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Rationale: It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea.Objectives: We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea.Methods: Twelve healthy subjects experienced three stimuli: stimulus 1: maximal eucapnic voluntary hyperpnea against inspiratory resistance, requiring 15 times the work of resting breathing; stimulus 2: Pet(CO(2)) 6.1 mm Hg above resting with ventilation restricted to less than spontaneous breathing; stimulus 3: Pet(CO(2)) 7.7 mm Hg above resting with ventilation further restricted. After each trial, subjects rated SI, A(1), and qualities of dyspnea on the Multidimensional Dyspnea Profile (MDP), a comprehensive instrument tested here for the first time.Measurements and Main Results: Stimulus 1 was always limited by subjects failing to meet a higher ventilation target; none signaled severe discomfort. This evoked work and effort sensations, with relatively low unpleasantness (mean A(1)/SI = 0.64). Stimulus 2, titrated to produce dyspnea ratings similar to those subjects gave during stimulus 1, evoked air hunger and produced significantly greater unpleasantness (mean A(1)/SI = 0.95). Stimulus 3, increased until air hunger was intolerable, evoked the highest intensity and unpleasantness ratings and high unpleasantness ratio (mean A(1)/SI = 1.09). When asked which they would prefer to repeat, all subjects chose stimulus 1.Conclusions: (1) Maximal respiratory work is less unpleasant than moderately intense air hunger in this brief test; (2) unpleasantness of dyspnea can vary independently from perceived intensity, consistent with the prevailing model of pain; (3) separate dimensions of dyspnea can be measured with the MDP. [ABSTRACT FROM AUTHOR]

Purpose: Hydrocephalus presents diagnostic and management challenges due to its heterogeneity. The ASPECT Hydrocephalus System, introduced in 2023, offers a comprehensive approach to describing patients with hydrocephalus. This study investigates the clinical applicability of the ASPECT Hydrocephalus System compared to the International Classification of Disease (ICD-10) and demonstrates its utility., Methods: Two hundred pediatric and adult patients with hydrocephalus treated at Copenhagen University Hospital between September 2019 and 2020 were described according to the ASPECT Hydrocephalus System. The latest brain imaging served as assessment point., Results: Forty-seven percent of patients had more than one ICD-10 code assigned, and 40.5% of patients had an unspecific ICD-10 code as the most recent. It was possible to apply factor A (anatomy), S (symptomatology), P (previous interventions), C (complications) and T (time of onset) to all patients. Factor E (etiology) categorized 15% of patients as 'unknown'. Combining factor A and S showed a similar incidence of acute high-pressure symptoms in patients with and without ventriculomegaly on imaging (39.7% vs 39.3%), demonstrating how symptoms and neuro-radiological findings do not necessarily correlate., Conclusion: The ASPECT Hydrocephalus System's applicability and utility were demonstrated in a large, diverse patient population. Except for 'Etiology', all factors could be applied to the entire population showing the system's robustness. While limitations in ICD-10 may force clinicians to choose between clinical measures, the ASPECT Hydrocephalus System allows comprehensive patient characterization, potentially aiding in clinical decision-making and research. Its use depends on registration quality. Application in prospective cohorts is warranted to assure feasibility., (© 2024. The Author(s).)

Purpose: Telemetric monitoring of intracranial pressure (ICP) facilitates long-term measurements and home monitoring, thus potentially reducing diagnostic imaging and acute hospital admissions in favour of outpatient appointments. Especially in paediatric patients, telemetric ICP monitoring requires a high level of collaboration and compliance from patients and parents. In this study, we aim to systematically investigate (1) patient and parent perception of telemetric ICP system utility and (2) hospital contact history and thus the potential cost-benefit of telemetric ICP monitoring in paediatric patients with a cerebrospinal fluid disorder., Methods: We conducted a nationwide questionnaire study, including paediatric patients with either a current or previous telemetric ICP sensor and their parents. Additionally, a retrospective review of electronic health records for all included children was performed., Results: We included 16 children (age range 3-16 years), with a total of 41 telemetric ICP sensors implanted. Following sensor implantation, the frequency of telephone contacts and outpatient visits increased. No corresponding decrease in hospital admissions or total length of stay was found. The telemetric ICP sensor provided most parents with an improved sense of security and was seen as a necessary and valuable tool in treatment guidance. The size and shape of the sensor itself were reported as disadvantages, while the external monitoring equipment was reported as easy to use but too large and heavy for a child to carry., Conclusion: Though, in quantitative terms, there was no cost-benefit of the telemetric ICP sensor, it contributed to extended parental involvement and a sense of improved safety., (© 2024. The Author(s).)

Objective: Optimizing the treatment of several neurosurgical and neurological disorders relies on knowledge of the intracranial pressure (ICP). However, exploration of normal ICP and intracranial pressure pulse wave amplitude (PWA) values in healthy individuals poses ethical challenges, and thus the current documentation remains scarce. This study explores ICP and PWA values for healthy adults without intracranial pathology expected to influence ICP., Methods: Adult patients (age > 18 years) undergoing surgery for an unruptured intracranial aneurysm without any other neurological co-morbidities were included. Patients had a telemetric ICP sensor inserted, and ICP was measured in four different positions: supine, lateral recumbent, standing upright, and 45-degree sitting, at day 1, 14, 30, and 90 following the surgery., Results: ICP in each position did not change with time after surgery. Median ICP was 6.7 mmHg and median PWA 2.1 mmHg in the supine position, while in the upright standing position median ICP was - 3.4 mmHg and median PWA was 1.9 mmHg. After standardization of the measurements from the transducer site to the external acoustic meatus, the median ICP midbrain was 8.3 mmHg in the supine position and 1.2 mmHg in the upright standing position., Conclusion: Our study provides insights into normal ICP dynamics in healthy adults following a uncomplicated surgery for an unruptured aneurysm. These results suggest a slightly wider normal reference range for invasive intracranial pressure than previously suggested, and present the first normal values for PWA in different positions. Further studies are, however, essential to enhance our understanding of normal ICP. Trial registration The study was preregistered at www., Clinicaltrials: gov (NCT03594136) (11 July 2018)., (© 2024. The Author(s).)

Purpose: Family-based treatment (FBT) has contributed significantly to the treatment of anorexia nervosa (AN) in young people (YP). However, parents are concerned that FBT and the active role of parents in the task of refeeding may have a negative impact on family relations. The aim of the review is to assess whether families engaged in FBT for AN are more or less impacted in their family wellbeing and caregiver burden, compared to families with a YP diagnosed with AN, who are not undergoing treatment with FBT., Method: Computerized searches across six databases complemented by a manual search resulted in 30 papers being included in the scoping review., Results: The review identified 19 longitudinal studies on change in family wellbeing in families in FBT-like treatments, and 11 longitudinal studies on change in family wellbeing in treatment where parents are not in charge of refeeding. Only three randomized controlled studies directly compare FBT to treatment without parent-led refeeding., Conclusion: The available research suggests no difference between intervention types regarding impact on family wellbeing. Approximately half of the studies find improvements in family wellbeing in both treatment with and without parent-led refeeding, while the same proportion find neither improvement nor deterioration. As parents play a pivotal role in FBT, there is a need for good quality studies to elucidate the impact of FBT on family wellbeing. Level of evidence Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees., (© 2024. The Author(s).)

Objective: To assess how well national sentinel lists of the most frequently consumed foods in each food group capture data at subnational levels to measure minimum diet diversity (MDD)., Design: We analysed data from seven surveys with 24-h open dietary recalls to evaluate: (1) the percentage of reported foods that were included in each sentinel food list; (2) whether these lists captured consumption of some food groups better than others and (3) differences between estimates of dietary diversity calculated from all food items mentioned in the open 24-h recall v . only food items included in the sentinel lists., Setting: Seven subnational areas: Bangladesh (2), Benin, Colombia, Kenya, Malawi and Nepal., Participants: 8094 women 15-49 years; 4588 children 6-23 months., Results: National sentinel food lists captured most foods reportedly consumed by women (84 %) and children (86 %). Food groups with the highest variability were 'other fruits' and 'other vegetables.' MDD calculated from the sentinel list was, on average, 6·5 (women) and 4·1 (children) percentage points lower than when calculated from open 24-h recalls, with a statistically significant difference in most subnational areas., Conclusion: National sentinel food lists can provide reliable data at subnational levels for most food groups, with some variability by country and sub-region. Assessing the accuracy of national sentinel food lists, especially for fruits and vegetables, before using them at the subnational level could avoid potentially underestimating dietary diversity and provide more accurate local information for programmes, policy and research.

Background Acute abdomen is often complicated by intra-abdominal infection requiring antibiotic therapy. Danish regional antibiotic guidelines emphasize the restricted use of broad-spectrum antibiotics such as cephalosporins. In this study, we aimed to evaluate antibiotic practices in relation to hospitalized patients with acute abdomen. Methodology This retrospective quality assurance study was conducted among patients admitted to the surgical emergency department at the North Denmark Regional Hospital during a four-month observation period. Data were extracted from electronic patient journals and entered in the Research Electronic Data Capture data management system for further analytical work. Results Of 331 patients, 174 (53%) were treated with antibiotics, of whom 98 (56%) had been treated with cephalosporin, 47 (27%) with benzylpenicillin and gentamicin, 22 (13%) with piperacillin/tazobactam, and seven (4%) with ciprofloxacin. Use of a cephalosporin-based antibiotic regimen was significantly more common in patients with acute appendicitis (75%) compared to other diagnostic groups, such as acute cholecystitis (57%), incarcerated hernia with strangulation (56%), acute pancreatitis (50%), and acute diverticulitis (30%). However, patients with uncomplicated diverticulitis (53%) were significantly more often treated with benzylpenicillin and gentamicin, whereas patients with complicated diverticulitis Hinchey stage 3-4 were significantly more often treated with piperacillin/tazobactam. In addition, as the severity of acute cholecystitis increased, it was more frequently treated with piperacillin/tazobactam. Conclusions The study revealed that cephalosporins are frequently used in patients hospitalized with acute abdomen. This finding conflicts with current regional antibiotic guidelines. Reinforcement of the guidelines is required as an essential measure against the development of antibiotic resistance associated with the use of cephalosporins., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ozen et al.)

Purpose: Overdrainage (OD) is one of the most frequent complications related to drainage of the cerebrospinal fluid (CSF). It is mostly associated with valve-bearing shunt systems but should probably be considered as a risk factor in any type of CSF diversion procedure. There is extreme variation in the reported incidence of OD due to the lack of consensus on defining criteria and an unclear perception of the pathophysiology. Hence, OD is probably underreported and underestimated. The objective of this paper was to establish a definition of OD, based on a systematic review of the literature., Methods: A systematic search was conducted in MEDLNE and EMBASE. Studies providing a definition or a description of diagnostic findings related to OD in ventriculoperitoneal shunt treated hydrocephalus were included. Non-English titles, abstracts and manuscripts were excluded. Extracted descriptions were graded into five groups (class I-V studies) based on how precise the terminology used to describe OD was. Class I studies were included for further analysis and characteristics of OD were extracted. The quality of included descriptions was assessed by a clinical expert panel., Results: A total of 1309 studies were screened, 190 were graded into groups, and 22, which provided specific definitions or descriptions of OD, were graded as class I studies. We extracted 32 different characteristics consistent with OD (e.g., clinical symptoms, radiological signs, and syndromes)., Conclusion: There was an overall agreement that CSF overdrainage following implantation of a ventriculoperitoneal shunt in a mixed pediatric and adult population is characterized as a persistent condition with clinically manifestations as postural dependent headache, nausea, and vomiting and/or radiological signs of slim ventricles and/or subdural collections., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Autism is more prevalent among persons with Restrictive type eating disorders (R-ED) compared to the general population and is associated with poorer outcomes across treatment modalities. Knowledge is sparse with regard to whether poorer outcomes are also associated with Family-based treatment (FBT), which is recommended as the first choice of treatment for young persons (YPs) with R-ED. This case series compares outcome between groups with and without autism in a large consecutive series of YPs with R-ED treated with FBT., Method: In an earlier described consecutive series of 157 YPs with R-ED treated with FBT, we compared the outcomes of the subgroup with (N = 16) and without (N = 141) comorbid autism. Primary ICD-10 diagnoses were typical (50.0) or atypical anorexia nervosa (AN) (F50.1), the latter implying a condition as typical AN but with a failure to meet one of the diagnostic criteria. Autism diagnoses were clinically assigned. The outcomes were receiving intensified care, weight normalisation and overall successful treatment., Results: 10.2% (N = 16) of the sample had autism. 2.5% (N = 4) had autism diagnosed prior to the Eating Disorder (ED), and an additional 7.7% (N = 12) were diagnosed with autism during ED treatment. Significantly more YPs with autism (50%, N = 8) compared with YPs without autism (16%, N = 23) received intensified care (day programme or inpatient treatment) during their treatment. No significant difference between groups regarding neither weight normalisation nor successful ending of the treatment were found., Conclusion: This small sample of YPs with autism suggests that comparable proportions of YPs with and without autism may restore normal weight and end the treatment successfully within 12 months. However, more YPs with comorbid autism needed more intensive treatment, indicating that outpatient treatment delivery may not be sufficient to bring about desired change in this patient group. Findings need confirmation in a larger sample with a systematic screening for autism., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Family-based treatment (FBT) has demonstrated efficacy for anorexia nervosa (AN) in youth in randomized, controlled trials. It is important to assess if it shows a similar effectiveness when implemented in standard care., Aim: To evaluate outcomes of FBT for restrictive-type eating disorders, delivered as standard care in a public mental health service. Outcomes are remission, frequency of hospital admissions and day-patient treatment, and frequency of other adaptations within 12 months from commencement of treatment. Second, to compare the collaborative clinical decisions of successful treatment in standard care made by family therapist at the end of treatment, with more objective definitions of recovery., Methods: The design is a prospective, uncontrolled study of a consecutive series of patients with restrictive-type eating disorders, treated with FBT in a specialty unit at the Child and Adolescent Mental Health Centre in the Capital Region of Denmark., Results: FBT was successfully completed within 12 months by 57% of participants, and 47% completed with 20 sessions or fewer. Weight restoration was achieved by 75% within 12 months, and 46% achieved both normalisation of body weight and behavioural symptoms of AN within 12 months. A total of 20% needed intensified treatment. All aspects of remission were often not present simultaneously, and the collaborative clinical decisions of successful treatment only partly aligned with other parameters of remission., Conclusion: FBT showed good results when implemented as standard care, and it can be adapted to the specifics of local service organisation without compromising effectiveness., (© 2021. The Author(s).)

Background: Caribou and reindeer across the Arctic spend more than two thirds of their lives moving in snow. Yet snow-specific mechanisms driving their winter ecology and potentially influencing herd health and movement patterns are not well known. Integrative research coupling snow and wildlife sciences using observations, models, and wildlife tracking technologies can help fill this knowledge void., Methods: Here, we quantified the effects of snow depth on caribou winter range selection and movement. We used location data of Central Arctic Herd (CAH) caribou in Arctic Alaska collected from 2014 to 2020 and spatially distributed and temporally evolving snow depth data produced by SnowModel. These landscape-scale (90 m), daily snow depth data reproduced the observed spatial snow-depth variability across typical areal extents occupied by a wintering caribou during a 24-h period., Results: We found that fall snow depths encountered by the herd north of the Brooks Range exerted a strong influence on selection of two distinct winter range locations. In winters with relatively shallow fall snow depth (2016/17, 2018/19, and 2019/20), the majority of the CAH wintered on the tundra north of the Brooks Range mountains. In contrast, during the winters with relatively deep fall snow depth (2014/15, 2015/16, and 2017/18), the majority of the CAH caribou wintered in the mountainous boreal forest south of the Brooks Range. Long-term (19 winters; 2001-2020) monitoring of CAH caribou winter distributions confirmed this relationship. Additionally, snow depth affected movement and selection differently within these two habitats: in the mountainous boreal forest, caribou avoided areas with deeper snow, but when on the tundra, snow depth did not trigger significant deep-snow avoidance. In both wintering habitats, CAH caribou selected areas with higher lichen abundance, and they moved significantly slower when encountering deeper snow., Conclusions: In general, our findings indicate that regional-scale selection of winter range is influenced by snow depth at or prior to fall migration. During winter, daily decision-making within the winter range is driven largely by snow depth. This integrative approach of coupling snow and wildlife observations with snow-evolution and caribou-movement modeling to quantify the multi-facetted effects of snow on wildlife ecology is applicable to caribou and reindeer herds throughout the Arctic., (© 2021. The Author(s).)

Background: The standard lumbar puncture position involves maximum flexion of both lumbar and cervical spine. The cerebrospinal fluid opening pressure (CSF op ) is measured in a horizontal position. This study investigated if flexion of hip and neck both separately and simultaneously influence intracranial pressure (ICP) to a clinically relevant extent., Methods: Thirty-nine patients, undergoing invasive ICP monitoring as part of diagnostic work-up, were included. The patients underwent either a vertical postural examination (n = 24) or a horizontal postural examination (n = 15) to examine a varying degree of spine flexion., Results: The vertical examination showed that ICP decreased by 15.2 mmHg when straightening the neck in a sitting lumbar puncture position (n = 24, IQR - 20.1 to - 9.7). In the horizontal examination, ICP increased in all but one patient when changing from supine position to lateral recumbent position (n = 15, median increase of 6.9 mmHg, IQR 3.1 to 9.9). Straightening the hips alone decreased ICP with 0.2 mmHg (n = 15, IQR - 0.5 to 2.0), while straightening the neck alone decreased ICP by 4.0 mmHg (n = 15, IQR - 5.9 to - 1.7). However, when straightening the hip and neck simultaneously ICP decreased by 6.4 mmHg (n = 6, IQR - 9.5 to - 4.4)., Conclusions: Neck flexion alone, and neck flexion and hip flexion in combination, has significant confounding influence on ICP. This may cause patients to shift from a normal ICP range to a pathological ICP range, which will potentially affect treatment decisions. Consensus on guidelines for body position including neck and hip flexion measuring CSF op may be needed.

Participant representativeness and statistical power are crucial elements of robust research with human participants, both of which relate to the successful recruitment of research participants. Nevertheless, such core features may often not be fully reported or duly considered in psychiatric research. Building on our experiences of collecting data in the context of forensic mental health services, we discuss issues regarding participant recruitment and representativeness in our field with its particular characteristics. A quick sampling and brief overview of the literature in four specialized forensic mental health journals is presented, demonstrating that published manuscripts rarely describe the data in sufficient detail for the reader to assess sample representativeness and statistical power. This lack of transparency leads not only to difficulties in interpreting the research; it also entails risks relating to the already meager evidence base of forensic mental health services being relevant only to a subset of patients. Accordingly, we provide suggestions for increased transparency in reporting and improved recruitment of research participants. We also discuss the balance of ethical considerations pertinent to the pursuit of increased participation rates in forensic mental health research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pedersen, Bergman, Berlin and Hartvigsson.)

Species conservation in a rapidly changing world requires an improved understanding of how individuals and populations respond to changes in their environment across temporal scales. Increased warming in the Arctic puts this region at particular risk for rapid environmental change, with potentially devastating impacts on resident populations. Here, we make use of a parameterized full life cycle, individual-based energy budget model for wild muskoxen, coupling year-round environmental data with detailed ontogenic metabolic physiology. We show how winter food accessibility, summer food availability, and density dependence drive seasonal dynamics of energy storage and thus life history and population dynamics. Winter forage accessibility defined by snow depth, more than summer forage availability, was the primary determinant of muskox population dynamics through impacts on calf recruitment and longer term carryover effects of maternal investment. Simulations of various seasonal snow depth and plant biomass and quality profiles revealed that timing of and improved/limited winter forage accessibility had marked influence on calf recruitment (±10-80%). Impacts on recruitment were the cumulative result of condition-driven reproductive performance at multiple time points across the reproductive period (ovulation to calf weaning) as a trade-off between survival and reproduction. Seasonal and generational condition effects of snow-rich winters interacted with age structure and density to cause pronounced long-term consequences on population growth and structure, with predicted population recovery times from even moderate disturbances of 10 years or more. Our results show how alteration in winter forage accessibility, mediated by snow depth, impacts the dynamics of northern herbivore populations. Further, we present here a mechanistic and state-based model framework to assess future scenarios of environmental change, such as increased or decreased snowfall or plant biomass and quality to impact winter and summer forage availability across the Arctic., (© 2020 John Wiley & Sons Ltd.)

Background: Although widely used in the evaluation of the diseased, normal intracranial pressure and lumbar cerebrospinal fluid pressure remain sparsely documented. Intracranial pressure is different from lumbar cerebrospinal fluid pressure. In addition, intracranial pressure differs considerably according to the body position of the patient. Despite this, the current reference values do not distinguish between intracranial and lumbar cerebrospinal fluid pressures, and body position-dependent reference values do not exist. In this study, we aim to establish these reference values., Method: A systematic search was conducted in MEDLINE, EMBASE, CENTRAL, and Web of Sciences. Methodological quality was assessed using an amended version of the Joanna Briggs Quality Appraisal Checklist. Intracranial pressure and lumbar cerebrospinal fluid pressure were independently evaluated and subdivided into body positions. Quantitative data were presented with mean ± SD, and 90% reference intervals., Results: Thirty-six studies were included. Nine studies reported values for intracranial pressure, while 27 reported values for the lumbar cerebrospinal fluid pressure. Reference values for intracranial pressure were -  5.9 to 8.3 mmHg in the upright position and 0.9 to 16.3 mmHg in the supine position. Reference values for lumbar cerebrospinal fluid pressure were 7.2 to 16.8 mmHg and 5.7 to 15.5 mmHg in the lateral recumbent position and supine position, respectively., Conclusions: This systematic review is the first to provide position-dependent reference values for intracranial pressure and lumbar cerebrospinal fluid pressure. Clinically applicable reference values for normal lumbar cerebrospinal fluid pressure were established, and are in accordance with previously used reference values. For intracranial pressure, this study strongly emphasizes the scarcity of normal pressure measures, and highlights the need for further research on the matter.

Tundra dominates two-thirds of the unglaciated, terrestrial Arctic. Although this region has experienced rapid and widespread changes in vegetation phenology and productivity over the last several decades, the specific climatic drivers responsible for this change remain poorly understood. Here we quantified the effect of winter snowpack and early spring temperature conditions on growing season vegetation phenology (timing of the start, peak, and end of the growing season) and productivity of the dominant tundra vegetation communities of Arctic Alaska. We used daily remotely sensed normalized difference vegetation index (NDVI), and daily snowpack and temperature variables produced by SnowModel and MicroMet, coupled physically based snow and meteorological modeling tools, to (1) determine the most important snowpack and thermal controls on tundra vegetation phenology and productivity and (2) describe the direction of these relationships within each vegetation community. Our results show that soil temperature under the snowpack, snowmelt timing, and air temperature following snowmelt are the most important drivers of growing season timing and productivity among Arctic vegetation communities. Air temperature after snowmelt was the most important control on timing of season start and end, with warmer conditions contributing to earlier phenology in all vegetation communities. In contrast, the controls on the timing of peak season and productivity also included snowmelt timing and soil temperature under the snowpack, dictated in part by the snow insulating capacity. The results of this novel analysis suggest that while future warming effects on phenology may be consistent across communities of the tundra biome, warming may result in divergent, community-specific productivity responses if coupled with reduced snow insulating capacity lowers winter soil temperature and potential nutrient cycling in the soil., (© 2020 John Wiley & Sons Ltd.)

Animals have adapted behavioral and physiological strategies to conserve energy during periods of adverse conditions. Heterothermy is one such adaptation used by endotherms. While heterothermy-fluctuations in body temperature and metabolic rate-has been shown in large vertebrates, little is known of the costs and benefits of this strategy, both in terms of energy and in terms of fitness. Hence, our objective was to model the energetics of seasonal heterothermy in the largest Arctic ungulate, the muskox ( Ovibos moschatus ), using an individual-based energy budget model of metabolic physiology. We found that the empirically based drop in body temperature (winter max ~-0.8°C) overwinter in adult females resulted in substantial fitness benefits in terms of reduced daily energy expenditure and body mass loss. Body mass and energy reserves were 8.98% and 14.46% greater in modeled heterotherms compared to normotherms by end of winter. Based on environmental simulations, we show that seasonal heterothermy can, to some extent, buffer the negative consequences of poor prewinter body condition or reduced winter food accessibility, leading to greater winter survival (+20%-30%) and spring energy reserves (+10%-30%), and thus increased probability of future reproductive success. These results indicate substantial adaptive short-term benefits of seasonal heterothermy at the individual level, with potential implications for long-term population dynamics in highly seasonal environments., Competing Interests: We declare no competing interests., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The existence and persistence of rhythmicity in animal activity during phases of environmental change is of interest in ecology, evolution and chronobiology. A wide diversity of biological rhythms in response to exogenous conditions and internal stimuli have been uncovered, especially for polar vertebrates. However, empirical data supporting circadian organization in behaviour of large ruminating herbivores remains inconclusive. Using year-round tracking data of the largest Arctic ruminant, the muskox ( Ovibos moschatus ), we modelled rhythmicity as a function of behaviour and environmental conditions. Behavioural states were classified based on patterns in hourly movements, and incorporated within a periodicity analyses framework. Although circadian rhythmicity in muskox behaviour was detected throughout the year, ultradian rhythmicity was most prevalent, especially when muskoxen were foraging and resting in mid-winter (continuous darkness). However, when combining circadian and ultradian rhythmicity together, the probability of behavioural rhythmicity declined with increasing photoperiod until largely disrupted in mid-summer (continuous light). Individuals that remained behaviourally rhythmic during mid-summer foraged in areas with lower plant productivity (NDVI) than individuals with arrhythmic behaviour. Based on our study, we conclude that muskoxen may use an interval timer to schedule their behavioural cycles when forage resources are low, but that the importance and duration of this timer are reduced once environmental conditions allow energetic reserves to be replenished ad libitum. We argue that alimentary function and metabolic requirements are critical determinants of biological rhythmicity in muskoxen, which probably applies to ruminating herbivores in general., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

A Lagrangian snow-evolution model (SnowModel-LG) was used to produce daily, pan-Arctic, snow-on-sea-ice, snow property distributions on a 25 × 25-km grid, from 1 August 1980 through 31 July 2018 (38 years). The model was forced with NASA's Modern Era Retrospective-Analysis for Research and Applications-Version 2 (MERRA-2) and European Centre for Medium-Range Weather Forecasts (ECMWF) ReAnalysis-5th Generation (ERA5) atmospheric reanalyses, and National Snow and Ice Data Center (NSIDC) sea ice parcel concentration and trajectory data sets (approximately 61,000, 14 × 14-km parcels). The simulations performed full surface and internal energy and mass balances within a multilayer snowpack evolution system. Processes and features accounted for included rainfall, snowfall, sublimation from static-surfaces and blowing-snow, snow melt, snow density evolution, snow temperature profiles, energy and mass transfers within the snowpack, superimposed ice, and ice dynamics. The simulations produced horizontal snow spatial structures that likely exist in the natural system but have not been revealed in previous studies spanning these spatial and temporal domains. Blowing-snow sublimation made a significant contribution to the snowpack mass budget. The superimposed ice layer was minimal and decreased over the last four decades. Snow carryover to the next accumulation season was minimal and sensitive to the melt-season atmospheric forcing (e.g., the average summer melt period was 3 weeks or 50% longer with ERA5 forcing than MERRA-2 forcing). Observed ice dynamics controlled the ice parcel age (in days), and ice age exerted a first-order control on snow property evolution., (©2020. The Authors.)

Childhood economic conditions are important for adult health, and welfare regimes may modify this relationship by altering exposure to social determinants of health. We examine the association between childhood economic stress (CES) and self-rated health (SRH) and cancer (any type), and how welfare regimes may influence these associations. We used data from European Social Survey round 7. Our study is based on 30 024 individuals between 25 to 75 years from 20 European countries grouped into five welfare regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern and Eastern). Multilevel models were used to assess the association between CES and SRH/cancer, and interactions between CES and welfare regimes. CES increased the risk of poor SRH (RR 1.41, 95% CI 1.29-1.54) and cancer (RR 1.19, 95% CI 1.02-1.37). Controlling for adult socioeconomic status slightly reduced risk for poor SRH, but not cancer. CES increased the probability of poor SRH in the Southern and Eastern regime, and the probability of cancer in the Anglo-Saxon regime, relative to the Scandinavian regime. Childhood economic stress increases the risk of poor self-rated health and cancer. More comprehensive welfare states mitigate these associations, which emphasizes the impact of welfare policies on long-term health outcomes of childhood economic conditions., Competing Interests: The authors declare that there are no potential conflicts of interest with respect to the research, authorship, or publication of this article., (© 2020 The Author(s).)

Background: In highly seasonal environments, animals face critical decisions regarding time allocation, diet optimisation, and habitat use. In the Arctic, the short summers are crucial for replenishing body reserves, while low food availability and increased energetic demands characterise the long winters (9-10 months). Under such extreme seasonal variability, even small deviations from optimal time allocation can markedly impact individuals' condition, reproductive success and survival. We investigated which environmental conditions influenced daily, seasonal, and interannual variation in time allocation in high-arctic muskoxen ( Ovibos moschatus ) and evaluated whether results support qualitative predictions derived from upscaled optimal foraging theory., Methods: Using hidden Markov models (HMMs), we inferred behavioural states (foraging, resting, relocating) from hourly positions of GPS-collared females tracked in northeast Greenland (28 muskox-years). To relate behavioural variation to environmental conditions, we considered a wide range of spatially and/or temporally explicit covariates in the HMMs., Results: While we found little interannual variation, daily and seasonal time allocation varied markedly. Scheduling of daily activities was distinct throughout the year except for the period of continuous daylight. During summer, muskoxen spent about 69% of time foraging and 19% resting, without environmental constraints on foraging activity. During winter, time spent foraging decreased to 45%, whereas about 43% of time was spent resting, mediated by longer resting bouts than during summer., Conclusions: Our results clearly indicate that female muskoxen follow an energy intake maximisation strategy during the arctic summer. During winter, our results were not easily reconcilable with just one dominant foraging strategy. The overall reduction in activity likely reflects higher time requirements for rumination in response to the reduction of forage quality (supporting an energy intake maximisation strategy). However, deep snow and low temperatures were apparent constraints to winter foraging, hence also suggesting attempts to conserve energy (net energy maximisation strategy). Our approach provides new insights into the year-round behavioural strategies of the largest Arctic herbivore and outlines a practical example of how to approximate qualitative predictions of upscaled optimal foraging theory using multi-year GPS tracking data., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Mentalization is a developmental achievement defined as the capacity to understand behavior in terms of mental states. This study investigated mentalization in psychoanalytic psychotherapy (PPT) and cognitive behavior therapy (CBT) through a secondary data analysis of findings from a randomized controlled trial for bulimia nervosa. It was hypothesized that mentalization would predict alliance and outcome in both treatments, whereas increase in mentalization was only expected after PPT. Furthermore, it was investigated whether change in mentalization predicted symptom change. A total of 70 participants with bulimia nervosa were randomized to PPT or CBT. Participants were assessed at 3 time points with the Eating Disorder Examination and the Adult Attachment Interview (rated for reflective functioning [RF]). Therapy sessions were rated with the Vanderbilt Therapeutic Alliance Scale. Higher intake RF significantly predicted better alliance, whereas no association was observed between RF and outcome. A significant interaction between time, therapy type, and RF found RF improving more in PPT than in CBT. There was a significant association between RF change and symptom change in the PPT group. The study suggests a relation between RF and psychotherapy process, whereas the relation between RF and outcome is more complex. Furthermore, PPT seems to enhance mentalization, which seems related to symptomatic improvement, suggesting that mentalization might serve as a specific mechanism of change in PPT. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Immunohistochemical (IHC) quantification of estrogen receptor-α (ER) is used for assessment of treatment regimen in breast cancer. Different ER IHC assays may produce diverging results, because of different antibody clones, protocols, and stainer platforms. Objective tissue-based techniques to assess sensitivity and specificity of IHC assays are therefore needed. We tested the usability of ER mRNA-in situ hybridization (mRNA-ISH) in comparison with assays based on clones SP1 and 6F11. We selected 56 archival specimens according to their reported ER IHC positivity, representing a wide spectrum from negative to strongly positive cases. The specimens were used to prepare 4 TMAs with 112 cores. Serial sections of each TMA were stained for ER and pan-cytokeratin (PCK) by IHC and ESR1 (ER gene) by mRNA-ISH. Digital image analysis (DIA) was used to determine ER IHC H-score. ESR1 mRNA-ISH was scored both manually and by DIA. DIA showed a nonlinear correlation between IHC and ESR1 mRNA-ISH with R-values of 0.80 and 0.78 for the ER antibody clones SP1 and 6F11, respectively. Comparison of manual mRNA-ISH scoring categories and SP1 and 6F11 IHC H-scores showed a highly significant relationship (P<0.001). In conclusion, the study showed good correlation between mRNA-ISH and IHC, suggesting that mRNA-ISH can be a valuable tool in the assessment of the sensitivity and specificity of ER IHC assays.

Purpose of Review: Monitoring of intracranial pressure (ICP) is an important and integrated part of the treatment algorithm for children with severe traumatic brain injury (TBI). Guidelines often recommend ICP monitoring with a treatment threshold of 20 mmHg. This focused review discusses; (1) different ICP technologies and how ICP should be monitored in pediatric patients with severe TBI, (2) existing evidence behind guideline recommendations, and (3) how we could move forward to increase knowledge about normal ICP in children to support treatment decisions. Summary: Current reference values for normal ICP in adults lie between 7 and 15 mmHg. Recent studies conducted in "pseudonormal" adults, however, suggest a normal range below this level where ICP is highly dependent on body posture and decreases to negative values in sitting and standing position. Despite obvious physiological differences between children and adults, no age or body size related reference values exist for normal ICP in children. Recent guidelines for treatment of severe TBI in pediatric patients recommend ICP monitoring to guide treatment of intracranial hypertension. Decision on ICP monitoring modalities are based on local standards, the individual case, and the clinician's choice. The recommended treatment threshold is 20 mmHg for a duration of 5 min. Both prospective and retrospective observational studies applying different thresholds and treatment strategies for intracranial hypertension were included to support this recommendation. While some studies suggest improved outcome related to ICP monitoring (lower rate of mortality and severe disability), most studies identify high ICP as a marker of worse outcome. Only one study applied age-differentiated thresholds, but this study did not evaluate the effect of these different thresholds on outcome. The quality of evidence behind ICP monitoring and treatment thresholds in severe pediatric TBI is low and treatment can potentially be improved by knowledge about normal ICP from observational studies in healthy children and cohorts of pediatric "pseudonormal" patients expected to have normal ICP. Acceptable levels of ICP - and thus also treatment thresholds-probably vary with age, disease and whether the patient has intact cerebral autoregulation. Future treatment algorithms should reflect these differences and be more personalized and dynamic., (Copyright © 2020 Pedersen, Lilja-Cyron, Astrand and Juhler.)

Purpose: Repeated intracranial pressure (ICP) measurements are essential in treatment of patients with complex cerebrospinal fluid (CSF) disorders. These patients often have a long surgical history with numerous invasive lumbar or intracranial pressure monitoring sessions and/or ventriculoperitoneal (VP) shunt revisions. Telemetric ICP monitoring might be an advantageous tool in treatment of these patients. In this paper, we evaluate our experience with this technology in paediatric patients., Methods: During a 4-year period, we implanted telemetric ICP sensors (Raumedic NEUROVENT-P-tel) in 20 paediatric patients to minimise the number of future invasive procedures. Patients were diagnosed with hydrocephalus, idiopathic intracranial hypertension (IIH) or an arachnoid cyst. Most patients (85%) had a VP shunt at the time of sensor implantation., Results: In total, 32 sensors were inserted in the 20 patients; the cause of re-implantation was technical malfunction of the implant. One sensor was explanted due to wound infection and one due to skin erosion. We experienced no complications directly related to the implantation/explantation procedures. A total of 149 recording sessions were conducted, including 68 home monitoring sessions. The median implantation period was 523 days with a median duration of clinical use at 202 days. The most likely consequence of a recording session was non-surgical treatment alteration (shunt valve adjustment or acetazolamide dose adjustment)., Conclusion: Telemetric ICP monitoring in children is safe and potentially decreases the number of invasive procedures. We find that telemetric ICP monitoring aids the clinical management of patients with complex CSF disorders and improves everyday life for both patient and parents. It allows continuous ICP measurement in the patient's home and thereby potentially reducing hospitalisations, leading to significant cost savings.

Ga-PSMA PET/CT has become a well-established imaging modality to detect prostate cancer (PCa) metastases in biochemical recurrence. Despite its claimed specificity for PCa, Ga-PSMA uptake in tissues unrelated to PCa, particularly in the neovascular tissue of other cancers, has been reported in numerous studies. A 73-year-old man underwent Ga-PSMA PET/CT for biochemical recurrence of PCa 7 years after radical prostatectomy. The Ga-PSMA PET/CT showed 1 lesion with PSMA uptake in the distal left ureter. Histology revealed a low-grade noninvasive papillary urothelial carcinoma. By immunohistochemistry, PSMA expression was observed in the neoplastic urothelial cells and in the vessels of the papillary structures.

Objective: In this paper, we test the reliability and validity of two novel ways of assessing mentalizing in the therapy context: the Reflective Functioning scale (RF) applied to code psychotherapy transcripts (In-session RF), and the Exploring scale of the Patient Attachment Coding System (PACS), which measures in-session autonomy and is linked with secure attachment in psychotherapy. Method: Before treatment, 160 patients in different types of psychotherapy and from three different countries were administered the Adult Attachment Interview (AAI), which was rated with the RF scale. One early psychotherapy session for each patient was independently rated with the In-session RF scale and with the PACS Exploring scale. Results: Both scales were found to be reliable and to have concurrent validity with the RF scale rated on the AAI, with the PACS Exploring scale found to be a better predictor of RF on the AAI. Conclusions: These results suggest that the PACS Exploring scale might be a practical method for assessing RF in psychotherapy research and a way for researchers and clinicians to track patients' RF on an ongoing basis. These results also provide information regarding the ways in which differences in RF manifest during psychotherapy sessions. Clinical or methodological significance of this article Researchers and clinicians can assess patients' mentalizing based on any single psychotherapy transcript, in many therapeutic modalities The Exploring scale of the Patient Attachment Coding System can yield a reliable measure of reflective functioning based on any single psychotherapy transcript, in many therapeutic modalities Client differences in mentalizing manifest in part independently of the therapist's contributions.

Objective: Extended release (ER) tablets/capsules in massive ingestion overdoses are prone to form pharmacobezoars potentially increasing the risk of late-appearing toxic effects and prolonged symptoms. Oral activated charcoal is often sufficient to prevent drug absorption, but in a recent massive ingestion of highly toxic substances, prior orogastric lavage might be considered. The disintegration characteristics of ER preparations in overdose situations is valuable to understand if the time line and course of the intoxication might be prolonged, but information on these characteristics are unavailable. Slow disintegration and/or pharmacobezoar formation, and the large size makes ER preparation impossible to evacuate using a 30F orogastric lavage tube. This study evaluates the disintegration and pharmacobezoar formation of a simulated massive ER tablet ingestion in an in vitro model, using a selection of extended release tablets, with different disintegrating characteristics when present in therapeutic numbers. Furthermore, the sizes of the formed pharmacobezoars were compared with the dimensions of a 30F orogastric lavage tube., Method: A standardized model mimicking the physical effects on pharmaceutical preparations in simulated gastric fluid (SGF) was developed and tested on three mono-depot ER tablets (quetiapine/Seroquel ® XR 50 mg, paracetamol/Pinex ® Retard 500 mg, verapamil/Isoptin ® Retard 240 mg), one poly-depot ER tablet (carbamazepine/Tegretol ® Retard 200 mg), and one immediate-release tablet (paracetamol/Panodil ® 500mg). Thirty tablets were placed in polyamide mesh bags, either together in one bag or in separate bags, immersed in 1 L SGF, and incubated at 37 °C for 48 h. Released drugs were quantified at 0.5-48 h., Results: Visual inspection showed that Seroquel ® XR, Pinex ® Retard, and Isoptin ® Retard tablets formed firm pharmacobezoars stable for more than 4 h and intact fractions remained for up to 24 h. Drug releases were reduced by 53%, 40%, and 31%, respectively, for up to 8 h compared to separated tablets. Light microscopy showed that contact with SGF transformed the coating of Seroquel ® XR and Pinex ® Retard to a diffusion-controlled swelled gel-layer, and the Isoptin ® Retard tablets into a rigid and slow-releasing matrix. Tegretol ® Retard disintegrated into microspheres within 30 min, and Panodil ® disintegrated within minutes., Discussion: The developed pharmacobezoars of mono-depot ER tablets demonstrated prolonged drug release. Neither the formed pharmacobezoars, nor the single tablets of the tested mono-depot ER preparations, would pass through the lumen of a standard orogastric lavage tube, rendering this modality ineffective for tablet removal in gastrointestinal decontamination.

Infusion of pituitary adenylate cyclase activating peptide-38 (PACAP-38) provokes migraine attacks in migraineurs and headache in non-migraineurs. Adverse events like long-lasting flushing and heat sensation can be terminated with oral antihistamine treatment, indicating the involvement of mast cell activation after PACAP-infusion. Degranulation of rat peritoneal mast cells was provoked by several isoforms of PACAP via previously unknown receptor pharmacology. The effect might thus be mediated either via specific splice variants of the PAC 1 -receptor or via an unknown receptor for PACAP-38. In the present study, we characterize degranulation of rat meningeal mast cells in response to PACAP-receptor ligands. Furthermore, we investigate if PACAP-38-induced mast cell degranulation is mediated via PAC 1 -receptor splice variants and/or via the orphan Mas-related G-protein coupled member B3 (MrgB 3 )-receptor. To address this, the pharmacological effect of different PACAP isoforms on meningeal mast cell degranulation was investigated in the hemisected skull model after toluidine blue staining followed by microscopic quantification. Presence of mRNA encoding PAC 1 -receptor splice variants and the MrgB 3 -receptor in rat mast cells was investigated by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis. The effect of PACAP isoforms on PAC 1 - and MrgB 3 -receptor-expressing Xenopus laevis oocytes were performed by two-electrode voltage-clamp (TEVC) electrophysiology. PACAP-38 is a more potent mast cell degranulating agent than Pituitary Adenylate Cyclase Activating Peptide-27 (PACAP-27) in the meninges. Presence of mRNA encoding the PAC 1 -receptor and its different splice variants could not be detected in peritoneal mast cells by RT-PCR, whereas the orphan MrgB 3 -receptor, recently suggested to be a mediator of basic secretagogues-induced mast cell degranulation, was widely present. In PAC 1 -receptor-expressing Xenopus laevis oocytes both PACAP-38, PACAP-27 and the specific PAC 1 -receptor agonist maxadilan were equipotent, however, only PACAP-38 showed a significant degranulatory effect on mast cells. We confirmed Pituitary Adenylate Cyclase Activating Peptide(6-38) [PACAP(6-38)] to be a PAC 1 -receptor antagonist, and we demonstrated that it is a potent mast cell degranulator and have an agonistic effect on MrgB 3 -receptors expressed in oocytes. The present study provides evidence that PACAP-induced mast cell degranulation in rat is mediated through a putative new PACAP-receptor with the order of potency being: PACAP-38 = PACAP(6-38) > > PACAP-27 = maxadilan. The results suggest that the observed responses are mediated via the orphan MrgB 3 -receptor.

The aim of this study is to assess the prognostic value of mechanical dyssynchrony defined as the standard deviation of the time to peak longitudinal strain (SD T2P LS) in predicting the development of heart failure (HF) after an ST-segment elevation myocardial infarction (STEMI). Three hundred and seventy-three patients were admitted with STEMI and treated with primary percutaneous coronary intervention. Left ventricular (LV) mechanical dyssynchrony was examined through speckle tracking echocardiography and defined as SD T2P LS. The association with the outcome of HF hospitalization was assessed using Cox proportional hazard models. During a median follow-up of 5.12 years, 144 patients (38.6%) were admitted due to HF. Worse dyssynchrony was associated with the outcome in unadjusted and multivariable analysis (multivariable hazard ratio 1.05, 95% confidence interval 1.00-1.10, p-value 0.039, per 10 ms increase), but not after further adjustment for LV ejection fraction (LVEF), E/e' and global longitudinal strain (GLS) (hazard ratio 1.01, 95% confidence interval 1.00-1.07, p-value 0.71, per 10 ms increase), nor in a model only adjusting for GLS (hazard ratio 1.01, 95% confidence interval 1.00-1.06, p-value 0.61, per 10 ms increase). These findings were reproduced in a competing risk analysis treating all-cause mortality as a competing risk. LV mechanical dyssynchrony, as assessed by SD T2P LS is not an independent predictor of post-STEMI HF development and mechanical dyssynchrony does not provide independent prognostic information regarding HF when GLS is known.

Background A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis ( P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion ( P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min ( P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.

Nutrition-sensitive interventions to improve overall diet quality are increasingly needed to improve maternal and child health. This study demonstrates feasibility of a structured process to leverage local expertise in formulating programmes tailored for current circumstances in South Asia and Africa. We assembled 41 stakeholders in 2 regional workshops and followed a prespecified protocol to elicit programme designs listing the human and other resources required, the intervention's mechanism for impact on diets, target foods and nutrients, target populations, and contact information for partners needed to implement the desired programme. Via this protocol, participants described 48 distinct interventions, which we then compared against international recommendations and global goals. Local stakeholders' priorities focused on postharvest food systems to improve access to nutrient-dense products (75% of the 48 programmes) and on production of animal sourced foods (58%), as well as education and social marketing (23%) and direct transfers to meet food needs (12.5%). Each programme included an average of 3.2 distinct elements aligned with those recommended by United Nations system agencies in the Framework for Action produced by the Second International Conference on Nutrition in 2014 and the Compendium of Actions for Nutrition developed for the Renewed Efforts Against Child Hunger initiative in 2016. Our results demonstrate that a participatory process can help local experts identify their own priorities for future investments, as a first step in a novel process of rigorous, transparent, and independent priority setting to improve diets among those at greatest risk of undernutrition., (© 2017 The Authors. Maternal and Child Nutrition published by John Wiley & Sons, Ltd.)

Background: No true reference values for intracranial pressure (ICP) in humans exist; current values are estimated from measurements in adults who undergo treatment in order to correct ICP. We report ICP values in a "pseudonormal" group of children and adults to examine if age affects ICP., Methods: We analyzed data from all nonshunted patients undergoing a 24-hour ICP monitoring as part of a diagnostic work-up and included patients with no subsequent suspicion of increased ICP and no need for pressure-relieving treatment with a minimum follow-up period of 3 years., Results: From February 2008 to November 2014, a 24-hour ICP monitoring was performed in 221 patients. Of these patients, 35 (14 children, 21 adults) met the inclusion criteria. Follow-up time to confirm absence of ICP-related disease was 3-9 years. Daytime ICP was 2.8 mmHg ± 2.2 in children and 1.9 mmHg ± 4.2 in adults (P = 0.39). Of 35 patients, 32 had higher nighttime ICP. The difference between daytime and nighttime ICP was similar in children (ΔICP = 5.8 mmHg ± 4.0, P < 0.0001) and adults (ΔICP = 6.1 mm Hg ± 3.3, P < 0.0001). ICP could be described as a decreasing function of age, with an ICP decrement of 0.69 mmHg per decade (P = 0.015)., Conclusions: We found similar differences in daytime and nighttime ICP between children and adults with no ICP-related disease. ICP seems to decrease with age across all ages. This has implications for therapeutic interventions (e.g., shunt valve selection or resistance in external ventricular drainage)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Distinct hybrid zones and phenotypic and genomic divergence is often observed between marine and freshwater threespine sticklebacks (Gasterosteus aculeatus). Nevertheless, cases also exist where marine-freshwater divergence is diffuse despite seemingly similar environmental settings. In order to assess what characterizes these highly different outcomes, we focused on the latter kind of system in the Odder River, Denmark. Here, a previous study based on RAD (Restriction site Associated DNA) sequencing found non-significant genome-wide differentiation between marine and freshwater sticklebacks. In the present study, we analyzed samples on a finer geographical scale. We assessed if the system should be regarded as panmictic, or if fine-scale genetic structure and local selection was present but dominated by strong migration. We also asked if specific population components, that is the two sexes and different lateral plate morphs, contributed disproportionally more to dispersal., Results: We assessed variation at 96 SNPs and the Eda gene that affects lateral plate number, conducted molecular sex identification, and analyzed morphological traits. Genetic differentiation estimated by F ST was non-significant throughout the system. Nevertheless, spatial autocorrelation analysis suggested fine scale genetic structure with a genetic patch size of 770 m. There was no evidence for sex-biased dispersal, but full-plated individuals showed higher dispersal than low- and partial-plated individuals. The system was dominated by full-plated morphs characteristic of marine sticklebacks, but in the upstream part of the river body shape and frequency of low-plated morphs changed in the direction expected for freshwater sticklebacks. Five markers including Eda were under possible diversifying selection. However, only subtle clinal patterns were observed for traits and markers., Conclusions: We suggest that gene flow from marine sticklebacks overwhelms adaptation to freshwater conditions, but the short genetic patch size means that the effect of gene flow on the most upstream region must be indirect and occurs over generations. The occurrence of both weak unimodal and strong bimodal hybrid zones within the same species is striking. We suggest environmental and demographic factors that could determine these outcomes, but also highlight the possibility that long-term population history and the presence or absence of genomic incompatibilities could be a contributing factor.

The trigeminal ganglia (TG) subserving the head and the dorsal root ganglia (DRG) subserving the rest of the body are homologous handling sensory neurons. Differences exist, as a number of signaling substances cause headache but no pain in the rest of the body. To date, very few genes involved in this difference have been identified. We aim to reveal basal gene expression levels in TG and DRG and detect genes that are differentially expressed (DE) between TG and DRG. RNA-Sequencing from six naïve rats describes the whole transcriptome expression profiles of TG and DRG. Differential expression analysis was followed by pathway analysis to identify DE processes between TG and DRG. In total, 64 genes had higher and 55 genes had lower expressed levels in TG than DRG. Higher expressed genes, including S1pr5 and Gjc2, have been related to phospholipase activity. The lower expressed genes, including several Hox genes and Slc5a7, have been related to tyrosine and phenylalanine metabolism. Tissue-specific expression was identified for Gabra6 and Gabrd in TG, and for several Hox genes in DRG. Furthermore, genes that were known to be associated with headache/migraine were mostly moderately to highly expressed in one or both tissues. We present a comprehensive overview of the expression profiles of whole tissue comparison of TG and DRG. Further, we showed DE genes/pathways between TG and DRG, including several known migraine-associated genes. This study provides a basis for further pain-related studies using TG and DRG in rats., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Climate-induced changes in vegetation phenology at northern latitudes are still poorly understood. Continued monitoring and research are therefore needed to improve the understanding of abiotic drivers. Here we used 14 years of time lapse imagery and climate data from high-Arctic Northeast Greenland to assess the seasonal response of a dwarf shrub heath, grassland, and fen, to inter-annual variation in snow-cover, soil moisture, and air and soil temperatures. A late snow melt and start of growing season is counterbalanced by a fast greenup and a tendency to higher peak greenness values. Snow water equivalents and soil moisture explained up to 77 % of growing season duration and senescence phase, highlighting that water availability is a prominent driver in the heath site, rather than temperatures. We found a significant advance in the start of spring by 10 days and in the end of fall by 11 days, resulting in an unchanged growing season length. Vegetation greenness, derived from the imagery, was correlated to primary productivity, showing that the imagery holds valuable information on vegetation productivity.

Widespread application of thermoelectric devices for waste heat recovery requires low-cost high-performance materials. The currently available n-type thermoelectric materials are limited either by their low efficiencies or by being based on expensive, scarce or toxic elements. Here we report a low-cost n-type material, Te-doped Mg 3 Sb 1.5 Bi 0.5 , that exhibits a very high figure of merit zT ranging from 0.56 to 1.65 at 300-725 K. Using combined theoretical prediction and experimental validation, we show that the high thermoelectric performance originates from the significantly enhanced power factor because of the multi-valley band behaviour dominated by a unique near-edge conduction band with a sixfold valley degeneracy. This makes Te-doped Mg 3 Sb 1.5 Bi 0.5 a promising candidate for the low- and intermediate-temperature thermoelectric applications.

Objectives: HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort., Methods: A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry., Results: Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery., Conclusions: Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry., (© 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Snow is a critically important and rapidly changing feature of the Arctic. However, snow-cover and snowpack conditions change through time pose challenges for measuring and prediction of snow. Plausible scenarios of how Arctic snow cover will respond to changing Arctic climate are important for impact assessments and adaptation strategies. Although much progress has been made in understanding and predicting snow-cover changes and their multiple consequences, many uncertainties remain. In this paper, we review advances in snow monitoring and modelling, and the impact of snow changes on ecosystems and society in Arctic regions. Interdisciplinary activities are required to resolve the current limitations on measuring and modelling snow characteristics through the cold season and at different spatial scales to assure human well-being, economic stability, and improve the ability to predict manage and adapt to natural hazards in the Arctic region.

Background & Aims: Understanding mature breastmilk immunology may benefit infants chronically exposed to infectious pathogens in resource-limited regions., Methods: This prospective rural/semi-rural Tanzanian cohort of women (n = 102 at delivery; 38% HIV-positive) and their infants (n = 102) investigated breastmilk, maternal and infant serum immunoglobulins (IgA/IgG1-4/IgM) and cytokines (IL-1β/IL-2/IL-6/IL-10/IL-12p70/IL-13/IL-15/TNF-α/IFN-γ) at 1, 2, 3, 6-months postpartum., Results: Milk immunoglobulins followed an inverse U-shaped pattern, while cytokine patterns were mixed. Exclusive breastfeeding duration and feeding intensity were associated with greater breastmilk total immunoglobulin and IgA, IgG1-3 and IL-12p70 concentrations. Maternal mastitis, fever or cough was associated with higher breastmilk total cytokine concentrations, while infant fever was associated with lower milk immunoglobulins or cytokines. Strong (r ≥ 0.40) to weak (r = 0.20-0.29) positive correlations between maternal serum-breastmilk or breastmilk-infant serum immunoglobulins were evident. Breastmilk cytokines were moderate to weakly negatively correlated with infant serum. Breastmilk immunology did not differ by maternal malnutrition or HIV-seropositivity., Conclusions: Mature breastmilk is a dynamic source of many specific and non-specific immune factors associated with maternal and infant health and infant nutrition. Breastfeeding practices are associated with differential breastmilk immunological composition providing immunological support for universal recommendations to exclusively breastfeed for 6-months., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information., Method: In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE)., Results: During a median-follow-up of 5.3 (IQR 2.5-6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters)., Conclusion: Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

Background/aims: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear. Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI)., Methods: We prospectively included 584 patients with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2006 to 2008. Blood samples were drawn immediately before PCI. Additionally, we included 42 patients who had 4 blood samples drawn before and after PCI. Plasma NGAL was measured using a time-resolved immunofluorometric assay. Cross-sectional analyses were performed in these two single-center, prospective study cohorts., Results: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p < 0.001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function., Conclusions: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI.

Background: Migraine patients develop attacks several hours after intravenous infusion of glyceryl trinitrate. Due to the short half-life of nitric oxide, this delayed migraine cannot be caused by a direct action of nitric oxide derived from glyceryl trinitrate. The involvement of meningeal inflammation and dural mast cell degranulation is supported by the effectiveness of prednisolone on glyceryl trinitrate-induced delayed headache., Methods: Using a newly developed rat model mimicking the human glyceryl trinitrate headache model, we have investigated the occurrence of dural mast cell degranulation after a clinically relevant dose of glyceryl trinitrate., Results: A 6-fold increase in degranulation was observed starting at 2 hours after glyceryl trinitrate infusion. Interestingly, pre-treatment with the effective anti-migraine substances L-nitro-arginine methyl ester and sumatriptan prevented glyceryl trinitrate-induced mast cell degranulation whereas the calcitonin gene-related peptide-receptor antagonist olcegepant and the substance P receptor antagonist L-733,060 did not affect mast cell degranulation. However, topical application of two different nitric oxide donors did not cause mast cell degranulation ex vivo., Conclusions: Direct application of an exogenous nitric oxide donor on dural mast cells does not cause mast cell degranulation ex vivo. In vivo application of the nitric oxide donor glyceryl trinitrate leads to a prominent level of degranulation via a yet unknown mechanism. This effect can be completely blocked by inhibition of the endogenous nitric oxide production and by 5-HT1B/1D receptor agonists but is unaffected by calcitonin gene-related peptide and substance P receptor antagonists., (© International Headache Society 2015.)

Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5 years. End points were all-cause mortality (n = 137) and the combined end point (n = 170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r = 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 ± 0.3 vs -0.1 ± 0.1 mg/L, p = 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of all-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p = 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p = 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)