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Conservation of endangered fishes commonly includes captive breeding, applied research, and management. Since 1996, a captive breeding program has existed for the federally threatened and California endangered Delta Smelt Hypomesus transpacificus, an osmerid fish endemic to the upper San Francisco Estuary. Although this program serves as a captive refuge population, with experimental releases being initiated to supplement the wild population, it was uncertain how individuals would survive, feed, and maintain condition outside hatchery conditions. We evaluated this and the effects of three enclosure designs (41% open, 63% open, and 63% open with partial outer mesh wrap) on growth, survival, and feeding efficacy of cultured Delta Smelt at two locations (Sacramento River near Rio Vista, CA and in Sacramento River Deepwater Ship Channel) in the wild. Enclosures exposed fish to semi-natural conditions (ambient environmental fluctuations and wild food resources) but prevented escape and predation. After four weeks, survival was high for all enclosure types (94-100%) at both locations. The change in condition and weight was variable between sites, increasing at the first location but decreasing at the second location. Gut content analysis showed that fish consumed wild zooplankton that came into the enclosures. Cumulatively, results show that captive-reared Delta Smelt can survive and forage successfully when housed in enclosures under semi-natural conditions in the wild. When comparing enclosure types, we observed no significant difference in fish weight changes (p = 0.58-0.81 across sites). The success of housing captive-reared Delta Smelt in enclosures in the wild provides preliminary evidence that these fish may be suitable to supplement the wild population in the San Francisco Estuary. Furthermore, these enclosures are a new tool to test the efficacy of habitat management actions or to acclimate fish to wild conditions as a soft release strategy for recently initiated supplementation efforts.

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (

ObjectivesWe set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV.DesignIMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858).MethodsIMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented.ResultsAmong 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value

Stable isotope analysis is an increasingly used molecular tool to reconstruct the diet and ecology of elusive primates such as unhabituated chimpanzees. The consumption of C4 plant feeding termites by chimpanzees may partly explain the relatively high carbon isotope values reported for some chimpanzee communities. However, the modest availability of termite isotope data as well as the diversity and cryptic ecology of termites potentially consumed by chimpanzees obscures our ability to assess the plausibility of these termites as a C4 resource. Here we report the carbon and nitrogen isotope values from 79 Macrotermes termite samples from six savanna woodland chimpanzee research sites across equatorial Africa. Using mixing models, we estimated the proportion of Macrotermes C4 plant consumption across savanna woodland sites. Additionally, we tested for isotopic differences between termite colonies in different vegetation types and between the social castes within the same colony in a subset of 47 samples from 12 mounds. We found that Macrotermes carbon isotope values were indistinguishable from those of C3 plants. Only 5 to 15% of Macrotermes diets were comprised of C4 plants across sites, suggesting that they cannot be considered a C4 food resource substantially influencing the isotope signatures of consumers. In the Macrotermes subsample, vegetation type and caste were significantly correlated with termite carbon values, but not with nitrogen isotope values. Large Macrotermes soldiers, preferentially consumed by chimpanzees, had comparably low carbon isotope values relative to other termite castes. We conclude that Macrotermes consumption is unlikely to result in high carbon isotope values in either extant chimpanzees or fossil hominins.

Floodplains represent critical nursery habitats for a variety of fish species due to their highly productive food webs, yet few tools exist to quantify the extent to which these habitats contribute to ecosystem-level production. Here we conducted a large-scale field experiment to characterize differences in food web composition and stable isotopes (δ¹³C, δ¹⁵N, δ³⁴S) for salmon rearing on a large floodplain and adjacent river in the Central Valley, California, USA. The study covered variable hydrologic conditions including flooding (1999, 2017), average (2016), and drought (2012-2015). In addition, we determined incorporation rates and tissue fractionation between prey and muscle from fish held in enclosed locations (experimental fields, cages) at weekly intervals. Finally, we measured δ³⁴S in otoliths to test if these archival biominerals could be used to reconstruct floodplain use. Floodplain-reared salmon had a different diet composition and lower δ13C and δ³⁴S (δ¹³C = -33.02±2.66‰, δ³⁴S = -3.47±2.28‰; mean±1SD) compared to fish in the adjacent river (δ¹³C = -28.37±1.84‰, δ³⁴S = +2.23±2.25‰). These isotopic differences between habitats persisted across years of extreme droughts and floods. Despite the different diet composition, δ¹⁵N values from prey items on the floodplain (δ¹⁵N = 7.19±1.22‰) and river (δ¹⁵N = 7.25±1.46‰) were similar, suggesting similar trophic levels. The food web differences in δ13C and δ³⁴S between habitats were also reflected in salmon muscle tissue, reaching equilibrium between 24-30 days (2014, δ¹³C = -30.74±0.73‰, δ³⁴S = -4.6±0.68‰; 2016, δ¹³C = -34.74 ±0.49‰, δ³⁴S = -5.18±0.46‰). δ³⁴S measured in sequential growth bands in otoliths recorded a weekly time-series of shifting diet inputs, with the outermost layers recording time spent on the floodplain (δ³⁴S = -5.60±0.16‰) and river (δ³⁴S = 3.73±0.98‰). Our results suggest that δ¹³C and δ³⁴S can be used to differentiate floodplain and river rearing habitats used by native fishes, such as Chinook Salmon, across different hydrologic conditions and tissues. Together these stable isotope analyses provide a toolset to quantify the role of floodplains as fish habitats.

Conservation of endangered fishes commonly includes captive breeding, applied research, and management. Since 1996, a captive breeding program has existed for the federally threatened and California endangered Delta Smelt Hypomesus transpacificus, an osmerid fish endemic to the upper San Francisco Estuary. Although this program serves as a captive refuge population, with experimental releases being initiated to supplement the wild population, it was uncertain how individuals would survive, feed, and maintain condition outside hatchery conditions. We evaluated this and the effects of three enclosure designs (41% open, 63% open, and 63% open with partial outer mesh wrap) on growth, survival, and feeding efficacy of cultured Delta Smelt at two locations (Sacramento River near Rio Vista, CA and in Sacramento River Deepwater Ship Channel) in the wild. Enclosures exposed fish to semi-natural conditions (ambient environmental fluctuations and wild food resources) but prevented escape and predation. After four weeks, survival was high for all enclosure types (94-100%) at both locations. The change in condition and weight was variable between sites, increasing at the first location but decreasing at the second location. Gut content analysis showed that fish consumed wild zooplankton that came into the enclosures. Cumulatively, results show that captive-reared Delta Smelt can survive and forage successfully when housed in enclosures under semi-natural conditions in the wild. When comparing enclosure types, we observed no significant difference in fish weight changes (p = 0.58-0.81 across sites). The success of housing captive-reared Delta Smelt in enclosures in the wild provides preliminary evidence that these fish may be suitable to supplement the wild population in the San Francisco Estuary. Furthermore, these enclosures are a new tool to test the efficacy of habitat management actions or to acclimate fish to wild conditions as a soft release strategy for recently initiated supplementation efforts.

Avoidance-based emotion regulation plays a central role in the development and maintenance of anxiety disorders across the life span. However, measures for children that account for different avoidance strategies, are scarce. Derived from Gross' Process Model of Emotion Regulation, the Bochum Assessment of Avoidance-based Emotion Regulation for Children (BAER-C) was developed to assess avoidance strategies (cognitive avoidance, behavioural avoidance, verbal reassurance, and social reassurance) and reappraisal in anticipatory anxious situations. In the present study, the BAER-C was administered to 129 school children aged 8 to 14 and 199 children with anxiety disorders aged 8 to 16 and their parents, along with established measures on anxiety, psychopathology, and emotion regulation. Factor structure, internal consistency, convergent, divergent and construct validity were analysed. Results of the anxious sample showed a satisfactory internal consistency (McDonald's ω = .94) for all scales as well as positive correlations with anxiety symptoms (all rs > .17, all ps < .05). Factor analysis supported a five-factor model. This model was confirmed in the student sample. Children with an anxiety disorder scored higher on behavioural avoidance, verbal reassurance, and social reassurance than school children (F (5,304) = 12.63, p = .003, ηp2 = .17). Results for construct validity were ambiguous. Our analyses suggest that the BAER-C is a promising theory-based new instrument to reliably assess different avoidance strategies in children. More research is needed to further analyse construct validity with other emotion regulation questionnaires.

When inundated by floodwaters, river floodplains provide critical habitat for many species of fish and wildlife, but many river valleys have been extensively leveed and floodplain wetlands drained for flood control and agriculture. In the Central Valley of California, USA, where less than 5% of floodplain wetland habitats remain, a critical conservation question is how can farmland occupying the historical floodplains be better managed to improve benefits for native fish and wildlife. In this study fields on the Sacramento River floodplain were intentionally flooded after the autumn rice harvest to determine if they could provide shallow-water rearing habitat for Sacramento River fall-run Chinook salmon (Oncorhynchus tshawytscha). Approximately 10,000 juvenile fish (ca. 48 mm, 1.1 g) were reared on two hectares for six weeks (Feb-March) between the fall harvest and spring planting. A subsample of the fish were uniquely tagged to allow tracking of individual growth rates (average 0.76 mm/day) which were among the highest recorded in fresh water in California. Zooplankton sampled from the water column of the fields were compared to fish stomach contents. The primary prey was zooplankton in the order Cladocera, commonly called water fleas. The compatibility, on the same farm fields, of summer crop production and native fish habitat during winter demonstrates that land management combining agriculture with conservation ecology may benefit recovery of native fish species, such as endangered Chinook salmon.

In this study, we show that virtual reality (VR) behaviometrics can be used for the assessment of compliance and physical laboratory skills. Drawing on approaches from machine learning and classical statistics, significant behavioral predictors were deduced from a logistic regression model that classified students and biopharma company employees as experts or novices on pH meter handling with 77% accuracy. Specifically, the game score and number of interactions in VR tasks requiring practical skills were found to be performance predictors. The study provides biopharma companies and academic institutions the possibility of assessing performance using an automatic, reliable, and simple alternative to traditional in-person assessment methods. Integrating the assessment into the training tool renders such laborious post-training assessments unnecessary.

The aim of this study was to explore differences in trunk muscle activity on a stable and mobile seat for people after stroke and healthy participants. Trunk control exercises are known to have a beneficial effect on trunk control, balance, and mobility after stroke. The effect of such exercises could be enhanced by the use of a mobile seat to provide further training stimuli. However, little research on the musculoskeletal effects of trunk training on mobile seats has been carried out. On a stable and a mobile seat, thirteen people after stroke and fifteen healthy participants performed two selective trunk control exercises, which were lateral flexion initiated by the pelvis and the thorax. The maximal surface electromyography relative to static sitting of the muscles multifidus, erector spinae, and obliquus externus was recorded bilaterally. The effects of group, seat condition, trunk control exercise, and muscle side were investigated employing within-subject linear-mixed-models. Compared to the stable seat, the maximal muscle activity of people after stroke on the mobile seat was higher during the thorax-initiated exercise and lower during the pelvis-initiated exercise. Healthy participants showed opposite results with higher muscle activity on the mobile seat during the pelvis-initiated exercise. For trunk control training on a mobile seat with high muscle activation people after stroke should perform trunk control exercises initiated by the thorax, for training with lower muscle activity people after stroke should initiate selective trunk movements by the pelvis. The results can support the planning of progressive trunk control rehabilitation programs.

Liquid manure (slurry) from livestock releases methane (CH4) that contributes significantly to global warming. Existing models for slurry CH4 production—used for mitigation and inventories—include effects of organic matter loading, temperature, and retention time but cannot predict important effects of management, or adequately capture essential temperature-driven dynamics. Here we present a new model that includes multiple methanogenic groups whose relative abundance shifts in response to changes in temperature or other environmental conditions. By default, the temperature responses of five groups correspond to those of four methanogenic species and one uncultured methanogen, although any number of groups could be defined. We argue that this simple mechanistic approach is able to describe both short- and long-term responses to temperature where other existing approaches fall short. The model is available in the open-source R package ABM (https://github.com/sashahafner/ABM) as a single flexible function that can include effects of slurry management (e.g., removal frequency and treatment methods) and changes in environmental conditions over time. Model simulations suggest that the reduction of CH4 emission by frequent emptying of slurry pits is due to washout of active methanogens. Application of the model to represent a full-scale slurry storage tank showed it can reproduce important trends, including a delayed response to temperature changes. However, the magnitude of predicted emission is uncertain, primarily as a result of sensitivity to the hydrolysis rate constant, due to a wide range in reported values. Results indicated that with additional work—particularly on the magnitude of hydrolysis rate—the model could be a tool for estimation of CH4 emissions for inventories.

PurposeTo adapt and validate a previously developed decision tree for youth to identify bedrest for use in preschool children.MethodsParents of healthy preschool (3-6-year-old) children (n = 610; 294 males) were asked to help them to wear an accelerometer for 7 to 10 days and 24 hours/day on their waist. Children with ≥3 nights of valid recordings were randomly allocated to the development (n = 200) and validation (n = 200) groups. Wear periods from accelerometer recordings were identified minute-by-minute as bedrest or wake using visual identification by two independent raters. To automate visual identification, chosen decision tree (DT) parameters (block length, threshold, bedrest-start trigger, and bedrest-end trigger) were optimized in the development group using a Nelder-Mead simplex optimization method, which maximized the accuracy of DT-identified bedrest in 1-min epochs against synchronized visually identified bedrest (n = 4,730,734). DT's performance with optimized parameters was compared with the visual identification, commonly used Sadeh's sleep detection algorithm, DT for youth (10-18-years-old), and parental survey of sleep duration in the validation group.ResultsOn average, children wore an accelerometer for 8.3 days and 20.8 hours/day. Comparing the DT-identified bedrest with visual identification in the validation group yielded sensitivity = 0.941, specificity = 0.974, and accuracy = 0.956. The optimal block length was 36 min, the threshold 230 counts/min, the bedrest-start trigger 305 counts/min, and the bedrest-end trigger 1,129 counts/min. In the validation group, DT identified bedrest with greater accuracy than Sadeh's algorithm (0.956 and 0.902) and DT for youth (0.956 and 0.861) (both PConclusionsThe DT-based algorithm initially developed for youth was adapted for preschool children to identify time spent in bedrest with high accuracy. The DT is available as a package for the R open-source software environment ("PhysActBedRest").

Stable isotope analysis is an increasingly used molecular tool to reconstruct the diet and ecology of elusive primates such as unhabituated chimpanzees. The consumption of C4 plant feeding termites by chimpanzees may partly explain the relatively high carbon isotope values reported for some chimpanzee communities. However, the modest availability of termite isotope data as well as the diversity and cryptic ecology of termites potentially consumed by chimpanzees obscures our ability to assess the plausibility of these termites as a C4 resource. Here we report the carbon and nitrogen isotope values from 79 Macrotermes termite samples from six savanna woodland chimpanzee research sites across equatorial Africa. Using mixing models, we estimated the proportion of Macrotermes C4 plant consumption across savanna woodland sites. Additionally, we tested for isotopic differences between termite colonies in different vegetation types and between the social castes within the same colony in a subset of 47 samples from 12 mounds. We found that Macrotermes carbon isotope values were indistinguishable from those of C3 plants. Only 5 to 15% of Macrotermes diets were comprised of C4 plants across sites, suggesting that they cannot be considered a C4 food resource substantially influencing the isotope signatures of consumers. In the Macrotermes subsample, vegetation type and caste were significantly correlated with termite carbon values, but not with nitrogen isotope values. Large Macrotermes soldiers, preferentially consumed by chimpanzees, had comparably low carbon isotope values relative to other termite castes. We conclude that Macrotermes consumption is unlikely to result in high carbon isotope values in either extant chimpanzees or fossil hominins.

This paper suggests and tests a psychological model of environmental art perception and subsequent support for climate change policies. The model is based on findings from art perception and environmental psychology, which indicate that the response of the viewer to the artwork is (1) first an emotional reaction, which can be positive and/or negative. The emotional activation leads to (2) evaluation of the perceived quality of the artwork. This forms the first impression of the artwork the viewer gets, which then triggers (3) reflections on the artwork that are finally related to support for climate policies. The model test uses data collected at the ArtCOP21 that accompanied the 21st UN climate summit in Paris. At 37 connected events, the research team collected 883 audience responses with a brief quantitative paper-pencil questionnaire. The data were analyzed using a multilevel-structural equation modeling approach. Results support the suggested theoretical model. Moreover, the effect of reflections on the artwork on support for climate policies is moderated by environmental attitudes, meaning the lower the environmental attitudes, the higher the effect of reflections on policy support. Finally, artwork features like color, size, displaying something personal, etc., could be identified that had a significant relation to differences on the artwork level regarding the first impression of the artwork and the reflections elicited. The study shows that being confronted with climate change-related artwork relates at least in the short run to increased climate policy support, which is mostly channeled through an emotional activation with following cognitive processing. Features of the artwork relate to how strongly and which emotions are activated.

ObjectivesWe set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV.DesignIMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858).MethodsIMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented.ResultsAmong 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value ConclusionsBone mineral density decline through week 74 postpartum was greater among breastfeeding HIV-infected women randomized to receive maternal TDF-ART during breastfeeding compared to those mothers whose infants received nevirapine prophylaxis.

Numerous health insurers offer bonus programmes that score customers' health behaviour, and car insurers offer telematics tariffs that score driving behaviour. In many countries, however, only a minority of customers participate in these programmes. In a population-representative survey of private households in Germany (N = 2,215), we study the acceptance of the criteria (features) on which the scoring programmes are based: the features for driver scoring (speed, texting while driving, time of driving, area of driving, accelerating and braking behaviour, respectively) and for health scoring (walking distance per day, sleeping hours per night, alcohol consumption, weight, participation in recommended cancer screenings, smoking status). In a second step, we model participants' acceptance of both programmes with regard to the underlying feature acceptance. We find that insurers in Germany rarely use the features which the participants consider to be the most relevant and justifiable, that is, smoking status for health scoring and smartphone use for driver scoring. Heuristic models (fast-and-frugal trees) show that programme acceptance depends on the acceptance of a few features. These models can help to understand customers' preferences and to design scoring programmes that are based on scientific evidence regarding behaviours and factors associated with good health and safe driving and are thus more likely to be accepted.

PurposeTo evaluate dual-energy CT (DE) and dedicated metal artifact reduction algorithms (iMAR) during CT-guided biopsy in comparison to single-energy CT (SE).MethodsA trocar was placed in the liver of six pigs. CT acquisitions were performed with SE and dose equivalent DE at four dose levels(1.7-13.5mGy). Iterative reconstructions were performed with and without iMAR. ROIs were placed in four positions e.g. at the trocar tip(TROCAR) and liver parenchyma adjacent to the trocar tip(LIVER-1) by two independent observers for quantitative analysis using CT numbers, noise, SNR and CNR. Qualitative image analysis was performed regarding overall image quality and artifacts generated by iMAR.ResultsThere were no significant differences in CT numbers between DE and SE at TROCAR and LIVER-1 irrespective of iMAR. iMAR significantly reduced metal artifacts at LIVER-1 for all exposure settings for DE and SE(p = 0.02-0.04), but not at TROCAR. SNR, CNR and noise were comparable for DE and SE. SNR was best for high dose levels of 6.7/13.5mGy. Mean difference in the Blant-Altman analysis was -8.43 to 0.36. Cohen's kappa for qualitative interreader-agreement was 0.901.ConclusionsiMAR independently reduced metal artifacts more effectively and efficiently than CT acquisition in DE at any dose setting and its application is feasible during CT-guided liver biopsy.

[This corrects the article DOI: 10.1371/journal.pone.0046425.].

INTRODUCTION:We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology. METHODS:Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 μm each) were investigated for dermal nerve fiber length (DNFL). RESULTS:In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p

OBJECTIVES:To compare image quality and metal artifact reduction between virtual monochromatic spectral imaging (VMSI), linearly blended dual-energy (DE) and single-energy (SE) images, each with and without dedicated iterative metal artifact reduction (iMAR) for CT-guided biopsy. MATERIALS AND METHODS:A biopsy trocar was positioned in the liver of six pigs. DE (Sn140/100kVp) and SE (120kVp/200mAs) acquisitions were performed with equivalent dose. From dual-energy datasets DE Q30-3 images and VMSI between 40-180 keV in steps of 20 keV were generated. From SE datasets I30-3 images were reconstructed. All images were reconstructed with and without iMAR. Objective image quality was analyzed applying density measurements at standardized positions (e.g. trocar tip and liver parenchyma adjacent to the trocar tip) and semi-automated threshold based segmentation. Subjective image quality was performed using semi-quantitative scores. Analyses were performed by two observers. RESULTS:At the trocar tip quantitative image analysis revealed significant difference in CT numbers between reconstructions with iMAR compared to reconstructions without iMAR for VMSI at lower keV levels (80 and 100 keV; p = 0.03) and DE (p = 0.03). For liver parenchyma CT numbers were significantly higher in VMSI at high keV compared to low keV (p≤0.01). VMSI at high keV also showed higher CT numbers compared to DE and SE images, though not the level of statistical significance. The best signal-to-noise ratio for VMSI was at 80 keV and comparable to DE and SE. Noise was lowest at 80 keV and lower than in DE and SE. Subjective image quality was best with VMSI at 80 keV regardless of the application of iMAR. iMAR significantly improved image quality at levels of 140 keV and 160 keV. Interreader-agreement was good for quantitative and qualitative analysis. CONCLUSION:iMAR improved image quality in all settings. VMSI with iMAR provided metal artifact reduction and better image quality at 80 keV and thus could improve the accurate positioning in CT-guided needle biopsy. In comparison, DE imaging did not improve image quality compared to SE.

Active Brownian particles (ABPs) are physical models for motility in simple life forms and easily studied in simulations. An open question is to what extent an increase of activity by a gradient of fuel, or food in living systems, results in an evolutionary advantage of actively moving systems such as ABPs over non-motile systems, which rely on thermal diffusion only. It is an established fact that within confined systems in a stationary state, the activity of ABPs generates density profiles that are enhanced in regions of low activity, which is thus referred to as 'anti-chemotaxis'. This would suggest that a rather complex sensoric subsystem and information processing is a precondition to recognize and navigate towards a food source. We demonstrate in this work that in non-stationary setups, for instance as a result of short bursts of fuel/food, ABPs do in fact exhibit chemotactic behavior. In direct competition with inactive, but otherwise identical Brownian particles (BPs), the ABPs are shown to fetch a larger amount of food. We discuss this result based on simple physical arguments. From the biological perspective, the ability of primitive entities to move in direct response to the available amount of external energy would, even in absence of any sensoric devices, encompass an evolutionary advantage.

The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.

Genital psoriasis affects 2-5% of psoriasis patients; generalised plaque or intertriginous psoriasis also affects the genital area in 29-40% of cases. Anogenital psoriasis has been associated with significant quality of life impairments, but little is known about specific patient needs/treatment goals. This study aimed to examine the overall and sex-related disease burden, patient needs and treatment benefits in patients with anogenital psoriasis, compared to patients with psoriasis not affecting the anal/genital areas. Within the cross-sectional nationwide survey, 2,009 participants were consecutively recruited in 157 randomly assigned German dermatology practices and clinics, according to the following inclusion criteria aged 18 years or over; diagnosis of psoriasis vulgaris; ability to answer the questionnaires; and written informed consent. Based on a high-resolution grid on the topical distribution of psoriasis, two groups were formed: anogenital psoriasis (n = 622) and comparison group (n = 1,303). Clinical severity was assessed by the Psoriasis Area and Severity Index (PASI). Patients completed the EuroQoL visual analogue scale (EQ VAS), the Dermatology Life Quality Index (DLQI), and the Patient Benefit Index (PBI). Patients with anogenital psoriasis had higher PASI (13.0±10.6 vs. 8.9±7.6, P < 0.001) and more DLQI impairments (8.9±6.9 vs. 7.0±6.2, P = 0.002) than controls. At the item-level, they also reported more sex-related DLQI impairments (DLQI-i9: 0.5±0.8 vs. 0.3±0.7, P < 0.001) and treatment needs (PBI-i17: 2.2±1.8 vs. 1.9±1.8, P = 0.001). A great percentage of missing/not-relevant responses was found for sex-related items (23.3-41.9%). These results suggest that the assessment of sex-related impairments and treatment needs should be prioritised in patients with anogenital psoriasis. Questionnaires may be used as a less uncomfortable way for patients to discuss their genital lesions and sexual function during healthcare visits. However, the great percentage of missing/not-relevant responses to sex-related items calls for in-depth assessments and effective patient-physician communication regarding these sensitive topics.

Similar to many large river valleys globally, the Sacramento River Valley has been extensively drained and leveed, hydrologically divorcing river channels from most floodplains. Today, the former floodplain is extensively managed for agriculture. Lack of access to inundated floodplains is recognized as a significant contributing factor in the decline of native Chinook Salmon (Oncorhynchus tshawytscha). We observed differences in salmon growth rate, invertebrate density, and carbon source in food webs from three aquatic habitat types-leveed river channels, perennial drainage canals in the floodplain, and agricultural floodplain wetlands. Over 23 days (17 February to 11 March, 2016) food web structure and juvenile Chinook Salmon growth rates were studied within the three aquatic habitat types. Zooplankton densities on the floodplain wetland were 53x more abundant, on average, than in the river. Juvenile Chinook Salmon raised on the floodplain wetland grew at 0.92 mm/day, 5x faster than fish raised in the adjacent river habitat (0.18 mm/day). Two aquatic-ecosystem modeling methods were used to partition the sources of carbon (detrital or photosynthetic) within the different habitats. Both modeling approaches found that carbon in the floodplain wetland food web was sourced primarily from detrital sources through heterotrophic pathways, while carbon in the river was primarily photosynthetic and sourced from in situ autotrophic production. Hydrologic conditions typifying the ephemerally inundated floodplain-shallower depths, warmer water, longer water residence times and predominantly detrital carbon sources compared to deeper, colder, swifter water and a predominantly algal-based carbon source in the adjacent river channel-appear to facilitate the dramatically higher rates of food web production observed in the floodplain. These results suggest that hydrologic patterns associated with seasonal flooding facilitate river food webs to access floodplain carbon sources that contribute to highly productive heterotrophic energy pathways important to the production of fisheries resources.

While flow is known to be a major driver of estuarine ecosystems, targeted flow manipulations are rare because tidal systems are extremely variable in space and time, and because the necessary infrastructure is rarely available. In summer 2018 we used a unique water control structure in the San Francisco Estuary (SFE) to direct a managed flow pulse into Suisun Marsh, one of the largest contiguous tidal marshes on the west coast of the United States. The action was designed to increase habitat suitability for the endangered Delta Smelt Hypomesus transpacificus, a small osmerid fish endemic to the upper SFE. The approach was to operate the Suisun Marsh Salinity Control Gates (SMSCG) in conjunction with increased Sacramento River tributary inflow to direct an estimated 160 x 106 m3 pulse of low salinity water into Suisun Marsh during August, a critical time period for juvenile Delta Smelt rearing. Three-dimensional modeling showed that directing additional low salinity water into Suisun Marsh ("Flow Action") substantially increased the area of low salinity habitat for Delta Smelt that persisted beyond the period of SMSCG operations. Field monitoring showed that turbidity and chlorophyll were at higher levels in Suisun Marsh, representing better habitat conditions, than the upstream Sacramento River region throughout the study period. The Flow Action had no substantial effects on zooplankton abundance, nor did Suisun Marsh show enhanced levels of these prey species in comparison to the Sacramento River. Fish monitoring data suggested that small numbers of Delta Smelt colonized Suisun Marsh from the Sacramento River during the 2018 Flow Action. Comparison of the salinity effects of the Flow Action to historical catch data for Suisun Marsh further supported our hypothesis that the Flow Action would have some benefit for this rare species. Our study provides insight into both the potential use of targeted flow manipulations to support endangered fishes such as Delta Smelt, and into the general response of estuarine habitat to flow management.

BackgroundDifficulties accessing surgical care (e.g., related to wait times, cancellations, cost, receiving a diagnosis) are understudied in Canada. Using population-based data, we studied difficulty accessing non-emergency surgical care, including (1) the incidence and annual changes in incidence, (2) types of difficulties, and (3) associated factors (e.g., sociodemographics, surgery characteristics).MethodsCross-sectional data from the Canadian Community Health Survey annual components were analyzed from 2005-2014. Weighted frequencies established the annual incidence of difficulty accessing surgical care, and total incidence of types of difficulties. Chi-square analyses, independent samples t-tests, and a multivariable logistic regression examined sociodemographic and surgery-related characteristics associated with difficulty accessing surgical care.ResultsAmong individuals who required past-year non-emergency surgery between 2005-2014 (weighted n = 3,052,072), 15.6% experienced difficulty accessing surgical care. The most common difficulty was "waited too long for surgery" (58.5%). There were significant differences in the incidence of difficulty according to year (Χ2 = 83.50, p < .001) from 2005-2014. The incidence of difficulty accessing surgery varied according to sex (Χ2 = 4.02, p < .05), surgery type (Χ2 = 96.09, p < .001), party responsible for cancellation/postponement (Χ2 range: 4.36-19.01, p < .05), and waiting time (t = 10.59, p < .001). In particular, males, orthopedic surgery, and surgery cancelled by the surgeon or hospital had the highest rates of difficulty.ConclusionResults provide insight into the difficulties experienced by patients accessing elective surgery, and the associated factors. These results may inform targeted healthcare interventions and resource reallocation to reduce these occurrences.

BackgroundMicroRNA (miRNA) mainly inhibit post-transcriptional gene expression of specific targets and may modulate disease severity.ObjectiveWe aimed to identify miRNA signatures distinguishing patient clusters with fibromyalgia syndrome (FMS).Subjects and methodsWe previously determined four FMS patient clusters labelled "maladaptive", "adaptive", "vulnerable", and "resilient". Here, we cluster-wise assessed relative gene expression of miR103a-3p, miR107, miR130a-3p, and miR125a-5p in white blood cell (WBC) RNA of 31 FMS patients and 16 healthy controls. Sum scores of pain-, stress-, and resilience-related questionnaires were correlated with miRNA relative gene expression. A cluster-specific speculative model of a miRNA-mediated regulatory cycle was proposed, and its potential targets verified by the online tool "target scan human".ResultsOne-way ANOVA revealed lower gene expression of miR103a-3p, miR107, and miR130a-3p in FMS patients compared to controls (p < 0.05). Follow-up post-hoc tests indicated the highest peak of gene expression of miR103a-3p for the adaptive cluster (p < 0.05), i.e. in patients with low disability in all symptom categories. Gene expression of miR103a-3p correlated with FMS related disability and miR107 with the score "physical abuse" of the trauma questionnaire (p < 0.05). Target scan identified sucrose non-fermentable serine/threonine protein kinase, nuclear factor kappa-b, cyclin dependent kinase, and toll-like receptor 4 as genetic targets of the miR103a/107 miRNA family.ConclusionWe show an association between upregulated gene expression of miR103a, tendentially of miR107, and adaptive coping in FMS patients. Validation of this pair of miRNA may enable to identify a somatic resilience factor in FMS.

Urban, peri-urban forests and other natural areas provide a wide range of material and non-material benefits to people known as ecosystem services. Access to these areas has been linked to benefits for physical and mental health of local populations. In the spring of 2020, the COVID-19 global pandemic forced many governments to impose a set of restrictions including the closure of businesses, cancelation of public events and schooling, social distancing, limitations on the size of social gatherings, and travel restrictions. During this period of restrictions, we conducted a study assessing the importance of urban and peri-urban forests and other natural areas to people living in and around the city of Burlington, Vermont, USA. We evaluated the self-reported use and changes in personal importance related to these natural areas before and during the period of restrictions. We received over 400 responses to our field survey. The results show that 69.0% of the respondents had increased or greatly increased their visitation rate to our natural areas and urban forests, and 80.6% of respondents considered that the importance of these areas, and access to them, either increased or greatly increased. Moreover 25.8% of the sample had either never, or very rarely accessed their local natural areas before the pandemic, but 69.2% of the first time or infrequent visitors reported that having access to these areas during COVID-19 as 'very important'. People reported that these areas were important for a wide range of activities from exercise to birding, but also reported values related to reducing stress in a time of global chaos. Our results indicate the increasing demand and value of such areas in times of crisis such as COVID-19. Experts in zoonotic disease predict the potential for more frequent pandemic events, thus predicating the importance for continued funding for, maintenance of, and improved access to, natural areas to our largely urban civilization.

Computed tomography (CT) scans represent the gold standard in the planning of functional endoscopic sinus surgeries (FESS). Yet, radiologists and otolaryngologists have different perspectives on these scans. In general, residents often struggle with aspects involved in both reporting and operation planning. The aim of this study was to compare the completeness of structured reports (SR) of preoperative CT images and structured operation planning (SOP) to conventional reports (CR) and conventional operation planning (COP) to potentially improve future treatment decisions on an individual level. In total, 30 preoperative CT scans obtained for surgical planning of patients scheduled for FESS were evaluated using SR and CR by radiology residents. Subsequently, otolaryngology residents performed a COP using free texts and a SOP using a specific template. All radiology reports and operation plannings were evaluated by two experienced FESS surgeons regarding their completeness for surgical planning. User satisfaction of otolaryngology residents was assessed by using visual analogue scales. Overall radiology report completeness was significantly higher using SRs regarding surgically important structures compared to CRs (84.4 vs. 22.0%, p

The parental stress scale (PSS) is a widely used instrument that assesses stress related to child rearing. Even though several studies have investigated the construct validity and reliability of the PSS, no consensus has been reached regarding which and how many of the original eighteen items that should be included, or a robust factor structure with satisfactory reliability. The present study tested the psychometric properties of the Norwegian version of the PSS and used the advantages of complementary exploratory and confirmatory factor analyses to investigate the underlying factor structure of the PSS items. Data stem from a community sample of 1096 parents from five counties in Norway with a one-year-old child. The sample was randomly split (N = 553/543), and exploratory and confirmatory analyses were performed on each of the samples. Using predefined criteria for the selection of robust items, results revealed a two-dimensional structure (Parental stressors and Lack of rewards) across 13 PSS items, displaying satisfactory reliability. Network analyses revealed differential associations within item constellations and with covariates. Implications of the findings and study limitations are discussed.

BackgroundCoping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS).ObjectiveWe aimed to identify somatic and psychosocial factors that might contribute to different coping strategies and resilience levels in FMS.Subjects and methodsStandardized questionnaires were used to assess coping, pain, and psychological variables in a cohort of 156 FMS patients. Quantitative real-time polymerase chain reaction (qRT-PCR) determined gene expression of selected cytokines in white blood cells of 136 FMS patients and 25 healthy controls. Data of skin innervation, functional and structural sensory profiles of peripheral nociceptive nerve fibers of a previous study were included into the statistics. An exploratory factor analysis was used to define variance explaining factors, which were then included into cluster analysis.Results54.9% of the variance was explained by four factors which we termed (1) affective load, (2) coping, (3) pain, and (4) pro-inflammatory cytokines (p < 0.05). Considering differences in the emerged factors, coping strategies, cytokine profiles, and disability levels, 118 FMS patients could be categorized into four clusters which we named "maladaptive", "adaptive", "vulnerable", and "resilient" (p < 0.05). The adaptive cluster had low scores in disability and in all symptom categories in contrast to the vulnerable cluster, which was characterized by high scores in catastrophizing and disability (p < 0.05). The resilient vs. the maladaptive cluster was characterized by better coping and a less pro-inflammatory cytokine pattern (p < 0.05).ConclusionOur data suggest that problem- and emotion-focused coping strategies and an anti-inflammatory cytokine pattern are associated with reduced disability and might promote resilience. Additional personal factors such as low anxiety scores, ability of acceptance, and persistence further favor a resilient phenotype. Individualized therapy should take these factors into account.

Cytosine-5 methylation within CpG dinucleotides is a potentially important mechanism of epigenetic influence on human traits and disease. In addition to influences of age and gender, genetic control of DNA methylation levels has recently been described. We used whole blood genomic DNA in a twin set (23 MZ twin-pairs and 23 DZ twin-pairs, N = 92) as well as healthy controls (N = 96) to investigate heritability and relationship with age and gender of selected DNA methylation profiles using readily commercially available GoldenGate bead array technology. Despite the inability to detect meaningful methylation differences in the majority of CpG loci due to tissue type and locus selection issues, we found replicable significant associations of DNA methylation with age and gender. We identified associations of genetically heritable single nucleotide polymorphisms with large differences in DNA methylation levels near the polymorphism (cis effects) as well as associations with much smaller differences in DNA methylation levels elsewhere in the human genome (trans effects). Our results demonstrate the feasibility of array-based approaches in studies of DNA methylation and highlight the vast differences between individual loci. The identification of CpG loci of which DNA methylation levels are under genetic control or are related to age or gender will facilitate further studies into the role of DNA methylation and disease.

In everyday life, we are often confronted with morally conflicting social interaction situations. Therefore, the main objective of the present set of studies was the development and validation of a new measure to assess decision-making in everyday moral conflict situations. All vignettes required a decision between an altruistic versus an egoistic behavioral response alternative. In three independent surveys (N = 200), we developed a 40-items measure with preferable mean rates of altruistic decisions (Study 1), clear representation of altruistic and egoistic response classes (Study 2), unambiguousness of social closeness classifications (socially close vs. socially distant protagonists; Studies 1 and 2), and high similarity to reality ratings (Studies 1 and 2). Additionally, we developed two parallelized item sets for future use in within-subjects design studies and investigated the measurement properties of our new scale (Studies 1 and 3). Results of Rasch model analyses and classical test theory fit indices showed unidimensionality and confirmed the appropriateness of the fragmentation into two parallelized item sets. Notably, in our data, there were neither effects of social closeness nor gender on the percentage of altruistic decisions. In sum, we propose the Everyday Moral Conflict Situations (EMCS) Scale as a promising new measurement tool that may facilitate further research in different research areas due to its broad applicability.

BACKGROUND:Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI). METHODS:Prospective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases. RESULTS:Mastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases. CONCLUSION:Our data do not support a clinical utility of the MDAPI to guide local therapy.

It is often assumed that word reading proceeds automatically. Here, we tested this assumption by recording event-related potentials during a psychological refractory period (PRP) paradigm, requiring lexical decisions about written words. Specifically, we selected words differing in their orthographic neighborhood size-the number of words that can be obtained from a target by exchanging a single letter-and investigated how influences of this variable depend on the availability of central attention. As expected, when attentional resources for lexical decisions were unconstrained, words with many orthographic neighbors elicited larger N400 amplitudes than those with few neighbors. However, under conditions of high temporal overlap with a high priority primary task, the N400 effect was not statistically different from zero. This finding indicates strong attentional influences on processes sensitive to orthographic neighbors during word reading, providing novel evidence against the full automaticity of processes involved in word reading. Furthermore, in conjunction with the observation of an underadditive interaction between stimulus onset asynchrony (SOA) and orthographic neighborhood size in lexical decision performance, commonly taken to indicate automaticity, our results raise issues concerning the standard logic of cognitive slack in the PRP paradigm.

Illusory face detection tasks can be used to study the neural correlates of top-down influences on face perception. In a typical functional magnetic resonance imaging (fMRI) study design, subjects are presented with pure noise images, but are told that half of the stimuli contain a face. The illusory face perception network is assessed by comparing blood oxygenation level dependent (BOLD) responses to images in which a face has been detected against BOLD activity related to images in which no face has been detected. In the present study, we highlight the existence of strong interindividual differences of BOLD activation patterns associated with illusory face perception. In the core system of face perception, 4 of 9 subjects had highly significant (p

BackgroundMagnetic resonance imaging (MRI) of the brain in children and adolescents is a well-established method in both clinical practice and in neuroscientific research. This practice is sometimes viewed critically, as MRI scans might expose minors (e.g. through scan-associated fears) to more than the legally permissible "minimal burden". While there is evidence that a significant portion of adults undergoing brain MRI scans experience anxiety, data on anxiety in children and adolescents undergoing brain MRI scans is rare. This study therefore aimed to examine the prevalence and level of anxiety in children and adolescents who had MRI scans of the brain, and to compare the results to adults undergoing brain MRI scans, and to children and adolescents undergoing electroencephalography (EEG; which is usually regarded a "minimal burden").MethodParticipants were 57 children and adolescents who had a brain MRI scan (MRI-C; mean age 12.9 years), 28 adults who had a brain MRI scan (MRI-A; mean age 43.7 years), and 66 children and adolescents undergoing EEG (EEG-C; mean age 12.9 years). Anxiety was assessed on the subjective (situational anxiety) and on the physiological level (arousal), before and after the respective examination.ResultsMore than 98% of children and adolescents reported no or only minimal fear during the MRI scan. Both pre- and post-examination, the MRI-C and the MRI-A groups did not differ significantly with respect to situational anxiety (p = 0.262 and p = 0.374, respectively), and to physiological arousal (p = 0.050, p = 0.472). Between the MRI-C and the EEG-C group, there were also no significant differences in terms of situational anxiety (p = 0.525, p = 0.875), or physiological arousal (p = 0.535, p = 0.189). Prior MRI experience did not significantly influence subjective or physiological anxiety parameters.ConclusionsIn this study, children and adolescents undergoing a brain MRI scan did not experience significantly more anxiety than those undergoing an EEG, or adults undergoing MRI scanning. Therefore, a general exclusion of minors from MRI research studies does not appear reasonable.

IntroductionEpoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice.MethodsIschemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-β, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9.ResultsIschemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-β, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-β, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone.ConclusionIn summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.

Back pain is a serious medical problem especially for those people sitting over long periods during their daily work. Here we present a system to help users monitoring and examining their sitting behavior. The Virtual-Spine Platform (VSP) is an integrated system consisting of a real-time body position monitoring module and a data visualization module to provide individualized, immediate, and accurate sitting behavior support. It provides a comprehensive spine movement analysis as well as accumulated data visualization to demonstrate behavior patterns within a certain period. The two modules are discussed in detail focusing on the design of the VSP system with adequate capacity for continuous monitoring and a web-based interactive data analysis method to visualize and compare the sitting behavior of different persons. The data was collected in an experiment with a small group of subjects. Using this method, the behavior of five subjects was evaluated over a working day, enabling inferences and suggestions for sitting improvements. The results from the accumulated data module were used to elucidate the basic function of body position recognition of the VSP. Finally, an expert user study was conducted to evaluate VSP and support future developments.

Sodium chloride promotes vascular fibrosis, arterial hypertension, pro-inflammatory immune cell polarization and endothelial dysfunction, all of which might influence outcomes following stroke. But despite enormous translational relevance, the functional importance of sodium chloride in the pathophysiology of acute ischemic stroke is still unclear. In the current study, we show that high-salt diet leads to significantly worse functional outcomes, increased infarct volumes, and a loss of astrocytes and cortical neurons in acute ischemic stroke. While analyzing the underlying pathologic processes, we identified the migrasome as a novel, sodium chloride-driven pathomechanism in acute ischemic stroke. The migrasome was previously described in vitro as a migrating organelle, which incorporates and dispatches cytosol of surrounding cells and plays a role in intercellular signaling, whereas a pathophysiological meaning has not been elaborated. We here confirm previously reported characteristics of the migrasome in vivo. Immunohistochemistry, electron microscopy and proteomic analyses further demonstrate that the migrasome incorporates and dispatches cytosol of surrounding neurons following stroke. The clinical relevance of these findings is emphasized by neuropathological examinations, which detected migrasome formation in infarcted brain parenchyma of human stroke patients. In summary, we demonstrate that high-salt diet aggravates stroke outcomes, and we characterize the migrasome as a novel mechanism in acute stroke pathophysiology.

BackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.MethodsPeripheral blood samples of 48 patients (62±10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 23 patients with left atrial low voltage areas (LVA), defined as ResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (qConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation.

We estimated the relative contribution of atmosphere (ic Nitrogen (N) input (wet and dry deposition and N fixation) to the epipelagic food web by measuring N isotopes of different functional groups of epipelagic zooplankton along 23°W (17°N-4°S) and 18°N (20-24°W) in the Eastern Tropical Atlantic. Results were related to water column observations of nutrient distribution and vertical diffusive flux as well as colony abundance of Trichodesmium obtained with an Underwater Vision Profiler (UVP5). The thickness and depth of the nitracline and phosphocline proved to be significant predictors of zooplankton stable N isotope values. Atmospheric N input was highest (61% of total N) in the strongly stratified and oligotrophic region between 3 and 7°N, which featured very high depth-integrated Trichodesmium abundance (up to 9.4×10(4) colonies m(-2)), strong thermohaline stratification and low zooplankton δ15N (~2‰). Relative atmospheric N input was lowest south of the equatorial upwelling between 3 and 5°S (27%). Values in the Guinea Dome region and north of Cape Verde ranged between 45 and 50%, respectively. The microstructure-derived estimate of the vertical diffusive N flux in the equatorial region was about one order of magnitude higher than in any other area (approximately 8 mmol m(-2) d(1)). At the same time, this region received considerable atmospheric N input (35% of total). In general, zooplankton δ15N and Trichodesmium abundance were closely correlated, indicating that N fixation is the major source of atmospheric N input. Although Trichodesmium is not the only N fixing organism, its abundance can be used with high confidence to estimate the relative atmospheric N input in the tropical Atlantic (r2 = 0.95). Estimates of absolute N fixation rates are two- to tenfold higher than incubation-derived rates reported for the same regions. Our approach integrates over large spatial and temporal scales and also quantifies fixed N released as dissolved inorganic and organic N. In a global analysis, it may thus help to close the gap in oceanic N budgets.

Species distribution models (SDMs) are increasingly applied in conservation management to predict suitable habitat for poorly known populations. High predictive performance of SDMs is evident in validations performed within the model calibration area (interpolation), but few studies have assessed SDM transferability to novel areas (extrapolation), particularly across large spatial scales or pelagic ecosystems. We performed rigorous SDM validation tests on distribution data from three populations of a long-ranging marine predator, the grey petrel Procellaria cinerea, to assess model transferability across the Southern Hemisphere (25-65°S). Oceanographic data were combined with tracks of grey petrels from two remote sub-Antarctic islands (Antipodes and Kerguelen) using boosted regression trees to generate three SDMs: one for each island population, and a combined model. The predictive performance of these models was assessed using withheld tracking data from within the model calibration areas (interpolation), and from a third population, Marion Island (extrapolation). Predictive performance was assessed using k-fold cross validation and point biserial correlation. The two population-specific SDMs included the same predictor variables and suggested birds responded to the same broad-scale oceanographic influences. However, all model validation tests, including of the combined model, determined strong interpolation but weak extrapolation capabilities. These results indicate that habitat use reflects both its availability and bird preferences, such that the realized distribution patterns differ for each population. The spatial predictions by the three SDMs were compared with tracking data and fishing effort to demonstrate the conservation pitfalls of extrapolating SDMs outside calibration regions. This exercise revealed that SDM predictions would have led to an underestimate of overlap with fishing effort and potentially misinformed bycatch mitigation efforts. Although SDMs can elucidate potential distribution patterns relative to large-scale climatic and oceanographic conditions, knowledge of local habitat availability and preferences is necessary to understand and successfully predict region-specific realized distribution patterns.

BackgroundRadiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes.Materials and methodsBlood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX.ResultsFor zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect.ConclusionAntioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes.

Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application.

Background The proximal humerus fracture is a common injury, but the optimal management is much debated. The decision for operative or nonoperative treatment is strongly influenced by patient specific factors, regional and cultural differences and the preference of the patient and treating surgeon. The aim of this study is to compare operative and nonoperative treatment of proximal humerus fractures for those patients for whom there is disagreement about optimal management. Methods and analysis This protocol describes an international multicenter prospective cohort study, in which all patients of 18 years and older presenting within three weeks after injury with a radiographically diagnosed displaced proximal humerus fracture can be included. Based on patient characteristics and radiographic images several clinical experts advise on the preferred treatment option. In case of disagreement among the experts, the patient can be included in the study. The actual treatment that will be delivered is at the discretion of the treating physician. The primary outcome is the QuickDash score at 12 months. Propensity score matching will be used to control for potential confounding of the relation between treatment modality and QuickDash scores. Discussion The LADON study is an international multicenter prospective cohort study with a relatively new methodological study design. This study is a “natural experiment” meaning patients receive standard local treatment and surgeons perform standard local procedures, therefore high participation rates of patients and surgeons are expected. Patients are only included after expert panel evaluation, when there is proven disagreement between experts, which makes this a unique study design. Through this inclusion process, we create two comparable groups whom received different treatments and where expert disagree about the already initiated treatment. Since we are zooming in on this particular patient group, confounding will be largely mitigated. Internationally the treatment of proximal humerus fractures are still much debated and differs much per country and hospital. This observational study with a natural experiment design will create insight into which treatment modality is to be preferred for patients in whom there is disagreement about the optimal treatment strategy. Trial registration Registered in Netherlands trial register NL9357 and Swiss trial register CH 2020–00961; https://clinicaltrials.gov/.

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (ResultsOver 15,580 person-years (PY) of follow-up, the incidence rate of NAFLD was 7.7 per 100 PY. In multivariate analysis adjusting for likely confounders, AD was associated with a 72% greater risk of NAFLD (IRR: 1.72 [95% CI:1.32-2.23]). Elevated blood glucose (IRR: 1.71 [95%CI: 1.29-2.28]) and physical inactivity (IRR: 1.46 [95%CI: 1.28-1.66]) were also independently associated with increased risk of NAFLD. In lean individuals, AD, elevated blood glucose and elevated BP were significantly associated with NAFLD although for elevated blood glucose, statistical significance was lost after adjusting for possible confounders. Physical inactivity and elevations in HsCRP were not associated with the risk of NAFLD in lean individuals only. Among lean (and non-lean) individuals, there was an independent association between progressively increasing waist circumference and NAFLD.ConclusionCardiometabolic risk factors are independently associated with NAFLD. However, there are significant differences in the metabolic risk predictors of NAFLD between lean and non-lean individuals. Personalized cardiovascular disease risk stratification and appropriate preventive measures should be considered in both lean and non-lean individuals to prevent the development of NAFLD.

BackgroundAtrial fibrillation (AF) has been linked to left atrial (LA) enlargement. Whereas most studies focused on 2D-based estimation of static LA volume (LAV), we used a fully-automatic convolutional neural network (CNN) for time-resolved (CINE) volumetry of the whole LA on cardiac MRI (cMRI). Aim was to investigate associations between functional parameters from fully-automated, 3D-based analysis of the LA and current classification schemes in AF.MethodsWe retrospectively analyzed consecutive AF patients who underwent cMRI on 1.5T systems including a stack of oblique-axial CINE series covering the whole LA. The LA was automatically segmented by a validated CNN. In the resulting volume-time curves, maximum, minimum and LAV before atrial contraction were automatically identified. Active, passive and total LA emptying fractions (LAEF) were calculated and compared to clinical classifications (AF Burden score (AFBS), increased stroke risk (CHA2DS2VASc≥2), AF type (paroxysmal/persistent), EHRA score, and AF risk factors). Moreover, multivariable linear regression models (mLRM) were used to identify associations with AF risk factors.ResultsOverall, 102 patients (age 61±9 years, 17% female) were analyzed. Active LAEF (LAEF_active) decreased significantly with an increase of AFBS (minimal: 44.0%, mild: 36.2%, moderate: 31.7%, severe: 20.8%, pConclusionsFully-automatic morphometry of the whole LA derived from cMRI showed significant relationships between LAEF_active with increased stroke risk and severity of AFBS. Furthermore, higher age, higher AFBS and presence of heart failure were independent predictors of reduced LAEF_active, indicating its potential usefulness as an imaging biomarker.