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The aim of this community service activity is to enhance the scientific literacy skills of lower-grade students in Kesetnana village through educational game-based lessons. The activity is conducted in several stages, including planning, preparation, implementation, evaluation, and reporting. The outcome of this initiative is the development of educational game media and its utilization in the teaching process, resulting in a significant increase in scientific literacy skills of over 65%. Additionally, students' interest in learning has risen by 68.8% according to indicators of learning motivation, demonstrating their positive response to the educational game-based approach. Therefore, efforts to promote scientific literacy among lower-grade elementary school students in Kesetnana village can be effectively carried out through regular lesson activities over a three-week period, leading to improved scientific literacy skills and increased learning motivation.

In the European Union (EU) a new framework was established in December of 2022, the “Safe and Sustainable-by-Design” framework. This framework was created to enhance the risk assessment of new chemicals in order to avoid regrettable substitutions, and integrate sustainable development goals in the invention of new thechnologies. To implement SSbD, interpretations of the framework were developed to facilitate its implementation. An example is the European Joint Research Centre (JRC) that developed an interpretation of SSbD. Perovskite are a broad class of crystalline materials of ABX3 chemical composition, where A and B are metal cations and X is a anion. The application of perovskites nowadays is very extensive from ferroelectrics, superconductors, solar cells and automotive catalysts. Oxide-perovskites are more specifically formed in the ABO3 formation. This thesis aims at presenting a case study of automotive catalysts oxide-perovskites LanthanumCobalt-Nickel (LaCoNi) and providing an overview of the JRC interpretation of the SSbD framework using the LaCoNi case study with a focus on environmental safety. For this, ecotoxic studies on the metal ions composing the perovskites and the material itself were conducted. The results were related to the JRC framework and a discussion on the relevance of the results was done to provide some insight of the application of the JRC SSbD framework. The ecotoxic study was conducted on R. subcapitata freshwater algae as well as D. magna freshwater daphids. The results showed an EC50 of 30.2 mg/L for LaCoNi on the algae and no effects on the daphnids in concentrations up-to 100 mg/L. These results showed that LaCoNi could be potentially harmful to the environment because of the leachability of nickel and cobalt, and that many more studies on the effect on human would be needed as required by the JRC framework. The applicability of the JR

Salah satu tanaman yang digunakan secara tradisional adalah tanaman Faloak. Tanaman faloak banyak digunakan dalam pengobatan tradisional di Nusa Tenggara Timur. Daun faloak diduga memiliki efek hepatoprotektif berdasarkan kemampuannya sebagai antioksidan, yaitu salah satu mekanisme hepatoprotektif untuk melawan radikal bebas yang berkontribusi terhadap kerusakan jaringan hati. Penelitian ini bertujuan Untuk Mengetahui dosis fraksi daun faloak (Sterculia quadrifida R. Br.) yang efektif terhadap hepatoprotektor dengan parameter makropatologi pada organ hati pada tikus. Penelitian ini merupakan penelitian eksperimen yang menggunakan hewan uji tikus putih jantan sebanyak 30 ekor yang dibagi dalam 6 kelompok perlakuan. Pada penelitian ini dilakukan penimbangan berat badan tikus pada hari ke 0 sampai hari ke-15 untuk mengetahui perubahan berat badan tikus yang terjadi. Hasil penimbangan berat badan tikus menunjukan bahwa tidak ada perbedaan secara signifikan. kerusakan pada organ hati ini tidak ditemukan pada kelompok yang diberikan kurkumin, fraksi air daun faloak dosis 50mg/kgBB, 100mg/kg/BB, 200mg/KgBB tetapi ditemukan dalam kelompok kontrol CMC 1%. Fraksi air daun faloak dosis 50mg/kgBB, 100mg/kgBB, 200mg/kgBB secara makroskopik mampu melindungi kerusakan hati akibat pemberian paracetamol dosis toksik.

Introduction Person-centred care (PCC) emphasises the need for the health care professional to prioritise individual patient needs, thereby fostering a collaborative and emphatic environment that empowers patients to actively participate in their own care. This article will explore the purpose of PCC in Nuclear Medicine (NM), while discussing strategies that may be used to implement PCC during diagnostic NM examinations performed on adult patients. Methods The scoping review was conducted in accordance with the Joanna Briggs Institute methodology. The search was performed on PubMed, Embase and Cinhal in June 2023 and included studies in English, Spanish, Portuguese and Italian. The research equation combined keywords and Medical Subject Heading terms (MeSH) related to person-centred care (PCC), for all types of nuclear medicine diagnostic examinations performed. Three independent review authors screened all abstracts and titles, and all eligible full-text publications were included in this scoping review. Results Fifty-three articles, published between 1993 and 2022, met the inclusion criteria for this scoping review. Seven articles were published in 2015 while 56.6 % of all included studies were performed in Europe. Most studies (n = 39/53) focused on the patients only, with the identified patient benefits being: improve patient experience (67.9 %), increase patient comfort (13.2 %), increase patient knowledge (5.7 %), reduction of patient anxiety (9.4 %) and reduction of waiting/scan time (3.8 %). Conclusion The scoping review identified a lack of research investigating the use of person-centred care strategies in NM. Future research will focus on using an international survey to explore this topic in nuclear medicine departments overseas. Implications for practice By applying PCC principles, the NM professional can improve the patient care pathway and increase patient satisfaction, leading to enhanced clinical outcomes.

Abrasion of tire tread, caused by friction between vehicle tires and road surfaces, causes release of tire wear particles (TWPs) into various environmental compartments. TWPs contribute to chemical-, microplastic-, and particulate matter pollution. Their fate remains largely unknown, especially regarding the extent and form in which they persist in the environment. This study investigated 1) the biodegradability of tread particles (TPs) in the form of ground tire tread, 2) how accelerated UV-weathering affect their biodegradability, and 3) which TP constituents are likely contributors to TP biodegradability based on their individual biodegradability. A series of closed bottle tests, with aerobic aqueous medium inoculated with activated sludge, were carried out for pristine TPs, UV-weathered TPs, and selected TP constituents; natural rubber (NR), isoprene rubber (IR), butadiene rubber (BR), and treated distillate aromatic extracts (TDAE). Biodegradation was monitored by manometric respirometry quantifying biological oxygen consumption over 28 days. Pristine TP biodegradability was found to be 4.5%. UV-weathered TPs showed higher biodegradability of 6.7% and 8.0% with similar and increased inoculum concentration, respectively. The observed TP biodegradation was mainly attributed to biodegradation of NR and TDAE, with individual biodegradability of 35.4% and 8.0%, respectively. IR and BR showed negligible biodegradability. These findings indicate biodegradability of individual constituents is decreased by a factor of 2 to 5 when compounded into TPs. Through scanning electron microscope (SEM) analysis, biodegradation was found to cause surface erosion. Processes of TP biodegradation are expected to change throughout their lifetime as new constituents are incorporated from the road and others degrade and/or leach out. Tire emissions likely persist as particles with an increased fraction of synthetic rubbers and carbon black.

Programming a robotic is a complex task, as it demands the user to have a good command of specific programming languages and awareness of the robot's physical constraints. We propose a framework that simplifies robot deployment by allowing direct communication using natural language. It uses large language models (LLM) for prompt processing, workspace understanding, and waypoint generation. It also employs Augmented Reality (AR) to provide visual feedback of the planned outcome. We showcase the effectiveness of our framework with a simple pick-and-place task, which we implement on a real robot. Moreover, we present an early concept of expressive robot behavior and skill generation that can be used to communicate with the user and learn new skills (e.g., object grasping)., Comment: Submitted to VLMNM 2024 - Workshop, ICRA 2024. This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

Buku ini di susun secara lengkap dengan tujuan untuk memudahkan para pembaca memahami isi buku ini. Buku ini membahas tentang teori pembelajaran, tantangan pembelajaran di era digital, konsep model dan aplikasi pembelajaran, strategi pemilihan model dan aplikasi pembelajaran, inovasi pembelajaran di era digital, pembelajaran daring dengan menggunakan platform edlink

Mikroalger kan dyrkes ved brug af saltvand og kræver ikke arealer, som traditionelt anvendes til landbrug eller naturformål, og kan dermed bidrage til en mere bæredygtig fødevareproduktion.

In 2004, the potential societal implications related to nanotechnology were highlighted in an influential report by the Royal Society and the Royal Academy of Engineering (RS & RAE). It was made clear that legislation is an important tool to tackle the challenges related to nanomaterials and a list of recommendations were put forward. Shortly after, the European Commission also proposed a list of recommendations on how to handle nanomaterial challenges and adopted the so-called "incremental approach", describing that current legislations should be adapted, where relevant, to handle nanomaterials. Now almost 20 years have passed and it seems relevant to take stock and investigate how legislations have been adapted to tackle nano-specific challenges. In this review, we analyze key pieces of European legislations relevant to nanomaterials and assess to what extent these legislations compare with the original recommendations from 2004 by the RS & RAE and the European Commission. We uncover the cross-cutting challenges that remain and provide recommendations on next steps that should be taken to address the risks of nanomaterials. For each recommendation, we assessed whether it was met to a high, medium or low degree by conducting targeted literature searches at Web of Science, screening legislations, guidance documents, databases etc., and applying expert judgement. We found that >90% of the recommendations put forward in 2004 by the RS & RAE and the European Commission have been either met to a high degree (13 out of 29) or met to a medium degree (14 out of 29). This suggests important advancements in the field of nanosafety. At the same time, it is important to address the concerns still left partly or fully unsolved. Such efforts entail e.g. further development of measuring instruments and standardised characterization and risk assessment methods for nanomaterials, application of a uniform nanomaterial definition, maximization of containment of free na

The increasing release of engineered nanoparticles (NPs) into aquatic ecosystems makes it crucial to understand the interactions of NPs with aquatic organisms, such as algae. In this study, the association of CeO2 NPs with unicellular algae (Raphidocelis subcapitata) and changes to the cellular elemental profile were investigated using three exposure concentrations (1, 50, and 1000 µg CeO2/L) at two different algal growth conditions—exponential and inhibited growth (1% glutaraldehyde). After a 24 h-exposure, algal suspensions were settled by gravity and CeO2-NP/algae association was analyzed by single-cell inductively coupled plasma quadrupole mass spectrometry (sc-ICP-QMS) and ICP time-of-flight MS (sc-ICP-TOFMS). Concurrent detection of the cellular fingerprint with cerium indicated NP association with algae (adsorption/uptake) and changes in the cellular elemental profiles. Less than 5% of cells were associated with NPs when exposed to 1 µg/L. For 50 µg/L exposures in growing and inhibited cell treatments, 4% and 16% of cells were associated with CeO2 NPs, respectively. ICP-TOFMS analysis made it possible to exclude cellular exudates associated with CeO2 NPs due to the cellular fingerprint. Growing and inhibited cells had different elemental profile changes following exposure to CeO2 NPs—e.g., growing cells had higher Mg and lower P contents independent of CeO2 concentration compared to inhibited cells.

The management of produced water (PW) discharges from offshore oil and gas installations in the North Atlantic is under the auspices of OSPAR (Oslo/Paris convention for Protection of the Marine Environment of the North-East Atlantic). In 2010, OSPAR introduced the Risk Based Approach (RBA) for PW management. The RBA includes a hazard assessment estimating PW ecotoxicity using two approaches: Whole Effluent Testing (WET) and Substance Based (SB). Set against the framework of the WET and SB approach, this study conducted a literature review on the magnitude and cause of PW ecotoxicity, respectively, and on the challenges of estimating these. A large variability in the reported magnitude of PW WET was found, with (E/L)C50-values ranging from 100% and a median of 11% (n=301). Metals, hydrocarbons, and production chemicals were identified as causing ecotoxicity across literature. However, this review reveals how knowledge gaps on PW composition and high sample- and species-dependency of PW ecotoxicity makes clear identification and generalization difficult. It also highlights how limitations regarding availability and reliability of ecotoxicity data result in large uncertainties in the subsequent risk estimates, which is not adequately reflected in the RBA output (e.g. environmental impact factors). Thus, it is recommended to increase the focus on improving ecotoxicity data quality before further use in the RBA, and that WET should play a more pronounced role in the testing strategy. To increase the reliability of the SB approach, more attention should be given to the actual composition of PW. Bioassay-directed chemical analysis, combining outcomes of WET and SB in toxicity identification evaluations, may hold the key to identifying drivers of ecotoxicity in PW. Finally, an uncertainty appraisal must be an integrated part of all reporting of risk estimates in the RBA, to avoid mitigation actions based on uncertainties rather than reliable ecotoxicity estimatio

Despite the increasing concern about the harmful effects of micro- and nanoplastics (MNPs), there are no harmonized guidelines or protocols yet available for MNP ecotoxicity testing. Current ecotoxicity studies often use commercial spherical particles as models for MNPs, but in nature, MNPs occur in variable shapes, sizes and chemical compositions. Moreover, protocols developed for chemicals that dissolve or form stable dispersions are currently used for assessing the ecotoxicity of MNPs. Plastic particles, however, do not dissolve and also show dynamic behavior in the exposure medium, depending on, for example, MNP physicochemical properties and the medium’s conditions such as pH and ionic strength. Here we describe an exposure protocol that considers the particle-specific properties of MNPs and their dynamic behavior in exposure systems. Procedure 1 describes the top-down production of more realistic MNPs as representative of MNPs in nature and particle characterization (e.g., using thermal extraction desorption-gas chromatography/mass spectrometry). Then, we describe exposure system development for short- and long-term toxicity tests for soil (Procedure 2) and aquatic (Procedure 3) organisms. Procedures 2 and 3 explain how to modify existing ecotoxicity guidelines for chemicals to target testing MNPs in selected exposure systems. We show some examples that were used to develop the protocol to test, for example, MNP toxicity in marine rotifers, freshwater mussels, daphnids and earthworms. The present protocol takes between 24 h and 2 months, depending on the test of interest and can be applied by students, academics, environmental risk assessors and industries.

I denne fokusanalyse giver vi en status på forskningsprojekter og initiativer indenfor dyrkning og anvendelse af tang og mikroalger til fødevarer. Formålet er at inspirere til nye initiativer på området for at få sat skub i innovation og etablering af en ny fødevaregruppe indenfor ”plantebaseret” seafood. Vi kalder det ”plantebaseret”, selvom tang og mikroalger ikke er planter men hhv. fler- og encellede organismer, altså to typer af alger. Overgangen fra animalsk til plantebaseret kost behøver ikke være på bekostning af smag og sundhed. På DTU Fødevareinstituttet forskes der i den blå biomasse og marine ressourcer. Det dækker alt fra bifangster såsom søstjerner til mikroalger. Men hovedformålet er, at vi skal blive bedre til at udnytte vores ressourcer og udvikle sunde, sikre og velsmagende fødevarer og ingredienser heraf. Tang og mikroalger er ideelle marine fødevarer, da deres næringssammensætning er meget lig den, vi ser i fisk og skaldyr. Vi har fået mere viden om, hvilke tangarter der er interessante ift. næringssammensætning og smag, hvordan vi kan så og dyrke tang med forskellige dyrkningssystemer, samt hvordan høstning optimeres, og hvordan tangen ændrer sammensætning afhængig af sæson. Alt dette med henblik på at få det optimale udbytte af f.eks. protein. Vi ved også nu, at det er muligt at udvælge, avle eller lave mutationer af mikroalger, alt sammen med det formål at optimere indholdsstofferne, f.eks. proteinindholdet. Ift. dyrkning af mikroalger er der behov for yderligere forskning i mulighederne for at udnytte industrielt procesvand som næringsmedie til fototrofe mikroalger. Smag og udseende spiller en stor rolle for forbrugernes accept af nye plantebaserede fødevarer. Igennem processering, som bl.a. fermentering, forskes der i at gøre tang og mikoalger appetitlige. Derudover kan tilsætning af antioxidanter være med til at forhindre harskning og udvikling af uønsket smag og lugt i produktet under processering, som p

Formålet med rapporten er at vurdere mulighederne for at fjerne tre nye pesticidnedbrydningsprodukter (R471811, LM5 og LM6) med aktivt kul og membranfiltrering i drikkevandsbehandling. Denne rapport skal ses som en udvidelse af den tidligere udgivet rapport om rensningsmuligheder for pesticider – med fokus på aktivt kul og membraner: Orientering fra Miljøstyrelsen nr. 53, oktober 2021

Baggrund: Sandsynligheden for overlevelse og død kan være svær at forudsige i føl med sepsis, her kan forskellige prognostiske markører og parametre være brugbare, men studier heri er begrænset. Formål: At undersøge om forskellige markører kan bruges til tidlig påvisning af sepsis og som markører for overlevelsesrate i føl. Sammenligning af forskellige komplikationer i relation til sepsis og overlevelse. Bestemmelse af effekten af antibiotika behandling forud for hospitalisering ift. overlevelse i septiske føl. Metodeafsnit: Retrospektivt studie med data fra 177 føl ≤ 30 dage indlagt på Universitets Hospitalet for Store Husdyr i Danmark fra 2018 til 2022. Følgende parametre blev undersøgt: komplikationer, antibiotika behandling forud for indlæggelse og prognostiske markører som serum amyloid A (SAA), laktat, neutrofile granulocytter, IgG, jern og hæmoglobin. Antibiotika behandling blev analyseret via en 2x2-tabel. Komplikationer og prognostiske markører blev undersøgt via en generaliseret lineær model med binomial variable og testet via ANOVA, samt pairs (hvis ANOVA-test blev fundet signifikant). Resultater: Et hundrede syvoghalvfjerds (54 cases og 123 kontroller) føl ≤ 30 var inkluderet i studiet. SAA var signifikant for sepsis (p < 0.01) men ikke for overlevelse. Laktat var signifikant for sepsis (p < 0.01) og for overlevelse i septiske og alle føl (p < 0.01; < 0.01, henholdsvis). Neutrofile var signifikant for sepsis og overlevelse i alle føl (p < 0.02; < 0.02, henholdsvis). IgG var signifikant for overlevelse i septiske og alle føl (p < 0.01; < 0.01, henholdsvis). Høj serum jern var associeret med bakteriæmi (p < 0.01) - hæmoglobin og jern/hæmoglobin kombineret var ikke signifikant for bakteriæmi. Omphalitis gav øget chance for overlevelse ift. septisk artritis, FPT og asfyksi (p ≤ 0.02). Septisk artritis var ikke signifikant ift. andre komplikationer (undtagen omphalitis). Antibiotika behandling forud for in, Background: Survival and non-survival can be difficult to predict in equine neonates with sepsis and different parameters and prognostic markers can be helpful - but studies in these are limited. Objectives: To determine if different clinicopathological variables can be used in early detection of sepsis and in prediction of survival rates. Comparison of different complications related to sepsis and survival rates. Determine if antibiotic treatment prior to hospitalization affects the survival in septic foals. Methods: Retrospective study with data from 177 foals ≤ 30 days of age admitted to the Large Animal Teaching Hospital in Denmark from 2018 to 2022. We evaluated complications, antibiotic treatment prior to admission and clinicopathological variables including serum amyloid A (SAA), lactate, neutrophil count, IgG, iron, and hemoglobin. Antibiotic treatment prior to referral were analyzed by a two-by-two table. Complications and clinicopathological variables were analyzed by a generalized linear model with binomial variables and tested by ANOVA and if significant effect, pairs was also used. Results: One hundred seventy-seven (54 cases and 123 controls) foals ≤ 30 days were included in the study. SAA was significant for diagnosing sepsis (p < 0.01) but not for survival. Lactate was significant for diagnosing sepsis (p < 0.01) and for survival in septic and all foals (p < 0.01; < 0.01, respectively). Neutrophils was significant for sepsis and survival in all foals (p < 0.02; < 0.02, respectively). IgG was significant for survival in septic foals and all foals (p < 0.01; < 0.01, respectively). High iron was associated with bacteremia (p < 0.01) - hemoglobin and iron/hemoglobin combined were not prognostic for bacteremia. The complication omphalitis was associated with increased chance of survival compared to septic arthritis, FPT, and asphyxia (p ≤ 0.02). Septic arthritis was not significant compared to all ot

Background: Functionally disruptive variants in the glucokinase gene (GCK) cause a form of mild non-progressive hyperglycemia, which does not require pharmacological treatment. A substantial proportion of patients with type 2 diabetes (T2D) carry GCK variants. We aimed to investigate whether carriers of rare GCK variants diagnosed with T2D have a glycemic phenotype and treatment response consistent with GCK-diabetes. Methods: Eight patients diagnosed with T2D from the Danish DD2 cohort who had previously undergone sequencing of GCK participated. Clinical examinations at baseline included an oral glucose tolerance test and continuous glucose monitoring. Carriers with a glycemic phenotype consistent with GCK-diabetes took part in a three-month treatment withdrawal. Results: Carriers of pathogenic and likely pathogenic variants had lower median fasting glucose and C-peptide levels compared to carriers of variants of uncertain significance and benign variants (median fasting glucose: 7.3 (interquartile range: 0.4) mmol/l vs. 9.5 (1.6) mmol/l, p = 0.04; median fasting C-peptide 902 (85) pmol/l vs. 1535 (295) pmol/l, p = 0.03). Four participants who discontinued metformin treatment and one diet-treated participant were reevaluated after three months. There was no deterioration of HbA1c or fasting glucose (median baseline HbA1c: 49 (3) vs. 51 (6) mmol/mol after three months, p = 0.4; median baseline fasting glucose: 7.3 (0.4) mmol/l vs. 7.0 (0.6) mmol/l after three months, p = 0.5). Participants did not consistently fulfill best practice guidelines for GCK screening nor clinical criteria for monogenic diabetes. Discussion: Carriers of pathogenic or likely pathogenic GCK variants identified by unselected screening in T2D should be reported, as they have a glycemic phenotype and treatment response consistent with GCK-diabetes. Variants of uncertain significance should be interpreted with care. Systematic genetic screening of patients with common T2D receiving routine care

The discharge of H2S scavenging wastewaters, containing spent and unspent scavengers (SUS), into the marine environment is a large contributor to the environmental impact of offshore oil and gas production. Hydrothermal oxidation (HTO) can be a viable method for on-site treatment of the SUS before discharge, but the effect of the process on the ecotoxicity of the effluent has not been investigated so far. The aim of this study was to investigate the potential of the HTO technology in reducing the environmental impact by linking the chemical process design with ecotoxicity reduction. For this, we combined HTO experiments on a SUS sample from an oil and gas platform in the North Sea with whole effluent ecotoxicity evaluation before and after the treatment. The HTO process was carried out under excess of oxygen, for temperatures and pressures in the range 199 to 350°C and 83 to 228 bar, respectively, and for reaction times of 5 to 360 min. Initially, the SUS sample exhibited very high ecotoxicity, which was drastically reduced by the HTO process. More specifically, the ecotoxicity towards bacteria was reduced more than 90% for all HTO conditions, while the reduction in algal toxicity was in the range 48% to 66%, 59% to 86% and 60% to 82% at reaction temperatures of 199°C, 279°C, and 350°C, respectively. Furthermore, this work shows how typical wastewater chemical analyses, such as COD and TOC, and ecotoxicity tests towards different organisms provide complementary information, which should be used in combination to optimize operating conditions of the HTO process.

The history of the Greenlandic population has contributed to a unique genetic composition in which high-impact and often novel genetic variants segregate at a high frequency. As a result, research in smaller populations like the Greenlandic has the potential to reveal genetic variation and associations that are not present or discoverable in other populations. In this review, we provide a summary of our research in Greenlanders and our findings of genetic variants with high impact on metabolic health, and outline the implications that this research has for the equitable distribution of genomic precision medicine.

Background Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. Methods We searched PubMed and Embase for publications that used ‘simple subclassification’ approaches using simple categorisation of clinical characteristics, or ‘complex subclassification’ approaches which used machine learning or ‘omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. Results Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. Conclusion Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes., BACKGROUND: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients.METHODS: We searched PubMed and Embase for publications that used 'simple subclassification' approaches using simple categorisation of clinical characteristics, or 'complex subclassification' approaches which used machine learning or 'omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches.RESULTS: Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes.CONCLUSION: Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.

Background Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)—with a high recurrence rate—and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. Methods This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). Conclusions The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. Trial registration: NCT03724318., Background: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)—with a high recurrence rate—and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. Methods: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). Conclusions: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. Trial registration: NCT03724318.

New synthetic chemicals and materials are rising rapidly and are already widespread as novel entities in our daily lives. Although knowledge of their disruptive and long-lasting effects on the Earth system is accumulating, unknowns remain. This Voices asks: what risks do novel entities pose, and what are the emerging concerns?

Worldwide most factories aim for low-cost and fast production ignoring resources and energy consumption. But, high revenues have been accompanied by environmental degradation. The United Nations reacted to the ecological problem and proposed the Sustainable Development Goals, and one of them is Sustainable Production (Goal 12). In addition, the participation of lightweight robots, such as collaborative robots, in modern industrial production is increasing. The energy consumption of a single collaborative robot is not significant, however, the consumption of more and more cobots worldwide is representative. Consequently, our research focuses on strategies to reduce the energy consumption of lightweight robots aiming for sustainable production. Firstly, the energy consumption of the lightweight robot UR10e is assessed by a set of experiments. We analyzed the results of the experiments to describe the relationship between the energy consumption and the evaluation parameters, thus paving the way to optimization strategies. Next, we propose four strategies to reduce energy consumption: 1) optimal standby position, 2) optimal robot instruction, 3) optimal motion time, and 4) reduction of dissipative energy. The results show that cobots potentially reduce from 3\% up to 37\% of their energy consumption, depending on the optimization technique. To disseminate the results of our research, we developed an AR game in which the users learn how to energy-efficiently program cobots.

BACKGROUND: Left atrial (LA) volumes and emptying fraction in the general population may address structural and functional aspects of atrial cardiomyopathy associated with long-term risk of ischemic stroke in the absence of atrial fibrillation or prior stroke. We investigated the association between LA volumes and function and ischemic stroke. METHODS AND RESULTS: In a community-based cohort, we measured LA minimal volume, LA maximal volume, and LA emptying fraction by transthoracic echocardiography. The primary end point was ischemic stroke. Participants with known atrial fibrillation or prior ischemic stroke were excluded, which resulted in 1866 participants. The mean age was 58±16 years, and 57% were women. During a median follow-up of 16.5 years (interquartile range: 11.4–16.8 years), 176 (9.4%) ischemic strokes occurred. In multivariable cause-specific regression models and competing risk models with death as a competing risk, LA emptying fraction was associated with ischemic stroke (hazard ratio [HR], 1.14 per 10% decrease [95% CI, 1.02–1.28]) and (subdistribution HR, 1.14 [95% CI, 1.01–1.29]). This association remained when adjusting for participants who developed atrial fibrillation during follow-up (HR, 1.12 per 10% decrease [95% CI, 1.00–1.26]). Indexed LA volumes were not associated with ischemic stroke in the same models. LA emptying fraction and indexed LA volumes were not associated with all-cause mortality. CONCLUSIONS: Lower LA emptying fraction measured by transthoracic echocardiography was associated with future ischemic stroke independently of incident atrial fibrillation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993172.

Regulation of plastics has emerged as a significant science-policy challenge, initiated by the increasing societal concerns regarding plastic pollution. A specific focus is now on plastic of sizes smaller than 1000 nm, often referred to as nanoplastics. The need to include nanoplastics in existing regulatory frameworks arises from the increased bioavailability and toxicity of smaller particles compared to larger fragments. (1) The size of particles plays a critical role in their uptake and influences particle reactivity and hazard potential, for example, production of reactive oxygen species. When considering nanoplastics, specific concerns are directed to size fractions of plastics <100 nm, consistent with the size-specific concerns regarding ultrafine particles and with the regulatory definition of nanomaterials. Thus, classification of nanoplastics as “nanomaterials” for regulatory purposes would seem logical. However, as nanoplastics consist mainly of polymers, they could also be regulated as polymers, which are currently exempted from registration under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). It is also noteworthy that the vast majority of micro- and nanoplastics in the environment arise from the weathering of plastic waste and as such would not be addressed under existing chemicals legislation, even if plastics required registration. Currently, three important policy and legislative processes are ongoing in parallel that will impact the future regulation of plastics in general and intentionally produced micro- and nanoplastics in particular. First, the European Commission (EC) is considering the restriction proposal commissioned to the European Chemicals Agency (ECHA) on intentionally added microplastics. (2) Second, there is a discussion about how to define polymers under the European Chemicals Regulation, REACH, so that polymers are not automatically exempted from registration and submission of health and en

Background: Glioblastomas are highly resistant to therapy, and virtually all patients experience tumor recurrence after standard-of-care treatment. Surgical tumor resection is a cornerstone in glioblastoma therapy, but its impact on cellular phenotypes in the local postsurgical microenvironment has yet to be fully elucidated. Methods: We developed a preclinical orthotopic xenograft tumor resection model in rats with integrated 18F-FET PET/CT imaging. Primary and recurrent tumors were subject to bulk and single-cell RNA sequencing. Differentially expressed genes and pathways were investigated and validated using tissue specimens from the xenograft model, 23 patients with matched primary/recurrent tumors, and a cohort including 190 glioblastoma patients. Functional investigations were performed in vitro with multiple patient-derived cell cultures. Results: Tumor resection induced microglia/macrophage infiltration, angiogenesis as well as proliferation and upregulation of several stem cell-related genes in recurrent tumor cells. Expression changes of selected genes SOX2, POU3F2, OLIG2, and NOTCH1 were validated at the protein level in xenografts and early recurrent patient tumors. Single-cell transcriptomics revealed the presence of distinct phenotypic cell clusters in recurrent tumors which deviated from clusters found in primary tumors. Recurrent tumors expressed elevated levels of pleiotrophin (PTN), secreted by both tumor cells and tumor-associated microglia/macrophages. Mechanistically, PTN could induce tumor cell proliferation, self-renewal, and the stem cell program. In glioblastoma patients, high PTN expression was associated with poor overall survival and identified as an independent prognostic factor. Conclusion: Surgical tumor resection is an iatrogenic driver of PTN-mediated self-renewal in glioblastoma tumor cells that promotes therapeutic resistance and tumor recurrence.

The Internet of Behaviors (IoB) puts human behavior at the core of engineering intelligent connected systems. IoB links the digital world to human behavior to establish human-driven design, development, and adaptation processes. This paper defines the novel concept by an IoB model based on a collective effort interacting with software engineers, human-computer interaction scientists, social scientists, and cognitive science communities. The model for IoB is created based on an exploratory study that synthesizes state-of-the-art analysis and experts interviews. The architecture of a real industry 4.0 manufacturing infrastructure helps to explain the IoB model and it's application. The conceptual model was used to successfully implement a socio-technical infrastructure for a crowd monitoring and queue management system for the Uffizi Galleries, Florence, Italy. The experiment, which started in the fall of 2016 and was operational in the fall of 2018, used a data-driven approach to feed the system with real-time sensory data. It also incorporated prediction models on visitors' mobility behavior. The system's main objective was to capture human behavior, model it, and build a mechanism that considers changes, adapts in real-time, and continuously learns from repetitive behaviors. In addition to the conceptual model and the real-life evaluation, this paper provides recommendations from experts and gives future directions for IoB to become a significant technological advancement in the coming few years., Comment: 11 pages, 3 tables, 5 figures

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Objective: Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors. Methods: Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). Results: The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups. Conclusion: Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.

The number and volume of advanced materials being manufactured is increasing. In order to mitigate future impacts from such materials, assessment methods that can provide early indications of potential environmental risk are required. This paper presents a further development and testing of an environmental risk screening method based on two proxy measures: aquatic ecotoxicity and global annual production volumes. In addition to considering current production volumes, this further developed method considers potential future production volumes, thereby enabling prospective environmental risk screening. The proxy measures are applied to seven advanced materials: graphene, graphene oxide, nanocellulose, nanodiamond, quantum dots, nano-sized molybdenum disulfide, and MXenes. Only MXenes show high aquatic ecotoxicity, though the number of test results is still very limited. While current production volumes are relatively modest for most materials, several of the materials (graphene, graphene oxide, nanocellulose, nano-sized molybdenum disulfide, and MXenes) have the potential to become high-volume materials in the future. For MXenes, with both high aquatic ecotoxicity and high potential future production volumes, more detailed environmental risk assessments should be considered. For the other materials with high potential future production volumes, the recommendation is to continuously monitor their aquatic ecotoxicity data. Based on the application of the proxy measures combined with future scenarios for production volumes, we recommend this environmental risk screening method be used in the early development of advanced materials to prioritize which advanced materials should be subject to more detailed environmental assessments.

In the European Union the Annexes of its chemical legislation (REACH) were revised and now clarify the technical data requirements for nanomaterials (NMs). These new provisions, effective from January 1, 2020, introduce requirements for manufacturers, importers and downstream users regarding registration and safety assessment of NMs. This study aims to assess the availability and suitability of methods needed to comply with the new regulatory provisions on NMs for physico-chemical characterisation and environmental fate and effects. The scientific literature and relevant test guideline frameworks were reviewed to identify applicable methods. These were subsequently evaluated and categorised as either: 'internationally accepted test guideline or standard (TGS)', 'internationally accepted test guideline or standard under development (TGSUD)', 'established as standard methods in scientific literature (SCI)', 'other methods and/or more research needed (O)' or 'no method (N)'. We find that 80% of the information requirements and a bit more than 40% of the waiving criteria in the new REACH Annexes are supported by methods that are available as TGS, TGSUD or SCI. Most of the relevant methods in the scientific literature are included in recent OECD guidance documents or ECHA guidance. We recommend that a targeted effort is made to develop protocols and guidelines for methods to determine NM adsorption/desorption, degradation, exposure scenarios and ability to cross biological membranes. Here methods to fulfil the information requirements and waiving criteria are currently lacking. Furthermore, we recommend that increasing attention is directed towards regulatory reliability and relevance of the information that is submitted by the registrants., QC 20210412

Tracer tests represent a well-established method for delineating key environmental processes in various media and engineered systems. Tracers like Rhodamine B and WT are frequently applied due to their strong fluorescence even at low concentrations. However, due to a lack of ecotoxicological data, limit values for these tracers cannot be determined. This study fills this critical data gap by providing ecotoxicity data for Rhodamine B and WT using a battery of short-term standardized tests, including growth rate inhibition tests with algae (Raphidocelis subcapitata) and lethality tests using crustaceans (Daphnia magna) and zebrafish (Danio rerio) embryos, and estimating EQS for surface water. For Rhodamine B, the effective and lethal concentration (EC50 and LC50) –causing 50% toxicity were in the range of 14–24 mg/L. For Rhodamine WT, no statistically significant effects were observed (p<0.05) at the tsted concentrations (up to 91, 100 and 200 mg/L for algae, crustaceans and fish embryos, respectively). Thus for all tested organisms, Rhodamine B was more toxic than Rhodamine WT (more than 14 times more toxic for R. subcapitata, 5.6 times for D. magna, 15 times for D. rerio embryos,based on EC10 and LC10 values). These results signify that read-across assessments using ecotoxicity data obtained with Rhodamine B is not advisable for estimating the ecotoxicity of Rhodamine WT. The annual-average quality standard (AA-QS) and maximum allowable concentration quality standard (MAC-QS) for Rhodamine B were found to be 14 and 140 µg/L, respectively. For Rhodamine WT, the corresponding values were estimated to >91 µg/L (AA-QS) and >910 µg/L (MAC-QS). Hence, concentrations below 140 µg/L or 910 µg/L for Rhodamine B and WT, respectively, are not expected to pose a risk to aquatic freshwater life in the case of intermittent discharges, e.g. tracer experiments released in streams.

With the intention to move away from animal testing for the toxicological evaluation of chemicals comes the need to develop new approach methodologies which are mechanism-anchored and target relevant key events leading to an adverse outcome. To date, no validated alternative methods are available for studying the acute inhalation toxicity potential of airborne chemicals but the constrained drop surfactometer measuring the surface tension of a drop of lung surfactant presents as a promising candidate. Indeed, the correlation of the increase in minimum surface tension of lung surfactant in vitro with changes in the breathing patterns of mice after inhalation of test compounds has been shown in multiple studies. However, the causal factors leading to lung surfactant inactivation remain speculative. This paper combines molecular and biophysical methods (constrained drop and captive bubble surfactometers, Langmuir-Blodgett balance, epifluorescence microscopy, cryogenic transmission electron microscopy, and differential scanning calorimetry) applied to purified porcine lung surfactant and dipalmitoylphosphatidylcholine interfacial films to gain insights into the disruption of lung surfactant function by three chemicals known to show acute inhalation toxicity (trimethoxyoctylsilane, methyl 3-oxo-2-pentylcyclopentaneacetate, and diisopentyl ether). The results of this study suggest that the test chemicals intercalate between the phospholipids at the air-liquid interface, reduce the stability of the films, and decrease the cohesivity of interface-associated multilayered structures thereby perturbing the lung surfactant surface activity. These findings contribute to a better understanding of chemically-induced lung surfactant function disruption.

Background: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). Objective: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. Methods: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30–98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. Results: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40–4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30–4.17). Conclusion: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.

Background Increased age has been shown to be associated with weaker external rotators and stronger internal rotators of the shoulder in pitchers and tennis players. Whether this age-associated change is present in elite badminton players is unknown. Purpose To compare the internal and external rotation strength of the shoulder in adolescent and adult elite badminton players. Study design Cross-sectional. Methods Thirty-one adolescent (12 females aged 16.8 ± 1.6 years and 19 males aged 17.1 ± 1.6 years) and 29 adult (10 females aged 25 ± 2.9 years and 19 males aged 26.2 ± 4.6 years) national level badminton players were tested pre-seasonally for external rotation (ER) and internal rotation (IR) isometric muscle strength bilaterally, using a hand-held dynamometer. Within-group ER to IR strength ratios were calculated (ER/IR×100%). Results The adolescents had stronger shoulder ER than the adults on both sides (p < 0.05). The adult males tended to have stronger IR of the dominant shoulder than the adolescent males (p = 0.071). In the dominant shoulders, the strength ratios for adult females and males were 77% and 78%, respectively, while the same ratio for adolescent females and males were 85% and 99%, respectively. In the non-dominant shoulders, the ER/IR strength ratios for adult females and males were 90% and 87%, respectively, while the ratios for adolescent females and males were 116% and 102%, respectively. Conclusion This study is the first to demonstrate that in shoulder injury-free national team badminton players, adolescents have stronger shoulder ER than adults on both sides. Therefore, increased age appears to be associated with weaker shoulder ER muscles in elite badminton players. Level of evidence 3b.

Tracer tests represent a well-established method for delineating key environmental processes in various media and engineered systems. Tracers like Rhodamine B and WT are frequently applied due to their strong fluorescence even at low concentrations. However, due to a lack of ecotoxicological data, limit values for these tracers cannot be determined. This study fills this critical data gap by providing ecotoxicity data for Rhodamine B and WT using a battery of short-term standardized tests, including growth rate inhibition tests with algae (Raphidocelis subcapitata) and lethality tests using crustaceans (Daphnia magna) and zebrafish (Danio rerio) embryos, and estimating EQS for surface water. For Rhodamine B, the effective and lethal concentration (EC50 and LC50) –causing 50% toxicity were in the range of 14–24 mg/L. For Rhodamine WT, no statistically significant effects were observed (p<0.05) at the tsted concentrations (up to 91, 100 and 200 mg/L for algae, crustaceans and fish embryos, respectively). Thus for all tested organisms, Rhodamine B was more toxic than Rhodamine WT (more than 14 times more toxic for R. subcapitata, 5.6 times for D. magna, 15 times for D. rerio embryos,based on EC10 and LC10 values). These results signify that read-across assessments using ecotoxicity data obtained with Rhodamine B is not advisable for estimating the ecotoxicity of Rhodamine WT. The annual-average quality standard (AA-QS) and maximum allowable concentration quality standard (MAC-QS) for Rhodamine B were found to be 14 and 140 µg/L, respectively. For Rhodamine WT, the corresponding values were estimated to >91 µg/L (AA-QS) and >910 µg/L (MAC-QS). Hence, concentrations below 140 µg/L or 910 µg/L for Rhodamine B and WT, respectively, are not expected to pose a risk to aquatic freshwater life in the case of intermittent discharges, e.g. tracer experiments released in streams.

Lipid oxidation is a major problem especially in foods containing unsaturated fatty acids causing undesirable off-flavors and reduced shelf life. Therefore, it is necessary to prevent this type of quality deterioration and sustain consumer acceptance by the addition of antioxidants. Synthetic antioxidants have been used in foods and personal care products to slow down or prevent lipid oxidation. However, the ever-growing consumers’ interest in natural ingredients and their concern for the safety of synthetic antioxidants has triggered researchers to replace them with natural antioxidants. Natural antioxidants can be extracted from terrestrial and marine environments. Fucus vesiculosus is a brown seaweed, which is growing in the waters of the Nordic countries and the Baltic Sea. This seaweed contains several compounds with antioxidant properties such as pigments, tocopherols, phenolic compounds, sulfated polysaccharides, and amino acids. In this study, the lipid-soluble fraction of F. vesiculosus (lipids, pigments, and carotenoids) was extracted using supercritical CO2 and the water-soluble fraction (polyphenols, and sulfated polysaccharide) was extracted using subcritical water. Two types of water-soluble fraction were prepared, one from residue obtained after extraction of lipid-soluble fractions, and the other from whole seaweed powder. The efficacy of the extracts to inhibit lipid oxidation of fish-oil-enriched mayonnaise was studied by adding either the lipid-soluble fraction in the oil phase or water-soluble fractions in the water phase. Moreover, the synergetic effect of oil and water-soluble fractions was studied by adding them in the oil and water phases respectively in the same mayonnaise formulation. The oxidation and physical stability of the mayonnaises was studied during a storage period of 4 weeks by evaluating droplet size, peroxide values, toco

This study updates and expands on the document “Nanomaterials in Waste Streams – Current Knowledge on Risks and Impacts" published by OECD in 2016. It covers ten topics: • Waste streams containing nanomaterials. • Behaviour and fate of nanomaterials in waste processes. • Exposure of waste management workers to nanomaterials. • Benefits and challenges of nanomaterials posed to the circular economy. • Impact of nanomaterials on recycling. • Main streams of nanomaterial recyclates. • Recycling abatement systems residues. • Potential for substitution of hazardous substances by nanomaterials in the recyclate streams. • Emission of nanomaterials. • Emission control and best available techniques. The review covered 276 publications, including books, research reports, research and review papers, databases, and other web resources. These publications were reviewed irrespective of the nanomaterial terminology used. However, the study specifically focuses on manufactured nanomaterials and incidental nanomaterials. This report refers to the definitions provided in CEN ISO/TS 80004-2:2017, where manufactured nanomaterial is "intentionally produced to have selected properties or composition", and incidental nanomaterial is "generated as an unintentional by-product of a process". The study focuses on the European Union situation and developments in nanomaterials, although relevant studies from other countries were reviewed where appropriate. To complement and validate the findings, twenty interviews were conducted with experts from academia, industry, international associations, national authorities, and non-profit organisations. The research topics have been addressed in three thematic sections of the study – "Nanomaterials in Waste", "Nanomaterials in Waste Management Processes", and "Nanomaterials in the circular economy".

Peter Blümler,1 Ralf P Friedrich,2 Jorge Pereira,3 Olga Baun,1 Christoph Alexiou,2 Volker Mailänder3,4 1Institute of Physics, Johannes Gutenberg-University Mainz, Mainz, 55128, Germany; 2Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, 91054, Germany; 3Department of Physical Chemistry, Max Planck Institute for Polymer Research, Mainz, 55128, Germany; 4Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, GermanyCorrespondence: Peter BlümlerInstitute of Physics, Johannes Gutenberg-University Mainz, Staudingerweg 7, Mainz, 55128, GermanyTel +49 6131 3924240Fax +49 6131 3925179Email bluemler@uni-mainz.deAbstract: Controlled and contactless movements of magnetic nanoparticles are crucial for fundamental biotechnological and clinical research (eg, cell manipulation and sorting, hyperthermia, and magnetic drug targeting). However, the key technological question, how to generate suitable magnetic fields on various length scales (μm–m), is still unsolved. Here, we present a system of permanent magnets which allows for steering of iron oxide nanoparticles (SPIONs) on arbitrary trajectories observable by microscopy. The movement of the particles is simply controlled by an almost force-free rotation of cylindrical arrangements of permanent magnets. The same instrument can be used to move suspended cells loaded with SPIONs along with predetermined directions. Surprisingly, it also allows for controlled movements of intracellular compartments inside of individual cells. The exclusive use of permanent magnets simplifies scaled up versions for animals or even humans, which would open the door for remotely controlled in vivo guidance of nanoparticles or micro-robots.Keywords: permanent magnets, Halbach, super-para

Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of 64Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG2-RM26 and NODAGA-PEG2-RM26. Methods: NOTA/NODAGA-PEG2-RM26 were labeled with 64Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [57Co]Co-NOTA/NODAGA-PEG2-RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG2-RM26 were stably labeled with 64Cu with quantitative yields. In vitro, binding of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was rapid and GRPR-specific with slow internalization. In vivo, [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [57Co]Co-NOTA/NODAGA-PEG2-RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [64Cu]Cu-NOTA-PEG2-RM26 had a significantly higher liver and pancreas uptake compared to other agents. 57Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the 64Cu-labeled counterparts. [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [55/57Co]Co-NOTA/NODAGA-PEG2-RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the 64Cu-labeled conjugates., De två första författarna delar förstaförfattarskapetDe två sista författarna delar sistaförfattarskapet

Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials., QC 20200322

Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling., QC 20200402