The Impacts of Tourism Stays on Residents' Self-Reported Health: A Pan-European Analysis on the Role of Age and Urbanization Level

Understanding the impacts of tourism on the quality of life of residents is a priority for the sustainable tourism agenda, and is especially relevant to the COVID-19 recovery period. However, the evidence is poor, and it is not clear whether the outcomes vary among sociodemographic groups. This study fills this gap by proposing a pan-European analysis of the effects of tourism stays per 1000 residents (as a measure of tourism pressure) on self-perceived health at a regional level, based on data from Eurostat, the EU-SILC (European Union Statistics on Income and Living Conditions survey), and the LFS (Labor Force Survey). Multilevel models with random effects were used, including three levels: region, time, and region-time. Results show that tourism pressure may benefit self-reported health but only among residents aged over 50 years old living in rural contexts, or over 65 living in low density urban areas. As for younger groups (under 50) living in high density cities, tourism is longitudinally associated with worsened self-reported health. These results, which are supported by instrumental-variable estimations, suggest that urban residents and younger groups do not benefit from tourism. This might be due to a number of side effects related to increased living costs, precarious labour, and conflicts related to public space. Therefore, our findings challenge the narrative that urban tourism universally improves residents' quality of life. Considering the global urgency of creating healthier and more equitable post-COVID-19 cities and societies, tourism should be considered together with health and equity dimensions

Artificial intelligence exceeds humans in epidemiological job coding

BACKGROUND: Work circumstances can substantially negatively impact health. To explore this, large occupational cohorts of free-text job descriptions are manually coded and linked to exposure. Although several automatic coding tools have been developed, accurate exposure assessment is only feasible with human intervention. METHODS: We developed OPERAS, a customizable decision support system for epidemiological job coding. Using 812,522 entries, we developed and tested classification models for the Professions et Catégories Socioprofessionnelles (PCS)2003, Nomenclature d'Activités Française (NAF)2008, International Standard Classifications of Occupation (ISCO)-88, and ISCO-68. Each code comes with an estimated correctness measure to identify instances potentially requiring expert review. Here, OPERAS' decision support enables an increase in efficiency and accuracy of the coding process through code suggestions. Using the Formaldehyde, Silica, ALOHA, and DOM job-exposure matrices, we assessed the classification models' exposure assessment accuracy. RESULTS: We show that, using expert-coded job descriptions as gold standard, OPERAS realized a 0.66-0.84, 0.62-0.81, 0.60-0.79, and 0.57-0.78 inter-coder reliability (in Cohen's Kappa) on the first, second, third, and fourth coding levels, respectively. These exceed the respective inter-coder reliability of expert coders ranging 0.59-0.76, 0.56-0.71, 0.46-0.63, 0.40-0.56 on the same levels, enabling a 75.0-98.4% exposure assessment accuracy and an estimated 19.7-55.7% minimum workload reduction. CONCLUSIONS: OPERAS secures a high degree of accuracy in occupational classification and exposure assessment of free-text job descriptions, substantially reducing workload. As such, OPERAS significantly outperforms both expert coders and other current coding tools. This enables large-scale, efficient, and effective exposure assessment securing healthy work conditions

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer

Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I–III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease‐free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II–III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893‐patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146‐patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (pinteraction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy

Potent inhibition of microRNA in vivo without degradation

Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported to show efficacy. Whether this is the most relevant endpoint for measuring miRNA inhibition has not been adequately addressed in the field although it has important implications for evaluating miRNA targeting studies. Using a novel approach to quantitate miRNA levels in the presence of excess ASO, we have discovered that the outcome of miRNA inhibition can vary depending on the chemical modification of the ASO. Although some miRNA inhibitors cause a decrease in mature miRNA levels, we have identified a novel 2′-fluoro/2′-methoxyethyl modified ASO motif with dramatically improved in vivo potency which does not. These studies show there are multiple mechanisms of miRNA inhibition by ASOs and that evaluation of secondary endpoints is crucial for interpreting miRNA inhibition studies

Selection of hyperfunctional siRNAs with improved potency and specificity

One critical step in RNA interference (RNAi) experiments is to design small interfering RNAs (siRNAs) that can greatly reduce the expression of the target transcripts, but not of other unintended targets. Although various statistical and computational approaches have been attempted, this remains a challenge facing RNAi researchers. Here, we present a new experimentally validated method for siRNA design. By analyzing public siRNA data and focusing on hyperfunctional siRNAs, we identified a set of sequence features as potency selection criteria to build an siRNA design algorithm with support vector machines. Additional bioinformatics filters were also included in the algorithm to increase RNAi specificity by reducing potential sequence cross-hybridization or microRNA-like effects. Independent validation experiments were performed, which indicated that the newly designed siRNAs have significantly improved performance, and worked effectively even at low concentrations. Furthermore, our cell-based studies demonstrated that the siRNA off-target effects were significantly reduced when the siRNAs were delivered into cells at the 3 nM concentration compared to 30 nM. Thus, the capability of our new design program to select highly potent siRNAs also renders increased RNAi specificity because these siRNAs can be used at a much lower concentration. The siRNA design web server is available at http://www5.appliedbiosystems.com/tools/siDesign/

Cholinergic neuroplasticity in asthma driven by TrkB signaling

Parasympathetic neurons in the airways control bronchomotor tone. Increased activity of cholinergic neurons are mediators of airway hyperresponsiveness (AHR) in asthma, however, mechanisms are not elucidated. We describe remodeling of the cholinergic neuronal network in asthmatic airways driven by brain-derived neurotrophic factor (BDNF) and Tropomyosin receptor kinase B (TrkB). Human bronchial biopsies were stained for cholinergic marker vesicular acetylcholine transporter (VAChT). Human lung gene expression and single nucleotide polymorphisms (SNP) in neuroplasticity-related genes were compared between asthma and healthy patients. Wild-type (WT) and mutated TrkB knock-in mice (Ntrk2tm1Ddg/J) with impaired BDNF signaling were chronically exposed to ovalbumin (OVA). Neuronal VAChT staining and airway narrowing in response to electrical field stimulation in precision cut lung slices (PCLS) were assessed. Increased cholinergic fibers in asthmatic airway biopsies was found, paralleled by increased TrkB gene expression in human lung tissue, and SNPs in the NTRK2 [TrkB] and BDNF genes linked to asthma. Chronic allergen exposure in mice resulted in increased density of cholinergic nerves, which was prevented by inhibiting TrkB. Increased nerve density resulted in AHR in vivo and in increased nerve-dependent airway reactivity in lung slices mediated via TrkB. These findings show cholinergic neuroplasticity in asthma driven by TrkB signaling and suggest that the BDNF-TrkB pathway may be a potential target

Alcohol Consumption and Risk of Parkinson's Disease: Data from a Large Prospective European Cohort

Background: Parkinson's disease (PD) etiology is not well understood. Reported inverse associations with smoking and coffee consumption prompted the investigation of alcohol consumption as a risk factor, for which evidence is inconclusive. Objective: To assess the associations between alcohol consumption and PD risk. Methods: Within NeuroEPIC4PD, a prospective European population-based cohort, 694 incident PD cases were ascertained from 209,998 PD-free participants. Average alcohol consumption at different time points was self-reported at recruitment. Cox regression hazard ratios were estimated for alcohol consumption and PD occurrence. Results: No associations between baseline or lifetime total alcohol consumption and PD risk were observed. Men with moderate lifetime consumption (5-29.9 g/day) were at ~50% higher risk compared with light consumption (0.1-4.9 g/day), but no linear exposure-response trend was observed. Analyses by beverage type also revealed no associations with PD. Conclusion: Our data reinforce previous findings from prospective studies showing no association between alcohol consumption and PD risk. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Landscapes in transition: an analysis of sustainable policy initiatives and emerging corporate commitments in the palm oil industry

The recent Southeast Asian haze crisis has generated intense public scrutiny over the rate, methods and types of landscape change in the tropics. Debate has centred on the environmental impacts of large-scale agricultural expansion, particularly the associated loss of high carbon stock forest and forests of high conservation value. Focusing on palm oil—a versatile food crop and source of bioenergy—this paper analyses national, international and corporate policy initiatives in order to clarify the current and future direction of oil palm expansion in Malaysia and Indonesia. The policies of ‘zero burn’, ‘no deforestation’ and ‘no planting on peatlands’ are given particular emphasis in the paper. The landscape implications of corporate commitments are analysed to determine the amount of land, land types and geographies that could be affected in the future. The paper concludes by identifying key questions related to the further study of sustainable land use policy and practice