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PubMed2006

Integrated analysis of transcriptomic and proteomic data of Desulfovibrio vulgaris: zero-inflated Poisson regression models to predict abundance of undetected proteins.

MOTIVATION: Integrated analysis of global scale transcriptomic and proteomic data can provide important insights into the metabolic mechanisms underlying complex biological systems. However, because the relationship between protein abundance and mRNA expression level is complicated by many cellular and physical processes, sophisticated statistical models need to be developed to capture their relationship. RESULTS: In this study, we describe a novel data-driven statistical model to integrate whole-genome microarray and proteomic data collected from Desulfovibrio vulgaris grown under three different conditions. Based on the Poisson distribution pattern of proteomic data and the fact that a large number of proteins were undetected (excess zeros), zero-inflated Poisson (ZIP)-based models were proposed to define the correlation pattern between mRNA and protein abundance. In addition, by assuming that there is a probability mass at zero representing unexpressed genes and expressed proteins that were undetected owing to technical limitations, a Potential ZIP model was established. Two significant improvements introduced by this approach are (1) the predicted protein abundance level values for experimentally detected proteins are corrected by considering their mRNA levels and (2) protein abundance values can be predicted for undetected proteins (in the case of this study, approximately 83% of the proteins in the D.vulgaris genome) for better biological interpretation. We demonstrated the use of these statistical models by comparatively analyzing proteomic and microarray results from D.vulgaris grown on lactate-based versus formate-based media. These models correctly predicted increased expression of Ech hydrogenase and decreased expression of Coo hydrogenase for D.vulgaris grown on formate.

Adenosine Triphosphate↗

PubMed2005

Asymmetry in RNA pseudoknots: observation and theory.

RNA can fold into a topological structure called a pseudoknot, composed of non-nested double-stranded stems connected by single-stranded loops. Our examination of the PseudoBase database of pseudoknotted RNA structures reveals asymmetries in the stem and loop lengths and provocative composition differences between the loops. By taking into account differences between major and minor grooves of the RNA double helix, we explain much of the asymmetry with a simple polymer physics model and statistical mechanical theory, with only one adjustable parameter.

Biopolymers↗

PubMed1994

Stress, coping, and well-being among third-year medical students.

BACKGROUND: Medical school is recognized as a stressful environment that often exerts a negative effect on the academic performance, physical health, and psychological well-being of the student. METHOD: Stress, coping, depression, and somatic distress were examined among 69 third-year students completing a psychiatry clerkship in 1992-93 at the University of Mississippi School of Medicine. Stress was assessed using the Medical Education Hassles Scale-R. Coping was assessed using the Coping Strategies Inventory. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale, and somatic distress was assessed using the Wahler Physical Symptoms Inventory. Statistical methods included correlational analysis and hierarchical regression. RESULTS: Clinical levels of depression were found in 16 (23%) of the students, and 39 (57%) endorsed high levels of somatic distress. Stress accounted for a large percentage of the distress variance (i.e., 29% to 50%). Coping efforts contributed significant variance to the prediction of distress above and beyond that accounted for by stress alone, especially in relation to depression. Coping efforts classified by Engagement strategies were associated with fever depressive symptoms, while coping efforts classified by Disengagement strategies were associated with higher levels of depressive symptoms. CONCLUSIONS: Because students who employed coping efforts characterized by Engagement strategies suffered from fewer depressive symptoms, the results suggest that training in these types of strategies may be a useful intervention to lessen the negative consequences of stress among medical students.

Adaptation, Psychological↗

PubMed1990

Psychosocial predictors of survival in end-stage renal disease.

Several psychosocial variables were investigated as predictors of 4-year survival in a sample of 97 end-stage renal disease (ESRD) patients undergoing treatment by hemodialysis, continuous ambulatory peritoneal dialysis, or renal transplantation. Hypothesized psychosocial predictors included depression, mood disturbance, life happiness, affect, pessimism, self-esteem, knowledge of renal disease and its treatment, perceived control over important life domains, perceived intrusiveness of ESRD into important life domains, illness-related concerns, difficulties in daily activities, number of regular leisure activities, somatic symptoms of distress, social networks, recent negative life events, and defensive response styles. Methodological controls were incorporated to test the prognostic significance of these variables and included a) exclusion of deaths attributable to "unnatural" causes; b) multivariate statistical controls for physical and demographic determinants of survival; c) widely used standardized psychosocial instruments; and d) temporally aggregated psychosocial measurements to enhance reliability. Hierarchical multiple regression analyses identified four variables as significant and independent predictors of increased survival times in ESRD: a) comparatively fewer serious nonrenal comorbid illnesses; b) younger age; c) regular involvement in an increased number of leisure activities; and d) overall life happiness described as "an even mixture of unhappiness and happiness" (as compared with "very happy"). However, no evidence was obtained to support the hypothesis that increased depressive symptoms and/or moods contribute to compromised survival in ESRD.

Adaptation, Psychological↗

PubMed1999

Measurement of health-related quality of life in patients with amyotrophic lateral sclerosis in clinical trials of new therapies.

OBJECTIVES: Recent trials of amyotrophic lateral sclerosis (ALS) therapies have included the Sickness Impact Profile (SIP) to evaluate health-related quality of life (HQL). The purpose of this study was to assess the feasibility, psychometric properties, and interpretation of the Sickness Impact Profile in this setting. METHODS: The Sickness Impact Profile was administered at baseline, 3, 6, and 9 months during a double-blind, placebo-controlled study of recombinant human insulin-like growth factor I. The frequency of missing Sickness Impact Profile data and administration time were recorded. Patients' scores on the Appel ALS (AALS) Rating Scale were used to identify a stable subgroup for reliability testing and clinically distinct groups for validity testing. Internal consistency reliability and reproducibility were evaluated using Cronbach's alpha and intraclass correlation coefficients, respectively. Analysis of variance (ANOVA) models and t tests were used to assess validity. Effect sizes and the responsiveness index were used to assess responsiveness. RESULTS: At baseline, 259 (97%) patients completed a 30-minute Sickness Impact Profile interview. At subsequent assessments, response rates ranged from 92% to 97% and mean administration times ranged from 25 to 27 minutes. The overall Sickness Impact Profile score demonstrated alpha reliability and 3-month stability coefficients of 0.94 and 0.80, respectively. Baseline overall Sickness Impact Profile scores discriminated between patients in the two AALS-defined groups with a mean of 13.0+/-7.8 and 24.0+/-11.7 in the better and worse AALS groups, respectively. Similarly, mean overall SIP change scores discriminated patients progressing at different rates (slow to moderate = 4.00+/-7.97; rapid = 10.74+/-8.76). With few exceptions, dimension and category scores met similar criteria. Responsiveness statistics for the physical and overall Sickness Impact Profile scores were lower at 3 months and higher at 6 and 9 months. CONCLUSIONS: The feasibility, psychometric, and interpretive findings support the validity of the Sickness Impact Profile for assessing outcomes of amyotrophic lateral sclerosis and its treatment. Based on these findings, we recommend including the Sickness Impact Profile in future amyotrophic lateral sclerosis clinical trials.

Activities of Daily Living↗

PubMed2006

Functional gastrointestinal disorders in African American children in primary care.

OBJECTIVE: To determine the prevalence of functional gastrointestinal disorders (FGIDs) in a primary care setting and to assess the usefulness of pediatric Rome criteria. METHODS: The Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) assessing the pediatric Rome criteria was administered to 243 school-age children visiting a general pediatric clinic for annual school physicals. Pearson chi statistics were used to determine the association of various demographic factors with FGIDs. RESULTS: All children were African American, 47.7% were girls, and the mean +/- standard deviation age of the group was 10.7 +/- 3.9 years. QPGS detected 52 children (21.4%) with FGID. Diagnoses included aerophagia (6), abdominal migraine (1), cyclic vomiting syndrome (2), functional dyspepsia (2), functional abdominal pain syndrome (1), functional constipation (39) and functional fecal retention (1). Thorough clinical evaluation identified 47 (19.3%) children with FGIDs. Five of the children (2.1%) identified as having FGID on QPGS were felt not to have FGID by the examining physician. Children with FGIDs were not different from healthy children in age, insurance, parent's education, employment or number of children in the family. FGIDs were more common in girls (29/47 girls, P = 0.028). Children with FGIDs tended to live in single-parent households and miss school more often than children without FGIDs (P = 0.08). CONCLUSIONS: Functional gastrointestinal disorders are common among African American children and adolescents in a primary care setting and predominantly affect girls. Symptom-based criteria are useful in the diagnosis of pediatric FGIDs.

Abdominal Pain↗

PubMed2000

Intermingled basins and on-off intermittency in a multistate system

We consider a dynamical system containing infinite low-dimensional symmetric invariant subspaces, each of which has a chaotic state. Intermingled basins are found between these multiple chaotic states when they are stable in the subspaces. As a parameter of the system varies, the largest Lyapunov exponent transverse to the invariant subspace can change from negative to positive; then, the system dynamics changes from an intermingled basin state to a multistate on-off intermittency. The statistical behavior and physical transportation property for different dynamic states are investigated in detail.

Journal Article↗

PubMed2002

Edge-preserving tomographic reconstruction with nonlocal regularization.

Tomographic image reconstruction using statistical methods can provide more accurate system modeling, statistical models, and physical constraints than the conventional filtered backprojection (FBP) method. Because of the ill posedness of the reconstruction problem, a roughness penalty is often imposed on the solution to control noise. To avoid smoothing of edges, which are important image attributes, various edge-preserving regularization methods have been proposed. Most of these schemes rely on information from local neighborhoods to determine the presence of edges. In this paper, we propose a cost function that incorporates nonlocal boundary information into the regularization method. We use an alternating minimization algorithm with deterministic annealing to minimize the proposed cost function, jointly estimating region boundaries and object pixel values. We apply variational techniques implemented using level-sets methods to update the boundary estimates; then, using the most recent boundary estimate, we minimize a space-variant quadratic cost function to update the image estimate. For the positron emission tomography transmission reconstruction application, we compare the bias-variance tradeoff of this method with that of a "conventional" penalized-likelihood algorithm with local Huber roughness penalty.

Algorithms↗

PubMed1985

Use of residence time moments in compartmental analysis.

Residence time moments, particularly mean residence times, can be very useful in the modeling and kinetic analysis of physiological systems. They are defined and illustrated, and their practical utility is then explored by comparing the model formulation based on these moments with three alternative formulations: component half-lives, compartmental model rate coefficients, and multiexponential model coefficients and exponents. The residence time moment formulation is shown to have several advantages: a smaller number of parameters are usually needed to describe a biological system; they have a clear physical interpretation; their statistical "power" to detect certain treatment differences is greater; and they are computationally simpler in many situations.

Animals↗

PubMed2004

The use of a spatial information system in the management of HIV/AIDS in South Africa.

BACKGROUND: South Africa is experiencing an HIV/AIDS pandemic of shattering dimensions. The availability and provision of antiretroviral (ARV) drugs could bring relief to the situation, but the treatment is unfortunately complex with each patient being assigned a different antiretroviral therapy varying in diet-medication regiment. The context of South Africa, its variety of urban and rural settings adds to the challenge of administering and monitoring the HIV+ person throughout the treatment, which will last for the rest of their lives. The lack of physical infrastructure, reliable statistics and adequate resources hinder the efficient management of HIV/AIDS. RESULTS: The collection of reliable data will be a first step to assess the status of HIV/AIDS in communities. A number of hospitals have started this process using the conventional approach to collect information about their patients using a paper-based system. Since time is of essence in the fight against the pandemic, data exchange between various hospitals, municipalities and decision-making bodies is becoming more and more important. The logical response to such a need is a computerised system, which will collect and administer HIV/AIDS related information within the local context and allow a monitored access to the data from a number of stakeholders. CONCLUSIONS: The purpose of this study was to design and develop an HIV/AIDS database, which is embedded in a Spatial Information Management System. The pilot study area is the Gugulethu township in Cape Town where more than 27% of the 325 000 residents are HIV+. It is shown that the implementation of the HIV/AIDS database and the Spatial Information Management System can play a critical role in determining where and when to intervene, improving the quality of care for HIV+ patients, increasing accessibility of service and delivering a cost-effective mode of information.

Journal Article↗

PubMed2000

Invariant cone-excitation ratios may predict transparency.

Cone-excitation ratios for pairs of surfaces are almost invariant under changes in illumination and offer a possible basis for color constancy [Proc. R. Soc. London Ser. B 257, 115 (1994)]. We extend this idea to the perception of transparency on the basis of the close analogy between the changes in color signals that occur for surfaces when the illumination changes and the changes in color signals when the surfaces are covered by a filter. This study presents measurements and simulations to investigate the conditions under which cone-excitation ratios are statistically invariant for physically transparent systems. The invariance breaks down when the spectral transmission of the filters is low at some or all wavelengths. We suggest that cone-excitation ratios might be useful to define the stimulus conditions necessary for the perception of transparency.

Color↗

PubMed2005

The effectiveness of different combinations of pulmonary rehabilitation program components: a randomized controlled trial.

STUDY OBJECTIVES: To study the short-term and long-term effects of combining activity training or lectures to exercise training on quality of life, functional status, and exercise tolerance. DESIGN: Randomized clinical trial. SETTING: Outpatient pulmonary rehabilitation center. PARTICIPANTS: Forty-three outpatients with COPD. INTERVENTIONS: Patients were randomized to one of three treatment groups: exercise training alone, exercise training plus activity training, and exercise training plus a lecture series. The mean treatment period was 10 weeks. MEASUREMENT: The Chronic Respiratory Disease Questionnaire, the modified version of the Pulmonary Functional Status and Dyspnea Questionnaire, and the COPD Self-Efficacy Scale were administered at baseline, and 6, 12, 18, and 24 weeks from the beginning of the rehabilitation program. The 6-min walk test was used to measure exercise tolerance. RESULTS: Benefits of activity training combined with exercise included less dyspnea (p < or = 0.04) and fatigue (p < or = 0.01), and increased activity involvement (p < or = 0.02) and total functional status (p < or = 0.02) in the short term compared to comparison treatment groups for comparatively older participants. Compared to the lecture series adjunct, the activity training adjunct resulted in significantly higher gains in total quality of life (p = 0.04) maintained at 24 weeks. Significantly worse emotional function and functional status resulted from the lecture series adjunct in the oldest participants (p < or = 0.03). Treatment groups did not differ significantly on exercise tolerance or self-efficacy. CONCLUSIONS: Evidence for additional benefits of activity-specific training combined with exercise was found. A behavioral method emphasizing structured controlled breathing and supervised physical activity was statistically significantly more effective than didactic instruction in facilitating additional gains and meeting participants' learning needs.

Age Factors↗

PubMed2006

Is the nausea and vomiting of early pregnancy really feto-protective?

BACKGROUND: Health care providers and popular press articles frequently advise women that nausea and vomiting of early pregnancy (NVP) portends a favorable fetal outcome. AIM: To investigate the claim that NVP protects against adverse fetal outcomes and improves placental and fetal growth. METHODS: Data were collected on a prospective cohort of 849 Ecuadorian prenatal patients beginning in early gestation until postpartum. A questionnaire collected information on NVP and other maternal characteristics. Fetal outcomes and placental characteristics were examined using anthropometry and physical examination. Multivariate statistical methods controlled for potential confounders. RESULTS: Women with nausea only (AOR = 0.45; 95% CI = 0.22-0.94) or nausea with vomiting (AOR = 0.66; 95% CI = 0.46-0.99) had significantly decreased miscarriage risk although the strength of the protection appeared less than that reported for other populations. NVP was not associated with low birth weight, preterm delivery, congenital anomaly, or other outcomes excepting slightly increased mean infant thigh skinfold (P = 0.024), mid-upper arm circumference (P = 0.049), and placental weight (P = 0.034). CONCLUSIONS: The data did not support the common belief that NVP protects against multiple adverse outcomes. Placental weight was slightly increased in women with NVP but this difference was not reflected in higher birth weights or other types of fetal growth except of marginally increased limb fat.

Abortion, Spontaneous↗

PubMed2003

[Pudendal neuropathy: correlation with demographic data, severity index and pressoric parameters in patients with fecal incontinence].

BACKGROUND: Fecal incontinence stands for inability in maintaining the control of defecation to a socially acceptable and adequate time and place, resulting in unwanted release of gas, liquid or solid stool. The diagnosis needs multiple exams. Anorectal manometry is mandatory for this study. The correlation between manometry with electophysiological studies and symptoms is not yet clear in the literature. AIMS: Correlate values of anal manometry, pudental nerve terminal motor latency and co morbidity in fecal incontinence patients. METHODOLOGY AND PATIENTS: Patients with clinical fecal incontinence, who attended the outpatient department of "Hospital Nossa Senhora da Concei o", Porto Alegre, RS, Brazil, between March 1997 and June 2000, were studied prospectively. Every single patient has undergone a general investigation, incontinence score, anal manometry, bilateral pudendal nerve terminal motor latency and physical examination. For statistical purposes the patients were separated in groups according to the results of the anal manometry, pudendal neuropathy, for age and sex. RESULTS/CONCLUSION: Thirty-nine patients were studied, 85,6% female, average age 60,1 years (+/- 12,89). The average index of the fecal incontinence was of 9,30 (+/- 4,93). In the anorectal manometry 23 patients showed low pressure. The pressures were significantly higher among males. The nerve terminal motor latency and pudental nerve (neuropathy) time was greater in 14 patients (35,9%). The age and the time of pudental nerve terminal motor were significantly co related. The other co relations were not statistically significant.

Adult↗

PubMed2005

Longitudinal assessment of quality of life in patients with type 2 diabetes and self-reported erectile dysfunction.

OBJECTIVE: In the context of the QuED (Quality of Care and Outcomes in Type 2 Diabetes) project, we evaluated the longitudinal changes over 3 years in quality of life (QoL) in patients with type 2 diabetes according to the presence or the development of erectile dysfunction (ED). RESEARCH DESIGN AND METHODS: Patients were requested to fill in a questionnaire investigating the presence of ED and QoL (SF-36 Health Survey, depression symptoms [Center for Epidemiologic Studies-Depression], and quality of sexual life) every 6 months for 3 years. The analyses were based on multilevel models, adjusted for patient clinical and sociodemographic characteristics. RESULTS: The study involved 1,456 patients, of whom 34% reported frequent erectile problems at baseline; 192 developed ED during the follow-up. No changes in QoL measures were detected in patients without ED; in those with ED at baseline, a worsening in all SF-36 scales was observed, reaching statistical significance for physical functioning (P = 0.03). Among patients who developed ED during the study, a deterioration in all SF-36 dimensions and a worsening in depressive symptoms preceded the development of ED. The onset of ED was associated with a further marked worsening in physical functioning (P = 0.0008), general health perception (P = 0.02), and social functioning (P = 0.04) on SF-36 subscales, as well as in the summary physical and mental components scores (P = 0.04 and P = 0.07, respectively). The development of ED was also associated with a highly significant increase in depressive symptoms (P = 0.001) and a marked decrease in quality of sexual life (P < 0.0001). CONCLUSIONS: This longitudinal study documents for the first time the impact of ED onset on several aspects of QoL in patients with type 2 diabetes. The study also shows that QoL tended to further decrease during 3 years in patients with ED at baseline but not in those without this condition.

Aged↗

PubMed1997

The effect of continuous passive motion duration and increment on range of motion in total knee arthroplasty patients.

There is insufficient information on continuous passive motion (CPM) parameters in total knee arthroplasty patients for optimal patient outcomes. We compared CPM duration and increments on active and passive range of motion (ROM) in patients who underwent a unilateral total knee arthroplasty due to degenerative joint disease. Forty-five total knee arthroplasty patients were randomly assigned to either a control group, a short CPM duration (3-5 hours per day) group with CPM ROM increased 5 degrees twice daily, a short CPM duration group with CPM ROM increased daily to patient tolerance, a long CPM duration (10-12 hours per day) group with CPM ROM increased 5 degrees twice daily, or a long CPM duration group with CPM ROM increased daily to patient tolerance. Active and passive flexion and extension were measured goniometrically on each postoperative day that the patient was treated by physical therapy. No statistically significant differences between groups were found for baseline and final postoperative ROM. The CPM groups did not maintain the parameters assigned and were combined, revealing an enhanced rate of change of flexion. Most patients opted for a CPM duration of between 4 and 8 hours per day and the patient-preferred CPM incremental increase in ROM was 6-7 degrees/day.

Aged↗

PubMed2004

Effects of training in direct observation of medical residents' clinical competence: a randomized trial.

BACKGROUND: Faculty observation of residents and students performing clinical skills is essential for reliable and valid evaluation of trainees. OBJECTIVE: To evaluate the efficacy of a new multifaceted method of faculty development called direct observation of competence training. DESIGN: Controlled trial of faculty from 16 internal medicine residency programs using a cluster randomization design. SETTING: Academic medical centers. PARTICIPANTS: 40 internal medicine teaching faculty members: 17 in the intervention group and 23 in the control group. MEASUREMENTS: Changes in faculty comfort performing direct observation, faculty satisfaction with workshop, and changes in faculty rating behaviors 8 months after completing the training. INTERVENTION: The direct observation of competence workshop combines didactic mini-lectures, interactive small group and videotape evaluation exercises, and evaluation skill practice with standardized residents and patients. RESULTS: 37 faculty members (16 in the intervention group and 21 in the control group) completed the study. Most of the faculty in the intervention group (14 [88%]) reported that they felt significantly more comfortable performing direct observation compared with control group faculty (4 [19%]) (P = 0.04), and all intervention faculty rated the training as outstanding. For 9 videotaped clinical encounters, intervention group faculty were more stringent than controls in their evaluations of medical interviewing, physical examination, and counseling; differences in ratings for medical interviewing and physical examination remained statistically significant even after adjustment for baseline rating behavior. LIMITATIONS: The study involved a limited number of residency programs, and faculty did not rate the performance of actual residents. CONCLUSION: Direct observation of competence training, a new multifaceted approach to faculty development, leads to meaningful changes in rating behaviors and in faculty comfort with evaluation of clinical skills.

Adult↗

PubMed2006

Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.

BACKGROUND: Alzheimer disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial. OBJECTIVE: To determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer disease. DESIGN: Prospective cohort study. SETTING: Group Health Cooperative, Seattle, Washington. PARTICIPANTS: 1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study and who were followed biennially to identify incident dementia. MEASUREMENTS: Baseline measurements, including exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E epsilon4); biennial assessment for dementia. RESULTS: During a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease. LIMITATIONS: Exercise was measured by self-reported frequency. The study population had a relatively high proportion of regular exercisers at baseline. CONCLUSION: These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons.

Age of Onset↗