A Survey of Psychiatrists' Attitudes Toward Treatment Guidelines

We developed a survey to look at psychiatrists' attitudes toward psychotropic prescribing guidelines, specifically the Texas Medication Algorithm Project (TMAP) algorithms. The 22-page survey was distributed to 24 psychiatrists working in 4 CMHC's; 13 completed the survey. 90% agreed that guidelines should be general and flexible. The majority also agreed that guidelines should define how to measure response to a specific agent; fewer agreed guidelines should specify dosage, side effect management, or augmentation strategies. Psychiatrists were familiar with TMAP; none referred to it in their practice. In spite of this, psychiatrists' medication preferences were similar to those suggested by guidelines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44317/1/10597_2004_Article_484143.pd

Clinical Equivalence of Generic Clozapine

Objective: To determine if mental health service utilization increases when patients are converted to generic clozapine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44320/1/10597_2005_Article_5981.pd

Pathways to cellular supremacy in biocomputing

Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the “genetic circuit” metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally limits the types of computation that may be engineered inside the cell, and fails to exploit the rich and diverse functionality available in natural living systems. We propose the notion of “cellular supremacy” to focus attention on domains in which biocomputing might offer superior performance over traditional computers. We consider potential pathways toward cellular supremacy, and suggest application areas in which it may be found.A.G.-M. was supported by the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1) and the European CSA on biological standardization BIOROBOOST (EU grant number 820699). T.E.G. was supported by a Royal Society University Research Fellowship (grant UF160357) and BrisSynBio, a BBSRC/ EPSRC Synthetic Biology Research Centre (grant BB/L01386X/1). P.Z. was supported by the EPSRC Portabolomics project (grant EP/N031962/1). P.C. was supported by SynBioChem, a BBSRC/EPSRC Centre for Synthetic Biology of Fine and Specialty Chemicals (grant BB/M017702/1) and the ShikiFactory100 project of the European Union’s Horizon 2020 research and innovation programme under grant agreement 814408

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Cardiovascular hyperreactivity to a psychological and a physical stressor in the Tecumseh community blood pressure study: Methodological issues and associations with risk factors for coronary heart disease.

Cardiovascular reactivity to two stressors, mental arithmetic and isometric handgrip, was investigated in a population-based study of 627 men and women (mean age: 32.2 years) in Tecumseh, Michigan. The results are presented in two papers which comprise chapters three and four, respectively, of this dissertation. The first focuses on methodological issues; the second on aspects of the hypothesis that cardiovascular hyperreactivity to stress is a physiologic link between environmental stress and coronary heart disease (CHD). The methodological findings indicated that: the distribution of reactivity measures are skewed to the right; the lowest baseline blood pressures were recorded at home in the morning; observer differences influenced the measurement of reactivity, particularly for responses to mental stress in women; blood pressure reactivity to the handgrip stressor was higher in men and in younger subjects, suggesting that strength may account for these differences; and there were weak but significant negative correlations between baseline cardiovascular levels and their corresponding reactivities. It was concluded that these factors should be accounted for in future studies of reactivity and CHD. The second paper examined the validity of two key assumptions underlying the basic hypothesis: that reactivity is a stable trait and that a subpopulation of hyperreactors could be identified. It also assessed a proposed mechanism for the hypothesis: that reactivity is a marker for a generalized hyperreactivity to stress manifested also by increased catecholamine and renin levels which, in turn, elicit increased levels of CHD risk factors. The findings showed that: both inter-task and intra-task stability of reactivity were significant but weak; probability-based mixture analyses identified hyperreactor subgroups for all reactivity measures, but the number of hyperreactors was less than 10 for all measures but responses to mental arithmetic in men; and there were very few significant or consistent associations of reactivity with catecholamines or renin or with risk factors such as serum lipids, insulin, glucose, obesity, left ventricular mass, smoking or alcohol. These data provide little support for the hypotheses that hyperreactivity is a unique, stable trait or that hyperreactivity is associated with CHD through its influence on CHD risk factors.Ph.D.Epidemiologic ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105901/1/9226905.pdfDescription of 9226905.pdf : Restricted to UM users only

Engaging children in the development of obesity interventions: Exploring outcomes that matter most among obesity positive outliers

Objective To explore outcomes and measures of success that matter most to 'positive outlier' children who improved their body mass index (BMI) despite living in obesogenic neighborhoods. Methods We collected residential address and longitudinal height/weight data from electronic health records of 22,657 children ages 6–12 years in Massachusetts. We defined obesity “hotspots” as zip codes where >15% of children had a BMI ≥95th percentile. Using linear mixed effects models, we generated a BMI z-score slope for each child with a history of obesity. We recruited 10–12 year-olds with negative slopes living in hotspots for focus groups. We analyzed group transcripts and discussed emerging themes in iterative meetings using an immersion/crystallization approach. Results We reached thematic saturation after 4 focus groups with 21 children. Children identified bullying and negative peer comparisons related to physical appearance, clothing size, and athletic ability as motivating them to achieve a healthier weight, and they measured success as improvement in these domains. Positive relationships with friends and family facilitated both behavior change initiation and maintenance. Conclusions The perspectives of positive outlier children can provide insight into children’s motivations leading to successful obesity management. Practice implications: Child/family engagement should guide the development of patient-centered obesity interventions

Adverse Childhood Exposures and Alcohol Dependence Among Seven Native American Tribes

Alcohol abuse and alcoholism are leading causes of death among Native Americans. Little is known about the impact of negative childhood exposures, including parental alcoholism, childhood maltreatment, and out-of-home placement, on risk of lifetime DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis of alcohol dependence in this population

Summary of results of loss and gain of N-glycosylation in the human proteome.

<p>Summary of results of loss and gain of N-glycosylation in the human proteome.</p