PubMed Health⌕ Search

Biomedical subjects

Michael Clark

Publications and source records attributed to Michael Clark.

At least 19 recordsLinked to original sources

A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We use transcriptomic and epigenomic cortical cell-type taxonomies from mouse and human to define marker genes and putative enhancers and create a large toolkit of transgenic lines and enhancer adeno-associated viruses (AAVs) for selective targeting of cortical cell populations. We report creation and evaluation of fifteen transgenic driver lines, two reporter lines, and >1,000 different enhancer AAV vectors covering most subclasses of cortical cells. The tools reported here have been made publicly available, and along with the scaled process of tool creation, evaluation, and modification, they will enable diverse experimental strategies toward understanding mammalian cortex and brain function.

Animals↗

Development of the Adelaide driving self-efficacy scale.

OBJECTIVE: To describe the development of the Adelaide Driving Self-Efficacy Scale (ADSES) and to report on its reliability and validity. METHODS: A set of 12 driving behaviours, developed through literature review, clinical experience and expert review, were rated for self-efficacy using a Likert scale. Internal consistency was investigated using a Cronbach's alpha coefficient and construct validity by comparing ADSES scores of stroke and non-stroke drivers. Criterion-related validity was examined by comparing ADSES scores with the result on a standardized on-road assessment. SETTING: A rehabilitation hospital in Adelaide, South Australia. PARTICIPANTS: Staff from the hospital and stroke patients from the rehabilitation unit. Data from a non-stroke sample (n -/ 79) and stroke patients (n -/ 81) were used to test internal consistency and construct validity. A separate group of 45 people recommended for a driving assessment, of whom 34 were stroke patients, were used to test criterion validity. RESULTS: Cronbach's alpha coefficient was 0.98, indicating high internal consistency. The non-stroke and stroke groups showed significant differences in ADSES scores (t(158)-/ 5.5, P B < 0.05), demonstrating construct validity. Differences in ADSES scores for those participants who passed or failed the on-road assessment were significant for both the entire driving assessment group (t(43)-/ 3.2, P B < 0.05) and the stroke subgroup (t(43)-/ 3.2, P B < 0.05), indicating criterion validity. CONCLUSION: The ADSES has demonstrated internal consistency and construct validity with the stroke and non-stroke population. The scale demonstrated criterion validity in its relationship with outcome of an on-road driving assessment. It appears to be a reliable and valid measure of driving self-efficacy.

Adult↗

Adherence with isoniazid for prevention of tuberculosis among HIV-infected adults in South Africa.

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH) is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH) urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. METHODS: Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. RESULTS: 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0) of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001). In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043). Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007). Belief in INH safety was associated with a positive test (p = 0.021). In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086). CONCLUSION: Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.

AIDS-Related Opportunistic Infections↗

The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID) incidence, above which BCG is associated with greater risk than benefit. METHODS: A Markov model was developed to simulate the natural histories of tuberculosis (TB) and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI) and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs). RESULTS: In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations) which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000. CONCLUSION: The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control--including early detection and treatment of infection--may be a safer, more effective alternative.

BCG Vaccine↗

Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.

Music therapy has decreased anxiety levels in many medical settings. This randomized clinical trial examined the effectiveness of a music listening intervention, delivered by a board-certified music therapist, in patients undergoing curative radiation therapy (RT). Emotional distress (anxiety, depression, and treatment-related distress) and symptoms (fatigue and pain) were measured at baseline, mid-treatment, and end of treatment in 63 patients undergoing RT. Although patients who listened to self-selected music reported lower anxiety and treatment-related distress, there was a decline in these outcomes for patients in both groups over the course of RT. Depression, fatigue, and pain were not appreciably affected by music therapy. Within the music group, there was a significant correlation between number of times music was used/week and the change in treatment-related distress, suggesting that higher doses of music produced greater declines in distress. While these findings provided some support for the use of music in reducing distress during RT, further research demonstrating clear differences between intervention and control conditions is needed. Physical symptoms were not affected by the use of music over the course of RT.

Adult↗

Measurement of lower leg compression in vivo: recommendations for the performance of measurements of interface pressure and stiffness: consensus statement.

BACKGROUND: Interface pressure and stiffness characterizing the elastic properties of the material are the parameters determining the dosage of compression treatment and should therefore be measured in future clinical trials. OBJECTIVE: To provide some recommendations regarding the use of suitable methods for this indication. METHOD: This article was formulated based on the results of an international consensus meeting between a group of medical experts and representatives from the industry held in January 2005 in Vienna, Austria. RESULTS: Proposals are made concerning methods for measuring the interface pressure and for assessing the stiffness of a compression device in an individual patient. CONCLUSIONS: In vivo measurement of interface pressure is encouraged when clinical and experimental outcomes of compression treatment are to be evaluated.

Bandages↗

Serious adverse events associated with bacille Calmette-Guérin vaccine in Canada.

BACKGROUND: Targeted Bacille Calmette-Guérin (BCG) vaccination is offered to neonates in some First Nations and Inuit (FNI) communities in Canada. Serious adverse events associated with BCG vaccine prompted a review to assess causality. METHODS: The Immunization Monitoring Program Active (IMPACT), a pediatric hospital-based active surveillance network, reported admissions for BCG-related adverse events between 1993 and April 2002. The Canadian Advisory Committee on Causality Assessment (ACCA) reviewed the reports to assess causality. Data between 1987 and September 2002 from the Vaccine-Associated Adverse Event Surveillance (VAAES) Program, a passive national reporting system, were also reviewed. RESULTS: IMPACT identified 21 pediatric cases; 19 were Canadian-born, and 18 were FNI. Six disseminated BCG cases were identified; 5 were FNI infants who subsequently died. All had immunodeficiencies and concurrent infections. Other adverse events included 2 cases of osteomyelitis, BCG abscesses and lymphadenitis. ACCA reviewed the 21 cases and determined that 14 were very likely associated with the vaccine, including the 6 disseminated BCGs; 5 were probably associated and 1 was possibly associated with the vaccine; 1 was unclassifiable. The VAAES program identified 157 adverse events. No additional serious systemic adverse events (disseminated BCG or osteomyelitis) were identified. CONCLUSIONS: Serious BCG vaccine-associated complications continue to occur in Canada. The numbers of FNI children with disseminated disease was greater than expected from reported rates in the literature.

Adverse Drug Reaction Reporting Systems↗

The use of maximum likelihood methods to estimate the risk of tuberculous infection and disease in a Canadian First Nations population.

BACKGROUND: Tuberculosis (TB) notification rates among First Nations people in British Columbia, Canada, are higher than those among non-First Nations people, although rates are declining more rapidly in the First Nations population. The epidemiology of tuberculous infection and disease during the period 1926-2000 in this population was investigated. METHODS: The trend in the annual risk of infection (ARI) since 1926 was estimated using tuberculous meningitis mortality statistics and skin testing data. Risks of progression from infection to disease were estimated by fitting model predictions of disease incidence to TB notifications, using maximum likelihood methods. Infectious TB notifications were matched with ARI estimates to obtain the number of transmissions per infectious case over time. RESULTS: We estimate that the ARI decreased from more than 10% during the prechemotherapy era to less than 0.1% by 2000. The risks of primary, reactivation, and exogenous re-infection disease among adults aged 25-44 years were 22%, 0.1%, and 6%, respectively. The number of transmissions per infectious case decreased from 16 to 2 from the early 1970s to the late 1990s. CONCLUSIONS: This study shows that the risk of infection among British Columbia First Nations people is decreasing, while the relative contribution of reactivation to disease incidence is increasing. Once infected, First Nations people may have a higher risk of developing disease than other populations.

Adolescent↗

Effect of compression on blood flow in lower limb wounds.

Blood flow is believed to be a key parameter in the formation and management of lower limb wounds. Patients with venous leg ulcers (VLUs) have high venous pressures, due to the partial or complete failure of calf muscle pump, which in turn disturbs the local blood flow within the lower limb. Compression has currently been the mainstay for treatment of VLUs and is thought to restore valvular competence and reduce or suppress superficial and deep venous reflux. Efficacy and assessment of compression therapy can be understood in a better way by measuring blood flow in lower limbs. Publications applicable to the effects of compression on lower limb blood flow parameters are summarised. However, they have shown varying results due to the different methodology and assessment techniques used. This article seeks to explore the methods of assessment of blood flow in the lower limb associated with wound management and compression in particular and provides suggestions for future explorations.

Bandages↗

Analysis of skin wound images using digital color image processing: a preliminary communication.

This article presents the use of digital image processing using hue, saturation, and intensity measurements as a technique for the color analysis of chronic wounds on the skin. An adaptive spline technique was used to segment the wound boundary in the images of venous leg ulcers. This technique was further used to approximate the position of venous leg ulcers. The amount of slough within the wound site was quantified using the software developed and was compared with a grading system based on visual inspection by an experienced clinician, and the results were compared by deriving Kappa (K) statistic. There was moderate agreement over all grades between the computer and clinician. At lower grades 1 and 2, there was excellent agreement. The results from this preliminary study suggest that this analytical technique has the potential to image process chronic skin wounds.

Journal Article↗