Hands-on Tutorial on a Modeling Framework for Projections of Climate Change Impacts on Health.

Reliable estimates of future health impacts due to climate change are needed to inform and contribute to the design of efficient adaptation and mitigation strategies. However, projecting health burdens associated to specific environmental stressors is a challenging task because of the complex risk patterns and inherent uncertainty of future climate scenarios. These assessments involve multidisciplinary knowledge, requiring expertise in epidemiology, statistics, and climate science, among other subjects. Here, we present a methodologic framework to estimate future health impacts under climate change scenarios based on a defined set of assumptions and advanced statistical techniques developed in time-series analysis in environmental epidemiology. The proposed methodology is illustrated through a step-by-step hands-on tutorial structured in well-defined sections that cover the main methodological steps and essential elements. Each section provides a thorough description of each step, along with a discussion on available analytical options and the rationale on the choices made in the proposed framework. The illustration is complemented with a practical example of study using real-world data and a series of R scripts included as Supplementary Digital Content; http://links.lww.com/EDE/B504, which facilitates its replication and extension on other environmental stressors, outcomes, study settings, and projection scenarios. Users should critically assess the potential modeling alternatives and modify the framework and R code to adapt them to their research on health impact projections

Extended two-stage designs for environmental research.

BACKGROUND: The two-stage design has become a standard tool in environmental epidemiology to model multi-location data. However, its standard form is rather inflexible and poses important limitations for modelling complex risks associated with environmental factors. In this contribution, we illustrate multiple design extensions of the classical two-stage method, all implemented within a unified analytic framework. METHODS: We extended standard two-stage meta-analytic models along the lines of linear mixed-effects models, by allowing location-specific estimates to be pooled through flexible fixed and random-effects structures. This permits the analysis of associations characterised by combinations of multivariate outcomes, hierarchical geographical structures, repeated measures, and/or longitudinal settings. The analytic framework and inferential procedures are implemented in the R package mixmeta. RESULTS: The design extensions are illustrated in examples using multi-city time series data collected as part of the National Morbidity, Mortality and Air Pollution Study (NMMAPS). Specifically, four case studies demonstrate applications for modelling complex associations with air pollution and temperature, including non-linear exposure-response relationships, effects clustered at multiple geographical levels, differential risks by age, and effect modification by air conditioning in a longitudinal analysis. CONCLUSIONS: The definition of several design extensions of the classical two-stage design within a unified framework, along with its implementation in freely-available software, will provide researchers with a flexible tool to address novel research questions in two-stage analyses of environmental health risks

Correction: Extended two-stage designs for environmental research.

The authors would like to make a correction to the article entitled “Extended two-stage designs for environmental research” published in Environmental Health in April 2022 [1]. Due to problems during the revision of the proofs, the R code and data to reproduce the examples described in the four case studies were not included in the original version of the article. The material is available in a GitHub repository, freely accessible by the readers. The following parts of the manuscript have been revised to provide this information: • Page 2, left column, last sentence of Introduction: “Notes, data, and R scripts for reproducing the examples are added as supplementary material, with an up-to-date version available on the GitHub pages of the first and last authors”. The sentence has been changed to: “An up-to-date version of the notes, data, and R scripts for reproducing the examples are available on a GitHub repository (see Availability of data and material)”. • Page 3, right column, last paragraph of Methods. The third sentence: “These summaries are made available in the Supplementary Material, together with the R code for the first-stage step to produce these quantities from the original data, and the R code and data for the second-stage step to reproduce the results of the case studies” has been revised to: “These data are made available in a GitHub repository, together with the R code for the first stage to produce these quantities from the original data, and for the second stage to reproduce the results of the case studies (see Availability of data and material)”. • Section Availability of data and materials. The text in this section has been revised to: “An up-to-date version of the R scripts and data to fully reproduce the examples described in the four case studies are added in a GitHub repository, available at https:// github. com/ gaspa rrini/ Exten ded2s tage.” This correction does not affect the results reported in the article and their interpretation. The authors apologise for the mistake. The original article has been updated

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

Chiral azole derivatives. 4. Enantiomers of bifonazole and related antifungal agents: synthesis, configuration assignment, and biological evaluation

The first synthesis, full stereochem. characterization and biol. evaluation of of both enantiomers of bifonazole (I) and the related II, III and IV are described

Future projections of temperature-related excess out-of-hospital cardiac arrest under climate change scenarios in Japan.

BACKGROUND: Recent studies have reported associations between global climate change and mortality. However, future projections of temperature-related out-of-hospital cardiac arrest (OHCA) have not been thoroughly evaluated. Thus, we aimed to project temperature-related morbidity for OHCA concomitant with climate change. METHODS: We collected national registry data on all OHCA cases reported in 2005-2015 from all 47 Japanese prefectures. We used a two-stage time series analysis to estimate temperature-OHCA relationships. Time series of current and future daily mean temperature variations were constructed according to four climate change scenarios of representative concentration pathways (RCPs) using five general circulation models. We projected excess morbidity for heat and cold and the net change in 1990-2099 for each climate change scenario using the assumption of no adaptation or population changes. RESULTS: During the study period, 739,717 OHCAs of presumed cardiac origin were reported. Net decreases in temperature-related excess morbidity were observed under higher emission scenarios. The net change in 2090-2099 compared with 2010-2019 was -0.8% (95% empirical confidence interval [eCI]: -1.9, 0.1) for a mild emission scenario (RCP2.6), -2.6% (95% eCI: -4.4, -0.8) for a stabilization scenario (RCP4.5), -3.4% (95% eCI: -5.7, -1.0) for a stabilization scenario (RCP6.0), and - 4.2% (95% eCI: -8.3, -0.1) for an extreme emission scenario (RCP8.5). CONCLUSIONS: Our study indicates that Japan is projected to experience a substantial net reduction in OHCAs in higher-emission scenarios. The decrease in risk is limited to a specific morbidity cause, and a broader assessment within climate change scenarios should consider other direct and indirect impacts

The way to ultrafast, high-throughput enantioseparations of bioactive compounds in liquid and supercritical fluid chromatography

Until less than 10 years ago, chiral separations were carried out with columns packed with 5 or 3 μm fully porous particles (FPPs). Times to resolve enantiomeric mixtures were easily larger than 30 min, or so. Pushed especially by stringent requirements from medicinal and pharmaceutical industries, during the last years the field of chiral separations by liquid chromatography has undergone what can be defined a “true revolution”. With the purpose of developing ever faster and efficient method of separations, indeed, very efficient particle formats, such as superficially porous particles (SPPs) or sub-2 μm FPPs, have been functionalized with chiral selectors and employed in ultrafast applications. Thanks to the use of short column (1–2 cm long), packed with these extremely efficient chiral stationary phases (CSPs), operated at very high flow rates (5–8 mL/min), resolution of racemates could be accomplished in very short time, in many cases less than 1 s in normal-, reversed-phase and HILIC conditions. These CSPs have been found to be particularly promising also to carry out high-throughput separations under supercritical fluid chromatography (SFC) conditions. The most important results that have been recently achieved in terms of ultrafast, high-throughput enantioseparations both in liquid and supercritical fluid chromatography with particular attention to the very important field of bioactive chiral compounds will be reviewed in this manuscript. Attention will be focused not only on the latest introduced CSPs and their applications, but also on instrumental modifications which are required in some cases in order to fully exploit the intrinsic potential of new generation chiral columns

Management of duodenal stump fistula after gastrectomy for gastric cancer: systematic review

AIM: To identify the most effective treatment of duodenal stump fistula (DSF) after gastrectomy for gastric cancer. METHODS: A systematic review of the literature was performed. PubMed, EMBASE, Cochrane Library, CILEA Archive, BMJ Clinical Evidence and UpToDate databases were analyzed. Three hundred eighty-eight manuscripts were retrieved and analyzed and thirteen studies published between 1988 and 2014 were finally selected according to the inclusion criteria, for a total of 145 cases of DSF, which represented our group of study. Only patients with DSF after gastrectomy for malignancy were selected. Data about patients' characteristics, type of treatment, short and long-term outcomes were extracted and analyzed. RESULTS: In the 13 studies different types of treatment were proposed: conservative approach, surgical approach, percutaneous approach and endoscopic approach (3 cases). The overall mortality rate was 11.7% for the entire cohort. The more frequent complications were sepsis, abscesses, peritonitis, bleeding, pneumonia and multi-organ failure. Conservative approach was performed in 6 studies for a total of 79 patients, in patients with stable general condition, often associated with percutaneous approach. A complete resolution of the leakage was achieved in 92.3% of these patients, with a healing time ranging from 17 to 71 d. Surgical approach included duodenostomy, duodeno-jejunostomy, pancreatoduodenectomy and the use of rectus muscle flap. In-hospital stay of patients who underwent relaparotomy ranged from 1 to 1035 d. The percutaneous approach included drainage of abscesses or duodenostomy (32 cases) and percutaneous biliary diversion (13 cases). The median healing time in this group was 43 d. CONCLUSION: Conservative approach is the treatment of choice, eventually associated with percutaneus drainage. Surgical approach should be reserved for severe cases or when conservative approaches fail

Static vs. dynamic electrostatic repulsion reversed phase liquid chromatography: solutions for pharmaceutical and biopharmaceutical basic compounds

Many efforts have been made to separate basic compounds, which are challenging to resolve in reversed phase liquid chromatography. In this process, they are strongly retained and the peak shape undergoes significant distortion. The principal origin of this has been identified with the non-negligible interaction with residual deprotonated silanols. Consequently, all solutions that efficiently shield silanols are being sought. This review is an upgrade on the use of the electrostatic repulsion reversed phase (ERRP) approach: retention of bases, in protonated form, can be achieved by modulating the charge repulsion caused by the presence of positive charges in the chromatographic system. This study successfully (i) introduced fixed positive charges in the structure of stationary phases, (ii) used cationic and hydrophobic additives in the mobile phase, and (iii) used the ERRP-like approach employed at the preparative level for peptide purification