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Scope: Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy., Methods and Results: Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6- 2 H 2 ]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0-90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0-90 min AUC., Conclusion: Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Early-age exposure to noise may have long-term health implications of which we have little knowledge of today. Age-specific hearing, learning inadequate coping strategies, and alterations in biological stress regulatory responses could play a role in the long-term health impacts. In Sweden about half a million children in the age between 1-5 years attend preschool. The noise exposure at preschools is intermittent and unpredictable and levels reach up to 84 dB LAeq (time indoors) with maximum levels of 118 dB LAF, mostly due to child activity. To increase the overall understanding of the possible implications of preschool noise environments for children, this paper describes children's behavioral and emotional reactions to and coping with their everyday sound environment from a teachers perspective. A postal questionnaire study performed in 2013-2014 with answers from 3,986 preschool teachers provided the data. Content analysis was combined with quantitative analysis. Eighty-two percent of the personnel considered that children's behavior was affected rather or very much by preschool noise. The most prevalent behaviors were categorized into: be heard, be distracted, show negative internal emotions, crowd, avoid, withdraw, be exhausted, and learning. The quantitative analyses confirmed an association between the perceived loudness and noise annoyance at preschool and affirmative reporting on noise affecting the children´s behavior. Age of the personnel, with the youngest age group reporting noise related behavior less often, and age distribution of the class, with 1-5 years old seeming less affected by noise, were also indicated, while pedagogic orientation was not a significant factor. Future studies should address the long-term health effects of these behaviors., Competing Interests: The authors have declared that no competing interests exist.

Context: GH responsiveness guides GH dosing during the catch-up growth (CUG) period; however, little is known regarding GH dosing during the prepubertal maintenance treatment period., Objective: To evaluate whether SD score (SDS) channel parallel growth with normal height velocity can be maintained after CUG by reducing the GH dose by 50% in children receiving doses individualized according to estimated GH responsiveness during the catch-up period., Design and Settings: Prepubertal children (n = 98; 72 boys) receiving GH during CUG (GH deficient, n = 33; non-GH deficient, n = 65), were randomized after 2 to 3 years to either a 50% reduced individualized dose (GHRID; n = 27; 20 boys) or unchanged individualized dose (GHUID; n = 38; 27 boys). Another 33 children (25 boys) continued a standard weight-based dose [43 µg/kg/d (GHFIX)]., Main Outcome Measures: The primary endpoint was the proportion of children with ΔheightSDS within ±0.3 at 1 year after GH dose reduction compared with two control groups: GHUID and GHFIX. The hypothesis was that heightSDS could be maintained within ±0.3 with a reduced individualized GH dose., Results: For the intention-to-treat population at 1 year, 85% of the GHRIDgroup maintained ΔheightSDS within ±0.3 vs 41% in the GHUIDgroup (P = 0.0055) and 48% in the GHFIXgroup (P = 0.0047). The ΔIGF-ISDS in the GHRID group was -0.75 ± 1.0 at 3 months (P = 0.003) and -0.72 ± 1.2 at 1 year compared with the GHUID group (0.15 ± 1.2; P = 0.005) and GHFIX group (0.05 ± 1.0; P = 0.02)., Conclusions: Channel parallel growth (i.e., normal height velocity) and IGF-ISDS levels within ±2 were maintained after completed CUG using a 50% lower individualized dose than that used during the CUG period.

Topochemical engineering of hybrid materials is an efficient way of synthesizing hydrophobic and highly tensile fiber composites by utilizing the intermolecular hydrogen bonds in natural materials. These materials include wood pulp fibers, abietic acid (resin acid) and inexpensive metal salts. In this work, a hybrid composite was created using bleached and unbleached kraft pulp fibers as cellulose platform. In situ co-precipitation of layered double hydroxide (LDH) was performed to grow LDH crystals on the surface of the cellulose fibers, followed by the immobilization of abietic acid (AA) on LDH-grafted cellulose. Here we aimed to benefit from the hydrogen bonding between -OH groups of cellulose and LDH, and the -COOH groups of AA to obtain charge-directed assembly of one material on the other material. Thus, composite hybrid fibers (C-HF) were produced and then characterized by optical (CAM), spectroscopic (XRD, IR) and microscopic techniques (SEM) to determine their average length and distribution, structure and purity, bonding, and morphology. These fibers further were tested for water contact angle (hydrophobicity), oil absorption (lipophilicity), tensile strength and ISO brightness measurements. The performance of C-HF was compared with unmodified reference fibers (REF), fibers composed with only AA (C-F) and LDH-hybridized fibers (HF). The results revealed a variety of correlations between materials and their properties due to characteristic surface morphology, functional groups, hydrogen bonding and natural co-materials such as lignin and hemicelluloses. Attractive and repulsive van der Waals forces between material entities play a crucial role in the resulting properties.

Extensive quantities of apple pomace are generated annually but its disposal is still challenging. This study addresses this issue by introducing a new, environmentally-friendly approach for the production of sustainable biomaterials from apple pomace, containing 55.47% free sugars and a water insoluble fraction, containing 29.42 ± 0.44% hemicelluloses, 38.99 ± 0.42% cellulose, and 22.94 ± 0.12% lignin. Solution casting and compression molding were applied to form bio-based films and 3D objects (i.e., fiberboards), respectively. Using glycerol as plasticizer resulted in highly compact films with high tensile strength and low elongation (16.49 ± 2.54 MPa and 10.78 ± 3.19%, respectively). In contrast, naturally occurring sugars in the apple pomace showed stronger plasticizing effect in the films and resulted in a fluffier and connected structure with significantly higher elongation (37.39 ± 10.38% and 55.41 ± 5.38%, respectively). Benefiting from the self-binding capacity of polysaccharides, fiberboards were prepared by compression molding at 100 °C using glycerol or naturally occurring sugars, such as plasticizer. The obtained fiberboards exhibited tensile strength of 3.02⁻5.79 MPa and elongation of 0.93%⁻1.56%. Possible applications for apple pomace biomaterials are edible/disposable tableware or food packaging., Competing Interests: The authors declare no conflicts of interest.

This paper presents the development and validation of a Monte Carlo-based singe photon emission computed tomography reconstruction program for parallel-hole collimation contained within the SIMIND Monte Carlo framework. The Monte Carlo code is used as an accurate forward-projector and is combined with a simplified back-projector to perform iterative tomographic reconstruction using the Maximum Likelihood Expectation Maximization and Ordered Subsets Expectation Maximization algorithms, together forming a program called SIMREC. The Monte Carlo simulation transforms the estimated source distribution directly from activity to counts in its projections. Hence, the reconstructed image is expressed in activity without reference to an external calibration. The program is tested using phantom measurements of spheres filled with 99m Tc, 177 Lu and 131 I placed in air and centrally and peripherally in a water-filled elliptical phantom. The feasibility of applying the reconstruction to patients is also demonstrated for a range of radiopharmaceuticals. The deviation in total activity in the spheres ranged between  -4.1% and 6.2% compared with the activity determined when preparing the phantom. The SIMREC program was found to be accurate with respect to activity estimation and to reconstruct visually acceptable images within a few hours when applied to patient examples.

Aim: Visceral obesity is associated with perioperative and postoperative complications in colorectal surgery. We aimed to investigate the association between the perirenal fat surface area (PRF) and postoperative complications., Method: Data on 610 patients undergoing curative, elective colon cancer resection between 2006 and 2016 at Stockholm South General Hospital were retrieved from a local quality register. We assessed perioperative and postoperative outcomes using a multinomial regression model adjusted for age, sex, American Society of Anesthesiologists classification and surgical approach (open/laparoscopy) in relation to PRF., Results: PRF could be measured in 605 patients; the median area was 24 cm 2 . Patients with PRF ≥ 40 cm 2 had longer operation time (median 223 vs 184 min), more intra-operative bleeding (250 vs 125 ml), reoperations (11% vs 6%), surgical complications (27% vs 13%) and nonsurgical infectious complications (16% vs 9%) than patients with PRF < 40 cm 2 , but there were no differences in the need for intensive care or duration of hospital stay. The multivariate analyses revealed an increased risk of any complication [OR 1.68 (95% CI 1.1-2.6)], which was even more pronounced for moderate complications [Clavien-Dindo II, OR 2.14 (CI 1.2-2.4]; Clavien-Dindo III, OR 2.35 (CI 1.0-5.5)] in patients with PRF ≥ 40 vs < 40 cm 2 . The absolute risk of complications was similar in men and women with PRF ≥ 40 cm 2 ., Conclusion: PRF, an easily measured indirect marker of visceral obesity, was associated with overall and moderate complications in men and women and could serve as a useful tool in the assessment of preoperative risk., (Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.)

Aim: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40., Methods: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries., Results: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher., Conclusion: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time-activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

Purpose: A hybrid planar-SPECT/CT method for tumor dosimetry in 177 Lu-DOTATATE therapy, applicable to datasets consisting of multiple conjugate-view images and one SPECT/CT, is developed and evaluated., Methods: The imaging protocol includes conjugate-view imaging at 1, 24, 96, and 168 h post infusion (p.i.) and a SPECT/CT acquisition 24 h p.i. The dosimetry method uses the planar images to estimate the shape of the time-activity concentration curve, which is then rescaled to absolute units using the SPECT-derived activity concentration. The resulting time-integrated activity concentration coefficient (TIACC) is used to calculate the tumor-absorbed dose. Semiautomatic segmentation techniques are applied for tumor delineation in both planar and SPECT images, where the planar image segmentation is accomplished using an active-rays-based technique. The selection of tumors is done by visual inspection of planar and SPECT images and applying a set of criteria concerning the tumor visibility and possible interference from superimposed activity uptakes in the planar images. Five different strategies for determining values from planar regions of interest (ROIs), based on entire or partial ROIs, and with and without background correction, are evaluated. Evaluation is performed against a SPECT/CT-based method on data from six patients where sequential conjugate-view and SPECT/CT imaging have been performed in parallel and against ground truths in Monte Carlo simulated images. The patient data are also used to evaluate the interoperator variability and to assess the validity of the developed criteria for tumor selection., Results: For patient images, the hybrid method produces TIACCs that are on average 6% below those of the SPECT/CT only method, with standard deviations for the relative TIACC differences of 8%-11%. Simulations show that the hybrid and SPECT-based methods estimate the TIACCs to within approximately 10% for tumors larger than around 10 ml, while for smaller tumors, all methods underestimate the TIACCs due to underestimations of the activity concentrations in the SPECT images. The planar image segmentation has a low operator dependence, with a median Dice similarity coefficient of 0.97 between operators. The adopted criteria for tumor selection manage to discriminate the tumors for which the absorbed-dose deviations between the hybrid and SPECT methods are the highest., Conclusions: The hybrid method is found suitable for studies of tumor-absorbed doses in radionuclide therapy, provided that selection criteria regarding the visibility and overlapping activities in the planar images are applied., (© 2018 American Association of Physicists in Medicine.)

Background: Vascularized lymph node transfer has shown promising results in the treatment of lower limb lymphedema, but little is known about the number of lymph nodes needed for the transfer to achieve optimal results. This study investigated the correlation between number of transferred lymph nodes in submental vascularized lymph node transfer and outcomes regarding limb circumference reduction and cellulitis incidence., Methods: Thirty-five patients who had received vascularized submental lymph node transfer to an ankle for lower limb lymphedema following gynecologic cancer treatment were included in the study. Limb circumference was determined by means of tape measurement preoperatively and postoperatively and was used to calculate the circumferential difference. Ultrasonography was performed postoperatively to determine the number of lymph nodes within the transferred flap. Patients were divided into groups A through C depending on the number of transferred lymph nodes: 1 or 2 (n = 10), 3 or 4 (n = 14), and 5 to 8 (n = 11), respectively., Results: The mean age of the patients was 60.0 ± 9.2 years. All flaps survived. The mean improvement of circumferential difference for the whole cohort was 19.8 ± 9.2 percent. Groups B and C both had significantly higher improvements in the circumferential difference than group A (p = 0.04 and p = 0.02, respectively), but when compared to each other, the difference was nonsignificant. All groups had significant reductions in the incidence of cellulitis postoperatively., Conclusions: Submental vascularized lymph node transfer for lower limb lymphedema reduced the incidence of cellulitis, regardless of the number of transferred lymph nodes. The transfer of three or more lymph nodes provided significantly better outcome regarding limb circumference reduction than the transfer of two or fewer lymph nodes., Clinical Question/level of Evidence: Therapeutic, III.

Background: Recently, 177 Lu-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done. The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours. As part of a clinical trial on 177 Lu-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses., Results: In general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD., Conclusions: Performing one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.

Background: Management of diabetes is demanding and requires efficient cognitive skills, especially in the domain of executive functioning. However, the impact of impaired executive functions on diabetes control has been studied to a limited extent. The aim of the study is to investigate the association between executive problems and diabetes control in adolescents with type 1 diabetes., Materials and Methods: Two hundred and forty-one of 477 (51%) of 12- to 18-year-old adolescents, with a diabetes duration of >2 years in Stockholm, Uppsala, and Jönköping participated. Parents and adolescents completed questionnaires, including Behavioral Rating Inventory of Executive Function (BRIEF), Attention-Deficit/Hyperactivity Disorder (ADHD)-Rating Scale (ADHD-RS) and demographic background factors. Diabetes-related data were collected from the Swedish Childhood Diabetes Registry, SWEDIABKIDS. Self-rated and parent-rated executive problems were analyzed with regard to gender, glycosylated hemoglobin (HbA1c), frequency of outpatient visits, and physical activity, using chi-square tests or Fisher's test, where P-values <.05 were considered significant. Furthermore, adjusted logistic regressions were performed with executive problems as independent variable., Results: Executive problems, according to BRIEF and/or ADHD-RS were for both genders associated with mean HbA1c >70 mmol/mol (patient rating P = .000, parent rating P = .017), a large number of outpatient visits (parent rating P = .015), and low physical activity (patient rating P = .000, parent rating P = .025). Self-rated executive problems were more prevalent in girls (P = .032), while parents reported these problems to a larger extent in boys (P = .028)., Conclusion: Executive problems are related to poor metabolic control in adolescents with type 1 diabetes. Patients with executive problems need to be recognized by the diabetes team and the diabetes care should be organized to provide adequate support for these patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of -0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Monte Carlo simulations provide accurate models of nuclear medicine imaging systems as they can properly account for the full physics of photon transport. The accuracy of the model included in the maximum-likelihood-expectation-maximization (ML-EM) reconstruction limits the overall accuracy of the reconstruction results. In this paper, we present a Monte Carlo-based ML-EM reconstruction method for pinhole single-photon emission computed tomography (SPECT) that has been incorporated into the SIMIND Monte Carlo program. The Monte Carlo-based model, which accounts for all of the physical and geometrical characteristics of the camera system, is used in the forward-projection step of the reconstruction, while a simpler model based on ray-tracing is used for back-projection. The aim of this work was to investigate the quantitative accuracy of this combination of forward- and back-projectors in the clinical pinhole camera GE Discovery NM 530c., Results: The total activity was estimated in 99m Tc-filled spheres with volumes between 0.5 and 16 mL. The total sphere activity was generally overestimated but remained within 10% of the reference activity defined by the phantom preparation. The recovered activity converged towards the reference activity as the number of iterations increased. Furthermore, the recovery of the activity concentrations within the physical boundaries of the spheres increased with increasing sphere volume. Additionally, the Monte Carlo-based reconstruction enabled recovery of the true activity concentration in the myocardium of a cardiac phantom mounted in a torso phantom regardless of whether the torso was empty or water-filled. A qualitative comparison to data reconstructed using the clinical reconstruction algorithm showed that the two methods performed similarly, although the images reconstructed using the clinical software were more uniform due to the incorporation of noise regularization and post-filtration in that reconstruction technique., Conclusions: We developed a Monte Carlo-based reconstruction method for pinhole SPECT and evaluated it using phantom measurements. The combination of a Monte Carlo-based forward-projector and a simplified analytical ray-tracing back-projector produced quantitative images of acceptable image quality. No explicit calibration is necessary in this method since the forward-projector model maintains a relationship between the number of counts and activity.

Background: Dosimetry in radionuclide therapy has the potential to allow for a treatment tailored to the individual patient. One therapeutic radiopharmaceutical where patient-specific dosimetry is feasible is 177 Lu-DOTATATE, used for the treatment of neuroendocrine tumours. The emission of gamma photons by 177 Lu allows for imaging with SPECT (single photon emission computed tomography). One important step for dosimetry using this imaging technique is the SPECT image segmentation, which needs to be robust and accurate for the estimated quantities to be reliable. This work investigates different methods for automatic tumour delineation in 177 Lu-DOTATATE SPECT images. Three segmentation methods are considered: a fixed 42% threshold (FT), the Otsu method (OM) and a method based on Fourier surfaces (FS). Effects of including resolution compensation in the iterative SPECT image reconstruction are also studied. Evaluation is performed based on Monte Carlo-simulated SPECT images from 24 h and 336 h post injection (p.i.), for determination of the volume, activity concentration and dice similarity coefficient. In addition, patient data are used to investigate the correspondence of tumour volumes when delineated in SPECT or morphological CT or MR images. Patient data are also used to examine the sensitivity to the operator-dependent initialization., Results: For simulated images from 24 h p.i. reconstructed without resolution compensation, a volume and activity-concentration root-mean-square error below 15% is typically obtained for tumours above approximately 10 cm 3 when using OM or FS, while FT performs considerably worse. When including resolution compensation, the tumour volume becomes underestimated and the activity concentration overestimated. The FS method appears to be robust to noise, as seen for the 336 h images. The differences between the tumour volumes estimated from the SPECT images and the volumes estimated from morphological images are generally larger than the discrepancies seen for the simulated data sets., Conclusions: Segmentation results are encouraging for future dosimetry of tumours with volumes above approximately 10 cm 3 . Using resolution compensation in the reconstruction may have a negative effect on volume estimation.

Objectives: We compared patients' assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians' assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (< 1 year) versus long (≥ 1 year) disease duration., Method: Patients filled out the SLAQ before physicians' assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearman's ρ. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests., Results: We included 203 patients (79% women), with a median age of 45 years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians' SLAM without laboratory items (SLAM-nolab) and patients' assessments were: SLAQ total, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 0.24). Patients' and physicians' assessments were notably more discordant for patients with short disease durations., Conclusion: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients' and physicians' assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.

Objective: Associations between maternal glucose levels and increased foetal growth are well established, and independent relationships with maternal weight, weight gain and insulin resistance are also observed. The relative roles of lipolysis and glucose production in the determination of these observations remain unclear., Design: We examined, through detailed physiological studies, the relationship between maternal late gestational energy substrate production (glucose and glycerol), maternal weight and weight gain, and estimated foetal size in the third trimester., Patients: Twenty-one nulliparous pregnant women, without gestational diabetes (GDM) assessed at 28 weeks with oral glucose tolerance test, were recruited., Measurements: Rates of hepatic glucose production (GPR) and rates of glycerol production (reflecting lipolysis) using [ 13 C 6 ]-glucose and [ 2 H 5 ]-glycerol were measured at 34-36 weeks of gestation. Respiratory quotient was assessed by indirect calorimetry and body composition by measurements of total body water (TBW; H 2 18 O) and body density (BODPOD). Foetal weight was estimated from ultrasound measures of biparietal diameter, femoral length and abdominal circumference., Results: At 34-36 weeks, bivariate analyses showed that GPR and lipolysis correlated with estimated foetal weight (r=.71 and .72, respectively) as well as with maternal weight, fat mass and fat-free mass, but not maternal weight gain. In multivariate analyses, rates of both glucose production (r=.42) and lipolysis (r=.47) were independently associated with foetal size explaining 63% of the variance., Conclusions: Both maternal rates of lipolysis and hepatic glucose production in late gestation are strongly related to estimated foetal weight., (© 2017 John Wiley & Sons Ltd.)

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants associated with adverse human health effects including cancer. However, the risk of exposure to mixtures is difficult to estimate, and risk assessment by whole mixture potency evaluations has been suggested. To facilitate this, reliable in vitro based testing systems are necessary. Here, we investigated if activation of DNA damage signaling in vitro could be an endpoint for developing whole mixture potency factors (MPFs) for airborne PAHs. Activation of DNA damage signaling was assessed by phosphorylation of Chk1 and H2AX using Western blotting. To validate the in vitro approach, potency factors were determined for seven individual PAHs which were in very good agreement with established potency factors based on cancer data in vivo. Applying the method using Stockholm air PAH samples indicated MPFs with orders of magnitude higher carcinogenic potency than predicted by established in vivo-based potency factors. Applying the MPFs in cancer risk assessment suggested that 45.4 (6% of all) cancer cases per year in Stockholm are due to airborne PAHs. Applying established models resulted in <1 cancer case per year, which is far from expected levels. We conclude that our in vitro based approach for establishing MPFs could be a novel method to assess whole mixture samples of airborne PAHs to improve health risk assessment.

Background: Interferon (IFN)-α is thought to have a pivotal role in systemic lupus erythematosus (SLE), and type III IFNs (IFN-λ) were recently also associated with SLE. In this study, we measured levels of IFN-α, IFN-λ1, and related cytokines, such as IL-17A, IL-23, and interferon-γ-induced protein 10 (IP-10), in a Karolinska University Hospital cohort of patients with SLE and control subjects. The objective of the study was to investigate if cytokine measurements could identify different subsets of patients with active SLE and higher disease damage., Methods: We included 261 patients with SLE and 261 population control subjects. All participants underwent a standardized clinical examination. Medical files were reviewed. Patients with SLE were assessed for current organ manifestations, disease activity, and damage. Routine blood parameters, complement levels, and serology were analyzed at the time of inclusion. Levels of IFN-λ1, IFN-α, IL-17A, IL-23, and IP-10 were measured by enzyme-linked immunosorbent assay., Results: IFN-λ1 and IFN-α were detected in 29% and 44% of patients, respectively, but their levels did not correlate. High serum levels of IFN-λ1 were positively associated with antinucleosome antibodies and lymphopenia but negatively with musculoskeletal damage. Positive correlations between levels of IFN-λ1, IL-17A, and IL-23 were observed. Patients with high levels of these three cytokines had more disease damage, especially renal impairment. High levels of IFN-α were associated with mucocutaneous disease; leukopenia; and low complement, Ro/SSA, and La/SSB. Vascular events and antiphospholipid antibodies were uncommon. We identified two subgroups with high disease activity: one with double-high IFN-λ1 and IFN-α and another with IP-10 high . The former had more neuropsychiatric manifestations, and the latter had more arthritis. Increased levels of both types I and III IFNs were found in a proportion of population control subjects. Therefore, high IFN levels do not seem to be SLE-specific biomarkers., Conclusions: Measurements of circulating IFN-λ1 and IFN-α define subsets of patients with SLE with different characteristics. Levels of IFN-λ1 correlate with T-helper type 17 cytokines and identify a subgroup with more damage. High disease activity is associated with either simultaneous upregulation of IFN-λ1 and IFN-α or independently with IP-10. Our findings could be of major importance when tailoring therapy for patients with SLE with agents targeting IFN pathways.

Objective: Severe growth hormone deficiency (GHD) leads to several metabolic effects in the body ranging from abnormal body composition to biochemical disturbances. However, less is known regarding these parameters in short children with GH peak levels in the lower normal range during provocation tests. Our aim was to study the metabolic profile of this group and compare it with that of healthy children of normal height., Design: Thirty-five pre-pubertal short children (<-2.5 SDS) aged between 7 and 10years, with peak levels of GH between 7 and 14μg/L in an arginine insulin tolerance test (AITT), were compared with twelve age- and sex-matched children of normal height. The metabolic profile of the subjects was analysed by blood samples, DEXA, frequently sampled intravenous glucose tolerance test, microdialysis and stable isotope examinations of rates of glucose production and lipolysis., Results: There were no overall significant metabolic differences between the groups. However, in the subgroup analysis, the short children with GH peaks <10μg/L had significantly lower fasting insulin levels which also correlated to other metabolic parameters., Conclusion: The short pre-pubertal children with GH peak levels between 7 and 14μg/L did not differ significantly from healthy children of normal height but subpopulations within this group show significant metabolic differences., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.

Background: Treatment responses to methylphenidate by adults with ADHD are generally monitored against DSM-IV/DSM-V symptomatology, rating scales or interviews during reviews., Aims: To evaluate the use of single- and dual-dimension processing-speed and efficiency measures to monitor the effects of pharmacological treatment with methylphenidate after a short period off medication., Methods: A Quick Test of Cognitive Speed (AQT) monitored the effects of immediate-release methylphenidate in 40 previously diagnosed and medicated adults with ADHD. Processing speed was evaluated with prior prescription medication, without medication after a 2-day period off ADHD medication, and with low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride (Medikinet IR)., Results: Thirty-three participants responded to the experimental treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant main effects for single dimension colour and form and dual-dimension colour-form naming. Post-hoc analysis indicated statistical differences between the no- and high-dose medication conditions for colour and form, measures of perceptual speed. For colour-form naming, a measure of cognitive speed, there was a significant difference between no- and low-dose medication and between no- and high-dose medications, but not between low- and high-dose medications., Conclusions: Results indicated that the AQT tests effectively monitored incremental effects of the methylphenidate dose on processing speed after a 2-day period off medication. Thus, perceptual (colour and form) and cognitive speed (two-dimensional colour-form naming) and processing efficiency (lowered shift costs) increased measurably with high-dose medication. These preliminary findings warrant validation with added measures of associated behavioural and cognitive changes.

Aim: To investigate the prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) in a population-based group of children and adolescents with Down syndrome, and to relate the findings to level of intellectual disability and to medical conditions., Method: From a population-based cohort of 60 children and adolescents with Down syndrome, 41 individuals (29 males, 12 females; mean age 11y, age range 5-17y) for whom parents gave consent for participation were clinically assessed with regard to ASD and ADHD. The main instruments used were the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Swanson, Nolan, and Pelham-IV Rating Scale, and the Adaptive Behavior Assessment System-II., Results: High rates of ASD and ADHD were found: 17 (42%) and 14 (34%) of the 41 children met DSM criteria for ASD and ADHD respectively., Interpretation: Children with Down syndrome and coexisting neurodevelopmental/neuropsychiatric disorders in addition to intellectual disability and medical disorders constitute a severely disabled group. Based on the results, we suggest that screening is implemented for both ASD and ADHD, at the age of 3 to 5 years and early school years respectively, to make adequate interventions possible., (© 2016 Mac Keith Press.)

Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality., Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors., Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls., Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined., Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046)., Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension., (Copyright © 2017 by the Endocrine Society)

A major reorganization of a university hospital included the clinical structure as well as the administrative structure of the hospital. The focus of the reorganization was to improve the coordination of patient flows through the hospital. An important part of the organizational change was the introduction of flow managers. The aim of the article is to describe and analyze the challenges of the flow managers in the implementation of the reorganization. The description is based on a number of individual and focus group interviews with professionals and managers on different organizational levels. The analysis is guided by a broad conceptual framework, focusing on the processes of change in a professional organization like a hospital. The results show that the flow managers started with a lot of uncertainty regarding their responsibilities. There was also a lot of resistance to the reorganization, which the flow managers came to personify. They proceeded by building relationships and shaping their role and tasks. They tried to balance proactive and reactive strategies of change. There were some positive results, but they felt that that the expectations placed on them had been unrealistic. The introduction of flow managers in a university hospital has touched upon many elements of the conceptual framework. There were a number of structural, cultural, financial and strategic barriers influencing the change process. The main conclusion of the analysis is that the flow managers need more power and legitimacy in the organization to deal with these barriers. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25-hydroxyvitamin D 3 and 1α,25-dihydroxyvitamin D 3 . The results demonstrate that primary dermal fibroblasts have an active vitamin D 3 -metabolizing system. High incidence of low bone mineral density is a concern for HIV-infected patients treated with antiretroviral drugs. Osteomalacia and severe vitamin D deficiency have been reported. We investigated whether drug-mediated gene regulation could be a possible mechanism behind these adverse drug effects. Fibroblasts were treated with different drugs used in HIV therapy, and the 1α,25-dihydroxyvitamin D 3 levels and relative mRNA levels for crucial enzymes were determined. Efavirenz, stavudine and ritonavir significantly down-regulated the bioactivating CYP2R1 and up-regulated the catabolic CYP24A1. The drugs reduced bioactivating enzyme activities and cellular levels of 1α,25-dihydroxyvitamin D 3 . The current results indicate that effects on gene expression may lead to disturbed vitamin D metabolism and decreased cellular levels of active vitamin D 3 . The data are consistent with the impaired bone health in patients treated with certain antiretroviral drugs., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells., (Copyright © 2016 by the American Society of Nephrology.)

Objectives: To investigate how the direct biofeedback on vocal loudness administered with a portable voice accumulator (VoxLog) should be configured, to facilitate an optimal learning outcome for individuals with Parkinson's disease (PD), on the basis of principles of motor learning., Study Design: Methodologic development in an experimental study., Methods: The portable voice accumulator VoxLog was worn by 20 participants with PD during habitual speech during semistructured conversations. Six different biofeedback configurations were used, in random order, to study which configuration resulted in a feedback frequency closest to 20% as recommended on the basis of previous studies., Results: Activation of feedback when the wearer speaks below a threshold level of 3 dB below the speaker's mean voice sound level in habitual speech combined with an activation time of 500 ms resulted in a mean feedback frequency of 21.2%., Conclusions: Settings regarding threshold and activation time based on the results from this study are recommended to achieve an optimal learning outcome when administering biofeedback on vocal loudness for individuals with PD using portable voice accumulators., (Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment., Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (ISS) or born small for gestational age (SGA)., Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982)., Main Outcome Measures: Death., Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001)., Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with (131)I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

The aim of the present study was to obtain baseline information about oral health, oral health behaviours and knowledge about prevention of oral diseases in newly arrived Somali children. All 310 Somali children arriving in four municipalities in Kronoberg County, Sweden, during 2013 participated. We collected interview data (background factors related to oral health) and performed a clinical examination (oral hygiene, marginal bone loss, malocclusion, dental caries) within the first two months after arrival.The children were analysed in three age groups: 3-6 years (n=49), 7-11 years (n=125), and 12-17years (n=136). The interview revealed that 78-82% of the children in the three groups had never visited a dental clinic in Somalia. Toothache was reported by 18-28% of the children. In the youngest group,71% of the parents did not assist with tooth-cleaning and children commonly used a Miswak stick for cleaning. About half the children had poor oral hygiene while 25-33% repor- ted daily intake of sugary snacks. Malocclusion affected 40% of the 7-11-year-olds and 50% of the 12-17-year-olds. Bone loss affected 13% of the 12-17-year-olds.The 3-6-year-olds had a high prevalence (37%) of missing primary, lower cuspids. Their mean number of decayed, extracted and filled primary teeth (deft) was 2.3, and 43% were free from caries. In the 7-11-year-olds, mean decayed and filled permanent teeth (DFT) was o.8, while in the 12--17-year-olds DFT was 2.2 with 40% caries-free. Comparison with resident children indicates substantially higher caries preva- lence among the Somali children. The study has shown that newly arrived Somali children often present with oral diseases and are in urgent need of treatment and have great need for oral health promotion.

A computer model of a patient-specific clinical (177)Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of (177)Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.

Patient-specific image-based dosimetry is considered to be a useful tool to limit toxicity associated with peptide receptor radionuclide therapy (PRRT). To facilitate the establishment and reliability of absorbed-dose response relationships, it is essential to assess the accuracy of dosimetry in clinically realistic scenarios. To this end, we developed pharmacokinetic digital phantoms corresponding to patients treated with (177)Lu-DOTATATE. Three individual voxel phantoms from the XCAT population were generated and assigned a dynamic activity distribution based on a compartment model for (177)Lu-DOTATATE, designed specifically for this purpose. The compartment model was fitted to time-activity data from 10 patients, primarily acquired using quantitative scintillation camera imaging. S values for all phantom source-target combinations were calculated based on Monte-Carlo simulations. Combining the S values and time-activity curves, reference values of the absorbed dose to the phantom kidneys, liver, spleen, tumours and whole-body were calculated. The phantoms were used in a virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and conventional methods for absorbed-dose calculations. The characteristics of the SPECT and WB planar images were found to well represent those of real patient images, capturing the difficulties present in image-based dosimetry. The phantoms are expected to be useful for further studies and optimisation of clinical dosimetry in (177)Lu PRRT.

Optical properties of natural photonic structures can inspire material developments in diversified areas, such as the spectral design of surfaces for camouflage. Here, reflectance, scattering, and polarization properties of the cuticle of the scarab beetle Cyphochilus insulanus are studied with spectral directional hemispherical reflectance, bidirectional reflection distribution function (BRDF) measurements, and Mueller-matrix spectroscopic ellipsometry (MMSE). At normal incidence, a reflectance (0.6-0.75) is found in the spectral range of 400-1600 nm and a weaker reflectance <0.2 in the UV range as well as for wavelengths >1600  nm. A whiteness of W=42 is observed for mainly the elytra of the beetle. Chitin is a major constituent of the insect cuticle which is verified by the close similarity of the measured IR spectrum to that of α-chitin. The BRDF signal shows close-to-Lambertian properties of the beetle for visible light at small angles of incidence. From the MMSE measurement it is found that the beetles appear as dielectric reflectors reflecting linearly polarized light at oblique incidence with low gloss and a low degree of polarization. The measured beetle properties are properties that can be beneficial in a camouflage material.

Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility., (Copyright © 2015, American Association for the Advancement of Science.)

Reports of hypocortisolism and overweight in pediatric ADHD motivate an investigation of blood glucose regulation in this group. Fasting blood glucose and HbA1c were investigated in 10 children (10-15 years) with ADHD and 22 comparisons. Fasting blood glucose was similar in both groups. HbA1c values were higher in the ADHD-group. BMI-SDS was also higher in the ADHD-group but did not predict HbA1c. The results suggest an association between ADHD and an altered blood glucose homeostasis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The association between low birth weight and adult disease is well known. Less is known on long-term effects of high birth weight., Objective: This study aims to investigate whether a high birth weight increases risk for adult metabolic disease., Methods: Swedish term single births, 1973-1982 (n = 759,999), were studied to age 27.5-37.5 years using Swedish national registers. Hazard ratios (HRs) were calculated in relation to birth weight for type 2 diabetes, obesity, hypertension and dyslipidaemia., Results: Men with birth weights between 2 and 3 standard deviation score (SDS) had a 1.9-fold increased risk (HR 1.91, 95% confidence interval [CI] 1.25-2.90) of type 2 diabetes, whereas those with birth weights above 3 SDS had a 5.4-fold increased risk (HR 5.44, 95% CI 2.70-10.96) compared to men with birth weights between -2 and 2 SDS. The corresponding HRs for women were 0.60 (95% CI 0.40-0.91) and 1.71 (95% CI 0.85-3.43) for birth weights 2-3 SDS and >3 SDS, respectively. Men with birth weights between 2 and 3 SDS had a 1.5-fold increased risk (HR 1.47, 95% CI 1.22-1.77) of obesity. The corresponding risk for women was 1.3-fold increased (HR 1.32, 95% CI 1.19-1.46). For men and women with birth weights above 3 SDS, the risks of adult obesity were higher, HR 2.46 (95% CI 1.63-3.71) and HR 1.85 (95% CI 1.44-2.37), respectively., Conclusions: A high birth weight, particularly very high, increases the risk of type 2 diabetes in male young adults. The risk of obesity increases with increasing birth weight in both genders., (© 2014 The Authors. Pediatric Obesity © 2014 World Obesity.)

Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.

Pyruvate dehydrogenase (PDH) deficiency is an inherited disorder of carbohydrate metabolism, resulting in lactic acidosis and neurological dysfunction. In order to provide energy for the brain, a ketogenic diet has been tried. Both the disorder and the ketogenic therapy may influence energy production. The aim of the study was to assess hepatic glucose production, lipolysis and resting energy expenditure (REE) in an infant, given a ketogenic diet due to neonatal onset of the disease. Lipolysis and glucose production were determined for two consecutive time periods by constant-rate infusions of [1,1,2,3,3-²H₅]-glycerol and [6,6-²H²]-glucose. The boy had been fasting for 2.5 h at the start of the sampling periods. REE was estimated by indirect calorimetry. Rates of glucose production and lipolysis were increased compared with those of term neonates. REE corresponded to 60% of normal values. Respiratory quotient (RQ) was increased, indicating a predominance of glucose oxidation. Blood lactate was within the normal range. Several mechanisms may underlie the increased rates of glucose production and lipolysis. A ketogenic diet will result in a low insulin secretion and reduced peripheral and hepatic insulin sensitivity, leading to increased production of glucose and decreased peripheral glucose uptake. Surprisingly, RQ was high, indicating active glucose oxidation, which may reflect a residual enzyme activity, sufficient during rest. Considering this, a strict ketogenic diet might not be the optimal choice for patients with PDH deficiency. We propose an individualised diet for this group of patients aiming at the highest glucose intake that each patient will tolerate without elevated lactate levels.

Background: Overweight and obesity are risk factors for cardiovascular disease. There is also an association between body mass index (BMI) and cognitive ability. Since low birth weight is associated with adult metabolic disease, particularly in obese subjects, the question emerges whether obesity has an additional negative effect on cognitive function in subjects with low birth weight., Objectives: The aim was to analyse whether overweight or obesity influence intellectual performance in young adults with particular focus on those with a low birth weight., Methods: Data were collected from the Swedish Medical Birth Register on 620,834 males born between 1973 and 1988 and matched to results on intellectual performance and BMI at conscription., Results: The risk for low intellectual performance was higher for those with high BMI compared to those with normal. The highest risk was found among subjects with low birth weight and overweight or obesity in young adulthood (odds ratios, 1.98 [1.73-2.22] and 2.59 [2.00-3.34], respectively). However, subjects with further high birth weight and a high BMI at conscription had no further increased risk., Conclusions: Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance. A high birth weight increases the risk for obesity, but a high adult BMI does not further increase the risk for subnormal performance., (© 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.)

Down syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall's corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Hardwired sensor installations using proprietary protocols found in today's district heating substations limit the potential usability of the sensors in and around the substations. If sensor resources can be shared and re-used in a variety of applications, the cost of sensors and installation can be reduced, and their functionality and operability can be increased. In this paper, we present a new concept of district heating substation control and monitoring, where a service oriented architecture (SOA) is deployed in a wireless sensor network (WSN), which is integrated with the substation. IP-networking is exclusively used from sensor to server; hence, no middleware is needed for Internet integration. Further, by enabling thousands of sensors with SOA capabilities, a System of Systems approach can be applied. The results of this paper show that it is possible to utilize SOA solutions with heavily resource-constrained embedded devices in contexts where the real-time constrains are limited, such as in a district heating substation.

Purpose: The purpose of this study was twofold: to verify a fast, clinically applicable method for determining off-axis refraction and to assess the impact of objectively obtained off-axis refractive correction on peripheral low-contrast visual acuity., Methods: We measured peripheral low-contrast resolution acuity with Gabor patches both with and without off-axis correction at 20 degrees in the nasal visual field of 10 emmetropic subjects; the correction was obtained using a commercial open-field Hartmann-Shack wavefront sensor, the COAS-HD VR aberrometer. Off-axis refractive errors were calculated for a 5-mm circular pupil inscribed within the elliptical wavefront by COAS using the instruments' inbuilt "Seidel sphere" method., Results: Most of the subjects had simple myopic astigmatism, at 20 degrees in the nasal visual field ranging from -1.00 to -2.00 DC, with axis orientations generally near 90 degrees. The mean uncorrected and corrected low-contrast resolution acuities for all subjects were 0.92 and 0.86 logMAR, respectively (an improvement of 0.06 logMAR). For subjects with a scalar power refractive error of 1.00 diopters or more, the average improvement was 0.1 logMAR. The observed changes in low-contrast resolution acuity were strongly correlated with off-axis astigmatism (Pearson r = 0.95; p < 0.0001), the J180 cross-cylinder component (Pearson r = 0.82; p = 0.0034), and power scalar (Pearson r = -0.75; p = 0.0126)., Conclusions: The results suggest that there are definite benefits in correcting even moderate amounts of off-axis refractive errors; in this study, as little as -1.50 DC of off-axis astigmatism gave improvements of up to a line in visual acuity. It may be even more pertinent for people who rely on optimal peripheral visual function, specifically those with central visual field loss; the use of open-field aberrometers could be clinically useful in rapidly determining off-axis refractive errors specifically for this patient group who are generally more challenging to refract.

Background and Aim: As a result of New Public Management, a number of industrial models of quality management have been implemented in health care, mainly in hospitals. At the same time, the concept of integrated care has been developed within other parts of the health sector. The aim of the article is to discuss the relevance of integrated care for hospitals., Theory and Methods: The discussion is based on application of a conceptual framework outlining a number of organizational models of integrated care. These models are illustrated in a case study of a Danish university hospital implementing a new organization for improving the patient flows of the hospital. The study of the reorganization is based mainly on qualitative data from individual and focus group interviews., Results: The new organization of the university hospital can be regarded as a matrix structure combining a vertical integration of clinical departments with a horizontal integration of patient flows. This structure has elements of both interprofessional and interorganizational integration. A strong focus on teamwork, meetings and information exchange is combined with elements of case management and co-location., Conclusions: It seems that integrated care can be a relevant concept for a hospital. Although the organizational models may challenge established professional boundaries and financial control systems, this concept can be a more promising way to improve the quality of care than the industrial models that have been imported into health care. This application of the concept may also contribute to widen the field of integrated care.