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Nikolay Pavlov,1 Alan Gary Haynes,2,3 Armin Stucki,4 Peter Jüni,5 Sebastian Robert Ott1 1Department of Pulmonary Medicine, University Hospital (Inselspital), University of Bern, Bern, Switzerland; 2CTU Bern, University of Bern, Bern, Switzerland; 3Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; 4Department of Internal Medicine, Spital Thun, Thun, Switzerland; 5Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada Purpose: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT), recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality. Patients and methods: We conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age- and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT

The “Year Without a Summer” in 1816 was characterized by extraordinarily cold and wet periods in central Europe, and it was associated with severe crop failures, famine, and socio-economic disruptions. From a modern perspective, and beyond its tragic consequences, the summer of 1816 represents a rare opportunity to analyze the adverse weather (and its impacts) after a major volcanic eruption. However, given the distant past, obtaining the high-resolution data needed for such studies is a challenge. In our approach, we use dynamical downscaling, in combination with 3D variational data assimilation of early instrumental observations, for assessing a cold-air outbreak in early June 1816. We find that the cold spell is well represented in the coarse-resolution 20th Century Reanalysis product which is used for initializing the regional Weather Research and Forecasting Model. Our downscaling simulations (including a 19th century land use scheme) reproduce and explain meteorological processes well at regional to local scales, such as a foehn wind situation over the Alps with much lower temperatures on its northern side. Simulated weather variables, such as cloud cover or rainy days, are simulated in good agreement with (eye) observations and (independent) measurements, with small differences between the simulations with and without data assimilation. However, validations with partly independent station data show that simulations with assimilated pressure and temperature measurements are closer to the observations, e.g., regarding temperatures during the coldest night, for which snowfall as low as the Swiss Plateau was reported, followed by a rapid pressure increase thereafter. General improvements from data assimilation are also evident in simple quantitative analyses of temperature and pressure. In turn, data assimilation requires careful selection, preprocessing, and bias-adjustment of the underlying observations. Our findings underline the great value of digitizing efforts of early instrumental data and provide novel opportunities to learn from extreme weather and climate events as far back as 200 years or more.

Abstract Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Wood has been utilized as a building material for thousands of years. Nowadays, its renewable nature and carbon-storing capacity can become important factors in climate change mitigation efforts. This has led to a resurgence of timber engineering in recent years, with impressive multi-story timber buildings worldwide. However, it should not be overlooked that the wood sector will face several challenges in the coming years and decades to pave the way to a leading role of wood in the desired transition toward bioeconomy. Based on the assumption that an increasing demand for wood will make it a more precious resource, a couple of strains will emerge across the entire value chain of wood processing. This calls for innovations to address issues arising from predicted changes in resource provision, to increase material yields, and to promote reuse after the end of life. Our conceptual article proposes a new wood separation and processing method. This approach is inspired by the well-known production of wood shingles and is currently being developed for the implementation of new wood-based products.

Summary: Background: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort. Methods: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseline until end of follow-up, road, railway, and aircraft noise was estimated at a residential level. Incident AF was ascertained via linkage to nationwide patient registries. Cox proportional hazards models were utilized to estimate associations between running 5-year time-weighted mean transportation noise (Lden) and AF after adjusting for sociodemographics, lifestyle, and air pollution. Findings: We identified 18,939 incident AF cases over a median follow-up of 19.6 years. Road traffic noise was associated with AF, with a hazard ratio (HR) and 95% confidence interval (CI) of 1.02 (1.00–1.04) per 10-dB of 5-year mean time-weighted exposure, which changed to 1.03 (1.01–1.06) when implementing a 53-dB cut-off. In effect modification analyses, the association for road traffic noise and AF appeared strongest in women and overweight and obese participants. Compared to exposures ≤40 dB, aircraft noise of 40.1–50 and > 50 dB were associated with HRs of 1.04 (0.93–1.16) and 1.12 (0.98–1.27), respectively. Railway noise was not associated with AF. We found a HR of 1.19 (1.02–1.40) among people exposed to noise from road (≥45 dB), railway (>40 dB), and aircraft (>40 dB) combined. Interpretation: Road traffic noise, and possibly aircraft noise, may be associated with elevated risk of AF. Funding: NordForsk.

Abstract Selective binding of TCR-like antibodies that target a single tumour-specific peptide antigen presented by human leukocyte antigens (HLA) is the absolute prerequisite for their therapeutic suitability and patient safety. To date, selectivity assessment has been limited to peptide library screening and predictive modeling. We developed an experimental platform to de novo identify interactomes of TCR-like antibodies directly in human tissues using mass spectrometry. As proof of concept, we confirm the target epitope of a MAGE-A4-specific TCR-like antibody. We further determine cross-reactive peptide sequences for ESK1, a TCR-like antibody with known off-target activity, in human liver tissue. We confirm off-target-induced T cell activation and ESK1-mediated liver spheroid killing. Off-target sequences feature an amino acid motif that allows a structural groove-coordination mimicking that of the target peptide, therefore allowing the interaction with the engager molecule. We conclude that our strategy offers an accurate, scalable route for evaluating the non-clinical safety profile of TCR-like antibody therapeutics prior to first-in-human clinical application.

Original citation: J Clin Invest. 2023;133(23):e168277. https://doi.org/10.n72/JCI168277. During the preparation of this manuscript, the dose for PMX205 used for in vitro experiments was stated incorrectly in the legend for Figure [...]

Background: Emerging evidence shows that long-term exposure to air pollution, road traffic noise, and greenness can each be associated with cardiovascular disease, but only few studies combined these exposures. In this study, we assessed associations of multiple environmental exposures and incidence of myocardial infarction using annual time-varying predictors. Materials and Methods: In a population-based cohort of 20,407 women in Sweden, we estimated a five-year moving average of residential exposure to air pollution (PM2.5, PM10 and NO2), road traffic noise (Lden), and greenness (normalized difference vegetation index, NDVI in 500 m buffers), from 1998 to 2017 based on annually varying exposures and address history. We used adjusted time-varying Cox proportional hazards regressions to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) of myocardial infarction per interquartile range (IQR). Furthermore, we investigated interactions between the exposures and explored potential vulnerable subgroups. Results: In multi-exposure models, long-term exposure to greenness was inversely associated with incidence of myocardial infarction (HR 0.89; 95 % CI 0.80, 0.99 per IQR NDVI increase). Stronger associations were observed in some subgroups, e.g. among women with low attained education and in overweight (BMI ≥ 25 kg/m2) compared to their counterparts. For air pollution, we observed a tendency of an increased risk of myocardial infarction in relation to PM2.5 (HR 1.07; 95 % CI 0.93, 1.23) and the association appeared stronger in women with low attained education (HR 1.30; 95 % CI 1.06, 1.58). No associations were observed for PM10, NO2 or road traffic noise. Furthermore, there were no clear interaction patterns between the exposures. Conclusion: Over a 20-year follow-up period, in multi-exposure models, we found an inverse association between residential greenness and risk of myocardial infarction among women. Furthermore, we observed an increased risk of myocardial infarction in relation to PM2.5 among women with low attained education. Road traffic noise was not associated with myocardial infarction.

Welfare assessment protocols have been developed for dairy cows and veal calves during the past decades. One practical use of such protocols may be conducting welfare assessments by using routinely collected digital data (i.e., data-based assessment). This approach can allow for continuous monitoring of animal welfare in a large number of farms. It recognises changes in the animal welfare status over time and enables comparison between farms. Since no comprehensive data-based assessment for veal calves is currently available, the purposes of this review are (i) to provide an overview of single existing data-based indicators for veal calves and (ii) to work out the necessary requirements for data-based indicators to be used in a comprehensive welfare assessment for veal calves in Switzerland. We used the Welfare Quality Protocol® (WQ) for veal calves and the Terrestrial Animal Health Code from the World Organisation of Animal Health for guidance throughout this process. Subsequently, routinely collected data were evaluated as data sources for welfare assessment in Swiss veal operations. The four WQ principles reflecting animal welfare, i.e., ‘good feeding’, ‘good housing’, ‘good health’ and ‘appropriate behaviour’ were scarcely reflected in routinely available data. Animal health, as one element of animal welfare, could be partially assessed using data-based indicators through evaluation of mortality, treatments, and carcass traits. No data-based indicators reflecting feeding, housing and animal behaviour were available. Thus, it is not possible to assess welfare in its multidimensionality using routinely collected digital data in Swiss veal calves to date. A major underlying difficulty is to differentiate between veal calves and other youngstock using routine data, since an identifying category for veal calves is missing in official Swiss databases. In order to infer animal welfare from routine data, adaptations of data collection strategies and animal identification are required. Data-based welfare assessment could then be used to complement on-farm assessments efficiently and, e.g., to attribute financial incentives for specifically high welfare standards accordingly.