Forecasting seasonal influenza activity in Canada-Comparing seasonal Auto-Regressive integrated moving average and artificial neural network approaches for public health preparedness.

INTRODUCTION: Public health preparedness is based on timely and accurate information. Time series forecasting using disease surveillance data is an important aspect of preparedness. This study compared two approaches of time series forecasting: seasonal auto-regressive integrated moving average (SARIMA) modelling and the artificial neural network (ANN) algorithm. The goal was to model weekly seasonal influenza activity in Canada using SARIMA and compares its predictive accuracy, based on root mean square prediction error (RMSE) and mean absolute prediction error (MAE), to that of an ANN. METHODS: An initial SARIMA model was fit using automated model selection by minimizing the Akaike information criterion (AIC). Further inspection of the autocorrelation function and partial autocorrelation function led to 'manual' model improvements. ANNs were trained iteratively, using an automated process to minimize the RMSE and MAE. RESULTS: A total of 378, 462 cases of influenza was reported in Canada from the 2010-2011 influenza season to the end of the 2019-2020 influenza season, with an average yearly incidence risk of 20.02 per 100,000 population. Automated SARIMA modelling was the better method in terms of forecasting accuracy (per RMSE and MAE). However, the ANN correctly predicted the peak week of disease incidence while the other models did not. CONCLUSION: Both the ANN and SARIMA models have shown to be capable tools in forecasting seasonal influenza activity in Canada. It was shown that applying both in tandem is beneficial, SARIMA better forecasted overall incidence while ANN correctly predicted the peak week.

A Scoping Review on the Epidemiology of Orthobunyaviruses in Canada, in the Context of Human, Wildlife, and Domestic Animal Host Species.

Background: Mosquito-borne orthobunyaviruses in Canada are a growing public health concern. Orthobunyaviral diseases are commonly underdiagnosed and in Canada, likely underreported as surveillance is passive. No vaccines or specific treatments exist for these disease agents. Further, climate change is facilitating habitat expansion for relevant reservoirs and vectors, and it is likely that the majority of the Canadian population is susceptible to these viruses. Methods: A scoping review was conducted to describe the current state of knowledge on orthobunyavirus epidemiology in Canada. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guideline was used. Literature searches were conducted in six databases and in gray literature. The epidemiology of orthobunyaviruses was characterized for studies focusing on host species, including spatiotemporal patterns, risk factors, and climate change impact. Results: A total of 172 relevant studies were identified from 1734 citations from which 95 addressed host species, including humans, wildlife, and domestic animals including livestock. The orthobunyaviruses-Cache Valley virus (CVV), Jamestown Canyon virus (JCV), Snowshoe Hare virus (SHV), and La Crosse virus (LACV)-were identified, and prevalence was widespread across vertebrate species. CVV, JCV, and SHV were detected across Canada and the United States. LACV was reported only in the United States, predominantly the Mid-Atlantic and Appalachian regions. Disease varied by orthobunyavirus and was associated with age, environment, preexisting compromised immune systems, or livestock breeding schedule. Conclusion: Knowledge gaps included seroprevalence data in Canada, risk factor analyses, particularly for livestock, and disease projections in the context of climate change. Additional surveillance and mitigation strategies, especially accounting for climate change, are needed to guide future public health efforts to prevent orthobunyavirus exposure and disease.

The role of glucagon-like peptide 1 receptor agonists for weight control in individuals with acquired hypothalamic obesity-A systematic review.

Hypothalamic obesity does not respond well to conventional interventions for obesity. GLP-1 receptor agonists have mechanisms independent of the hypothalamus which may be potentially beneficial for managing hypothalamic obesity. This systematic review summarizes the efficacy and safety of GLP-1 receptor agonists use in hypothalamic obesity. A PRISMA-compliant systematic review was performed. Data was extracted from included studies and analysed based on change in weight, body mass index, glycaemic control, satiety, and safety profile with GLP-1 receptor agonist use. Ten studies comprising 5 case reports, 4 case series and 1 randomized-controlled trial included 54 patients (24 males, 30 females) with mean age of 25.2 (range 13-71) years with hypothalamic obesity who had received GLP-1 receptor agonists (exenatide = 48, liraglutide = 5 and dulaglutide = 1) over a mean duration of treatment of 12 (range 3-51) months. Mean weight reduction of 7.4 (SD 7.92) kg was observed in patients in whom weight was reported, with 85.7% of patients experiencing weight loss. All patients on liraglutide had weight reduction post-therapy. The sole trial had reported a non-significant reduction in BMI post-exenatide. Glycaemic control had either improved/maintained in all patients in whom this was measured. The main side effects of GLP-1 receptor agonist in individuals with hypothalamic obesity were nausea and vomiting; there were no major safety concerns. Based on limited published experience, GLP-1RA may be effective and safe for weight control in hypothalamic obesity, with the added benefit of improved glycaemic control in those with concurrent diabetes mellitus.

Professional identity formation amongst peer-mentors in a research-based mentoring programme.

BACKGROUND: Mentoring plays a pivotal yet poorly understood role in shaping a physician's professional identity formation (PIF) or how they see, feel and act as professionals. New theories posit that mentoring nurtures PIF by functioning as a community of practice through its structured approach and its support of a socialisation process made possible by its assessment-directed personalized support. To test this theory and reshape the design, employ and support of mentoring programs, we evaluate peer-mentor experiences within the Palliative Medicine Initiative's structured research mentoring program. METHODS: Semi-structured interviews with peer mentors under the Palliative Medicine Initiative (PMI) at National Cancer Centre Singapore were conducted and triangulated against mentoring diaries to capture longitudinal data of their PMI experiences. The Systematic Evidence-Based Approach (SEBA) was adopted to enhance the trustworthiness of the data. SEBA employed concurrent content and thematic analysis of the data to ensure a comprehensive review. The Jigsaw Perspective merged complementary themes and categories identified to create themes/categories. The themes/categories were compared with prevailing studies on mentoring in the Funnelling Process to reaffirm their accuracy. RESULTS: Twelve peer-mentors participated in the interviews and eight peer-mentors completed the mentoring diaries. The domains identified were community of practice and identity work. CONCLUSIONS: The PMI's structured mentoring program functions as a community of practice supporting the socialisation process which shapes the peer-mentor's belief system. Guided by a structured mentoring approach, stage-based assessments, and longitudinal mentoring and peer support, peer-mentors enhance their detection and evaluation of threats to their regnant belief system and adapt their self-concepts of identity and personhood to suit their context. These insights will help structure and support mentoring programs as they nurture PIF beyond Palliative Medicine.

Assessing the effects of a mentoring program on professional identity formation.

BACKGROUND: Medical education has enjoyed mixed fortunes nurturing professional identity formation (PIF), or how medical students think, feel and act as physicians. New data suggests that structured mentoring programs like the Palliative Medicine Initiative (PMI) may offer a means of developing PIF in a consistent manner. To better understand how a well-established structured research mentoring program shapes PIF, a study of the experiences of PMI mentees is proposed. METHODOLOGY: Acknowledging PIF as a sociocultural construct, a Constructivist approach and Relativist lens were adopted for this study. In the absence of an effective tool, the Ring Theory of Personhood (RToP) and Krishna-Pisupati Model (KPM) model were used to direct this dual Systematic Evidence-Based Approach (Dual-SEBA) study in designing, employing and analysing semi-structured interviews with PMI mentees and mentoring diaries. These served to capture changes in PIF over the course of the PMI's mentoring stages. Transcripts of the interviews and mentoring diaries were concurrently analysed using content and thematic analysis. Complementary themes and categories identified from the Split Approach were combined using the Jigsaw Approach and subsequently compared with mentoring diaries in the Funnelling Process. The domains created framed the discussion. RESULTS: A total of 12 mentee interviews and 17 mentoring diaries were analysed, revealing two domains-PMI as a Community of Practice (CoP) and Identity Formation. The domains confirmed the centrality of a structured CoP capable of facilitating longitudinal mentoring support and supporting the Socialisation Process along the mentoring trajectory whilst cultivating personalised and enduring mentoring relationships. CONCLUSION: The provision of a consistent mentoring approach and personalised, longitudinal mentoring support guided along the mentoring trajectory by structured mentoring assessments lay the foundations for more effective mentoring programs. The onus must now be on developing assessment tools, such as a KPM-based tool, to guide support and oversight of mentoring relationships.

The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.

The control of Wnt receptor abundance is critical for animal development and to prevent tumorigenesis, but the mechanisms that mediate receptor stabilization remain uncertain. We demonstrate that stabilization of the essential Wingless/Wnt receptor Arrow/LRP6 by the evolutionarily conserved Usp46-Uaf1-Wdr20 deubiquitylase complex controls signaling strength in Drosophila. By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses. Usp46 inactivation in Wingless-responding cells destabilizes Arrow, reduces cytoplasmic accumulation of the transcriptional coactivator Armadillo/ß-catenin, and attenuates or abolishes Wingless target gene activation, which prevents the concentration-dependent regulation of signaling strength. Consequently, Wingless-dependent developmental patterning and tissue homeostasis are disrupted. These results reveal an evolutionarily conserved mechanism that mediates Wnt/Wingless receptor stabilization and underlies the precise activation of signaling throughout the spatial range of the morphogen gradient.

The USP46 complex deubiquitylates LRP6 to promote Wnt/ß-catenin signaling.

The relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells. We find that the USP46 complex is similarly required for Wnt signaling in Xenopus and zebrafish embryos. We demonstrate that Wnt signaling promotes the association between the USP46 complex and cell surface Wnt coreceptor, LRP6. Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6. In contrast, overexpression of the USP46 complex blocks ubiquitylation of LRP6 by the ubiquitin ligases RNF43 and ZNFR3. Size exclusion chromatography studies suggest that the size of the USP46 cytoplasmic complex increases upon Wnt stimulation. Finally, we show that USP46 is essential for Wnt-dependent intestinal organoid viability, likely via its role in LRP6 receptor homeostasis. We propose a model in which the USP46 complex increases the steady-state level of cell surface LRP6 and facilitates the assembly of LRP6 into signalosomes via a pruning mechanism that removes sterically hindering ubiquitin chains.

Cache a Killer: Cache Valley virus seropositivity and associated farm management risk factors in sheep in Ontario, Canada.

Cache Valley virus (CVV) disease is a mosquito-borne zoonosis endemic to North America. CVV disease is reported most often in sheep, causing lethal congenital deformities. There are limited data on CVV in Ontario, which is the largest sheep producing province in Canada. This study aimed to determine CVV seroprevalence in Ontario sheep flocks and investigate farm management factors associated with CVV exposure. A cross-sectional study was performed including 364 mature ewes across 18 farms selected from the five largest sheep districts in the province. A questionnaire was administered at each farm to determine farm management practices pertinent to the flock and ewes specifically sampled. Mixed multivariable logistic regression with a random effect for farm was conducted to assess associations between CVV seropositivity (outcome variable) and farm management risk factors (predictor variables). CVV seroprevalence was 33.2% in individual ewes (95% CI: 28.4%-38.1%) as determined by a virus neutralization assay with a titre > 4. Sixteen of the eighteen flocks (88.9%) had at least one CVV seropositive ewe. Increased age, smaller flock size, and sheep housing near wetlands, lakes, or ponds were found to be significantly associated with higher odds of CVV seropositivity. These findings are valuable in guiding breeding practices and housing during mosquito season to minimize infection and, ultimately, CVV disease in the flock.

Large Decrease in the Melting Point of Benzoquinones via High-n Eutectic Mixing Predicted by a Regular Solution Model.

Decreasing the melting point (Tm) of a mixture is of interest in cryopreservatives, molten salts, and battery electrolytes. One general strategy to decrease Tm, exemplified by deep eutectic solvents, is to mix components with favorable (negative) enthalpic interactions. We demonstrate a complementary strategy to decrease Tm by mixing many components with neutral or slightly positive enthalpic interactions, using the number of components (n) to increase the entropy of mixing and decrease Tm. In theory, under certain conditions this approach could achieve an arbitrarily low Tm. Furthermore, if the components are small redox-active molecules, such as the benzoquinones studied here, this approach could lead to high energy density flow battery electrolytes. Finding the eutectic composition of a high-n mixture can be challenging due to the large compositional space yet is essential for ensuring the existence of a purely liquid phase. We reformulate and apply fundamental thermodynamic equations to describe high-n eutectic mixtures of small redox-active molecules (benzoquinones and hydroquinones). We illustrate a novel application of this theory by tuning the entropy of melting, rather than the enthalpy, in systems highly relevant to energy storage. We demonstrate with differential scanning calorimetry measurements that 1,4-benzoquinone derivatives exhibit eutectic mixing that decreases their Tm, despite slightly positive enthalpies of mixing (0-5 kJ/mol). By rigorously investigating all 21 binary mixtures of a set of seven 1,4-benzoquinone derivatives with alkyl substituents (Tm's between 44 and 120 °C), we find that the eutectic melting point of a mixture of all seven achieves a large decrease in Tm to -6 °C. We further determine that the regular solution model shows improvement over an ideal solution model in predicting the eutectic properties for this newly investigated type of mixture composed of many small redox-active organic molecules.

SELENOP modifies sporadic colorectal carcinogenesis and WNT signaling activity through LRP5/6 interactions.

Although selenium deficiency correlates with colorectal cancer (CRC) risk, the roles of the selenium-rich antioxidant selenoprotein P (SELENOP) in CRC remain unclear. In this study, we defined SELENOP's contributions to sporadic CRC. In human single-cell cRNA-Seq (scRNA-Seq) data sets, we discovered that SELENOP expression rose as normal colon stem cells transformed into adenomas that progressed into carcinomas. We next examined the effects of Selenop KO in a mouse adenoma model that involved conditional, intestinal epithelium-specific deletion of the tumor suppressor adenomatous polyposis coli (Apc) and found that Selenop KO decreased colon tumor incidence and size. We mechanistically interrogated SELENOP-driven phenotypes in tumor organoids as well as in CRC and noncancer cell lines. Selenop-KO tumor organoids demonstrated defects in organoid formation and decreases in WNT target gene expression, which could be reversed by SELENOP restoration. Moreover, SELENOP increased canonical WNT signaling activity in noncancer and CRC cell lines. In defining the mechanism of action of SELENOP, we mapped protein-protein interactions between SELENOP and the WNT coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). Last, we confirmed that SELENOP-LRP5/6 interactions contributed to the effects of SELENOP on WNT activity. Overall, our results position SELENOP as a modulator of the WNT signaling pathway in sporadic CRC.

USP47 deubiquitylates Groucho/TLE to promote Wnt-ß-catenin signaling.

The Wnt-ß-catenin signal transduction pathway is essential for embryonic development and adult tissue homeostasis. Wnt signaling converts TCF from a transcriptional repressor to an activator in a process facilitated by the E3 ligase XIAP. XIAP-mediated monoubiquitylation of the transcriptional corepressor Groucho (also known as TLE) decreases its affinity for TCF, thereby allowing the transcriptional coactivator ß-catenin to displace it on TCF. Through a genome-scale screen in cultured Drosophila melanogaster cells, we identified the deubiquitylase USP47 as a positive regulator of Wnt signaling. We found that USP47 was required for Wnt signaling during Drosophila and Xenopus laevis development, as well as in human cells, indicating evolutionary conservation. In human cells, knockdown of USP47 inhibited Wnt reporter activity, and USP47 acted downstream of the ß-catenin destruction complex. USP47 interacted with TLE3 and XIAP but did not alter their amounts; however, knockdown of USP47 enhanced XIAP-mediated ubiquitylation of TLE3. USP47 inhibited ubiquitylation of TLE3 by XIAP in vitro in a dose-dependent manner, suggesting that USP47 is the deubiquitylase that counteracts the E3 ligase activity of XIAP on TLE. Our data suggest a mechanism by which regulated ubiquitylation and deubiquitylation of TLE enhance the ability of ß-catenin to cycle on and off TCF, thereby helping to ensure that the expression of Wnt target genes continues only as long as the upstream signal is present.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Quantifying the economic gains associated with COVID-19 vaccination in the Canadian population: A cost-benefit analysis.

Background: Vaccination has been a key part of Canada's coronavirus disease 2019 (COVID-19) pandemic response. Although the clinical benefits of vaccination are clear, an understanding of the population-level benefits of vaccination relative to the programmatic costs is of value. The objective of this article is to quantify the economic impact of COVID-19 vaccination in the Canadian population between December 2020 and March 2022. Methods: We conducted a model-based cost-benefit analysis of Canada's COVID-19 vaccination program. We used an epidemiological model to estimate the number of COVID-19 symptomatic cases, hospitalizations, post-COVID condition (PCC) cases, and deaths in the presence and absence of vaccination. Median, lower and upper 95% credible interval (95% CrI) outcome values from 100 model simulations were used to estimate the direct and indirect costs of illness, including the value of health. We used a societal perspective and a 1.5% discount rate. Results: We estimated that the costs of the vaccination program were far outweighed by the savings associated with averted infections and associated downstream consequences. Vaccination increased the net benefit by CAD $298.1 billion (95% CrI: 27.2-494.6) compared to the no vaccination counterfactual. The largest benefits were due to averted premature mortality, resulting in an estimated $222.0 billion (95% CrI: 31.2-379.0) benefit. Conclusion: Our model-based economic evaluation provides a retrospective assessment of COVID-19 vaccination during the first 16 months of the program in Canada and suggests that it was welfare-improving, considering the decreased hospitalizations and use of healthcare resources, deaths averted and lower morbidity from conditions such as PCC.

The role of mentoring, supervision, coaching, teaching and instruction on professional identity formation: a systematic scoping review.

BACKGROUND: Mentoring's pivotal role in nurturing professional identity formation (PIF) owes much to its combined use with supervision, coaching, tutoring, instruction, and teaching. However the effects of this combination called the 'mentoring umbrella' remains poorly understood. This systematic scoping review thus aims to map current understanding. METHODS: A Systematic Evidence-Based Approach guided systematic scoping review seeks to map current understanding of the 'mentoring umbrella' and its effects on PIF on medical students and physicians in training. It is hoped that insights provided will guide structuring, support and oversight of the 'mentoring umbrella' in nurturing PIF. Articles published between 2000 and 2021 in PubMed, Scopus, ERIC and the Cochrane databases were scrutinised. The included articles were concurrently summarised and tabulated and concurrently analysed using content and thematic analysis and tabulated. The themes and categories identified were compared with the summaries of the included articles to create accountable and reproducible domains that guide the discussion. RESULTS: A total of 12201 abstracts were reviewed, 657 full text articles evaluated, and 207 articles included. The three domains identified were definitions; impact on PIF; and enablers and barriers. The mentoring umbrella shapes PIF in 3 stages and builds a cognitive base of essential knowledge, skills and professional attitudes. The cognitive base informs thinking, conduct and opinions in early supervised clinical exposure in Communities of practice (COP). The COPs' individualised approach to the inculcation of desired professional characteristics, goals, values, principles and beliefs reshapes the individual's identity whilst the socialisation process sees to their integration into current identities. CONCLUSION: The mentoring umbrella's provides personalised longitudinal support in the COP and socialisation process. Understanding it is key to addressing difficulties faced and ensuring holistic and timely support.

Counterfactuals of effects of vaccination and public health measures on COVID-19 cases in Canada: What could have happened?

This study illustrates what may have happened, in terms of coronavirus disease 2019 (COVID-19) infections, hospitalizations and deaths in Canada, had public health measures not been used to control the COVID-19 epidemic, and had restrictions been lifted with low levels of vaccination, or no vaccination, of the Canadian population. The timeline of the epidemic in Canada, and the public health interventions used to control the epidemic, are reviewed. Comparisons against outcomes in other countries and counterfactual modelling illustrate the relative success of control of the epidemic in Canada. Together, these observations show that without the use of restrictive measures and without high levels of vaccination, Canada could have experienced substantially higher numbers of infections and hospitalizations and almost a million deaths.

Modelling the impact of age-stratified public health measures on SARS-CoV-2 transmission in Canada.

Public health measures applied exclusively within vulnerable populations have been suggested as an alternative to community-wide interventions to mitigate SARS-CoV-2 transmission. With the population demography and healthcare capacity of Canada as an example, a stochastic age-stratified agent-based model was used to explore the progression of the COVID-19 epidemic under three intervention scenarios (infection-preventing vaccination, illness-preventing vaccination and shielding) in individuals above three age thresholds (greater than or equal to 45, 55 and 65 years) while lifting shutdowns and physical distancing in the community. Compared with a scenario with sustained community-wide measures, all age-stratified intervention scenarios resulted in a substantial epidemic resurgence, with hospital and ICU bed usage exceeding healthcare capacities even at the lowest age threshold. Individuals under the age threshold were severely impacted by the implementation of all age-stratified interventions, with large numbers of avoidable deaths. Among all explored scenarios, shielding older individuals led to the most detrimental outcomes (hospitalizations, ICU admissions and mortality) for all ages, including the targeted population. This study suggests that, in the absence of community-wide measures, implementing interventions exclusively within vulnerable age groups could result in unmanageable levels of infections, with serious outcomes within the population. Caution is therefore warranted regarding early relaxation of community-wide restrictions.

Zika virus outbreak in Brazil under current and future climate.

INTRODUCTION: Zika virus (ZIKV) is primarily transmitted byAedes aegypti and Aedes albopictus mosquitoes between humans and non-human primates. Climate change may enhance virus reproduction in Aedes spp. mosquito populations, resulting in intensified ZIKV outbreaks. The study objective was to explore how an outbreak similar to the 2016 ZIKV outbreak in Brazil might unfold with projected climate change. METHODS: A compartmental infectious disease model that included compartments for humans and mosquitoes was developed to fit the 2016 ZIKV outbreak data from Brazil using least squares optimization. To explore the impact of climate change, published polynomial relationships between temperature and temperature-sensitive mosquito population and virus transmission parameters (mosquito mortality, development rate, and ZIKV extrinsic incubation period) were used. Projections for future outbreaks were obtained by simulating transmission with effects of projected average monthly temperatures on temperature-sensitive model parameters at each of three future time periods: 2011-2040, 2041-2070, and 2071-2100. The projected future climate was obtained from an ensemble of regional climate models (RCMs) obtained from the Co-Ordinated Regional Downscaling Experiment (CORDEX) that used Representative Concentration Pathways (RCP) with two radiative forcing values, RCP4.5 and RCP8.5. A sensitivity analysis was performed to explore the impact of temperature-dependent parameters on the model outcomes. RESULTS: Climate change scenarios impacted the model outcomes, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the duration of the ZIKV outbreak. Comparing 2070-2100 to 2016, using RCP4.5, the peak incidence was 22,030 compared to 10,473; the time to epidemic peak was 12 compared to 9 weeks, and the outbreak duration was 52 compared to 41 weeks. Comparing 2070-2100 to 2016, using RCP8.5, the peak incidence was 21,786 compared to 10,473; the time to epidemic peak was 11 compared to 9 weeks, and the outbreak duration was 50 compared to 41weeks. The increases are due to optimal climate conditions for mosquitoes, with the mean temperature reaching 28 °C in the warmest months. Under a high emission scenario (RCP8.5), mean temperatures extend above optimal for mosquito survival in the warmest months. CONCLUSION: Outbreaks of ZIKV in locations similar to Brazil are expected to be more intense with a warming climate. As climate change impacts are becoming increasingly apparent on human health, it is important to quantify the effect and use this knowledge to inform decisions on prevention and control strategies.

Modelling the impact of shutdowns on resurging SARS-CoV-2 transmission in Canada.

BACKGROUND: Shutdowns are enacted when alternative public health measures are insufficient to control the epidemic and the population is largely susceptible. An age-stratified agent-based model was developed to explore the impact of shutdowns to control SARS-CoV-2 transmission in Canada under the assumption that current efforts to control the epidemic remains insufficient and in the absence of a vaccine. METHODS: We estimated the current levels of interventions in Canada to generate a baseline scenario from 7 February to 7 September 2020. Four aspects of shutdowns were explored in scenarios that ran from 8 September 2020 to 7 January 2022, these included the impact of how quickly shutdowns are implemented, the duration of shutdowns, the minimum break (delays) between shutdowns and the types of sectors to shutdown. Comparisons among scenarios were made using cases, hospitalizations, deaths and shutdown days during the 700-day model runs. RESULTS: We found a negative relationship between reducing SARS-CoV-2 transmission and the number of shutdown days. However, we also found that for shutdowns to be optimally effective, they need to be implemented fast with minimal delay, initiated when community transmission is low, sustained for an adequate period and be stringent and target multiple sectors, particularly those driving transmission. By applying shutdowns in this manner, the total number of shutdown days could be reduced compared to delaying the shutdowns until further into the epidemic when transmission is higher and/or implementing short insufficient shutdowns that would require frequent re-implementation. This paper contrasts a range of shutdown strategies and trade-offs between health outcomes and economic metrics that need to be considered within the local context. INTERPRETATION: Given the immense socioeconomic impact of shutdowns, they should be avoided where possible and used only when other public health measures are insufficient to control the epidemic. If used, the time it buys to delay the epidemic should be used to enhance other equally effective, but less disruptive, public health measures.

Yellow fever virus outbreak in Brazil under current and future climate.

INTRODUCTION: Yellow fever (YF) is primarily transmitted by Haemagogus species of mosquitoes. Under climate change, mosquitoes and the pathogens that they carry are expected to develop faster, potentially impacting the case count and duration of YF outbreaks. The aim of this study was to determine how YF virus outbreaks in Brazil may change under future climate, using ensemble simulations from regional climate models under RCP4.5 and RCP8.5 scenarios for three time periods: 2011-2040 (short-term), 2041-2070 (mid-term), and 2071-2100 (long-term). METHODS: A compartmental model was developed to fit the 2017/18 YF outbreak data in Brazil using least squares optimization. To explore the impact of climate change, temperature-sensitive mosquito parameters were set to change over projected time periods using polynomial equations fitted to their relationship with temperature according to the average temperature for years 2011-2040, 2041-2070, and 2071-2100 for climate change scenarios using RCP4.5 and RCP8.5, where RCP4.5/RCP8.5 corresponds to intermediate/high radiative forcing values and to moderate/higher warming trends. A sensitivity analysis was conducted to determine how the temperature-sensitive parameters impacted model results, and to determine how vaccination could play a role in reducing YF in Brazil. RESULTS: Yellow fever case projections for Brazil from the models varied when climate change scenarios were applied, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the outbreak duration. Overall, a decrease in YF cases and outbreak duration was observed. Comparing the observed incidence in 2017/18 to the projected incidence in 2070-2100, for RCP4.5, the cumulative case incidence decreased from 184 to 161, and the outbreak duration decreased from 21 to 20 weeks. For RCP8.5, the peak case incidence decreased from 184 to 147, and the outbreak duration decreased from 21 to 17 weeks. The observed decrease was primarily due to temperature increasing beyond that suitable for Haemagogus mosquito survival. CONCLUSIONS: Climate change is anticipated to have an impact on mosquito-borne diseases. We found outbreaks of YF may reduce in intensity as temperatures increase in Brazil; however, temperature is not the only factor involved with disease transmission. Other factors must be explored to determine the attributable impact of climate change on mosquito-borne diseases.

Application of natural language processing algorithms for extracting information from news articles in event-based surveillance.

The focus of this article is the application of natural language processing (NLP) for information extraction in event-based surveillance (EBS) systems. We describe common information extraction applications from open-source news articles and media sources in EBS systems, methods, value in public health, challenges and emerging developments.