Search

Table S1 shows the clinicopathological characteristics of the cases included in final analysis.

The Colorado checkered whiptail (Aspidoscelis neotesselatus) is a parthenogenetic lizard that is listed as a “species of special concern” in the state of Colorado. A. neotesselatus occupies a small range that includes the US Army Fort Carson Military Base in Colorado Springs, Colorado. The species is exposed to a variety of military disturbances, including aircraft flyover noise. We sampled 82 females during the 2021 reproductive season to assess whether scheduled flyovers would impact the behavior, stress, and metabolism of A. neotesselatus, while controlling for size and reproductive stage differences. We measured corticosterone (CORT) as a marker of anthropogenically induced stress during flyovers compared to a control. We further tested for the downstream effects of flyovers on plasma glucose (free energy available to tissues), elevated metabolism with oxidative stress (ROMs), and ketone bodies (alternative cerebral energy substrates to glucose). When disturbed by flyovers, these lizards spent less time moving but more time eating. Aircraft noise also increased CORT when controlling for clutch size, indicating a stress response driven by flyovers, as well as an independent effect of reproductive investment on CORT. CORT did not affect plasma glucose. Flyovers led to a marginally decrease in circulating ROMs, with gravid females experiencing lower plasma ROMs than non-gravid females, but that later effect was independent of flyovers. Flyovers significantly increased ketone bodies, with smaller animals experiencing higher ketone concentrations than larger individuals, yet the effect of size on ketone bodies was independent of the flyover treatment. Although A. neotesselatus seem to adjust their behavior and eat more to buffer the potentially negative effect of flyovers on energetic pathways, they still appear to suffer a metabolic cost driven by the stress response via ketone accumulation, as well as a reproductive cost driven by clutch size investment that is independent of flyover disturbance. We suggest that military aircraft operators attempt to avoid dense populations of A. neotesselatus during the reproductive season or fly at altitudes that lead to decibel reads that fall below 50 dB at ground level, as a cautious management step that ensures the resilience and local abundance of A. neotesselatus at Fort Carson.

Background Only few epidemiological studies have investigated whether chronic exposure to air pollution from different sources have different impacts on risk of diabetes. We aimed to investigate associations between air pollution from traffic versus non-traffic sources and risk of type 2 diabetes in the Danish population. Methods We estimated long-term exposure to traffic and non-traffic contributions of particulate matter with a diameter 35 years were included, of whom 148 020 developed type 2 diabetes during follow-up. We applied Cox proportional hazards models for analyses, using 5-year time-weighted running means of air pollution and adjustment for individual- and area-level demographic and socioeconomic covariates. Results We found that 5-year exposure to all particle measures (PM2.5, UFP and EC) and NO2 were associated with higher type 2 diabetes risk. We observed that for UFP, EC and potentially PM2.5, the pollution originating from traffic was associated with higher risks than the non-traffic contributions, whereas for NO2 similar hazard ratios (HR) were observed. For example, in two-source models, hazard ratios (HRs) per interquartile change in traffic UFP, EC and PM2.5 were 1.025, 1.045 and 1.036, respectively, whereas for non-traffic UFP, EC and PM2.5, the HRs were 1.013, 1.018 and 1.001, respectively. Conclusions Our finding of stronger associations with particulate matter from traffic compared with non-traffic sources implies that prevention strategies should focus on limiting traffic-related particulate matter air pollution.

Background There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC). Objective To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra – and extrahepatic cholangiocarcinoma. Methods In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics. Results Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8–5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0–2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2–1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123–159) for biliary tract, 38.6 (95% CI 29.2–50.0) for hepatocellular, and 9.0 (95% CI 6.3–12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients. Conclusions The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.

Contains fulltext : 251806.pdf (Publisher’s version ) (Closed access) Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD. This is a multicenter nested case control study conducted in the Netherlands. Cases are hospital known patients with IRD requiring hospitalization for COVID-19 between March 1, 2020, and May 31, 2020. Controls are hospital known patients with IRD not requiring hospitalization for COVID-19 in this period, included at a 4:1 ratio. Patient, disease, and treatment characteristics were extracted from electronic medical records and a questionnaire. Potential risk factors were analyzed using unconditional logistic regression, corrected for confounders and multiple testing. Eighty-one cases and 396 controls were included. General risk factors of older age and obesity apply to patients with IRD as well (odds ratio (OR) for age ≥ 75 3.5, 95% confidence interval (CI) 1.9-6.3, OR for body mass index ≥ 40 4.5, 95% CI 1.5-14). No significantly increased ORs for COVID-19 hospitalization were found for any antirheumatic agent or IRD. A protective effect was found for use of methotrexate (OR 0.53, 95% CI 0.31-0.92). In conclusion, similar to the general population, elderly and obese patients with IRD have a higher risk for hospitalization for COVID-19. We did not identify a specific antirheumatic agent or IRD to increase the risk of COVID-19 hospitalization in patients with IRD, except for a possible protective effect of methotrexate.

Objectives The REDO trial (REtreatment with Rituximab in RhEumatoid arthritis: Disease Outcome after Dose Optimisation) showed that ultra-low-dose rituximab (500 mg or 200 mg) was similarly effective to a 1000 mg dosage in the majority of RA patients. This pre-planned secondary analysis investigated (1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADAs) and B-cell counts and (2) the predictive value of pharmacokinetic and pharmacodynamic parameters, and of patient, disease and treatment characteristics in relation to response to ultra-low-dose rituximab. Methods For 140 RA patients from the REDO trial, differences in drug levels, ADAs and B-cell counts were examined at baseline, and at 3 and 6 months after dosing. Treatment response was defined as absence of flare and no extra rituximab or >1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses. Results Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels or B-cell counts, and 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet the response criteria in, respectively, the 1000 mg, 500 mg and 200 mg dosage groups. Drug levels, ADAs, B-cell counts, and patient, disease and treatment characteristics were not predictive for response to ultra-low-dose rituximab. Conclusion The results of this study further support the hypothesis that continued treatment with 500 or 200 mg rituximab is similarly effective to a 1000 mg dosage in RA patients doing well on rituximab. These results, combined with lack of finding a clinical dose–response relationship in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.

BackgroundDue to anatomical deviations, assumptions of the conventional calibration method for gait analysis may be violated in individuals with rotational deformities of the femur. We compared functional calibration methods with conventional methods in this group for 1) localization of the hip joint center (HJC) and knee axis orientation, and 2) gait kinematics.MethodsTwenty-four adolescents with idiopathic rotational deformity of the femur underwent gait analysis and a CT scan. During standing, distance between HJCs and knee axis orientation were compared between calibration methods, with CT serving as reference for HJC estimation. Gait kinematics were compared using statistical parameter mapping (SPM).FindingsFunctional calibration methods estimated the HJC closer to the CT reference (26±21mm more lateral) than the conventional method (38±21mm more medial). In the full sample, orientation of the knee joint axis was not different between calibration methods, but in adolescents with increased femoral anteversion, the knee was more internally rotated with the functional method (3.3±6.2°). During gait, SPM revealed significantly more hip flexion, more internal hip rotation during the stance phase, less knee varus-valgus motion, and larger knee flexion angles when applying the functional calibration method.InterpretationFunctional calibration methods better approximated the HJC, and showed a knee axis orientation that was more towards the direction of the deformity. This resulted in less knee joint angle crosstalk during gait. Although differences between calibration methods on gait kinematics were within clinically acceptable limits for the sagittal plane, relatively larger differences on transversal hip kinematics may hold clinical importance.

Objectives Immunomodulatory agents are safe and effective as treatment for various immune-mediated inflammatory diseases (IMIDs), but are associated with a slightly increased infection risk. It is uncertain whether, in the event of an infection, continuation or temporary interruption of immunomodulatory agents leads to better outcomes. Owing to this uncertainty, it is of importance to explore the perspectives of health-care providers (HCPs) and patients on this topic. In this study, we set out to identify and provide an overview of reasons for both treatment strategies. Methods Semi-structured interviews were conducted with HCPs involved in the pharmacological treatment of IMIDs and with IMID patients using one or more immunomodulatory agent. Purposive sampling was used to enrich data variation. Interviews were conducted until data saturation was reached and subsequently analysed using qualitative content analysis. Results In total, 13 HCPs and 19 IMID patients were interviewed. A wide range of reasons for both treatment strategies were identified, categorized into 10 overarching themes, including IMID characteristics, infection characteristics and the patient–HCP relationship. Conclusion In this interview study, we identified various reasons for continuation or temporary interruption of immunomodulatory agents during infections for both IMID patients and HCPs. We found overlapping themes, such as IMID characteristics; however, the content and interpretation of these themes might differ between HCPs and patients. Both HCPs and patients mentioned that the decision for a treatment strategy is often about weighing benefits against risks (e.g. infection severity vs disease flare).

Supplemental material, sj-docx-1-sjp-10.1177_14034948231178076 for Perspectives on environment and health research in Denmark by Henriette T. Horsdal, Marianne G. Pedersen, Jörg Schullehner, Cecilie S. Østergaard, John J. Mcgrath, Esben Agerbo, Allan Timmermann, Ane Marie Closter, Jørgen Brandt, Jesper H. Christensen, Lise M. Frohn, Camilla Geels, Matthias Ketzel, Jibran Khan, Pia V. Ørby, Yulia Olsen, Gregor Levin, Jens-Christian Svenning, Kristine Engemann, Steen Gyldenkærne, Birgitte Hansen, Ole Hertel, Clive E. Sabel, Christian Erikstrup, Torben Sigsgaard and Carsten B. Pedersen in Scandinavian Journal of Public Health

Cutaneous T-cell lymphoma (CTCL) is a devastating lymphoid malignancy characterized by the accumulation of malignant T cells in the dermis and epidermis. Skin lesions cause serious symptoms that hamper quality of life and are entry sites for bacterial infection, a major cause of morbidity and mortality in advanced diseases. The mechanism driving the pathological processes that compromise the skin barrier remains unknown. Here, we report increased transepidermal water loss and compromised expression of the skin barrier proteins filaggrin and filaggrin-2 in areas adjacent to TOX-positive T cells in CTCL skin lesions. Malignant T cells secrete mediators (including cytokines such as interleukin 13 [IL-13], IL-22, and oncostatin M) that activate STAT3 signaling and downregulate filaggrin and filaggrin-2 expression in human keratinocytes and reconstructed human epithelium. Consequently, the repression of filaggrins can be counteracted by a cocktail of antibodies targeting these cytokines/receptors, small interfering RNA–mediated knockdown of JAK1/STAT3, and JAK1 inhibitors. Notably, we show that treatment with a clinically approved JAK inhibitor, tofacitinib, increases filaggrin expression in lesional skin from patients with mycosis fungoides. Taken together, these findings indicate that malignant T cells secrete cytokines that induce skin barrier defects via a JAK1/STAT3-dependent mechanism. As clinical grade JAK inhibitors largely abrogate the negative effect of malignant T cells on skin barrier proteins, our findings suggest that such inhibitors provide novel treatment options for patients with CTCL with advanced disease and a compromised skin barrier.

Objectives Rituximab (RTX) is a safe and effective treatment for RA. A dose-dependent infection risk was found in the REDO trial. Some studies associate RTX use with higher infection risks, possibly explained by low immunoglobulin levels and/or neutropenia. Additionally, a higher infection risk shortly after RTX infusion is reported. The objectives of this study were (i) to compare incidence rates of infections between doses and over time, and (ii) to assess B-cell counts, immunoglobulin levels, neutrophil counts and corticosteroid/disease modifying rheumatic drug use as mediating factors between RTX study dose and infection risk. Methods Post hoc analyses of the REDO trial were performed. Infection incidence rates between RTX dosing groups and between time periods were compared using Poisson regression. A step-wise mediation analysis was performed to investigate if any of the factors mentioned above act as a mediator in the observed dose-dependent difference in infection risk. Results The potential mediators that were investigated (circulating B-cell counts, immunoglobulin levels, neutrophil counts and drug use) did not explain the dose-dependent infection risk observed in the REDO trial. Additionally, a trend towards a time-dependent infection risk was found, with higher infection rates shortly after RTX infusion. Conclusions These secondary analyses of the REDO trial confirmed the observed dose-dependent infection risk. Additionally, we found that infection risks were higher shortly after RTX infusion. However, a mediating pathway was not found.

BACKGROUND Implementation of digital hospital services (DHS), defined as digital technologies for use by patients offered by the hospital, is progressing slowly. In-depth insight into patients’ preferences and needs regarding DHS might improve its use. OBJECTIVE To describe when patients want to use DHS, how patients want to communicate or receive information digitally and what factors influence use of DHS in clinical practice. METHODS A multiple methods study design was conducted, using the Citizen Platform method. Two interactive days of ~ 5.5 hours with plenary and break-out sessions were held with 22 patients from the rheumatology, orthopedics and rehabilitation departments of a Dutch hospital specialized in musculoskeletal disorders. Assignments were performed during break-out sessions in which qualitative (e.g. semi-structured interview questions) and quantitative (i.e. voting and ranking factors) data were collected. RESULTS When patients want to use DHS varied between patients and phases of the patient journey. Preference for how patients want to communicate digitally depended on the need for interaction with an HCP. The interaction need is in its turn influenced by the degree to which information/communication is tailored (i.e. specific to an individual patient) and impactful (i.e. leading to significant consequences for the patient). The five most important factors influencing the use of DHS were: access to medical information (e.g. electronic health records), perceived control over disease management, correctness/completeness of information, data security and access to information or an HCP at any time. The five least important factors influencing DHS use were: Help with using digital devices, having internet/equipment, digital skills, attitude/emotions towards DHS and societal benefits. CONCLUSIONS Patients see possibilities for using DHS during all stages of the patient journey. However, preferences for DHS varied between patients and moments in the patient journey. As a consequence, DHS should be tailored to fit individual patients’ needs, but also regarding topics (tailored, impactful) by offering a variety of digital channels with a gradient of interaction possibilities. Furthermore, requirements such as digital skills and having internet might become less important to focus on in the future. Improving DHS use by patients may be achieved by providing patients access to correct and safe (medical) information and more control over their care.

BACKGROUND: Ambient fine particulate matter (PM2.5) causes millions of deaths every year worldwide. Identification of the most harmful types of PM2.5 would facilitate efficient prevention strategies.OBJECTIVES: The aim of this study was to investigate associations between components of PM2.5 and mortality in a nation-wide Danish population.METHODS: Our study base was Danes born 1921-1985 and aged 30-85 years, who were followed up for mortality from 1991 to 2015. We included 678,465 natural cause mortality cases and selected five age, sex and calendar time matched controls to each case from the study base. We retrieved the address history of the study population from Danish registries and assessed five-year average concentrations of eight PM2.5 components using deterministic Chemistry-Transport Models air pollution models. We estimated mortality rate ratios (MRRs) by conditional logistic regression and adjusted for socio-demographical factors at individual and neighborhood level.RESULTS: Single pollutant models showed the strongest associations between natural cause mortality and an interquartile increase in sulfate particles (SO4--) (MRR: 1.123; 95 % CI: 1.100-1.147 per 1.5 µg/m3) and secondary organic aerosol (SOA) (MRR: 1.054; 95 % CI: 1.048-1.061 per 0.050 µg/m3). Two-pollutant models showed robust associations between SO4-- and SOA and natural cause mortality. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.CONCLUSION: This nation-wide study found robust associations between natural cause mortality and SO4-- particles and SOA, which is in line with the results of previous studies. Elemental carbon and mineral dust showed robust associations with higher respiratory and lung cancer mortality.

Background Quinolones comprise a class of antibiotics that are globally preferred for treating a wide range of bacterial infections due to their potency, broad coverage, favorable pharmacologic profile, and mostly mild to moderate adverse reactions. Spontaneous reports on adverse drug events (ADE) and data from some pharmacoepidemiologic studies have raised concerns regarding quinolones and risk of retinal detachment (RD). This study examined ADE reports submitted to FDA adverse event reporting system (FAERS) for evidence on quinolone-associated RD risk. Research design and methods We identified all reports of RD in FAERS between 2010-2019. We compared ADE signals between quinolones and selected medications that were previously associated with RD, and with reference drugs not known to cause RD. For signal detection, we used two disproportionality techniques: the proportional reporting ratio (PRR) and multi-item gamma Poisson shrinker (MGPS), which are known for their higher sensitivity and specificity for ADE signal detection, respectively. Results Moxifloxacin showed a positive and significant PRR signal for RD [PRR: 2.54 (1.60, 4.04)], and a marginally significant EBGM signal [EBGM: 2.21 (1.41, 3.02)]. Conclusion Moxifloxacin is the only quinolone showing a positive disproportionality signal for RD. Further epidemiologic research is needed to clarify the association between moxifloxacin and the risk of RD.

Objectives We investigated the effect of disease activity-guided dose optimization (DAGDO) of TNF inhibitor (TNFi) on disease activity and TNFi dose in PsA and axial spondyloarthritis (axSpA) patients with low disease activity (LDA). Methods A retrospective cohort study was conducted in PsA and axSpA patients doing well on TNFi and eligible for TNFi DAGDO. Three different treatment periods were defined: (i) full dose continuation period, (ii) TNFi DAGDO period, and (iii) period with stable TNFi dose after DAGDO. A mixed-model analysis was used to estimate mean Disease Activity Score 28-joint count CRP (DAS28-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) during these periods, and a mean percentage of the daily defined dose (%DDD) was calculated as secondary outcome. Results Three hundred and twenty-four patients (153 PsA and 171 axSpA) were included, with a mean of 6.5 DAS28-CRP and 6.4 BASDAI measurements and a median follow-up duration of 46 and 44 months, respectively. A corrected difference of 0.06 (95% CI: −0.09, 0.21) in mean DAS28-CRP was found for the TNFi DAGDO period and 0.03 (95% CI: −0.14, 0.20) for the period with stable TNFi dose, compared with full dose continuation period. Differences for BASDAI were 0.03 (95% CI: −0.21, 0.27) and 0.05 (95% CI: −0.24, 0.34), respectively. The mean %DDD for the three treatment periods was for PsA 108%, 62% and 78%, and for axSpA 108%, 62% and 72%, respectively. Conclusion DAGDO of TNFi reduces drug exposure and has no negative effects on disease activity in PsA and axSpA patients compared with full dose continuation.

ObjectivesTo determine the clinical and economic impact of a community-based, hybrid model of in-person and virtual care by comparing health-system performance of the rural jurisdiction where this model was implemented with neighbouring jurisdictions without such a model and the broader regional health system.DesignA cross-sectional comparative study.SettingOntario, Canada, with a focus on three largely rural public health units from April 1, 2018, until March 31, 2021.ParticipantsAll residents of Ontario, Canada under the age of 105 eligible for the Ontario Health Insurance Plan (OHIP) during the study period.InterventionsAn innovative, community-based, hybrid model of in-person and virtual care, the Virtual Triage and Assessment Centre (VTAC), was implemented in Renfrew County, Ontario on March 27, 2020.Main outcome measuresPrimary outcome was change in emergency department (ED) visits anywhere in Ontario, secondary outcomes included changes in hospitalizations and health-system costs, using percent changes in mean monthly values of linked health-system administrative data for two years pre-implementation and one year post-implementation.ResultsRenfrew County saw larger declines in ED visits (−34.4%, 95% confidence interval -41.9% to -26.0%) and hospitalizations (−11.1%, 95% confidence interval -19.7% to -1.5%), and slower growth in health-system costs than other rural regions studied. VTAC patients’ low-acuity ED visits decreased by -32.9%, high-acuity visits increased by 8.2%, and hospitalizations increased by 30.0%.ConclusionAfter implementing VTAC, Renfrew County saw reduced ED visits and hospitalizations and slower health-system cost growth compared to neighbouring rural jurisdictions. VTAC patients experienced reduced unnecessary ED visits and increased appropriate care. Community-based, hybrid models of in-person and virtual care may reduce the burden on emergency and hospital services in rural, remote and underserved regions. Further study is required to evaluate potential for scale and spread.Trial registrationNot applicable.STRENGTHS AND LIMITATIONS OF THE STUDYThis study uses population-level health administrative data to investigate the empirical effects of a community-based, hybrid model of in-person and virtual care in rural, remote, and underserved communities, where access to comprehensive primary care is insufficient.Population-level data from administrative datasets were linked using unique encoded identifiers and analyzed at ICES, Ontario’s population health data steward.The intervention jurisdiction is compared with two similar adjoining jurisdictions and with the whole Province.Because of the relatively short time period studied — two years before the intervention and one year post — it remains to be seen whether the observed differences will persist over time.This study’s design does not allow firm inferences about causality; however, the observed changes are in the right temporal sequence and benefit from local comparisons of similar jurisdictions.

Current methods of characterizing plastic debris use arbitrary, predetermined categorizations and assume that the properties of particles are independent. Here we introduce Gaussian mixture models (GMM), a technique suitable for describing non-normal multivariate distributions, as a method to identify mutually exclusive subsets of floating macroplastic and microplastic particles (latent class analysis) based on statistically defensible categories. Length, width, height and polymer type of 6,942 particles and items from the Atlantic Ocean were measured using infrared spectroscopy and image analysis. GMM revealed six underlying normal distributions based on length and width; two within each of the lines, films, and fragments categories. These classes differed significantly in polymer types. The results further showed that smaller films and fragments had a higher correlation between length and width, indicating that they were about the same size in two dimensions. In contrast, larger films and fragments showed low correlations of height with length and width. This demonstrates that larger particles show greater variability in shape and thus plastic fragmentation is associated with particle rounding. These results offer important opportunities for refinement of risk assessment and for modeling the fragmentation and distribution of plastic in the ocean. They further illustrate that GMM is a useful method to map ocean plastics, with advantages over approaches that use arbitrary categorizations and assume size independence or normal distributions.

Previous European land-use regression (LUR) models assumed fixed linear relationships between air pollution concentrations and predictors such as traffic and land use. We evaluated whether including spatially-varying relationships could improve European LUR models by using geographically weighted regression (GWR) and random forest (RF). We built separate LUR models for each year from 2000 to 2019 for NO2, O3, PM2.5 and PM10 using annual average monitoring observations across Europe. Potential predictors included satellite retrievals, chemical transport model estimates and land-use variables. Supervised linear regression (SLR) was used to select predictors, and then GWR estimated the potentially spatially-varying coefficients. We developed multi-year models using geographically and temporally weighted regression (GTWR). Five-fold cross-validation per year showed that GWR and GTWR explained similar spatial variations in annual average concentrations (average R2 = NO2: 0.66; O3: 0.58; PM10: 0.62; PM2.5: 0.77), which are better than SLR (average R2 = NO2: 0.61; O3: 0.46; PM10: 0.51; PM2.5: 0.75) and RF (average R2 = NO2: 0.64; O3: 0.53; PM10: 0.56; PM2.5: 0.67). The GTWR predictions and a previously-used method of back-extrapolating 2010 model predictions using CTM were overall highly correlated (R2 > 0.8) for all pollutants. Including spatially-varying relationships using GWR modestly improved European air pollution annual LUR models, allowing time-varying exposure-health risk models.

Altered miRNA expressions are assigned pathogenic properties in several cancers including mycosis fungoides and could play a role in the early onset of the disease. The aim of this study was to examine disease-specific miRNA expression in early-stage mycosis fungoides patch and plaque lesions. A quantitative real-time PCR platform of 384 human miRNAs was used to study miRNA expression in 154 diagnostic mycosis fungoides biopsies. A total of 110 miRNAs were significantly differentially expressed (>2-fold, p 2-fold, p

Background: Air pollution, road traffic noise, and green space are correlated factors, associated with risk of stroke. We investigated their independent relationship with stroke in multi-exposure analyses and estimated their cumulative stroke burden. Methods: For all persons, ≥50 years of age and living in Denmark from 2005 to 2017, we established complete address histories and estimated running 5-year mean exposure to fine particles (PM2.5), ultrafine particles, elemental carbon, nitrogen dioxide (NO2), and road traffic noise at the most, and least exposed façade. For air pollutants, we estimated total, and non-traffic contributions. Green space around the residence was estimated from land use maps. Hazard ratios (HR) and 95% confidence limits (CL) were estimated with Cox proportional hazards models and used to calculate cumulative risk indices (CRI). We adjusted for the individual and sociodemographic covariates available in our dataset (which did not include information about individual life styles and medical conditions). Findings: The cohort accumulated 18,344,976 years of follow-up and 94,256 cases of stroke. All exposures were associated with risk of stroke in single pollutant models. In multi-pollutant analyses, only PM2.5 (HR: 1.058, 95% CI: 1.040–1.075) and noise at most exposed façade (HR: 1.033, 95% CI: 1.024–1.042) were independently associated with a higher risk of stroke. Both noise and air pollution contributed substantially to the CRI (1.103, 95% CI: 1.092–1.114) in the model with noise, green space, and total PM2.5 concentrations. Interpretation: Environmental exposure to air pollution and noise were both independently associated with risk of stroke. Funding: Health Effects Institute (HEI) (Assistance Award No. R-82811201).

Air pollution is associated with increased risk of myocardial infarction (MI), but it is unresolved to what extent the association is modified by factors such as socioeconomic status, comorbidities, financial stress, residential green space, or road traffic noise. We formed a cohort of all (n = 1,964,702) Danes, aged 50–85 years, with 65,311 cases of MI during the followed-up period 2005–2017. For all participants we established residential five-year running average exposure to particulate matter 2.5), ultrafine particles (UFP, 2). We evaluated risk in population strata, using Aalen additive hazards models to estimate absolute risk and Cox proportional hazards models to estimate relative risk of MI with 95% confidence intervals (CI). PM2.5 and the other pollutant were associated with MI. Lower education and lower income were associated with higher absolute risks of MI from air pollution, whereas no clear effect modification was apparent for relative risk estimates. For example, 5 μg/m3 higher PM2.5 was associated with HR for MI of 1.16 (95% CI: 1.10–1.22) among those with only mandatory education and 1.13 (95% CI: 1.03–1.24) among those with long education. The corresponding rate differences per 100,000 person years were 243 (95% CI: 216–271) and 358 (95% CI: 338–379), respectively. Higher level of comorbidity was consistently across all four pollutants associated with both higher absolute and relative risk of MI. In conclusion, people with comorbid conditions or of lower SES appeared more vulnerable to long-term exposure to air pollution and more cases of MI may be prevented by focused interventions in these groups.

Life history theory predicts that there should be an inverse relationship between offspring size and number, because individuals cannot simultaneously maximize both when resources are limited. Although extensively studied in avian species, the occurrence and determinants of reproductive tradeoffs in oviparous reptiles are far less understood, particularly in parthenogenetic species. We studied this trade-off in the Colorado Checkered Whiptail, Aspidoscelis neotesselatus, a female-only parthenogenetic lizard. Using data previously collected in 2018 and 2019, we tested for clutch and egg size trade-offs and determined whether this relationship could be influenced by female size and aspects of physiological condition. Physiological condition included energy-mobilizing hormone (i.e. corticosterone ‘CORT’), oxidative stress (i.e. reactive oxygen metabolites ‘ROMs’), and innate immune function (bacterial killing ability ‘BKA’). We found the effect of clutch size on follicle size was significant, but not linear. Specifically, follicle size was on average larger in females with clutches of two follicles when compared to clutches of one follicle, but smaller in females with clutches of three when compared to clutches of two. In addition, females that were larger produced larger follicles regardless of clutch size. Neither CORT nor BKA affected the relationship between follicle size and clutch size. However, ROMs did explain variability in this relationship: oxidative stress was more elevated in females that produced larger clutches and larger follicles. We conclude that clutch size and body size are key life history traits that shape follicle size, and that investments into larger clutches and follicle size come at the cost of oxidative damage.