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Abstract Background Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias. Methods This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8–17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient

Extracellular vesicles (EVs) are membrane-bound particles released from cells, and their cargo can alter the function of recipient cells. EVs from X-irradiated cells have been shown to play a likely role in non-targeted effects. However, EVs derived from proton irradiated cells have not yet been studied. We aimed to investigate the proteome of EVs and their cell of origin after proton or X-irradiation. The EVs were derived from a human oral squamous cell carcinoma (OSCC) cell line exposed to 0, 4, or 8 Gy from either protons or X-rays. The EVs and irradiated OSCC cells underwent liquid chromatography–mass spectrometry for protein identification. Interestingly, we found different protein profiles both in the EVs and in the OSCC cells after proton irradiation compared to X-irradiation. In the EVs, we found that protons cause a downregulation of proteins involved in cell growth and DNA damage response compared to X-rays. In the OSCC cells, proton and X-irradiation induced dissimilar cell death pathways and distinct DNA damage repair systems. These results are of potential importance for understanding how non-targeted effects in normal tissue can be limited and for future implementation of proton therapy in the clinic.

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.

Aronia melanocarpa berries are rich in antioxidants and possess a high antioxidant capacity. Aronia berries have shown potential in type 2 diabetes mellitus (T2DM) treatment, and previous studies indicate improvements in glycemia after supplementation. Unfortunately, the effectiveness of aronia berries is limited by the low bioavailability of aronia, which fermentation could potentially overcome. The objective of this study was to compare the effects of fermented or non-fermented aronia pulp with placebo in subjects with T2DM. This study was a triple-blinded, triple-crossover study with eight-week intervention periods with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo. Extracts were incorporated in snack bars with 37% aronia (FAE or AE) or wheat bran (placebo) and 63% raisins and coconut oil. Pre- and post-treatment period, we did fasting blood samples, including hemoglobin A1c, fructosamine, insulin, glucose, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and glucagon, oral glucose tolerance tests, and anthropometric measurements. Of 36 randomized participants, 23 completed the trial. Aside from a higher increase in GIP after FAE supplementation compared to after placebo supplementation, aronia extracts had no effect. The increase in GIP levels after FAE supplementation may hold potential benefits, but the overall clinical impact remains unclear.

Background: Bullying and poor theory of mind (ToM) are both considered to negatively impact academic performance. However, it is unclear if they have separate effects. Aim: The aim of the current study was to examine the potentially separate associations of bullying and ToM with academic performance. Sample: A general population sample of 1,170 children aged 11-12 years. Methods: Information on bullying, type of involvement (none, victim (only), bully (only), victim-bully (both)), ToM, and estimated intelligence was obtained at face-to-face assessments. Information on academic performance was obtained from Danish school registers. Results: ToM was positively associated with academic performance, and involvement in bullying was negatively associated with academic performance. Academic performance differed between types of involvement in bullying. Pairwise post hoc analyses showed that in the full sample, the only significant difference was between those not involved and those involved as victim (only). This was also the case for girls. Adjusting for potential shared variance with gender, estimated intelligence and ToM being victim (only) and victim-bully (both) were negatively associated with academic performance compared to no involvement. Thus, being a victim (or victim-bully) contributes negatively to academic performance beyond the effects of ToM and intelligence, and regardless of gender. Similarly, ToM remained positively associated with academic performance after adjusting for shared variance. Conclusion: ToM and involvement in bullying were both separately associated with later academic performance. These results remained even after adjusting for shared variance, and for shared variance with gender and estimated IQ.

Abstract Background A proinflammatory response has been suggested to be involved in the pathophysiology of depression in a subgroup of patients. However, comprehensive largescale studies on neuroimmunological investigations of the cerebrospinal fluid (CSF) are lacking and no largescale longitudinal CSF studies comparing patients with depression to healthy controls currently exist. Methods A longitudinal case-control study including at least 100 patients with first time depression (ICD-10: F32) within the past year with ongoing symptoms and at least 100 sex and age matched healthy controls with collection of CSF, blood, and fecal samples. All individuals will be evaluated by neurological examination including neurological soft signs, interviewed for psychopathology assessment and have symptomatology evaluated by relevant rating scales. Level of functioning and quality of life will be evaluated by a panel of interview questions and rating scales, and cognitive function assessed by a relevant test battery. In addition, a large number of potential confounders will be registered (BMI, smoking status, current medication etc.). Primary outcomes: CSF white cell count, CSF/serum albumin ratio, CSF total protein levels, IgG index, CSF levels of IL-6 and IL-8, and the prevalence of any CNS-reactive autoantibody in CSF and/or blood. Secondary outcomes: exploratory analyses of a wide range of neuroimmunological markers and specific autoantibodies. Power calculations are computed for all primary outcomes based on previous CSF studies including patients with depression and healthy controls. Discussion This study will represent the hitherto largest investigation of CSF in patients with recent onset depression compared to healthy controls. We expect to elucidate neuroimmunological alterations in individuals with depression and characterize an immunological profile paving the way for the development of effective treatments based on biomarkers. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Both eutrophication and salinization are growing global environmental problems in freshwater ecosystems, threatening the water quality and various aquatic organisms. However, little is known about their interactive effects on theses stressors and the role of lake depth on these interactions. We used field surveys to compared zooplankton assemblages over four seasons in eight Yunnan Plateau lakes with different trophic states, salinization levels, and water depths. The results showed that: 1) the species number (S), density (DZoop), and biomass (BZoop) of zooplankton exhibited strong seasonal dynamics, being overall higher in the warm seasons. 2) Data collected over four seasons and summer data both revealed highly significant positive relationships of S, DZoop, and BZoop with total nitrogen (TN), total phosphorus (TP), and phytoplankton chlorophyll a (Chl a). 3) S, DZoop, and BZoop displayed a unimodal relationship with salinity, peaking at 400–1000 μS/cm (conductivity, to reflect salinity). 4) The two large-sized taxa (cladocerans and copepods) generally increased at low-moderate levels of TN, TP, Chl a, and Cond and was constant or decreased at high levels. The average body mass (biomass/density) of crustaceans decreased with increasing TN, TP, Chl a, and conductivity. Our findings indicate that zooplankton may be more vulnerable in deep lakes than in shallow lakes when exposed to conductivity stress even under mesotrophic conditions, and the overall decrease in size in zooplankton assemblages under the combined stress of eutrophication and salinization may result in a lowered grazing effect on phytoplankton.

Patients with lung cancer face a substantially increased risk of thromboembolic disease. Patients with localized non-small cell lung cancer (NSCLC) who are unfit for surgery due to age or comorbidity have additional thrombotic risk factors. Thus, we aimed to investigate markers of primary and secondary hemostasis, since this could assist in treatment decisions. We included 105 patients with localized NSCLC. Ex vivo thrombin generation was determined by calibrated automated thrombogram and in vivo thrombin generation was determined by measurement of thrombin–antithrombin complex (TAT) levels and prothrombin fragment F1 + 2 concentrations (F1 + 2). Platelet aggregation was investigated by impedance aggregometry. Healthy controls were used for comparison. TAT and F1 + 2 concentrations were significantly higher in NSCLC patients than in healthy controls ( P

Background: This study examines the level of eHealth literacy (eHL) of COPD patients and registered nurses (RN) prior to the implementation of a new national telehealth service. The objective was to provide the nurses with an understanding of eHL and to provide knowledge about the patients’ eHL level, socio-demographic characteristics, and digital behaviour for the nurses to be better able to support the patients’ adoption and usage of telehealth. Method: The eHealth Literacy Questionnaire (eHLQ) was administered in an outpatient clinic in February and March 2020 (N = 42). The staff-eHLQ was administered by web in November 2019 and at a conference in January 2020 (N = 39). The RNs were asked about workplace and experience with telehealth and the patients about gender, age, and educational level as well as their digital health behaviour.A multiple linear regression analysis tested for relations between the socio-demographic and digital behaviour variables and the eHLQ-scores for the COPD patients. Results: The RNs’ eHLQ-scores relating to engagement with information, motivation, and experience with digital services signified an insufficient eHL level which may influence their ability to motivate and promote the usage of telehealth to patients.The patients’ scores were higher than the RNs’ with respect to motivation and experience with digital services but seemed to have an insufficient level in relation to using technology to process information and actively engage with digital services. Conclusion: The patients need support in relation to processing information and interacting with services. The RNs’ eHLQ-scores being lower than the patients are problematic as it may influence how well they are able to support the adoption of the new telehealth service.

ObjectiveCerebral venous sinus thrombosis (CVST) is increasingly being recognized in the setting of traumatic brain injury (TBI), but its effect on TBI patients and its management remains uncertain. Here, we systematically review the currently available evidence on the complications, effect on mortality and the diagnostic and therapeutic management and follow-up of CVST in the setting of TBI.MethodsKey clinical questions were posed and used to define the scope of the review within the following topics of complications; effect on mortality; diagnostics; therapeutics; recanalization and follow-up of CVST in TBI. We searched relevant databases using a structured search strategy. We screened identified records according to eligibility criteria and for information regarding the posed key clinical questions within the defined topics of the review.ResultsFrom 679 identified records, 21 studies met the eligibility criteria and were included, all of which were observational in nature. Data was deemed insufficiently homogenous to perform meta-analysis and was narratively synthesized. Reported rates of venous infarctions ranged between 7 and 38%. One large registry study reported increased in-hospital mortality in CVSP and TBI compared to a control group with TBI alone in adjusted analyses. Another two studies found midline CVST to be associated with increased risk of mortality in adjusted analyses. Direct data to inform the optimum diagnostic and therapeutic management of the condition was limited, but some data on the safety, and effect of anticoagulation treatment of CVST in TBI was identified. Systematic data on recanalization rates to guide follow-up was also limited, and reported complete recanalization rates ranged between 41 and 86%. In the context of the identified data, we discuss the diagnostic and therapeutic management and follow-up of the condition.ConclusionCurrently, the available evidence is insufficient for evidence-based treatment of CVST in the setting of TBI. However, there are clear indications in the presently available literature that CVST in TBI is associated with complications and increased mortality, and this indicates that management options for the condition must be considered. Further studies are needed to confirm the effects of CVST on TBI patients and to provide evidence to support management decisions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: PROSPERO [CRD42021247833].

Toft-Bertelsen et al. describe repurposing of anti-influenza drug amantadine and its derivatives for the treatment of SARS-CoV-2. They show that Amantadine, Emodin and Xanthene show significant blockage of ionchannels formed by SARS-CoV-2 which are crucial for its assembly and pathophysiology.

Global warming is expected to affect stream metabolism significantly; and higher temperatures may lead to higher respiration and thus higher risk of oxygen depletion. It is, therefore, crucial to obtain reliable data on the oxygen dynamics in the different stream compartments. Determination of sediment oxygen demand (SOD) is typically based on lab or field measurement using cores or benthic chamber in which the actual physical conditions in the streams are not possible to mimic perfectly. We compared SOD based on lab core incubations with SOD measured in situ in stream sections where the oxygen exchange between water and air was eliminated artificially. The in situ SOD increased with increasing oxygen concentrations and both the temperature and the oxygen dependency of SOD increased with increasing organic content in the surface sediment. The laboratory rates reached 17 - 83% of the rates obtained in situ. The percentages were especially low at low stream velocity, likely reflecting a pure imitation of the physical conditions near the sediment in the lab when the sediment organic content was high (at low velocity). Therefore, alternative methods, simulating the natural horizontal water flow, are needed to provide reliable information on SOD in streams.

What is this summary about? This is a plain language summary of the STEP TEENS research study, which was originally published in the New England Journal of Medicine. As more teenagers are living with obesity than ever before, researchers are searching for new treatments. This was the first study looking at how well the medicine semaglutide works as a treatment for obesity in teenagers. What were the results? In this study, researchers looked at the effect of semaglutide on body mass index (BMI) and weight loss compared to a dummy medicine (placebo). A 17% decrease in BMI was reported for teenagers treated with semaglutide compared with placebo. For weight loss, an 18 kg decrease was seen when comparing semaglutide with placebo. Researchers found that there were more teenagers who had weight loss of 5%, 10%, 15%, and 20% or more in the group given semaglutide compared with the group given placebo. Improvements were also seen with semaglutide treatment for some risk factors for other diseases caused by obesity. Semaglutide was generally well tolerated by the teenagers with obesity in this study, and serious medication side effects did not happen very often. What do the results mean? The results from this study showed that there were no safety issues with semaglutide in teenagers with obesity, and that semaglutide can be used to help them lose weight.

Abstract We present the synthesis, crystal structures and optical properties of three thiostannates prepared by using 1-(2-aminoethyl)piperazine (AEPz) as structure directing agent. Two of the thiostannates are layered materials (AEPz-SnS-1 and AEPz:EtOH-SnS-1) consisting of [Sn3S7 2−]n sheets with organic cations located in-between. The third compound is a molecular thiostannate (Sn2S6(AEPzH2)2) composed of dimeric Sn2S6 4− and AEPzH2 2+. In preparation of the layered compounds, the use of AEPz as the only solvent results in AEPz-SnS-1 with regular hexagonal pores and crystallographically disordered organic cations. In contrast, a mixture of AEPz and absolute ethanol gives AEPz:EtOH-SnS-1 with distorted hexagonal pores and ordered cations between the layers. The influence of cation order on the light absorption properties and the material thermal stability was investigated through thermal treatment of the layered compounds up to 200 °C. Both compounds show colour changes when heated, but cation order results in larger thermal stability. For AEPz-SnS-1, a decreased inter-layer distance and substantial loss of organic matter was observed when heated. However, pair distribution function analysis reveals that the local in-layer thiostannate structure of AEPz-SnS-1 remains unchanged. In contrast, AEPz:EtOH-SnS-1 does not undergo noticeable structural changes by the thermal treatment. All materials are optical semiconductors with band gaps of 3.0–3.1 eV.

Abstract Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-covalently associate the peptide to serum albumin thus serving as a circulating depot. This approach is generally considered in the scientific and patent community as a standard approach to protract almost any given peptide. However, it is not trivial to prolong the half-life of peptides by lipidation and still maintain high potency and good formulation properties. Here we show that attaching a fatty acid to the obesity-drug relevant peptide PYY3-36 is not sufficient for long pharmacokinetics (PK), since the position in the backbone, but also type of fatty acid and linker strongly influences PK and potency. Furthermore, understanding the proteolytic stability of the backbone is key to obtain long half-lives by lipidation, since backbone cleavage still occurs while associated to albumin. Having identified a PYY analogue with a sufficient half-life, we show that in combination with a GLP-1 analogue, liraglutide, additional weight loss can be achieved in the obese minipig model.

Jonas Mortensen,1 Sune Møller Skov-Jeppesen,1,2 Peter Bill Juul Ladegaard,1 Lars Lund1,2 1Department of Urology, Odense University Hospital, Odense, Denmark; 2Institute of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Jonas MortensenDepartment of Urology, Odense University Hospital, Sdr. Boulevard 29, Odense, 5000, DenmarkTel +45 40172260Email Jonas.Mortensen2@rsyd.dkPurpose: The aim of this study was to investigate whether ESWT with a higher energy as an add-on therapy to vacuum-pump followed by manipulation exercises could reduce the penile curvature, pain and improve IIEF-5 score.Materials and Methods: Men aged > 18 and < 80 years and diagnosed with PD in stable phase with no history of penile surgery or previous ESWT treatment were eligible to participate. They were randomised to either active ESWT (n = 16) or sham ESWT (n = 16). Both groups were treated once a week for five weeks. Each treatment session consisted of 2000 shockwaves at 0.5mJ/mm2. All patients in both groups used a vacuum pump followed by manipulation exercises.Results: Thirty men completed the study protocol. Mean age in the treatment group was 61.7 (SD 8.3) and 63 (SD 7.35) in the control group. After six months, mean change in penile curvature was − 12.8 (SD 13) degrees in the treatment group and − 6.6 (SD 8.9) in the control group (p = 0.204). Mean IIEF-5 score decreased by 0.17 (SD 3) in the treatment group and 3.06 (SD 5.5) in the control group (p = 0.086) at six-month follow-up. Pain was assessed using both VAS and PDQ and demonstrated no difference between the groups after six months (p = 0.648).Conclusion: In the treatment group, we observed a greater but non-significant change in penile curvature and no adverse effects.Keywords: Peyronie’s disease, ESWT, vacuum pump, erectile dysfunction, manipulation exercises

Benthivorous fish disturbance and nitrogen loading are two important factors that influence the community structure of submersed macrophytes, but their interactive effect is not well elucidated. We conducted an outdoor mesocosm experiment to examine the individual and combined effects of these two factors on the growth of two submersed macrophytes of different growth forms, i.e., the rosette-forming Vallisneria natans and the canopy-forming Myriophyllum spicatum. The treatments involved two levels of fish (Carassius auratus) disturbance crossed with two levels (0 and 12 g NH4Cl per month) of ammonium (NH4+-N) loading. For M. spicatum, we found that maximum height (MH) was reduced by 30.7%, 26.4%, and 51.0% in fish addition alone (F) and nitrogen addition treatments (N, F + N), respectively, compared with the control (C) treatment. The density of M. spicatum declined by 20%, 62% and 68.8% in the F, N and F + N treatment. The above-ground biomass (AGB) of M. spicatum respectively reduced by 56.7%, 94%, and 96.5% in the F, N and F + N treatments, and the roots/shoots ratio (R/S) increased by 114%, and 176% in N and N + F treatments, respectively. Regarding V. natans, only the MH in the N treatment was reduced (71.9%), and the density exhibited a reduction of 59.1% and 64.5% in the N and F + N treatments, respectively. The AGB of V. natans was significantly lower in the N (90.3%) and N + F (78.4%) treatments compared with the C treatment, while increased by 60.3% in F treatment. The R/S of V. natans increased by 227%, and 74.4% in the N and F + N treatments compared with the C treatment. The interactive effect of fish disturbance and high N on MH and AGB of V. natans and density of M. spicatum were antagonistic. However, the interactive effect on density and BGB of V. natans and AGB of M. spicatum were negatively synergistic. Moreover, fish activity significantly increased the concentration of total suspended solids (TSS) in the water, while total nitrogen (TN), ammonium, total phosphorus (TP), light, pH and salinity were unaffected. When fish and nitrogen were combined, TN, TP, TSS and salinity increased significantly, while pH decreased. Our study reveals that the interactive effects of fish disturbance and high N are synergistic and/or antagonistic, suggesting that the same stressor interaction may vary from synergistic to antagonistic depending on the response variables and growth forms of the macrophytes examined. Our study contributes to the understanding of how different factors can interact with each other and affect submersed macrophytes in aquatic ecosystems. This is timely and relevant knowledge, considering the range of multiple stressors involved in the decline of aquatic ecosystems worldwide at present.

Unraveling how microbial co-occurrences respond to cyanobacterial blooms is central to our understanding of the stability of aquatic ecosystems. Here, we examined the effects of a Microcystis bloom on the inter-domain eukaryotic and two size-fractionated bacterial networks in a subtropical reservoir. Eukaryotes, especially protists, had a central role in microbial networks, followed by particle-attached (PA) bacteria and free-living (FL) bacteria. Eukaryotes had more negative correlations with PA bacteria than with FL bacteria. The environmental changes related to the Microcystis bloom (i.e., water temperature, pH, chlorophyll a, total carbon, total organic carbon and nitrite nitrogen) strongly affected eukaryotes and PA bacteria network as reflected by the dynamics of community composition in major modules. Importantly, the network complexity and stability significantly increased in the post-bloom periods, and eukaryotes (especially protists) enhanced the stability of the microbial network. Compared to keystone FL bacteria, eukaryotic and PA bacterial hubs mainly determined the network structure and key functional potentials (i.e., nitrogen cycling, carbon fixation and carbon degradation). Thus, some keystone eukaryotes and PA bacteria might be used as indicators of the structure and function stability of microbial communities in reservoir ecosystems. Our study highlights the importance of considering microbial cross-kingdom and multiple size-fractionation correlations in evaluating the effects of environmental disturbances on microbial networks.

Abstract Observations by the Emirates eXploration Imager (EXI) on‐board the Emirates Mars Mission are used to characterize the diurnal, seasonal, and spatial behavior of aphelion cloud belt during Mars Year 36 LS ∼ 30°–190°. Building from previous work with the Mars Color Imager (MARCI) onboard the Mars Reconnaissance Orbiter, we retrieve water ice extinction optical depth (τice) with an uncertainty ±0.0232 (excluding particle size effects). We connect EXI and MARCI using radiance and τice. Zonal and meridional diurnal trends are analyzed over 6–18 hr Local True Solar Time. The retrievals show large morning‐evening asymmetries about a minimum near 12 hr. The latitudinal distributions in early morning are extensive and particularly striking near mid‐summer. Comparisons to the Mars Planetary Climate Model show reasonable agreement with basic diurnal behavior, but noticeable departures include too much water ice in early morning, the general latitudinal extent, and behavior at smaller scales like the volcanoes and other topographically distinct features.

Abstract This is the protocol for a Campbell systematic review. The main objective of the review is to answer the following research question: What is the effect of performance pay on employee health?

Temperature and precipitation patterns are changing considerably worldwide because of global climate change [...]

Salinization of freshwater ecosystems is one of the major challenges imposed largely by climate change and excessive water abstraction for irrigated crop farming. Understanding how aquatic ecosystems respond to salinization is essential for mitigation and adaptation to the changing climate, especially in arid landscapes. Field observations provide invaluable data for this purpose, but they rarely include sufficient spatial and temporal domains; however, experimental approaches are the key to elucidating complex ecosystem responses to salinization. We established similar experimental mesocosm facilities in two different climate zones in Turkey, specifically designed to simulate the effects of salinization and climate change on shallow lake ecosystems. These facilities were used for two case-study experiments: (1) a salinity gradient experiment consisting of 16 salinity levels (range: 0–50 g/L); and (2) a heatwave experiment where two different temperature regimes (no heatwave and +6 °C for two weeks) were crossed with two salinity levels (4 and 40 g/L) with four replicates in each treatment. The experiments lasted 8 and 2 months, respectively, and the experimental mesocosms were monitored frequently. Both experiments demonstrated a significant role of salinization modulated by climate on the structure and function of lake ecosystems. Here, we present the design of the mesocosm facilities, show the basic results for both experiments and provide recommendations for the best practices for mesocosm experiments conducted under saline/hypersaline conditions.

Body size is a master trait in aquatic ecosystems to complement traditional taxonomic diversity measures. Based on a dataset of fish communities from 40 Turkish lakes covering a wide environmental gradient and continental to dry cold steppe to Mediterranean climates, we elucidated the key variables controlling size diversity, geometric mean length and number of size classes in the fish community. We further examined how these three size measures were related to species diversity and species richness. A GLM analysis revealed that both size diversity and the number of sizes were strongly related to taxonomic diversity and richness. Furthermore, fish size diversity decreased with decreasing annual precipitation, while the number of size classes increased with increasing lake area but decreased with increasing salinity. The geometric mean length of fish decreased with total nitrogen and increased with altitude. The inter-relatedness between the number of size classes and lake area suggests an increase in fish niches with increasing ecosystem size, while fish are smaller and have fewer size classes in lakes with higher salinity. We conclude that size measures provide valuable integrating information on lake fish diversity; thus, they may complement, but not replace, more traditional taxonomic fish measures.

Arctic char (Salvelinus alpinus) is a top predator and the most widespread fish in Arctic lakes. The presence of Arctic char affects the predator–prey dynamics of the key species in the food webs in these lakes. This study sought to elucidate the effects of habitat (littoral, pelagic, or profundal) and lake morphometry on the trophic position of this char in the food web. Using stomach content and stable isotope analyses, we investigated the effect of fish length, habitat, and time (individual survey years: 2008, 2013, 2018, and 2019) on the dietary niches of landlocked Arctic char populations during summer in two west Greenland lakes: Badesø (area 0.8 km2, mean depth 9.2 m) and Langesø (area 0.3 km2, mean depth 5.0 m). The small char (

Sune Moeller Skov-Jeppesen,1– 3 Knud Bonnet Yderstraede,3,4 Boye L Jensen,5 Claus Bistrup,3,6 Milad Hanna,7 Lars Lund1,3 1Department of Urology, Odense University Hospital, Odense, Denmark; 2OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark; 3Clinical Institute, University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology, Odense University Hospital, Odense, Denmark; 5Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; 6Department of Nephrology, Odense University Hospital, Odense, Denmark; 7Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UKCorrespondence: Sune Moeller Skov-JeppesenDepartment of Urology, Odense University Hospital, Sdr. Boulevard 29, Odense C, 5000, DenmarkTel +45 51210911Fax +45 65411726Email sun_mjep@hotmail.comPurpose: Treatment with low-intensity shockwave therapy (LI-ESWT) is associated with angiogenesis and is suggested as a treatment for different types of vascular diseases. It was hypothesized that LI-ESWT improves the renal filtration barrier and halts the progression of GFR decline in diabetic kidney disease (DKD) potentially through VEGF and NO formation. We present the first data on LI-ESWT in human DKD.Methods: The study was designed as an interventional, prospective, one-arm, Phase 1 study. We investigated change in GFR and albuminuria in 28 patients with DKD treated with six sessions of LI-ESWT over three weeks. The patients were followed for six months. Urine excretion of kidney injury markers, vascular endothelial growth factor (VEGF) and nitric oxide metabolites (NOx) was studied after LI-ESWT.Results: There were no significant changes in GFR and albuminuria up to six months after LI-ESWT compared to baseline. Urine VEGF was transiently reduced one month after LI-ESWT, but there were no other significant changes in urine VEGF or NOx after LI-ESWT. Secondary analysis showed that NOx increased after LI-ESWT in patients who had low levels of NOx at baseline. Kidney injury marker trefoil factor 3 (TFF3) increased acutely after the first session of LI-ESWT indicating transient endothelial repair. Other markers of kidney injury were stable in relation to LI-ESWT.Conclusion: LI-ESWT treatment did not significantly improve kidney function and albumin excretion. It is concluded that LI-ESWT is not harmful. A randomized blinded study should be performed to clarify whether adjunctive treatment with LI-ESWT is superior to standard treatment of DKD.Keywords: albuminuria, clinical trial, diabetic kidney disease, glomerular filtration rate, ESWT, extracorporeal shockwave therapy

The North Water polynya is a unique but vulnerable ecosystem, home to Indigenous people and Arctic keystone species. New palaeoecological records from Greenland suggest human abandonment c. 2200–1200 cal yrs BP occurred during climate-forced polynya instability, foreshadowing future ecosystem declines.

Abstract Background Freshwater salinization may result in significant changes of microbial community composition and diversity, with implications for ecosystem processes and function. Earlier research has revealed the importance of large shifts in salinity on microbial physiology and ecology, whereas studies on the effects of smaller or narrower shifts in salinity on the microeukaryotic community in inland waters are scarce. Our aim was to unveil community assembly mechanisms and the stability of microeukaryotic plankton networks at low shifts in salinity. Results Here, we analyzed a high-resolution time series of plankton data from an urban reservoir in subtropical China over 13 consecutive months following one periodic salinity change ranging from 0 to 6.1‰. We found that (1) salinity increase altered the community composition and led to a significant decrease of plankton diversity, (2) salinity change influenced microeukaryotic plankton community assembly primarily by regulating the deterministic-stochastic balance, with deterministic processes becoming more important with increased salinity, and (3) core plankton subnetwork robustness was higher at low-salinity levels, while the satellite subnetworks had greater robustness at the medium-/high-salinity levels. Our results suggest that the influence of salinity, rather than successional time, is an important driving force for shaping microeukaryotic plankton community dynamics. Conclusions Our findings demonstrate that at low salinities, even small increases in salinity are sufficient to exert a selective pressure to reduce the microeukaryotic plankton diversity and alter community assembly mechanism and network stability. Our results provide new insights into plankton ecology of inland urban waters and the impacts of salinity change in the assembly of microbiotas and network architecture. Video abstract

A segmented Si-telescope and HPGe array, STARS-LIBERACE, was used to study the 156Gd(p, tγ)154Gd direct reaction by particle- γ coincidence spectroscopy. New cross sections with a 25MeV proton beam are reported and compared to previous (p,t) and (t,p) studies. Furthermore, additional evidence for coexisting Kπ=01+,21+ and 02+, 22+ configurations at N = 90 is presented. Direct and indirect population patterns of the low-lying states are also explored. Review of the new and existing evidence favors an interpretation based on a configuration-dependent pairing interaction. The weakening of monopole pairing strength and an increase in quadrupole pairing strength could bring 2p-2h 0 + states below 2 Δ. This may account for a large number of the low-lying 0 + states observed in two-nucleon transfer reactions. A hypothesis for the origin of the 02+ and 03+ states is provided.

Summary: The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013–2018), Phase 2 of the program (ERCC2, 2019–2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2’s current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Image-based methods for species identification offer cost-efficient solutions for biomonitoring. This is particularly relevant for invertebrate studies, where bulk samples often represent insurmountable workloads for sorting, identifying, and counting individual specimens. On the other hand, image-based classification using deep learning tools have strict requirements for the amount of training data, which is often a limiting factor. Here, we examine how classification accuracy increases with the amount of training data using the BIODISCOVER imaging system constructed for image-based classification and biomass estimation of invertebrate specimens. We use a balanced dataset of 60 specimens of each of 16 taxa of freshwater macroinvertebrates to systematically quantify how classification performance of a convolutional neural network (CNN) increases for individual taxa and the overall community as the number of specimens used for training is increased. We show a striking 99.2% classification accuracy when the CNN (EfficientNet-B6) is trained on 50 specimens of each taxon, and also how the lower classification accuracy of models trained on less data is particularly evident for morphologically similar species placed within the same taxonomic order. Even with as little as 15 specimens used for training, classification accuracy reached 97%. Our results add to a recent body of literature showing the huge potential of image-based methods and deep learning for specimen-based research, and furthermore offers a perspective to future automatized approaches for deriving ecological data from bulk arthropod samples.

Ammonium (NH4-N) produces a paradoxical effect on submersed macrophytes because it is not only the preferred nitrogen source for the growth of plants but also threatens the growth of plants at high concentration. Whether short-term and small-scale physiological toxicity experiments at an individual level can reflect the effects of high ammonium on populations of submersed macrophytes in natural conditions is still unclear. In this study, an 18-month experiment was conducted in six 600 m2 ponds subjected to different levels of ammonium loading. The effects of high ammonium on populations of canopy-forming Myriophyllum spicatum and rosette-forming Vallisneria natans were explored. The results showed that M. spicatum and V. natans populations can develop high cover and height at high ammonium concentration (7 mg/L) at short-term exposures, and V. natans may be tolerant to 18 mg/L ammonium concentration. However, the cover of M. spicatum and the height of both species were inhibited at 2.4 mg/L at long-term exposures. The height of M. spicatum was two to six times higher than that of V. natans across all treatments and control by the end of the experiment, and the cover of M. spicatum was 7–11 times higher than that of V. natans in most NH4-N loading treatments, except the cover of M. spicatum in the highest NH4-N loading treatment with 18 mg/L NH4-N. The rosette-forming V. natans resists ammonium stress by slow growth (shoot elongation) to reduce consumption, while canopy-forming species resist ammonium stress by shoot elongation and canopy development to capture light. Although increasing ammonium concentration may induce severe stress on M. spicatum, the morphological characteristics of this species may, to some extent, release the plants from this stress. Our present study indicates that the negative effects of ammonium stress on the development of populations increased with exposure duration, and the submersed macrophyte community with stronger ability for light capture and dispersal may resist high ammonium stress. Nevertheless, in strongly ammonium-enriched systems, competition and succession cannot be neglected.

Introduction Biomarkers in CSF could provide etiological clues and diagnostic tools for psychotic disorders. However, an overview of all CSF findings in individuals with psychotic disorders compared to healthy controls is lacking. Objectives To analyse CSF findings from individuals with psychotic disorders compared to healthy controls. Methods PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO were searched November 3rd, 2021. Case-control studies including patients with non-affective, psychotic disorder compared to healthy controls measuring at least one biomarker in CSF are included. Standardized Mean Differences (SMD) and random-effects analyses were used. Results 141 studies, covering 192 biomarkers, were included. 161 biomarkers have not previously been included in meta-analyses. Most markers measured showed no significant differences, including the dopamine metabolites HVA and DOPAC. Patients with psychotic disorders showed increased CSF levels of noradrenaline (SMD, 0.53; 95% CI, 0.15-0.90), MHPG (SMD, 0.30; 95% CI, 0.05-0.55), 5-HIAA (SMD, 0.11; 95 % CI, 0.01-0.21), kynurenic acid (SMD, 1.58; 95% CI, 0.26-2.91), kynurenine (SMD, 1.00; 95% CI, 0.58-1.42), IL-6 (SMD, 0.58; 95% CI, 0.39-0.77), IL-8 (SMD, 0.47; 95% CI, 0.18-0.77), anandamide (SMD, 0.78; 95% CI, 0.53-1.02), albumin ratio (SMD, 0.53; 95% CI, 0.10-0.96), total protein (SMD, 0.31; 95% CI, 0.14-0.48), and glucose (SMD, 0.57; 95% CI, 0.08-1.06). Neurotensin (SMD, -0.67; 95% CI, -0.89 to -0.46) and GABA (SMD, -0.29; 95% CI, -0.50 to -0.09) were decreased. Conclusions These findings suggest that dysregulation of the immune and adrenergic system and blood-brain barrier dysfunction might play a role in the pathophysiology of psychotic disorders. Disclosure No significant relationships.

Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations and paranoid ideations despite receiving current treatment. Virtual reality assisted treatment offers the potential of advancing current psychotherapies for psychotic symptoms by creating virtual environments that can elicit responses (e.g. thoughts, feelings, behaviours) mirroring real-world settings. In two large-scale randomised clinical trials, we are investigating whether targeted virtual reality assisted psychotherapy can reduce psychotic symptoms and increase daily life functioning and quality of life. The CHALLENGE trial examines whether nine sessions of virtual reality-assisted psychotherapy is superior to nine sessions of standard treatments in reducing the severity, frequency, and distress of auditory hallucinations in patients with psychosis. In the Face your Fears trial we are investigating whether virtual reality assisted cognitive behavioral therapy (CBT) is superior to standard CBT in reducing levels of paranoid ideation in patients with psychosis spectrum disorders. Methods: The CHALLENGE and Face your Fears trials are randomised, assessor-blinded parallel-groups superiority clinical trials, allocating a total of 266 and 256 patients, respectively to either the experimental intervention or a control condition. The trials are currently enrolling patients; thus, no quantitative data is available yet. The main objective of this presentation is to give a qualitative account of this new psychotherapeutic methods as it is applied in both trials. Results: Qualitative data comprising case descriptions and video material will be presented at the conference. Discussion: The preliminary findings indicate great potential for these innovative treatments albeit important concerns regarding implementation will be raised.

BackgroundTime is considered an essential determinant in the initial care of trauma patients. In Norway, response time (ie, time from dispatch center call to ambulance arrival at scene) is a controversial national quality indicator. However, no national requirements for response times have been established. There is an ongoing debate regarding the optimal configuration of the Norwegian trauma system. The recent centralization of trauma services and closure of emergency hospitals have increased prehospital transport distances, predominantly for rural trauma patients. However, the impact of trauma system configuration on early trauma management in urban and rural areas is inadequately described. ObjectiveThe project will assess injured patients’ initial pathways through the trauma system and explore differences between central and rural areas in a Norwegian trauma cohort. This field is unexplored at the national level, and existing evidence for an optimal organization of trauma care is still inconclusive regarding the impact of prehospital time. MethodsThree quantitative registry-based retrospective cohort studies are planned. The studies are based on data from the Norwegian Trauma Registry (NTR; studies 1, 2, and 3) and the local Emergency Medical Communications Center (study 2). All injured patients admitted to a Norwegian hospital and registered in the NTR in the period between January 1, 2015, and December 31, 2020, will be included in the analysis. Trauma registry data will be analyzed using descriptive and relevant statistical methods to compare prehospital time in rural and central areas, including regression analyses and adjusting for confounders. ResultsThe project received funding in fall 2020 and was approved by the Oslo University Hospital data protection officer, case number 18/02592. Registry data including approximately 40,000 trauma patients will be extracted during the first quarter of 2022, and analysis will begin immediately thereafter. Results are expected to be ready for publication from the third quarter of 2022. ConclusionsFindings from the study will contribute to new knowledge regarding existing quality indicators and with an increasing centralization of hospitals and residents, the study will contribute to further development of the Norwegian trauma system. A high generalizability to other trauma systems is expected, given the similarities between demographical changes and trauma systems in many high-income countries. International Registered Report Identifier (IRRID)PRR1-10.2196/30656

Abstract We have recently reported the discovery of a new distinct nanoparticle by ultracentrifugation of the supernatant of exomeres at 376,000 x g for 16 hours. We termed the resulting pellet, supermeres (supernatant of exomeres). The Witwer team raised the legitimate question that these two membraneless nanoparticles may arise from a continuous population of extracellular particles. We have reviewed our data here and present additional analyses that reinforce supermeres as distinct nanoparticles.

Abstract Background From 2014 to 17, a large-scale project, ‘The User-involving Hospital’, was implemented at a Danish university hospital. Research highlights leadership as crucial for the outcome of change processes in general and for implementation processes in particular. According to the theory on organizational learning by Agyris and Schön, successful change requires organizational learning. Argyris and Schön consider that the assumptions of involved participants play an important role in organizational learning and processes. The purpose was to explore leaders’ assumptions concerning implementation of patient involvement methods in a hospital setting. Methods Qualitative explorative interview study with the six top leaders in the implementation project. The semi-structured interviews were conducted and analyzed in accordance with Kvale and Brinkmanns’ seven stages of interview research. Result The main leadership assumptions on what is needed in the implementation process are in line with the perceived elements in organizational learning according to the theory of Argyris and Schön. Hence, they argued that implementation of patient involvement requires a culture change among health care professionals. Two aspects on how to obtain success in the implementation process were identified based on leadership assumptions: “The health care professionals’ roles in the implementation process” and “The leaders’ own roles in the implementation process”. Conclusion The top leaders considered implementation of patient involvement a change process that necessitates a change in culture with health care professionals as crucial actors. Furthermore, the top leaders considered themselves important facilitators of this implementation process.

Abstract Background Randomised controlled trials suggest that family therapy has a positive effect on the course of depression, schizophrenia and anorexia nervosa. However, it is largely unknown whether a positive link also exists between caregiver involvement and patient outcome in everyday psychiatric hospital care, using information reported directly from patients, i.e. patient-reported experience measures (PREM), and their caregivers. The objective of this study is to examine whether caregiver-reported involvement is associated with PREM regarding patient improvement and overall satisfaction with care. Methods Using data from the National Survey of Psychiatric Patient Experiences 2018, we conducted a nationwide cross-sectional study in Danish psychiatric hospitals including patients and their caregivers who had been in contact with the hospital (n = 940 patients, n = 1008 caregivers). A unique patient identifier on the two distinct questionnaires for the patient and their caregiver enabled unambiguous linkage of data. In relation to PREM, five aspects of caregiver involvement were analysed using logistic regression with adjustment for patient age, sex and diagnosis. Results We consistently find that high caregiver-reported involvement is statistically significantly associated with high patient-reported improvement and overall satisfaction with care with odds ratios (OR) ranging from 1.69 (95% confidence interval (CI) 0.95–2.99) to 4.09 (95% CI 2.48–6.76). This applies to the following aspects of caregiver-reported involvement: support for the patient-caregiver relationship, caregiver information, consideration for caregiver experiences and the involvement of caregivers in decision making. No statistically significant association is observed regarding whether caregivers talk to the staff about their expectations for the hospital contact. Conclusion This nationwide study implies that caregiver involvement focusing on the patient-caregiver relationship is positively associated with patient improvement and overall satisfaction with care in everyday psychiatric hospital care.