Upscaling of Denitrification Rates from Point to Catchment Scales for Modeling of Nitrate Transport and Retention.

The spatial and temporal variability of denitrification makes it challenging to integrate conceptual, process-based understandings of nitrate transport and retention into numerical modeling at the catchment scale, although it is critical for the realism and predictive power of the model. In this study, we propose a novel approach where the conceptual understandings of the spatial structure of denitrification zones and the corresponding representative denitrification rates are transformed into a form that can be integrated into a multi-point statistical simulation framework. This is done by constructing a denitrification training image (TI) coupled to a geophysically based TI of the hydrogeological structure. The field observations and laboratory analyses of denitrification rates and the chemistry of water and sediment revealed that the study catchment's subsurface can be characterized by three zones: (1) the oxic zone with no nitrate reduction; (2) the slow-denitrification zone (mean of ln-transformed rate = -1.19 ± 0.52 mg N L-1 yr-1); and (3) the high-denitrification zone (mean of ln-transformed rate = 3.86 ± 1.96 mg N L-1 yr-1). The underlying controls on the spatial distribution of these zones and the representativeness of denitrification rates were investigated. Then, a TI illustrating the subsurface structure of the denitrification zone was constructed by synthesizing the results of these geochemical interpretations and the hydrogeology TI.

Crowding in the emergency department in the absence of boarding - a transition regression model to predict departures and waiting time.

BACKGROUND: Crowding in the emergency department (ED) is associated with increased mortality, increased treatment cost, and reduced quality of care. Crowding arises when demand exceed resources in the ED and a first sign may be increasing waiting time. We aimed to quantify predictors for departure from the ED, and relate this to waiting time in the ED before departure. METHODS: We utilised administrative data from the ED and calculated number of arrivals, departures, and the resulting queue in 30 min time steps for all of 2013 (N = 17,520). We build a transition model for each time step using the number of past departures and pre-specified risk factors (arrivals, weekday/weekend and shift) to predict the expected number of departures and from this the expected waiting time in the ED. The model was validated with data from the same ED collected March through August 2014. RESULTS: We found that the number of arrivals had the greatest independent impact on departures with an odds ratio of 0.942 (95%CI: 0.937;0.948) corresponding to additional 7 min waiting time per new arrival in a 30 min time interval with an a priori time spend in the ED of two hours. The serial correlation of departures was present up to one and a half hour previous but had very little effect on the estimates of the risk factors. Boarding played a negligible role in the studied ED. CONCLUSIONS: We present a transition regression model with high predictive power to predict departures from the ED utilising only system level data. We use this to present estimates of expected waiting time and ultimately crowding in the ED. The model shows good internal validity though further studies are needed to determine generalisability to the performance in other settings.

A generic method for evaluating crowding in the emergency department.

BACKGROUND: Crowding in the emergency department (ED) has been studied intensively using complicated non-generic methods that may prove difficult to implement in a clinical setting. This study sought to develop a generic method to describe and analyse crowding from measurements readily available in the ED and to test the developed method empirically in a clinical setting. METHODS: We conceptualised a model with ED patient flow divided into separate queues identified by timestamps for predetermined events. With temporal resolution of 30 min, queue lengths were computed as Q(t + 1) = Q(t) + A(t) - D(t), with A(t) = number of arrivals, D(t) = number of departures and t = time interval. Maximum queue lengths for each shift of each day were found and risks of crowding computed. All tests were performed using non-parametric methods. The method was applied in the ED of Aarhus University Hospital, Denmark utilising an open cohort design with prospectively collected data from a one-year observation period. RESULTS: By employing the timestamps already assigned to the patients while in the ED, a generic queuing model can be computed from which crowding can be described and analysed in detail. Depending on availability of data, the model can be extended to include several queues increasing the level of information. When applying the method empirically, 41,693 patients were included. The studied ED had a high risk of bed occupancy rising above 100 % during day and evening shift, especially on weekdays. Further, a 'carry over' effect was shown between shifts and days. CONCLUSIONS: The presented method offers an easy and generic way to get detailed insight into the dynamics of crowding in an ED.

Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics.

OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS: Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION: In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.

Exposure-affecting factors of dairy farmers' exposure to inhalable dust and endotoxin.

INTRODUCTION: Studies on determinants of dairy farmers' exposure to dust and endotoxin have been sparse and so far none has addressed the combined effect of tasks and farm characteristics. OBJECTIVE: To study whether and how work tasks and specific stable characteristics influence the level of dairy farmers' personal exposure to inhalable dust and endotoxin. METHODS: We applied an observational design involving full-shift repeated personal measurements of inhalable dust and endotoxin exposure among 77 subjects (owners and farm workers) from 26 dairy farms. Performed tasks were self-registered in activity diaries, and information on stable characteristics was collected through personal interviews and walk-through surveys. Associations between exposure, tasks, and stable characteristics were examined in linear mixed-effect models with individual and farm treated as random effects. Separate as well as combined models for tasks and stable characteristics were elaborated. RESULTS: The 124 personal samples collected had a geometric mean level (geometric standard deviation) of 360 EU m(-3) (3.8) for endotoxin exposure and of 1.0mg m(-3) (2.7) for dust exposure. Identified factors that increased endotoxin exposure included a lower outdoor temperature and use of slope-based or back-flushed slurry systems along with milking, distribution of bedding, and handling of feed and seeds in barns. For dust, exposure was higher when fully automatic (robotic) milking was used and during re-penning of animals, handling of feed and seeds, handling of silos and when distributing bedding. Dust exposure increased also as a result of use of rail feed dispensers in a model without fully automatic milking. CONCLUSIONS: The current exposure to dust and in particular endotoxin among Danish dairy farmers demand effective strategies to reduce their exposure. The present findings suggest that future interventions should focus on feeding and manure handling systems. Use of respirators during handling of feed and distribution of bedding should be advised until adequate risk management measures have been established. The expected increased use of fully automatic milking in the future might increase dust exposure of dairy farmers.

Prediction of aortic dilation in Turner syndrome--the use of serial cardiovascular magnetic resonance.

BACKGROUND: Identification of the subset females with Turner syndrome who face especially high risk of aortic dissection is difficult, and more optimal risk assessment is pivotal in order to improve outcomes. This study aimed to provide comprehensive, dynamic mathematical models of aortic disease in Turner syndrome by use of cardiovascular magnetic resonance (CMR). METHODS: A prospective framework of long-term aortic follow-up was used, which comprised diameters of the thoracic aorta prospectively assessed at nine positions by CMR at the three points in time (baseline [n = 102, age 38 ± 11 years], follow-up [after 2.4 ± 0.4 years, n = 80] and end-of-study [after 4.8 ± 0.5 years, n = 78]). Mathematical models were created that cohesively integrated all measurements at all positions, from all visits and for all participants, and using these models cohesive risk factor analyses were conducted based on which predictive modeling was performed on which predictive modelling was performed. RESULTS: The cohesive models showed that the variables with effect on aortic diameter were aortic coarctation (P < 0.0001), bicuspid aortic valves (P < 0.0001), age (P < 0.0001), diastolic blood pressure (P = 0.0008), body surface area (P = 0.015) and antihypertensive treatment (P = 0.005). Oestrogen replacement therapy had an effect of borderline significance (P = 0.08). From these data, mathematical models were created that enabled preemption of aortic dilation from CMR derived aortic diameters in scenarios both with and without known risk factors. The fit of the models to the actual data was good. CONCLUSION: The presented cohesive model for prediction of aortic diameter in Turner syndrome could help identifying females with rapid growth of aortic diameter, and may enhance clinical decision-making based on serial CMR.

The Bandim tuberculosis score: reliability and comparison with the Karnofsky performance score.

BACKGROUND: This study was carried out in Guinea-Bissau's capital Bissau among inpatients and outpatients attending for tuberculosis (TB) treatment within the study area of the Bandim Health Project, a Health and Demographic Surveillance Site. Our aim was to assess the variability between 2 physicians in performing the Bandim tuberculosis score (TBscore), a clinical severity score for pulmonary TB (PTB), and to compare it to the Karnofsky performance score (KPS). METHOD: From December 2008 to July 2009 we assessed the TBscore and the KPS of 100 PTB patients at inclusion in the TB cohort and/or at 1 or more follow-up visits; 61 baseline and 130 follow-up double assessments were obtained. RESULTS: The inter-observer variability of the TBscore (5 symptoms and 6 clinical findings) varied from slight to almost perfect agreement. For the TBscore, all 3 severity classes (SC I-III) were observed, while the KPS only yielded 2 of its 3 possible classes. The grading of PTB patients into severity classes showed moderate agreement for both the TBscore (κ(w) = 0.52, 95% confidence interval 0.46-0.56) and the KPS (κ(w) = 0.49, 95% confidence interval 0.33-0.65). The intra-class correlation coefficient (ICC) was larger for the TBscore than for the KPS (0.822 vs 0.632). CONCLUSIONS: The Bandim TBscore had an acceptable inter-observer variability, seemed to be more disease-related, and performed better than the KPS.

A Prospective Study of Lipids in Adult Women With Turner Syndrome.

Context: Turner syndrome (TS) is a rare genetic syndrome with an increased mortality, mainly attributed to cardiovascular disease. Objective: This work aimed to investigate and correlate the lipid profile in adult women with TS to clinical characteristics. Methods: A 12-year prospective cohort study, including 4 study visits, was conducted at a specialist hospital. A total of 102 women with TS qualified for inclusion. Excluding missing variables and participants lost to follow-up, 86 women (mean age 38.1 years; range, 18.4-62.1 years) were included in this study. Fifty-three women completed the study. Repeated-measurement analysis was performed, using total cholesterol (Total-C), low-density lipoprotein (LDL), triglycerides (TGs), and high-density lipoprotein (HDL) as outcome variables and age, karyotype, body mass index (BMI), treatment with statins, antidiabetics, and hormone replacement therapy as explanatory variables. Principal component analysis (PCA) and partial least squares (PLS) analysis were performed at the first study visit. Results: Hyperlipidemia was present in 30% of the TS cohort. Total-C increased with age (0.12 mmol/L/y; P = .016). LDL (P = .08), TGs (P = .14), and HDL (P = .24) were not associated with age. BMI significantly increased total-C (0.19 mmol/L/kg/m2; P = .006), LDL (0.63 mmol/L/kg/m2; P < .001), and TGs (0.80 mmol/L/kg/m2; P < .001) and decreased HDL (-0.59 mmol/L/kg/m2; P < .001). PCA and PLS analysis found correlations between weight and BMI and total-C, LDL, and TGs. Conclusion: Hyperlipidemia is more prevalent in adult women with TS across adulthood compared to the background population. Total-C, LDL, TGs, and HDL were significantly associated with BMI characterizing the atherogenic profile in adult women with TS.

Demographic and clinical characteristics in relation to patient and health system delays in a tuberculosis low-incidence country.

BACKGROUND: Delays in the diagnosis and treatment of tuberculosis (TB) are commonly encountered. METHODS: A study was undertaken among pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients in a Danish university hospital to describe demographic and clinical characteristics in relation to delay. RESULTS: Of the 313 patients enrolled, 213 (68%) were diagnosed with PTB and 100 (32%) with EPTB only. Logistic regression analysis of EPTB showed an association with female sex and non-Danish ethnicity. Mean total delay from onset of symptoms until initiation of TB treatment was 123 (95% confidence interval (CI) 106-138) days. Mean patient delay was significantly longer than mean health system delay: 90 (95% CI 74-105) vs 33 (95% CI 23-44) days (p < 0.0001). Delay was independent of ethnicity and significantly shorter for PTB patients compared to EPTB patients. Fever was found to be strongly predictive of a short patient delay (<1 month), whereas weight loss was associated with a long patient delay (> 3 months). In contrast, weight loss was associated with a short health system delay (<1 week). Elevated inflammatory markers were also associated with a short delay in the diagnosis of TB. CONCLUSIONS: This study confirmed a typical delay of months in duration in the diagnosis and treatment of TB in the low endemic country of Denmark. Increased TB awareness is needed, in particular in communities with immigrants originating from high-endemic areas.

Predictors of monoterpene exposure in the Danish furniture industry.

OBJECTIVES: Individuals who work with pine in the furniture industry may be exposed to monoterpenes, the most abundant of which are α-pinene, ß-pinene, and Δ(3)-carene. Monoterpenes are suspected to cause dermatitis and to harm the respiratory system. An understanding of the predictors of monoterpene exposure is therefore important in preventing these adverse effects. These predictors may include general characteristics of the work environment and specific work operations. We sought to assess the extent to which workers are exposed to monoterpenes and to identify possible predictors of monoterpene exposure in the pine furniture industry in Denmark. METHODS: Passive measurements of the levels of selected monoterpenes (α-pinene, ß-pinene, and Δ(3)-carene) were performed on 161 subjects from 17 pine furniture factories in Viborg County, Denmark; one sample was acquired from each worker. Additionally, wood dust samples were collected from 145 workers. Data on potential predictors of exposure were acquired over the course of the day on which the exposure measurements were recorded and could be assigned to one of four hierarchic ordered levels: worker, machine, department, and factory. In addition to univariate analyses, a mixed model was used to account for imbalances within the data and random variation with each of the hierarchically ordered levels. RESULTS: The geometric mean (GM) monoterpene content observed over the 161 measurements was 7.8 mg m(-3) [geometric standard deviation (GSD): 2.4]; the GM wood dust level over 145 measurements was 0.58 mg m(-3) (GSD: 1.49). None of the measured samples exceeded the occupational exposure limit for terpenes in Denmark (25 ppm, 150 mg m(-3)). In the univariate analyses, half of the predictors tested were found to be significant; the multivariate model indicated that only three of the potential predictors were significant. These were the recirculation of air in rooms used for the processing of wood (a factory level predictor), the presence of a supplementary cold air intake (departmental level), and the operation of a glue press (machine level). However, only one factory of the 17 examined used a supplementary cold air intake, and while very high monoterpene levels were observed there, this may be due to factors other than the supplementary intake. In contrast to the situation with wood dust, we found that the bulk of the variation in the data (65%) was attributable to variability on the factory level, with comparatively little being due to the departmental (16%) and machine (0.5%) levels. The fixed terms in the model accounted for 31.8% of the total variance. CONCLUSIONS: The predictors of monoterpenes are not the same as those for wood dust exposure; this has implications for the implementation of preventative measures in factories. In order to decrease monoterpene exposure, efforts should be focused on minimizing the recirculation of air in rooms used for woodworking and on increasing awareness of the importance of effective ventilation and enclosure when operating a glue press.

End-of-life practices in Danish ICUs: development and validation of a questionnaire.

BACKGROUND: Practices for withholding or withdrawing therapy vary according to professional, cultural and religious differences. No Danish-validated questionnaire examining withholding and withdrawing practices exists, thus the aim of this study was to develop and validate a questionnaire for surveying the views of intensive care nurses, intensivists, and primary physicians regarding collaboration and other aspects of withholding and withdrawing therapy in the ICU. METHODS: A questionnaire was developed on the basis of literature, focus group interviews with intensive care nurses and intensivists, and individual interviews with primary physicians. The questionnaire was validated in the following 3 phases: a qualitative test with 17 participants; a quantitative pilot test with 60 participants; and a survey with 776 participants. The validation process included tests for face and content validity (by interviewing participants in the qualitative part of the pilot study), reliability (by assessing the distribution of responses within the individual response categories), agreement (by conducting a test-retest, evaluated by paired analyses), known groups' validity (as a surrogate test for responsiveness, by comparing two ICUs with a known difference in end-of-life practices), floor and ceiling effect, and missing data. RESULTS: Face and content validity were assessed as good by the participants in the qualitative pilot test; all considered the questions relevant and none of the participants found areas lacking. Almost all response categories were used by the participants, thus demonstrating the questionnaires ability to distinguish between different respondents, agreement was fair (the average test-retest agreement for the Likert scale responses was 0.54 (weighted kappa; range, 0.25-0.73), and known groups' validity was proved by finding significant differences in level of satisfaction with interdisciplinary collaboration and in experiences of withdrawal decisions being unnecessarily postponed. Floor and ceiling effect was in accordance with other questionnaires, and missing data was limited to a range of 0-7% for all questions. CONCLUSIONS: The validation showed good and fair areas of validity of the questionnaire. The questionnaire is considered a useful tool to assess the perceptions of collaboration and other aspects of withholding and withdrawing therapy practices in Danish ICUs amongst nurses, intensivists, and primary physicians.

Trend reversal of nitrate in Danish groundwater--a reflection of agricultural practices and nitrogen surpluses since 1950.

This paper assesses the long-term development in the oxic groundwater nitrate concentration and nitrogen (N) loss due to intensive farming in Denmark. First, up to 20-year time-series from the national groundwater monitoring network enable a statistically systematic analysis of distribution, trends, and trend reversals in the groundwater nitrate concentration. Second, knowledge about the N surplus in Danish agriculture since 1950 is used as an indicator of the potential loss of N. Third, groundwater recharge CFC (chlorofluorocarbon) age determination allows linking of the first two data sets. The development in the nitrate concentration of oxic groundwater clearly mirrors the development in the national agricultural N surplus, and a corresponding trend reversal is found in groundwater. Regulation and technical improvements in the intensive farming in Denmark have succeeded in decreasing the N surplus by 40% since the mid 1980s, while at the same time maintaining crop yields and increasing the animal production of especially pigs. Trend analyses prove that the youngest (0-15 years old) oxic groundwater shows more pronounced significant downward nitrate trends (44%) than the oldest (25-50 years old) oxic groundwater (9%). This amounts to clear evidence of the effect of reduced nitrate leaching on groundwater nitrate concentrations in Denmark.

Natural History of Hypertension in Turner Syndrome During a 12-Year Pragmatic Interventional Study.

Turner syndrome is caused by complete or partial X monosomy in some or all cells. Cardiovascular complications are dominant, including increased blood pressure (BP), leading to early-onset hypertension. The aim is to describe the debut, development, and treatment of hypertension in Turner syndrome during a 12-year pragmatic interventional study to help identify risk factors associated with hypertension. One hundred and two women (aged 38±11 years, range: 18-62 years) with Turner syndrome verified by karyotyping (45, X: n=58 [57%]) were included consecutively. Ambulatory BPs were recorded over 24 hours with oscillometric measurements every 20 minutes. Antihypertensive treatment was recommended if the BP was above 135/85 mm Hg during the daytime. Overall, systolic BP, diastolic BP, and pulse pressure increased during the study, while heart rate decreased. The number of patients treated with antihypertensive medicine increased from 29 (28.71%) at baseline to 34 (53.13%) at the end of study. Twenty-four-hour systolic BP and 24-hour pulse pressure increased significantly with age, while 24-hour heart rate decreased with age, and diastolic BP was insignificantly affected by age. Antihypertensive treatment lowered systolic BP (24-hour: -5 mm Hg), diastolic BP (24-hour: -5 mm Hg), and diminished the pulse pressure (24-hour: -6 mm Hg) but did not affect nighttime systolic BP. Antihypertensive treatment did not affect heart rate. Our study showed that both systolic and diastolic BP increases significantly in women with Turner syndrome resulting in an increased risk of cardiovascular comorbidities. This increment should be considered of multifactorial origin with many contributing factors which is supported by our results.

A Quantitative General Population Job Exposure Matrix for Occupational Noise Exposure.

Occupational noise exposure is a known risk factor for hearing loss and also adverse cardiovascular effects have been suggested. A job exposure matrix (JEM) would enable studies of noise and health on a large scale. The objective of this study was to create a quantitative JEM for occupational noise exposure assessment of the general working population. Between 2001-2003 and 2009-2010, we recruited workers from companies within the 10 industries with the highest reporting of noise-induced hearing loss according to the Danish Working Environment Authority and in addition workers of financial services and children day care to optimize the range in exposure levels. We obtained 1343 personal occupational noise dosimeter measurements among 1140 workers representing 100 different jobs according to the Danish version of the International Standard Classification of Occupations 1988 (DISCO 88). Four experts used 35 of these jobs as benchmarks and rated noise levels for the remaining 337 jobs within DISCO 88. To estimate noise levels for all 372 jobs, we included expert ratings together with sex, age, occupational class, and calendar year as fixed effects, while job and worker were included as random effects in a linear mixed regression model. The fixed effects explained 40% of the total variance: 72% of the between-jobs variance, -6% of the between-workers variance and 4% of the within-worker variance. Modelled noise levels showed a monotonic increase with increasing expert score and a 20 dB difference between the highest and lowest exposed jobs. Based on the JEM estimates, metal wheel-grinders were among the highest and finance and sales professionals among the lowest exposed. This JEM of occupational noise exposure can be used to prioritize preventive efforts of occupational noise exposure and to provide quantitative estimates of contemporary exposure levels in epidemiological studies of health effects potentially associated with noise exposure.

Ambulatory arterial stiffness index in Turner syndrome: the impact of sex hormone replacement therapy.

BACKGROUND: Morbidity and mortality from congenital and acquired cardiovascular (CV) disease is increased in Turner syndrome (TS), where traditional indices of CV risk are widely present but the single most common feature remains estrogen deficiency. AIM: To investigate CV risk in TS as expressed by the widely available ambulatory arterial stiffness index (AASI) and the impact of female sex hormone replacement therapy (HRT) hereon. METHODS: TS women (n = 26) were examined following HRT washout and again during 6 months of HRT. Age-matched healthy female controls (n = 24) were examined once. 24-Hour ambulatory blood pressures, AASI in addition to metabolic and anthropometric indices of CV risk were measured. RESULTS: The relatively tachycardic TS women had higher systolic and diastolic blood pressures. HRT reduced diastolic blood pressures with an increase in physical fitness, worsening of glucose tolerance, and a reduction in high-density lipoprotein. AASI was significantly elevated in TS when compared to controls (0.36 (0.02) vs. 0.26 (0.03), p = 0.01) but unaffected by HRT. Major explanatory variables to AASI were status (being TS or not), age, and diurnal pulse variability. CONCLUSION: AASI was elevated in TS, possibly indicating elevated CV risk with no impact of short-term HRT.

Frequency of sensitization to methyl aminolaevulinate after photodynamic therapy.

BACKGROUND: Allergic contact dermatitis to methyl aminolaevulinate (Metvix) after topical application in photodynamic therapy (PDT) has previously been described in case reports. OBJECTIVE: To compare the frequency of sensitization to Metvix cream in a group of patients previously treated at least five times with Metvix-PDT with the frequency observed in an unexposed control group. METHODS: Twenty patients treated five times or more with Metvix-PDT and 60 controls with no prior exposure to Metvix were patch tested with Metvix cream and Metvix placebo cream. Subsequently, the patients were interviewed to determine the relevance of a positive patch test reaction to Metvix. RESULTS: Of 20 patients treated with Metvix-PDT, 7 were sensitized to Metvix cream, giving a sensation risk of 35%. In the control group, 1 of 60 became sensitized after a single exposure to Metvix cream (1.7%). There was no reaction to the placebo cream. The positive patch tests to Metvix were considered relevant in four of seven patients (57%). CONCLUSIONS: This study demonstrates a considerable risk of sensitization after Metvix-PDT. We suggest that the patients are interviewed to detect late or persistent local reactions after PDT. These reactions are often considered to be local infections but may represent allergic contact dermatitis, and therefore, patients should be offered patch testing with Metvix cream.

A placebo-controlled randomized study with testosterone in Klinefelter syndrome: beneficial effects on body composition.

CONTEXT AND OBJECTIVE: Males with Klinefelter syndrome (KS) are typically hypogonadal with a high incidence of metabolic disease, increased body fat and mortality. Testosterone treatment of hypogonadal patients decrease fat mass, increase lean body mass and improve insulin sensitivity, but whether this extends to patients with KS is presently unknown. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, BMI-matched cross-over study, 13 males with KS (age: 34.8 years; BMI: 26.7 kg/m2) received testosterone (Andriol®) 160 mg per day (testosterone) or placebo treatment for 6 months. Thirteen age- and BMI-matched healthy controls were recruited. DEXA scan, abdominal computed tomography (CT) scan and a hyperinsulinemic-euglycemic clamp, muscle strength and maximal oxygen uptake measurement were performed. RESULTS: Total lean body mass and body fat mass were comparable between testosterone-naïve KS and controls using DEXA, whereas visceral fat mass, total abdominal and intra-abdominal fat by CT was increased (P < 0.05). Testosterone decreased total body fat (P = 0.01) and abdominal fat by CT (P = 0.04). Glucose disposal was similar between testosterone-naïve KS and controls (P = 0.3) and unchanged during testosterone (P = 0.8). Free fatty acid suppression during the clamp was impaired in KS and maximal oxygen uptake was markedly lower in KS, but both were unaffected by treatment. Testosterone increased hemoglobin and IGF-I. CONCLUSION: Testosterone treatment in adult males with KS for 6 months leads to favorable changes in body composition with reductions in fat mass, including abdominal fat mass, but does not change measures of glucose homeostasis.

Five-Year Randomized Study Demonstrates Blood Pressure Increases in Young Women With Turner Syndrome Regardless of Estradiol Dose.

We evaluated the development in blood pressure (BP) and heart rate in young women with Turner syndrome (TS) and investigated potential influencing cofactors. Twenty TS women (mean±SD, 22.9±2.3 years of age) were investigated in a 5-year prospective setting. Data were derived from a randomized controlled clinical trial investigating 2 different doses of estradiol treatment (2 mg 17ß-estradiol per day and placebo or 2+2 mg 17ß-estradiol per day). A control group of 12 healthy age-matched young women (mean±SD, 23.11±2.2 years of age) was examined at the end of the study. BP and lipids were monitored yearly. At the end of the study, TS (n=15) and controls were examined by 24-hour ambulatory BP monitoring. Systolic and diastolic BPs increased regardless of estradiol dose ( P=0.005 and P=0.009) in TS patients, whereas heart rate decreased ( P=0.05). Neither body mass index, height, weight, nor lipids contributed significant to the changes. There was no difference in BP, heart rate, or lipids because of treatment. At the end of the study, diastolic BP and heart rate were significantly higher in TS during day, night, and over 24 hours. Systolic BP increased insignificantly. Lipids did not change during the study period, but body mass index determined individual levels. In conclusion, systolic and diastolic BPs increase significantly in late adolescence and early adulthood in TS. It remains an enigma why BP increases early in life in TS. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00134745.

Aortic growth rates are not increased in Turner syndrome-a prospective CMR study.

BACKGROUND: Aortic disease is a key determinant of outcomes in Turner syndrome (TS). The present study characterized aortic growth rates and outcomes over nearly a decade in adult women with TS. METHODS AND RESULTS: Prospective observational study assessing aortic diameters twice with cardiovascular magnetic resonance imaging in women with TS [N = 91; mean follow-up 8.8 ± 3.3 (range 1.6-12.6) years] and healthy age-matched female controls [N = 37; mean follow-up 6.7 ± 0.5 (range 5.9-8.1) years]. Follow-up also included aortic outcomes and mortality, antihypertensive treatment and ambulatory blood pressure. Aortic growth rates were similar or smaller in TS, but the variation was larger. The proximal aorta in TS grew by 0.20 ± 0.26 (mid-ascending) to 0.32 ± 0.36 (sinuses) mm/year. This compared to 0.26 ± 0.14 (mid-ascending) and 0.32 ± 0.17 (sinuses) mm/year in the controls. During 799 years at risk, 7 suffered an aortic outcome (1 aortic death, 2 aortic dissections, 2 aortic interventions, 2 surgical aortic listings) with further 2 aortic valve replacements. At baseline, two women were excluded. One died during subacute aortic surgery (severe dilatation) and one had a previously undetected type A dissection. The combined aortic outcome rate was 1126 per 100 000 observation years. The aortic and all-cause mortality rates were 1 per 799 years (125 deaths per 100 000 observation years) and 9 per 799 years (1126 deaths per 100 000 observation years). Aortic growth patterns were particularly perturbed in bicuspid aortic valves (BAV) and aortic coarctation (CoA). CONCLUSION: Aortic growth rates in TS are not increased. BAVs and CoA are major factors that impact aortic growth. Aortic outcomes remain a concern.

Determinants of wood dust exposure in the Danish furniture industry--results from two cross-sectional studies 6 years apart.

OBJECTIVES: This paper investigates determinants of wood dust exposure and trends in dust level in the furniture industry of Viborg County, Denmark, using data from two cross-sectional studies 6 years apart. METHODS: During the winter 1997/1998, 54 factories were visited (hereafter study 1). In the winter 2003/2004, 27 factories were revisited, and personal dust measurements were repeated. In addition, 14 new factories were included (hereafter study 2). A total of 2303 woodworkers participated in study 1, and 2358 measurements from 1702 workers were available. From study 2, 1581 woodworkers participated and 1355 measurements from 1044 workers were available. Information on occupational variables describing potential determinants of exposures like work task, exhaust ventilation, enclosure and cleaning procedures were collected. A total of 2627 measurements and 1907 persons were included in the final mixed model in order to explore determinants of exposure and trends in dust level. RESULTS: The overall inhalable wood dust concentration (geometric means (geometric standard deviation)) has decreased from 0.95 mg/m(3) (2.05) in study 1 to 0.60 mg/m(3) (1.63) in study 2, representing a 7% annual decrease in dust concentration, which was confirmed in the mixed model. From study 1 to study 2 there has been a change towards less manual work and more efficient cleaning methods, but on the contrary also more inadequate exhaust ventilation systems. The following determinants were found to 'increase' dust concentration: sanding; use of compressed air; use of full-automatic machines; manual work; cleaning of work pieces with compressed air; kitchen producing factories and small factories (<20 employees). The following determinants of exposure were found to 'decrease' dust concentration: manual assembling/packing; sanding with adequate exhaust ventilation; adequate exhaust ventilation; vacuum cleaning of machines and special cleaning staff. CONCLUSIONS: Despite a substantial drop in the dust concentration during the last 6 years in the furniture industry in Viborg County, further improvements are possible. There should be more focus on improved exhaust ventilation, professional cleaning methods and avoiding use of compressed air.