Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

Litter on the seafloor along the African coast and in the Bay of Bengal based on trawl bycatches from 2011 to 2020.

We present the occurrence of seafloor litter on the coast of Africa and in the Bay of Bengal based on records from the EAF-NANSEN Programme in 2011 to 2020. Litter bycatch records from 534 bottom trawls were standardized to km2 before analysis. Three percent of the records indicated areas of high littering and the highest densities occurred from 100 to 300 m in depth and 50 to 100 km from the coast. Littering was lower in the Indian Ocean compared to Atlantic Africa. Plastic objects and fishing gear dominated the recorded items (47 % and 22 % respectively) but, regional differences were pronounced. Plastic dominated North Atlantic and East African records (58 % and 80 % respectively) and fishing gear dominated (69 %) in South Atlantic Africa while records from the Bay of Bengal were a mix of categories. The relation between littering and population density, marine industry, major cities, and rivers is discussed.

Mortality and Urological Complications After Open Groin Hernia Repair in Local, General, and Regional Anesthesia: A Nationwide Linked Register Study.

BACKGROUND AND AIMS: The choice of anesthesia method may influence mortality and postoperative urological complications after open groin hernia repair. We aimed to investigate the association between type of anesthesia and incidence of urinary retention, urethral stricture, prostate surgery, and 1-year mortality after open groin hernia repair. MATERIALS AND METHODS: Data were linked from the Danish Hernia Database, the national patient register, and the register of causes of death. We investigated data on male adult patients receiving open groin hernia repair from 1999 to 2013 with either local anesthesia, regional anesthesia, or general anesthesia. In relation to the type of anesthesia, we compared mortality and urological complications up to 1 year postoperatively. We adjusted for covariates in a logistic regression assessing urological complications and with the Cox regression assessing mortality. RESULTS: We included 113,069 open groin hernia repairs in local anesthesia, regional anesthesia, or general anesthesia. The risk of urinary retention adjusted for covariates was higher after both general anesthesia (adjusted odds ratio = 1.64, 95% confidence interval = 1.05-2.57, p = 0.031) and regional anesthesia (odds ratio = 2.99, 95% confidence interval = 1.67-5.34, p < 0.0005) compared with local anesthesia. The adjusted risk of prostate surgery was also higher for both general anesthesia (odds ratio = 1.58, 95% confidence interval = 1.23-2.03, p < 0.0005) and regional anesthesia (odds ratio = 1.90, 95% confidence interval = 1.40-2.58, p < 0.0005) compared with local anesthesia. Type of anesthesia did not influence 1-year mortality or the risk for urethral stricture. CONCLUSION: Patients undergoing open groin hernia repair in local anesthesia experience the lowest rate of urological complications and have equally low mortality compared with patients undergoing repair in general anesthesia or regional anesthesia.

Inequality, Familial Aggregation, and Risk Prediction of Caries in Siblings.

INTRODUCTION: Social and family conditions are likely of great importance to dental health; however, limited evidence of familial aggregation of caries among adolescent siblings exists. Moreover, social and family-level factors have never been evaluated as isolated caries predictors at the individual level. OBJECTIVES: The objectives were to evaluate socioeconomic patterning of caries among siblings, assess sibling-specific aggregation of caries within families, and examine if such aggregation differed by parental socioeconomic position (SEP). We also evaluated the discriminant ability of sibling caries, SEP, and other social and familial factors in predicting caries in cosiblings. METHODS: This nationwide register-based study included all 15-y-olds in Denmark in 2003 (index siblings) and their biological siblings born within ±3 y (cosiblings). Clinical and sociodemographic data for each subject were compiled from Danish national dental, social, and population registers. Caries was measured by the decayed, missing, and filled tooth surfaces (DMFS) index. Predictors included SEP (parental education, income, and occupational social class), gender, birth order, immigration status, and household type. Adjusted SEP-caries associations were estimated using negative binomial regression. Familial aggregation was evaluated using adjusted pairwise odds ratios from alternating logistic regressions. Caries prediction was based on classification and regression tree (CART) analyses. RESULTS: The study included 23,847 sibling pairs (n = 47,694). Socioeconomic patterning of caries was similar among the index and cosiblings with significant graded SEP-caries associations. Significant sibling-specific aggregation of caries was observed; cosiblings of caries-affected index siblings had odds of having caries 3.9 times (95% confidence interval: 3.65-4.18) as high as that of cosiblings with caries-free index siblings. This sibling similarity was stronger in socioeconomically disadvantaged families (adjusted pairwise odds ratios: 3.08-5.47). CART revealed index sibling caries as the single most important caries predictor, with caries predicted in ≥84% of cosiblings of adolescents with ≥3 carious tooth surfaces. CONCLUSIONS: Caries in a sibling should prompt preventive family-based approaches targeting cosiblings. KNOWLEDGE TRANSFER STATEMENT: This study revealed significant socioeconomic patterning of caries in adolescent siblings. Prediction modeling indicated that the single most important caries predictor among cosiblings was index sibling caries. Information on sibling caries level should be routinely combined with clinical evaluation to identify children at risk. Moreover, information on social and family conditions should be used to target prevention and health promotion at the school or municipal level. These approaches could possibly contribute to reducing the existing caries inequalities.

Risk of incarceration in children with inguinal hernia: a systematic review.

BACKGROUND: Surgical repair is recommended for all children with inguinal hernia due to fear of incarceration. The aim of this study was to assess the risk of incarceration and strangulation of inguinal hernias in children treated with delayed surgery or no surgery. METHODS: Systematic searches were conducted in three databases. We included studies reporting on children with inguinal hernia, with the majority ≤ 10 years old. The interventions were non-acute inguinal hernia surgery or no surgery. The main outcomes were incarceration and strangulation. Secondary outcomes were postoperative complications. Randomized controlled trials, non-randomized controlled trials, and observational studies were included. RESULTS: We included 22 studies with 14,959 children. All studies reported on elective repairs. None of the studies specifically reported on watchful waiting. Of the studies reporting wait time as mean or median, the median wait time was 46 days (range 1-552). The crude incarceration rate across the included studies was 7% for all children and 11% for preterm children. The testicular atrophy rate was 1% and the recurrence rate was 1%. CONCLUSIONS: The risk of incarceration in children awaiting inguinal hernia surgery is substantial. In general, we cannot support delaying surgery unnecessarily. However, there may be benefits of delaying surgery in individual cases. In such cases, the surgeon should assess if the benefits may overrule the risk of incarceration.

The association between seasonal influenza-like illness cases and foetal death: a time series analysis.

It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.

Criterion validity of the Physical Activity Scale (PAS2) in Danish adults.

BACKGROUND: The Physical Activity Scale (PAS2) was developed to measure physical activity (PA) during work, transportation and leisure time, in the Danish adult population. The objective of this study was to assess the criterion validity of PAS2 against a combined accelerometer and heart rate monitor in Danish adults and to investigate if the criterion validity differed by socio-demographic factors and body mass index. METHOD: A total of 330 Danish adults (mean age = 46.7 years, 38.5% men) participating in the Health2008 study completed the PAS2 questionnaire and wore a combined accelerometer and heart rate sensor for seven days. Average daily estimates from PAS2 were categorised into time spent in sedentary behaviour, light PA, moderate PA and vigorous PA and were compared to the objective measures. RESULTS: PAS2 accounted for 19.5 hours/day on average. Time spent in sedentary behaviour, light and moderate-intensity PA was weakly correlated with objective data (polychoric correlation coefficients (PCC): 0.18-0.20), whereas vigorous intensity PA was moderately correlated (PCC: 0.54, p = 0.04). Mean bias was -2.3 hours/day (95% limits of agreement (LoA): -9.04 to 4.34) for sedentary behaviour, 1.68 hours/day (LoA: 8.02 to -4.62) for light activity, 0.55 hours/day (LoA: 3.37 to -2.26) for moderate activity and 0.12 hours/day (LoA: 0.57 to 0.33) for vigorous activity. Criterion validity was lower in women, in participants who were above 40 years, overweight, had short education and were unemployed. CONCLUSIONS: PAS2 overestimated time spent on light, moderate and vigorous intensity PA and underestimated time spent on sedentary behaviour. Validity differed by key socio-demographic characteristics.

Differences in biological traits composition of benthic assemblages between unimpacted habitats.

There is an implicit requirement under contemporary policy drivers to understand the characteristics of benthic communities under anthropogenically-unimpacted scenarios. We used a trait-based approach on a large dataset from across the European shelf to determine how functional characteristics of unimpacted benthic assemblages vary between different sedimentary habitats. Assemblages in deep, muddy environments unaffected by anthropogenic disturbance show increased proportions of downward conveyors and surface deposit-feeders, while burrowing, diffusive mixing, scavenging and predation traits assume greater numerical proportions in shallower habitats. Deep, coarser sediments are numerically more dominated by sessile, upward conveyors and suspension feeders. In contrast, unimpacted assemblages of coarse sediments in shallower regions are proportionally dominated by the diffusive mixers, burrowers, scavengers and predators. Finally, assemblages of gravelly sediments exhibit a relatively greater numerical dominance of non-bioturbators and asexual reproducers. These findings may be used to form the basis of ranking habitats along a functional sensitivity gradient.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

AIMS: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). METHODS: Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. RESULTS: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). CONCLUSIONS: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18-30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen's d 0.60-1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = -0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

Erratum to: Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

[This corrects the article DOI: 10.1186/s40064-016-2862-5.].

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent.

AIM: Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults. METHODS: The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 µg/24 µg, adolescents and adults: 400 µg/24 µg) via DPI. RESULTS: The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001). CONCLUSION: The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries.

OBJECTIVE: To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). METHODS: Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). RESULTS: There were 9,028,802 deliveries (3,031,399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. CONCLUSION: Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia.

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study.

STUDY QUESTION: Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? SUMMARY ANSWER: Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies and external causes. WHAT IS KNOWN ALREADY: Advanced paternal age has previously been associated with adverse reproductive outcomes and some long-term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION: A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were followed until 31 December 2009. The children were censored on date of turning 5 years, date of death or date of emigration, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from population-covering registers from Statistics Denmark including the Integrated Database for Labour Market Research, the Medical Birth Registry and the Registry of Causes of Death was linked using the unique civil registry number. Hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of under-five mortality. The effect of paternal age was examined using restricted cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with children born to fathers aged 30-34 years, a statistically significant excess risk was found for children born to fathers aged 40-44 years [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR: 1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI: 1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65 (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes. LIMITATIONS, REASONS FOR CAUTION: Specific causes of death might be misclassified; however, this is not likely to be dependent on paternal age. In some cases, the biological father may differ from the father registered. This misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE FINDINGS: The excess risk of mortality among children born to older fathers is in accordance with the literature. The association needs further attention as it can provide valuable knowledge of the etiology of genetic diseases. Also, the association could become of greater importance in the future if the proportion of fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S): None.

Suppression of Cucumber Powdery Mildew by Supplemental UV-B Radiation in Greenhouses Can be Augmented or Reduced by Background Radiation Quality.

This study demonstrates that the spectral quality of radiation sources applied with ultraviolet-B (UV-B; background radiation) affects the suppression of cucumber powdery mildew (Podosphaera xanthii) by UV-B. Suppression provided by daily UV-B exposure of 1 W/m2 for 10 min was greatest in the presence of red light or by a complete lack of background light, and powdery mildew suppression was least in the presence of ultraviolet-A (UV-A) or blue radiation compared with plants exposed only to 16 h of daily natural light supplemented with high-pressure sodium lamps that supply broad-spectrum radiation with peaks in the yellow-orange region. Exposure of powdery mildew-inoculated plants to supplemental red light without UV-B, beginning at the end of the daylight period, also reduced disease severity; however, supplemental blue light applied in the same fashion had no effect. Daily application of UV-B at 1 W/m2 beginning on the day of inoculation significantly reduced the severity of powdery mildew to 15% compared with 100% severity on control plants. Maximum suppression of powdery mildew was observed following 15 min of exposure to UV-B (1.1% severity compared with 100% severity on control plants) but exposure time had to be limited to 5 to 10 min to reduce phytotoxicity. There was no additional disease suppression when plants were exposed to UV-B beginning 2 days prior to inoculation compared with plants exposed to UV-B beginning on the day of inoculation. UV-B inhibited germination, infection, colony expansion, and sporulation of P. xanthii. The results suggest that efficacy of UV-B treatments, alone or in combination with red light, against P. xanthii can be enhanced by exposure of inoculated plants to these wavelengths of radiation during the night, thereby circumventing the counteracting effects of blue light and UV-A radiation. The effect of UV-B on powdery mildew seemed to be directly upon the pathogen, rather than induced resistance of the host. Night exposure of plants to 5 to 10 min of UV-B at 1 W/m2 and inexpensive, spectral-specific, light-emitting diodes may provide additional tools to suppress powdery mildews of diverse greenhouse crops.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

Restorative proctocolectomy for ulcerative colitis: development and validation of a new scoring system for pouch dysfunction and quality of life.

AIM: The purpose of this study was to develop and validate a pouch dysfunction score that could identify the aspects of function which have the greatest impact on quality of life as perceived by the patient. METHOD: All (n = 1757) patients having restorative proctocolectomy in Denmark between 1980 and 2010 were identified. Of these, 1229 were available for study and were sent a questionnaire on bowel function and quality of life (QoL) designed specifically for this study. Function was correlated with QoL in a multivariate model using ordinal logistic regression with QoL as a dependent variable. The pouch dysfunction score was developed from a randomly selected half of the study population and the validity was tested on the other half. RESULTS: 1047 (85%) patients returned the questionnaire. On multivariate analysis, the symptom domains of 'incomplete emptying', 'severity of urgency', 'number of bowel movements/24 h', 'major incontinence' and 'use of anti-diarrhoeal medication' were associated with reduced QoL. The score was divided into three categories including 'none', 'minor' and 'some/major' pouch dysfunction. The corresponding coefficients gave the score a range from 0 to 7.5. There was a highly significant difference (P < 0.001) in score between the categories. The area under the receiver operating curve was 0.81. CONCLUSION: Urgency, incomplete emptying, number of bowel movements/24 h, major incontinence and use of anti-diarrhoeal medication have a major impact on QoL. There was a high accuracy for the score, demonstrating its potential clinical usefulness in relating symptoms to QoL.

VEGFA variants are associated with pre-school lung function, but not neonatal lung function.

BACKGROUND: Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood. METHODS: We analysed 13 SNPs in the VEGFA gene in 411 children from the COPSAC2000 high-risk birth cohort. Asthma was diagnosed prospectively, and lung function measurements were obtained at birth and 6 years of age. Plasma VEGF levels were measured at 18 months of age. We used a Bonferroni adjusted significance level. Findings were replicated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort at age 8. RESULTS: At age six, three SNPs from the same linkage block were associated with FEV1 (rs699947, P = 1.31E-05), independent of asthma, and there were suggestive associations between FEV1/FVC ratio and rs833052 and maximal mid-expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV1 and rs699947 and significant meta-analysis result. SNPs upstream and nearby rs699947 were nominally associated with VEGF plasma levels. VEGF levels were not associated with asthmatic symptoms or lung function measures. CONCLUSIONS AND CLINICAL RELEVANCE: VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.