Magnetic resonance imaging of the cerebral metabolic rate of oxygen (CMRO₂)

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 120-128).Oxygen consumption is an essential process of the functioning brain. The rate at which the brain consumes oxygen is known as the cerebral metabolic rate of oxygen (CMRO₂). CMRO₂ is intimately related to brain health and function, and will change in settings of disease and functional activation. Accurate CMRO₂ measurement will enable detailed investigation of neuropathology and facilitate our understanding of the brain's underlying functional architecture. Despite the importance of CMRO₂ in both clinical and basic neuroscience settings, a robust CMRO₂ mapping technique amenable to functional and clinical MRI has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from post-capillary venular blood on a voxel-by-voxel basis. This isolated signal can be related to venular oxygen saturation, oxygen extraction fraction, and ultimately CMRO₂. This thesis first explores fundamental theory behind the QUIXOTIC technique, including design of a novel MRI pulse sequence, explanation of the principal sequence parameters, and results from initial human experiences. A human trial follows, in which QUIXOTIC is used to measure cortical gray matter CMRO₂ in ten healthy volunteers.(cont.) QUIXOTIC-measured CMRO₂ is found to be within the expected physiological range and is comparable to values reported by other techniques. QUIXOTIC is then applied to evaluate CMRO₂ response to carbon-dioxide-induced hypercapnia in awake humans. In this study, CMRO₂ is observed to decrease in response to mild hypercapnia. Finally, pilot studies that show feasibility of QUIXOTIC-based functional MRI (fMRI) and so-called "turbo" QUIXOTIC are presented and discussed.by Divya Sanam Bolar.Ph.D

The Sunday Night Productions Without Decor at the Royal Court Theatre, 1957-1975 (England, Playwriting, Drama).

The Sunday night productions without decor were a series of ninety-nine fully rehearsed plays each presented with minimal scenery or costumes for one or two nights at the Royal Court Theatre, in London, from 1957-1975. This program, along with the main bill productions of the English Stage Company, staged the works of new playwrights who gave voice to the concerns and problems of the young and the working class, two groups previously ignored in the English theatre. After the success of John Osborne\u27s Look Back in Anger (1956), the ESC, under the leadership of George Devine, was unable to accommodate many of the new scripts that arrived at the Royal Court. Devine needed a second stage also in order to test and train directors for future responsibility in the company. The productions without decor, created by Devine in 1957, satisfied both of these requirements. During the late fifties this series not only introduced several significant playwrights, such as John Arden and N. F. Simpson, but was instrumental in discovering three important directors for the ESC: John Dexter, Lindsay Anderson, and William Gaskill. During the sixties the private club status of the English Stage Society allowed the productions without decor to evade the scrutiny of the Lord Chamberlain and played a role in abolishing censorship in British theatre. Edward Bond and Christopher Hampton were two of the major playwrights who emerged through the Sunday night series in the sixties. The production without decor of A Collier\u27s Friday Night in 1966, helped launch Peter Gill\u27s directing career and led to the discovery of D. H. Lawrence as a dramatist. In 1969 the ESC opened by the Theatre Upstairs in the roof of the Royal Court to provide another outlet for new scripts. This space consumed a great deal of the company\u27s energy during the seventies. Because of the loss of critical attention, the rise of alternative or fringe theatre, and increasing union scales for actors and technicians, the Sunday night series became undesirable as a means for staging plays. Although the productions without decor were terminated in 1975, the ESC has continued its commitment to developing new playwrights and young talent through the Young People\u27s Theatre Scheme and a series of Rehearsed Readings

The effects of molecular composition on thermal, electrochemical, and mechanical properties of hyperbranched polymer electrolytes

This dissertation examines how changing the hyperbranching density and structure of polymer host backbones affects the physical properties of solid state polymer electrolytes. The structure of interest in this dissertation is the hyperbranching polymer backbone, which includes tetrabranching and tribranching architectures of varying hyperbranching densities. For a series of poly(ethylene glycol)-based polymers, we consider how molecular architecture impacts the electrochemical, thermal, and mechanical properties of the electrolytes on both the bulk and macromolecular scales. For both architectures, decreasing hyperbranching densities lead to improved conductivities (tetra- at 9.45 • 10-4 S/cm and tri- at 1.95 • 10-3 S/cm at 80 ºC) and improved shear storage moduli (tetra- at 0.63 MPa and tri- at 1.24 at 90 ºC). While having superior ionic conductivity and shear strength, the tribranching electrolytes were not compatible with lithium, which is a necessity for lithium-ion battery application. Following successful synthesis and material characterization, the tetrabranching electrolytes of various hyperbranching densities and structures are further probed as electrolytes in lithium-ion batteries. This series showed improved cycling performance with decreasing hyperbranching density (specific capacity of 1175 mAh/gSi after 50 cycles), with improved energy storage capabilities relative to the liquid control electrolyte (763 mAh/gSi after 50 cycles). Ultimately, the solid state polymer electrolytes synthesized in this work are promising candidates for further use in energy storage devices due to their observed thermal, electrochemical, and mechanical stabilities

Synergistic activity of endochitinase and exochitinase from Trichoderma atroviride (T. harzianum) against the pathogenic fungus (Venturia inaequalis) in transgenic apple plants

Genes from the biocontrol fungus Trichoderma atroviride encoding the antifungal proteins endochitinase or exochitinase (N-acetyl-β-D-hexosaminidase) were inserted into ‘Marshall McIntosh' apple singly and in combination. The genes were driven by a modified CaMV35S promoter. The resulting plants were screened for resistance to Venturia inaequalis, the causal agent of apple scab, and for effects of enzyme expression on growth. Disease resistance was correlated with the level of expression of either enzyme when expressed alone but exochitinase was less effective than endochitinase. The level of expression of endochitinase was negatively correlated with plant growth while exochitinase had no consistent effect on this character. Plants expressing both enzymes simultaneously were more resistant than plants expressing either single enzyme at the same level; analyses indicated that the two enzymes acted synergistically to reduce disease. Selected lines, especially one expressing low levels of endochitinase activity and moderate levels of exochitinase activity, were highly resistant in growth chamber trials and had negligible reduction in vigor relative to control plants. We believe that this is the first report of resistance in plants induced by expression of an N-acetylhexosaminidase and is the first report of in planta synergy between an exochitinase and an endochitinas

Robust estimation of limit loads of plates using secant rigidity

A robust method for the estimation of limit loads of structures has been adopted for plate structures. It involves the use of modified secant rigidity. The method makes use of repeated linear elastic analyses to predict limit behavior. The results from an initial elastic analysis are used to obtain the principal moments. A suitable yield criterion (such as Tresca or Von Mises) in terms of generalized forces is used. A set of equivalent moments is then computed for the plate. This is used to modify the secant rigidity of the plate. The modified structure is re-analyzed iteratively until convergence is reached. The moment distribution from the convergent analysis shows the collapse mechanism for the plate. The average of the equivalent moments along the collapse (or yield) lines of the plate is scaled to the plastic moment capacity of the section to obtain the limit load factor. The method has several advantages in comparison to other traditional methods. -- This method has been implemented on ANSYS software using APDL routines. Problems solved include: simply supported and fixed square and circular plates with uniform and concentrated loads, plates with irregular boundary conditions and shapes as well as continuous plates with checkerboard loading. The results from the above analyses match analytical results very closely, thus demonstrating the usefulness of the method used

Efficiency of Galanti and Guisti Method of ADA Estimation in Comparison with the Gold Standard

BACKGROUND: Adenosine Deaminase, the key enzyme of purine metabolism catalyzing the irreversible hydrolytic deamination of adenosine to inosine is implicated in a varied spectrum of human diseases ranging from SCID to TB and pneumonia. Estimation of ADA offers an easy, relatively affordable and reliable diagnostic alternative and/ or adjunct (specially in a TB endemic nation) which emphasizes the necessity of a feasible and implementable alternative method to the Diazyme method of ADA estimation requiring high end autoanalyzer and infrastructural setup.METHODS: Sixty body fluids samples (irrespective of gender, age, diagnosis or sample type) received by the Clinical Biochemistry Laboratory, Kasturba Medical College, Manipal for fluid ADA estimation by the Diazyme assay method (cobas 6000) was simultaneously processed by the Galanti and Guisti manual method to estimate the comparability and the aggregability of results obtained by the two analytical techniques.RESULTS: The Galanti and Guisti manual method of ADA estimation showed aggregability with the Diazyme autoanalyzer method for 90% of the assayed study samples with the manual method uniformly showing higher values when compared to the analyzer method. A correction factor of 2.44 was arrived at which could effectively achieve comparability between the two assay methods.CONCLUSION: The Galanti and Guisti manual method of ADA estimation might be a feasible, rapid, reliable and costeffective method for estimation of fluid ADA when compared to the cost and infrastructure intensive autoanalyzer

Context Matters: A Community-Based Study of Urban Minority Parents’ Views on Child Health

Background: Among children, there are substantial ethno-racial minority disparities across a broad range of health-related behaviors, experiences, and outcomes. Addressing these disparities is important, as childhood and adolescence establish health trajectories that extend throughout life. Methods: The current study employed a community-based participatory research approach to gain community insight on child health priorities and to frame an intervention aimed at improving the health of minority children. Eight focus groups were conducted among seventy-five African American parents in a Southeastern city. The current study was guided by an ecological theoretical framework. Results: Although the focus of this investigation was on community identification of child health priorities, participants cited, as root determinants, contextual factors, which included lack of healthy food options, lack of spaces for physical activity, and community violence. These co-occurring factors were related to limited engagement in outdoor activities and physical activity, increased obesity, and poor mental health and coping. Poor parenting was cited as the most substantial barrier to improving child health outcomes, and quality parenting was identified as the most important issue to address for community programs focused on promoting the health and success of children. For improving health outcomes for children in their neighborhoods, establishment of positive social capital and constructive activities were also cited. Conclusions: These results reinforce social determinants of health as influences on child health outcomes and describe how community engagement can address potential solutions through interventions that resonate with program participants

Utilization of a Community-based Participatory Approach to Design and Implement a Peer-led Parenting Pilot Intervention to Influence Child Nutritional and Physical Activity Behaviors

Parents and primary child guardians within the household play critical roles in shaping their children’s nutritional and physical activity behaviors, which are among the individual-level determinants of childhood obesity and other chronic conditions. There are well-established correlations between race, socioeconomic status and the risk for obesity calling for both contextually- and individual-centered interventions that are community-driven. The Using Quality Parenting (UQP) pilot intervention was a peer-led, parenting education intervention developed in collaboration with community residents in Atlanta, Georgia to influence child nutritional and physical activity behaviors in African American low socioeconomic status communities. A community-based participatory research (CBPR) framework was used to conduct a mixed-methods needs assessment designed to the UQP curriculum. The UQP program targeted parents of children ages 6-14. The overarching aim was to increase quality parenting and address community identified child obesity disparities and inequities in early and middle childhood. The topics pertaining to parenting to children’s health/well-being addressed by the UQP included nutrition, physical activity, socio-emotional development, positive parenting, coping skills, child advocacy, and community development. Analyses were conducted using PSAW 18 statistical software. Descriptive statistics, including frequencies, means, standard deviations, and ranges for the individual survey items were conducted. A t-test was performed comparing pre- and post-program participation. A repeated measure analysis of variance was conducted on the items that demonstrated a significant t-test. The analytic sample was composed of 46 African American parents, with over 50% of the sample earning an annual household income of $25,000 or less. Participating parents reported significantly higher levels of water consumption for their children post-program in comparison to pre-test reports (p = .010). Additionally, based on t-test analyses, parents reported that their children consumed significantly higher levels of proteins, grains, fruits and vegetables at each meal, post-program (p=0.03). These findings highlight the potential efficacy of community-informed, parent-led interventions in improving health disparities and related outcomes for children

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth