Effectiveness and cost effectiveness of a stress management training for leaders of small and medium sized enterprises - study protocol for a randomized controlled-trial.

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).

Long-term functional results after excisional haemorrhoidectomy.

AIM: The aim of this work was to perform a long-term evaluation of a randomized trial focusing on functional aspects after excisional haemorrhoidectomy with a minimum follow-up of 9 years. METHOD: A questionnaire-based study including patients operated on for haemorrhoids in Sweden between 1999 and 2003. A total of 225 patients were randomized to Milligan's or Ferguson's operation. Twenty-six patients had died and 151 (76%) participated after a median follow-up of 10.7 years (range 9.2-12.6 years). RESULTS: Seventy-seven patients were in the Milligan group and 74 in the Ferguson group. Forty-eight (32%) reported recurrence. Anal bleeding was reported in 80% at baseline but in 28% at long-term follow-up (P < 0.0001). At baseline, 49% had spontaneous anal pain and 25% pain at defaecation. At follow-up, these figures were 17% and 11%. At follow-up, 19% described a sense of anal stenosis. At baseline, soiling was reported in 51% but in 20% at long-term follow-up (P < 0.001). Nineteen per cent used pads preoperatively and 6% at follow-up (P < 0.0001). Straining at defaecation was reported by 35% at baseline. At follow-up, this figure was 25% (P = 0.055). CONCLUSION: Symptoms associated with haemorrhoids were reduced at long-term follow-up. The most common problems were perceived recurrence and a sense of anal stenosis.

Thickness uniformity measurements and damage threshold tests of large-area GaAs/AlGaAs crystalline coatings for precision interferometry.

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

Effect of Histophilus somni on Heart and Brain Microvascular Endothelial Cells.

Histophilus somni is a pathogenic gram-negative bacterium responsible for pneumonia and septicemia in cattle. Sequelae include infectious thrombotic meningoencephalitis (ITME), myocarditis, arthritis, and abortion. These syndromes are associated with widespread vasculitis and thrombosis, implicating a role for endothelium in pathogenesis. Histopathologic and immunohistochemical investigation of 10 natural cases of bovine H. somni myocarditis and 1 case of ITME revealed intravascular H. somni in large biofilm-like aggregates adherent to the luminal surface of microvascular endothelium. Ultrastructurally, bacterial communities were extracellular and closely associated with degenerating or contracted endothelial cells. Histophilus somni was identified by bacterial culture and/or immunohistochemistry. Western blots of the bacterial isolates revealed that they expressed the immunodominant protective 40 kDa OMP and immunoglobulin-binding protein A (IbpA) antigens. The latter is a large surface antigen and shed fibrillar antigen with multiple domains. The cytotoxic DR2Fic domain of IbpA was conserved as demonstrated by polymerase chain reaction. Treatment of endothelial cells in vitro with IbpA in crude culture supernatants or purified recombinant GST-IbpA DR2Fic (rDR2) cytotoxin induced retraction of cultured bovine brain microvascular endothelial cells. By contrast, no retraction of bovine endothelium was induced by mutant rDR2H/A with an inactive Fic motif or by a GST control, indicating that the cytotoxic DR2Fic motif plays an important role in endothelial cell retraction in vasculitis. The formation of biofilm-like aggregates by H. somni on bovine microvascular endothelium may be fundamental to its pathogenesis in heart and brain.

Early lactation production, health, and welfare characteristics of cows selected for extended lactation.

Some cows are able to achieve relatively high milk yields during extended lactations beyond 305 d in milk, and farmers may be able to use this potential by selecting the most suitable cows for an extended lactation. However, the decision to postpone insemination has to rely on information available in early lactation. The main objectives of this study were, therefore, to assess the association between the information available in early lactation and the relative milk production of cows on extended lactation, and to investigate if this information can be used to differentiate time of first insemination between cows. Data came from 4 Danish private herds practicing extended lactation in which some cows are selected to have a delayed time of planned first insemination. Average herd size varied from 93 to 157 cows, and milk yield varied from 7,842 to 12,315 kg of energy-corrected milk (ECM) per cow per year across herds. The analysis was based on 422 completed extended lactations (427 ± 87 d), and each lactation was assigned to 1 of 3 (low, medium, and high) milk performance groups (MPG) within parity group within herd based on a standardized lactation yield. For cows in the high MPG, peak ECM yield, and ECM yield at dry off were significantly greater, the relative reduction in milk yield between 60 and 305 d in milk was significantly smaller, and a smaller proportion had a body condition score (scale: 1-5) at dry off of 3.5 or greater compared with cows in low MPG. Previous lactation days in milk at peak ECM yield and ECM yield at dry off were higher, the relative reduction in milk yield between 60 and 305 d in milk was smaller, and the number of inseminations per conception was higher for multiparous cows in high MPG compared with low. Current lactation ECM yield at second and third milk recording were greater for cows in high MPG compared with low. A principal component analysis indicated that variables related to fertility, diseases, and milk yield explained most of the total variation between primiparous cows, whereas variables related to milk yield, fertility, and days in milk at peak yield were the most dominating for multiparous cows. Our study indicated that milk yields in previous lactation and at second and third milk recording correlate well with milk production potential, and therefore, may be promising indicators when selecting the most suitable cows for extended lactation.

Effect of calving interval and parity on milk yield per feeding day in Danish commercial dairy herds.

The idea of managing cows for extended lactations rather than lactations of the traditional length of 1 yr primarily arose from observations of increasing problems with infertility and cows being dried off with high milk yields. However, it is vital for the success of extended lactation practices that cows are able to maintain milk yield per feeding day when the length of the calving interval (CInt) is increased. Milk yield per feeding day is defined as the cumulated lactation milk yield divided by the sum of days between 2 consecutive calvings. The main objective of this study was to investigate the milk production of cows managed for lactations of different lengths, and the primary aim was to investigate the relationship between CInt, parity, and milk yield. Five measurements of milk yield were used: energy-corrected milk (ECM) yield per feeding day, ECM yield per lactating day, cumulative ECM yield during the first 305 d of lactation, as well as ECM yield per day during early and late lactation. The analyses were based on a total of 1,379 completed lactations from cows calving between January 2007 and May 2013 in 4 Danish commercial dairy herds managed for extended lactation for several years. Herd-average CInt length ranged from 414 to 521 d. The herds had Holstein, Jersey, or crosses between Holstein, Jersey, and Red Danish cows with average milk yields ranging from 7,644 to 11,286 kg of ECM per cow per year. A significant effect of the CInt was noted on all 5 measurements of milk yield, and this effect interacted with parity for ECM per feeding day, ECM per lactating day and ECM per day during late lactation. The results showed that cows were at least able to produce equivalent ECM per feeding day with increasing CInt, and that first- and second-parity cows maintained ECM per lactating day. Cows with a CInt between 17 and 19 mo produced 476 kg of ECM more during the first 305 d compared with cows with a CInt of less than 13 mo. Furthermore, early-lactation ECM yield was greater for all cows and late-lactation ECM yield was less for second-parity and older cows when undergoing an extended compared with a shorter lactation. Increasing CInt increased the dry period length with 3 to 5d. In conclusion, the group of cows with longer CInt were able to produce at least equivalent amounts of ECM per feeding day when the CInt was up to 17 to 19 mo on these 4 commercial dairy farms.

Effects of an individual weight-adjusted feeding strategy in early lactation on milk production of Holstein cows during extended lactation.

Extending lactation by voluntarily delaying rebreeding aims to improve fertility and milk production in the modern dairy cow. Previous studies have shown that increased energy concentrations in the ration induced greater total milk yield and lactation persistency defined by the duration and the shape of the lactation curve. In this paper, we hypothesized that increasing the supply of energy during the early lactation mobilization period would have a positive carryover effect on milk production during extended lactation. A total of 53 Holstein cows completed a 16-mo lactation, including 30% primiparous cows. The cows were divided into 2 feeding strategies: half of the cows received a high-energy density diet (HD) in early lactation followed by a lower-energy density diet (LD; strategy HD-LD). The change in diet was defined individually after 42 d of lactation, and when the live weight (LW) gain of the cow was ≥ 0 based on a 5-d average. The other half of the cows were fed the LD diet during the entire lactation (strategy LD-LD). Both groups received 3 kg of concentrates per day during milking. Weekly milk composition (fat, protein, lactose, and somatic cells), daily milk production, daily feed intake, daily LW, and body condition score every second week were recorded. The fda package of R was used to model the curves of these different variables for the 53 cows that had a lactation over 400 d. The fitted values of these curves and the associated slopes were then compared for parity and treatment effects using a linear mixed-effects model. The HD-LD and LD-LD cows had a similar length of lactation (461 ± 7 d). The HD diet reduced the intensity of the mobilization period and increased the milk production of the multiparous cows in early lactation compared with the cows fed the LD diet. The primiparous cows used the extra energy to grow and gain weight, but not to produce more milk. After the shift in diet, the treatment had little short-term carryover effect on milk yield or LW, but it affected the slopes of some curves. From 0 to 50 d from shift, milk fat content of the LD-LD cows decreased faster than that of the HD-LD cows whereas milk lactose increased. From 250 to 350 d from shift, the energy-corrected milk decreased faster for the HD-LD cows than for the LD-LD cows. The lactose content in milk decreased faster for the LD-LD cows than for the HD-LD cows, and the fat content in milk was significantly higher for the primiparous HD-LD than for the primiparous LD-LD cows. In conclusion, the supply of extra energy during the mobilization period had a 300-d negative carryover effect on lactation persistency.

Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.

BACKGROUND AND AIMS: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. RESULTS: Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. CONCLUSION: This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

Lung function changes in mice sensitized to ammonium hexachloroplatinate.

Occupational exposure to halogenated platinum salts can trigger the development of asthma. The risk to the general population that may result from the use of platinum in catalytic converters and its emerging use as a diesel fuel additive is unclear. To investigate pulmonary responses to platinum, we developed a mouse model of platinum hypersensitivity. Mice were sensitized through application of ammonium hexachloroplatinate (AHCP) to the shaved back on days 0, 5 and 19, and to each ear on days 10, 11 and 12. On days 24 and 29, mice were challenged by oropharyngeal aspiration with AHCP in saline. Before and immediately after challenge, pulmonary responses were assessed using whole body plethysmography (WBP). A dose-dependent increase in immediate responses was observed in AHCP-sensitized and challenged mice. On days 26 and 31, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Lymph node cell counts indicate a proliferative response in lymph nodes draining the sites of application. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 5% eosinophils compared to less than 0.5% in non-sensitized mice (p < 0.05); significant increases in total serum immunoglobulin E were observed for all sensitized mice. Although a second airway challenge on day 29 affected some results, only one airway challenge was needed to observe changes in lung function.

A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype.

BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE: Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. RESULTS: One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. CONCLUSION: We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.

Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state.

OBJECTIVE: Mesenchymal stem cells (MSCs) are a promising cell type for the repair of damaged cartilage in osteoarthritis (OA). However, OA synovial fluid and factors secreted by synovium impede chondrogenic differentiation of MSCs, and the mechanism responsible for this effect remains unclear. In this study, we sought to investigate whether M1 and M2 synovial macrophages can contribute to the inhibition of MSC chondrogenesis. DESIGN: The constitution of synovial macrophage subsets was analysed by immunohistochemical staining of human OA synovium sections for CD86 (M1 marker) and CD206 (M2 marker). To assess the effect of synovial macrophages on chondrogenesis, collagen type II (COL2) and aggrecan (ACAN) gene expression were compared between MSCs undergoing chondrogenic differentiation in medium conditioned (CM) by human OA synovial explants, human synovial macrophages and fibroblasts, or peripheral blood derived primary human monocytes differentiated towards an M1 or M2 phenotype. RESULTS: OA synovium contained both M1 and M2 macrophages. Medium conditioned by synovial macrophages (CD45 + plastic adherent cells) down-regulated chondrogenic gene expression by MSCs. Additionally, CM of M1 polarised monocytes significantly decreased COL2 and ACAN gene expression by MSCs; this effect was not observed for treatment with CM of M2 polarised monocytes. CONCLUSION: MSC chondrogenesis is inhibited by OA synovium CM through factors secreted by synovial macrophages and our findings suggest that M1 polarised subsets are potential mediators of this anti-chondrogenic effect. Modulation of macrophage phenotype may serve as a beneficial strategy to maximise the potential of MSCs for efficient cartilage repair.

Diabetes in people with an intellectual disability: a systematic review of prevalence, incidence and impact.

AIMS: To establish the prevalence and incidence of type 1 and type 2 diabetes in people with an intellectual and developmental disability and determine their impact on health and well-being and to appraise the evidence available to inform good practice in diabetes management for people with intellectual and developmental disabilities. METHODS: We conducted separate searches of multiple databases (EMBASE, CINAHL, MEDLINE, PsycINFO, SCOPUS, Web of Science, PUBMED and Cochrane Library) to find relevant articles. RESULTS: A total of 13 studies were identified: 13 addressed the prevalence of diabetes in people with intellectual and developmental disability, three addressed the impact of diabetes on their health and well-being and three addressed the management of diabetes. The prevalence of diabetes in people with intellectual and developmental disability remains uncertain, and the incidence of diabetes in this group of people is unknown. There is some evidence to support the assertion that people with intellectual and developmental disability might be at greater risk of diabetes than the general population. Overall, the quality of the evidence on which to base prevention and management strategies is variable. CONCLUSIONS: There is a paucity of research focusing on the prevalence, incidence and impact of diabetes among people with intellectual and developmental disability. Further research is needed to inform policy and practice in this area and, in particular, work is needed to develop methodologies, evaluation tools, educational resources and diabetes care support services appropriate to the needs of people with intellectual and developmental disability.

Combination of immunoglobulins and natural killer cells in the context of CMV and EBV infection.

Cytomegalovirus (CMV)-specific hyperimmunoglobulin (CMV-HIG) is used to treat and prevent CMV infection in immunocompromised patients, and anti-CD20 monoclonal antibody is successfully used in the treatment for post-transplant lymphoproliferative disease caused by Epstein-Barr virus (EBV). Two immunological approaches have been suggested to further improve the control of viral reproduction in patients with active disease: first, the use of monoclonal antibodies with specificity against viral epitopes and second, coadministration of cells with the capacity to promote antibody-dependent cell-mediated cytotoxicity. Here, we have evaluated the effectiveness of these strategies in vitro (alone and in combination) with neutralization and cytotoxicity assays. Our results indicate that monoclonal antibodies (in particular SM5-1) can be as effective as CMV-HIG in neutralizing-cell-free CMV. Moreover, our data indicate that antibody-mediated elimination (either by moAb or by HIG) of EBV-infected cells can be significantly enhanced by NK cells. Using human NK cells that have been purified, cultured and expanded under GMP conditions, we were able to demonstrate that the combination of NK cells and antibodies could represent a feasible and highly effective clinical approach to achieve control of EBV infections. Especially in leukopenic patients with low numbers of ADCC-promoting cells, the combination of adoptively transferred NK cells and antiviral antibodies offers a promising strategy that should be tested in clinical trials.

Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

Efficacy of LIFT for recurrent anal fistula.

AIM: Ligation of the intersphincteric fistula tract (LIFT) is a novel sphincter-preserving technique for anal fistula. This pilot study was designed to evaluate the results in patients with a recurrent fistula. METHOD: Seventeen patients [nine men; median age 49 (range, 30-76) years] with a recurrent trans-sphincteric fistula were treated with a LIFT procedure between June 2008 and February 2011. All were followed prospectively for a median of 16 (range, 5-27) weeks with clinical examination. Fifteen followed for 13.5 (range, 8-26) months by clinical examination also had three-dimensional (3D) anal ultrasound. RESULTS: The duration of the procedure was 35 (range, 18-70) min. One patient developed a small local haematoma and one had a subcutaneous infection, but otherwise there was no morbidity. At follow up, 11 (65%) patients had a successful closure, two (12%) had a remaining sinus and four (23%) had a persistent fistula. The incidence of persistent or recurrent fistulae at 13.5 months was six (40%) of 15 patients. No de novo faecal incontinence was reported. CONCLUSION: LIFT is a safe procedure for patients with recurrent anal fistula, with healing at short-term and medium-term follow-up comparable with or superior to that of other sphincter-preserving techniques. Larger studies with a longer follow up are needed to define the ultimate role of LIFT in patients with recurrence.

Comparison of three methods of cervical measurement in the first trimester: single-line, two-line, and tracing.

OBJECTIVES: To compare three methods of cervical length measurements using ultrasound in the first trimester: single-line, two-line, and tracing. METHODS: Images appropriate for cervical length measurements were obtained using transvaginal ultrasound between 11 + 0 and 13 + 6 weeks' gestation. The cervix was measured on stored images using three methods: a single straight line, two segments (two-line method), and by tracing the distance along the cervical canal. Results were compared for intraoperator repeatability and interoperator variability. The degree of the cervical curvature was measured. RESULTS: The mean cervical measurement using the single-line measurement was 32.8 (SD 4.4) mm. The mean cervical length was essentially the same using the two-line and tracing measurement: 34.4 (SD 4.7) mm and 34.5 (SD 4.7) mm, respectively. Both intra- and interoperator agreement was high. The degree of curvature of the cervical canal was variable, with a resultant variability in the difference between the single straight line measurement and the other two types of measurement. CONCLUSIONS: Using stored images, each of the measurement techniques is highly reproducible. Both the two-line and the tracing methods yield larger measurements than the single-line technique. Therefore, it appears that in select cases the straight line measurement significantly underestimates the actual cervical length.

Susceptibility of adult and senescent Brown Norway rats to repeated ozone exposure: an assessment of behavior, serum biochemistry and cardiopulmonary function.

Ozone (O3) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O3; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O3 exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O3 for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O3 exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O3 7 d after exposure in both age groups was observed. O3 had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O3 affected 6/58; 2/58 showed an age-O3 interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O3 than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.

General population normative data from seven European countries for the K10 and K6 scales for psychological distress.

The 10-item Kessler Psychological Distress scale (K10) and its 6-item short-form version (K6) measure psychological distress, particularly anxiety or depressive symptoms. While these questionnaire scales are widely used in various settings and populations, general population normative data are rarely available. To facilitate the interpretation of K10 and K6 scores, we provide normative general population data from seven European countries. We used an online survey to collect K10 data from general population samples in Austria, Italy, Germany, France, the Netherlands, Poland and Spain. We calculated the age- and sex-specific normative values separately for each country. For more specific estimates of K10 and K6 scores for individuals or groups, we also established a multivariable regression model based on socio-demographic and health data. In total, N = 7,087 adults participated in our study (51.6% women; mean age, 49.6 years). The mean K10 score in the total sample was 8.5 points (standard deviation, 7.3) on 0-40 points metric, with mean scores in individual countries ranging from 6.9 (the Netherlands) to 9.9 (Spain). Women showed higher scores than men and younger participants scored higher than older participants. Our study is the first to present normative K10 and K6 data from several European countries using a consistent sampling approach. These reference values will facilitate the interpretation of K10 and K6 scores in clinical research and practice and also highlight the variation in psychological distress levels across countries and groups according to their socio-demographic and health characteristics.