Time course of Salmonella shedding and antibody response in naturally infected pigs during grower-finisher stage.

A longitudinal trial was conducted to determine the course of Salmonella shedding and antibody response in naturally infected grower-finisher pigs. Ten-week-old pigs (n = 45) were transferred from a farm with history of salmonellosis and housed at a research facility. Weekly fecal samples (weeks 1 to 11) as well as tissue samples at slaughter were cultured for Salmonella. Serum samples were tested for presence of Salmonella antibody by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using a multilevel mixed-effects logistic regression model. Over 10 wk, 91% and 9% of pigs shed Salmonella ≤ 4 and > 5 times, respectively. The estimated median of Salmonella shedding duration was 3 to 4 wk but some pigs shed Salmonella for up to 8 wk. Salmonella shedding increased 1 wk post-arrival but followed a decreasing pattern afterwards up to week 11 (P < 0.05). Salmonella isolates (n = 29), which were recovered from 18 pigs at different occasions, were S. Typhimurium (28%), S. Livingstone (21%), S. Infantis (14%), S. Montevideo (7%), S. Benfica (3%), S. Amsterdam (3%), S. Senftenberg (17%), and S. I:Rough-O (7%). Of 11 pigs from which the first and last isolates were serotyped, 10 pigs were reinfected with a different serotype. At slaughter, Salmonella was isolated from 7 pigs, of which 5 (71%) had not tested positive for at least 7 wk prior to slaughter. Antibody response peaked 4 wk after the peak of Salmonella infection; Salmonella shedding reduced as antibody response elevated (P < 0.05). These findings indicate that pigs may shed Salmonella into the mid-point of the grower-finisher stage and may be reinfected with different serotypes.

Un essai longitudinal a été réalisé afin de déterminer la progression de l'excrétion de Salmonella et la réponse en anticorps chez des porcs en période de croissance-finition naturellement infectés. Des porcs âgés de 10 semaines (n = 45) ont été transférés d'une ferme avec une histoire de salmonellose et hébergés dans une installation de recherche. Des échantillons de fèces ont été prélevés à chaque semaine (semaines 1 à 11) de même que des échantillons de tissus lors de l'abattage et ont été cultivés pour Salmonella. Des échantillons de sérum ont été testés pour la présence d'anticorps contre Salmonella par une épreuve immunoenzymatique (ELISA). Les résultats ont été analysés par un modèle de régression logistique multiniveaux à effets mixtes. Au-delà de 10 semaines, 91 % et 9 % des porcs excrétaient Salmonella ≤ 4 et > 5 fois, respectivement. La médiane estimée de la durée d'excrétion de Salmonella était de 3 à 4 sem mais quelques porcs ont excrété Salmonella jusqu'à 8 sem. L'excrétion de Salmonella augmenta 1 sem après l'arrivée mais fut suivie par la suite d'un patron de diminution jusqu'à la semaine 11 (P < 0,05). Les isolats de Salmonella (n = 29) qui ont été obtenus de 18 porcs à différentes occasions, étaient S. Typhimurium (28 %), S. Livingstone (21 %), S. Infantis (14 %), S. Montevideo (7 %), S. Benfica (3 %), S. Amsterdam (3 %), S. Senftenberg (17 %) and S. I :Rough-O (7 %). De 11 porcs pour lesquels les premiers et les derniers isolats furent sérotypés, 10 porcs étaient réinfectés avec un sérotype différent. Lors de l'abattage, Salmonella a été isolé de sept porcs, parmi lesquels cinq (71 %) n'avaient pas eu de culture positive pour au moins 7 sem avant l'abattage. La réponse en anticorps a présenté un pic 4 sem après le pic d'infection par Salmonella; l'excrétion de Salmonella a diminué alors que la réponse en anticorps augmentait (P < 0,05). Ces résultats indiquent que les porcs peuvent excréter Salmonella jusqu'au milieu de leur période de croissance-finition et peuvent être réinfectés avec un sérotype différent.(Traduit par Docteur Serge Messier).

Endovascular Repair of Three Concurrent Mycotic Pseudoaneurysms.

INTRODUCTION: Mycotic pseudoaneurysm has traditionally been repaired surgically with excision of the infected artery and revascularization via extra-anatomical or in situ bypass. There have been reports of endovascular repair for high-risk patients for formal surgical repair. We present a case of a patient with 3 large pseudoaneurysms arising from the right subclavian artery, descending thoracic aorta, and right popliteal artery treated with endovascular and hybrid intervention. CASE: A 74-year-old male with remote history of coronary artery bypass graft and recent sternoclavicular joint abscess developed 3 concurrent pseudoaneurysms arising from the right subclavian artery, distal descending thoracic aorta, and right popliteal artery. He underwent right axillary to common carotid bypass with endovascular stent graft placement in the distal innominate and proximal subclavian artery, and subsequently had thoracic endovascular aortic repair and right popliteal stent graft. Four months later, he presented with hemoptysis due to compression of the lung secondary to the pseudoaneurysm. He underwent right anterior thoracotomy and debridement of the pseudoaneurysm. Patient recovered from the procedure and discharged. CONCLUSION: Endovascular repair of mycotic pseudoaneurysm is an acceptable alternative for high-risk patients. Even when open approach became necessarily, endovascular stent graft decreased blood loss and morbidity.

Effects of dialysate to serum sodium (Na+) alignment in chronic hemodialysis (HD) patients: retrospective cohort study from a quality improvement project.

BACKGROUND: Evidence indicates favorable effects of dialysate (DNa+) to serum sodium concentration (SNa+) alignment, however, results from larger sample populations are needed. For this reason, we conducted a retrospective propensity score-matched cohort study from a quality improvement project to investigate the effects of alignment on population of maintenance hemodialysis patients. METHODS: At 4 participating hemodialysis (HD) clinics, patients with SNa+ lower than the standard DNa+ of 137 mEq/L who received HD with DNa+ aligned to the average of the last 4 SNa+ measurements were evaluated (clinicaltrials.gov # NCT01825590 ). In this retrospective data analysis, an intention-to-treat (primary) and an as-treated "intervention" (secondary) cohort were created. "Aligned" patients from both cohorts (N = 163 for the primary and N = 137 for the secondary) were then propensity-score matched in a 1:1 fashion to "unaligned" patients from the Renal Research Institute database. The propensity score was generated based on age, gender, white race, Hispanic ethnicity, absence or presence of diabetes, hemodialysis vintage, interdialytic weight gain (IDWG; as a percentage of postdialysis body weight), catheter as primary dialysis access, predialysis systolic blood pressure, serum sodium concentration, hospitalization count during baseline. T-Test was employed for group comparisons of changes to the primary (volume-related and hemodynamic parameters) and tertiary outcomes. All-cause and fluid overload-related hospitalization admission rates were compared using Wilcoxon Rank Sum test and Cox regression analysis for repeated events. RESULTS: In the primary analysis, aligned and unaligned subjects showed comparable demographics at baseline. Treatment effects were significant for IDWG [-0.12 (95% CI -0.24 to 0) L] and showed decreasing non-significant trends for pre-dialysis hemodynamic parameters. Count comparison and Cox regression analysis showed no clear advantage of alignment in terms of all-cause and fluid overload-related hospitalization. CONCLUSIONS: Results from the largest sodium alignment program to date suggest positive treatment effects on volume-related and hemodynamic parameters, but no clear effect on risk of hospitalization. Well-matched control patients minimized confounding effects. Small effects and lack of significant differences may be explained by a low baseline DNa+ limiting the interventional change.

Evidence of a sewer vapor transport pathway at the USEPA vapor intrusion research duplex.

The role of sewer lines as preferential pathways for vapor intrusion is poorly understood. Although the importance of sewer lines for volatile organic compound (VOC) transport has been documented at a small number of sites with vapor intrusion, sewer lines are not routinely sampled during most vapor intrusion investigations. We have used a tracer study and VOC concentration measurements to evaluate the role of the combined sanitary/storm sewer line in VOC transport at the USEPA vapor intrusion research duplex in Indianapolis, Indiana. The results from the tracer study demonstrated gas migration from the sewer main line into the duplex. The migration pathway appears to be complex and may include leakage from the sewer lateral at a location below the building foundation. Vapor samples collected from the sewer line demonstrated the presence of tetrachloroethene (PCE) and chloroform in the sewer main in front of the duplex and at multiple sample locations within the sewer line upstream of the duplex. These test results combined with results from the prior multi-year study of the duplex indicate that the sewer line plays an important role in transport of VOCs from the subsurface source to the immediate vicinity of the duplex building envelope.

Processes, contexts, and rationale for disinvestment: a protocol for a critical interpretive synthesis.

BACKGROUND: Practical solutions are needed to support the appropriate use of available health system resources as countries are continually pressured to 'do more with less' in health care. Increasingly, health systems and organizations are exploring the reassessment of possibly obsolete, inefficient, or ineffective health system resources and potentially redirecting funds to those that are more effective and efficient. Such processes are often referred to as 'disinvestment'. Our objective is to gain further understanding about: 1) whether how and under what conditions health systems decide to pursue disinvestment; 2) how health systems have chosen to undertake disinvestment; and 3) how health systems have implemented their disinvestment approach. METHODS/DESIGN: We will use a critical interpretive synthesis (CIS) approach, to develop a theoretical framework based on insights drawn from a range of relevant sources. We will conduct systematic searches of databases as well as purposive searches to identify literature to fill conceptual gaps that may emerge during our inductive process of synthesis and analysis. Two independent reviewers will assess search results for relevance and conceptually map included references. We will include all empirical and non-empirical articles that focus on disinvestment at a system level. We will then extract key findings from a purposive sample of articles using frameworks related to government agendas, policy development and implementation, and health system contextual factors and then synthesize and integrate the findings to develop a framework about our core areas of interest. Lastly, we will convene a stakeholder dialogue with Canadian and international policymakers and other stakeholders to solicit targeted feedback about the framework (e.g., by identifying any gaps in the literature that we may want to revisit before finalizing it) and deliberating about barriers for developing and implementing approaches to disinvestment, strategies to address these barriers and about next steps that could be taken by different constituencies. DISCUSSION: Disinvestment is an emerging field and there is a need for evidence to inform the prioritization, development, and implementation of strategies in different contexts. Our CIS and the framework developed through it will support the actions of those involved in the prioritization, development, and implementation of disinvestment initiatives. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014013204.

Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan-Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0-100% Tx) and dialysis facility (11.1-25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre-HD systolic blood pressure, higher difference between prescribed and achieved post-HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

Factorial validity and invariance of a survey measuring psychosocial correlates of colorectal cancer screening in Ontario, Canada--a replication study.

Psychosocial constructs have been used to predict colorectal cancer screening and are frequently targeted as intermediate outcomes in behavioral intervention studies. Few studies have conducted analyses to adequately test construct validity. The psychometric analyses undertaken with U.S. populations of 16 theory-based, colorectal cancer screening items designed to measure five factors (salience-coherence, cancer worries, perceived susceptibility, response efficacy, and social influence) are an exception. The current investigation replicates previous work by examining factor validity and invariance in a random sample of Ontario, Canada residents. A survey instrument was administered to 1,013 Ontario male (49%) and female (51%) residents randomly selected by the Canada Survey Sample. Single-group confirmatory factor analyses (CFA) assessed data fit to the proposed five-factor model for males and females separately, and then a multigroup CFA evaluated if the factor structure was invariant for men and women. The five-factor model provided good fit for both males and females. Tests for factorial invariance between sexes, however, found mixed results. chi2 difference test was significant (P = 0.025); however, DeltaRMSEA = 0.0001. Factor loadings were similar by sex except for two social influence items, with item frequency distributions suggesting an extreme response style, in females, on these items. Overall, the single-group and multigroup CFA results support factorial validity and partial invariance of the five-factor model first identified in the U.S. populations. The items can be used to evaluate and compare psychosocial correlates across U.S. and Canadian samples. Additional research is needed to show invariance for other ethnocultural and national subgroups.

Stakeholder preferences for cancer care performance indicators.

PURPOSE: The purpose of this paper is to show that performance data use could be promoted with a better understanding of the type of indicators that are important to different stakeholders. This study explored patient, nurse, physician and manager preferences for cancer care quality indicators. DESIGN/METHODOLOGY/APPROACH: Interviews were held with 30 stakeholders between March and June 2004. They were asked to describe how they would use a cancer "report card", and which indicators they would want reported. Transcripts were reviewed using qualitative analysis. FINDINGS: Role (patient, nurse, physician, manager) influenced preferences and perceived use of performance data. Patients and physicians were more skeptical than nurses and managers; patients and managers expressed some preferences distinct from nurses and physicians; and patients and nurses interpreted indicators more broadly than physicians and managers. All groups preferred technical process over outcome or interpersonal process indicators. RESEARCH LIMITATIONS/IMPLICATIONS: Expressed views are not directly applicable beyond this setting, or to the general public but findings are congruent with attitudes to performance data for other conditions, and serve as a conceptual basis for further study. PRACTICAL IMPLICATIONS: Strategies for maximizing the relevance of performance reports might include technical process indicators, selection by multi-stakeholder deliberation, information that facilitates information application and customizable report interfaces. ORIGINALITY/VALUE: Performance data preferences have not been thoroughly examined, particularly in the context of cancer care. Factors were identified that influence stakeholder views of performance data, and this framework could be used to confirm findings among larger and different populations.

Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains.

Pluripotent stem cell lines with similar phenotypes can be derived from both blastocysts (embryonic stem cells, ESC) and primordial germ cells (embryonic germ cells, EGC). Here, we present a compendium DNA microarray analysis of multiple mouse ESCs and EGCs from different genetic backgrounds (strains 129 and C57BL/6) cultured under standard conditions and in differentiation-promoting conditions by the withdrawal of Leukemia Inhibitory Factor (LIF) or treatment with retinoic acid (RA). All pluripotent cell lines showed similar gene expression patterns, which separated them clearly from other tissue stem cells with lower developmental potency. Differences between pluripotent lines derived from different sources (ESC vs. EGC) were smaller than differences between lines derived from different mouse strains (129 vs. C57BL/6). Even in the differentiation-promoting conditions, these pluripotent cells showed the same general trends of gene expression changes regardless of their origin and genetic background. These data indicate that ESCs and EGCs are indistinguishable based on global gene expression patterns alone. On the other hand, a detailed comparison between a group of ESC lines and a group of EGC lines identified 20 signature genes whose average expression levels were consistently higher in ESC lines, and 84 signature genes whose average expression levels were consistently higher in EGC lines, irrespective of mouse strains. Similar analysis identified 250 signature genes whose average expression levels were consistently higher in a group of 129 cell lines, and 337 signature genes whose average expression levels were consistently higher in a group of C57BL/6 cell lines. Although none of the genes was exclusively expressed in either ESCs versus EGCs or 129 versus C57BL/6, in combination these signature genes provide a reliable separation and identification of each cell type. Differentiation-promoting conditions also revealed some minor differences between the cell lines. For example, in the presence of RA, EGCs showed a lower expression of muscle- and cardiac-related genes and a higher expression of gonad-related genes than ESCs. Taken together, the results provide a rich source of information about the similarities and differences between ESCs and EGCs as well as 129 lines and C57BL/6 lines. Such information will be crucial to our understanding of pluripotent stem cells. The results also underscore the importance of studying multiple cell lines from different strains when making comparisons based on gene expression analysis.

Endoscopic follow-up of positive fecal occult blood testing in the Ontario FOBT Project.

BACKGROUND: The Ontario FOBT Project is a pilot study of fecal occult blood testing (FOBT) for colorectal cancer screening conducted among age-eligible volunteers (50 to 75 years) in 12 of 37 public health regions in Ontario. METHODS: Volunteers responded to invitations from primary care practitioners (PCPs) in six regions, and from public health programs in the remaining regions. FOBT collection kits were distributed from routine laboratory specimen collection sites, to which completed kits were returned. Results were sent to PCPs in all 12 regions, with copies sent to the study office at Cancer Care Ontario (Toronto, Ontario). Follow-up of positive results was at the discretion of the PCPs. The study files contained the unique Ontario Health Insurance Numbers, the date of the analyses, the number of satisfactory slides and the results for each slide. The Ontario Health Insurance Numbers were encrypted for each participant, and along with the study file, were linked to medical billing claims, hospital records and aggregate demographic data. RESULTS: Among participants with positive results (men 3.5% and women 2.2%), the median time from date of FOBT analysis to date of colonoscopy was 121 days among men and 202 days among women. At the end of follow-up, after positive FOBT (six to 17 months), 73% of men and 56% of women had proceeded to colonoscopy. CONCLUSION: Although colonoscopy appeared to be acceptable to the majority of participants with positive FOBT, accessibility problems was the likely explanation for lengthy intervals between the date of positive FOBT and its performance. Differences between the experiences of men and women require further investigation.

Factors that influence cancer patients' overall perceptions of the quality of care.

OBJECTIVE: This study outlines predictors of cancer patients' overall perceptions of the quality of care. DESIGN AND SETTING: Our sample included 2790 patients who received cancer care services during 2004 in 15 comprehensive cancer programmes across Ontario, Canada. Patients were classified into three groups: those receiving both chemotherapy and radiotherapy (n = 752), those receiving only chemotherapy (n = 1044), and those receiving only radiotherapy (n = 994). An ordinal logistic regression model for each patient group was performed to determine which variables most affected the probabilities of the patients' overall evaluations of the quality of care. Potential control variables were patients' age, sex, type of cancer, self-assessed health, and who completed the survey. RESULTS: Among seven common predictors of the overall quality perception across the three models, four should be of particular interest because patients perceived them as relatively problematic aspects of care. These are 'was informed about follow-up care after completing treatment', 'knew next step in care', 'knew who to go to with questions', and 'providers were aware of test results'. These predictors explained between 25 and 34% of the variance (depending on the model) of the overall perception of quality. The explanatory power of these predictors did not change across sex and age group. 'Self-assessed health' was the only control variable that remained in all three models. CONCLUSIONS: From a practical perspective, improvement efforts are best focused on factors that are strong predictors as well as on those for which there is a low score. Thus, on the basis of this study, practitioners' improvement efforts might be constructively focused on the four predictors mentioned above.

Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.

Emery-Dreifuss muscular dystrophy (EDMD1) is caused by mutations in either the X-linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene. Here, we describe the derivation of mice lacking emerin in an attempt to derive a mouse model for EDMD1. Although mice lacking emerin show no overt pathology, muscle regeneration in these mice revealed defects. A bioinformatic array analysis of regenerating Emd null muscle revealed abnormalities in cell-cycle parameters and delayed myogenic differentiation, which were associated with perturbations to transcriptional pathways regulated by the retinoblastoma (Rb1) and MyoD genes. Temporal activation of MyoD transcriptional targets was significantly delayed, whereas targets of the Rb1/E2F transcriptional repressor complex remained inappropriately active. The inappropriate modulation of Rb1/MyoD transcriptional targets was associated with up-regulation of Rb1, MyoD and their co-activators/repressors transcripts, suggesting a compensatory effort to overcome a molecular block to differentiation at the myoblast/myotube transition during regeneration. This compensation appeared to be effective for MyoD transcriptional targets, although was less effective for Rb1 targets. Analysis of Rb1 phosphorylation states showed prolonged hyper-phosphorylation at key developmental stages in Emd null myogenic cells, both in vivo and in vitro. We also analyzed the same pathways in Lmna null muscle, which shows extensive dystrophy. Surprisingly, Lmna null muscle did not show the same perturbations to Rb- and MyoD-dependent pathways. We did observe increased transcriptional expression of Lap2alpha and delayed expression of Rb1, which may regulate alternative transcriptional pathways in the Lmna null myoblasts. We suggest that the dominant LMNA mutations seen in many clinically disparate laminopathies may similarly alter Rb function, with regard to either the timing of exit from the cell cycle or terminal differentiation programs or both.

Methylmercury, fish consumption, and the precautionary principle.

This paper considers several broad issues in the context of probabilistic assessment of the benefits of curtailing mercury (Hg) emissions from U.S. coal-fired power plants, based on information developed from recent literature and epidemiology studies of health effects of methylmercury. Exposure of the U.S. population is considered on the national scale, in large part because of recent questions arising from survey and experimental data about the relative importance of local deposition of airborne Hg. Although epidemiological studies have provided useful information, safe levels of Hg exposure remain uncertain, in part because of other dietary considerations in the populations that were studied. For example, much of the seafood consumed in one of the major studies was also contaminated with polychlorinated biphenyls, as are fish taken from some U.S. fresh waters. The primary epidemiological approach involves cross-study comparisons in relation to mean exposures, rather than detailed critiques of individual effects reported in each study. U.S. exposures are seen to be well below the levels at which adverse health effects are reported. This analysis supports the conclusion that unilateral reduction of Hg emissions from U.S. coal-fired power plants alone is unlikely to realize significant public health benefits.

Mutations in the mouse Lmna gene causing progeria, muscular dystrophy and cardiomyopathy.

At least ten different diseases have been linked to mutations in proteins associated with the nuclear envelope (NE). Eight of these diseases are associated with mutations in the lamin A gene (LMNA). These diseases include the premature ageing or progeric diseases Hutchinson-Gilford progeria and atypical Werner's syndrome, diseases affecting striated and cardiac muscle including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting white fat deposition and skeletal development and a peripheral neuropathy resulting in motor neuron demyelination. To understand how these diseases arise from different mutations in the same protein, we established mouse lines carrying some of the same mutations found in the human LMNA gene, as both mouse and human lamin genes show a very high degree of sequence conservation. We have generated mice with different mutations resulting in progeria, muscular dystrophy and dilated cardiomyopathy. Our mouse lines are providing novel insights into how changes to the nuclear lamina affect the mechanical integrity of the nucleus and in turn intracellular signalling, such as the NF-kappaB pathway, as well as cell proliferation and survival, cellular functions that, when disrupted, may be the basis for the origin of such diseases.

Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice.

Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina. Zmpste24 deficiency results in the accumulation of prelamin A within cells, a complete loss of mature lamin A, and misshapen nuclear envelopes. Zmpste24-deficient (Zmpste24(-/-)) mice exhibit retarded growth, alopecia, micrognathia, dental abnormalities, osteolytic lesions in bones, and osteoporosis, which are phenotypes shared with Hutchinson-Gilford progeria syndrome, a human disease caused by the synthesis of a mutant prelamin A that cannot undergo processing to lamin A. Zmpste24(-/-) mice also develop muscle weakness. We hypothesized that prelamin A might be toxic and that its accumulation in Zmpste24(-/-) mice is responsible for all of the disease phenotypes. We further hypothesized that Zmpste24(-/-) mice with half-normal levels of prelamin A (Zmpste24(-/-) mice with one Lmna knockout allele) would be subjected to less toxicity and be protected from disease. Thus, we bred and analyzed Zmpste24(-/-)Lmna(+/-) mice. As expected, prelamin A levels in Zmpste24(-/-)Lmna(+/-) cells were significantly reduced. Zmpste24(-/-)Lmna(+/-) mice were entirely normal, lacking all disease phenotypes, and misshapen nuclei were less frequent in Zmpste24(-/-)Lmna(+/-) cells than in Zmpste24(-/-) cells. These data suggest that prelamin A is toxic and that reducing its levels by as little as 50% provides striking protection from disease.

Reconstructing cancer services in Ontario.

This paper draws upon experience gained in the recent restructuring of cancer services in Ontario that can provide insights for broader regionalization efforts. Although Ontario is the only province in Canada not to regionalize its healthcare system, the Ontario cancer services system, like most others in Canada, is based on a regionalized system. However, the growing burden of cancer and predictable crises in cancer services in Ontario necessitated a rethinking of how the cancer system should be structured and how services should be delivered. Based on recommendations by the Cancer Services Implementation Committee in 2001, Ontario's cancer services system has recently gone through major restructuring, which has established new institutional arrangements for the Ministry of Health and Long-Term Care, Cancer Care Ontario (CCO) (the provincial cancer agency) , a new Quality Council and 11 new regionally based Integrated Cancer Programs (ICPs). This restructuring has created several levers for promoting regional change and motivating performance improvement, including (1) public reporting on performance with a new quality mandate, (2) fiscal and performance-based agreements between CCO and the ICPs, (3) leading and coordinating communities of practice and (4) direct ministerial access. While institutional relationships are still developing, these experiences may provide important insights for regionalization efforts in other jurisdictions and sectors in Canada.

Declining trends in work-related morbidity and disability, 1993-1998: a comparison of survey estimates and compensation insurance claims.

OBJECTIVES: This study compared trends in the incidence of work-related morbidity and disability across 3 sources of surveillance data in a Canadian province. METHODS: Time series estimates of workplace injuries and work-related disability based on 2 panel surveys in the province of Ontario, Canada, for the period 1993-1998 were compared with rates of work-related injury and illness compensation claims during the same period. RESULTS: Lost-time compensation claims declined by 28.8% over this 6-year period. The incidence of self-reported work-related injury declined by 28.2%, and the self-reported incidence of work absence for work-related causes declined by 32.2%. CONCLUSIONS: Parallel reductions in work-related morbidity were seen in 3 independent data sources. These results support an interpretation that there has been an important reduction in injury risk in Ontario workplaces over the past decade.

Managed care's perspective on treatment of plaque psoriasis.

Sullivan discussed the potential for acceptance of biologic drugs for treatment of psoriasis in the context of how managed care organizations currently respond to new therapies. The apparent effectiveness of biologic therapies, compared with conventional treatments, led Sullivan to suggest that traditional methods of evaluating and "tiering" pharmaceutical products may not necessarily prove appropriate for biologic therapies.