Search

BackgroundSporadic late onset nemaline myopathy is a rare, progressive muscle disease, presenting in adulthood, mainly affecting proximal limb and bulbar muscles. Muscle biopsies show characteristic nemaline rods. The putative mechanism is considered immune-related. Other manifestations aside from neuromuscular symptoms have not been described previously.Case presentationWe present a case with atypical sporadic late onset nemaline myopathy (SLONM) of a non-HIV, non-MGUS subtype, where skin manifestations preceded neuromuscular symptoms, and a residual thymus with the histology of thymic follicular hyperplasia was detected during the diagnostic workup. Thorough dermatological investigations could not explain the skin presentations. Muscle biopsy revealed variation in fiber diameter, ragged-red and COX-negative fibers associated with discrete fibrosis. Electron microscopy detected atrophic muscle fibres with disorganization of the myofibrils, nemaline rods and abnormal mitochondria. Single-fiber EMG suggested signs of a neuromuscular transmission defect, EMG showed signs of myopathy. Analyses of antibodies associated with myasthenia gravis were negative. The patient showed improvement after intravenous immunoglobulin treatment regarding both the skin and the muscle symptoms.ConclusionsOur case highlights the heterogeneity of SLONM with its varied spectrum of presentation. A unique combination of dermatological symptoms and SLONM could be seen with skin lesions as primary presenting symptoms. An association can be considered between the different manifestations, presumably based on immune etiology, where immunosuppressive therapy has been beneficial.

As Earth's climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it remains unclear how paleo-climate shapes spatial variation in biodiversity. Here, we assessed the influence of Quaternary climate change on spatial dissimilarity in taxonomic, phylogenetic, and functional composition among neighboring 200-kilometer cells (beta-diversity) for angiosperm trees worldwide. We found that larger glacial-interglacial temperature change was strongly associated with lower spatial turnover (species replacements) and higher nestedness (rich-ness changes) components of beta-diversity across all three biodiversity facets. Moreover, phylogenetic and functional turnover was lower and nestedness higher than random expectations based on taxonomic beta -di-versity in regions that experienced large temperature change, reflecting phylogenetically and functionally se-lective processes in species replacement, extinction, and colonization during glacial-interglacial oscillations. Our results suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide. W.-B.X. and A.O. acknowledge support from the Aarhus University Research Foundation (AUFF) Starting Grant (AUFF-F-2018-7-8). J.-C.S. acknowledges support from the Danish Council for Independent Research|Natural Sciences (grant 6108-00078B) to the TREECHANGE Project. J.-C.S. also considers this work a contribution to the Center for Ecological Dynamics in a Novel Biosphere (ECONOVO) funded by Danish National Research Foundation (grant DNRF173) and the VILLUM Investigator project “Biodiversity Dynamics in a Changing World” funded by VILLUM FONDEN (grant 16549). W.L.E. was supported by the VILLUM FONDEN (grant 00025354). M.A. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grants program. C.B. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1A2C1003504). A.G.G. was supported by the ANID PIA/BASAL (grant FB210006) and FONDECYT (grant 1200468). R.E.O. was supported by the German Research Foundation to German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig (DFG-FZT 118, 202548816). J.Pe. was supported by the Fundación Ramón Areces project (CIVP20A6621) and Spanish Government project (PID2019-110521GB-I00). J.Pi. was supported by the Estonian Research Council Grants (PUT1355, PRG 1405) and Mobilitas Pluss (MOBERC11). V.D.P. was supported by the National Council of Scientific and Technological Development (CNPq) of Brazil (grant 307689/2014-0).

As Denmark seeks to be a pioneering country in terms of sustainability, the voluntary sustainability class, also known as the frivillige bæredygtighedsklasse (FBK) in Danish, is the most recent initiative from the political and industrial sides to leverage more sustainability into the construction industry. Currently, there is an ongoing test period for FBK to obtain industrial experience and acquire feedback on the provisions and whether they fit the industry level. The intention is to investigate the possible integration of minimum requirements within the Danish building legislation. This paper will present the first results of a field research study of the potential of FBK within the Danish construction industry. The study adopts a qualitative comparative approach through triangulating knowledge obtained from literature reviews, the result of an actual studied case - a daycare institution in the test phase of FBK (located in Malling, Aarhus Municipality, Denmark) - and five semi-structured interviews. The interviews were conducted with professionals who were carefully selected based on their work with FBK while ensuring a nuanced picture of different working roles with FBK. It is concluded that the early design integration (i.e., the outline and project proposal) is very crucial for the final project outcome. The case study shows that the provisions need initial consideration in the design phase, as many key elements are decided here to avoid redesigning solutions later to accommodate the requirements of FBK. Further research can be carried out, exploring the final form of the provisions in the main project to investigate the development process through the design phase.

Background & aims: Individuals can develop an addiction-like attraction towards highly processed foods, which has led to the conceptualization of food addiction, a phenotype linked to obesity. In this study, we investigated whether food addiction is associated with type 2 diabetes (T2D).Methods: 1699 adults from the general population and 1394 adults from a population with clinically verified mental disorder completed a cross-sectional survey including the Yale Food Addiction Scale 2.0. Logistic regression was employed to examine the association between food addiction and T2D, the latter operationalized via Danish registers.Results: Food addiction was strongly associated with T2D in the general population (adjusted odds ratio (AOR) = 6.7) and among individuals with mental disorder (AOR = 2.4) in a dose-response-like manner.Conclusion: This is the first study to demonstrate a positive association between food addiction and T2D in a general population sample. Food addiction may be a promising target for prevention of T2D. Background & aims: Individuals can develop an addiction-like attraction towards highly processed foods, which has led to the conceptualization of food addiction, a phenotype linked to obesity. In this study, we investigated whether food addiction is associated with type 2 diabetes (T2D).Methods: 1699 adults from the general population and 1394 adults from a population with clinically verified mental disorder completed a cross-sectional survey including the Yale Food Addiction Scale 2.0. Logistic regression was employed to examine the association between food addiction and T2D, the latter operationalized via Danish registers.Results: Food addiction was strongly associated with T2D in the general population (adjusted odds ratio (AOR) = 6.7) and among individuals with mental disorder (AOR = 2.4) in a dose-response-like manner.Conclusion: This is the first study to demonstrate a positive association between food addiction and T2D in a general population sample. Food addiction may be a promising target for prevention of T2D.

In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death.The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68-84%) when using initial risk group stratification alone to 83% (95% CI 73-91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10. In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death.The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68-84%) when using initial risk group stratification alone to 83% (95% CI 73-91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10.

Multiple myeloma (MM) is an incurable bone marrow cancer characterized by the development of osteolytic lesions due to the myeloma-induced increase in osteoclastogenesis and decrease in osteoblastic activity. The standard treatment of MM often involves proteasome inhibitors (PIs), which can also have a beneficial off-target bone anabolic effect. However, long-term treatment with PIs is unadvised due to their high side-effect burden and inconvenient route of administration. Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown. Here, we describe the 3-month results of a single-center phase II clinical trial investigating the effect of ixazomib treatment on bone formation and bone microstructure. Thirty patients with MM in stable disease not receiving antimyeloma treatment for ≥3 months and presenting ≥2 osteolytic lesions received monthly ixazomib treatment cycles. Serum and plasma samples were collected at baseline and monthly thereafter. Sodium 18F-Fluoride positron emission tomography (NaF-PET) whole-body scans and trephine iliac crest bone biopsies were collected before and after three treatment cycles. The serum levels of bone remodeling biomarkers suggested an early ixazomib-induced decrease in bone resorption. NaF-PET scans indicated unchanged bone formation ratios; however, histological analyses of bone biopsies revealed a significant increase in bone volume per total volume after treatment. Further analyses of bone biopsies showed unchanged osteoclast number and COLL1A1High-expressing osteoblasts on bone surfaces. Next, we analyzed the superficial bone structural units (BSUs), which represent each recent microscopic bone remodeling event. Osteopontin staining revealed that following treatment, significantly more BSUs were enlarged (>200,000 μm2), and the distribution frequency of their shape was significantly different from baseline. Overall, our data suggest that ixazomib induces overflow remodeling-based bone formation by decreasing the level of bone resorption and promoting longer bone formation events, making it a potentially valuable candidate for future maintenance treatment.

Vastuullisuusviestintää koskevat kysymykset ovat nousseet ajankohtaisiksi kaikenkokoisten yritysten arjessa. Tutkimus on aiemmin keskittynyt suurimpien kansainvälisten suuryritysten julkiseen vastuullisuusraportointiin, mutta nyt se on alkanut osoittaa kiinnostusta myös pienempien yritysten vastuullisuusviestintään. Tässä artikkelissa, jonka aineisto ja taustakirjallisuus perustuu vuoden 2021 pro gradu -tutkielmaan (Takki 2021), tarkastelemme haastattelututkimuksen keinoin vastuullisuusviestintää koskevaa ajattelua suomalaisissa keskisuurissa ja suurissa yrityksissä. Tutkimme vastuullisuusviestintään johtavia paineita ja motiiveja sekä siihen liitettyjä ongelmia ja haasteita. Esitämme, että vastuullisuusviestinnän paineet ja haasteet tuottavat yrityksille ristipainetta, joka johtaa jopa paradoksaalisiin tilanteisiin.

AIM: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark.METHODS: The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2 ) based on self-reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO.RESULTS: Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow-up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion.CONCLUSIONS: Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow-up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs.

Air pollution is a significant contributor to the global burden of disease with a plethora of associated health effects such as pulmonary and systemic inflammation. C-reactive protein (CRP) is associated with a wide range of diseases and is associated with several exposures. Studies on the effect of air pollution exposure on CRP levels in low to moderate pollution settings have shown inconsistent results. In this cross-sectional study high sensitivity CRP measurements on 18,463 Danish blood donors were linked to modelled air pollution data for NOx, NO2, O3, CO, SO2, NH3, mineral dust, black carbon, organic carbon, sea salt, secondary inorganic aerosols and its components, primary PM2.5, secondary organic aerosols, total PM2.5, and total PM10 at their residential address over the previous month. Associations were analysed using ordered logistic regression with CRP quartile as individuals outcome and air pollution exposure as scaled deciles. Analyses were adjusted for health related and socioeconomic covariates using health questionnaires and Danish register data. Exposure to different air pollution components was generally associated with higher CRP (odds ratio estimates ranging from 1.11 to 1.67), while exposure to a few air pollution components was associated with lower CRP. For example, exposure to NO2 increased the odds of high CRP 1.32-fold (95%CI 1.16-1.49), while exposure to NH3 decreased the odds of high CRP 0.81-fold (95%CI 0.73-0.89). This large study among healthy individuals found air pollution exposure to be associated with increased levels of CRP even in a setting with low to moderate air pollution levels.

BackgroundLong-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation.MethodIn this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6–12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology.ImpactThis integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU. Background: Long-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation. Method: In this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6–12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology. Impact: This integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.

Background Exposure to adversities in early childhood is associated with psychotic experiences and disorders in adulthood. We aimed to examine whether early childhood adversities are associated with middle childhood psychotic experiences in a cohort of children at familial high risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (controls). Methods Four hundred and forty-six children from The Danish High Risk and Resilience Study – VIA7 and VIA11 participated in this study (FHR-SZ = 170; FHR-BP = 103; controls = 173). Exposure to early childhood adversities and psychotic experiences were assessed using face-to-face interviews. Having childhood adversities assessed at baseline (age 7) was used as predictor. Psychotic experiences assessed at follow-up (age 11) were used as outcome. Results Across the sample, exposure to early childhood interpersonal adversities was associated with an increased risk for any middle childhood psychotic experiences and subclinical delusions when adjusting for relevant confounders (OR 1.8, 95% CI 1.0–3.1, p = 0.05; OR 3.0, 95% CI 1.6–5.6, p < 0.001). There was no significant dose–response effect of exposure to multiple types of childhood adversities on any psychotic experiences. There were no interaction effects between early childhood adversities and FHR on middle childhood psychotic experiences. Exploratory analyses revealed that experiencing domestic violence in early childhood was associated with any middle childhood psychotic experiences (OR 2.8, 95% CI 1.5–5.1, p = 0.001). Conclusions Exposure to interpersonal adversities during early childhood is associated with an increased risk for middle childhood psychotic experiences including specifically subclinical delusions. Future studies should examine associations between exposure to childhood adversities and conversion to psychosis within this cohort.

Modern hyper-prolific sows produce large litters with a high within-litter variation in birth weight and an increased number of low-birth-weight piglets per litter with higher mortality rates and lower growth rates compared to heavier littermates. This study aimed to describe fetal development in hyper-prolific sows, to characterize differences between large and small fetuses, and to determine when within-litter variation in fetal weight can be detected. Forty-seven multiparous sows were blood-sampled and slaughtered at day 28, 33, 45, 50, and 56 of gestation. Number of fetuses were counted, fetal body and organ weights were measured, and the intrauterine positioning was recorded. Length, width, and area of each placenta was measured and the fetus weight/placental weight ratio was calculated. The umbilical cords of the smallest, medium and the largest fetus of each litter were sampled for histological analysis. In total measurements were obtained for 1161 fetuses. The results revealed no difference in fetal survival between the gestational days (P > 0.05). Intrauterine positioning near the cervix significantly reduced fetal weight at day 56 (P < 0.05). Total litter weight and average fetal weight increased with gestational age and individual fetal weight was negatively affected by litter size from day 33 and onwards (P < 0.05). The coefficient of variation for within-litter variation in fetal weight was higher at day 28 compared to the other gestational days (P < 0.05). Relative brain- and heart weights decreased from day 28–56 (P < 0.001). Small fetuses had relatively heavier brains and hearts at day 45, 50 and 56 (P < 0.001). Size of placenta, fetus weight/placental weight ratio and length of umbilical cord increased with gestational age (P < 0.001). There was a positive correlation between size of placenta and weight of individual fetus (P < 0.001), the weight of the fetus was positively correlated with umbilical cord length (P < 0.001) and the umbilical cross-sectional area was correlated to fetal weight at day 56 (P < 0.01). Individual fetal weight was positively correlated to the fetus weight/placental weight ratio (P < 0.001). In conclusion, fetal growth was affected by litter size, placental weight, and -area, and umbilical cord length. Lightweight fetuses were characterized by having placentas with lower weight and area and shorter umbilical cords. Lastly, within-litter variation in fetal weight was detectable at day 28, and the coefficient of variance remained stable from day 33–56.

In this article we take an embodied and interactional perspective on how ethical dilemmas are being managed in situated interaction. Accordingly, we aim at linking ethical principles to real-life clinical practices in order to show how ethical dilemmas are less about abstract decision-making, and more about reasoning constrained by inter-bodily dynamics, affect and adaptive behaviour in situated interaction. We present two real-life cases of ethical dilemma management in a psychotherapeutic setting. We use the innovative method, Cognitive Event Analysis, to investigate the interaction in which the dilemmas emerge. The analytical findings, we claim, pave the way for a more embodied code of ethics, which, in turn, has consequences for the theoretical assumptions that inform the models and guide­lines for action in practice.

BACKGROUND: Patient and public involvement in randomised clinical trials has received increased focus, including in intensive care trials, but the frequency, method and extent is unknown. This meta-epidemiological study investigated patient and public involvement in contemporary, large ICU trials.METHODS: We systematically searched PubMed for large (≥225 randomised patients), contemporary trials (published between 1 January 2019 and 31 January 2022) assessing interventions in adult patients in ICU settings. Abstracts and full-text articles were assessed independently and in duplicate. Data were extracted using a pre-defined, pilot-tested data extraction form with details on trials, patient and public involvement including categories and numbers of individuals involved, methods of involvement, and trial stage(s) with involvement. Trials authors were contacted as necessary.RESULTS: We included 100 trials, with 18 using patient and public involvement; these were larger and conducted in more centres than trials without patient and public involvement. Among trials with patient and public involvement, patients (in 14/18 trials), clinicians (13 trials), and family members (12 trials) were primarily involved, mainly in the development of research design (15 trials) and development of research focus (13 trials) stages and mostly by discussion (12 trials) and solo interviews (10 trials). A median of 65 individuals (range 1-6894) were involved.CONCLUSIONS: We found patient and public involvement in a fifth of large, contemporary ICU trials. Primarily patients, families, and clinicians were included, particularly in the trial planning stages and mostly through interviews and discussions. Increased patient and public involvement in ICU trials is warranted.

Individuals with obesity are vulnerable to low rates of preventive health screening. Veterans with obesity seeking bariatric surgery are also hypothesized to have gaps in preventive health screening. Evaluation in a multidisciplinary bariatric surgery clinic is a point of interaction with the healthcare system that could facilitate improvements in screening.This is a retrospective cohort study of 381 consecutive patients undergoing bariatric surgery at a Veterans Affairs Hospital from January 2010 to October 2021. Age- and sex-appropriate health screening rates were determined at initial referral to a multidisciplinary bariatric surgery clinic and at the time of surgery. Rates of guideline concordance at both time points were compared using McNemar's test. Univariate and multivariate analyses were performed to identify the risk factors for nonconcordance.Concordance with all recommended screening was low at initial referral and significantly improved by time of surgery (39.1%‒63.8%; p0.001). Screening rates significantly improved for HIV (p0.001), cervical cancer (p=0.03), and colon cancer (p0.001). Increases in BMI (p=0.005) and the number of indicated screening tests (p=0.029) were associated with reduced odds of concordance at initial referral. Smoking history (p=0.012) and increasing distance to the nearest Veterans Affairs Medical Center (p=0.039) were associated with reduced odds of change from nonconcordance at initial referral to concordance at the time of surgery.Rates of preventive health screening in Veterans with obesity are low. A multidisciplinary bariatric surgery clinic is an opportunity to improve preventive health screening in Veterans referred for bariatric surgery.

Purpose: Streptococcal bloodstream infections (BSIs) are common, yet prognostic factors are poorly investigated. We aimed to investigate the mortality according to streptococcal species and seasonal variation.Methods: Patients with streptococcal BSIs from 2008 to 2017 in the Capital Region of Denmark were investigated, and data were crosslinked with nationwide registers for the identification of comorbidities. A multivariable logistic regression analysis was performed to assess mortality according to streptococcal species and season of infection.Results: Among 6095 patients with a streptococcal BSI (mean age 68.1 years), the 30-day mortality was 16.1% and the one-year mortality was 31.5%. With S. pneumoniae as a reference, S. vestibularis was associated with a higher adjusted mortality both within 30 days (odds ratio (OR) 2.89 [95% confidence interval (CI) 1.20-6.95]) and one year (OR 4.09 [95% CI 1.70-9.48]). One-year mortality was also higher in S. thermophilus, S. constellatus, S. parasanguinis, S. salivarius, S. anginosus, and S. mitis/oralis. However, S. mutans was associated with a lower one-year mortality OR 0.44 [95% CI 0.20-0.97], while S. gallolyticus was associated with both a lower 30-day (OR 0.42 [95% CI 0.26-0.67]) and one-year mortality (OR 0.66 [95% CI 0.48-0.93]). Furthermore, with infection in the summer as a reference, patients infected in the winter and autumn had a higher association with 30-day mortality.Conclusions: The mortality in patients with streptococcal BSI was associated with streptococcal species. Further, patients with streptococcal BSIs infected in the autumn and winter had a higher risk of death within 30 days, compared with patients infected in the summer. Purpose: Streptococcal bloodstream infections (BSIs) are common, yet prognostic factors are poorly investigated. We aimed to investigate the mortality according to streptococcal species and seasonal variation.Methods: Patients with streptococcal BSIs from 2008 to 2017 in the Capital Region of Denmark were investigated, and data were crosslinked with nationwide registers for the identification of comorbidities. A multivariable logistic regression analysis was performed to assess mortality according to streptococcal species and season of infection.Results: Among 6095 patients with a streptococcal BSI (mean age 68.1 years), the 30-day mortality was 16.1% and the one-year mortality was 31.5%. With S. pneumoniae as a reference, S. vestibularis was associated with a higher adjusted mortality both within 30 days (odds ratio (OR) 2.89 [95% confidence interval (CI) 1.20-6.95]) and one year (OR 4.09 [95% CI 1.70-9.48]). One-year mortality was also higher in S. thermophilus, S. constellatus, S. parasanguinis, S. salivarius, S. anginosus, and S. mitis/oralis. However, S. mutans was associated with a lower one-year mortality OR 0.44 [95% CI 0.20-0.97], while S. gallolyticus was associated with both a lower 30-day (OR 0.42 [95% CI 0.26-0.67]) and one-year mortality (OR 0.66 [95% CI 0.48-0.93]). Furthermore, with infection in the summer as a reference, patients infected in the winter and autumn had a higher association with 30-day mortality.Conclusions: The mortality in patients with streptococcal BSI was associated with streptococcal species. Further, patients with streptococcal BSIs infected in the autumn and winter had a higher risk of death within 30 days, compared with patients infected in the summer.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

A second opinion or a prognostic algorithm may increase prognostic accuracy. This study assessed the level to which clinicians integrate advice perceived to be coming from another clinician or a prognostic algorithm into their prognostic estimates, and how participant characteristics and nature of advice received affect this.An online double-blind randomised controlled trial was conducted. Palliative doctors, nurses and other types of healthcare professionals were randomised into study arms differing by perceived source of advice (algorithm or another clinician). In fact, the advice was the same in both arms (emanating from the PiPS-B14 prognostic model). Each participant reviewed five patient summaries. For each summary, participants: (1) provided an initial probability estimate of two-week survival (0% 'certain death'-100% 'certain survival'); (2) received advice (another estimate); (3) provided a final estimate. Weight of Advice (WOA) was calculated for each summary (0 '100% advice discounting' - 1 '0% discounting') and multilevel linear regression analyses were conducted.NCT04568629.A total of 283 clinicians were included in the analysis. Clinicians integrated advice from the algorithm more than advice from another clinician (WOA difference = -0.12 [95% CI -0.18, -0.07], p 0.001). There was no interaction between study arm and participant profession, years of palliative care or overall experience. Advice of intermediate strength (75%) was given a lower WOA (0.31) than advice received at either the 50% (WOA 0.40) or 90% level (WOA 0.43). The overall interaction between strength of advice and study arm on WOA was significant (p 0.001).Clinicians adjusted their prognostic estimates more when advice was perceived to come from a prognostic algorithm than from another clinician. Research is needed to understand how clinicians make prognostic decisions and how algorithms are used in clinical practice.

Background: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD.Materials and methods: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests.Results: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94).Conclusion: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles. Background: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD.Materials and methods: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests.Results: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94).Conclusion: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles.

ObjectivesOsteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need for joint placement. Therefore, we aimed to investigate whether the genetic associations of knee and hip osteoarthritis differ between patients treated with joint replacement and patients without joint replacement.MethodsWe included knee and hip osteoarthritis cases along with healthy controls, altogether counting >700 000 individuals. The cases were divided into two groups based on joint replacement status (surgical vs non-surgical) and included in four genome-wide association meta-analyses: surgical knee osteoarthritis (N = 22 525), non-surgical knee osteoarthritis (N = 38 626), surgical hip osteoarthritis (N = 20 221) and non-surgical hip osteoarthritis (N = 17 847). In addition, we tested for genetic correlation between the osteoarthritis groups and the pain phenotypes intervertebral disc disorder, dorsalgia, fibromyalgia, migraine and joint pain.ResultsWe identified 52 sequence variants associated with knee osteoarthritis (surgical: 17, non-surgical: 3) or hip osteoarthritis (surgical: 34, non-surgical: 1). For the surgical phenotypes, we identified 10 novel variants, including genes involved in autophagy (rs2447606 inATG7) and mechanotransduction (rs202127176 inPIEZO1). One variant, rs13107325 inSLC39A8, associated more strongly with non-surgical knee osteoarthritis than surgical knee osteoarthritis. For all other variants, significance and effect sizes were higher for the surgical phenotypes. In contrast, genetic correlations with pain phenotypes tended to be stronger in the non-surgical groups.ConclusionsOur results indicate differences in genetic associations between knee and hip osteoarthritis depending on joint replacement status.

A diversity of institutional logics can impede public-private collaboration. In this paper, we explore how individ­uals use different strategies as interaction modes to foster institutional logic convergence in a public-private col­laboration project. To do this, we rely on research on public-private collaboration and institutional logics and a single case study of a public-private smart city development project in the city of Aguas, Brazil. This paper con­tributes to the research on institutional logic diversity in three ways. First, we find that individuals use different strategies as interaction modes to achieve institutional logic convergence, but these strategies serve diverse pur­poses over time in a project. Second, when the organizational and individual goals in a project are balanced, this eases institutional logic convergence. Third, individuals can be facilitators of institutional logic convergence if they can unite diverse institutional logics and are perceived to have a central position in a project.

Anders Tønnesen, Gro Sandkjær Hanssen, Karsten Bruun Hansen, Sandra C. Valencia, Integrative climate leadership in multi-level policy packages for urban mobility - A study of governance systems in two Nordic urban regions, Transport Policy, Volume 128, 2022, Pages 309-317, ISSN 0967-070X, https://doi.org/10.1016/j.tranpol.2022.05.007 (https://www.sciencedirect.com/science/article/pii/S0967070X2200138X) This paper involves a comparative study of policymaking related to urban transport in the Gothenburg and Oslo regions. It sets out to show how strong climate leadership relates to the integration of policy measures and governance systems. Methodologically, we apply document analysis and qualitative interviews with key informants. Our clearest finding is the importance of the city's contextual governance framework for integrative climate leadership. The strong components of the leadership in Oslo—involving both horizontal and upward coordination—rely on a well-developed governance framework with operationalised goals, strategies and steering tools. This enables them to utilise multiple types of climate leadership. This contrasts with the lower degree of integration and defensiveness in Gothenburg, in terms of willingness to use effective but politically sensitive policy measures.

The aim of this study was to explore patients' experiences after gynaecological day surgery one and 30 days postoperatively, as well as potential factors influencing these experiences.The study had a multicentre, quantitative, longitudinal design.The study was conducted in three different hospitals' day surgical unit and included patients undergoing gynaecological surgery in general anaesthesia. We used a questionnaire including the European Quality of Life tool (EQ5D3L), the Quality-of-Recovery-15 questionnaire (QoR-15) and items relating to patient experiences, the first day (T1, n = 444) and 30 days (T2, n = 193) after surgery. Data were collected in the period March 2019 to March 2020.Results show that patients mainly had positive experiences and ranged quality of recovery high, even though some areas needed improvement. Patient scores on the QoR-15 relating to their experiences 24 h postoperative were rated higher at T1 than at T2. Twenty per cent of the respondents experienced complications such as infection, haemorrhage and pain. About 1/5 of these contacted healthcare services, and three per cent was hospitalized. EQ5D score was the only factor that made an statistically significant impact on patients' experiences with quality of recovery (R

Background and Hypothesis Subgroups with distinct levels of neurocognitive functioning exist in children of parents with schizophrenia or bipolar disorder. However, studies investigating the temporal stability of subgroup membership are currently lacking. We hypothesized that a minority of children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) would transition to a different neurocognitive subgroup from age 7 to 11 and that most transitions would be to a more impaired subgroup. Study Design Latent profile analysis was used to identify subgroups at two assessments (age 7 and 11) based on the performance of 320 children at FHR-SZ or FHR-BP across eight neurocognitive functions. Temporal stability in subgroup membership was evaluated with latent profile transition analysis. Population-based controls (age 7, n = 199; age 11, n = 178) were included as a reference group. Children transitioning to a more impaired subgroup were compared with nontransitioning children on sex, FHR-status, global functioning, and psychopathology. Study Results At both assessment points, we identified three subgroups based on neurocognitive performance: a moderately–severely impaired, a mildly impaired, and an above-average subgroup. A total of 12.8% of children transitioned to a different subgroup, of which the majority (85.2%) moved to a more impaired subgroup. Parental diagnosis of schizophrenia, but neither parental diagnosis of bipolar disorder, global functioning at age 7, psychopathology, nor sex significantly differentiated children transitioning to a more impaired subgroup from nontransitioning children. Conclusions During pre-adolescence, neurocognitive developmental lag is associated with being at FHR-SZ. Close attention to these children’s neurocognitive development is indicated.

The study aims to explore (1) the perspectives of health professionals on increased attendance of physical therapists (PTs) and occupational therapists (OTs) in clearly defined work assignments in two in-hospital departments and (2) the perspectives of geriatric patients on physical activity during hospitalization. A mixed-methods study using a focus group interview and a questionnaire in assessing the impact of an intervention on increased attendance of PTs and OTs in clearly defined work assignments. The patients’ perspectives on physical activity were explored in one-on-one interviews. The health professionals reported that the intervention led to a higher degree of patients’ mobilization, increased collaboration, improved the health professionals’ competencies, and provided more time for monodisciplinary assignments. The six patients stated that encouragements promoted physical activity. Increased attendance of PTs showed a positive impact on both the patients’ level of physical activity and the health professionals’ monodisciplinary assignments.

Background: Complementary therapies are widely used in palliative care settings. Qualitative research found that people with advanced disease report a range of physical and psychological benefits from complementary therapies, however evidence of their effectiveness from clinical trials is inconclusive. This may be because trials are limited by use of inappropriate outcome measures. Aims: To identify tools which capture the impact of massage, reflexology and aromatherapy in people with advanced disease. We (1) identified multi-domain tools used to evaluate these therapies in populations with any chronic health condition and (2) assessed whether tools were valid and psychometrically robust in populations with advanced disease. Design: A two-stage systematic review was conducted using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines (PROSPERO: CRD42020161199). Data sources: Six databases were searched (August 2021). Study methodological quality, tool psychometric properties and evidence quality were assessed. A global comparison score was generated. Results: Stage 1: 66 trials using 40 different multi-domain tools were identified. Stage 2: Of these tools, we identified papers for seven tools regarding development or validation in advanced disease populations. The majority of psychometric data were inconsistent or inconclusive. Data were mostly of low quality due to methodological issues. Conclusion: Of the tools identified, ‘Functional Assessment of Cancer Therapy – General’ appears to be the most suitable alternative tool against COMSIN criteria, for trials of massage, reflexology and aromatherapy in palliative care. Further tool validation is required before firm recommendations can be made. Co-development of a core outcome set could ensure relevant domains are assessed.

UNLABELLED: The hormones used in fertility treatment come in various forms. Progesterone used for luteal phase support is often administered vaginally as either suppositories, tablets or gel. However, in Denmark the administration of progesterone as a subcutaneous injection has newly been introduced. The aim of the study was to explore patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration of progesterone in Assisted Reproductive Technology (ART) treatments.METHODS AND ANALYSIS: A qualitative study with online and face to face interviews with a total of 19 women undergoing an ART treatment. Only women with at least one previous blastocyst transfer using vaginal progesterone or subcutaneous progesterone could be recruited. All participants were included from either the Fertility Clinic at Copenhagen University Hospital - Herlev and Gentofte or from the Fertility Unit at Aalborg University Hospital.RESULTS: The analysis resulted in four themes: (1) medication, (2) everyday life, (3) bodily experiences and (4) infertility or hope. Most informants highlighted the administration of subcutaneous progesterone only once a day and avoidance of the vaginal discharge as clear advantages. Reasons for preferring the vaginal administration were inconvenience of bringing the subcutaneous medication along and resistance to inject oneself.CONCLUSION: The findings of this study suggest that the satisfaction with the subcutaneous progesterone is generally positive. However, valuable thoughts have given insights into possible areas, which could be improved. Further, that some women prefer vaginal progesterone. The results show that the women are interested in being included in the decision-making when choosing the administration form of progesterone.

Fundamental axes of variation in plant traits result from trade-offs between costs and benefits of resource-use strategies at the leaf scale. However, it is unclear whether similar trade-offs propagate to the ecosystem level. Here, we test whether trait correlation patterns predicted by three well-known leaf- and plant-level coordination theories – the leaf economics spectrum, the global spectrum of plant form and function, and the least-cost hypothesis – are also observed between community mean traits and ecosystem processes. We combined ecosystem functional properties from FLUXNET sites, vegetation properties, and community mean plant traits into three corresponding principal component analyses. We find that the leaf economics spectrum (90 sites), the global spectrum of plant form and function (89 sites), and the least-cost hypothesis (82 sites) all propagate at the ecosystem level. However, we also find evidence of additional scale-emergent properties. Evaluating the coordination of ecosystem functional properties may aid the development of more realistic global dynamic vegetation models with critical empirical data, reducing the uncertainty of climate change projections., Nature Communications, 14 (1), ISSN:2041-1723

PURPOSE: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE.METHODS: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE.RESULTS: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species.CONCLUSION: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species.

Background: Despite the genetic overlap between bipolar disorder and schizophrenia, working memory impairments are mainly found in children of parents with schizophrenia. However, working memory impairments are characterized by substantial heterogeneity, and it is unknown how this heterogeneity develops over time. We used a data-driven approach to assess working memory heterogeneity and longitudinal stability in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). Methods: Based on the performances on four working memory tasks by 319 children (FHR-SZ, N = 202, FHR-BP, N = 118) measured at age 7 and 11, latent profile transition analysis was used to test for the presence of subgroups, and the stability of subgroup membership over time. Population-based controls (VIA 7, N = 200, VIA 11, N = 173) were included as a reference group. The working memory subgroups were compared based on caregiver- and teacher ratings of everyday working memory function, and dimensional psychopathology. Results: A model with three subgroups characterized by different levels of working memory function (an impaired subgroup, a mixed subgroup, and an above average subgroup) best fitted the data. The impaired subgroup had the highest ratings of everyday working memory impairments and psychopathology. Overall, 98 % (N = 314) stayed in the same subgroup from age 7 to 11. Conclusion: Persistent working memory impairments are present in a subset of children at FHR-SZ and FHR-BP throughout middle childhood. Attention should be given to these children, as working memory impairments influence daily life, and may serve as a vulnerability marker of transition to severe mental illness.

Purpose To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC trial). Methods We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1-year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. Results Among 1554 randomised patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points (99% confidence interval (CI) -4.8 to 7.8). Mean differences were 0.00 (99% CI -0.06 to 0.05) for EQ-5D-5L index values, -0.65 for EQ VAS (-5.40 to 4.08), and − 0.14 for Mini MoCA (-1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. Conclusions Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL and cognitive function at one year, but clinically important differences could not be ruled out.

Objectives: The prevalence of childhood obesity increases globally, and noninvasive methods are needed to identify metabolic dysfunction and obesity-related complications such as pediatric metabolic associated fatty liver disease (MAFLD). We investigated whether uric acid (UA) and the macrophage marker soluble form of cysteine scavenger receptor CD163 (sCD163) can be used as biomarkers for deteriorated metabolism or pediatric MAFLD in children with overweight or obesity. Methods: Cross-sectional clinical and biochemical data from 94 children with overweight or obesity was included. Surrogate liver markers were calculated, and correlations were investigated using Pearson's or Spearman's correlation test. Results: UA and sCD163 correlated with BMI standard deviation score (r=0.23, p

Objective: Treatment options in Graves' disease (GD) are limited and do not target the underlying autoimmunity, and relapse rates following a course of antithyroid drug (ATD) reach 50%. Previous research has shown promising results for a role of vitamin D in GD. We aimed to investigate whether vitamin D reduces failure to enter and sustain remission in patients with GD treated with ATD. Design: A multicenter, double-blinded, randomized placebo-controlled trial comparing vitamin D 70 mcg once daily (2800 IU) or placebo. The intervention was given first as add-on to ATD treatment, maximally 24 months, and then for 12 months after ATD cessation. Inclusion period was from 2015 to 2017 and study completion by December 2020. Patients included were adults with a first-time diagnosis of GD treated with ATD. Exclusion criteria included pregnancy and glucocorticoid treatment. The primary endpoint was failure to enter and sustain remission defined as relapse of hyperthyroidism within 12 months after ATD cessation, inability to stop ATD within 24 months, or radioiodine treatment or thyroidectomy. Two hundred seventy-eight patients were included in the study, and 4 patients withdrew consent. No adverse effects were found. Results: Participants were aged 44 ± 14 years at enrollment and 79% were female. The risk of failure to enter and sustain remission was 42% [95% confidence interval (CI) 33-50%] in the vitamin D group and 32% [CI 24-40%] in the placebo group corresponding to a relative risk of 1.30 [CI 0.95-1.78]. Conclusions: Vitamin D supplementation did not improve the treatment of GD in patients with normal or insufficient vitamin D status. Thus, supplementation with high-dose vitamin D cannot be recommended for GD. Study registration: ClinicalTrials.gov NCT02384668.

This supplement contains Mario Blaser's response to the concepts of Political Ontology and Practical Ontology as discussed by Casper Bruun Jensen in his paper »Practical Ontologies Redux«. This article appeared in 2021 Berliner Blätter (issue 84), edited by Michaela Meurer and Kathrin Eitel. It also provides a response by Jensen to Blaser's critique. Not Reviewed

This supplement contains Mario Blaser's response to the concepts of Political Ontology and Practical Ontology as discussed by Casper Bruun Jensen in his paper »Practical Ontologies Redux«. This article appeared in 2021 Berliner Blätter (issue 84), edited by Michaela Meurer and Kathrin Eitel. It also provides a response by Jensen to Blaser's critique.

The objective was to test the hypothesis of no difference in radiographic outcome after maxillary sinus floor augmentation (MSFA) with allogeneic adipose tissue-derived stem cells (ASCs) seeded on deproteinized bovine bone mineral (DBBM) (test) compared with excipient on DBBM (control). Eighteen minipigs were assigned into three groups of six animals and euthanised after one month (T1), two months (T2), and four months (T3), respectively. Each maxillary sinus was randomly allocated to either test or control with an equal volume of graft. Computed tomography scans (CTs) after MSFA (T0) were compared with CTs after euthanasia to evaluate graft volume (GV) changes and bone density (BD) using three-dimensional measurements and Hounsfield units. GV was larger in test compared with control at T1 (P = 0.046), whereas GV was larger in control compared with test at T3 (P = 0.01). BD increased from T0 to T1-T3 (P < 0.001) with both treatments. Higher BD was observed in control compared with test at T3 (P = 0.01), while no significant difference was observed at T1 and T2. Conclusively, the present study demonstrate that allogeneic ASCs seeded on DBBM in conjunction with MSFA seemed not to improve the radiographic outcome compared with excipient on DBBM. However, radiological outcomes need to be supplemented by bone histomorphometry before definitive conclusions can be provided about the beneficial use of allogeneic ASCs seeded on DBBM in conjunction with MSFA compared with DBBM alone.