Extensive research has been devoted to the goal of understanding how a single cell of embryonic o... more Extensive research has been devoted to the goal of understanding how a single cell of embryonic origin can give rise to every somatic cell type and the germ cell lineage, a hallmark defined as "pluripotency." The aggregate of this work supports fundamentally important roles for the gene transcription networks inherent to the pluripotent cell. Transcription networks have been identified that are both required for pluripotency, as well as sufficient to reprogram somatic cells to a naive pluripotent state. Several members of the nuclear receptor (NR) superfamily of transcription factors have been identified to play diverse roles in the regulation of pluripotency. The ligand-responsive nature of NRs coupled with the abundance of genetic models available has led to a significant advance in the understanding of NR roles in embryonic stem cell pluripotency. Furthermore, the presence of a ligand-binding domain may lead to development of small molecules for a wide range of therapeutic and research applications, even in cases of NRs that are not known to respond to physiologic ligands. Presented here is an overview of NR regulation of pluripotency with a focus on the transcriptional, proteomic, and epigenetic mechanisms by which they promote or suppress the pluripotent state.
Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75... more Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II softwa...
We conducted a community survey to estimate the prevalence and describe the features, risk factor... more We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in AC...
The journal of the American Academy of Psychiatry and the Law, 2002
This study examines self-reported coercion in subjects with severe mental illness who were random... more This study examines self-reported coercion in subjects with severe mental illness who were randomly assigned in an experimental study to continue under, or be released from, involuntary outpatient commitment (OPC) subsequent to hospital discharge. After review of bivariate relationships, multivariable analyses demonstrated significantly higher levels of reported coercion among subjects who experienced longer periods of OPC; who were African American; who were single and not cohabiting; and who had ongoing substance abuse problems, poor insight into illness, and severe symptoms. Case managers' verbal reminders to subjects about the consequences of nonadherence to treatment partially account for higher reports of coercion. Previous reports from this study have found that OPC, if sustained and combined with frequent outpatient mental health services, can improve some outcomes. The current analyses demonstrate that a consequence of OPC is increased perceptions of coercion in the tre...
In the mental health law debate over justification for civil commitment of mentally ill persons, ... more In the mental health law debate over justification for civil commitment of mentally ill persons, coercion has been a central issue. Participants in the debate have tended to separate into two opposing camps. On one side have been civil rights advocates who argued for minimal deprivations to freedom and choice, and then only in cases of dangerousness and only with formal legal procedures to assure due process (LaFond &amp;amp;amp;amp; Durham, 1992; Morse, 1982; Stefan, 1987). On the other side have been mental health clinicians who wanted to ...
This study examined beliefs about the provisions of outpatient commitment and their effects among... more This study examined beliefs about the provisions of outpatient commitment and their effects among 306 people with severe and persistent mental illness who were awaiting a period of outpatient commitment. More than 80 percent of the respondents perceived that the court order for outpatient commitment required them to keep their appointments at the mental health center and to take medication as prescribed. More than three-quarters believed that the outpatient commitment order made it more likely that people would keep their mental health appointments, take their medication, and stay out of the hospital.
Extensive research has been devoted to the goal of understanding how a single cell of embryonic o... more Extensive research has been devoted to the goal of understanding how a single cell of embryonic origin can give rise to every somatic cell type and the germ cell lineage, a hallmark defined as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;pluripotency.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; The aggregate of this work supports fundamentally important roles for the gene transcription networks inherent to the pluripotent cell. Transcription networks have been identified that are both required for pluripotency, as well as sufficient to reprogram somatic cells to a naive pluripotent state. Several members of the nuclear receptor (NR) superfamily of transcription factors have been identified to play diverse roles in the regulation of pluripotency. The ligand-responsive nature of NRs coupled with the abundance of genetic models available has led to a significant advance in the understanding of NR roles in embryonic stem cell pluripotency. Furthermore, the presence of a ligand-binding domain may lead to development of small molecules for a wide range of therapeutic and research applications, even in cases of NRs that are not known to respond to physiologic ligands. Presented here is an overview of NR regulation of pluripotency with a focus on the transcriptional, proteomic, and epigenetic mechanisms by which they promote or suppress the pluripotent state.
Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75... more Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II softwa...
We conducted a community survey to estimate the prevalence and describe the features, risk factor... more We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in AC...
The journal of the American Academy of Psychiatry and the Law, 2002
This study examines self-reported coercion in subjects with severe mental illness who were random... more This study examines self-reported coercion in subjects with severe mental illness who were randomly assigned in an experimental study to continue under, or be released from, involuntary outpatient commitment (OPC) subsequent to hospital discharge. After review of bivariate relationships, multivariable analyses demonstrated significantly higher levels of reported coercion among subjects who experienced longer periods of OPC; who were African American; who were single and not cohabiting; and who had ongoing substance abuse problems, poor insight into illness, and severe symptoms. Case managers' verbal reminders to subjects about the consequences of nonadherence to treatment partially account for higher reports of coercion. Previous reports from this study have found that OPC, if sustained and combined with frequent outpatient mental health services, can improve some outcomes. The current analyses demonstrate that a consequence of OPC is increased perceptions of coercion in the tre...
In the mental health law debate over justification for civil commitment of mentally ill persons, ... more In the mental health law debate over justification for civil commitment of mentally ill persons, coercion has been a central issue. Participants in the debate have tended to separate into two opposing camps. On one side have been civil rights advocates who argued for minimal deprivations to freedom and choice, and then only in cases of dangerousness and only with formal legal procedures to assure due process (LaFond &amp;amp;amp;amp; Durham, 1992; Morse, 1982; Stefan, 1987). On the other side have been mental health clinicians who wanted to ...
This study examined beliefs about the provisions of outpatient commitment and their effects among... more This study examined beliefs about the provisions of outpatient commitment and their effects among 306 people with severe and persistent mental illness who were awaiting a period of outpatient commitment. More than 80 percent of the respondents perceived that the court order for outpatient commitment required them to keep their appointments at the mental health center and to take medication as prescribed. More than three-quarters believed that the outpatient commitment order made it more likely that people would keep their mental health appointments, take their medication, and stay out of the hospital.
Uploads