Sample size issues in time series regressions of counts on environmental exposures.

BACKGROUND: Regression analyses of time series of disease counts on environmental determinants are a prominent component of environmental epidemiology. For planning such studies, it can be useful to predict the precision of estimated coefficients and power to detect associations of given magnitude. Existing generic approaches for this have been found somewhat complex to apply and do not easily extend to multiple series studies analysed in two stages. We have sought a simpler approximate approach which can easily extend to multiple series and give insight into factors determining precision. METHODS: We derive approximate expressions for precision and hence power in single and multiple time series studies of counts from basic statistical theory, compare the precision predicted by these with that estimated by analysis in real data from 51 cities of varying size, and illustrate the use of these estimators in a realistic planning scenario. RESULTS: In single series studies with Poisson outcome distribution, precision and power depend only on the usable variation of exposure (i.e. that conditional on covariates) and the total number of disease events, regardless of how many days those are spread over. In multiple time series (eg multi-city) studies focusing on the meta-analytic mean coefficient, the usable exposure variation and the total number of events (in all series) are again the sole determinants if there is no between-series heterogeneity or within-series overdispersion. With heterogeneity, its extent and the number of series becomes important. For all but the crudest approximation the estimates of standard errors were on average within + 20% of those estimated in full analysis of actual data. CONCLUSIONS: Predicting precision in coefficients from a planned time series study is possible simply and given limited information. The total number of disease events and usable exposure variation are the dominant factors when overdispersion and between-series heterogeneity are low

Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA

Background. Previous research focused on the clinical evidence supporting new cancer drugs’ initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. Objectives. To examine the clinical trial evidence supporting new targeted cancer drugs’ initial and supplementary indication approval in the US, EU, Canada, and Australia. Data and Methods. 25 cancer drugs across 100 indications were identified with FDA approval between 2009–2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ 2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). Results. Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07–6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38–8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17–5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14–30.65], p < 0.05) than supplementary indications. Initial indications’ pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93–0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09–0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01–1.39], p < 0.05). Conclusions. Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication’s differential clinical and economic value

The need for detailed COVID-19 data in Spain

The COVID-19 epidemic has impacted the population of Spain far more than most feared or projected. As of Sept 25, 2020, more than 700 000 individuals had tested positive, and more than 31 000 deaths with a positive test had been recorded.1 Earlier in this pandemic, the Spanish Ministry of Health provided data by age and sex for the whole country in its daily COVID-19 situation updates (in Adobe PDF format), as well as daily data on total hospitalisations, intensive care unit admissions, discharges, and deaths by region. However, since May 19, 2020, disaggregated data have not been provided in the daily updates.1 In recent months, data improvements have been made by the National Centre of Epidemiology (CNE), and open data on total counts by region are updated and revised daily.2 However, at the time of writing, age-specific data from the CNE is given only in weekly publications (as Adobe PDF files), without geographic detail or retrospective corrections, and with cumulative counts tabulated only from mid-May onwards. Therefore, properly merging age-specific time series after the first wave is difficult or impossible.Peer reviewe

Authenticating wireless nodes in building automation : challenges and approaches

Modern wireless nodes in building automation systems interconnect natively through the Internet Protocol (IP). As a result, the emerging coalescence of existing IT networks with networks on the field level presents many challenges. Specifically, mutual authentication of devices in an IT environment is one of the main issues. Moreover, this mutual authentication has to take place with embedded devices in the field that feature manifold constraints and require a simple but secure provisioning. The Fairhair Alliance is in the process of standardizing an autonomic secure bootstrapping process to tackle these challenges. The paper outlines this automated approach and shows the successful implementation of a real-life prototype. This demonstrates that the required cryptographic functions and procedures are feasible on a constrained low power device

The need for detailed COVID-19 data in Spain

CP received a grant from the Catalan Government for monitoring the post-lockdown COVID-19 process in Catalonia (Spain). All other authors declare no competing interests. ST-L gratefully acknowledges funding from the European Research Council (ERC-2019-CoG-GA No 864616-HEALIN project)Postprint (published version

Synthesis of merlinoite from Chinese coal fly ashes and its potential utilization as slow release K-fertilizer

This study focuses on the synthesis of merlinoite from Chinese coal fly ashes by KOH direct conversion method, with special emphasis on the application of synthetic merlinoite as fertilizer. These fly ashes were collected from two pulverized-coal combustion (PCC) power plants in Xinjiang, Northwest China. The synthesis results are influenced by fly ash characteristics and different synthesis conditions (KOH solution concentrations, activation temperature, time, and KOH/fly ash ratios). A high quality merlinoite-rich product was synthesized under optimal activation conditions (KOH concentration of 5 M, activation temperature of 150 °C, activation time of 8 h and KOH/fly ash ratio of 2 l/kg), with a cation exchange capacity (CEC) of 160 cmol kg−1. The synthetic merlinoite is proved to be an efficient slow release K-fertilizer for plant growth, indicating that it can be widely used for high-nutrient demanding crops growing in nutrient-limited soils and for large-area poor soil amendment in opencast coal mine areas around the power plants that will substantially grow with the increasing coal combustion in Xinjiang in the near future