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The global number of vulnerable citizens in areas of landslide risk is expected to increase due to the twin forces of climate change and growing urbanization. Self-constructed or informal settlements are frequently built in hazardous terrain such as on landslide-prone slopes. They are characterized by high dynamics of growth, simple construction methods and strong social dynamics and are exposed to unsteady political approaches. Landslide early warning systems (LEWSs) can contribute to decreasing their vulnerability, but precise, affordable and culturally integrated LEWSs need to be further developed. In this paper, we present a 4-year living-lab research project called Inform@Risk that aimed to develop a LEWS prototype in the neighborhood of Bello Oriente, located on the urban–rural border of Medellín, Colombia. Its research team is composed of landscape architects, geo-engineers, and remote sensing and geo-informatics experts. The research team collaborated with a multitude of stakeholders: civil society, private enterprises, non-governmental agencies and various branches of government. A preliminary LEWS with the last functionalities still to be developed has been designed, implemented and handed over to the government. It has entered a test and calibration phase (i.e., warning-threshold development, procedures for warning and alert dissemination through the sensor system), which is on hold due to legal constraints. Our first findings indicate that the integrative development of technical aspects of a LEWS in informal settlements can be challenging, albeit manageable, whereas the level of social and political support is beyond the control of the designer. Steady political will is needed to increase technical capacities and funding of the operation and maintenance of an increased amount of monitoring equipment. Social outreach has to be continuous in order to inform, train, maintain the trust and increase the self-help capacities of the often rapidly changing population of an informal settlement. Legal requirements for a transfer of academic research projects to municipal authorities have to be clear from the start. Satisfying replacement housing options for the case of evacuation have to be in place in order to not lose the overall acceptance of the LEWS. As political will and municipal budgets can vary, a resilient LEWS for informal settlements has to achieve sufficient social and technical redundancy to maintain basic functionality even in a reduced-governmental-support scenario.

Landslides are socio-natural hazards. In Colombia, for example, these are the most frequent hazards. The interplay of climate change and the mostly informal growth of cities in landslide-prone areas increases the associated risks. Landslide early warning systems (LEWSs) are essential for disaster risk reduction, but the monitoring component is often based on expensive sensor systems. This study presents a data-driven approach to localize landslide-prone areas suitable for low-cost and easy-to-use LEWS instrumentation, as well as to estimate the associated costs. The approach is exemplified in the landslide-prone city of Medellín, Colombia. A workflow that enables decision-makers to balance financial costs and the potential to protect exposed populations is introduced. To achieve this, city-level landslide susceptibility is mapped using data on hazard levels, landslide inventories, geological and topographic factors, and a random forest model. Then, the landslide susceptibility map is combined with a population density map to identify highly exposed areas. Subsequently, a cost function is defined to estimate the cost of LEWS monitoring sensors at the selected sites, using lessons learned from a pilot LEWS in Bello Oriente, a neighbourhood in Medellín. This study estimates that LEWS monitoring sensors could be installed in several landslide-prone areas with a budget ranging from EUR 5 to EUR 41 per person (roughly COP 23 000 to 209 000), improving the resilience of over 190 000 exposed individuals, 81 % of whom are located in precarious neighbourhoods; thus, the systems would particularly reduce the risks of a social group of very high vulnerability. The synopsis of all information allows us to provide recommendations for stakeholders on where to proceed with LEWS instrumentation. These are based on five different cost-effectiveness scenarios. This approach enables decision-makers to prioritize LEWS deployment to protect exposed populations while balancing the financial costs, particularly for those in precarious neighbourhoods. Finally, the limitations, challenges, and opportunities for the successful implementation of a LEWS are discussed.

Abstract Background Persistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections. Methods We performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates. Results Our literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7–95.1% and 60.4–67.7%, respectively) and seemed robust to violations of underlying assumptions. Conclusions As the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.

Background: Acute kidney injury (AKI) is a potentially fatal complication of Coronavirus Disease-2019 (COVID-19). Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, to its viral receptor, angiotensin converting enzyme 2 (ACE2), results in viral entry and may cause AKI. Objectives: We performed a systematic review and meta-analysis of the frequencies of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients and compared those frequencies with patients who were infected by respiratory viruses that bind or downregulate ACE2 (ACE2-associated viruses) and viruses that do not bind nor downregulate ACE2 (non-ACE2-associated viruses). Design: Systematic review and meta-analysis. Setting: Observational studies on COVID-19 and other respiratory viral infections reporting AKI and RRT were included. The exclusion criteria were non-English articles, non-peer-reviewed articles, review articles, studies that included patients under the age of 18, studies including fewer than 10 patients, and studies not reporting AKI and RRT rates. Patients: Adult COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza patients. Measurements: We extracted the following data from the included studies: author, year, study location, age, sex, race, diabetes mellitus, hypertension, chronic kidney disease, shock, vasopressor use, mortality, intensive care unit (ICU) admission, ICU mortality, AKI, and RRT. Methods: We systematically searched PubMed and EMBASE for articles reporting AKI or RRT. AKI was defined by authors of included studies. Critical illness was defined by ICU admission. We performed a random effects meta-analysis to calculate pooled estimates for the AKI and RRT rate within each virus group using a random intercept logistic regression model. Results: Of 23 655 hospitalized, critically ill COVID-19 patients, AKI frequencies were not significantly different between COVID-19 patients (51%, 95% confidence interval [CI]: 44%-57%) and critically ill patients infected with ACE2-associated (56%, 95% CI: 37%-74%, P = .610) or non-ACE2-associated viruses (63%, 95% CI: 43%-79%, P = .255). Pooled RRT rates were also not significantly different between critically ill, hospitalized patients with COVID-19 (20%, 95% CI: 16%-24%) and ACE2-associated viruses (18%, 95% CI: 8%-33%, P = .747). RRT rates for both COVID-19 and ACE2-associated viruses were significantly different ( P < .001 for both) from non-ACE2-associated viruses (49%, 95% CI: 44%-54%). After adjusting for shock or vasopressor use, AKI and RRT rates were not significantly different between groups. Limitations: Limitations of this study include the heterogeneity of definitions of AKI that were used across different virus studies. We could not match severity of infection or do propensity matching across studies. Most of the included studies were conducted in retrospective fashion. Last, we did not include non-English publications. Conclusions: Our findings suggest that viral ACE2 association does not significantly alter the rates of AKI and RRT among critically ill patients admitted to the ICU. However, the rate of RRT is lower in patients with COVID-19 or ACE2-associated viruses when compared with patients infected with non-ACE2-binding viruses, which might partly be due to the lower frequencies of shock and use of vasopressors in these two virus groups. Prospective studies are necessary to demonstrate whether modulation of the ACE2 axis with Renin-Angiotensin System inhibitors impacts the rates of AKI and whether they are beneficial or harmful in COVID-19 patients.

Abstract Background Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). Methods Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. Results CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). Conclusion Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

Objectives:. Non-mortality septic shock outcomes (e.g., Sequential Organ Failure Assessment score) are important clinical endpoints in pivotal sepsis trials. However, comparisons of observed longitudinal non-mortality outcomes between study groups can be biased if death is unequal between study groups or is associated with an intervention (i.e., informative censoring). We compared the effects of vasopressin versus norepinephrine on the Sequential Organ Failure Assessment score in the Vasopressin and Septic Shock Trial to illustrate the use of joint modeling to help minimize potential bias from informative censoring. Design:. Secondary analysis of the Vasopressin and Septic Shock Trial data. Setting:. Twenty-seven ICUs in Canada, Australia, and United States. Subjects:. Seven hundred sixty-three participants with septic shock who received blinded vasopressin (n = 389) or norepinephrine infusions (n = 374). Measurements and Main Results:. Sequential Organ Failure Assessment scores were calculated daily until discharge, death, or day 28 after randomization. Mortality was numerically higher in the norepinephrine arm (28 d mortality of 39% vs 35%; p = 0.25), and there was a positive association between higher Sequential Organ Failure Assessment scores and patient mortality, characteristics that suggest a potential for bias from informative censoring of Sequential Organ Failure Assessment scores by death. The best-fitting joint longitudinal (i.e., linear mixed-effects model) and survival (i.e., Cox proportional hazards model for the time-to-death) model showed that norepinephrine was associated with a more rapid improvement in the total Sequential Organ Failure Assessment score through day 4, and then the daily Sequential Organ Failure Assessment scores converged and overlapped for the remainder of the study period. Conclusions:. Short-term reversal of organ dysfunction occurred more rapidly with norepinephrine compared with vasopressin, although differences between study arms did not persist after day 4. Joint models are an accessible methodology that could be used in critical care trials to assess the effects of interventions on the longitudinal progression of key outcomes (e.g., organ dysfunction, biomarkers, or quality of life) that may be informatively truncated by death or other censoring events.

In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8–21.8 mL/kg/min), women in the highest tertile (25.0–27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p

We describe here a quantitative realtime PCR assay for the detection of single-base-pair differences that does not require fluorescently labeled gene-specific probes or complicated primer combinations. Following PCR or RT-PCR of a gene segment that may contain allele-specific differences, 100 pg amplified product are used for a real-time PCR with allele-specific primers and SYBR® Green. The use of HEPES buffer at a pH of 6.95 together with Ampli-Taq® DNA polymerase results in a threshold difference between the correct template and the mismatched template of as many as 20 cycles, depending on the mismatch. Correct matches can be detected in an excess of mismatched template at least at the 0.01 level for the six primer-template matches versus mismatches tested: GC vs. A·C, AT vs. G·T, GC vs. C·C, GC vs. G·G, AT vs. C·T, and GC vs. G·A. Because the initial amplification is separate from real-time detection, conditions can be independently optimized for each step, making the assay particularly suitable for the detection of allele-specific expression in single cells.

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