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Background Infertility affects 15-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives Three overall questions will be studied: 1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? 2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And 3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up? Material and methods ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skane University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of bio-specimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem. This article is protected by copyright. All rights reserved.

Introduction The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology-related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses. Methods Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals’ gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF-α and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection. Results A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-α concentrations (R2 = 40.4%). Discussion Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.

International audience; AimsDilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe.Methods and resultsPatients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01).ConclusionsWe observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence.

Unhealthy sleep duration, either short or long, is associated with worse health and central subjective dimensions of sleep and health such as fatigue. It has been argued that the link between sleep duration and health may depend on the quality of the slept hours, and on its functional impact (ie, fatigue). The present study therefore assessed whether the relationship between last night's sleep duration and general self-rated health (SRH) differs as a function of sleep quality, and secondly, whether current fatigue and sleep quality are factors linking sleep duration and SRH. The present cross-sectional dataset involved 1304 individuals (57% female, Mage = 28.8, range 18–79). Participants completed surveys for general SRH, previous night's sleep duration and sleep quality, and current fatigue. Results showed the expected inverted U-shaped (ie, quadratic) relation between last night's sleep duration and SRH and a linear relation between last night's sleep quality and SRH. However, long sleep duration was only associated with poorer SRH in individuals who also reported poor sleep quality. Further, the quadratic relationship between sleep duration and SRH was partially mediated by fatigue and sleep quality. The results of this multi-study analysis suggest that SRH is particularly poor in those who slept both long and with poor quality the night before, while good sleep quality may protect those with a long sleep duration from poor SRH. Thus, last night's long sleep does not seem to be associated with poor subjective health unless it is coupled with poor sleep quality. Furthermore, fatigue and sleep quality are potential pathways linking short and long sleep duration with SRH. Different dimensions of sleep interact in their association with health, and future research will benefit from an integrative approach.

We have identified a clinical need for a sensitive, specific, flexible, comprehensive and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practice of surveilled urine sampling is uncomfortable for the patient; hence, more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography–high-resolution mass spectrometry (LC--HRMS) method for the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional DoA, prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of 99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting-out liquid–liquid extraction sample preparation and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. Seventy-one percent of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. New psychoactive substances were detected in 189 samples (1.0%). The occurrence of polydrug use was common; 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using LC--HRMS and the largest dataset published on the detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.

Purpose The aim of this study was to compare 99mTc-HMPAO-WBC-SPECT/CT combined with 99mTc-nanocollloid SPECT/CT and 18F-FDG-WBC-PET/CT combined with 99mTc-Nanocollloid SPECT/CT for the diagnosis and treatment evaluation of chronic prosthetic joint infection (PJI). Methods Patients with suspected chronic PJI were examined with 99mTc-HMPAO-WBC SPECT/CT, 18F-FDG-WBC PET/CT, and 99mTc-nanocolloid SPECT/CT (to visualize bone marrow). The location and patterns of uptake were noted and compared between the two leukocyte examinations. Both leukocyte examinations were evaluated visually for infection. The PET examinations were also evaluated semiquantitatively. Chronic PJI was verified clinically by microbial culture and successfully treated PJI was confirmed by 12 months symptom-free follow-up after cessation of antibiotics. Results Nineteen patients were included with 10 hip prostheses and nine knee prostheses. Fourteen were diagnosed with chronic PJI and five with successfully treated PJI. The sensitivity of visual evaluation of 99mTc-WBC-HMPAO SPECT/CT for all joints was 0.31 and for 18F-FDG-WBC PET/CT 0.38. The specificity was 0.80 and 0.83, respectively. All patients with a true-positive SPECT examination had a false-negative PET examination and vice versa. Semiquantitative evaluation of the hips gave an area under the curve of 0.905 using the iliac crest as the background. Semiquantitative evaluation of the knees did not produce significant results. Conclusion This pilot study showed no difference in the sensitivity or specificity of 99mTc-HMPAO-WBC SPECT/CT and 18F-FDG-WBC PET/CT when combined with 99mTc-nanocollloid SPECT/CT in the diagnosis or treatment evaluation of suspected late chronic PJI.

Introduction The aim of this study was to evaluate the impact of womens body mass index (BMI) on the probability of a successful external cephalic version (ECV). Material and methods A retrospective population-based observational study including all women that underwent an ECV in the southeast region of Sweden from January 2014 to December 2019. Data were collected from electronic medical records, Obstetrix, Cerner. The women were divided into BMI categories according to the World Health Organization classification. Women with a BMI below 25 kg/m(2) formed the reference group. Crude and adjusted odds ratios for unsuccessful ECV in each BMI group were calculated using binary logistic regression. Furthermore, the association between maternal characteristics and clinical and ultrasound variables at the time of the ECV and unsuccessful ECV was evaluated. Results A total of 2331 women were included. The overall success rate of ECV was 53.4%. Women with a BMI below 25 kg/m(2) had a success rate of 51.3% whereas obese women had a success rate of 58.6%. The risk of an unsuccessful ECV among obese women (BMI >= 30 kg/m(2)) had an OR of 0.74 (95% CI 0.59-0.94) compared with women with a BMI below 25 kg/m(2). After adjusting for suitable confounding factors, the association was no longer significant. Higher maternal age, multiparity, higher gestational age, posterior placenta position, polyhydramnios and higher estimated weight of the fetus at the ECV significantly decreased the risk of an unsuccessful ECV. Conclusions Maternal obesity does not seem to negatively influence the success rate of ECV. This is a finding that may encourage both caregivers and obese pregnant women to consider an ECV and so avoid a planned cesarean section for breech presentation in this group. Funding Agencies|Medical Research Council of Southeast Sweden (FORSS) [FORSS 909171]; ALF grants, Region Ostergotland

INTRODUCTION Infections due to COVID-19 can lead to life threatening pneumonia. Accompanying severe disease are more prominent pulmonary changes on Computed Tomography (CT) scan of the chest. The goal of this study was to describe pulmonary CT changes during acute COVID-19 and at follow up and whether the extent of changes correlate with severity of illness, demographics or other risk factors. MATERIALS AND METHODS Included in this study are all individuals that had confirmed COVID-19 and came for a follow up CT of the chest at Landspitali from May to September 2020. Information regarding medical history was obtained retrospectively from medical charts. All CT scans were reviewed using an international staging system to evaluate the extent of lung changes. RESULTS Eighty-five patients with a mean age of 59 years were included in the study. Sixty patients (71%) were hospitalized during the acute phase and 18 (21%) were admitted to the ICU. During the acute phase more pronounced lung involvement was seen in males and patients admitted to the ICU. At follow-up females had less lung involvement but there was a significant relationship between a higher CT score and age, ICU admissions and days in the ICU. Full recovery was seen at follow-up CT in 31% of patients (median 68,5 days between acute and follow-up imaging). CONCLUSION Patients with severe COVID-19 have more pronounced lung involvement on CT than patients with milder disease during the acute phase and follow-up. Older patients and males are at greater risk of acute and persistent COVID-19 related lung changes.

The work presented here is a culmination of developments within the Swedish project COIN: Co-adaptive human-robot interactive systems, funded by the Swedish Foundation for Strategic Research (SSF), which addresses a unified framework for co-adaptive methodologies in human–robot co-existence. We investigate co-adaptation in the context of safe planning/control, trust, and multi-modal human–robot interactions, and present novel methods that allow humans and robots to adapt to one another and discuss directions for future work.

Contains fulltext : 244306.pdf (Publisher’s version ) (Open Access) Patients are the stewards of their own care and hence their voice is important when designing and implementing research. Patients should be involved not only as participants in research that impacts their care, as the recipients of that care and any associated harms, but also as research collaborators in prioritising important questions from the patient perspective and designing the research and the ways in which is it most appropriate to involve patients. The PIONEER Consortium, an international multistakeholder collaboration lead by the European Association of Urology, has developed a core outcome set (COS) for localised and metastatic prostate cancer relevant to all stakeholders in particular patients. Throughout the work of PIONEER, patient representatives were involved as collaborators in setting the research agenda, and a wider group of patients was involved as participants in developing COSs, for instance in consensus meetings on choosing important outcomes and appropriate definitions. This publication showcases the process for COS development and highlights the most important recommendations to ultimately inform future research projects co-created between patients and other stakeholders. PATIENT SUMMARY: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is the development of a core outcome set (COS) that is relevant to all stakeholders. This report highlights the patient participation throughout our PIONEER COS development. TAKE HOME MESSAGE: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is to develop a core outcome set (COS) that is relevant to all stakeholders. As part of the work of the PIONEER Consortium, we aim to highlight the patient participation throughout our PIONEER COS development.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic drastically reduced learning opportunities for medical students. We sought to determine the cost and success of implementation of a podcast for a surgical department in a large academic hospital. METHODS: We created a podcast series for Israeli medical students during the COVID-19 epidemic based on the Medical Student Core Curriculum of the American College of Surgeons / Association for Surgical Education. Episodes were available for free download or streaming on a designated website and popular podcast platforms. Podcast analytics were used to measure public listeners and uptake. RESULTS: Total development time was 90 hours at an estimated cost of $7091 USD. A total of 10 episodes were released between March 21, 2020 and August 31, 2020. An average of 9 ± 1.26 h (range 2-6) was required to generate each episode, including 3.4 ± 1.26 h (2-6) for content review and 5.6 ± 2 h (4-10) for audio production. An average episode ran for 35.9 ± 4.3 min (28-42). Podcasts recorded a total of 5678 downloads, with an average of 228 and 336 downloads per episode in the first 30 and 90 days, respectively. The average daily downloads before the students returned to clinical rotations (March 21-April 30) was 48 ± 58.3 (7-283;) compared to 16 ± 7.4 after their return (1-38; P< 0.01). Estimated costs to produce a video-based education series would have been significantly more. CONCLUSION: Podcasts can serve as a cost-effective and quickly produced instructional tool to supplement online learning. Further research is required to determine the efficacy of podcasts versus video-based education modules.

Objective: To determine the prevalence of sexual dysfunction and to identify the factors associated with sexual dysfunction in young adult childhood cancer survivors. Methods: All survivors of childhood cancer (aged 19-40 years) in Sweden were invited to this population-based study, and 2546 men and women (59%) participated. Sexual function was examined with the PROMIS Sexual Function and Satisfaction Measure. Logistic regression was used to assess the differences between survivors and a general population sample (n = 819) and to identify the factors associated with sexual dysfunction in survivors. Results: Sexual dysfunction in at least one domain was reported by 57% of female and 35% of male survivors. Among females, dysfunction was most common for Sexual interest (36%), Orgasm -ability (32%) and Vulvar discomfort -labial (19%). Among males, dysfunction was most common for the domains satisfaction with sex life (20%), Sexual interest (14%) and Erectile function ( 9%). Compared with the general population, male survivors more frequently reported sexual dysfunction in >2 domains (OR = 1.67, 95% CI: 1.03-2.71), with an increased likelihood of dysfunction regarding Orgasm -ability (OR = 1.82; 95% CI: 1.01-3.28) and Erectile function (OR = 2.30; 95% CI: 1.18-4.49). Female survivors reported more dysfunction regarding Orgasm pleasure (9% versus 5%, OR Z 1.86; 95% CI: 1.11-3.13). A more intensive cancer treatment, emotional distress and body image disturbance were associated with sexual dysfunction in survivors. Conclusions: The findings underscore the need for routine assessment of sexual health in follow-up care of childhood cancer survivors and highlight that those treated with more intensive cancer treatment and who experience concurrent psychological concerns may benefit from targeted screening and interventions. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. Objective: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients ( n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001–2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. Results: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499–2744] ng/L) than those without relapse (264 [125–537] ng/L, p Conclusions: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.

Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict postoperative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m(2) (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR

Background: The aim of the study was to examine the treatment outcome for patients with cardiovascular implantable electronic device (CIED) infections after extraction. Methods: Patients who underwent CIED extractions due to an infection at Karolinska University Hospital 2006–2015 were analyzed. Results: In total, 165 patients were reviewed, 104 (63%) with pocket infection and 61 (37%) with systemic infection. Of the patients with systemic infection, 34 and 25 patients fulfilled the criteria for definite and possible endocarditis, respectively. Complications after extraction occurred only in one patient. Reimplantation was made after a mean of 9.5 days and performed in 81% of those with pocket infection and 44.3% in systemic infection. Infection with the new device occurred in 4.6%. The mean length of hospital stay for patients with pocket infection was 5.7 days, compared to 38.6 days in systemic infection. One-year mortality was 7.7% and 22.2% in pocket infection and systemic infection, respectively. Patients with Staphylococcus aureus infection had a higher mortality. Conclusions: In this study, the majority of the patients had a pocket CIED infection, with a short hospital stay. Patients with a systemic infection, and S. aureus etiology, had a prolonged hospital stay and a higher mortality.

Fetal growth restriction is a strong risk factor for perinatal morbidity and mortality. Reliable standards are indispensable, both to assess fetal growth and to evaluate birthweight and early postnatal growth in infants born preterm. The aim of this study was to create updated Swedish reference ranges for estimated fetal weight (EFW) from gestational week 12–42. This prospective longitudinal multicentre study included 583 women without known conditions causing aberrant fetal growth. Each woman was assigned a randomly selected protocol of five ultrasound scans from gestational week 12 + 3 to 41 + 6. Hadlock’s 3rd formula was used to estimate fetal weight. A two-level hierarchical regression model was employed to calculate the expected median and variance, expressed in standard deviations and percentiles, for EFW. EFW was higher for males than females. The reference ranges were compared with the presently used Swedish, and international reference ranges. Our reference ranges had higher EFW than the presently used Swedish reference ranges from gestational week 33, and higher median, 2.5th and 97.5th percentiles from gestational week 24 compared with INTERGROWTH-21st. The new reference ranges can be used both for assessment of intrauterine fetal weight and growth, and early postnatal growth in children born preterm.

Threats posed by the climate crisis have created an urgent need for sustainable green energy. Geothermal resources have the potential to provide up to 150 GWe of sustainable energy by 2050. However, the key challenge in successfully locating and drilling geothermal wells is to understand how the heterogeneous structure of the subsurface controls the existence of exploitable fluid reservoirs. In this Review, we discuss how key geological factors contribute to the profitable utilization of intermediate-temperature to high-temperature geothermal resources for power generation. The main driver of geothermal activity is elevated crustal heat flow, which is focused in regions of active magmatism and/or crustal thinning. Permeable structures such as faults exercise a primary control on local fluid flow patterns, with most upflow zones residing in complex fault interaction zones. Major risks in geothermal resource assessment and operation include locating sufficient permeability for fluid extraction, in addition to declining reservoir pressure and the potential of induced seismicity. Advanced computational methods permit effective integration of multiple datasets and, thus, can reduce potential risks. Future innovations involve engineered geothermal systems as well as supercritical and offshore geothermal resources, which could greatly expand the global application of geothermal energy but require detailed knowledge of the respective geological conditions. Successful discovery and operation of geothermal resources requires a thorough understanding of the heterogeneous geological subsurface. This Review discusses the key geological factors that contribute to the effective exploration of intermediate-temperature to high-temperature geothermal resources used for power generation and direct use applications.

Background and purpose The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration. Materials and methods For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen’s fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack. Results Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration. Conclusions Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.

Monitoring the underwater environment is important for maritime security, marine conservation, and mine countermeasures. With developments in computation and artificial intelligence, it is increasingly important to measure and classify underwater ship signatures. In this work, we design an artificial neural network that classifies commercial ships based on their multi-influence signature. In total, 103 ship passages were included in the considered data set, with signatures recorded as the ship crossed a line of passive underwater sensors. The multi-influence signature was formed by feature-level sensor fusion of the hydroacoustic signature, the underwater electric potential, and the static and alternating magnetic signatures. Ships were classified according to size, or type, as broadcast on the AIS. With feature-level fusion, the neural network will optimize the relationship between different types of signatures, emphasizing features with greater predictive power. At the same time, weak features, even if not independently adequate for classification, can add information that improves accuracy further. The developed neural network achieved a classification accuracy of 87.4% when classifying according to size. With augmented data to balance the classes, 85.0% classification accuracy was achieved when classifying according to ship type. This is a large improvement on the found classification accuracy when using only hydroacoustic or electromagnetic signatures. This article verifies the value of feature-level sensor fusion in classification, and provides guidance on classifier design depending on the exact ship classification task.

There is an urgent need for new treatment options in metastatic drug-resistant prostate cancer. Combining immunotherapy with other targeted therapies may be an effective strategy for advanced prostate cancer. In the present study, we sought to investigate to enhance the efficacy of anti-CTLA-4 therapy against prostate cancer by the combination with STAT3 inhibition. Male C57BL6 mice were subcutaneously inoculated with the murine prostate cancer cell line RM-1. Tumor progression was monitored following treatment with vehicle, the small molecule STAT3 inhibitor GPB730, anti-CTLA-4 or GPB730 + anti-CTLA-4. Treatment with anti-CTLA-4 or anti-CTLA-4 + GPB730 significantly inhibited tumor growth and enhanced survival compared to vehicle. Combining anti-CTLA-4 treatment with GPB730 resulted in a significantly prolonged survival compared to anti-CTLA-4 alone. GPB730 significantly increased infiltration of CD45 + cells in tumors of anti-CTLA-4-treated mice compared to anti-CTLA-4 alone. The levels of tumor-infiltrating Tregs were significantly decreased and the CD8:Treg ratio significantly increased by GPB730 treatment in combination with anti-CTLA-4 compared to anti-CTLA-4 alone. Immunohistochemical analysis showed a significant increase in CD45-positive cells in anti-CTLA-4 and anti-CTLA-4 + GPB730-treated tumors compared to vehicle or GPB730 monotherapy. Plasma levels of IL10 were significantly increased by anti-CTLA-4 compared to vehicle but no increase was observed when combining anti-CTLA-4 with GPB730. In conclusion, STAT3 inhibition by GPB730 enhances the antitumoral activity of anti-CTLA-4 and decreases the intratumoral Treg frequency in a prostate cancer mouse model. These results support the combination of STAT3 inhibition with anti-CTLA-4 therapy to increase clinical responses in patients with prostate cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02915-6.

Electrical stimulation has been used to treat spasticity in children with cerebral palsy. Building on the benefits of electrical stimulation, a new assistive device, electro-suit Mollii® with imbedded electrodes has been tested. The aim of the study was to evaluate the possible effect of Mollii® on body function, activity and participation in self-selected activities. Six children, five to ten years of age, used the electro-suit for one hour, every other day for three months. The impact was evaluated after four weeks and after three months by measuring passive range of motion (ROM), muscle tone, pain, gross motor function and participation. All participants improved in the total score for Canadian Occupational Performance Measure (COPM), three of them showed significant clinical improvements. Pain was reduced for children who estimated pain when the study started. There were also small changes in Electro-suit Mollii® had a positive impact on activity and participation in self-selected activities among the children in this study. Further studies with more children over a longer time are necessary to evaluate the impact and usefulness over time.

Purpose Radiotherapy (RT) causes an inflammatory reaction of the tissue which leads to fibrosis and reduced functioning of the pelvic organs. Few studies have shown significant relationships between side effects and RT in uterine tumors. Here, the urological, lymphedema, pelvic pain and gastrointestinal (GI) symptoms were studied before and after RT in patients with primary uterine tumors using the EORTC QLQ-EN24, specifically designed for uterine cancer patients. Methods This prospective cohort study comprised patients with primary uterine tumors who received pelvic radiotherapy (RT). A total of 43 patients were included from May 2014 to February 2019. Patients completed the questionnaires for global health status and functioning before the start of RT and at 3 and 12 months after RT. Results We found a significant worsening of the urological symptoms 3 months after RT which persisted up to 12 months after RT compared to baseline values prior to start of RT (p = 0.007). An exacerbation of the urinary symptoms was seen in patients with vaginal brachytherapy/boost compared to patients with pelvic RT at 12 months after RT (p = 0.053). The severity of lymphedema symptoms increased from RT start to 12 months after RT (p = 0.019) and the pelvic pain were higher at 3 months after RT compared to before RT (p = 0.004). Also, the level of GI symptoms was significantly higher 12 months after RT compared to the RT start (p Conclusions The urologic, lymphedema, pelvic pain and GI symptoms all increase after RT.

Background Patient with dizziness are challenging in prehospital care. The aim was to describe final diagnosis among patients assessed by EMS as suffering from dizziness with focus on time-critical conditions. Methods Consecutive patients assessed by an EMS clinician during 12 months in a single large EMS system in Gothenburg, Sweden (660,000 inhabitants), were assessed. The study comprised patients given ESS code 11 dizziness. The main end-point was the final diagnosis (ICD code). Results There were 58,575 primary missions, of which 2,048 (3.5%) were assessed as ESS code 11 (dizziness). Of these, 161 (8%) were excluded. Among the remaining 1887 cases, there were 230 different ICD codes and 96 (5%) had a time-critical condition. The majority (88%) had a cerebrovascular disease. The most typical symptoms among time-critical conditions were an acute onset (63%) and nausea, vomiting (61%). When compared with non-time-critical conditions, those with time-critical conditions were older and had a higher median systolic blood pressure at EMS arrival. Conclusion Among primary missions by the EMS, 3.5% had dizziness. Of these, 5% had a time-critical condition and the majority had a cerebrovascular disease. Instruments to identify time-critical conditions among patients seen by EMS due to dizziness are required.

BACKGROUND AND AIM Gastrointestinal complications post cardiac surgery are infrequent but difficult to diagnose and carry a high mortality. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations and the relationship between I-FABP, gastrointestinal dysfunction, and postoperative outcomes were investigated in patients who developed gastrointestinal dysfunction (acute gastrointestinal injury [AGI] grade ≥2) and those with normal gastrointestinal function. METHODS Patients with (AGI 2 group, n = 11) and without (matched controls, AGI 0 group, n = 22) early postoperative gastrointestinal dysfunction were extracted from a larger single-center prospective observational study, including adults undergoing elective cardiac surgery with extracorporeal circulation, and investigated in this nested case-control analysis. RESULTS Both groups displayed variations in I-FABP concentrations with higher I-FABP on postoperative Day 1 compared to baseline and postoperative Days 2 and 3 (p

Homografts have long been used for right ventricular outflow tract (RVOT) reconstruction. Tissue banks struggle to meet the clinical demand of tissue, with insufficient donor availability and strict recommendations on tissue quality with high proportions of discards. This study analyzes the long-term outcome of patients receiving a homograft with small fenestrations of the cusps or other structural changes, to evaluate if minor impairment of the homograft affects the durability. Homograft characteristics and patient outcome were described. Follow-up was maximum 24 years. Structural changes of the homografts were analyzed in relation to patient outcome, using univariable and multivariable Cox proportional hazard regression. Between 1995 and 2018, 468 patients received 535 homografts in the RVOT in Lund. Median recipient age was 13 years. There were 137 (26.9%) reinterventions. Freedom from reintervention was 75.8% (95% CI 71.3–79.7%) at 10 years and 57.4% (95% CI 50.0–64.0%) at 20 years. Small fenestrations of the cusps, fibrosis of the cusps and minor atheromatosis of the vessel did not show any statistically significant impact on long-term outcome, hazard ratio = 0.46 (95% CI 0.11–1.87, p = 0.276) and hazard ratio = 0.80 (95% CI 0.25–2.56, p = 0.704). Minor structural changes of the homografts seem to be acceptable without affecting the long-term durability.

PurposeThe purpose of this paper is to clarify the methodological logic of coproductive research approaches like action research, collaborative research, interactive research and participatory research in a way that can clarify its effectiveness and scientific qualities in high quality knowledge production, and show the way that it can be integrated with institutionalized textbook science.Design/methodology/approachThe paper clarifies the character of coproduction as research methodology concept, the logic of coproductive research approaches, and its characteristics compared to quantitative and qualitative methodology. A model for characterizing research approaches from leading textbook social science is developed to specify the character of coproductive research approaches and support integration in mainstream research methodology discussions.FindingsThe paper develops a research methodology framework for coproductive logic and approaches to research, to support the integration of this type of approaches in mainstream research methodology.Research limitations/implicationsThe developed model of coproductive research approaches is not empirically described. Therefore, researchers are encouraged to test and further develop the model in relation to cases and designs of research projects.Practical implicationsThe paper is helpful for guiding the design of coproductive research in practice, i.e., in research project development or in research methodology education.Social implicationsThe development of coproductive research approaches supports making science relevant and useful for solving pressing problems and improving social conditions. It also is enabling stakeholders to participate in research and development processes, thus the democratization of research and knowledge production.Originality/valueThe paper contributes to integration of the family of coproductive approaches in mainstream research methodology discussion through the development and elaboration of a framework for organizing the description and development of coproductive research approaches. The aim is that the framework is valuable for both academics, practitioners and students in designing coproductive research projects.

Purpose Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters. Methods Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers. Results Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP. Conclusions In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

Background Definite noninvasive characterisation of renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) examination including renal oncocytomas (ROs), hybrid oncocytic chromophobe tumours (HOCTs), and chromophobe renal cell carcinoma (chRCC) is currently not feasible. Objective To investigate whether combined 99mTc-sestamibi SPECT/CT and in situ metabolomic profiling can accurately characterise renal tumours exhibiting 99mTc-sestamibi uptake. Design, setting, and participants A tissue microarray analysis of 33 tumour samples from 28 patients was used to investigate whether their in situ metabolomic status correlates with their features on 99mTc-sestamibi SPECT/CT examination. In order to validate emerging data, an independent cohort comprising 117 tumours was subjected to matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). Outcome measurements and statistical analysis MALDI MSI data analysis and image generation were facilitated by FlexImaging v. 4.2, while k-means analysis by SCiLS Lab software followed by R-package CARRoT analysis was used for assessing the highest predictive power in the differential of RO versus chRCC. Heatmap-based clustering, sparse partial least-squares discriminant analysis, and volcano plots were created with MetaboAnalyst 3.0. Results and limitations We identified a discriminatory metabolomic signature for 99mTc-sestamibi SPECT/CT–positive Birt-Hogg-Dubè–associated HOCTs versus other renal oncocytic tumours. Metabolomic differences were also evident between 99mTc-sestamibi–positive and 99mTc-sestamibi–negative chRCCs, prompting additional expert review; two of three 99mTc-sestamibi–positive chRCCs were reclassified as low-grade oncocytic tumours (LOTs). Differences were identified between distal-derived tumours from those of proximal tubule origin, including differences between ROs and chRCCs. Conclusions The current study expands the spectrum of 99mTc-sestamibi SPECT/CT–positive renal tumours, encompassing ROs, HOCTs, LOTs, and chRCCs, and supports the feasibility of in situ metabolomic profiling in the diagnostics and classification of renal tumours. Patient summary For preoperative evaluation of solid renal tumours, 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) is a novel examination method. To increase diagnostic accuracy, we propose that 99mTc-sestamibi–positive renal tumours should be biopsied and followed by a combined histometabolomic analysis., Take Home Message Our study provides novel molecular insights into renal neoplasia, and supports the feasibility of integrated in situ metabolomic profiling for the diagnostics and classification of renal tumours. The results of this study suggest that renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography should be biopsied and analysed in an integrated fashion to inform clinical management.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a fatal disease requiring palliative care. End-of-life care has been well studied in patients with incurable cancer, but less is known about the quality of such care for patients with ALS. AIM To study whether the quality of end-of-life care the last week in life for patients dying from ALS differed compared to patients with cancer in terms of registered symptoms, symptom management, and communication. DESIGN This retrospective comparative registry study used data from the Swedish Registry of Palliative Care for 2012-2016. Each patient with ALS (n = 825) was matched to 4 patients with cancer (n = 3,300). RESULTS Between-group differences in assessments for pain and other symptoms were significant (p

Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.

Effective antiretroviral treatment of HIV-1, defined as continuously undetectable virus in blood, has substantial effects on the infectiousness and spread of HIV.This paper outlines the assessment of the Swedish Reference Group for Antiviral Therapy (RAV) and Public Health Agency of Sweden regarding contagiousness of HIV-infected persons on antiretroviral therapy (ART).

PurposeThe purpose was to investigate what effect an intervention of low-dose, high-frequency cardiopulmonary resuscitation (CPR) training with feedback for one month would have on professionals' subjective self-assessment skill of CPR.Design/methodology/approachThis study had a quantitative approach. In total, 38 firefighters performed CPR for two minutes on a Resusci Anne QCPR. They then self-assessed their CPR through four multiple-choice questions regarding compression rate, depth, recoil and ventilation volume. After one month of low-dose, high-frequency training with visual feedback, the firefighters once more performed CPR and self-assessed their CPR.FindingsWith one month of low-dose, high-frequency training with visual feedback, the level of self-assessment was 87% (n = 33) correct self-assessment of compression rate, 95% (n = 36) correct self-assessment of compression depth, 68% (n = 26) correct self-assessment of recoil and 87% (n = 33) correct self-assessment of ventilations volume. The result shows a reduced number of firefighters who overestimate their ability to perform CPR.Originality/valueWith low-dose, high-frequency CPR training with visual feedback for a month, the firefighters develop a good ability to self-assess their CPR to be performed within the guidelines. By improving their ability to self-assess their CPR quality, firefighters can self-regulate their compression and ventilation quality.

Background Analysis of comparative effectiveness uses different metrics to ensure that a new treatment is both effective and economical. However, there is a lack of financial frameworks to estimate the costs of introducing new technologies in medical and surgical education. Methods After conducting a literature review, we created and applied a framework ('REC') for the evaluation of three recent neurosurgery video modules aimed at medical students at Harvard Medical School. Results The most expensive component of these video-based education (VBE) modules was time cost. This cost was highly variable depending on the level of clinical seniority of the individuals involved in the video production process. Conclusion Application of the REC framework to the three modules showed highly variable time and monetary cost differences between the modules. Usage of the REC framework will enable educators to institute effective planning, efficiently use resources, and clearly define a minimal viable education product to achieve desired learning outcomes.

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000–2012; n = 6,541), the Framingham Heart Study (2005–2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002–2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.

Objectives The aim of this study was to investigate the sentinel lymph node biopsy (SLNB) method in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) guided by preoperative hybrid single-photon emission tomography/computed tomography (SPECT/CT) lymphoscintigraphy. Methods Thirty-nine patients with stage T1-T3, any N-stage, M0 cancer of the oesophagus or GOJ planned for curatively intended esophagectomy underwent preoperative SPECT/CT lymphoscintigraphy following endoscopically guided submucosal injection of radiocolloid and intraoperative radio-guided SLNB using a hand-held gamma scintillation device. Results The detection rate in preoperative SPECT/CT imaging was 88%. The median number of detected SLN stations in preoperative imaging was 1 (range 0-4). At least one suspected SLN was identified in all intraoperative SLNP procedures. In six cases, no lymph nodes were identified in the SLNB. In six cases, the SLNB was false negative. The sensitivity for successful SLNB procedures was 20%, the specificity was 100% and the accuracy was 75%. Conclusions Preoperative SLN mapping using SPECT/CT yields a high number of detected SLN stations compared to previous studies using planar imaging. The accuracy of the SLNB method in patients with predominantly ≥T3-stage tumours and with a history of previous neoadjuvant treatment is poor, and the method is not recommended in these patient groups.

Introduction Obesity-associated adverse obstetric outcomes are well-known but still relatively rare and difficult to predict. Not all obese individuals are unhealthy; some have metabolically healthy obesity (MHO) and others have metabolic unhealthy obesity (MUO). Our aim was to investigate whether the MHO and MUO classification could be used for prediction of obesity-associated complications in pregnancy. Material and methods We included 547 pregnant women with obesity, 2302 pregnant women with overweight and 5852 normal weight pregnant women. The women with obesity were classified as MUO (n = 181, 33.1%) or MHO (n = 366, 66.9%) based on first trimester blood pressure, lipoprotein levels and nonfasting glucose levels. The risk of obstetric outcomes was evaluated by multivariable logistic regression. We compared cardiovascular risk markers in blood between obese pregnant women with MUO and MHO. Results Overall, 45.9% of women with MUO developed at least one adverse obesity-associated obstetric outcome, whereas corresponding proportions in women with MHO, overweight and normal weight were 35.0%, 27.6% and 21.2%, respectively. Following adjustment, the overall risk of at least one obesity-associated obstetric or perinatal complication in women with MUO, vs women with MHO, was increased (adjusted odds ratio 1.49, 95% confidence interval 1.03-2.15), but the predictive value of the model was low. Women with MUO had altered levels of cardiovascular risk markers such as cathepsin S, adiponectin, and cystatin C in comparison with women with MHO. Conclusions Women with MUO had an overall increased risk of adverse obstetric outcomes in comparison to women with MHO, but the classification had little relevance for risk prediction beyond that of body mass index.

Background/aim Previous studies have shown discrepancies between patient's desired and actual death place. As planning of family support and involvement of palliative home care teams seem to improve the chance to meet patients preferences, geographical availability of specialized palliative home care could influence place of death. Patients and methods Data of patients diagnosed and deceased between January 2011 until December 2014 with lung, brain, colorectal, breast and prostate cancer was collected from Swedish national registers and multiple regression analyses were performed. Results Patients with lung, brain, colorectal, and prostate cancer who resided in rural municipalities had a higher likelihood of dying at home than dying in hospital settings, compared to those who lived in urban areas. Conclusion Patients in Sweden, with the exception of breast cancer patients, have a higher likelihood of home death than inpatient hospital death when residing in rural areas compared to when residing in urban areas.

Background Antenatally diagnosed urinary tract dilatation (UTD) still burdens healthcare providers and parents. This study was conducted to establish long-term outcome in an unselected group of children with antenatally detected UTD. Methods Seventy-one out of 103 children born in 2003–2005 and diagnosed with antenatal UTD agreed to participate in a 12–15-year follow-up including blood and urine samples, a kidney ultrasound exam, and kidney scintigraphy. The records were searched for previous urinary tract infections. Results Among children with an anteroposterior diameter (APD) ≤ 7 mm and no calyceal, kidney, ureteral, or bladder pathology in the early postnatal period, no one tested had reduced estimated glomerular filtration rate (eGFR), albuminuria, or UTD at the follow-up at a mean age of 13.6 years. One child had kidney damage not affecting kidney function. Among children with postnatal APD > 7 mm and/or kidney, calyceal, ureteral, or bladder pathology, 15% had persistent UTD and 32–39% (depending on the method used) had kidney damage. Major postnatal urinary tract ultrasound abnormalities and a congenital anomalies of the kidney and urinary tract (CAKUT) diagnosis were factors associated with an increased risk for permanent kidney damage (odds ratios 8.9, p = 0.016; and 14.0, p = 0.002, respectively). No one had reduced eGFR. One child (1/71, 1%) had a febrile urinary tract infection after the age of 2. Conclusions We conclude that in children with postnatal APD ≤ 7 mm, no calyceal dilatation, normal bladder, ureters, and kidney parenchyma, the outcome is excellent. There is no need for long-term follow-up in these patients.

Introduction Resuscitative endovascular balloon occlusion of the aorta (REBOA) in zone I increases systemic blood pressure during cardiopulmonary resuscitation (CPR), while also obstructing the blood flow to distal organs. The aim of the study was to compare the effects on systemic blood pressure and visceral blood flow of REBOA-III (zone III, infrarenal) and REBOA-I (zone I, supraceliac) during non-traumatic cardiac arrest and CPR. Methods Cardiac arrest was induced in 61 anesthetized pigs. Thirty-two pigs were allocated to a hemodynamic study group where the primary outcomes were systemic arterial pressures and 29 pigs were allocated to a blood flow study group where the primary outcomes were superior mesenteric arterial (SMA) and internal carotid arterial (ICA) blood flow. After 7–8 min of CPR with a mechanical compression device, REBOA-I, REBOA-III or no aortic occlusion (control group) were initiated after randomization. Results Systemic mean and diastolic arterial pressures were statistically higher during CPR with REBOA-I compared to REBOA-III (50 mmHg and 16 mmHg in REBOA-I vs 38 mmHg and 1 mmHg in REBOA-III). Systemic systolic, mean and diastolic arterial pressures were statistically elevated during CPR in the REBOA-I group compared to the controls. The SMA blood flow increased by 49% in REBOA-III but dropped to the levels of the controls within minutes. The ICA blood flow increased the most in REBOA-I compared to REBOA-III and the control group (54%, 19% and 0%, respectively). Conclusion In experimental non-traumatic cardiac arrest and CPR, REBOA-I increased systemic blood pressures more than REBOA-III, and the potential enhancement of visceral organ blood flow by REBOA-III was short-lived.

Poststress dc characteristics of AlGaN/GaN HEMTs can be used to study the effect of high-power stress on the noise figure (NF) and gain of low-noise amplifiers (LNAs) subjected to large input overdrives. This enables a shift from circuit- to transistor-level measurements to investigate the impact of variations in HEMT design parameters on the robustness (including both recovery time and survivability) by mimicking LNA operation. Using this method, a tradeoff between survivability and recovery time is demonstrated for different AlGaN/GaN interface profiles (sharp interface, standard interface, and AlN interlayer). Furthermore, the impact of different surface passivation schemes (Si-rich, Si-poor, and bilayer SiN x ) on robustness is investigated. The bilayer passivation, which features low leakage current and small gain compression under overdrive stress, exhibits relatively weak survivability. The mechanisms influencing the robustness are analyzed based on transistor physics. The short recovery time is mainly due to impeding the injection of hot electrons into surface traps and high reverse current, whereas the survivability is dependent on the local or global peak electrical fields around the gate under high power stress.

Background: Hereditary transthyretin amyloid (ATTRv) is a systemic amyloidosis with mainly neurological and cardiac symptoms. The aim of this study was to evaluate the outcome of [18F]Flutemetamol PET/CT-scan of the heart in long-term survivors with ATTRV30M amyloidosis. Methods: Twenty-one patients with ATTRV30M amyloidosis and predominantly neurological symptoms, mainly negative on cardiac 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD)-scintigraphy, were examined with a dynamic [18F]Flutemetamol PET/CT-scan. Five patients suffering from Alzheimer’s disease and one healthy individual served as controls. Volumes of interests were drawn over the intraventricular septum, lateral wall of the left ventricle and free wall of the right ventricle. Clinical records were reviewed for data from previous completed DPD-scintigraphy of the heart and echocardiography. Results: Patients with ATTRv amyloidosis had a higher cardiac uptake than the control-group in all analysed regions of the heart and could be identified with high accuracy (sensitivity 88%, specificity 100%) in static image acquisition at 30 or 60 min. We found no correlation between cardiac [18F]Flutemetamol uptake and clinical variables. Conclusion: In this small study of selected patients, cardiac [18F]Flutemetamol PET/CT could differentiate between healthy individuals and patients with ATTRV30M. [18F]Flutemetamol PET/CT imaging of amyloidosis in patients with a negative DPD-scintigraphy has a potential as a diagnostic method.

Purpose To better understand underutilisation of psychiatric care among migrant children, we compared utilisation of psychiatric care among unaccompanied refugee minors and accompanied migrant minors, with Swedish-born minors. Methods Using a large longitudinal database of linked national registers, we established a retrospective cohort of 1,328,397 people born 1984–1988 comparing minors born in Sweden to 2 Swedish-born parents (95.4%) to minors who had been arriving in Sweden between 2002 and 2011 with a permanent resident permit and were either unaccompanied refugee minors (0.4%), or accompanied migrant minors (4.0%). The outcome measures were different measures of psychiatric care including in- and outpatient care, and prescribed psychotropic medication. Result Compared with the Swedish-born minors the unaccompanied refugee minors had a higher likelihood of utilisation of all psychiatric care except ADHD medication. However, compared with accompanied migrant minors, the Swedish-born minors had a higher likelihood of having utilised psychiatric care. Conclusion Our study shows that during the first years of living in Sweden, there seems to be fewer barriers to psychiatric care for unaccompanied refugee minors compared to the accompanied migrant minors. There are a number of possible reasons for this including stronger ties with the Swedish society.

Purpose This paper centers round outsourcing. The purpose of this paper is to direct attention to outsourcing in the public sector and focus on what could be special when considering outsourcing in such contexts. The authors try to portray the business activities in private and in public sector settings and identify some similarities and – more importantly – some significant differences. Design/methodology/approach The authors use two analytical tools, a classification system of various interfaces between a selling and buying firm and a two-fold scheme for strategic analyses of outsourcing or not as well as in what ways to outsource. These tools have been developed in studies of private sector outsourcing but are applicable, as tools, also in public sector contexts. Two empirical cases from public sector outsourcing are used to illustrate options and obstacles for outsourcing ventures in the public sector. Findings The analytical discussion aims at pointing out when and how outsourcing should be a straightforward choice in the public sector. The authors also point at situations when it is a much more complicated process and thus restricted. Originality/value This study gives strong support for the need to identify which theoretical model has been used by the involved organizations in their evaluation of the situation.

Background and objectives: The most efficient long-term treatment strategy for achalasia has yet to be established. This study compared the long-term results (≥ 10 years) after either pneumatic dilatations or laparoscopic myotomy using treatment failure as the primary outcome. Secondary objectives were; the frequency and degree of dysphagia and effects on health-related quality of life (QoL). Patients and methods: Out of the 53 patients with achalasia who were initially randomized to either laparoscopic myotomy with a posterior partial fundoplication (LM) or repetitive pneumatic dilatation (PD), 43 remained for scrutiny after a median observation period of 170 months (LM; n = 20 and PD; n = 23). Results: At the follow-up of 60 months, 10 patients (36%) in the PD group and two patients (8%) in the LM group were classified as treatment failures (p = 0.016). At the latest follow-up time point (≥ 10 years), the corresponding numbers were 13 (57%) and 4 (20%), respectively. The Kaplan–Meier analysis of the cumulative incidence of treatment failure revealed a significant advantage of LM over the dilatation strategy (p = 0.036)). QoL assessed by the generic instrument PGWB and the more disease-specific instrument GSRS revealed scores which were similar in the two study groups with no obvious changes over time. Reflux was better controlled in the LM group (p = 0.02 regarding PPI consumption). Conclusions: After more than a decade of follow-up, laparoscopic myotomy reinforces its superiority over repetitive pneumatic dilatation treatment strategy in the management of newly diagnosed achalasia.

Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. Methods We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. Results POTS patients were younger (26 vs. 31 years; p p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. Conclusions Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

Background The gut microbiota of children delivered by cesarean section differs from that of children delivered vaginally. In light of the gut-brain axis hypothesis, cesarean section may influence risk of affective disorders. Methods Population based prospective cohort study included Danish children born 1982 through 2001, with follow-up until 2015. The effect of delivery mode on the risk of affective disorders was assessed using a standard Cox model and two types of Cox sibling models. Diagnostic codes or prescriptions for antidepressants and lithium were used to define cases of affective disorders. Results 1,009,444 children were followed for 8,880,794 person-years from the age of 13 years, with relevant covariates available from birth. There are strong calendar time trends in the occurrence of affective disorders with an increasingly younger age at first diagnosis and with a hotspot between the years 2007–2012. Fully adjusted standard Cox models showed an increased risk of affective disorders for both pre-labor (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.08–1.15) and intrapartum (HR, 1.07; 95% CI, 1.05–1.10) cesarean section, compared to vaginal delivery. This effect disappeared in the between–within sibling model for pre-labor (HR, 1.00; 95% CI, 0.94–1.07) but not intrapartum (HR, 1.05; 95% CI, 1.00–1.12) cesarean section. Limitations Interpretation of results from sibling models may not be relevant to children without siblings. Conclusions These results do not support the hypothesis that a delivery-mode dependent change in gut microbiota is a cause of subsequent affective disorders, despite an apparent association with delivery mode.

Background: Left atrial diameter (LAd) is included in the European Society for Cardiology's (ESC) risk model for assessment of sudden cardiac death (SCD) risk in hypertrophic cardiomyopathy (HCM), but the recommended measure of LA size is left atrial volume (LAv). Hypothesis: We hypothesized that LAv could be used instead of LAd in the HCM risk-SCD model. We aimed to determine the relation between LAd and LAv and to assess the impact of using LAv instead of LAd. Methods: Echocardiographic measurements of anteroposterior LAd in the parasternal long-axis window and LAv from Simpson's biplane method of disks were used. The 5-year risk of SCD by measured LAd and by LAd predicted from LAv were estimated using the ESC risk-SCD model. Results: In 205 HCM patients (age 56 ± 14 years, 62% male), the relation between LAd and LAv was linear. Median 5-year risk of SCD was 2.4% (interquartile range [IQR]: 1.6; 3.8) using measured LAd and 2.4% (IQR: 1.6; 3.7) using predicted LAd. The correlation between the SCD risk assessed by measured vs predicted LAd was excellent (r2 = 0.96). Use of predicted LAd resulted in four patients (2%) being recategorized between the moderate and high-risk categories. Conclusions: The relation between LAd and LAv was linear with good agreement. On a population level, the correlation between the risk of SCD using measured LAd or LAd predicted from LAv was excellent. On a patient level, using LAd predicted from LAv resulted in the vast majority remaining in the same risk category; however, for a minority of patients, it changed the recommendation.

Background: The number of elderly persons with cardiovascular disease is increasing. In Sweden, the incidence of acute myocardial infarction is the highest among individuals aged 85 years and over. However, there is still little evidence about whether this population benefits from established treatments. Furthermore, the values and preferences of octogenarians (age ⩾80 years), as well as how they could be involved in treatment decisions, have been largely overlooked in research. Overall, increased knowledge about the preferences and expectations of octogenarians is needed to incorporate their treatment expectations into the decision-making process. Aims: This study aimed to describe the treatment choice preferences and post-treatment life expectations of octogenarians with acute coronary syndrome. Methods: A total of 19 patients (eight women, 11 men) aged 80 years and older and diagnosed with non-ST-elevation myocardial infarction or unstable angina were enrolled in this qualitative study. Data were collected between May 2011 and June 2013 through semistructured interviews. The data were analysed using qualitative content analysis. Results: We identified two main categories: Wanting the best and Hope for increased wellbeing. Participant preferences were influenced by their own and others’ previous experiences and their confidence in healthcare professionals. With respect to treatment outcomes, the participants hoped to get well, stay active, experience fewer symptoms and regain vitality. Conclusion: The studied octogenarians desired the best treatment option and trusted that their healthcare providers will make appropriate recommendations. These patients expected their treatment to result in increased wellbeing and fewer symptoms.

An analysis of a data set consisting of 3 years of high time resolution radioxenon stack measurements from the three nuclear reactors at the Forsmark nuclear power plant in Sweden, as well as measurements of atmospheric radioxenon in Stockholm air, 110 km away, is presented. The main causes for the stack releases, such as the function of the xenon mitigation systems, presence of leaking fuel elements, and reactor operations such as shutdown and startup, are discussed in relation to the stack data. The relation between radioxenon releases and reactor operation is clearly illustrated by the correlation between the stack measurements and thermal reactor power. In general, the isotopic ratios of the Stockholm measurements, which are shown to mainly originate from Forsmark releases, agree well with stack measurements, and with a modeled reactor operational sequence. Results from a forward atmospheric dispersion calculation agree very well with observed plume arrival times and widths, and with some exceptions, also with absolute activity concentrations. The results illustrates the importance of detailed knowledge of radioxenon emissions from nuclear power plants when interpreting radioxenon measurements for nuclear test ban verification, and provide new input to this kind of analysis. Furthermore, it demonstrates the possibility to use sensitive radioxenon detection systems to remotely detect and verify reactor operation.