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Background and Aim: Individuals exposed to heavy metals are known to experience physiological and biochemical changes, which raise questions regarding possible health effects. In our earlier research, significant concentrations of vanadium (V), mercury (Hg), cadmium (Cd), and arsenic (As) were found in food and medical packaging materials. This study aimed to evaluate the cognitive, physiological, and biomarker effects of select heavy metal exposure in Wistar rats., Materials and Methods: Over a 13-week period, five groups of rats (six rats per group, with both males and females) were assessed to study the effects of oral exposure to V, Hg, Cd, and As. The study focused on evaluating physiological, cognitive, and biochemical markers, with the results compared to those of a control group., Results: Comparing all groups of rats treated with heavy metals, the study revealed significant deficits in learning and spatial orientation (water maze test); rats treated with V, Cd, and Hg showed signs of depression. Rats treated with As also showed signs of hyperactivity, which may indicate a connection to attention-deficit hyperactivity disorder (rat tail suspension test). The groups exposed to different heavy metals varied in their physiological (water and food intake, urine and feces output) and biochemical responses (enzyme-linked immunosorbent assay, prostate-specific antigen, T3, T4, thyroid-stimulating hormone, carcinoembryonic antigen, and blood glucose analysis), with Hg exhibiting the strongest impacts. Rats given Hg showed signs of hypothyroidism, such as increased food intake and weight gain., Conclusion: This study clarifies the complex relationships between exposure to heavy metals and various biological systems, shedding light on their potential health impacts. The findings provide insight into the effects of heavy metals on neural and thyroid tissues, as well as their propensity to cause cellular dedifferentiation. However, the study has certain limitations, such as the relatively short duration of exposure and the use of only a few selected biomarkers. Future research should focus on long-term exposure studies, incorporate a broader range of biomarkers, and explore the underlying mechanisms at a molecular level to better understand the full spectrum of health risks associated with heavy metal exposure., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mukhi, et al.)

Background: In 2017, the Canadian Partnership Against Cancer, a Canadian federally sponsored organisation, initiated a national multijurisdictional quality improvement (QI) initiative to maximise the use of synoptic data to drive cancer system improvements, known as the Evidence for Surgical Synoptic Quality Improvement Programme. The goal of our study was to evaluate the outcomes, determinants and learning of this nationally led initiative across six jurisdictions in Canada, integrating a mix of cancer surgery disease sites and clinicians., Methods: A mixed-methods evaluation (surveys, semistructured interviews and focus groups) of this initiative was focused on the ability of each jurisdiction to use synoptic reporting data to successfully implement and sustain QI projects to beyond the completion of the initiative and the lessons learnt in the process. Resources provided to the jurisdictions included operational funding, training in QI methodology, national forums, expert coaches, and ad hoc monitoring and support. The programme emphasised foundational concepts of the QI process including data literacy, audit and feedback reports, communities of practice (CoP) and positive deviance methodology., Results: 101 CoP meetings were held and 337 clinicians received feedback reports. There were 23 projects, and 22 of 23 (95%) showed improvements with 15 of 23 (65%) achieving the proposed targets. Enablers of effective data utilisation/feedback reports for QI included the need for clinicians to trust the data, have comparative data for feedback, and the engagement of both data scientists and clinicians in designing feedback reports. Enablers of sustainability of QI within each jurisdiction included QI training for clinicians, the ability to continue CoP meetings, executive and broad stakeholder engagement, and the ability to use pre-existing organisational infrastructures and processes. Barriers to continue QI work included lack of funding for core team members, lack of automated data collection processes and lack of clinician incentives (financial and other)., Conclusion: Success and sustainability in data-driven QI in cancer surgery require skills in QI methodology, data literacy and feedback, dedicated supportive personnel and an environment that promotes the process of collective learning and shared accountability. Building these capabilities in jurisdictional teams, tailoring interventions to facility contexts and strong leadership engagement will create the capacity for continued success in QI for cancer surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Food and drug packaging materials are an integral part of our everyday life.  Noxious elements can inadvertently be included in packaging materials in various stages of their production. Adulterants, adhesives, colorants and heavy metal interference are the common sources of contamination in food packaging materials. Heavy metal toxicity has far-reaching ill effects on living organisms. The present study aimed at qualitatively and quantitatively analysing heavy metal content of various materials that are used for food and drug packaging in India., Methods: The qualitative detection was done by rapid assay and heavy metals were quantified with the help of inductively coupled plasma-optical emission spectrometry (ICP-OES). A total of thirteen types of food and drug packaging materials were procured from local market and analysed for four heavy metals viz. arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd). The concentration of each heavy metal in the samples was compared with the permissible values published by the European Council., Results: Heavy metals were qualitatively detected in ten out of thirteen samples. Among the ten samples mercury and arsenic were detected the most followed by cadmium and vanadium. Quantitative estimation by ICP-OES showed presence of vanadium and cadmium in ten samples and arsenic and mercury in all the thirteen samples above the permissible range., Conclusions: The notable elevation in mercury concentration, followed by cadmium, arsenic and vanadium registering the least, presents a potential health hazard to consumers and compromises the food quality., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Mukhi S et al.)

Background: Typhoid fever is commonly found until today, especially in developing countries. It has fatal complications and measures must be taken to reduce the incidence of typhoid. Vaccinations are a key factor in prevention. This is a phase II randomized observer-blind clinical trial on a novel Vi-DT conjugate vaccine on 200 subjects 12 to 40 years of age., Methods: Subjects were screened for eligibility after which a blood sample was taken and one dose of vaccine was administered. Investigational vaccine used was Vi-DT and control was Vi-PS. Twenty-eight days after vaccination, subjects visited for providing blood sample to assess immunogenicity and were asked about local and systemic adverse reactions that occurred in the first 28 days., Results: Subjects had minor adverse reactions. Pain was the most common local reaction. Muscle pain was the most common systemic reaction. There were no serious adverse events up to 28 days post vaccination. Seroconversion rates were 100% in the Vi-DT group and 95.96% in the Vi-PS group. Post vaccination GMTs were increased in both groups but it was significantly higher in the Vi-DT group (p < 0.001)., Conclusions: Vi-DT typhoid conjugate vaccine is safe and immunogenic in healthy Indonesian subjects 12 to 40 years., Trial Registration: Approved by ClinicalTrials.gov., Clinical Trial Registration Number: NCT03460405. Registered on 09/03/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03460405 ., (© 2024. The Author(s).)

Several scientific investigations have revealed that the leaching of metals from packaging material into the packed food is an unavoidable process. Hence, this study is aimed at investigating the effect of leached heavy metals from food packing materials on normal human gut flora. We analysed the effect of vanadium, arsenic, cadmium, and mercury present in digested packaging materials (DPM) on standard strains of Escherichia coli ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70063, and Enterococcus faecalis ATCC 29212. The minimum inhibitory concentration (MIC) of laboratory-grade heavy metal salts and heavy metals present in DPM was determined by the agar dilution method. For all four bacteria, the MIC of cadmium and arsenic in the DPM was 7  μ g/ml and 1.6  μ g/ml, respectively. The MIC of mercury in DPM was 1.6  μ g/ml for E. coli , K. pneumoniae , and E. faecalis and 1.4  μ g/ml for P. aeruginosa . MIC of vanadium for E. coli , P. aeruginosa , and E. faecalis was 2.2  μ g/ml, and for K. pneumoniae was 2.0  μ g/ml. The difference in MICs of heavy metals in DPMs and heavy metal salts was not statistically significant. MICs were within CODEX-specified permissible levels. Though heavy metals in packaging material have not shown a deleterious effect on representative human gut flora, there is scope to study their effect on the gut microbiome. Thus, understanding the risk of heavy metal ingestion through unknown sources and avoiding any possible ingestion is crucial to preventing chronic diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Senna Mukhi et al.)

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for robust surveillance of respiratory viruses. Syndromic surveillance continues to be an important surveillance component recommended by the World Health Organization (WHO). While FluWatchers, Canada's syndromic surveillance system, has been in place since 2015, the COVID-19 pandemic provided a valuable opportunity to expand the program's scope and underlying technology infrastructure. Following some structural changes to FluWatchers syndromic questionnaire, participants are now able to contribute valuable data to the non-specific surveillance of respiratory virus activity across Canada. This article examines the performance of FluWatchers' syndromic surveillance over the three years of the COVID-19 pandemic in Canada. More specifically, this article examines FluWatchers' performance with respect to the correlation between the FluWatchers influenza-like illness (ILI) and acute respiratory infection (ARI) indicators and total respiratory virus detections (RVDs) in Canada, including influenza, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other respiratory viruses., Competing Interests: Competing interests None.

Background: Aided by a collaborative partnership dating back to 2011, the Canadian Network for Public Health Intelligence (CNPHI) and the Canadian Paediatric Surveillance Program (CPSP) quickly undertook substantial enhancements to the CPSP's data collection instruments on the CNPHI platform to characterize the impacts of the coronavirus disease 2019 (COVID-19) on children and youth in Canada. Faced with an emerging public health threat with impacts yet unknown, the objective of the intervention was to rapidly complete enhancements to existing data collection and analytical tools to enable the CPSP's ability to characterize the impacts of COVID-19 in Canadian children and youth., Intervention: Reporting frequency from CPSP's network of paediatric practitioners was increased from monthly to weekly, and the flexibility of detailed case data collection was substantially enhanced using complex survey instruments, interactively designed using CNPHI's Web Data technology. To ensure their data collection proceeded along all required lines of surveillance, CPSP's data collection tools were enhanced to collect demographic, epidemiological, microbiological and clinical data including comorbidities of cases identified., Outcomes: Less than a month after the World Health Organization declared the COVID-19 pandemic, CPSP was able to start collecting detailed weekly case data on emerging cases of COVID-19 among Canadian children and youth. By May 2020, CPSP was able to launch a detailed study, supporting research into potential risk factors for severe COVID-19-related illness in children and youth., Conclusion: In response to a novel public health threat, CNPHI and CPSP were able to implement rapid adaptations and enhancements to existing data collection instruments while fortifying their preparedness to do the same in the future, when needed. With innovative and agile technologies at the ready, this experience helps to emphasize the importance of established collaborative partnerships across public health disciplines as a factor contributing to preparedness and agility to respond to the unforeseen. Canadian Network for Public Health Intelligence's Web Data technology showed agile adaptability and a capacity for complex and detailed data collection, supporting timely surveillance and response., Competing Interests: Competing interests None.

COVID-19 had a global impact, claiming many lives and disrupting healthcare systems even in many developed countries. Various mutations of the severe acute respiratory syndrome coronavirus-2, continue to be an impediment to early detection of this disease, which is vital for social well-being. Deep learning paradigm has been widely applied to investigate multimodal medical image data such as chest X-rays and CT scan images to aid in early detection and decision making about disease containment and treatment. Any method for reliable and accurate screening of COVID-19 infection would be beneficial for rapid detection as well as reducing direct virus exposure in healthcare professionals. Convolutional neural networks (CNN) have previously proven to be quite successful in the classification of medical images. A CNN is used in this study to suggest a deep learning classification method for detecting COVID-19 from chest X-ray images and CT scans. Samples from the Kaggle repository were collected to analyse model performance. Deep learning-based CNN models such as VGG-19, ResNet-50, Inception v3 and Xception models are optimized and compared by evaluating their accuracy after pre-processing the data. Because X-ray is a less expensive process than CT scan, chest X-ray images are considered to have a significant impact on COVID-19 screening. According to this work, chest X-rays outperform CT scans in terms of detection accuracy. The fine-tuned VGG-19 model detected COVID-19 with high accuracy-up to 94.17% for chest X-rays and 93% for CT scans. This work thereby concludes that VGG-19 was found to be the best suited model to detect COVID-19 and chest X-rays yield better accuracy than CT scans for the model., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Higher global prevalence of non-alcoholic fatty liver disease (NAFLD) is associated with obesity, steatosis, and insulin resistance (IR), and often progresses to steatohepatitis (NASH). Even after more than twenty years of research, there is still no FDA approved therapy for the treatment of fatty liver disease/NASH though, Saroglitazar - a dual PPAR α/γ agonist has been recently approved as a therapeutic option for the fatty liver disease in India. Hepatoprotective Ayurvedic formulations are widely used and are considered safe. In the present study, C57BL/6 male mice on HFHF diet for four weeks were treated with vehicle, Saroglitazar (3 mg/kg/po), and Hepano - a formulation of five herbs (200 mg/kg/po), at the human equivalent therapeutic doses for additional eight weeks. These animals were evaluated after 12 weeks for obesity, body mass index (BMI), systemic insulin resistance, hyperglycaemia, dyslipidaemia, and hepatic lipid accumulation. Differential liquid chromatography-mass spectrometry (LC-MS/MS) based lipidomics analysis demonstrated significant changes in the different class of lipids [phospholipids, sphingolipids, diglycerides and triglycerides (TG)] in HFHF fed group. The protective effects of both Saroglitazar and Hepano were evident against IR, obesity and in the modulation of different class of lipids in the circulation and hepatic tissue. Saroglitazar reduced TG as well as modulated phospholipids levels, while Hepano modulated only phospholipids, ceramides, oxidised lipids, and had no effect on hepatic or circulating TG levels in HFHF fed mice. In addition, in vitro studies using HepG2, THP1 and LX2 cells demonstrated safety of both the test substances where Hepano possess better anti-inflammatory as well as anti-fibrotic potential. Overall, Saroglitazar seems to be more efficacious than Hepano in the regimen used against HFHF induced IR, obesity, and dyslipidaemia., (Copyright © 2021. Published by Elsevier Masson SAS.)

Competing Interests: Competing interests: None.

Background: Sentinel influenza-like illness (ILI) surveillance is an essential component of a comprehensive influenza surveillance program. Community-based ILI surveillance systems that rely solely on sentinel healthcare practices omit important segments of the population, including those who do not seek medical care. Participatory surveillance, which relies on community participation in surveillance, may address some limitations of traditional ILI systems., Objective: We aimed to evaluate FluWatchers, a crowdsourced ILI application developed to complement and complete ILI surveillance in Canada., Methods: Using established frameworks for surveillance evaluations, we assessed the acceptability, reliability, accuracy and usefulness of the FluWatchers system 2015-2016, through 2018-2019. Evaluation indicators were compared against national surveillance indicators of ILI and of laboratory confirmed respiratory virus infections., Results: The acceptability of FluWatchers was demonstrated by growth of 50%-100% in season-over-season participation, and a consistent season-over-season retention of 80%. Reliability was greater for FluWatchers than for our traditional ILI system, although both systems had week-over-week fluctuations in the number of participants responding. FluWatchers' ILI rates had moderate correlation with weekly influenza laboratory detection rates and other winter seasonal respiratory virus detections including respiratory syncytial virus and seasonal coronaviruses. Finally, FluWatchers has demonstrated its usefulness as a source of core FluWatch surveillance information and has the potential to fill data gaps in current programs for influenza surveillance and control., Conclusion: FluWatchers is an example of an innovative digital participatory surveillance program that was created to address limitations of traditional ILI surveillance in Canada. It fulfills the surveillance system evaluation criteria of acceptability, reliability, accuracy and usefulness., Competing Interests: Competing interests: None.

Background: FluWatch is Canada's national surveillance system that monitors the spread of influenza. Its syndromic surveillance component monitors the spread of influenza-like illness (ILI) in near-real time for signals of unusual or increased activity. Syndromic surveillance data are collected from two main sources: the Sentinel Practitioner ILI Reporting System and FluWatchers.We evaluated the representativeness of the most recent participant population to understand changes in representativeness since 2015, to identify demographic and geographic gaps and correlates/determinants of participation to characterize a typical participant., Methods: In this serial cross-sectional study, characteristics of participants during four consecutive influenza seasons (2015-2016, 2016-2017, 2017-2018 and 2018-2019) were compared with the 2016 Canadian Census and the 2015-2016, 2016-2017, 2017-2018 and 2018-2019 National Seasonal Influenza Vaccination Coverage Surveys. Associations between demographic factors and the level of user participation were also analyzed among the 2018-2019 FluWatchers population., Results: Infants (0-4 years) and older adults (65 years and older) were under-represented in FluWatchers across all four influenza seasons. Female and urban participants were significantly over-represented. Vaccination coverage remained significantly higher among the FluWatchers populations from the past four influenza seasons across all age groups. Level of participation among FluWatchers was associated with age and vaccination status, but not with sex or geography. Over its four years of implementation, the FluWatchers participant population became more representative of the Canadian population with respect to age and geography (urban/rural and provincial/territorial)., Conclusion: FluWatchers participants under-represent the tails of Canada's age distribution and over-represent those who engage in health promoting behaviours as indicated by high influenza vaccine coverage, consistent with typical volunteer-based survey response biases. Representativeness would likely improve with targeted recruitment of under-represented groups, such as males, older adults and Canadians living in rural areas., Competing Interests: Competing interests: None.

Importance: Every year, respiratory viruses exact a heavy burden on Canadian hospitals during winter months. Generalizable seasonal patterns of respiratory virus transmission may estimate the evolution of SARS-CoV-2 or other emerging pathogens., Objective: To describe the annual and biennial variation in respiratory virus seasonality in a northern climate., Design, Setting, and Participants: This cohort study is an epidemiological assessment using population-based surveillance of patients with medically attended respiratory tract infection from 2005 through 2017 in Alberta, Canada. Incident cases of respiratory virus infection and infant respiratory syncytial virus (RSV) hospitalizations in Alberta were extracted from the Data Integration for Alberta Laboratories platform and Alberta Health Services Discharge Abstract Database, respectively. A deterministic susceptible-infected-recovered-susceptible mathematical model with seasonal forcing function was fitted to the data for each virus. The possible future seasonal course of SARS-CoV-2 in northern latitudes was modeled on the basis of these observations. The analysis was conducted between December 15, 2020, and February 10, 2021., Exposures: Seasonal respiratory pathogens., Main Outcomes and Measures: Incidence (temporal pattern) of respiratory virus infections and RSV hospitalizations., Results: A total of 37 719 incident infections with RSV, human metapneumovirus, or human coronaviruses 229E, NL63, OC43, or HKU1 among 35 375 patients (18 069 [51.1%] male; median [interquartile range], 1.29 [0.42-12.2] years) were documented. A susceptible-infected-recovered-susceptible model mirrored the epidemiological data, including a striking biennial variation with alternating severe and mild winter peaks. Qualitative description of the model and numerical simulations showed that strong seasonal contact rate and temporary immunity lasting 6 to 12 months were sufficient to explain biennial seasonality in these various respiratory viruses. The seasonality of 10 212 hospitalizations among children younger than 5 years with RSV was also explored. The median (interquartile range) rate of hospitalizations per 1000 live births was 18.6 (17.6-19.9) and 11.0 (10.4-11.7) in alternating even (severe) and odd (less-severe) seasons, respectively (P = .001). The hazard of admission was higher for children born in severe (even) seasons compared with those born in less-severe (odd) seasons (hazard ratio, 1.68; 95% CI, 1.61-1.75; P < .001)., Conclusions and Relevance: In this modeling study of respiratory viruses in Alberta, Canada, the seasonality followed a pattern estimated by simple mathematical models, which may be informative for anticipating future waves of pandemic SARS-CoV-2.

Trifluoroiodomethane (CF 3 I) is a fire suppressant gas with potential for use in low global-warming refrigerant blends. Data from studies in rats suggest that the most sensitive health effect of CF 3 I is thyroid hormone perturbation, but the rat is a particularly sensitive species for disruption of thyroid homeostasis. Mice appear to be less sensitive than rats but still a conservative model with respect to humans. The purpose of this study was to test tolerance and thyroid response to CF 3 I in B6C3F1 male mice. Male mice were exposed to CF 3 I for 6 h per day, for 28 days, via whole body exposure at concentrations of 2500, 5000 and 10,000 ppm. A 16-day recovery period was included to evaluate reversibility. No adverse clinical signs were observed throughout the study, and body weights were unaffected by exposure. CF 3 I exposure had no effect on thyroid histology. An increase in relative thyroid weight was observed at 10,000 ppm on day 28 but not in a separate group of animals evaluated on day 29, and thyroid weight was not different from controls at 44 days. Slight and sporadic changes in serum triiodothyronine, thyroxine, and thyroid-stimulating hormone were observed but did not follow a consistent pattern with respect to timing, dose, or direction. Overall, exposure at up to 10,000 ppm (1.0%) of CF 3 I gas for 28 days produced no overt general toxicity and only transient, recoverable effects on thyroid weight and hormones at certain concentrations. On the basis of the effect of CF 3 I exposure on the thyroid, including evaluation of thyroid histopathology, the no observed adverse effect level for this study is 10,000 ppm. Considering the apparently greater toxicity reported in prior studies in male rats, our data suggest a species difference between rats and mice in terms of susceptibility to CF 3 I-induced thyroid hormone perturbation.

Trans-1233zd was developed as a refrigerant and propellant in consumer products; its toxicity has been studied extensively. The scope of this assessment is to apply the confirmed NOAEC to conduct Benchmark Dose Modeling (BMD) and determine the Point of Departure (POD). In a previously published 13-week inhalation study, a NOAEC was identified at 4000 ppm. Due to uncertainty concerning the cardiac lesion, an external pathology peer review of heart tissues was undertaken using published best practices and consistent nomenclature and diagnostic criteria. The cardiac lesion observed at 4000 ppm was considered to be spontaneous based on lesion location and microscopic features. BMD was applied to derive the BMDL 05 and BMDL 10 ; the more conservative BMDL 05 was used as the POD for risk assessment to calculate the Reference Exposure Levels (RELs). The 2-Box Air Dispersion Model was used to calculate the exposure to consumer products. Both the acute and chronic exposure concentrations calculated were compared to the acute and chronic RELs. The acute and chronic exposure to trans-1233zd in the assessed consumer products are below the RELs and deemed safe for their intended uses., Competing Interests: Declaration of Competing Interest The authors are either employed by Honeywell, or have been retained by Honeywell in a consulting capacity, and played a role in outlining the issues raised by the risk assessment with respect to the use of propellants in consumer products., (Copyright © 2020. Published by Elsevier B.V.)

Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)-specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 × 10 7 to 2 × 10 7 cells/m 2 ) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Serious viral infections, due to delayed immune reconstitution, are a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Thus, many transplant centers prospectively track cellular immune recovery by evaluating absolute cell numbers and the phenotypic profile of reconstituting T cell subsets to identify individuals who are at highest risk of infection. Conventional assessments, however, fail to measure either the antigen specificity or functional capacity of reconstituting cells-both factors that correlate with endogenous antiviral protection. In this pilot study, we sought to address this limitation by prospectively investigating the tempo of endogenous immune reconstitution in a cohort of 23 pediatric HSCT patients using both quantitative (flow cytometry) and qualitative (IFNγ ELISpot) measures, which we correlated with either the presence or absence of infections associated with cytomegalovirus, adenovirus, Epstein-Barr virus, BK virus, human herpes virus 6, respiratory syncytial virus, parainfluenza, influenza, and human metapneumovirus. We present data spanning 12 months post-transplant demonstrating the influence of conditioning on immune recovery and highlighting the differential impact of active viral replication on the quantity and quality of reconstituting cells. Judicious use of standard (phenotypic) and novel (functional) monitoring strategies can help guide the clinical care and personalized management of allogenic HSCT recipients with infections., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for relapsed or refractory acute myeloid leukemia (AML). However, more than half ultimately experience disease relapse that is associated with a dismal median survival of just 6 months, highlighting the need for novel therapies. In the current study we explore the therapeutic potential of targeting cyclin A1 (CCNA1), a cancer-testis antigen that is overexpressed in malignant blasts and leukemic stem cells. We demonstrate the immunogenicity of this antigen to native T cells, with >90% of donors screened mounting a specific response. The expanded cells were Th1 polarized, polyfunctional, and cytotoxic toward CCNA1+/HLA-matched tumor cell lines. Furthermore, these cells were exquisitely specific for CCNA1 and exhibited no reactivity against other cyclin family members, including CCNA2, which shares 56% homology with CCNA1 and is ubiquitously expressed in dividing cells. Lastly, the detection of CCNA1-specific T cells in AML patients post-HSCT was associated with prolonged disease remission, suggesting the protective potential of such endogenous cells. Taken together, our findings demonstrate the feasibility of targeting CCNA1 and the potential for therapeutic benefit associated with the adoptive transfer of reactive cells., (© 2020 by The American Society of Hematology.)

Background: Public health surveillance is essential to inform programs that aim to eradicate child maltreatment (CM) and to provide services to children and families. However, collection of CM data imposes a burden on child welfare workers (CWWs). This study assesses the feasibility of hiring coders to abstract the required information from administrative records and case narratives., Methods: Based on a convenience sample of child welfare data from Manitoba, Canada, two coders abstracted information on 181 alleged CM cases. The coders completed a short web-based questionnaire for each case to identify which of five types of CM had been investigated, level of substantiation for each type, and risk of future CM. The CWWs responsible for each case completed the same questionnaire. Percentages of the occurrence of CM by the three sources were compared. The validity of the coders' classifications was assessed by calculating sensitivity, specificity, and positive and negative predictive values, against the CWWs' classifications as the "gold standard." Cohen's kappa was also calculated., Results: The coders' classifications of physical abuse, sexual abuse and neglect generally matched those of CWWs; for exposure to intimate partner violence, agreement was weak for one coder. Coding of emotional maltreatment and risk investigations could not be evaluated., Conclusion: Results were promising. Abstraction was not time-consuming. Differences between coders and CWWs can be largely explained by the administrative data system, child welfare practice, and legislation. Further investigation is required to determine if additional training could improve coders' classifications of CM., (Copyright © 2019. Published by Elsevier Ltd.)

Influenza A virus in swine is of significant importance to human and veterinary public health. Environmental sampling techniques that prove practical would enhance surveillance for influenza viruses in swine. The primary objective of this study was to demonstrate the feasibility of bioaerosol and surface sampling for the detection of influenza virus in swine barns with a secondary objective of piloting a mobile application for data collection. Sampling was conducted at a large swine operation between July 2016 and August 2017. Swine oral fluids and surface swabs were collected from multiple rooms. Room-level air samples were collected using four bioaerosol samplers: a low volume polytetrafluoroethylene (PTFE) filter sampler, the National Institute for Occupational Safety and Health's low volume cyclone sampler, a 2-stage Andersen impactor and/or one high volume cyclonic sampler. Samples were analysed using quantitative RT-PCR. Data and results were reported using a mobile data application. Eighty-nine composite oral fluid samples, 70 surface swabs and 122 bioaerosol samples were analysed. Detection rates for influenza virus RNA in swine barn samples were 71.1% for oral fluids, 70.8% for surface swabs and 71.1% for the PTFE sampler. Analysis revealed a statistically significant relationship between the results of the PTFE sampler and the surface swabs with oral fluid results (p < 0.001 and p < 0.01 respectively). In addition, both the PTFE sampler (p < 0.01) and surface swabs (p = 0.03) significantly correlated with, and predicted oral fluid results. Bioaerosol sampling using PTFE samplers is an effective hands-off approach for detecting influenza virus activity among swine. Further study is required for the implementation of this approach for surveillance and risk assessment of circulating influenza viruses of swine origin. In addition, mobile data collection stands to be an invaluable tool in the field by allowing secure, real-time reporting of sample collection and results., (© 2019 Blackwell Verlag GmbH.)

Objectives: The Canadian Network for Public Health Intelligence (CNPHI) is a secure, web-based scientific informatics and biosurveillance platform that leverages disparate public health information resources and expertise for the direct benefit of local, regional and national decision makers. CNPHI fosters collaboration and consultation through innovation in disease surveillance, intelligence exchange, research and response to protect, promote and support public health. The objective of this article is to present the CNPHI 'on the go' mobile application, and to discuss preliminary evaluation of the technology. The mobile application is intended to enable rapid mobile data collection using both online and offline modes supporting various stages of surveillance and response through the extension of data collection and analysis to the mobile environment., Methods: Two needs assessment meetings were held with stakeholders representing individuals from government, academia and research institutions, to inform the development of the CNPHI "on the go" mobile application. An initial version of the mobile technology (an "app") was developed and piloted by end-users with expertise in the field. Two focused pilots were conducted to test the technology: Pilot 1: 17-7-2017 to 21-11-2017 (6 participants); Pilot 2: 25-7-2017 to 15-9-2017 (2 participants). An initial consultation was held with the project leads to identify data elements for mobile data collection. A custom data collection form was designed using CNPHI's Web Data technology for each pilot, which was then made available through the mobile app. The technology was assessed using feedback received during each pilot as well as through a survey that was conducted at the conclusion of pilots., Results: Pilot participants reported that the mobile technology allowed seamless data collection, data management and rapid information sharing. Participants also reported that the entire process was seamless, simple, efficient, and that fewer steps were required for data collection and management. Further, significant efficiencies were gained by directly entering information using the mobile app without having to transfer handwritten information into an electronic database. An overall positive experience was reported by participants from both pilots., Discussion: Literature suggests that traditional methods of surveillance and data collection using a paper based methodology pose many challenges such as data loss and duplication, difficulty in managing the database, and lack of timely access to the data. Accurate and rapid access is critical for public health professionals in order to effectively make decisions and respond to public health emergencies. Results show that the CNPHI "on the go" app is well poised to address some of the suggested challenges. A limitation of this study was that sample size for pilot participation was small for capturing overall feedback on the readiness of the technology for integration into regular surveillance activities and response procedures., Conclusions: CNPHI "on the go" is a customizable technology developed within an already thriving collaborative CNPHI platform used by public health professionals, and performs well as a tool for rapid data collection and secure information sharing.

Objectives: To review user signal rating activity within the Canadian Network for Public Health Intelligence's (CNPHI's) Knowledge Integration using Web-based Intelligence (KIWI) technology by answering the following questions: (1) who is rating, (2) how are users rating, and (3) how well are users rating?, Methods: KIWI rating data was extracted from the CNPHI platform. Zoonotic & Emerging program signals with first rating occurring between January 1, 2016 and December 31, 2017 were included. Krippendorff's alpha was used to estimate inter-rater reliability between users. A z-test was used to identify whether users tended to rate within 95% confidence interval (versus outside) the average community rating., Results: The 37 users who rated signals represented 20 organizations. 27.0% (n = 10) of users rated ≥10% of all rated signals, and their inter-rater reliability estimate was 72.4% (95% CI: 66.5-77.9%). Five users tended to rate significantly outside of the average community rating. An average user rated 58.4% of the time within the signal's 95% CI. All users who significantly rated within the average community rating rated outside the 95% CI at least once., Discussion: A diverse community of raters participated in rating the signals. Krippendorff's Alpha estimate revealed moderate reliability for users who rated ≥10% of signals. It was observed that inter-rater reliability increased for users with more experience rating signals., Conclusions: Diversity was observed between user ratings. It is hypothesized that rating diversity is influenced by differences in user expertise and experience, and that the number of times a user rates within and outside of a signal's 95% CI can be used as a proxy for user expertise. The introduction of a weighted rating algorithm within KIWI that takes this into consideration could be beneficial.

Bilateral striopallidodentate calcinosis, commonly known as Fahr's disease, is a rare syndrome characterised by symmetrical calcification over the basal ganglion and dentate nucleus. No case of Fahr's disease with associated manic symptoms has been described in the literature to date. We report an unusual case of Fahr's Disease in a 18 year old unmarried male who presented to the emergency department of Universal College of Medical Sciences - Teaching Hospital, Nepal with symptoms of mania. Computed tomographic scan of the patient demonstrated extensive symmetrical calcification over the basal ganglia and dentate nuclei. No underlying cause for the bilateral calcification was found. This rare case of Fahr's disease, which has never been reported in Indian literature has been reported to highlight this unusual condition and its differentiation from the commoner Fahr's syndrome.

Purpose: To validate the utility and effectiveness of a standardized tool for prioritization of information sources for early detection of diseases., Methods: The tool was developed with input from diverse public health experts garnered through survey. Ten raters used the tool to evaluate ten information sources and reliability among raters was computed. The Proc mixed procedure with random effect statement and SAS Macros were used to compute multiple raters' Fleiss Kappa agreement and Kendall's Coefficient of Concordance., Results: Ten disparate information sources evaluated obtained the following composite scores: ProMed 91%; WAHID 90%; Eurosurv 87%; MediSys 85%; SciDaily 84%; EurekAl 83%; CSHB 78%; GermTrax 75%; Google 74%; and CBC 70%. A Fleiss Kappa agreement of 50.7% was obtained for ten information sources and 72.5% for a sub-set of five sources rated, which is substantial agreement validating the utility and effectiveness of the tool., Conclusion: This study validated the utility and effectiveness of a standardized criteria tool developed to prioritize information sources. The new tool was used to identify five information sources suited for use by the KIWI system in the CEZD-IIR project to improve surveillance of infectious diseases. The tool can be generalized to situations when prioritization of numerous information sources is necessary.

Objectives: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects., Methods: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto-parietal networks were also investigated., Results: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist - Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA., Conclusions: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631-642).

This status report on the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), an emergency department-based injury and poisoning surveillance system, describes the result of migrating from a centralized data entry and coding process to a decentralized process, the web-based eCHIRPP system, in 2011. This secure system is improving the CHIRPP's overall flexibility and timeliness, which are key attributes of an effective surveillance system. The integrated eCHIRPP platform enables near real-time data entry and access, has user-friendly data management and analysis tools, and allows for easier communication and connectivity across the CHIRPP network through an online collaboration centre. Current pilot testing of automated data monitoring and trend analysis tools-designed to monitor and flag incoming data according to predefined criteria (for example, a new consumer product)-is revealing eCHIRPP's potential for providing early warnings of new hazards, issues and trends.

Background: Invasive pneumococcal disease (IPD) causes significant morbidity in Canada, yet even with routine surveillance, it is difficult to interpret current IPD trends in serotype distribution and antimicrobial resistance. The enhanced Invasive Pneumococcal Disease Surveillance System (eIPDSS) pilot project was designed to facilitate a better understanding of IPD trends at the national level by linking epidemiologic and laboratory (epi-lab) data., Objectives: To evaluate the eIPDSS by assessing five attributes (usefulness, data quality, simplicity, acceptability and timeliness) and to develop recommendations for future national IPD surveillance., Methods: An evaluation was developed that assessed the five key attributes through a qualitative survey sent to eight eIPDSS users as well as a quantitative analysis of the eIPDSS database. Recommendations were based on the results of both the survey and the analysis., Results: The response rate to the survey was 100%. The majority of the survey respondents found the eIPDSS to be useful (75%), simple (100%) and acceptable (86%). Analysis of the eIPDSS database revealed that the majority of IPD cases (61%) were assessed as timely. Data quality and data management mechanisms were identified as issues by both survey respondents and the analysis of the database. Consultation with public health, regular audits and upgrades to the platform are recommended to address data quality and management issues., Conclusion: The epi-lab linked data of the eIPDSS enables the detection and analysis of IPD serotype distribution and antimicrobial resistance trends. This web-based system facilitates data collection and is simple, acceptable and timely. With improvements that address data quality and management issues, it is feasible to develop a national surveillance system that links epi-lab data., Competing Interests: Conflict of interest: None.

Background: Samasharkara Churna, a polyherbal Ayurvedic formulation, is prescribed for treating various conditions such as asthma and cough. Literature review suggested that characterization parameters of Samasharkara Churna are not reported., Objective: To report characteristic parameters of Samasharkara Churna to conform its identity, quality and purity., Materials and Methods: Samasharkara Churna was evaluated for pharmacognostic, physicochemical, microbiological, and chromatographic parameters., Results: The chromatographic analysis was able to showed presence of all ingredients in Samasharkara Churna., Conclusion: The characterization parameters presented in this paper may serve as standard reference for the quality control analysis of Samasharkara Churna., (Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Enterovirus D68 (EV-D68) has been detected infrequently and has not been associated with severe disease in Canada. In the early fall of 2014, following an unusual case increase in the United States, clusters of EV-D68 among children and some adults manifesting severe symptoms were reported in Canada., Objective: To provide an initial epidemiological summary of pediatric cases hospitalized with EV-D68 in Canada., Methods: A time-limited surveillance pilot was conducted collecting information on pediatric cases (less than 18 years of age) hospitalized with EV-D68 between September 1 and 30, 2014., Results: In total, 268 cases were reported from Ontario (n=210), Alberta (n=45), and British Columbia (n=13). Of the 268 reported cases, 64.9% (n=174) were male; the sex difference was statistically significant (p<0.01). Age was reported for 255 cases, with a mean age for males of 5.4 years and for females of 5.3 years. For cases with data available, 6.8% (18/266) were admitted to an intensive care unit. Of those where clinical illness was recorded, respiratory illness alone was present in 98.3% (227/231), neurologic illness alone was present in 0.4% (n=1), and both illnesses were present in 0.9% of cases (n=2); cases with neither respiratory nor neurologic illness were rare (n=1). Of the 90 cases with additional clinical information available, 43.3% were reported as having asthma. No deaths were reported among the 268 cases., Conclusion: The EV-D68 outbreak in Canada in September 2014 represents the beginning of a novel outbreak associated with severe illness in children. These findings provide the first epidemiological summary of severe cases of EV-D68 as an emergent respiratory pathogen in Canada. The continued investigation of this pathogen is necessary to build on these results and capture the full spectrum of associated illness., Competing Interests: Conflict of interest: None

This paper examines the accountability structures within primary healthcare (PHC) in Ontario; in particular, who is accountable for what and to whom, and the policy tools being used. Ontario has implemented a series of incremental reforms, using expenditure policy instruments, enforced through contractual agreements to provide a defined set of publicly financed services that are privately delivered, most often by family physicians. The findings indicate that reporting, funding, evaluation and governance accountability requirements vary across service provider models. Accountability to the funder and patients is most common. Agreements, incentives and compensation tools have been used but may be insufficient to ensure parties are being held responsible for their activities related to stated goals. Clear definitions of various governance structures, a cohesive approach to monitoring critical performance indicators and associated improvement strategies are important elements in operationalizing accountability and determining whether goals are being met., (Copyright © 2014 Longwoods Publishing.)

Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis-based WoE framework was recently published focusing on the U.S. EPA's Tier 1 Endocrine Screening Battery (ESB) as an example. The framework recommends weighting each experimental endpoint according to its relevance for deciding eight hypotheses addressed by the ESB. Here we present detailed rationale for weighting the ESB endpoints according to three rank ordered categories and an interpretive process for using the rankings to reach WoE determinations. Rank 1 was assigned to in vivo endpoints that characterize the fundamental physiological actions for androgen, estrogen, and thyroid activities. Rank 1 endpoints are specific and sensitive for the hypothesis, interpretable without ancillary data, and rarely confounded by artifacts or nonspecific activity. Rank 2 endpoints are specific and interpretable for the hypothesis but less informative than Rank 1, often due to oversensitivity, inclusion of narrowly context-dependent components of the hormonal system (e.g., in vitro endpoints), or confounding by nonspecific activity. Rank 3 endpoints are relevant for the hypothesis but only corroborative of Ranks 1 and 2 endpoints. Rank 3 includes many apical in vivo endpoints that can be affected by systemic toxicity and nonhormonal activity. Although these relevance weight rankings (WREL ) necessarily involve professional judgment, their a priori derivation enhances transparency and renders WoE determinations amenable to methodological scrutiny according to basic scientific premises, characteristics that cannot be assured by processes in which the rationale for decisions is provided post hoc., (© 2014 Wiley Periodicals, Inc.)

We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p < 0.05].

Purpose: Increased activity of mTOR Complex 1 (mTORC1) has been demonstrated in cortical dysplasia and tuberous sclerosis complex, as well as in animal models of epilepsy. Recent studies in such models revealed that inhibiting mTORC1 with rapamycin effectively suppressed seizure activity. However, seizures can recur after treatment cessation, and continuous rapamycin exposure can adversely affect animal growth and health. Here, we evaluated the efficacy of an intermittent rapamycin treatment protocol on epilepsy progression using neuron subset-specific-Pten (NS-Pten) conditional knockout mice., Methods: NS-Pten knockouts were treated with a single course of rapamycin during postnatal weeks 4 and 5, or intermittently over a period of 5 months. Epileptiform activity was monitored using video-electroencephalography (EEG) recordings, and mossy fiber sprouting was evaluated using Timm staining. Survival and body weight were assessed in parallel., Key Findings: NS-Pten knockouts treated with a single course of rapamycin had recurrence of epilepsy 4-7 weeks after treatment ended. In contrast, epileptiform activity remained suppressed, and survival increased if knockout mice received additional rapamycin during weeks 10-11 and 16-17. Aberrant mossy fiber sprouting, present by 4 weeks of age and progressing in parallel with epileptiform activity, was also blocked by rapamycin., Significance: These findings demonstrate that a single course of rapamycin treatment suppresses epileptiform activity and mossy fiber sprouting for several weeks before epilepsy recurs. However, additional intermittent treatments with rapamycin prevented this recurrence and enhanced survival without compromising growth. Therefore, these studies add to the growing body of evidence implicating an important role for mTORC1 signaling in epilepsy., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

The tadpole pancreas has differentiated acinar cells but an underdeveloped ductal system. At the climax of metamorphosis thyroid hormone (TH) induces the tadpole acinar cells to dedifferentiate to a progenitor state. After metamorphosis is complete the exocrine pancreas redifferentiates in the growing frog forming a typical vertebrate pancreas including a complex ductal system. A micro array analysis found that TH up regulates stromelysin 3 (ST3, matrix metalloproteinase 11) in the exocrine pancreas at metamorphic climax. Transgenic tadpoles were prepared with an elastase promoter driving either the ST3 gene or the constitutively active form of Notch (IC). Expression of the transgenes was controlled by the tetracycline system. A few days after either of these transgenes is activated by doxycycline the pancreatic acinar cells turn into duct-like cells. This transdetermination occurs without cell division since both acinar and ductal markers can be visualized transiently in the same cell. We propose that remodeling of the tadpole acinar cells is initiated when ST3 is up regulated by TH. Stromelysin-3 then cleaves and activates Notch., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Emergency Department (ED) overcrowding is an important healthcare issue facing increasing public and regulatory scrutiny in Canada and around the world. Many approaches to alleviate excessive waiting times and lengths of stay have been studied. In theory, optimal ED patient flow may be assisted via balancing patient loads between EDs (in essence spreading patients more evenly throughout this system). This investigation utilizes simulation to explore "Crowdinforming" as a basis for a process control strategy aimed to balance patient loads between six EDs within a mid-sized Canadian city., Methods: Anonymous patient visit data comprising 120,000 ED patient visits over six months to six ED facilities were obtained from the region's Emergency Department Information System (EDIS) to (1) determine trends in ED visits and interactions between parameters; (2) to develop a process control strategy integrating crowdinforming; and, (3) apply and evaluate the model in a simulated environment to explore the potential impact on patient self-redirection and load balancing between EDs., Results: As in reality, the data available and subsequent model demonstrated that there are many factors that impact ED patient flow. Initial results suggest that for this particular data set used, ED arrival rates were the most useful metric for ED 'busyness' in a process control strategy, and that Emergency Department performance may benefit from load balancing efforts., Conclusions: The simulation supports the use of crowdinforming as a potential tool when used in a process control strategy to balance the patient loads between EDs. The work also revealed that the value of several parameters intuitively expected to be meaningful metrics of ED 'busyness' was not evident, highlighting the importance of finding parameters meaningful within one's particular data set. The information provided in the crowdinforming model is already available in a local context at some ED sites. The extension to a wider dissemination of information via an Internet web service accessible by smart phones is readily achievable and not a technological obstacle. Similarly, the system could be extended to help direct patients by including future estimates or predictions in the crowdinformed data. The contribution of the simulation is to allow for effective policy evaluation to better inform the public of ED 'busyness' as part of their decision making process in attending an emergency department. In effect, this is a means of providing additional decision support insights garnered from a simulation, prior to a real world implementation.

Primary Health Care (PHC) is the most common health care experienced by Canadians and is an important source of chronic disease prevention and management; however, PHC providers say they have little information about their patient populations, especially groups of patients with multiple conditions. The Canadian Institute for Health Information in collaboration with 50 PHC providers examined the ability to extract and use a subset of PHC EMR data from four disparate environments in an agreed and privacy sensitive manner. Findings describing the feasibility of clinician engagement, EMR data extraction, EMR content standards and data utility gaps, information system requirements, and systemic enablers and barriers are described in this paper. Ability to collect and use discrete and standardized clinical and administrative information is fundamental to improving practice efficiency, optimal use of information, and patient quality of care. Improving quality of EMR data captured at the point of service will considerably enable our ability to measure and understand PHC across Canada; promote dialogue to identify priority information needs; and support health system information uses for clinical program and health system management, research, and population surveillance.

There are many benefits that derive from real-time knowledge of the health status of the national livestock population. Effective animal disease surveillance is a requirement for countries that trade in live animals and their products in order to comply with the World Organization for Animal Health (OIE) guidelines. Rapid identification of introduced and emerging disease allows rapid response and mitigation of the economic consequences. Connections between animal and human disease caused by a common pathogen can be recognized and control measures implemented, thereby protecting public health and maintaining public confidence in the food supply. Production-limiting diseases can be monitored, and control programmes be evaluated with benefits accruing from decreased economic losses associated with disease as well as reducing the welfare concerns associated with diseased animals. Establishing a surveillance programme across a wide area with diverse ecosystems and political administrations as Canada is a complex challenge. When funding became available from a government programme to enable early detection of a bio-terrorist attack on livestock, the Canadian Animal Health Surveillance Network (CAHSN) became officially established. An existing web-based information platform that supports intelligence exchange, surveillance and response for public health issues in Canada was adapted to link the network animal health laboratories. A minimum data set was developed that facilitated sharing of results between participating laboratories and jurisdictions as the first step in creating the capacity for national disease trend analysis. In each of the network laboratories, similar quality assurance and bio-containment systems have been funded and supported, and diagnostic staff have been trained and certified on a suite of diagnostic tests for foreign animal diseases. This ensures that national standards are maintained throughout all of the diagnostic laboratories. This paper describes the genesis of CAHSN, its current capability and governance, and potential for future development., (© 2010 Blackwell Verlag GmbH.)

During the climax of amphibian metamorphosis many tadpole organs remodel. The different remodeling strategies are controlled by thyroid hormone (TH). The liver, skin, and tail fibroblasts shut off tadpole genes and activate frog genes in the same cell without DNA replication. We refer to this as "gene switching". In contrast, the exocrine pancreas and the intestinal epithelium dedifferentiate to a progenitor state and then redifferentiate to the adult cell type. Tadpole and adult globin are not present in the same cell. Switching from red cells containing tadpole-specific globin to those with frog globin in the liver occurs at a progenitor cell stage of development and is preceded by DNA replication. Red cell switching is the only one of these remodeling strategies that resembles a stem cell mechanism., (Copyright 2009 Elsevier Inc. All rights reserved.)

Amphibian metamorphosis is accompanied by extensive intestinal remodeling. This process, mediated by thyroid hormone (TH) and its nuclear receptors, affects every cell type. Gut remodeling in Xenopus laevis involves epithelial and mesenchymal proliferation, smooth muscle thickening, neuronal aggregation, formation of intestinal folds, and shortening of its length by 75%. Transgenic tadpoles expressing a dominant negative TH receptor (TRDN) controlled by epithelial-, fibroblast-, and muscle-specific gene promoters were studied. TRDN expression in the epithelium caused abnormal development of virtually all cell types, with froglet guts displaying reduced intestinal folds, thin muscle and mesenchyme, absence of neurons, and reduced cell proliferation. TRDN expression in fibroblasts caused abnormal epithelia and mesenchyme development, and expression in muscle produced fewer enteric neurons and a reduced inter-muscular space. Gut shortening was inhibited only when TRDN was expressed in fibroblasts. Gut remodeling results from both cell-autonomous and cell-cell interactions.

Understanding how the pancreas develops is vital to finding new treatments for a range of pancreatic diseases, including diabetes and pancreatic cancer. Xenopus is a relatively new model organism for the elucidation of pancreas development, and has already made contributions to the field. Recent studies have shown benefits of using Xenopus for understanding both early patterning and lineage specification aspects of pancreas organogenesis. This review focuses specifically on Xenopus pancreas development, and covers events from the end of gastrulation, when regional specification of the endoderm is occurring, right through metamorphosis, when the mature pancreas is fully formed. We have attempted to cover pancreas development in Xenopus comprehensively enough to assist newcomers to the field and also to enable those studying pancreas development in other model organisms to better place the results from Xenopus research into the context of the field in general and their studies specifically. Developmental Dynamics 238:1271-1286, 2009. (c) 2009 Wiley-Liss, Inc.

Insulin-producing beta-cells are present as single cells or in small clusters distributed throughout the pancreas of the Xenopus laevis tadpole. During metamorphic climax when the exocrine pancreas dedifferentiates to progenitor cells, the beta-cells undergo two changes. Insulin mRNA is down regulated at the beginning of metamorphic climax (NF62) and reexpressed again near the end of climax. Secondly, the beta-cells aggregate to form islets. During climax the increase in insulin cluster size is not caused by cell proliferation or by acinar-to-beta-cell transdifferentiation, but rather is due to the aggregation of pre-existing beta-cells. The total number of beta-cells does not change during the 8 days of climax. Thyroid hormone (TH) induction of premetamorphic tadpoles causes an increase in islet size while prolonged treatment of tadpoles with the goitrogen methimazole inhibits this increase. Expression of a dominant negative form of the thyroid hormone receptor (TRDN) driven by the elastase promoter not only protects the exocrine pancreas of a transgenic tadpole from TH-induced dedifferentiation but also prevents aggregation of beta-cells at climax. These transgenic tadpoles do however undergo normal loss and resynthesis of insulin mRNA at the same stage as controls. In contrast transgenic tadpoles with the same TRDN transgene driven by an insulin promoter do not undergo down regulation of insulin mRNA, but do aggregate beta-cells to form islets like controls. These results demonstrate that TH controls the remodeling of beta-cells through cell-cell interaction with dedifferentiating acinar cells and a cell autonomous program that temporarily shuts off the insulin gene.

In 2006 the Canadian Institute for Health Information (CIHI) released a set of 105 pan-Canadian Primary Health Care (PHC) indicators. This was followed by an assessment of data gaps, which prevented the calculation of the indicators, and the data collection options available to close the gaps. A quality review of Electronic Medical Record (EMR) data indicated a requirement for content standards. In order to assist the provinces as they developed requests for proposal for PHC-based EMRs, the EMR content standards project was born. Considerable effort was made to identify standards for the Electronic Health Record (EHR) including existing national and international EHR content. As well, CIHI attempted to align the content standards with those of other projects such as the Physician Office System Requirements (POSR). The outcome of this project was a set of EMR content standards for 12 pan-Canadian PHC indicators. The standards will be used to develop a prototype of a PHC reporting system that collects and analyzes data to generate clinical quality indicators for regional and longitudinal comparisons. In late 2008, CIHI will release the pan-Canadian PHC Core Reporting Data Set. This project has developed EMR content standards to better understand PHC in Canada.

At metamorphosis the Xenopus laevis tadpole exocrine pancreas remodels in two stages. At the climax of metamorphosis thyroid hormone (TH) induces dedifferentiation of the entire exocrine pancreas to a progenitor state. The organ shrinks to 20% of its size, and approximately 40% of its cells die. The acinar cells lose their zymogen granules and approximately 75% of their RNA. The mRNAs that encode exocrine-specific proteins (including the transcription factor Ptf1a) undergo almost complete extinction at climax, whereas PDX-1, Notch-1, and Hes-1, genes implicated in differentiation of the progenitor cells, are activated. At the end of spontaneous metamorphosis when the endogenous TH has reached a low level, the pancreas begins to redifferentiate. Exogenous TH induces the dedifferentiation phase but not the redifferentation phase. The tadpole pancreas lacks the mature ductal system that is found in adult vertebrate pancreases, including the frog. Exocrine pancreases of transgenic tadpoles expressing a dominant negative form of the TH receptor controlled by the elastase promoter are resistant to TH. They do not shrink when subjected to TH. Their acinar cells do not dedifferentiate at climax, nor do they down-regulate exocrine-specific genes or activate Notch-1 and Hes-1. Even 2 months after metamorphosis these frogs have not developed a mature ductal system and the acinar cells are abnormally arranged. The TH-dependent dedifferentiation of the tadpole acinar cells at climax is a necessary step in the formation of a mature frog pancreas.

Mixed-sex populations of young adult zebrafish (~2-month-old) were exposed to measured RDX concentrations of 0, 1 or 9.6 ppm for up to 12 weeks followed by a 15-day rearing period in untreated water. RDX caused high mortality at 9.6 ppm, with most deaths occurring within the first 8 weeks of exposure. RDX at 9.6 ppm caused lower body weights at 4 and 8 weeks of exposure; and at 1 ppm, lower body weight was observed only at 4 weeks. Fish length was not affected by treatment at any time during the exposure period. The bioconcentration factor for RDX seemed to be influenced by time of exposure but not by water RDX concentration; its overall values were 1.01+/-0.13, 0.91+/-0.06 and 2.23+/-0.04 at 4, 8 weeks and 12 weeks, respectively. RDX was not detected in fish collected after the 15-day recovery period. In a separate experiment, adult females and males were separately exposed to RDX at measured concentrations of 0, 0.5 and 3.2 ppm for a period of 6 weeks. Reproductive performance was evaluated by biweekly breeding of the fish and measuring packed-egg volume (PEV) as index of fecundity. At 0.5 ppm, RDX caused elevated PEV levels relative to the control value at 2 weeks but not at 4 or 6 weeks, whereas no significant effects were noted at 3.2 ppm. Egg fertilization and embryo hatching rates were not affected by RDX at any of the concentrations tested. In conclusion, RDX at sublethal concentrations causes short-term negative effects on growth and, at 0.5 ppm, positive effects on fecundity.

Microcystin-LR (MCLR) is the most common hepatotoxic cyanotoxin produced primarily by Microcystis aeruginosa. In this study, young F344 rats were intraperitoneally injected with a single dose (25, 50, 100, and 150 microg/kg) of MCLR to explore possible toxic effect and toxic response indicators. Acute toxic symptoms, including body weight loss and death, were monitored for 7 days. Mortality reached 100% (9/9) in rats treated with a single MCLR dose of 150 microg/kg. Histopathological examination showed spot necrosis in the liver of animals treated at low doses, while massive hemorrhage and widespread necrotic foci occurred at higher doses, indicating extensive liver damage. Protein phosphatase 2A (PP2A) expression showed a dose-dependent decrease in the liver. Immunohistochemical localization indicated that nuclear PP2A was affected first, followed by cytoplasmic PP2A. In addition, there was a significant increase in sphingolipid levels at higher doses, indicating the involvement of a ceramide-mediated apoptotic pathway. Expression of apoptosis and cell cycle regulatory proteins like Bax, Bcl2, and Bad showed a dose-dependent decrease. This study demonstrated that treatment with a single dose of MCLR caused liver damage, increased sphingolipid levels, and decreased PP2A expression, which ultimately down-regulated the expression of Bcl2 family proteins.