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We examine trends in intergenerational educational mobility throughout the 20th century in Denmark. We demonstrate that major reforms in compulsory schooling substantially increased not only the levels of education but also intergenerational mobility in education for children born in the 1940s through to the 1960s. However, even as college education has expanded significantly for children born in the 1970s and 1980s, educational mobility has been declining. We empirically test different mechanisms that could account for this decline in educational mobility. [ABSTRACT FROM AUTHOR]

Nitrogen isotope analyses of amino acids (δ15N‐AA) are being increasingly used to decipher trophic dynamics. Interpretation of δ15N‐AA in consumers relies on the assumption that consumer physiological status and nutritional status of prey have negligible influences on the trophic discrimination factor (TDF), hence a constant TDF value is used in trophic position (TP) equations. Recent experiments have shown that this is not always the case and there is also a need to validate derived TP estimates in the field. We take advantage of the uniquely long time series of environmental monitoring data and archived (frozen) samples from the species‐poor Baltic Sea. We analyzed δ15N‐AA in similar sized individuals of cod and in its prey herring from four decades, 1980–2018; including time periods where dramatic reduction in condition status of cod has occurred. We expected that TDF in trophic AAs would increase during periods of poor cod condition, resulting in inflated TP estimates. We found that calculated TP and empirical estimates of TDF (difference in δ15N in trophic AAs between cod and herring) for cod increased in recent decades and that this was linked to condition status, herring (prey) lipid content and the hypoxic state of the ecosystem. Statistically adjusting TP for condition and prey lipid content as well as environmental stress (hypoxia) resulted in lower cod TP which better resembled the observed decrease in herring TP in recent decades. TP calculated from stomach analysis data in cod individuals over the same period showed no trend over time and confirmed that adjusted TP estimates mirror the real dietary TP better than unadjusted. By simultaneously measuring condition/nutritional status in both predator and prey it is possible to adjust for them as confounding variables and decipher actual consumer TP, partly overcoming the issues of unknown and variable TDF‐values. Our study also highlights the importance of including environmental stressors (here hypoxia) when interpreting TP and reconstructing food webs. [ABSTRACT FROM AUTHOR]

Scholars of social mobility increasingly study the role of family background in shaping attainment throughout the entire life course. However, research has yet to establish whether the family characteristics influencing early career attainment are the same as those influencing late career attainment. In this research note, I apply an extended sibling correlation approach to analyze brothers' life cycle earnings and family income, using data from the U.S. National Longitudinal Survey of Youth 1979. My analysis reveals a near‐perfect correlation in the family characteristics that affect attainment at early, mid, and late career stages. This finding has significant implications for how mobility scholars conceptualize the impact of family background across a career. It suggests that family background forms a single, consistent dimension in determining attainment throughout the life course. Further analysis also indicates that the imperfect relationship between current and lifetime income is exclusively driven by within‐family processes. [ABSTRACT FROM AUTHOR]

A new approach is presented for gaining additional insights from the molecular weight distribution and intrinsic viscosity of polymers as obtained using size‐exclusion chromatography in combination with refractive index, viscometry, and multiangle light scattering detectors. The approach allows for a more quantitative interpretation of the Mark‐Houwink plot by assessing the variation of the slope as a function of molecular weight. No prior information on the inter‐ and intramolecular interactions of the polymer is needed. The proposed curvature parameter can be correlated to the structural and chemical properties (e.g., branching, composition, randomness) of the polymer. The influence of the covered molecular weight interval and the sample concentration on the precision of the method was studied. This new workflow can be utilized to assess the effect of the solvent system and conditions on the solvation behavior of polymers. To evaluate the applicability of the workflow, three case studies have been performed, including an analysis of ethylene‐propylene‐diene monomer, cellulose ether, and polyamide‐4,10 samples. In addition, an open‐access tool is provided, to aid polymer researchers in incorporating this approach in their work. The developed method can be used to quickly investigate whether an industrial polymer batch contains unwanted branched species or exhibits particular solvation behavior. [ABSTRACT FROM AUTHOR]

Reconstructing the original geometry of a high‐pressure tectonic unit is challenging but important to understand the mechanisms of mountain building. While a single nappe is subducted and exhumed, nappe‐internal thrusts may disrupt it into several subunits. The Middle‐CBU nappe of the Cycladic Blueschist Unit (Hellenide subduction orogen, Greece) shows evidence of such disruption along a Trans‐Cycladic‐Thrust (TCT), however, the timing of this thrusting is unknown. Here, we report multi‐petrological and geochronological data from the Middle‐CBU nappe from the Thera and Ios islands (Greece). Using Zr‐in‐rutile thermometry coupled with quartz‐in‐garnet elastic barometry, average P–T and phase equilibrium thermodynamic modelling, we show that garnet growth in Ios occurred during prograde metamorphism at 6.7 ± 1.4 kbar to 13.0 ± 1.6 kbar and 326 ± 20°C to 506 ± 13°C (2σ uncertainty) followed by early exhumation to 10.1 ± 0.6 kbar and 484 ± 14°C and a greenschist facies overprint at 5.7 ± 1.2 kbar and 416 ± 14°C. For Thera, we constrain peak HP conditions of 7.6 ± 1.8 kbar and 331 ± 18°C, followed by exhumation and equilibration at ~2 kbar and ~275°C using average P–T and phase equilibrium thermodynamic modelling. For Ios, Uranium‐Pb garnet geochronology provides ages of 55.7 ± 5.0 Ma (2σ uncertainties) for prograde and 40.1 ± 1.4 Ma for peak HP metamorphism. Combining our new P–T–t data from Thera and Ios islands with existing data from Naxos island, we conclude that the studied nappe segments represent remnants of a former coherent nappe. The P–T–t data define an Eocene subduction rate of 2.1 ± 1.0 km/Ma, which is distinctly slower than the current subduction rate of 40–45 km/Ma. After subduction, the exhumation of the Middle‐CBU nappe occurred during the Oligocene at different rates for different localities. The Middle‐CBU nappe of Naxos was exhumed at a rate of ~6 km/Ma, contrasting with the exhumation rate of ~3 km/Ma calculated for Ios. This result suggests that the Middle‐CBU nappe of Naxos rocks was thrust on the Ios one during the Oligocene. Using P–T–t data and assuming realistic subduction angles during the Eocene and the Oligocene, we present a 2D structural reconstruction of the Middle‐CBU nappe of these islands. This reconstruction helps to understand the mechanisms of subduction of a continental margin and its disruption during exhumation. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to examine the relationship between alcohol consumption and hip osteoarthritis in women. Alcohol has been associated with both adverse and beneficial health effects generally; however, the relationship between alcohol consumption and hip osteoarthritis has been minimally studied. Methods: Among women in the Nurses' Health Study cohort in the US, alcohol consumption was assessed every 4 years, starting in 1980. Intake was computed as cumulative averages and simple updates with latency periods of 0–4 through 20–24 years. We followed 83,383 women without diagnosed osteoarthritis in 1988 to June 2012. We identified 1,796 cases of total hip replacement due to hip osteoarthritis defined by self‐report of osteoarthritis with hip replacement. Results: Alcohol consumption was positively associated with hip osteoarthritis risk. Compared with nondrinkers, multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were HR 1.04 (95% CI 0.90, 1.19) for drinkers of >0 to <5 grams/day, HR 1.12 (95% CI 0.94, 1.33) for 5 to <10 grams/day, HR 1.31 (95% CI 1.10, 1.56) for 10 to <20 grams/day, and HR 1.34 (95% CI 1.09, 1.64) for ≥20 grams/day (P for trend < 0.0001). This association held in latency analyses of up to 16–20 years, and for alcohol consumption between 35–40 years of age. Independent of other alcoholic beverages, the multivariable HRs (per 10 grams of alcohol) were similar for individual types of alcohol intake (wine, liquor, and beer; P = 0.57 for heterogeneity among alcohol types). Conclusion: Higher alcohol consumption was associated with greater incidence of total hip replacement due to hip osteoarthritis in a dose‐dependent manner in women. [ABSTRACT FROM AUTHOR]

Objective: Ultraviolet (UV) radiation exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort. Methods: The Nurses' Health Study (NHS) enrolled 121,700 US female nurses in 1976; in 1989, 116,429 nurses were enrolled in NHS II. Biennial questionnaires collected lifestyle and medical data. Self‐reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) across tertiles of time‐varying cumulative average UV. We examined SLE risk overall and stratified by anti‐Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHS II), adjusting for confounders. Results: With 6,054,665 person‐years of exposure, we identified 297 incident SLE cases; the mean ± SD age at diagnosis was 49.8 ± 10.6 years. At diagnosis, 16.8% of women had +anti‐Ro/La, and 80% had either +anti‐Ro/La or ≥1 cutaneous manifestation. Compared with the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96–1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04–2.52]). Conclusion: Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women. [ABSTRACT FROM AUTHOR]

Mapping wetland types in northern‐latitude regions with Earth Observation (EO) data is important for several practical and scientific applications, but at the same time challenging due to the variability and dynamic nature in wetland features introduced by differences in geophysical conditions. The objective of this study was to better understand the ability of Sentinel‐1 radar data, Sentinel‐2 optical data and terrain derivatives derived from Copernicus digital elevation model to distinguish three main peatland types, two upland classes, and surface water, in five contrasting landscapes located in the northern parts of Alaska, Canada and Scandinavia. The study also investigated the potential benefits for classification accuracy of using regional classification models constructed from region‐specific training data compared to a global classification model based on pooled reference data from all five sites. Overall, the results show high promise for classifying peatland types and the three other land cover classes using the fusion approach that combined all three EO data sources (Sentinel‐1, Sentinel‐2 and terrain derivatives). Overall accuracy for the individual sites ranged between 79.7% and 90.3%. Class specific accuracies for the peatland types were also high overall but differed between the five sites as well as between the three classes bog, fen and swamp. A key finding is that regional classification models consistently outperformed the global classification model by producing significantly higher classification accuracies for all five sites. This suggests for progress in identifying effective approaches for continental scale peatland mapping to improve scaling of for example, hydrological‐ and greenhouse gas‐related processes in Earth system models. Plain Language Summary: Up‐to‐date land cover maps are of key importance to study and monitor areas experiencing rapid environmental change, such as northern latitude regions. This study focused on mapping wetland types (bog, fen and swamp) as well as other basic land cover classes (forest, other open land and water) using satellite remote sensing data from Sentinel‐1 and Sentinel‐2. In addition, data from Copernicus digital elevation model was included to characterize variations in the terrain. We tested the mapping approach in five areas with differences in land cover conditions located in Alaska, Canada and Scandinavia. The focus on five sites enabled us to compare different strategies for performing the land cover mapping, including how reference data should be handled to increase classification accuracy. The results from all five sites show high accuracy for both wetland types and other land cover classes, with the overall accuracy ranging between 79.7% and 90.3%. Our study also show that accuracy can be substantially increased if local reference data are used to train classification models. These results point to the need for identifying effective approaches to stratify northern latitude areas prior to conducting large scale mapping of detailed land cover classes such as wetland types. Key Points: Peatland types in five contrasting high‐latitude areas were mapped with high accuracy using freely available Earth Observation dataWide‐scale mapping efforts should consider using stratified classification to account for variability in peatland characteristicsAvailability of high‐quality reference data distributed throughout high‐latitude regions is key for achieving wide‐scale peatland mapping [ABSTRACT FROM AUTHOR]

Serum periostin is lower in asthmatics with T2DM using GLP-1RAs compared to alternative diabetes therapies. Prior studies identifying candidate biomarkers of GLP-1RA use critically lacked inclusion of patients with asthma.[[4]] Increasing data support periostin as a potential biomarker of GLP-1RA use. In conclusion, GLP-1RA use may attenuate the increased risk for poor asthma outcomes in patients with metabolic dysregulation and obesity by impacting pathways relevant to airway inflammation in humans. Consistent with prior asthma literature, patients with comorbid asthma (Biobank cohort) had higher mean levels of periostin than the non-asthma patients (RCT cohort). [Extracted from the article]

Objective: To investigate whether a healthy lifestyle, defined by a healthy lifestyle index score (HLIS), was associated with rheumatoid arthritis (RA) risk, overall and with seropositive/seronegative subtypes. Methods: We analyzed female nurses in the Nurses' Health Study (NHS, 1986–2016) and NHSII (1991–2017). Lifestyle and medical information were collected on biennial questionnaires. Medical records confirmed incident RA and serostatus. The HLIS index includes 5 modifiable components: smoking, alcohol consumption, body mass index, physical activity, and diet. Cox regression, adjusted for confounders, modeled associations between HLIS and incident RA. The population attributable risk estimated the proportion of incident RA preventable if participants adopted ≥4 healthy lifestyle factors. Results: A total of 1,219 incident RA cases (776 seropositive, 443 seronegative) developed in 4,467,751 person‐years. Higher (healthier) HLIS was associated with lower overall RA risk (hazard ratio [HR] 0.86 [95% confidence interval (95% CI) 0.82–0.90]), seropositive RA risk (HR 0.85 [95% CI 0.80–0.91]), and seronegative RA risk (HR 0.87 [95% 0.80–0.94]). Women with 5 healthy lifestyle factors had the lowest risk (HR 0.42 [95% CI 0.22–0.80]). The population attributable risk for adhering to ≥4 lifestyle factors was 34% for RA. Conclusion: In this prospective cohort, healthier lifestyle was associated with a lower RA risk. A substantial proportion of RA may be preventable by a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Aim: Children with sickle cell disease (SCD) have historically weighed less than their healthy peers. More recently, a retrospective chart review from six institutions in New England reported nearly one-quarter of children and adolescents with SCD had raised body mass index (BMI). This study aimed to examine rates of children with SCD with raised BMI in Mississippi compared to state and national norms and assess the correlation between haemoglobin and BMI.Methods: A retrospective chart review of paediatric patients with SCD at the University of Mississippi Medical Center (UMMC) was conducted using data from the most recent clinic visit. Mississippi and national weight status estimates for youth 10-17 years were obtained from the 2016-2017 National Survey of Children's Health.Results: For youth 10-17 years with SCD (n = 345), 21.4.% of children with SS/Sβ° and 36.1% with SC/Sβ+ had raised BMI compared to Mississippi and national rates, 39.2 and 31%, respectively. The prevalence of children with raised BMI with SC/Sβ+ did not differ from state and national rates, while children with SS/Sβ° were half as likely as their Mississippi peers to have raised BMI. Haemoglobin levels were different among children with SCD who had low BMI (8.80 g/dL), average BMI (9.2 g/dL) and raised BMI (10.5 g/dL) (P < 0.001).Conclusions: Children with SCD evaluated at UMMC have similar rates of raised BMI compared to state and national norms. Children with raised BMI have higher mean haemoglobin levels compared to children with SCD with low or average BMI.Implications and Contribution: Historically, patients with SCD have been underweight and normal weight. Our paediatric and adolescent patients with SCD now have prevalence rates of raised BMI that approach state and national rates. Further work must be done to determine whether this reflects healthier children with SCD or raises concerns about life-style-related comorbidities. [ABSTRACT FROM AUTHOR]

High‐throughput sequencing‐based analysis of microbial diversity has evolved vastly over the last decade. Currently, the go‐to method for studying microbial eukaryotes is short‐read metabarcoding of variable regions of the 18S rRNA gene with <500 bp amplicons. However, there is a growing interest in applying long‐read sequencing of amplicons covering the rRNA operon for improving taxonomic resolution. For both methods, the choice of primers is crucial. It determines if community members are covered, if they can be identified at a satisfactory taxonomic level, and if the obtained community profile is representative. Here, we designed new primers targeting 18S and 28S rRNA based on 177,934 and 21,072 database sequences, respectively. The primers were evaluated in silico along with published primers on reference sequence databases and marine metagenomics data sets. We further evaluated a subset of the primers for short‐ and long‐read sequencing on environmental samples in vitro and compared the obtained community profile with primer‐unbiased metagenomic sequencing. Of the short‐read pairs, a new V6‐V8 pair and the V4_Balzano pair used with a simplified PCR protocol provided good results in silico and in vitro. Fewer differences were observed between the long‐read primer pairs. The long‐read amplicons and ITS1 alone provided higher taxonomic resolution than V4. Together, our results represent a reference and guide for selection of robust primers for research on and environmental monitoring of microbial eukaryotes. [ABSTRACT FROM AUTHOR]

Objective: While previous studies have demonstrated an association between individual factors related to lifestyle and the risk of systemic lupus erythematosus (SLE), it is unclear how the combination of these factors might affect the risk of incident SLE. This study was undertaken to prospectively evaluate whether a combination of healthy lifestyle factors is associated with a lower risk of incident SLE and its subtypes (anti–double‐stranded DNA [anti‐dsDNA]–positive and anti‐dsDNA–negative SLE). Methods: The study included 185,962 women from the Nurses' Health Study (NHS) and NHSII cohorts, among whom there were 203 incident cases of SLE (96 with anti‐dsDNA–positive SLE, 107 with anti‐dsDNA–negative SLE) during 4,649,477 person‐years of follow‐up. The Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 2 years during follow‐up, with scores assigned for 5 healthy lifestyle factors: alcohol consumption, body mass index, smoking, diet, and exercise. A time‐varying Cox proportional hazards regression model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the risk of SLE. In addition, the percentage of partial population attributable risk (PAR%) of SLE development was calculated. Results: A higher HLIS was associated with a lower risk of SLE overall (HR 0.81 [95% CI 0.71–0.94]) and a lower risk of anti‐dsDNA–positive SLE (HR 0.78 [95% CI 0.63–0.95]). Women with ≥4 healthy lifestyle factors had the lowest risk of SLE overall (HR 0.42, 95% CI 0.25–0.70) and lowest risk of anti‐dsDNA–positive SLE (HR 0.35, 95% CI 0.17–0.75) as compared to women with only 1 healthy behavior or no healthy behaviors. The PAR% of SLE development was 47.7% (95% CI 23.1–66.6%), assuming that the entire population had adhered to at least 4 healthy lifestyle behaviors. Conclusion: These results indicate that the risk of developing SLE, a disease in which significant evidence of genetic involvement has been established, might be reduced by nearly 50% with adherence to modifiable healthy lifestyle behaviors. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) manifests with high clinical variability and warrants sensitive and specific assays to analyze immune responses in infected and vaccinated individuals. Using Single Molecule Arrays (Simoa), we developed an assay to assess antibody neutralization with high sensitivity and multiplexing capabilities based on antibody‐mediated blockage of the ACE2‐spike interaction. The assay does not require live viruses or cells and can be performed in a biosafety level 2 laboratory within two hours. We used this assay to assess neutralization and antibody levels in patients who died of COVID‐19 and patients hospitalized for a short period of time and show that neutralization and antibody levels increase over time. We also adapted the assay for SARS‐CoV‐2 variants and measured neutralization capacity in pre‐pandemic healthy, COVID‐19 infected, and vaccinated individuals. This assay is highly adaptable for clinical applications, such as vaccine development and epidemiological studies. [ABSTRACT FROM AUTHOR]

Objective: To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking. Methods: We analyzed the Nurses' Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of 1) maternal smoking during pregnancy (in utero exposure), 2) childhood parental smoking, and 3) years lived with smokers since age 18. Incident RA and serostatus were determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early‐life factors and time‐updated adulthood factors including personal smoking. Results: Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during a median of 27.7 years of follow‐up. Maternal smoking during pregnancy was associated with RA after adjustment for confounders, with a hazard ratio (HR) of 1.25 (95% confidence interval [95% CI] 1.03–1.52), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjustment for confounders (HR 1.41 [95% CI 1.08–1.83]). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03–2.98]) after controlling for adulthood personal smoking, and the association was accentuated among ever smokers (HR 2.18 [95% CI 1.23–3.88]). There was no significant association of adulthood passive smoking with RA (HR 1.30 for ≥20 years of living with a smoker versus none [95% CI 0.97–1.74]). Conclusion: We found a potential direct influence of childhood parental smoking on adult‐onset incident seropositive RA even after controlling for adulthood personal smoking. [ABSTRACT FROM AUTHOR]

Objective: Smoking has been associated with increased systemic lupus erythematosus (SLE) risk, but the biologic basis for this association is unknown. Our objective was to investigate whether women's smoking was positively associated with SLE‐associated proinflammatory chemokines/cytokines (stem cell factor [SCF], B lymphocyte stimulator [BLyS], interferon‐γ–inducible 10‐kd protein [IP‐10], and interferon‐α); or negatively associated with antiinflammatory cytokine interleukin‐10 (IL‐10); and whether associations were modified by SLE‐related autoantibody status. Methods: The Nurses' Health Study (NHS, n = 121,700) and NHSII (n = 116,429) cohorts were begun in 1976 and 1989. In 1988–1990 (NHS) and 1996–1999 (NHSII), ~25% of participants donated blood samples. We identified 1,177 women without SLE with banked samples, and we tested by enzyme‐linked immunoassay (ELISA) for chemokines/cytokines as well as anti‐Sm, anti‐Ro/SSA, anti‐La/SSB, and anti‐RNP. Antinuclear antibodies (ANAs) were detected by HEp‐2 cell indirect immunofluorescence, and anti–double‐stranded DNA antibodies and were assayed by ELISA. Smoking was assessed until blood draw. Separate tobit and linear regression analyses, adjusted for potential confounders, modeled associations between smoking and log‐transformed chemokine/cytokine concentrations. Analyses were stratified by autoantibody status. Effect estimates were calculated as ratios of geometric means expressed as percentage differences. Results: Among the 15% of current/recent versus 85% of past/never smokers, BLyS levels were 8.7% higher (P < 0.01) and were 24% higher (P < 0.0001) among those who were ANA positive. Current/recent smokers had IL‐10 concentrations 46% lower (P < 0.01) than past/never smokers; each 10 pack‐years of smoking was associated with a 17% decrease in IL‐10 level (P < 0.001). Smoking was not associated with IP‐10 or SCF. Conclusion: Elevated BLyS and lower IL‐10 levels among current smokers, particularly among ANA‐positive women, may be involved in SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti–double‐stranded DNA (anti‐dsDNA) positive versus negative subtypes. Methods: We studied 79,568 women in the Nurses' Health Study (1984–2014) and 93,554 in the Nurses' Health Study II (1991–2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI‐2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time‐varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti‐dsDNA, for cumulative average dietary quality score tertiles and individual AHEI‐2010 components. Results: We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI‐2010 HR 0.78 [95% CI 0.54–1.14], aMed HR 0.82 [95% CI 0.56–1.18], DASH HR 1.16 [95% CI 0.81–1.66], EDIP HR 0.83 [95% CI 0.57–1.21]). No association was demonstrated for anti‐dsDNA+ or anti‐dsDNA– SLE risk. Women in the highest (versus lowest) AHEI‐2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40–0.87]). No association was demonstrated for other AHEI‐2010 components and SLE risk. Conclusion: We observed no association between long‐term adherence to the AHEI‐2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation. [ABSTRACT FROM AUTHOR]

Young children spend a substantial part of their waking time in preschools. It is therefore important to reduce the load of hazardous semivolatile organic compounds (SVOCs) in the preschools' indoor environment. The presence and levels of five SVOC groups were evaluated (1) in a newly built preschool, (2) before and after renovation of a preschool, and (3) in a preschool where SVOC‐containing articles were removed. The new building and the renovation were performed using construction materials that were approved with respect to content of restricted chemicals. SVOC substance groups were measured in indoor air and settled dust and included phthalates and alternative plasticizers, organophosphate esters (OPEs), brominated flame retardants, and bisphenols. The most abundant substance groups in both indoor air and dust were phthalates and alternative plasticizers and OPEs. SVOC concentrations were lower or of the same order of magnitude as those reported in comparable studies. The relative Cumulative Hazard Quotient (HQcum) was used to assess the effects of the different reduction measures on children's SVOC exposure from indoor air and dust in the preschools. HQcum values were low (1.0–6.1%) in all three preschools and decreased further after renovation and article substitution. The SVOCs concentrations decreased significantly more in the preschool renovated with the approved building materials than in the preschool where the SVOC‐containing articles were removed. [ABSTRACT FROM AUTHOR]

Background: Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high-dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability.Methods: We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large-scale genome-wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk.Results: Polygenic risk was associated with increased odds of incident depression, and physical activity showed a protective effect of similar but opposite magnitude, even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk.Conclusions: Real-world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active. [ABSTRACT FROM AUTHOR]

We explore the influence of between‐school ability placement at lower secondary education on earnings across the life course in England and Denmark. We go beyond the mid‐career snapshot provided by previous studies by exploiting the availability of four decades worth of earnings data for individuals born in the mid‐1950s. Members of this cohort who were judged to be among the most academically able attended grammar schools in England (19%) and advanced secondary schools (Realskole) in Denmark (51%) prior to the start of comprehensivization. This key difference makes England and Denmark interesting cases for comparison, not least since pro‐selection policies have re‐emerged in England based on the claim that grammar schools lead to better educational and labor market outcomes. Our analysis of the influence of selective school placement on earnings finds little support for this contention. We find that those from socioeconomically disadvantaged backgrounds were strikingly under‐represented in schools ear‐marked for higher ability pupils in both countries, even after taking into account social class differences in measured ability. Our analysis for England finds only modest earnings returns to attending a grammar school, totalling just £39,000 across the life course, while in Denmark the lifetime earnings returns to attending Realskole are somewhat larger (£194,000). Because those from advantaged backgrounds were substantially over‐represented at grammar schools and Realskoles, these returns accrue disproportionately to pupils from more advantaged backgrounds. Lower secondary school placement in Denmark accounts for 40% of the intergenerational reproduction of socioeconomic advantage and disadvantage, more than half of which is due to selection into school types based on socioeconomic background rather than measured ability. Our findings question the wisdom of expanding grammar schools when they appear to do little to improve individuals' earnings or increase social mobility. [ABSTRACT FROM AUTHOR]

Objective: To investigate elevation of anti–citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma. Methods: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self‐reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre‐RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre‐RA, pre‐RA ACPA+, or pre‐RA ACPA– phenotypes each compared to their matched non‐RA controls. Results: We analyzed 283 women who were pre‐RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty‐nine women (20.8%) were pre‐RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person‐years of follow‐up. Pre‐RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33–7.00]) after adjusting for covariates including smoking pack‐years. Pre‐RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72–4.24), similar to the risk of asthma for pre‐RA ACPA– (HR 1.65 [95% CI 1.11–2.46]). Conclusion: Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre‐RA ACPA status. [ABSTRACT FROM AUTHOR]

Ocean climate change strongly affects organisms and ecosystems, and the causes, consequences, and underlying mechanisms need to be documented. In the Baltic Sea, a marginal sea under severe eutrophication stress, a longer productive season, and changes in the phytoplankton community over the last few decades have likely impacted diet and condition of keystone species, from individual to population level. This study uses stable isotopes (δ13C, δ15N, and derived isotope niche metrics) to trace energy and nutrient flows in archived samples of blue mussel (Mytilus edulis trossulus) spanning 24 yr (1993-2016). We test if long-term changes in isotope and elemental composition in mussels, as well as population abundance and biomass, can be explained by changes in abiotic and biotic variables, using partial least square regressions and structural equation modeling. We found decreasing trends in δ13C and δ15N as well as in mean size and total biomass of mussels, but no unidirectional changes in their stoichiometry or condition index. Changes in isotope composition were best explained by nitrogen-fixing cyanobacteria, by increased terrestrial organic carbon from land runoff (reflecting precipitation) and by decreases in dissolved inorganic nitrogen (indicative of successful eutrophication mitigation) and in biomass of a mixotrophic ciliate species. The trophic niche (assessed from isotope niche) was included as the best predictor for both mussel body condition and the observed decline in their total biomass. This study reveals that altered trophic relationships from climate-induced changes in the productivity base may strongly impact keystone species, with potential knock-on effects on ecosystem functions. [ABSTRACT FROM AUTHOR]

Objective: To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA). Methods: We performed a matched cohort study among women in the Nurses' Health Study (1976–2018). We identified women with incident RA and matched each by age and year to 10 non‐RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators. Results: We identified 1,007 patients with incident RA and matched them to 10,070 non‐RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non‐RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality. Conclusion: We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) is a type of systematic vasculitis that primarily involves the lung and kidney. Diffuse alveolar hemorrhage (DAH) and associated acute respiratory failure are uncommon but devastating complications of GPA. Experience in using extracorporeal membrane oxygenation (ECMO) to manage DAH caused by GPA is limited. We report two GPA patients with DAH that were successfully managed using ECMO support. Examining 13 cases identified in the literature and two of our own, we observed that most patients experienced rapid deterioration in respiratory function in conjunction with a precedent respiratory infection. All 15 patients received veno‐venous ECMO support. The median duration of ECMO support was 11 days (interquartile range: 7.5–20.75 days). Bleeding was the most common complication, seen in four (26.7%) cases. All patients were successfully weaned off ECMO after a median length of hospital stay of 42 days (interquartile range: 30–78 days). We demonstrated that the use of ECMO is a reasonable and effective support option in the management of GPA patients with DAH. The risk of bleeding is high but maybe reduced using a lower anticoagulation goal. [ABSTRACT FROM AUTHOR]

Survivors of childhood cancer may be at risk of experiencing pain, and a systematic review would advance our understanding of pain in this population. The objective of this study was to describe: 1) the prevalence of pain in survivors of childhood cancer, 2) methods of pain measurement, 3) associations between pain and biopsychosocial factors, and 4) recommendations for future research. Data sources for the study were articles published from January 1990 to August 2019 identified in the PubMed, PsycINFO, EMBASE, and Web of Science data bases. Eligible studies included: 1) original research, 2) quantitative assessments of pain, 3) articles published in English, 4) cancers diagnosed between birth and age 21 years, 5) survivors at 5 years from diagnosis and/or at 2 years after therapy completion, and 6) a sample size >20. Seventy‐three articles were included in the final review. Risk of bias was considered using the Cochrane risk of bias tool. The quality of evidence was evaluated according to Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. Common measures of pain were items created by the authors for the purpose of the study (45.2%) or health‐related quality‐of‐life/health status questionnaires (42.5%). Pain was present in from 4.3% to 75% of survivors across studies. Three studies investigated chronic pain according the definition in the International Classification of Diseases. The findings indicated that survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Fatigue was consistently associated with pain, females reported more pain than males, and other factors related to pain will require stronger evidence. Theoretically grounded, multidimensional measurements of pain are absent from the literature. Survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Future research is urgently needed to discern the true prevalence of pain among this vulnerable population and to develop interventions to enhance the quality of survivorship. [ABSTRACT FROM AUTHOR]

Constitutive and inducible terpene production is involved in conifer resistance against insects and fungal infestations. To gain knowledge about local defence responses of Norway spruce bark against pathogens and to find potential chemical markers for resistance breeding, we inoculated the stem of 8‐year‐old Norway spruce (Picea abies) clonal trees with both Endoconidiophora polonica (Ep, a common fungal pathogen associated with the spruce bark beetle Ips typographus) and Heterobasidion parviporum (Hp, a severe pathogen causing root and stem rot disease). Three weeks after inoculation, the fungal‐inoculated and intact bark from each tree was sampled. The terpenes in tree bark were extracted with hexane and characterized by gas chromatography–mass spectrometry (GC‐MS). The two fungi induced varied terpene responses in the four spruce clones used. Three of the clones showed a 2.3‐fold to 5.7‐fold stronger terpene response to Hp relative to Ep inoculation, while one clone responded similarly to inoculation with the two fungal pathogens. The amount of the diterpenes thunbergol and geranyllinalool varied between the clones. The level of thunbergol was higher in both intact and fungal‐inoculated bark from the less susceptible clones compared with the more susceptible clones. Geranyllinalool was present in higher amounts in the susceptible clones and is thus a possible marker for susceptibility. Our observations show that Norway spruce employs a similar chemical mechanism against the two fungal pathogens. Based on the present and earlier published data, we suggest that certain Norway spruce genotypes have a strong defence reaction against these two pathogens. The diterpenes thunbergol and geranyllinalool might be useful markers of susceptibility in tree‐breeding programmes and should be the focus of further detailed investigations. [ABSTRACT FROM AUTHOR]

Objective: To identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE). Methods: For the study, 673 patients with SLE (diagnosed according to the American College of Rheumatology 1997 updated classification criteria) were matched by age, sex, and race (first 3 genetic principal components) to 3,272 control subjects without a history of connective tissue disease. Smoking status was classified as current smoking/having recently quit smoking within 4 years before diagnosis (or matched index date for controls) versus distant past/never smoking. In total, 86 single‐nucleotide polymorphisms and 10 classic HLA alleles previously associated with SLE were included in a weighted genetic risk score (wGRS), with scores dichotomized as either low or high based on the median value in control subjects (low wGRS being defined as less than or equal to the control median; high wGRS being defined as greater than the control median). Conditional logistic regression models were used to estimate both the risk of SLE and risk of anti–double‐stranded DNA autoantibody–positive (dsDNA+) SLE. Additive interactions were assessed using the attributable proportion (AP) due to interaction, and multiplicative interactions were assessed using a chi‐square test (with 1 degree of freedom) for the wGRS and for individual risk alleles. Separate repeated analyses were carried out among subjects of European ancestry only. Results: The mean ± SD age of the SLE patients at the time of diagnosis was 36.4 ± 15.3 years. Among the 673 SLE patients included, 92.3% were female and 59.3% were dsDNA+. Ethnic distributions were as follows: 75.6% of European ancestry, 4.5% of Asian ancestry, 11.7% of African ancestry, and 8.2% classified as other ancestry. A high wGRS (odds ratio [OR] 2.0, P = 1.0 × 10−51 versus low wGRS) and a status of current/recent smoking (OR 1.5, P = 0.0003 versus distant past/never smoking) were strongly associated with SLE risk, with significant additive interaction (AP 0.33, P = 0.0012), and associations with the risk of anti‐dsDNA+ SLE were even stronger. No significant multiplicative interactions with the total wGRS (P = 0.58) or with the HLA‐only wGRS (P = 0.06) were found. Findings were similar in analyses restricted to only subjects of European ancestry. Conclusion: The strong additive interaction between an updated SLE genetic risk score and current/recent smoking suggests that smoking may influence specific genes in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

According to ecological theory, two species cannot occupy the same niche. Using nitrogen isotope analyses (δ15N) of amino acids, we tested the extent to which two sympatric deposit‐feeding amphipods, Monoporeia affinis and Pontoporeia femorata, partition their trophic resources. We found that trophic position (TP) and resynthesis index (∑V; a proxy for degradation status of ingested material prior to assimilation by the consumer) differ between species. The surface‐feeding M. affinis had higher TP and intermediate ∑V, both pointing to a large contribution of metazoans in its diet. P. femorata, which feeds in the subsurface layers, had lower TP and a bimodal distribution of the ∑V values, supporting previous experimental evidence of a larger feeding niche. We also evaluated whether TP and ∑V values have consequences for amphipod fecundity and embryo viability and found that embryo viability in M. affinis was negatively linked to TP. Our results indicate that the amino acid‐δ15N data paired with information about reproductive status are useful for detecting differences in the trophic ecology of sympatric amphipods. [ABSTRACT FROM AUTHOR]

The pine weevil Hylobius abietis is an important pest causing severe damage to conifer seedlings in reforestation areas in Europe and Asia. Plants that have no evolutionary history with the pine weevil are of special interest in the search for compounds with a strong antifeedant activity. Thus, the essential oils of nine aromatic plants, viz Amomum subulatum, Cinnamomum tamala, Curcuma longa, Laurus nobilis, Ocimum basilicum, Origanum majorana, Origanum vulgare, Syzygium aromaticum and Trachyspermum ammi were extracted by hydrodistillation. The essential oil constituents were identified by gas chromatography–mass spectrometry, and antifeedant properties towards the pine weevil were assessed using choice feeding bioassay. The essential oils of C. longa, O. majorana, S. aromaticum and T. ammi showed an excellent antifeedant activity towards the pine weevil for 24 hr, whereas the essential oil of other plants showed the activity for 6 hr. There was a positive correlation between the amount of benzenoid compounds and the antifeedant activity of the essential oils. This study suggests that pine weevil non‐host plant compounds have potential to be used for the protection of seedlings against pine weevil feeding. However, further study will be needed to explore the antifeedant activity of individual components and oils in the laboratory as well as in the field. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize the prevalence and risk of pain, pain interference, and recurrent pain in adult survivors of childhood cancer in comparison with siblings.Methods: This study analyzed longitudinal data from survivors (n = 10,012; 48.7% female; median age, 31 years [range, 17-57 years]; median time since diagnosis, 23 years) and siblings (n = 3173) from the Childhood Cancer Survivor Study. Survivors were diagnosed between 1970 and 1986 at 1 of 26 participating sites. Associations between risk factors (demographics, cancer-related factors, and psychological symptoms) and pain, pain interference, and recurrent pain (5 years apart) were assessed with multinomial logistic regression. Path analyses examined cross-sectional associations between risk factors and pain outcomes.Results: Twenty-nine percent of survivors reported moderate to severe pain, 20% reported moderate to extreme pain interference, and 9% reported moderate to severe recurrent pain. Female sex, a sarcoma/bone tumor diagnosis, and severe/life-threatening chronic medical conditions were associated with recurrent pain. Depression and anxiety were associated with increased risk for all pain outcomes. Poor vitality mediated the effects of anxiety on high pain and pain interference (root mean square error of approximation, 0.002).Conclusions: A large proportion of adult survivors report moderate to severe pain and pain interference more than 20 years after their diagnosis. Increased screening and early intervention for pain interference and recurrent pain are warranted. [ABSTRACT FROM AUTHOR]

Plants can form an immunological memory known as defense priming, whereby exposure to a priming stimulus enables quicker or stronger response to subsequent attack by pests and pathogens. Such priming of inducible defenses provides increased protection and reduces allocation costs of defense. Defense priming has been widely studied for short‐lived model plants such as Arabidopsis, but little is known about this phenomenon in long‐lived plants like spruce. We compared the effects of pretreatment with sublethal fungal inoculations or application of the phytohormone methyl jasmonate (MeJA) on the resistance of 48‐year‐old Norway spruce (Picea abies) trees to mass attack by a tree‐killing bark beetle beginning 35 days later. Bark beetles heavily infested and killed untreated trees but largely avoided fungus‐inoculated trees and MeJA‐treated trees. Quantification of defensive terpenes at the time of bark beetle attack showed fungal inoculation induced 91‐fold higher terpene concentrations compared with untreated trees, whereas application of MeJA did not significantly increase terpenes. These results indicate that resistance in fungus‐inoculated trees is a result of direct induction of defenses, whereas resistance in MeJA‐treated trees is due to defense priming. This work extends our knowledge of defense priming from model plants to an ecologically important tree species. This article demonstrates that methyl jasmonate treatment prior to a natural bark beetle attack primes Norway spruce defenses and decreases tree mortality. This work extends our knowledge of defense priming from model plants to an ecologically important tree species. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk of progression to rheumatoid arthritis (RA) in patients who were cyclic citrullinated peptide (CCP) antibody positive without RA at initial presentation.Methods: We performed a retrospective cohort study of CCP+ individuals seen at a US tertiary care system between 2009 and 2018 who were without RA or other systemic rheumatic disease by medical record review at the time of CCP antibody positivity. Progression to classifiable RA was determined through medical record review. We investigated the risk of progression to RA overall and stratified by CCP antibody level (low: >1 to 2× the upper limit of normal [ULN]; medium: >2 to 3× ULN; high: >3× ULN). Multivariable Cox regression estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for RA by CCP antibody level.Results: We identified 340 CCP+ patients who were without RA or other rheumatic disease at baseline. During 1,047 person-years of follow-up, 73 patients (21.5%) developed RA. The risk of progression to RA increased with CCP antibody level, with 46.0% (95% CI 34.7-55.3) of patients with high-level CCP antibodies progressing to RA by 5 years. Compared to low CCP antibody level, medium (HR 3.00 [95% CI 1.32-6.81]) and high (HR 4.83 [95% CI 2.51-9.31]) CCP antibody levels were strongly associated with progression to RA, adjusting for age, sex, body mass index, smoking, family history of RA, and rheumatoid factor level.Conclusion: Among CCP+ patients without RA, the risk for progression to RA increased substantially with increasing CCP antibody level. This study provides further support for close monitoring for development of RA among CCP+ patients and identifying strategies to mitigate this risk. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate rheumatoid arthritis (RA) disease activity and risk of RA‐associated interstitial lung disease (RA‐ILD). Methods: We investigated disease activity and risk of RA‐ILD using the Brigham RA Sequential Study (BRASS, 2003–2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA‐ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA‐ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA‐ILD, using annually updated DAS28 data, with adjustment for known RA‐ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules. Results: Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA‐ILD during a mean ± SD follow‐up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28–3.82) for RA‐ILD compared to the remission/low disease activity group. Risk of RA‐ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61–3.28) for low disease activity, 2.08 (95% CI 1.06–4.05) for moderate disease activity, and 3.48 (95% CI 1.64–7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA‐ILD increased by 35% (95% CI 14–60%). Results were similar in analyses that included follow‐up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules. Conclusion: Active articular RA was associated with an increased risk of developing RA‐ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA‐ILD development. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of long‐term physical activity on subsequent risk of rheumatoid arthritis (RA) in a prospective cohort study. Methods: This study investigated physical activity and RA risk among women from the Nurses' Health Study II (1989–2015). Physical activity exposures and covariates were prospectively obtained using biennial questionnaires. Two rheumatologists independently reviewed the medical records of women who self‐reported a new diagnosis of RA on biennial questionnaires and who screened positive for RA based on a supplemental survey. All incident RA cases met the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA. The primary analysis investigated the long‐term cumulative average number of hours spent in recreational physical activity 2–8 years prior to the RA diagnosis, a time span chosen to reduce the potential for reverse causation bias, since early RA affects physical activity prior to diagnosis. Estimated Cox regression hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the risk of RA serologic phenotypes (all, seropositive, or seronegative) in relation to physical activity categories. The analyses were adjusted for body mass index (BMI) at age 18 years and time‐varying potential confounders, and the mediating effect of updated BMI on the interaction between physical activity and RA risk was quantified. Results: Among the 113,366 women analyzed, 506 incident RA cases (67.0% with seropositive RA) were identified during 2,428,573 person‐years of follow‐up. After adjustment for confounders, including smoking, dietary quality, and BMI at age 18 years, increasing cumulative average total hours of recreational physical activity was associated with a reduced risk of RA, as follows: HR 1.00 for <1 hour/week (reference), HR 1.00 (95% CI 0.78–1.29) for 1 to <2 hours/week, HR 0.92 (95% CI 0.72–1.17) for 2 to <4 hours/week, HR 0.84 (95% CI 0.63–1.12) for 4 to <7 hours/week, and HR 0.67 (95% CI 0.47–0.98) for ≥7 hours/week (P for trend = 0.02). The proportion of the effect between physical activity and RA mediated by updated BMI was 14.0% (P = 0.002) for all RA and 20.0% (P = 0.001) for seropositive RA. Conclusion: Higher levels of physical activity were associated with reduced RA risk. These results add to the literature implicating metabolic factors in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact and timing of smoking cessation on developing rheumatoid arthritis (RA) and serologic phenotypes. Methods: We investigated smoking cessation and RA risk in the Nurses' Health Study (NHS) (1976–2014) and the NHS II (1989–2015). Smoking exposures and covariates were obtained by biennial questionnaires. Self‐reported RA was confirmed by medical record review for American College of Rheumatology/European League Against Rheumatism criteria. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA serologic phenotypes (all, seropositive, seronegative) according to smoking status, intensity, pack‐years, and years since cessation. Results: Among 230,732 women, we identified 1,528 incident cases of RA (63.4% of which were seropositive) during 6,037,151 person‐years of follow‐up. Compared with never smoking, current smoking increased the risk of all RA (multivariable HR 1.47, 95% CI 1.27–1.72) and seropositive RA (HR 1.67, 95% CI 1.38–2.01) but not seronegative RA (HR 1.20, 95% CI 0.93–1.55). An increasing number of smoking pack‐years was associated with an increased trend for the risk of all RA (P < 0.0001) and seropositive RA (P < 0.0001). With increasing duration of smoking cessation, a decreased trend for the risk of all RA was observed (P = 0.009) and seropositive RA (P = 0.002). Compared to recent quitters (<5 years), those who quit ≥30 years ago had an HR of 0.63 (95% CI 0.44–0.90) for seropositive RA. However, a modestly increased risk of RA was still detectable 30 years after quitting smoking (for all RA, HR 1.25 [95% CI 1.02–1.53]; for seropositive RA, HR 1.30 [95% CI 1.01–1.68]; reference, never smoking). Conclusion: These results confirm that smoking is a strong risk factor for developing seropositive RA and demonstrate for the first time that a behavior change of sustained smoking cessation could delay or even prevent seropositive RA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence and predictors of dyspnea on exertion among subjects with rheumatoid arthritis (RA). Methods: We investigated dyspnea on exertion using a prospective cohort, the Brigham RA Sequential Study (BRASS). Clinically significant dyspnea on exertion was defined as a score of ≥ 3 (unable to ambulate without breathlessness or worse) on the validated Medical Research Council (MRC) scale (range 0‐5). We analyzed subjects with MRC score < 3 at BRASS baseline and at ≥ 1 year of follow‐up. The MRC scale was administered annually. We determined the incidence rate (IR) of dyspnea on exertion. We used Cox regression to estimate the hazard ration (HR) for dyspnea on exertion occurring one year after potential predictors were assessed. Results: We analyzed 829 subjects with RA and no clinically significant dyspnea on exertion during a mean follow‐up period of 3.0 years (SD 1.9). At baseline, mean age was 55.7 years (SD 13.6), 82.4% of subjects were female, and median RA duration was 8 years. During follow‐up, 112 subjects (13.5%) developed incident dyspnea on exertion during 2476 person‐years of follow‐up (incidence rate 45.2 per 1000 person‐years). Independent predictors of incident dyspnea on exertion were older age (HR 1.03 per year, 95% CI, 1.01‐1.04), female sex (HR 2.22, 95% CI, 1.14‐4.29), mild dyspnea (HR 2.62, 95% CI, 1.60‐4.28), and worsened Multi‐Dimensional Health Assessment Questionnaire score (HR 2.36 per unit, 95% CI, 1.54‐3.60). Methotrexate use, RA disease activity, and seropositivity were not associated with incident dyspnea on exertion after accounting for other dyspnea risk factors. Conclusion: Dyspnea on exertion occurred commonly in patients with RA. Older women with impaired physical function were especially vulnerable to developing dyspnea on exertion. [ABSTRACT FROM AUTHOR]

A better understanding of the oviposition behaviour of malaria vectors might facilitate the development of new vector control tools. However, the factors that guide the aquatic habitat selection of gravid females are poorly understood. The present study explored the relative attractiveness of similar artificial ponds (0.8 m2) aged at varying lengths prior to opening in such a way that wild Anopheles arabiensis could choose between ponds that were freshly set up, or were aged 4 or 17 days old, to lay eggs. Physicochemical parameters, bacterial profile and volatile organic compounds emitted from ponds were investigated over three experimental rounds. Fresh ponds contained on average twice as many An. arabiensis instar larvae (mean 50, 95% confidence interval (CI) = 29–85) as the ponds that had aged 4 days (mean = 24, 95% CI = 14–42) and 17 days (mean = 20, 95% CI: 12–34). Fresh ponds were associated with a significantly higher turbidity combined with higher water temperature, higher nitrite levels and a lower pH and chlorophyll level than the older ponds. Round by round analyses suggested that bacteria communities differed between age groups and also that 4‐heptanone, 2‐ethylhexanal and an isomer of octenal were exclusively detected from the fresh ponds. These characteristics may be useful with respect to developing attract and kill strategies for malaria vector control. Fresh ponds contained on average twice as many Anopheles arabiensis instar larvae as the ponds that had aged 4 days and 17 days.The fresh ponds differed from the older ponds with respect to physicochemical characteristics, as well as bacteria and volatile chemical profiles of the water, before colonization, potentially explaining the habitat selection by gravid females.By contrast with previous field studies, which investigated water qualities of already colonized water, it was possible to observe cues emanating from pond water directly preceding oviposition. [ABSTRACT FROM AUTHOR]

Background: Relatively little is known about antepartum suicidal behaviour and pregnancy outcomes. We examined associations of antepartum suicidal behaviour, alone and in combination with psychiatric disorders, with adverse infant and obstetric outcomes.Methods: We included 188 925 singleton livebirths from a retrospective cohort (1996-2016). Suicidal behaviour, psychiatric disorders, and outcomes were derived from electronic medical records. We performed multivariable logistic regressions with generalised estimating equations to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95%CI).Results: The prevalence of antepartum suicidal behaviour was 152.44 per 100 000 singleton livebirths. Nearly two-thirds (64.24%) of women with suicidal behaviour also had psychiatric disorders. Compared to women without psychiatric disorders and suicidal behaviour, women with psychiatric disorders alone had 1.3-fold to 1.4-fold increased odds of delivering low birthweight or preterm infants and 1.2-fold increased odds of experiencing obstetric complications. Women with suicidal behaviour alone had increased odds of preterm labour (aOR 2.05, 95% CI 1.16, 3.62). Women with both suicidal behaviour and psychiatric disorders had > twofold increased odds of delivering low birthweight (aOR 2.52, 95% CI 1.40, 4.54), preterm birth (aOR 2.44, 95% CI 1.63, 3.66), and low birthweight/preterm birth (aOR 2.30, 95% CI 1.54, 3.44) infants; the odds of preterm labour (aOR 1.62, 95% CI 1.06, 2.47), placental abruption (aOR 2.33, 95% CI 1.20, 4.51), preterm rupture of membranes (aOR 1.63, 95% CI 1.08, 2.46), and postpartum haemorrhage (aOR 1.93, 95%CI 1.09, 3.40) were elevated.Conclusions: Antepartum suicidal behaviour, when co-occurring with psychiatric disorders, is associated with increased odds of adverse infant and obstetric outcomes. Future studies are warranted to understand the causal roles of suicidal behaviour and psychiatric disorders in pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To assess knowledge of rheumatoid arthritis (RA) risk factors among unaffected first-degree relatives (FDRs) and to study whether a personalized RA education tool increases risk factor knowledge.Methods: We performed a randomized controlled trial assessing RA educational interventions among 238 FDRs. The web-based Personalized Risk Estimator for RA (PRE-RA) tool displayed personalized RA risk results (genetics, autoantibodies, demographics, and behaviors) and educated about risk factors. Subjects were randomly assigned to a Comparison arm (standard RA education; n = 80), a PRE-RA arm (PRE-RA alone; n = 78), or a PRE-RA Plus arm (PRE-RA and a one-on-one session with a trained health educator; n = 80). The RA Knowledge Score (RAKS), the number of 8 established RA risk factors identified as related to RA, was calculated at baseline and post-education (immediate/6 weeks/6 months/12 months). We compared RAKS and its components at each post-education point by randomization arm.Results: At baseline before education, few FDRs identified behavioral RA risk factors (15.6% for dental health, 31.9% for smoking, 47.5% for overweight/obesity, and 54.2% for diet). After education, RAKS increased in all arms, higher in PRE-RA and PRE-RA Plus than Comparison at all post-education points (P < 0.05). PRE-RA subjects were more likely to identify risk factors than those who received standard education (proportion agreeing that smoking is a risk factor at 6 weeks: 83.1% in the PRE-RA Plus arm, 71.8% in the PRE-RA arm, and 43.1% in the Comparison arm; P < 0.05 for PRE-RA versus Comparison).Conclusion: Despite being both familiar with RA and at increased risk, FDRs had low knowledge about RA risk factors. A web-based personalized RA education tool successfully increased RA risk factor knowledge. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.Methods: We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans-theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intent-to-treat analyses using generalized estimating equations for the binary outcome.Results: Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).Conclusion: Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA-related autoantibody production or RA development. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of weight loss after bariatric surgery among patients with rheumatoid arthritis (RA).Methods: We conducted a retrospective cohort study of RA patients who underwent bariatric surgery (Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or sleeve gastrectomy) at 2 medical centers. We obtained information on anthropometrics, laboratory values, RA disease activity, and medication use at baseline (prior to surgery), at 6 and 12 months following surgery, and at the most recent followup visits. RA disease activity was determined by clinical or validated measures. At each postsurgical visit, characteristics were compared to baseline.Results: We identified 53 RA patients who underwent bariatric surgery. At baseline prior to surgery, mean ± SD body mass index was 47.8 ± 7.7 kg/m(2), mean ± SD weight was 128.2 ± 24.1 kg, and 57% had moderate to high RA disease activity. Twelve months following surgery, subjects lost a mean ± SD weight of 41.0 ± 17.3 kg, mean ± SD 70% ± 24% excess weight (P < 0.001). RA disease activity significantly improved at postsurgical visits (P < 0.001). At 12 months following surgery, 6% had moderate to high disease activity, compared to 57% at baseline (P < 0.001). At the most recent followup (mean ± SD 5.8 ± 3.2 years after surgery), 74% were in remission, compared to 26% at baseline (P < 0.001). Subjects had significantly lower erythrocyte sedimentation rate, C-reactive protein level, and RA-related medication use at followup visits compared to baseline (P < 0.05).Conclusion: After substantial weight loss from bariatric surgery, RA patients had lower disease activity, decreased serum inflammatory markers, and less RA-related medication use. Weight loss may be an important nonpharmacologic strategy to reduce RA disease activity. However, other factors, such as improved efficacy of medications, improved physical activity, and metabolic changes, may also have contributed to these postsurgical improvements. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality.Methods: We identified an incident RA cohort in the Nurses' Health Study (NHS; 1976-2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within 4 years of the RA/index date. We used Cox regression to obtain hazard ratios (HRs) for mortality, comparing sustained smoking cessation to continued smoking.Results: Among 121,700 women in the NHS, we identified 938 with incident RA matched to 8,951 non-RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period, compared to 36.1% of comparators (odds ratio for sustained cessation 1.18 [95% confidence interval (95% CI) 0.88, 1.58]). There were 313 deaths (33.4%) in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58 [95% CI 0.33, 1.01]) and comparison (HR 0.47 [95% CI 0.39, 0.58]) cohorts. Women with RA had higher mortality for >5 post-RA pack-years (HR 3.67 [95% CI 2.80, 4.81]) than comparators with >5 post-index pack-years (HR 1.88 [95% CI 1.62, 2.17]; P < 0.001 for interaction; reference: ever-smoker non-RA women with 0 post-index pack-years).Conclusion: Sustained smoking cessation within 4 years of RA diagnosis reduced mortality risk, with a similar effect observed among non-RA comparators. Smoking >5 pack-years after RA diagnosis significantly increased mortality beyond the risk of non-RA comparators. [ABSTRACT FROM AUTHOR]

Objective To investigate whether weight change during the early rheumatoid arthritis ( RA) period is associated with subsequent mortality and to evaluate whether there is an RA-specific effect. Methods We identified patients with incident RA during the Nurses' Health Study (NHS; 1976-2016) and created a comparison cohort by matching each RA patient with up to 10 non- RA comparators by age and calendar year of the RA diagnosis (index date). To capture weight change around the early RA period ('peri- RA/index'), we used weight measurements collected 2-4 years before and 2-4 years after the index date. We used Cox regression analysis to estimate hazard ratios ( HRs) for mortality according to peri- RA/index weight change categories, separately in each cohort and in the combined cohorts, evaluating for an RA-specific effect. Results Among 121,701 women in the NHS, 902 patients with incident RA were identified and matched to 7,884 non- RA comparators. In the RA cohort, 371 deaths (41.1%) occurred during a mean follow-up of 17.0 years after the early RA period, and 2,303 deaths (29.2%) occurred in the comparison cohort during a mean follow-up of 18.4 years. Weight loss of >30 pounds during the peri- RA period had a hazard ratio ( HR) for mortality of 2.78 (95% confidence interval [95% CI] 1.58-4.89) compared to stable weight; results in the comparison cohort were similar ( HR 2.16, 95% CI 1.61-2.88). A weight gain of >30 pounds had no association with mortality in patients with RA ( HR 1.45, 95% CI 0.69-3.07) or comparators ( HR 1.19, 95% CI 0.89-1.59). For mortality, there was no statistically significant interaction between RA/comparator status and weight change category ( P = 0.68). Conclusion Severe weight loss during the early RA period was associated with an increased subsequent mortality risk for women with and those without RA. These results extend prior observations by including non- RA comparators and finding no protective association between weight gain and mortality, providing evidence against an RA-specific obesity paradox for mortality. [ABSTRACT FROM AUTHOR]