The EU-Project "TROPOS"

The global population is growing and the demand for food and energy is steadily increasing. Coastal space all over the world becomes increasingly limited and near-shore resources are often already heavily exploited. The use of offshore regions may provide new opportunities, but also involves major challenges such as the development of designs and technologies suitable for offshore condition. The floating TROPOS ‘Green & Blue’ modular multi-use platform concept introduced in this chapter is especially designed for offshore conditions and provides solutions for the problems and obstacles involved in “moving offshore”. The Green & Blue platform concept integrates fish and algae aquaculture with a wind farm. The floating multi-use approach allows for platform operation in deep waters and the promotion of synergies such as joint logistics, shared infrastructure and services, thereby making the use of offshore resources viable and profitable

Calcifying invertebrates succeed in a naturally CO2 enriched coastal habitat but are threatened by high levels of future acidification

CO2 emissions are leading to an acidification of the oceans. Predicting marine community vulnerability towards acidification is difficult, as adaptation processes cannot be accounted for in most experimental studies. Naturally CO2 enriched sites thus can serve as valuable proxies for future changes in community structure. Here we describe a natural analogue site in the Western Baltic Sea. Seawater pCO2 in Kiel Fjord is elevated for large parts of the year due to upwelling of CO2 rich waters. Peak pCO2 values of >230 Pa (>2300 μatm) and pHNBS values of 400 Pa (>4000 μatm). These changes will most likely affect calcification and recruitment, and increase external shell dissolution

Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. METHODS:   DESIGN: systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. ELIGIBILITY CRITERIA: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. STUDY RECORDS: title/abstract and full-text screening by two reviewers. RISK OF BIAS: Cochrane Collaboration revised tool. DATA SYNTHESIS: results reported separately for different settings and sufficiently comparable studies meta-analysed. RESULTS: forty-nine heterogeneous studies were included. COMMUNITY: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85–1.29, I(2) = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I(2) = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I(2) = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I(2) = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I(2) = 72% %, 2 s) for number of fallers after and during admission, respectively. LONG-TERM CARE: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72–1.02, I(2) = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I(2) = 92%, 7 s) for number of falls. CONCLUSIONS: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls. PROSPERO registration number: CRD4202021823

Long- term remission status in pediatric obsessive-compulsive disorder : Evaluating the predictive value of symptom severity after treatment

Funding Information: This work was supported by the Tryg Foundation [grant number 122892] and the Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Psychiatry. Publisher Copyright: © 2022 The Author(s)It is unknown if long-term remission for pediatric obsessive-compulsive disorder (OCD) patients is associated with post-treatment OCD symptom severity. The aim of the present study was to evaluate if post-treatment symptom severity cut-offs can discriminate remitters from non-remitters in pediatric OCD patients during three years of follow-up. All participants (N = 269) from the Nordic Long-term OCD Treatment Study (NordLOTS) undergoing stepped-care treatment were included. Patients were rated with the Clinical Global Impression – Severity Scale (CGI-S) one (n = 186), two (n = 167), and three years (n = 166) after first-line cognitive-behavioral therapy. Post-treatment symptom severity scores as well as percentage reductions during treatment evaluated with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were analyzed using receiver operating characteristics according to the CGI-S remission scores (< 2) at follow-up. Post-treatment CY-BOCS severity scores acceptably discriminated remitters from non-remitters at one-year follow-up, but poorly for the two- and three-year follow-up. Severity percentage reduction during treatment did not discriminate remission status acceptably at any follow-up point. Post-treatment OCD symptom severity status seems to have little discriminative value for long-term remission status in pediatric patients. Further research is warranted to detect post-treatment factors of prognostic value.Peer reviewe

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

The crystal structure of an ‘All Locked’ nucleic acid duplex

‘Locked nucleic acids’ (LNAs) are known to introduce enhanced bio- and thermostability into natural nucleic acids rendering them powerful tools for diagnostic and therapeutic applications. We present the 1.9 Å X-ray structure of an ‘all LNA’ duplex containing exclusively modified β-d-2′-O-4′C-methylene ribofuranose nucleotides. The helix illustrates a new type of nucleic acid geometry that contributes to the understanding of the enhanced thermostability of LNA duplexes. A notable decrease of several local and overall helical parameters like twist, roll and propeller twist influence the structure of the LNA helix and result in a widening of the major groove, a decrease in helical winding and an enlarged helical pitch. A detailed structural comparison to the previously solved RNA crystal structure with the corresponding base pair sequence underlines the differences in conformation. The surrounding water network of the RNA and the LNA helix shows a similar hydration pattern