Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis.

RATIONALE: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. METHODS: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. RESULTS: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11ß-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11ß-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11ß-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11ß-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. CONCLUSIONS: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern.

BACKGROUND: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both. METHODS: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns. RESULTS: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively). CONCLUSION: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

Changes over time in latent patterns of childhood-to-adulthood BMI development in Great Britain: evidence from three cohorts born in 1946, 1958, and 1970.

BACKGROUND: Most studies on secular trends in body mass index (BMI) are cross-sectional and the few longitudinal studies have typically only investigated changes over time in mean BMI trajectories. We aimed to describe how the evolution of the obesity epidemic in Great Britain reflects shifts in the proportion of the population demonstrating different latent patterns of childhood-to-adulthood BMI development. METHODS: We used pooled serial BMI data from 25,655 participants in three British cohorts: the 1946 National Survey of Health and Development (NSHD), 1958 National Child Development Study (NCDS), and 1970 British Cohort Study (BCS). Sex-specific growth mixture models captured latent patterns of BMI development between 11 and 42 years. The classes were characterised in terms of their birth cohort composition. RESULTS: The best models had four classes, broadly similar for both sexes. The 'lowest' class (57% of males; 47% of females) represents the normal weight sub-population, the 'middle' class (16%; 15%) represents the sub-population who likely develop overweight in early/mid-adulthood, and the 'highest' class (6%; 9%) represents those who likely develop obesity in early/mid-adulthood. The remaining class (21%; 29%) reflects a sub-population with rapidly 'increasing' BMI between 11 and 42 years. Both sexes in the 1958 NCDS had greater odds of being in the 'highest' class compared to their peers in the 1946 NSHD but did not have greater odds of being in the 'increasing' class. Conversely, males and females in the 1970 BCS had 2.78 (2.15, 3.60) and 1.87 (1.53, 2.28), respectively, times higher odds of being in the 'increasing' class. CONCLUSIONS: Our results suggest that the obesity epidemic in Great Britain reflects not only an upward shift in BMI trajectories but also a more recent increase in the number of individuals demonstrating more rapid weight gain, from normal weight to overweight, across the second, third, and fourth decades of life.

Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study.

OBJECTIVE: To examine the relationship between height gain across childhood and adolescence with knee osteoarthritis in the MRC National Survey of Health and Development (NSHD). MATERIALS AND METHODS: Data are from 3035 male and female participants of the NSHD. Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at ages 20 years. Associations between (1) height at each age (2) height gain during specific life periods (3) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity, and knee osteoarthritis at 53 years were tested. RESULTS: In sex-adjusted models, estimated associations between taller height and decreased odds of knee osteoarthritis at age 53 years were small at all ages - the largest associations were an OR of knee osteoarthritis of 0.9 per 5 cm increase in height at age 4, (95% CI 0.7-1.1) and an OR of 0.9 per 5 cm increase in height, (95% CI 0.8-1.0) at age 6. No associations were found between height gain during specific life periods or the SITAR growth curve variables and odds of knee osteoarthritis. CONCLUSIONS: There was limited evidence to suggest that taller height in childhood is associated with decreased odds of knee osteoarthritis at age 53 years in this cohort. This work enhances our understanding of osteoarthritis predisposition and the contribution of life course height to this.

Fire safety and emergency evacuation guidelines for intensive care units and operating theatres: for use in the event of fire, flood, power cut, oxygen supply failure, noxious gas, structural collapse or other critical incidents: Guidelines from the Association of Anaesthetists and the Intensive Care Society.

The need to evacuate an ICU or operating theatre complex during a fire or other emergency is a rare event but one potentially fraught with difficulty: Not only is there a risk that patients may come to harm but also that staff may be injured and unable to work. Designing newly-built or refurbished ICUs and operating theatre suites is an opportunity to incorporate mandatory fire safety features and improve the management and outcomes of such emergencies: These include well-marked manual fire call points and oxygen shut off valves (area valve service units); the ability to isolate individual zones; multiple clear exit routes; small bays or side rooms; preference for ground floor ICU location and interconnecting routes with operating theatres; separate clinical and non-clinical areas. ICUs and operating theatre suites should have a bespoke emergency evacuation plan and route map that is readily available. Staff should receive practical fire and evacuation training in their clinical area of work on induction and annually as part of mandatory training, including 'walk-through practice' or simulation training and location of manual fire call points and fire extinguishers, evacuation routes and location and operation of area valve service units. The staff member in charge of each shift should be able to select and operate fire extinguishers and lead an evacuation. Following an emergency evacuation, a network-wide response should be activated, including retrieval and transport of patients to other ICUs if needed. A full investigation should take place and ongoing support and follow-up of staff provided.

A Sharing Meanings Approach for Interdisciplinary Hazards Research.

Hazards researchers frequently examine complex socioenvironmental problems, a difficult undertaking that is further compounded by the challenge of navigating the many disciplinary approaches in the field. This article draws on key insights from studies of the interdisciplinary process and proposes the "sharing meanings approach" for improving interdisciplinary collaboration in hazards research. The sharing meanings approach addresses common challenges to interdisciplinary teamwork and organizes them into four focal areas: (1) worldviews (including ontological, epistemological, and philosophical perspectives), (2) language, (3) research design, and (4) project goals. The approach emphasizes the process of sharing rather than seeking to develop a single set of shared meanings related to the four focal areas. The article identifies common challenges and recommends strategies and actions within each focal area for guiding teams toward sharing their implicit meanings. A hypothetical example is introduced to demonstrate how the approach offers a path for revealing and overcoming the common roadblocks experienced in interdisciplinary hazards research. By making interdisciplinary hazards teams' implicit assumptions explicit, the sharing meanings approach offers an operational process to seize on moments of difference as productive tension and to see such challenges as opportunities-rather than obstacles-for innovating toward hybrid methodological research designs in hazards research.

11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.

OBJECTIVE: In rheumatoid arthritis, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is highly expressed at sites of inflammation, where it converts inactive glucocorticoids (GC) to their active counterparts. In conditions of GC excess it has been shown to be a critical regulator of muscle wasting and bone loss. Here we examine the contribution of 11ß-HSD1 to the pathology of persistent chronic inflammatory disease. METHODS: To determine the contribution of 11ß-HSD1 to joint inflammation, destruction and systemic bone loss associated with persistent inflammatory arthritis, we generated mice with global and mesenchymal specific 11ß-HSD1 deletions in the TNF-transgenic (TNF-tg) model of chronic polyarthritis. Disease severity was determined by clinical scoring. Histology was assessed in formalin fixed sections and fluorescence-activated cell sorting (FACS) analysis of synovial tissue was performed. Local and systemic bone loss were measured by micro computed tomography (micro-CT). Measures of inflammation and bone metabolism were assessed in serum and in tibia mRNA. RESULTS: Global deletion of 11ß-HSD1 drove an enhanced inflammatory phenotype, characterised by florid synovitis, joint destruction and systemic bone loss. This was associated with increased pannus invasion into subchondral bone, a marked polarisation towards pro-inflammatory M1 macrophages at sites of inflammation and increased osteoclast numbers. Targeted mesenchymal deletion of 11ß-HSD1 failed to recapitulate this phenotype suggesting that 11ß-HSD1 within leukocytes mediate its protective actions in vivo. CONCLUSIONS: We demonstrate a fundamental role for 11ß-HSD1 in the suppression of synovitis, joint destruction, and systemic bone loss. Whilst a role for 11ß-HSD1 inhibitors has been proposed for metabolic complications in inflammatory diseases, our study suggests that this approach would greatly exacerbate disease severity.

Early menarche and blood pressure in adulthood: systematic review and meta-analysis.

Background: It has been reported that early menarche is associated with high blood pressure and hypertension. However, some studies have failed to observe such association. We carried out a systematic review and meta-analysis on the association of early menarche with hypertension and high blood pressure in adulthood. Methods: PUBMED, SciELO, Scopus and LILACS databases were searched. Studies that evaluated the association of early menarche with hypertension or high blood pressure, among women aged 20 years or more were included. Random effects models were used to pool the estimates. Meta-regression was used to evaluate the contribution of different co-variables to heterogeneity. Results: We identified 17 studies with 18 estimates on the association of early menarche with hypertension and high blood pressure. The odds of hypertension/high blood pressure was higher among women with early menarche [pooled (OR):1.25; 95% confidence interval (CI): 1.17-1.34; P < 0.001]. In the meta-regression analysis, studies evaluating 1500 subjects or more had a higher pooled OR [1.27; 95%CI (1.19;1.36)] than those with less participants. Although funnel plots showed some asymmetry, Egger tests were not statistically significant. Therefore, it is unlikely that the observed association was to publication bias. Conclusions: Early menarche is associated with hypertension among adult woman.

Chemical Characterization and Source Apportionment of PM2.5 in a Nonattainment Rocky Mountain Valley.

Severe air pollution has significant adverse health effects and poses a threat to public health in many communities, including nonattainment areas in the Unites States. To develop effective control strategies to reduce air pollution with minimum economic cost, one of the biggest challenges is to quantify the contributions from different sources. By combining chemical analyses, Positive Matrix Factorization modeling, and emission inventory development, this study identified primary and secondary sources of particulate matter with a diameter of <2.5 µm (PM) in a nonattainment Rocky Mountain valley (i.e., West Silver Valley [WSV]) in Idaho. The results show that biomass burning is the dominant source and contributes ∼84% of the PM concentration in the valley. The study also identified influences on the WSV PM concentrations from traffic (7.4%), soil dust (3.4%), and secondary aerosols (4.8%). The results of this paper represent the first report on the chemical composition and source apportionment of PM in mountain valleys of northern Idaho and have been used to develop effective strategies to reduce the PM concentrations in the WSV. Moreover, this study provides detailed equations and methods in PM speciation, accounting for artifacts of the chemical analysis, Positive Matrix Factorization modeling, and emission inventory development, which can be used for source apportionment of severe air pollution in other regions.

Evaluating the success of public participation in integrated catchment management.

Recognition of the need to manage the water environment in more holistic ways has resulted in the global growth of Integrated Catchment Management (ICM). ICM is characterised by horizontal integration, encouraging interdisciplinary working between traditionally disparate management sectors, alongside vertical integration, characterised by the engagement of communities; central is the promotion of participatory governance and management decision-making. ICM has been translated into policy through, for example, the EU Water Framework Directive and at a national level by policies such as the Catchment Based Approach in England. Research exploring the implementation of these policies has reported success at a catchment level, but further research is required to explore practices of management at local level within catchments. This paper presents the findings of participatory research undertaken with a catchment partnership in the northeast of England to explore the integration of top-down policy translation with how local communities interact with management agencies at sub-catchment scale (a bottom-up perspective). The research found that supra-catchment scale drivers dominate the vertical interplay between management systems at more local levels. These drivers embed traditional practices of management, which establishes public participation as a barrier to delivery of top-down management objectives, resulting in practices that exclude communities and participatory movements at the local level. Although collaboration between agencies at the partnership scale offers a potential solution to overcoming these obstacles, the paper recommends changes to supra-catchment governance structures to encourage flexibility in developing local participatory movements as assets. Further research is necessary to develop new practices of management to integrate local people more effectively into the management process.

Adolescent self-control behavior predicts body weight through the life course: a prospective birth cohort study.

BACKGROUND: Weight gain has become one of the biggest issues for healthy aging in middle- and high-income countries. Self-control of emotional reward cues is an important behavioral factor for regulation of weight gain through voluntary diet control and physical activity. METHODS: We tested the associations between teacher-rated self-control at ages 13 and 15 years, and measured body mass index (BMI) between ages 15 and 60-64 years, controlling for confounding factors such as affective symptoms and cognition, using 3873 study members in the Medical Research Council National Survey of Health and Development, also known as the British 1946 birth cohort. RESULTS: Multivariable regression analysis after adjustment for all covariates showed that lower self-control was associated with higher BMI in all measure points (P<0.05). Multilevel modeling using a cubic model showed that there was an association between self-control and BMI at 15 years in females (male: BMI=-0.00 kg m(-2) per 1 s.d. on the self-control score (95% confidence interval (CI): -0.12 to 0.11), P =0.94; female: BMI=-0.27 (-0.42 to -0.11), P<0.001). The association became stronger with age in both sexes (BMI=-0.065 (-0.082 to -0.048), P<0.001; BMI=-0.036 (-0.057 to -0.015), P<0.001). By age 60-64 years, the association between self-control and BMI in men had increased to -0.70 (-0.96 to -0.44) and -0.67 (-1.04 to -0.30) in women. CONCLUSIONS: Lower adolescent self-control was associated with higher BMI through the life course, and this becomes stronger with age. Investigations to test whether intervention to self-control improves obesity are recommended.

Noncapped Alphavirus Genomic RNAs and Their Role during Infection.

UNLABELLED: Alphaviruses are enveloped positive-sense RNA viruses that exhibit a wide host range consisting of vertebrate and invertebrate species. Previously we have reported that the infectivity of Sindbis virus (SINV), the model alphavirus, was largely a function of the cell line producing the viral particles. Mammalian-cell-derived SINV particles, on average, exhibit a higher particle-to-PFU ratio than mosquito cell-derived SINV particles. Nevertheless, the outcome of nonproductive infection, the molecular traits that determine particle infectivity and the biological importance of noninfectious particles were, prior to this study, unknown. Here, we report that the incoming genomic RNAs of noninfectious SINV particles undergo rapid degradation following infection. Moreover, these studies have led to the identification of the absence of the 5' cap structure as a primary molecular determinant of particle infectivity. We show that the genomic RNAs of alphaviruses are not universally 5' capped, with a significant number of noncapped genomic RNA produced early in infection. The production of noncapped viral genomic RNAs is important to the establishment and maintenance of alphaviral infection. IMPORTANCE: This report is of importance to the field of virology for three reasons. First, these studies demonstrate that noncapped Sindbis virus particles are produced as a result of viral RNA synthesis. Second, this report is, to our knowledge, the first instance of the direct measurement of the half-life of an incoming genomic RNA from a positive-sense RNA virus. Third, these studies indicate that alphaviral infection is likely a concerted effort of infectious and noninfectious viral particles.

Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.

BACKGROUND/OBJECTIVES: There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age. SUBJECTS/METHODS: Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests. RESULTS: In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model. CONCLUSIONS: Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.

Irregular consumption of energy intake in meals is associated with a higher cardiometabolic risk in adults of a British birth cohort.

BACKGROUND/OBJECTIVES: A potential risk factor for cardiometabolic diseases is irregular or inconsistent eating, however, research on this topic is scarce. We aimed to study associations between irregular consumption of energy intake in meals and cardiometabolic risk factors. SUBJECT AND METHODS: Dietary intake data were derived from 5-day estimated diet diaries of 1768 participants of the National Survey of Health and Development. Energy intakes during predefined meals (breakfast, lunch, dinner, between meals) and daily totals were analyzed using a score for irregularity based on the deviation from the 5-day mean energy intake. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for having the metabolic syndrome or one of its components. Models were adjusted for sex, physical activity, socioeconomic status, marital status and smoking. RESULTS: Irregularity scores of energy intake ranged from 0-160 and were highest for between meals. An increased risk of the metabolic syndrome was associated with more irregular energy intake during breakfast (OR=1.34 (0.99, 1.81); P trend=0.04) and between meals (OR=1.36 (1.01, 1.85); P trend=0.04). Moreover, increased waist circumference was associated with irregular energy intake during breakfast (OR=1.90 (1.47, 2.45); P trend <0.01), evening meal (OR=1.36 (1.06, 1.75); P trend=0.02) and daily total (OR=1.34 (1.04, 1.72); P trend=0.01). No significant associations were found for the other components of the metabolic syndrome. CONCLUSIONS: Individuals with a more irregular intake of energy, especially during breakfast and between meals, appeared to have an increased cardiometabolic risk.

Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development.

OBJECTIVE: High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. SUBJECTS: A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60-64 years. METHODS: Associations of birth weight and standardised weight and height (0-2 (weight only), 2-4, 4-7, 7-11, 11-15, 15-20 years) gain velocities with outcome measures were examined. RESULTS: Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60-64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. CONCLUSION: Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios.

Radiation release at the nation's only operating deep geological repository--an independent monitoring perspective.

Recent incidents at the nation's only operating deep geologic nuclear waste repository, the Waste Isolation Pilot Plant (WIPP), resulted in the release of americium and plutonium from one or more defense-related transuranic (TRU) waste containers into the environment. WIPP is a U.S. Department of Energy mined geologic repository that has been in operation since March, 1999. Over 85,000 m3 of waste in various vented payload containers have been emplaced in the repository. The primary radionuclides within the disposed waste are 239+240Pu and 241Am, which account for more than 99% of the total TRU radioactivity disposed and scheduled for disposal in the repository. For the first time in its 15 years of operation, there was an airborne radiation release from the WIPP at approximately 11:30 PM Mountain Standard Time (MST) on Friday, February 14, 2014. The radiation release was likely caused by a chemical reaction inside a TRU waste drum that contained nitrate salts and organic sorbent materials. In a recent news release, DOE announced that photos taken of the waste underground showed evidence of heat and gas pressure resulting in a deformed lid, in material expelled through that deformation, and in melted plastic and rubber and polyethylene in the vicinity of that drum. Recent entries into underground Panel 7 have confirmed that at least one waste drum containing a nitrate salt bearing waste stream from Los Alamos National Laboratory was breached underground and was the most likely source of the release. Further investigation is underway to determine if other containers contributed to the release. Air monitoring across the WIPP site intensified following the first reports of radiation detection underground to ascertain whether or not there were releases to the ground surface. Independent analytical results of air filters from sampling stations on and near the WIPP facility have been released by us at the Carlsbad Environmental Monitoring & Research Center and confirmed trace amounts of 241Am and 239+240Pu, at ratios reflecting the suspect waste stream. The highest activity detected offsite was 115.2 µBq/m3 for 241Am and 10.2 µBq/m3 for 239+240 Pu. These concentrations in air were very small, localized, and below any level of public health or environmental concern.

Anthropogenic, biogenic, and photochemical influences on surface formaldehyde and its significant decadal (2006-2017) decrease in the Lewiston-Clarkston valley of the northwestern United States.

Formaldehyde (HCHO) is a key carcinogen and plays an important role in atmospheric chemistry. Both field measurements and Positive Matrix Factorization (PMF) modeling have been employed to investigate the concentrations and sources of HCHO in the Lewiston-Clarkston (LC) valley of the mountainous northwestern U.S. Different instruments were deployed to measure surface formaldehyde and other related compounds in July of 2016 and 2017. The measurements reveal that the average HCHO concentrations have significantly decreased to 2-5 ppb in the LC valley in comparison to its levels (10-20 ppb) observed in July 2006. This discovery with surface measurements deserves attention given that satellite retrievals showed an increasing long-term trend from 2005 to 2014 in total vertical column density of HCHO in the region, suggesting that satellite instruments may not adequately resolve small valleys in the mountainous region. Our PMF modeling identified four major sources of HCHO in the valley: (1) emissions from a local paper mill, (2) secondary formation and background, (3) biogenic sources, and (4) traffic. This study reveals that the emissions from the paper mill cause high HCHO spikes (6-19 ppb) in the early morning. It is found that biogenic volatile organic compounds (VOCs) in the area are influenced by national forests surrounding the region (e.g., Nez Perce-Clearwater, Umatilla, Wallowa-Whitman, and Idaho Panhandle National Forests). The results provide useful information for developing strategies to control HCHO levels and have implications for future HCHO studies in atmospheric chemistry, which affects secondary aerosols and ozone formation.

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals.

AIMS/HYPOTHESIS: Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. METHODS: We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. RESULTS: We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 × 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 × 10(-3)), independent of BMI and/or WHR. CONCLUSIONS/INTERPRETATION: These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.

Time-of-day and nutrient composition of eating occasions: prospective association with the metabolic syndrome in the 1946 British birth cohort.

BACKGROUND: Diet is a key modifiable factor in the prevention and treatment of the metabolic syndrome. However, few studies have examined the prospective association between time-of-day of nutrient intake and the metabolic syndrome. OBJECTIVE: To examine the association between time-of-day and nutrient composition of eating occasions and the long-term development of metabolic syndrome in the Medical Research Council (MRC) National Survey of Health and Development (NSHD; 1946 British birth cohort). METHODS: The analysis comprised 1488 survey members who completed at least 3 days of estimated diet records at age 43 years (1989) and for whom data on metabolic syndrome at age 53 years (1999) were available. Dietary records were divided into seven meal slots: breakfast, mid-morning, lunch, mid-afternoon, dinner, late evening and extras. Metabolic syndrome was defined by the criteria of the adult treatment panel (ATPIII8), and was modified to include glycosylated haemoglobin instead of fasting glucose. Associations between time-of-day of nutrient intake at age 43 years and prevalence of metabolic syndrome at age 53 years were assessed using multivariate nutrient density logistic models after adjustment for sex, social class, smoking status, region, alcohol intake and recreational physical activity. RESULTS: There were 390 cases of metabolic syndrome at age 53 years. Substituting 5% of energy from carbohydrate for a similar amount of energy from fat at breakfast (odds ratio=0.93; 95% confidence interval=0.89-0.98; P=0.002) and mid-morning at age 43 years (odds ratio=0.96; 95% confidence interval=0.93-0.99; P=0.011) was associated with lower odds of the metabolic syndrome at age 53 years. Carbohydrate intake at breakfast or mid-morning was particularly protective against abdominal obesity (P0.001). Increasing carbohydrate intake at breakfast while simultaneously decreasing fat intake was also negatively related to triacylglycerols (P0.001). CONCLUSIONS: Increasing carbohydrate intake in the morning while simultaneously reducing fat intake could be protective against long-term development of the metabolic syndrome and its components.