Ph.D.CommunicationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91389/1/fogelj_1.pd

Validation of Diffuse Correlation Spectroscopic Measurement of Cerebral Blood Flow Using Phase-Encoded Velocity Mapping Magnetic Resonance Imaging

Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R = 0.88, p \u3c 0.001, slope = 0.91 ± 0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R = 0.77, slope = 0.99 ± 0.12, p \u3c 0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R = 0.46, slope = 1.77 ± 0.45, p \u3c 0.001

NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia

African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Relevance of Quality Measurement to Integrative Healthcare in the United States.

With the advent of new models for payment and delivery of healthcare services, the use of quality measures for continual improvement of clinical healthcare is now an integral feature of medical practice in the United States. However, quality measurement and quality improvement activities are not common practice among integrative health providers. This article discusses the import and application of quality measurement to the practice of integrative healthcare. It reviews developments in the healthcare quality improvement movement, explores the relevance of quality measures to integrative healthcare, describes examples of the current use of quality measures in integrative health practice, discusses discriminatory policies that may prevent participation in quality improvement by integrative health practitioners, and makes recommendations for practice and policy

Assessing the association between pre-operative feeding and the development of oral feeding skills in infants with single ventricle heart disease: An analysis of the NPC-QIC dataset

Pre-operative feeding may improve long-term feeding outcomes in single ventricle patients, including weaning from supplemental tube feedings in infancy. This study examines the association between pre-operative enteral feeding and subsequent long-term feeding outcomes while also assessing the counterbalancing risk of necrotizing enterocolitis (NEC). Secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative database was performed. The association between pre-operative feeding practice and achieving all oral feeds through the first year of life was examined using a multivariable regression model. Similarly, the association between pre-operative oral feeding and NEC was also assessed. Of 944 patients with 1-year feeding outcomes available, 58% were fed preoperatively (41.3% exclusively oral) and 12.3% were not fed per institutional approach. At hospital discharge after Stage 1 palliation, 57% required a feeding tube, while 39% required a feeding tube at their first birthday. In infants who were orally fed, the odds ratio to achieving tube-free feeding at 1 year was not significantly increased (1.3, confidence interval 0.8-2.0). Of 1740 infants with pre-operative feeding and Stage 1 there was no statistically significant difference in NEC among patients who were preoperatively fed versus those that were not fed per institutional approach (p = 0.2). Pre-operative feeding of infants with single ventricle heart disease was not associated with early achievement of tube-free feeding in the first year of life. However, pre-operative oral feeding was also not associated with increased risk of NEC, suggesting that it can be safely offered among appropriate patients

Proteomic Identification of DNA-PK Involvement within the RET Signaling Pathway

<div><p>Constitutive activation of the Rearranged during Transfection (RET) proto-oncogene leads to the development of MEN2A medullary thyroid cancer (MTC). The relatively clear genotype/phenotype relationship seen with RET mutations and the development of MEN2A is unusual in the fact that a single gene activity can drive the progression towards metastatic disease. Despite knowing the oncogene responsible for MEN2A, MTC, like most tumors of neural crest origin, remains largely resistant to chemotherapy. Constitutive activation of RET in a SK-N-MC cell line model reduces cell sensitivity to chemotherapy. In an attempt to identify components of the machinery responsible for the observed RET induced chemoresistance, we performed a proteomic screen of histones and associated proteins in cells with a constitutively active RET signaling pathway. The proteomic approach identified DNA-PKcs, a DNA damage response protein, as a target of the RET signaling pathway. Active DNA-PKcs, which is phosphorylated at site serine 2056 and localized to chromatin, was elevated within our model. Treatment with the RET inhibitor RPI-1 significantly reduced s2056 phosphorylation in RET cells as well as in a human medullary thyroid cancer cell line. Additionally, inhibition of DNA-PKcs activity diminished the chemoresistance observed in both cell lines. Importantly, we show that activated DNA-PKcs is elevated in medullary thyroid tumor samples and that expression correlates with expression of RET in thyroid tumors. These results highlight one mechanism by which RET signaling likely primes cells for rapid response to DNA damage and suggests DNA-PKcs as an additional target in MTC.</p></div

Components of an active RET signaling pathway are observed in MTC and correlate to DNA-PKcs.

<p>Immunohistochemistry of MTC array samples for phosphorylated ERK 1/2 and phosphorylated AKT indicated the presence of both of these components of an active RET signaling pathway in MTC similar to staining observed for ps2056 DNA-PKcs. 10x images of whole tissue array sample are shown.</p

List of proteins found to be significantly altered in RET 9 and RET 51 lines compared to control lines.

<p>Fold change ≤1.5 is considered increased expression and between 0.2 and 0.6 is decreased expression.</p><p>List of proteins found to be significantly altered in RET 9 and RET 51 lines compared to control lines.</p