Optimal risk-based allocation of disease surveillance effort for clustered disease outbreaks.

Designing a disease surveillance program to detect a disease is challenging when animals are organized into herds, in part because disease cases are likely to be clustered. Clustered diseases are often surveilled using two-stage sampling, which allocates tests both among herds and within herds. Finding the optimal allocation of tests is computationally difficult, so some surveillance programs simply seek an approximate solution.

Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo.

Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.

Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways.

Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models.

Condensin I recruitment to base damage-enriched DNA lesions is modulated by PARP1.

Condensin I is important for chromosome organization and segregation in mitosis. We previously showed that condensin I also interacts with PARP1 in response to DNA damage and plays a role in single-strand break repair. However, whether condensin I physically associates with DNA damage sites and how PARP1 may contribute to this process were unclear.

Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells.

Proper recognition and repair of DNA damage is critical for the cell to protect its genomic integrity. Laser microirradiation ranging in wavelength from ultraviolet A (UVA) to near-infrared (NIR) can be used to induce damage in a defined region in the cell nucleus, representing an innovative technology to effectively analyze the in vivo DNA double-strand break (DSB) damage recognition process in mammalian cells. However, the damage-inducing characteristics of the different laser systems have not been fully investigated.

In situ analysis of DNA damage response and repair using laser microirradiation.

A proper response to DNA damage is critical for the maintenance of genome integrity. However, it is difficult to study the in vivo kinetics and factor requirements of the damage recognition process in mammalian cells. In order to address how the cell reacts to DNA damage, we utilized a second harmonic (532 nm) pulsed Nd:YAG laser to induce highly concentrated damage in a small area in interphase cell nuclei and cytologically analyzed both protein recruitment and modification.

Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair.

Condensins are essential protein complexes critical for mitotic chromosome organization. Little is known about the function of condensins during interphase, particularly in mammalian cells. Here we report the interphase-specific interaction between condensin I and the DNA nick-sensor poly(ADP-ribose) polymerase 1 (PARP-1).

Differential post-transcriptional activation of human phagocytes by different Pseudomonas aeruginosa isolates.

Pseudomonas aeruginosa is a pulmonary pathogen in individuals with impaired mucociliary clearance such as cystic fibrosis or mechanical ventilation. Non-opsonic phagocytosis of P. aeruginosa can be mediated by either CR3 or CD14 and different strains appear to have a bias towards one or the other receptor.

Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery.

Proper patterns of genome-wide DNA methylation, mediated by DNA methyltransferases DNMT1, -3A and -3B, are essential for embryonic development and genomic stability in mammalian cells. The de novo DNA methyltransferase DNMT3B is of particular interest because it is frequently overexpressed in tumor cells and is mutated in immunodeficiency, centromere instability and facial anomalies (ICF) syndrome. In order to gain a better understanding of DNMT3B, in terms of the targeting of its methylation activity and its role in genome stability, we biochemically purified endogenous DNMT3B from HeLa cells.

Nonopsonic phagocytosis of Pseudomonas aeruginoas: insights from an infant with leukocyte adhesion deficiency.

Children with leukocyte adhesion deficiency type I are at risk for overwhelming infection because their neutrophils lack surface beta 2 integrins (CD18/CD11) that normally interact with endothelial cell adhesion molecules and mediate migration to sites of bacterial invasion. In vitro studies of phagocytic cells from an infant with leukocyte adhesion deficiency type I demonstrated that complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some Pseudomonas aeruginosa strains and might play a control role in the control of Pseudomonas infections at sites where there are low levels of opsonins.

Two distinct receptors mediate nonopsonic phagocytosis of different strains of Pseudomonas aeruginosa.

Complement receptor 3 (CR3) mediates both opsonic and nonopsonic phagocytosis of bacteria. Leukocyte adhesion deficiency (LAD) allows for the study of CR3-dependent phagocyte-bacterial ingestion, since LAD phagocytes do not express this receptor. Phagocytes from an infant with LAD were unable to ingest 50% of the Pseudomonas aeruginosa strains studied, which indicates a requirement for CR3.

Protein kinase C agonists enhance phagocytosis of P. aeruginosa by murine alveolar macrophages.

Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently.

Using healthy life years (HeaLYs) to assess programming needs in a public health unit.

In December 1997, public health units in Ontario received revised mandatory program guidelines from the Ministry of Health in advance of the downloading of public health to municipalities. Public health units face difficult decisions in allocating municipal resources to meet the Province's mandated programs. To set priorities for resource allocation, it is critical to assess need across program areas and to use a common unit in doing so.

Helping children adjust--a Tri-Ministry Study: II. Program effects.

This report describes program effects of the Tri-Ministry Study a school-based, longitudinal trial carried out over a 5-year period to assess the effectiveness of classwide social skills training (SS), partner reading (RE), and a combination of both (SS & RE) to reduce maladjustment among children in the primary division (up to grade 3) of Ontario schools. It also places these effects in the context of other school-based prevention studies and discusses them in view of important methodological and programmatic issues. The incremental effects attributable to the intervention programs were small and sporadic.

Helping children adjust--a Tri-Ministry Study: I. Evaluation methodology.

This report describes the evaluation methodology of the Tri-Ministry Study--a school-based trial evaluating the effectiveness of three universal programs: (a) a classwide social skills program (SS), (b) a partner reading program (RE); and, (c) a combination of both (SS & RE), to reduce and prevent behavioural maladjustment among children in the primary division (up to grade 3) of Ontario schools. The trial was done between 1991 and 1995. Sixty schools in 11 boards of education took part and were assigned randomly to program(s) during the study.

1992 Ontario Survey of Public Health Nurses: perceptions of roles and activities.

A survey of public health nurses (PHNs) who work in official public health units in Ontario was undertaken to determine whether their perceptions of their roles and activities concurred with a 1990 Canadian Public Health Association report which describes the roles and qualifications of public health nursing in Canada. The survey questionnaire was completed by 1,849 PHNs in all 42 public health units (response rate = 85%). About one tenth of the PHNs reported no activity as a caregiver/service provider.

Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls.

Pain threshold was measured using a pressure algometer in 126 subjects, of whom 54 were females and 72 males. These subjects included 18 males and 18 females with rheumatoid arthritis, 18 males and 18 females with osteoarthritis, 18 males with ankylosing spondylitis, and 18 male and 18 female healthy control volunteers. Six points were studied on each side of the body: 2 cm above the eyebrow on the forehead, lateral aspect of the arm at the insertion of the deltoid muscle, midpoint of the ulna, hypothenar eminence in the palm, midpoint of the quadriceps muscle, and midpoint of the antero-medial aspect of the tibia.

A randomized controlled trial assessing the impact of problem-based versus didactic teaching methods in CME.

A Continuing Medical Education short course was designed to examine the effect of presenting topics in three learning formats - traditional lectures, large-group, case discussions or small-group, problem-solving sessions, on knowledge and performance of family physicians. The physicians in the small group session rated the CME short course higher and performed better on one aspect of patient management than the lecture or large group physicians but there were no other differences between groups on knowledge or physician performance.