Quantitation of contacts among sensory, motor, and serotonergic neurons in the pedal ganglion of aplysia.

Present models of long-term sensitization in Aplysia californica indicate that the enhanced behavioral response is due, at least in part, to outgrowth of sensory neurons mediating defensive withdrawal reflexes. Presumably, this outgrowth strengthens pre-existing connections by formation of new synapses with follower neurons. However, the relationship between the number of sensorimotor contacts and the physiological strength of the connection has never been examined in intact ganglia. As a first step in addressing this issue, we used confocal microscopy to examine sites of contact between sensory and motor neurons in naive animals. Our results revealed relatively few contacts between physiologically connected cells. In addition, the number of contact sites was proportional to the amplitude of the EPSP elicited in the follower motor neuron by direct stimulation of the sensory neuron. This is the first time such a correlation has been observed in the central nervous system. Serotonin is the neurotransmitter most closely examined for its role in modulating synaptic strength at the sensorimotor synapse. However, the structural relationship of serotonergic processes and sensorimotor synapses has never been examined. Surprisingly, serotonergic processes usually made contact with sensory and motor neurons at sites located relatively distant from the sensorimotor synapse. This result implies that heterosynaptic regulation is due to nondirected release of serotonin into the neuropil.

The medical malpractice insurance "crises" and federal medical malpractice tort reform: Collection and analysis of bills passed by the United States House of Representatives from 1995--2005

There have been three medical malpractice insurance "crises" in the United States over a time spanning roughly the past three decades (Poisson, 2004, p. 759-760). Each crisis is characterized by a number of common features, including rapidly increasing medical malpractice insurance premiums, cancellation of existing insurance policies, and a decreased willingness of insurers to offer or renew medical malpractice insurance policies (Poisson, 2004, p. 759-760). Given the recurrent "crises," many sources argue that medical malpractice insurance coverage has become too expensive a commodity—one that many physicians simply cannot afford (U.S. Department of Health and Human Services [HHS], 2002, p. 1-2; Physician Insurers Association of America [PIAA], 2003, p. 1; Jackiw, 2004, p. 506; Glassman, 2004, p. 417; Padget, 2003, p. 216). ^ The prohibitively high cost of medical liability insurance is said to limit the geographical areas and medical specializations in which physicians are willing to practice. As a result, the high costs of medical liability insurance are ultimately said to affect whether or not people have access to health care services. ^ In an effort to control the medical liability insurance crises—and to preserve or restore peoples' access to health care—every state in the United States has passed "at least some laws designed to reduce medical malpractice premium rates" (GAO, 2003, p.5-6). More recently, however, the United States has witnessed a push to implement federal reform of the medical malpractice tort system. Accordingly, this project focuses on federal medical malpractice tort reform. This project was designed to investigate the following specific question: Do the federal medical malpractice tort reform bills which passed in the House of Representatives between 1995 and 2005 differ in respect to their principle features? To answer this question, the text of the bills, law review articles, and reports from government and private agencies were analyzed. Further, a matrix was compiled to concisely summarize the principle features of the proposed federal medical malpractice tort reform bills. Insight gleaned from this investigation and matrix compilation informs discussion about the potential ramifications of enacting federal medical malpractice tort reform legislation. ^

Clinical and microbiological aspects of linezolid resistance mediated by the cfr gene encoding a 23S rRNA methyltransferase.

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), the erm(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette mec type I. We were unable to detect the cfr gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the cfr gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of cfr-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method.

Respiratory rhythm generation: A modeling study of the respiratory central pattern generator and the phrenic motor neuron

The respiratory central pattern generator is a collection of medullary neurons that generates the rhythm of respiration. The respiratory central pattern generator feeds phrenic motor neurons, which, in turn, drive the main muscle of respiration, the diaphragm. The purpose of this thesis is to understand the neural control of respiration through mathematical models of the respiratory central pattern generator and phrenic motor neurons. ^ We first designed and validated a Hodgkin-Huxley type model that mimics the behavior of phrenic motor neurons under a wide range of electrical and pharmacological perturbations. This model was constrained physiological data from the literature. Next, we designed and validated a model of the respiratory central pattern generator by connecting four Hodgkin-Huxley type models of medullary respiratory neurons in a mutually inhibitory network. This network was in turn driven by a simple model of an endogenously bursting neuron, which acted as the pacemaker for the respiratory central pattern generator. Finally, the respiratory central pattern generator and phrenic motor neuron models were connected and their interactions studied. ^ Our study of the models has provided a number of insights into the behavior of the respiratory central pattern generator and phrenic motor neurons. These include the suggestion of a role for the T-type and N-type calcium channels during single spikes and repetitive firing in phrenic motor neurons, as well as a better understanding of network properties underlying respiratory rhythm generation. We also utilized an existing model of lung mechanics to study the interactions between the respiratory central pattern generator and ventilation. ^

Identifying the roles of the Escherichia coli FtsZ-associated proteins by minimizing the requirements for division

Formation of the FtsZ ring (Z ring) in Escherichia coli is the first step in assembly of the divisome, a molecular machine composed of 14 known proteins which are all required for cell division. Although the biochemical functions of most divisome proteins are unknown, several of these have overlapping roles in ensuring that the Z ring assembles at the cytoplasmic membrane and is active. ^ We identified a single amino acid change in FtsA, R286W, renamed FtsA*, that completely bypasses the requirement for ZipA in cell division. This and other data suggest that FtsA* is a hyperactive form of FtsA that can replace the multiple functions normally assumed by ZipA, which include stabilization of Z rings, recruitment of downstream cell division proteins, and anchoring the Z ring to the membrane. This is the first example of complete functional replacement of an essential prokaryotic cell division protein by another. ^ Cells expressing ftsA* with a complete deletion of ftsK are viable and divide, although many of these ftsK null cells formed multiseptate chains, suggesting a role in cell separation for FtsK. In addition, strains expressing extra ftsAZ, ftsQ, ftsB, zipA or ftsN, were also able to survive and divide in the absence of ftsK. The cytoplasmic and transmembrane domains of FtsQ were sufficient to allow viability and septum formation to ftsK deleted strains. These findings suggest that FtsK is normally involved in stabilizing the divisome and shares functional overlap with other cell division proteins. ^ As well as permitting the removal of other divisome components, the presence of FtsA* in otherwise wild-type cells accelerated Z-ring assembly, which resulted in a significant decrease in the average length of cells. In support of its role in Z-ring stability, FtsA* suppressed the cell division inhibition caused by overexpressing FtsZ. FtsA* did not affect FtsZ turnover within the Z ring as measured by fluorescence recovery after photobleaching. Turnover of FtsA* in the ring was somewhat faster than wild-type FtsA. Yeast two-hybrid data suggest that FtsA* has an increased affinity for FtsZ relative to wild-type FtsA. These results indicate that FtsA* interacts with FtsZ more strongly, and its enhancement of Z ring assembly may explain why FtsA* can permit survival of cells lacking ZipA or FtsK.^

Cultural competence in an HIV dedicated dental clinic: Application of the National Standards for Culturally and Linguistically Appropriate Services in Health Care (CLAS)

This dissertation investigated perspectives on cultural competence among African-American women patients, staff, and the administrator of a dental clinic serving people living with HIV/AIDS; and evaluated the role of the National Standards for Culturally and Linguistically Appropriate Services in Health Care (CLAS) in advancing the provision of culturally competent care in the clinic. ^ The study was qualitative with data collection via focus groups and individual interviews with a sample of African-American women patients, and individual interviews with a sample of staff and the clinic administrator. Transcripts were coded and themes identified using the software program ATLAS.ti. A cultural audit template was developed and applied to evaluate cultural competency. ^ Among attitudes and behaviors that contributed to the provision of culturally competent care at the clinic were respect and empathic communication. Formal cultural competency was not featured strongly in the methods by which the staff learned to work with diverse populations. Instead cultural competence among the staff was based on thoughtful hiring practices, natural aptitude and a climate that encouraged learning through informal sharing of experiences. The staff and administrator felt that an African-American dentist would be an asset in improving culturally competent care at the clinic. Previous research and national policy also promote the provider-patient racial/ethnic concordance to improve care. In this study, however, the patients were happy with the care provided regardless of the race/ethnicity of the staff, probably reflecting the well developed cultural competence skills of clinic staff overall. ^ The clinic administrator was unaware of the CLAS standards although the clinic was implicitly operated under their mandates. This occurred because the clinic is supported by federal funding and the CLAS standards were incorporated into the requirements. Incorporation into and monitoring of the CLAS standards in federally funded programs therefore appears to be an effective means for ensuring that they are implemented. ^ This study illustrates that cultural competence, though not universally understood, can be systematically investigated to identify what constitutes appropriate care and the factors that support or inhibit it. Among important elements of culturally competent care are respect and empathic communication. ^

The results of a barrier analysis on complementary feeding practices among mothers in the Central River Division of the Gambia

Currently, the barriers to appropriate infant feeding practices are largely unknown in the Central River Division of the Gambia. A questionnaire was developed and implemented by a local Non Governmental Organization (NGO), the Gambia Food and Nutrition Agency, in order to gain more information and ultimately to improve the child mortality rate of the country. There were two participant groups: 88 Doers who are women who had adopted the appropriate complementary feeding practice guidelines as defined by the World Health Organization and 87 Non Doers who are women who had in some way strayed from the appropriate complementary feeding practice guidelines. The questionnaire included aspects of the Health Belief Model which can be used in the development of a future intervention. The Yes/No questions were analyzed using the Chi-square statistical method and the open-ended questions used a descriptive analysis method of evaluation. The constructs for perceived susceptibility, perceived action efficacy, perceived self efficacy, cues for action and perception of divine showed significant differences between the Doers and the Non Doers (p<0.05). The descriptive analysis revealed that both participant groups had a limited understanding of the preventative qualities of the adoption of appropriate complementary feeding practices. The women in both of groups also showed a strong perception of divine will. Women in the Central River Division perceive their husband and in-laws to be the most influential in the decision-making process regarding infant feeding practices. Recommendations for future interventions must acknowledge the importance and influence of the community surrounding the women in their adoption of the appropriate infant feeding practices. It would also be important to educate women about of the specific guidelines of the appropriate complementary feeding practices, specifically the delay in early initiation of complementary feeding. The results of this barrier analysis provide useful information to plan and implement an effective intervention to improve the child mortality rate in the Gambia. ^

Disparities in medical expenditure and utilization among hypertensive men and women in the U.S.: Cross-section and lifetime analysis

Objectives. To investigate procedural gender equity by assessing predisposing, enabling and need predictors of gender differences in annual medical expenditures and utilization among hypertensive individuals in the U.S. Also, to estimate and compare lifetime medical expenditures among hypertensive men and women in the U.S. ^ Data source. 2001-2004 the Medical Expenditure Panel Survey (MEPS);1986-2000 National Health Interview Survey (NHIS) and National Health Interview Survey linked to mortality in the National Death Index through 2002 (2002 NHIS-NDI). ^ Study design. We estimated total medical expenditure using four equations regression model, specific medical expenditures using two equations regression model and utilization using negative binomial regression model. Procedural equity was assessed by applying the Aday et al. theoretical framework. Expenditures were estimated in 2004 dollars. We estimated hypertension-attributable medical expenditure and utilization among men and women. ^ To estimate lifetime expenditures from ages 20 to 85+, we estimated medical expenditures with cross-sectional data and survival with prospective data. The four equations regression model were used to estimate average annual medical expenditures defined as sum of inpatient stay, emergency room visits, outpatient visits, office based visits, and prescription drugs expenditures. Life tables were used to estimate the distribution of life time medical expenditures for hypertensive men and women at different age and factors such as disease incidence, medical technology and health care cost were assumed to be fixed. Both total and hypertension attributable expenditures among men and women were estimated. ^ Data collection. We used the 2001-2004 MEPS household component and medical condition files; the NHIS person and condition files from 1986-1996 and 1997-2000 sample adult files were used; and the 1986-2000 NHIS that were linked to mortality in the 2002 NHIS-NDI. ^ Principal findings. Hypertensive men had significantly less utilization for most measures after controlling predisposing, enabling and need factors than hypertensive women. Similarly, hypertensive men had less prescription drug (-9.3%), office based (-7.2%) and total medical (-4.5%) expenditures than hypertensive women. However, men had more hypertension-attributable medical expenditures and utilization than women. ^ Expected total lifetime expenditure for average life table individuals at age 20, was $188,300 for hypertensive men and $254,910 for hypertensive women. But the lifetime expenditure that could be attributed to hypertension was $88,033 for men and $40,960 for women. ^ Conclusion. Hypertensive women had more utilization and expenditure for most measures than hypertensive men, possibly indicating procedural inequity. However, relatively higher hypertension-attributable health care of men shows more utilization of resources to treat hypertension related diseases among men than women. Similar results were reported in lifetime analyses.^ Key words: gender, medical expenditures, utilization, hypertension-attributable, lifetime expenditure ^

The influence of social connectedness and self-esteem on participant retention in a bi-ethnic longitudinal study

In prospective studies it is essential that the study sample accurately represents the target population for meaningful inferences to be drawn. Understanding why some individuals do not participate, or fail to continue to participate, in longitudinal studies can provide an empirical basis for the development of effective recruitment and retention strategies to improve response rates. This study examined the influence of social connectedness and self-esteem on long-term retention of participants, using secondary data from the “San Antonio Longitudinal Study of Aging” (SALSA), a population-based study of Mexican Americans (MAs) and European Americans (EAs) aged over 65 years residing in San Antonio, Texas. We tested the effect of social connectedness, self-esteem and socioeconomic status on participant retention in both ethnic groups. In MAs only, we analyzed whether acculturation and assimilation moderated these associations and/or had a direct effect on participant retention. ^ Low income, low frequency of social contacts and length of recruitment interval were significant predictors of non-completer status. Participants with low levels of social contacts were almost twice as likely as those with high levels of social contacts to be non-completers, even after adjustment for age, sex, ethnic group, education, household income, and recruitment interval (OR = 1.95, 95% CI: 1.26–3.01, p = 0.003). Recruitment interval consistently and strongly predicted non-completer status in all the models tested. Depending on the model, for each year beyond baseline there was a 25–33% greater likelihood of non-completion. The only significant interaction, or moderating, effect observed was between social contacts and cultural values among MAs. Specifically, MAs with both low social contacts and low acculturation on cultural values (i.e., placed high value on preserving Mexican cultural origins) were three and half times more likely to be non-completers compared with MAs in other subgroups comprised of the combination of these variables, even after adjustment for covariates. ^ Long term studies with older and minority participants are challenging for participant retention. Strategies can be designed to enhance retention by paying special attention to participants with low social contacts and, in MAs, participants with both low social contacts and low acculturation on cultural values. Minimizing the time interval between baseline and follow-up recruitment, and maintaining frequent contact with participants during this interval should also be is integral to the study design.^

Assessing the relationship between board composition and nonprofit hospital financial performance from a multi-theoretic perspective

This dissertation assesses the relationship between board composition and financial performance for the top 71 major nonprofit hospitals in the United States during the period 2004-2009. The underlying data were collected from copies of IRS Form 990 available at http://www.guidestar.org . The dissertation investigates five factors: board size, board independence (percentage of outsiders), number of MDs, CEO succession and CEO compensation. And it evaluates the results within a multi-theoretic framework drawing on agency theory, resource dependence theory, institutional theory and social network theory. Corporate governance literature suggests that board composition has an important impact on firm financial performance. This dissertation examines whether the same may be true for nonprofit hospitals. The results should help hospital executives make better governance decisions during trying economic times.^