The direct start of oral intake after surgery improves short-term outcomes in patients undergoing minimally invasive esophagectomy. Based on recent insights, improvements in short-term outcomes may also lead to additional benefits in the long term. The current study investigated the overall survival and disease-free survival in patients receiving direct versus delayed oral feeding after minimally invasive esophagectomy in a randomized controlled cohort . The current study showed that patients in the direct oral feeding group had improved 3-year overall survival and 5-year disease-free survival compared to standard care. These findings are unexpected and may provide a new target to improve long-term outcomes in this patient group. p = 0.027), but not at 5 years (p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group (p = 0.047) and a trend towards improved DFS was shown at 3 years (p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials.Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group ( Esophagectomy with or without neoadjuvant therapy is the cornerstone of curative treatment for esophageal cancer ,2. HowevOur previous findings have indicated that further optimization of ERAS can be achieved by initiating oral intake directly after minimally invasive esophagectomy (MIE) ,9. In thInterestingly, a reduction in short-term complications not only benefits short-term outcomes, but is also associated with improved long-term survival ,11,12. OIn this planned sub-study of the randomized controlled NUTRIENT II trial, we investigated the influence of direct oral intake versus delayed oral intake on long-term survival.Patients who participated in the NUTRIENT II trial were included in this follow-up study. Patients who died within 90 days of surgery were excluded to solely focus on long-term outcomes after esophagectomy ,13,14. The NUTRIENT II trial was a prospective, international, multicenter, open-label, randomized controlled trial executed in three hospitals , Hospital Group Twente , and Karolinska University Hospital ), and included patients aged 18 years or above who underwent a minimally invasive Ivor Lewis esophagectomy (MIE-IL) between 1 October 2015 and 14 May 2018. The participants were randomized prior to surgery to receive either direct oral feeding (intervention group) or delayed oral feeding (control group) following esophagectomy. A detailed description of the methodology was published previously [All patients underwent an MIE-IL with a two-field lymphadenectomy. Intrathoracic anastomoses were performed side-to-side stapled or end-to-end hand sewn robotically. A feeding jejunostomy was routinely placed in all patients and was only used in the control group or in the occurrence of complications that prohibited oral intake in the intervention group. After surgery, the patients stayed in the ICU or a specialized postoperative ward unit for one night before returning to a regular surgical ward as part of the standard postoperative protocol. Standardized postoperative care for all patients also included early mobilization, no nasogastric tube placement, and optimal pain management. In patients allocated to the intervention group, oral intake (pureed and liquid food) was started directly after surgery. The patients were allowed to drink sips of water up to 250 cc on the day of surgery, and 500 cc of oral intake  was allowed on postoperative day (POD) 1. The intake was gradually increased to a maximum of 1500 cc on POD 5. From POD 15 onwards, the patients could eat solid foods without any restrictions. The patients in the control group  had a delay in oral intake and were only allowed to drink sips of water up to 250 cc in the days following surgery. Additionally, they received nutrition through the jejunostomy. From POD 5 onwards, the patients were allowed to gradually increase their oral intake similarly to the intervention group. The intake of solid food without restrictions was allowed from POD 15. The complete nutritional protocol of both treatment arms was disclosed in earlier work . Tube feeding via jejunostomy was initiated in patients for whom complications prohibited oral intake or in patients in the intervention group with an intake lower than 50% of their calculated caloric need on POD 5. A routine chest X-ray was performed daily, and when gastric conduit dilatation was visible or clinical signs of gastroparesis emerged, a nasogastric tube was  inserted.Routine follow-up visits were scheduled postoperatively according to the local protocol within each hospital. On indication, visits were scheduled earlier. In general, no routine radiologic investigations were carried out and diagnostic assessments were primarily guided by the symptoms of the patient. After five years, no routine follow-up visits were planned and visits were only planned on indication. Comparisons were made between the delayed and direct oral feeding groups. The primary outcome was overall survival, defined as all deaths occurring within 3 and 5 years from the time of surgery from any cause. The secondary outcome was disease-free survival, defined as locoregional recurrence or metastatic disease diagnosed within 3 and 5 years from the time of surgery that was related to the primary esophageal cancer. Other outcomes included the impact of complications and caloric intake on 3- and 5-year overall survival. Patient characteristics and postoperative data until 90 days after surgery were prospectively collected. Recurrence and vital status data were prospectively registered and retrospectively collected from the electronic patient dossier. If not up to date, vital status data were obtained by assessing the municipal administrative database, which contains information about all (former) inhabitants of a country. 2 test or Fisher’s exact test and presented as absolute values with a corresponding percentage. After an assessment of normality, continuous variables were analyzed using the T-test or Mann–Whitney U and presented as the median with interquartile range (IQR). Analyses were carried out according to the intention-to-treat principle. A two-tailed p-value of <0.05 was considered statistically significant. Statistical analyses were performed using Statistical Software for the Social Sciences (SPSS) version 29 (IBM Software Group). Figures were made with Prism 8.2 .Categorical data were assessed using the χ2 test. The 5-year overall and disease-free survival in the delayed and direct oral feeding groups were estimated using the Kaplan–Meier method and compared with the log-rank test. Time to event was calculated from the date of surgery to the date of event (death/recurrence) or last follow-up (censor). Patients were censored if they were alive 5 years after surgery. The overall survival and disease-free survival rates at 3 years were compared between the delayed and direct oral feeding group using the χ2 test.Further analyses were conducted to assess the impact of additional characteristics on 3-year and 5-year overall survival within this cohort. To evaluate the influence of postoperative complications on overall survival, analyses were performed separately for patients with and without complications occurring within 30 days of surgery. Also, the impact of the severity of complications according to the CD classification was investigated . Moreover, the impact of caloric intake on survival outcomes was examined. The percentage of caloric need was calculated  on POD5 and divided into quartiles. The overall survival of these quartiles was compared. The 5-year overall survival between groups was estimated using the Kaplan–Meier method and compared with the log-rank test. The 3-year survival was compared between groups using the χIn total, 145 of 148 patients who participated in the NUTRIENT II trial were included in this follow-up study. Three patients were excluded because of death within 90 days of surgery. Of the included patients, 63 (43.4%) received direct oral feeding after esophagectomy.p = 0.034). Other postoperative complications, including pneumonia, anastomotic leakage, postoperative ileus, conduit necrosis/fistula, and jejunostomy complications, were equally distributed between both groups. Also, the severity of complications according to the Clavien–Dindo (CD) classification was comparable. The baseline characteristics are shown in p = 0.115, p = 0.027). All patients in this cohort died as a result of metastatic disease from the primary esophageal cancer, with the exception of one patient in each group who died due to non-cancer related causes .After five years of follow-up, 46.2% of patients were alive in the delayed oral feeding group compared to 61.9% in the direct oral feeding group . In the direct oral feeding group, recurrence data were missing for one person and three patients were lost to follow-up (between 48 and 53 months after surgery).For disease-free survival, the Kaplan–Meier curves showed an early separation between groups favoring the direct oral feeding group that continued over time; however, this did not reach statistical significance at 3 and 5 years. Disease-free survival at 5-year follow-up was 33.3% versus 52.9% (p = 0.502) and 5-year overall survival .The characteristics of patients with or without complications were comparable at baseline. In this cohort, the occurrence of postoperative complications did not seem to influence 3- (p < 0.001) in the delayed oral feeding group. The corresponding median percentage of caloric need was 96.0% (IQR 74.6–112.2%) and 55.9%  in the delayed and direct oral feeding group, respectively. After segmenting the percentage of caloric need into quartiles and subsequently comparing them in relation to overall survival, no differences among the quartiles were observed at 3 and 5 years  in the early oral intake group versus 1968 kcal enteral intake could have contributed to the outcomes. The study by Okada et al. showed that postoperative nutrition, mostly based on enteral intake, negatively influenced overall survival when compared to oral intake as a more physiological route , underlin = 1) or incomplete (n = 3). Also, the relatively small sample size of the NUTRIENT II cohort might have influenced the statistical power to detect certain long-term associations. Although this is a planned sub-study of the NUTRIENT II trial, the initial study was powered for functional recovery and it might well be that it was underpowered for accurately assessing long-term survival outcomes. The current study holds an important strength as it builds upon the multicenter randomized controlled NUTRIENT II trial. The patients in this trial were not selected based on advantageous characteristics, making the results comparable with daily clinical practice. Additionally, most data were prospectively collected as part of the standard follow-up. However, this study also has some limitations. Recurrence data were retrospectively collected from the electronic patient dossier and, therefore, some recurrence data are missing (The outcomes of the current follow-up study from the randomized controlled NUTRIENT II trial show a trend towards improved 3-year overall survival and 5-year disease-free survival in patients receiving direct oral feeding following MIE-IL when compared to delayed oral feeding. These findings suggest a potential survival benefit associated with direct oral feeding. However, additional research is needed to substantiate a potential relation between this intervention and long-term survival.


In vitro articles reporting on the DC, polymerization shrinkage/shrinkage stress, and flexural strength of flowable BF-RBCs strength were included. The QUIN risk-of-bias (RoB) tool was used for assessing the study quality. From initially 684 found articles, 53 were included. Values for DC ranged between 19.41 and 93.71%, whereas polymerization shrinkage varied between 1.26 and 10.45%. Polymerization shrinkage stresses reported by most studies ranged between 2 and 3 MPa. Flexural strength was above 80 MPa for most materials. A moderate RoB was observed in most studies. Flowable BF-RBCs meet the requirements to be indicated for bulk fill restoration technique in the posterior region. However, important variations among composition and properties hinder extrapolation of the results to materials different from those reported here. Clinical studies are urgently required to assess their performance under a real working scenario.Flowable bulk-fill resin-based composites (BF-RBCs) represent a new and interesting alternative for the bulk-fill restorative techniques in the posterior region. However, they comprise a heterogeneous group of materials, with important differences in composition and design. Therefore, the aim of the present systematic review was to compare the main properties of flowable BF-RBCs, including their composition, degree of monomer conversion (DC), polymerization shrinkage and shrinkage stress, as well as flexural strength. The search was conducted following PRISMA guidelines in the Medline (PubMed), Scopus and Web of Science databases.  Bulk-fill resin-based composites (BF-RBCs) were introduced to the dental market during the last decade, aiming to solve issues associated with the incremental technique in posterior teeth. Initially, the term bulk-fill was used to designate resin composites that allowed 4–5 mm thick increments, being adequate for the full-body and base bulk-fill techniques . HoweverResin composites aiming to be included into the BF-RBC category need to comply with two fundamental requirements: (1) an adequate degree of monomer conversion (DC) throughout the material; and 2) the ability to compensate or dissipate polymerization shrinkage stress at the cavity margins  the abil the lattCurrent commercial BF-RBCs can be classified according to their viscosity in flowable (low viscosity) and sculptable . Flowable RBCs have been known in the past to display inferior mechanical properties than high-viscosity RBCs, mainly due to the higher amount of filler particles in the latter . AccordiTo date, a large number of flowable BF-RBCs are available in the market. Despite their common seek for higher DC and reduced polymerization shrinkage stresses, manufacturers have gone different ways to achieve these goals, which in turn has led to different degrees of success. Accordingly, material selection and indication has become a difficult task for clinicians around the world. In this vein, the aim of the present systematic review was to compare, on the base of available scientific evidence, the main properties of flowable BF-RBCs, including their composition, DC, polymerization shrinkage and shrinkage stress, as well as flexural strength.in vitro studies on the DC, polymerization shrinkage/shrinkage stress, and flexural strength of flowable BF-RBCs, were included. Systematic reviews and meta-analysis, articles written in any other language than English, as well as nonavailable full-text references were excluded. Studies that did not describe the exposure time to the light-curing unit or used any type of dual-curing BF-RBCs were also excluded. The inclusion criteria for each variable are summarized in th of August 2022. Data were independently extracted by one reviewer (E.P.), and systematically classified in excel tables.This systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . The sysThe risk-of-bias (RoB) was assessed using the recently developed QUIN tool . BrieflyStudies were then graded according to their RoB as high (<50%), medium (between 50 and 70%) or low risk (>70%).Following duplicate removal (467), 217 eligible papers were identified (title selection). After abstract reading, 79 articles met the eligibility criteria, and their full texts were obtained and read. Subsequently, another 20 articles were excluded due to discrepancies in their methods and the inclusion criteria. Further three were excluded as no full text was available. The qualitative analysis was conducted on a total of 53 articles .In total, 12 materials were studied in the included literature. The manufacturer’s information on their composition is listed in A high variability was found for the DC of flowable BF-RBCs in the current systematic review . WhereasPolymerization shrinkage reported by the studies included in this systematic review ranged between 1.26% and 10.45%, although most of them were around 3.5% . A similA high variation was also observed for the polymerization shrinkage stress , with thMost studies included in this systematic review reported mean flexural strength values above 80 MPa , fulfillTable S1 in the Supplemental Material).Regarding the RoB analysis, only four studies were graded as ‘low risk’, whereas one study was categorized as ‘high risk’ and the remaining 48 had a medium bias risk . Most stTable S1 in the Supplemental Material). Guidelines for reporting in vitro studies are still a pending matter in the dental field, an issue that has been thoroughly worked out in clinical and epidemiological studies, as well as in case reports and systematic reviews. Development of instruments to assess RoB, like the QUIN tool [in vitro studies.The overall quality of the studies was rated with a moderate risk of bias. This implied in most studies that part of the information regarding sampling, test conduction and blinding was missing or incorrectly reported  by others with lower molecular weight (e.g. Bis-EMA), may contribute to limit volumetric reduction, and thus polymerization shrinkage stress . IncorpoManufacturer’s recommendations of most commercially available flowable BF-RBCs is to cover the restoration with a final layer of conventional resin composite . This alResults of this systematic review highlight the good standard achieved by contemporary flowable BF-RBCs. In terms of DC, flexural strength and polymerization shrinkage/shrinkage stress, they meet necessary requirements to be indicated for the bulk-fill restoration techniques in the posterior region. However, important variations among composition and design of this “new” class of RBCs hinder extrapolation of the results to materials different from those reported here. In addition, clinical studies are urgently required to assess their performance under a real working scenario.Click here for additional data file.


Invasive GAS (iGAS) affects more than 600,000 patients globally p.a., with a mortality rate of 25%1. Untreated or insufficiently treated, GAS infections can also trigger serious immune-related sequelae such as acute rheumatic fever, rheumatic heart disease (RHD), and inflammatory glomerulonephritis2. The IHME Global Burden of Disease estimates that globally there are more than 40 million cases of RHD3 with the majority of cases occurring in low- and middle- income countries (LMIC). Rheumatic fever is most common in children aged 5 to 15 years, and approximately 460,000 new cases occur each year. RHD contributes significantly to morbidity and mortality in LMIC, with over 300,000 deaths annually and over 10 million disability-adjusted life years4. Globally, GAS continues to be among the top ten infectious diseases responsible for causing mortality, highlighting the need to develop a GAS vaccine5. The WHO has taken the lead in this effort by publishing in 2018 a roadmap for the development of the first GAS vaccine6.Group A Streptococcus (GAS) is a ubiquitous pathogen that causes a wide spectrum of human diseases. These include mild conditions such as tonsillitis and impetigo (with over 600 million cases emm-type genomic sequence that determines the serotype-specific M-protein (emm). Despite this serotype diversity, different geographical regions experience dissimilar emm-types. In the absence of a GAS vaccine, antibiotics are relied upon for the effective treatment and prevention of transmission. However, there are stark discrepancies in treatment and diagnosis between high-income countries (HIC) and LMIC, where vaccines would have an even greater impact. Although no cases of GAS resistance to beta-lactam antibiotics have been reported, there have been reports of reduced susceptibility8. Importantly, GAS laboratory surveillance has revealed no antibiotic resistance in the new clusters responsible for recent outbreaks and no newly-emerged emm types9. Over the past two decades, general antimicrobial resistance has increased, and certain GAS serotypes associated with severe infections have shown increased resistance to clindamycin and macrolides10. However, the excessive use of antibiotics for treating GAS pharyngitis and impetigo has played a major role in driving resistance in bystander pathogens11.More than 250 GAS serotypes have been identified and annotated based on their https://savac.ivi.int/) and the Australian Strep A Vaccine Initiative . Their primary objective is to ensure the development of safe, effective, and affordable GAS vaccines, but they also facilitate connectivity among researchers, analysis of the value of a GAS vaccine, and development of business cases to encourage stakeholder involvement. Economic assessments in the United States estimated that the annual costs of iGAS and upper respiratory infections exceed $5 billion12. Therefore, implementing a vaccine programme in the HIC that reduces the GAS infection rate by 20% across all age groups could potentially save approximately $1 billion p.a. in the US alone, providing further incentive for funding bodies, including governments, to support GAS vaccine research.In 2019 a further positive movement towards the development and implementation of GAS vaccines was achieved through the establishment of two key initiatives: The Strep A Vaccine Global Consortium  M-protein-based vaccine antigen and ii) non-M-protein-based vaccines targeting a diverse range of important GAS factors, including pyrogenic exotoxins such as Streptococcus pyogenes Adhesion and Division protein (SpyAD) and Streptococcus pyogenes cell envelope proteinase (SpyCEP), streptolysin O, C5a peptidase, and carbohydrate-based antigens15.As a result of the ASAVI and SAVAC initiatives, new collaborations have been formed, positive advocacy for GAS vaccines has increased, and funding commitments for GAS vaccine development have grown. Today, many different candidates are undergoing testing for safety and immunogenicity in rodents and rabbits, as outlined in review articleshttp://www.globaldata.com/ as being tested in clinical trials or scheduled for Phase I clinical trials14. StreptAnova is a 30-valent vaccine candidate that targets M-proteins found on the surface of 30 GAS serotypes. Phase I clinical trials conducted in 2020 demonstrated the vaccine’s safety and ability to trigger an immunogenic response in healthy adults without causing autoimmunity. Individuals who received StreptAnova produced functional (opsonophagocytic) antibodies17. Another M-protein-based vaccine is StrepInCor, which consists of a 55-amino acid peptide from the C-terminal region of the M-protein. This region is highly conserved among GAS serotypes. Animal immunisation studies have shown high levels of specific antibodies with no cross-reactivity to cardiac proteins19. StrepInCor intends to start clinical trials by the end of 202314. One promising approach presently in clinical trials is a combination of two synthetic peptides: two M-protein epitopes (the modified p*17 and J8) have been paired with an epitope from the streptococcal anti-neutrophil factor, Spy-CEP (K4S2)20. Preclinical models showed no cardiac or neurological pathologies using p*17- K4S2 and J8-K4S2, leading to the initiation of clinical trials in 202221.Three GAS vaccine candidates are recorded on 15). The recent success of mRNA-based COVID vaccines has stimulated exploration of this approach for GAS non-M-protein-based vaccine development. Researchers at the University of Queensland , in collaboration with Moderna, secured funding from the Leducq Foundation to develop an mRNA vaccine formulation building upon their protein-based multi-component vaccine candidates22.Several non-M-protein-based candidates are in pre-clinical trials to test the safety and immunogenicity in rodent models (see reviews in refs. 23). This approach has been encouraged by the successful targeting of many Streptococcus pneumoniae serotypes through the development and deployment of capsule polysaccharide-based vaccines. However, the GAS capsule is mainly composed of hyaluronic acid, a molecule present in humans and therefore unsuitable for use as a human vaccine. Several research groups have targeted the GAS-specific surface carbohydrate, the Group A Carbohydrate (GAC). This could be considered a universal vaccine candidate as it is present in every GAS isolate and therefore is a promising candidate for targeting all GAS serotypes.In addition to protein- and peptide-based candidates, carbohydrate-based GAS vaccine candidates have been under development for the past decade (reviewed in ref. 27. Antibodies against GAC-derivatives protect against GAS infection in animal models of systemic and intranasal challenges28. These antibodies have also been shown to promote the clearance of multiple clinical strains of GAS in an opsonophagocytic killing assay29. Funding from CARB-X, Open Philanthropy and Wellcome supports researchers in developing and validating GAC-based vaccine candidates in animal models. CARB-X funding support has enabled Vaxcyte [24] and GSK Vaccines Institute for Global Health [26] to pursue combination vaccine approaches that target GAS specific proteins in conjunction with the GAC. This funding also encompasses Phase I clinical trials after reaching important milestones.Considering the essential nature of its gene clusters and the complexity of remodelling carbohydrates for a pathogenic bacterium it is logical to test several GAC derivatives in several different systemsRecent outbreaks of iGAS in several countries have emphasised that our global goal must remain to develop an effective GAS vaccine. There are numerous potential benefits of a GAS vaccine, including prevention of infections, reduced incidence of complications, improved public health, and decreased use of antibiotics, thereby averting antimicrobial resistance.30. Such commitments are urgently needed to increase the likelihood of developing the first licensed GAS vaccine to stem this global problem within the next decade. Much work lies ahead, but a GAS vaccine is within reach and the mission is gaining the necessary momentum. Researchers worldwide, along with increased funding support, have made ground-breaking contributions to this field. The pivotal work led by SAVAC/ASAVI and their ambitious plans for the next five years, combined with the WHO published roadmap for a GAS vaccine providing a strategic framework for researchers, creates an ideal environment to make this mission a reality.Funding bodies, including global charities such as Wellcome, Leducq Foundation, Open Philanthropy, and CARB-X, as well as government funding from organisations in the USA, New Zealand, and Australia have significantly increased their financial commitments to rectify the long-standing neglect of GAS disease


Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg . Sections were analyzed regarding structural damage of the fibrous connective tissue and inflammatory cell infiltration. Alterations to the collagen and elastin constitution were assessed by Masson–Goldner trichrome and Elastica van Gieson staining. Inflammatory cell infiltration, response and transformation were assessed by CD45 and IL-1β immunohistochemistry and von Kossa staining. The extent of aneurysmal wall alterations was assessed by semiquantitative gradings and was compared between the groups using Fisher’s exact test. IL-1β was significantly more present in the tunica media in mult-AA compared to sing-AAA (p = 0.022). The increased expression of IL-1β in mult-AA compared to sing-AAA indicates inflammatory processes play a role in aneurysm formation in patients with multiple arterial aneurysms.The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms ( Despite the highly established diagnostic and therapeutic standards, arterial aneurysms continue to pose a life-threatening hazard for affected patients. Clinical observations have led to the assumption that patients with multiple arterial aneurysms differ in their course of disease from patients with a single abdominal aortic aneurysm (AAA), both natural and post-interventional. Few prior studies have addressed this subject. However, for patients with multiple aneurysms, more subsequent aneurysms and higher complication rates for thrombotic and embolic events have been described ,2,3. FolIn AAA formation, proteolytic and chronic inflammatory processes lead to vessel wall degeneration. The infiltration of inflammatory cells along with the interaction of the vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM) reduces vessel wall stability and functionality, eventually causing aneurysm formation and, consequently, rupture ,6. The pmult-AA group), whereas 972 patients had a single abdominal aortic aneurysm (the sing-AAA group).The selection and characteristics of patients enrolled in this study have been described previously . In the Paraffin-embedded abdominal aortic wall specimens of patients from both groups were derived from the Vascular Biomaterial Bank Heidelberg (VBBH) . RespectAtherosclerotic risk factors, comorbidities, age at time of surgery, maximum AAA diameter, and preoperative C-reactive protein (CRP) and leukocyte blood levels of patients with available aortic wall specimens were assessed and compared between the two groups using the Mann–Whitney U test and Fisher’s exact test.p-values < 0.05 were considered statistically significant. Analysis was conducted using GraphPad Prism 9.3.1. Statistical consultation was provided by the Institute of Medical Biometry at the University of Heidelberg. The study protocol was approved by the Ethics Committee of the Medical Faculty of the University of Heidelberg (file reference: S-452/2016 and S-301/2013).mult-AA and 19 patients of sing-AAA [From our previous study, AAA wall specimens were available from 12 patients of sing-AAA . All patp = 0.705, sing-AAA group than in the mult-AA group  arterial aneurysms and patients with a single AAA were investigated. Our data indicate that IL-1β expression in the AAA wall is increased in patients with multiple arterial aneurysms compared to that in patients with a single abdominal aortic aneurysm. Moreover, more degradation of elastic fibers was present in the single AAA group, but was statistically not significant. The two patient groups did not differ regarding atherosclerotic risk factors, comorbidities, age at surgery, AAA size, or CRP and leukocyte blood levels.To our knowledge, studies of multiple arterial aneurysms are rare, with no histopathologic analyses reported thus far. The available literature includes terms such as diffuse aneurysmal disease, aneurysmosis, and arteriomegaly ,2,10,11.The formation of abdominal aortic aneurysms is multifactorial, with inflammatory processes and the degeneration of the aortic wall resulting from the loss of structural proteins. As a result of a systemic process with additional local biomechanical stress, inflammatory processes with increased matrix metalloprotease (MMP) activity and apoptosis of vascular smooth muscle cells are observed in the vessel wall. Transmural inflammatory cell infiltration includes neutrophils, B-cells, T-cells, mast cells, macrophages and natural killer cells . ElastasIL-1β is a proinflammatory cytokine. In addition to its role in the physiological immune response, it also contributes to the development of inflammatory pathologies. IL-1β induces local inflammatory processes and activates neutrophilic granulocytes, monocytes and macrophages . As a reHigher IL-1β levels in the tunica media of AAA specimens of patients with multiple arterial aneurysms might point to an increase in inflammasome activity compared to patients with a single AAA. However, given the complex sequence of inflammatory processes in AAAs, a corresponding interpretation can only be made with great caution. Further signaling processes involved in the development of multiple arterial aneurysms would need to be investigated.mult-AA group, less degeneration of elastic fibers was observed in the present study, which in turn, supports the chronically degenerative character found in the sing-AAA group.In contrast to an increased inflammatory state in AAA specimens in the A limitation of this study is the retrospective study design for the identification of patients in each group. In addition, the number of samples analyzed is very small, owing to the rare occurrence of multiple arterial aneurysms, and thus, the availability of corresponding tissue from open aneurysm surgeries. Finally, at the time of histopathological analysis—when surgical repair is indicated—the AAA is already in a far-progressed stage with correspondingly pronounced structural vessel wall alterations. Therefore, statements on the mechanism of origin can only be made with reservations.Although specific etiologic mechanisms are suspected in the development of multiple arterial aneurysms, this does not impact the clinical management of affected patients at this current time. Nevertheless, further studies should be conducted on both etiologic differentiation and natural and postinterventional outcomes. Eventually, further insights could optimize diagnostic and therapeutic actions and timing for the affected patients.The increased expression of IL-1β and less degeneration of elastic fibers in AAA wall specimens in patients with multiple arterial aneurysms compared to patients with a single AAA suggests that inflammatory rather than chronically degenerative processes play a role in aneurysm formation in patients with multiple arterial aneurysms. Different underlying pathological mechanisms could influence future therapeutic approaches. Further research is required to substantiate the results presented herein.


Patient-reported outcome (PRO) measures can inform clinical decision making and planning of treatment in the health care system. The aim of this study was to examine whether patient-reported health domains influence the use of health care services in outpatients with epilepsy.This was a prognostic cohort study of 2,426 epilepsy outpatients referred to PRO-based follow-up at the Department of Neurology, Aarhus University Hospital, Denmark. Patients filled out a questionnaire covering health literacy areas, self-efficacy, well-being and general health. The main outcome was a record of contact to the epilepsy outpatient clinic, inpatient ward and/or emergency room within 1 year, retrieved from health register data. Associations were analysed by multivariable binomial logistic regression.A total of 2,017 patients responded to the questionnaire and 1,961 were included in the final analyses. An outpatient contact was more likely among patients with very low health literacy : odds ratio (OR) 1.5 (95% CI: 1.1–2.1), very low and low self-efficacy: OR 1.7 (95% CI: 1.2–2.3) and OR 1.4 (95% CI: 1.0–1.8), low and medium well-being: OR 2.2 (95% CI: 1.6–3.0) and OR 1.4 (95% CI: 1.1–1.9), and patients rating their general health as fair: OR 2.8 (95% CI: 1.7–4.6). Inpatient contact and emergency room contact were associated with the health domains of self-efficacy and general health.PRO questionnaire data indicated that patients with low health literacy , well-being, self-efficacy and self-rated general health had an increased use of health care services at 1 year.These results suggest that PRO measures may provide useful information in relation to the possibility of proactive efforts and prevention of disease-related issues and to help identify efficiency options regarding resource utilization.The online version contains supplementary material available at 10.1186/s41687-023-00641-4. The use of patient reported outcomes (PRO) measures to monitor and plan treatment in health care has become increasingly common in recent years. In this study, we examined whether PRO measures of patients self-perceived levels of health knowledge, confidence in managing their health, overall sense of well-being, and general perception of their health could predict the need for contact in an epilepsy outpatient clinic during a 12 months’ period. An outpatient contact was more likely among patients with lower levels of health literacy, well-being, self-efficacy and self-rated general health. The study indicates that PRO measures may hold useful information to inform clinical decision making and planning of care among outpatients with epilepsy.The online version contains supplementary material available at 10.1186/s41687-023-00641-4. Epilepsy is a chronic neurological disease characterized by recurrent seizures that affects approximately 0.5–1% of the world’s population and is seen in all age groups . EpilepsThe use of patient-reported outcomes (PROs) in clinical practice has become increasingly common in recent years . PROs arThe concept of health literacy has been defined as: a person’s ability to understand and use information to make decisions about their health” . HoweverIn 2015, an American study demonstrated that low self-rated general health on the day of hospital discharge was predictive of re-utilization within 14 days among general medical and intensive care patients . These fThe aim of this study was to examine whether PRO-assessed health literacy, self-efficacy, well-being and general health status were independently associated with seeking health care in outpatients with epilepsy. We hypothesized that patients with low levels in these domains would be more likely to seek outpatient health care services.This study was conducted as a prognostic cohort study with one-year register based follow up data –25.This study was conducted within the context of the AmbuFlex system. AmbuFlex is a generic clinical application developed in Central Denmark Region that supports PRO-based outpatient follow-up. The aim of AmbuFlex is to support clinical decision-making, improve quality of care and achieve greater flexibility and ability to prioritize resources to outpatients with actual need or wish for clinical attention , 26–28. AmbuFlex/Epilepsy has been in operation since 2012, and by April 2021, 2,983 patients had been referred to AmbuFlex/Epilepsy in three neurological outpatient clinics in Central Denmark Region. In PRO-based follow-up, patients report disease-specific symptoms and health status from home instead during traditional outpatient follow-up with fixed appointments Patients are referred to AmbuFlex as a part of their treatment, based on other formal inclusion criteria than the clinician’s subjective clinical judgement and the patient’s own preferences for attending PRO-based follow-up and their consent to participate . There aEach referred patient is prompted to fill out the questionnaires every 3rd, 6th or 12th month, and responses are handled by a PRO-based automatic decision algorithm  The source population for the analyses was outpatients with epilepsy referred to PRO-based follow-up at the Department of Neurology, Aarhus University Hospital, Denmark. From January 2016 to January 2017, the patients were sent an additional research questionnaire combined with a scheduled epilepsy questionnaire. The additional questionnaire contained information concerning personal and health-related aspects including health literacy, well-being, self-efficacy and general health. The index date of the observation period was the return date of the additional questionnaire, which was filled out electronically or by paper. A 7-day shipment period was added to the index date of paper replies. Participants were excluded in the case of death or migration within the follow-up time. Subsequently, the associations between the health domains and contact to health care services were examined.The Danish Data Protection Agency approved the PhD study (reference number 1-16-02-691-14) from which data were used . The eliMeasured 1 year from the index date of the observation period, we extracted all records of contacts under primary and a secondary ICD-10 diagnosis of epilepsy from the outpatient clinic and the inpatient ward at the Department of Neurology and the emergency room at Aarhus University Hospital. Data were obtained from the Business Intelligence Register in Central Denmark Region, which contains information about current or previous patients in Central Denmark Region, defined by individual unique personal numbers. Contact with the epilepsy outpatient clinic included face-to-face or telephone consultations with physicians or nurses, and administrative contact by web/e-mails or by letter. Contact with the inpatient ward included hospitalizations, and emergency room contact included epilepsy-related emergency visits. The outcome was the patients need for contact defined as at least one contact (i.e. ≥ 1 contact versus no contact) within the follow period.Health Literacy. The Health Literacy Questionnaire (HLQ) is a 44-item questionnaire divided into nine conceptual domain scales of health literacy. The development of HLQ was validity-driven and consisted in-depth grounded consultations, psychometric analysis and cognitive interviews [terviews . It has terviews . The subWell-being. The WHO-Five Well-Being Index (WHO-5) is a five-item questionnaire measuring subjective psychological well-being and has psychometric properties that have been assessed in several chronic diseases [diseases –37. Everdiseases .Self-Efficacy. The General Self-Efficacy scale (GSE) is a 10-item psychometric questionnaire designed to assess one’s belief in own competence to cope with difficult demands, and the psychometric properties have been assessed in different countries and populations [ulations , 39. EacGeneral health. The Short Form Health Survey (SF-36) measures health-related quality of life in a 36-item questionnaire [ionnaire . Only thTo control for the potential influence of other factors, we include five additional variables: age, gender, educational level, years with epilepsy diagnosis and seizure frequency obtained from either the AmbuFlex system or by questionnaire , 12–15.The variable, educational level, was divided into three categories: low , middle  and high (more than 4 years of study). Years with diagnosis of epilepsy was a dichotomous variable defined </≥ 2 year, and seizure frequency was defined </≥ 1 seizure during the last 12 months.Patient characteristics were presented with descriptive variables by number and percentage for categorical variables, whereas continuous variables were presented by mean and standard deviation (SD) or median and inter quartile range (IQR) depending on their distribution. Wilcoxon rank sum test and chi-square test were used to assess potential age and gender differences between respondents and non-respondents. Next, the associations between each potential determinant and outcome variable (≥ 1 contact versus no contact) were analysed by binomial logistic regression. Age, sex, educational level, years with epilepsy diagnosis and seizure frequency during the last year were added as potential confounders in adjusted analyses. Assumptions for numbers of variables needed to avoid over-fitting the model were based on the rule-of-thumb of at least 10 cases per variable . EstimatSupplemental analyses were performed by excluding 339 patients, who were allocated to patient-initiated follow-up as part of a randomized controlled study conducted within the AmbuFlex system . ParticiA total of 2,426 patients were sent the additional questionnaire in the period from January 2016 to January 2017, and 2,017 (83.1%) patients responded  patients in the social support for health scale (HLQ4), 146 (7.4%) patients in the WHO-5, Ability to actively engage with health care providers scale (HLQ6) and Understanding health information scale (HLQ9), 162 (8.3%) patients in the GSE and 33 (1.7%) patients in the general health question (SF-36). A total of 365 (18.6%) patients did not disclose the year of diagnosis, 147 (7.5%) patients did not answer the education question, and 125 (6.3%) patients did not answer the seizure frequency question.Patients with very low HLQ4 scores  were more likely to have an outpatient contact than patients who had high HLQ4 scores  Table . SimilarThe associations between health domains and an inpatient and emergency room contact resented in Fig. The results of the analyses excluding participants with no pre-schedule PRO follow-up in the randomized controlled study are presented in supporting information The use of health care outpatient services was more frequent among patients with low levels of health literacy , well-being, self-efficacy and self-rated general health. These findings are in line with our specified hypothesis. Contrary to this study’s hypothesis, the observed associations between an outpatient contact and the two health literacy domains “ability to actively engage with health care providers” and “understanding health information well enough to know what to do” failed to reach statistical significance. Only a few associations with an inpatient and emergency room contact and health domains were statistically significant. These findings may indicate that PRO measures provides useful additional information in terms of proactive efforts and planning health care services in patients with epilepsy. In comparison to our findings the study by Howard et al. found similar associations between levels of health literacy and the outpatient contact  and a moIn accordance with our findings, Chamberlain et al. examined the first question of self-rated general health in the 12-item Short Form Health Survey as a predictor for use of health care services among patients with heart failure , but no The study population is most likely a representative sample of the population of AmbuFlex/Epilepsy at Aarhus University Hospital because almost the entire population, except those with proxy questionnaires, were included. With a relative high participation rate (83.1%), we believe the risk of a systematic selection into to the study to be limited. Although, non-responders were significantly younger than the responders, it seems unlikely that young non-respondents differed from young responders with respect to our outcome variable – i.e. future contacts to health care services.A strength of the study is the prospective design, and almost complete data were available through registers within the follow-up period, with only 3% of the patients lost to follow-up due to death or migration. The disadvantage of collecting information on hospital contact via a register is that registers are collected for administrative purposes and not for research, which may result in a lower quality of data. However, missing registration of contact in relation to epilepsy probably has personal consequences for the patients involved and must therefore be limited. Our categorization of health outcomes resulted in few cases of patients with a health care contact. This of course increased the uncertainty of the estimates especially for the results of inpatient contact and emergency room contact, where broad confidence intervals question the statistical strength – even though estimates were significant. These associations no longer reached statistical significance, when excluding participants who did not receive pre-schedule PRO in our supplemental analyses. However, overall our supplemental analyses did not differ substantially from the main analyses and we therefore believe this to be a result of a low number of cases in these outcomes rather than a systematic effect of patient-initiated follow-up .Similar categorization of potential confounders and missing items regarding educational level, years with diagnosis of epilepsy and seizure frequency may have led to some residual confounding. Furthermore, there may be recall bias regarding years with a diagnosis of epilepsy because it was self-reported. There would probably have been fewer missing data regarding years with a diagnosis of epilepsy if the information had been collected from hospital records, although this method requires more resources and time. Other factors such as living alone and number of chronic conditions may also have been relevant in the analyses, as they have been associated with different levels of sub-scale 4 in the HLQ. Beauchamp et al. found that people living alone and with ≥ 4 chronic conditions reported having less social support for health . HoweverLower levels of health literacy , well-being, self-efficacy and self-rated general health were associated with a greater need for contact to outpatient services at 1 year. Patients with lower levels of self-efficacy and fair general health perception also seem more likely to have inpatient contact and an emergency room visit. This study demonstrated that PRO measures may provided useful information in relation to the possibility of proactive efforts, prevention of disease-related issues and implementation of efficiency options regarding resource utilization. However, our findings would need to be confirmed in other epilepsy populations.Below is the link to the electronic supplementary material.Supplementary Material 1: S1 Appendix


A flexible, non-enzymatic glucose sensor was developed and tested on a polyethylene terephthalate (PET) substrate. The sensor’s design involved printing Ag (silver) as the electrode and utilizing mixtures of either gold–copper oxide-modified reduced graphene oxide (Au-CuO-rGO) or gold–copper oxide-modified reduced graphene oxide-multi-walled carbon nanotubes (Au-CuO-rGO-MWCNTs) as the carrier materials. A one-pot synthesis method was employed to create a nanocomposite material, consisting of Au-CuO-rGO mixtures, which was then printed onto pre-prepared flexible electrodes. The impact of different weight ratios of MWCNTs (0~75 wt%) as a substitute for rGO was also investigated on the sensing characteristics of Au-CuO-rGO-MWCNTs glucose sensors. The fabricated electrodes underwent various material analyses, and their sensing properties for glucose in a glucose solution were measured using linear sweep voltammetry (LSV). The LSV measurement results showed that increasing the proportion of MWCNTs improved the sensor’s sensitivity for detecting low concentrations of glucose. However, it also led to a significant decrease in the upper detection limit for high-glucose concentrations. Remarkably, the research findings revealed that the electrode containing 60 wt% MWCNTs demonstrated excellent sensitivity and stability in detecting low concentrations of glucose. At the lowest concentration of 0.1 μM glucose, the nanocomposites with 75 wt% MWCNTs showed the highest oxidation peak current, approximately 5.9 μA. On the other hand, the electrode without addition of MWCNTs displayed the highest detection limit (approximately 1 mM) and an oxidation peak current of about 8.1 μA at 1 mM of glucose concentration. Research has demonstrated that individuals with diabetes exhibit elevated glucose levels in their bodily fluids such as urine, saliva, and sweat, offering the possibility of inferring their blood glucose concentration . As a reRemarkable advancements have been achieved in the optimization of bio-sensors that utilize glucose oxidase. These advancements are primarily attributed to their specificity, sensitivity, and improved manufacturing techniques . ResearcCopper oxide-based glucose sensors have attracted considerable attention because of their exceptional catalytic activity and the ease of adjusting their physical and chemical properties. In the realm of electrochemical biosensors, a vital approach to enhancing charge transfer involves the development of composite materials that combine highly electrocatalytic substances with materials possessing high conductivity ,12. NotaThese modifications have shown promising results in enhancing the overall performance of glucose sensors. Reduced graphene oxide (rGO) is a specific form of graphene obtained through the reduction of graphene oxide, a process that eliminates oxygen functional groups from the material . Using rAnother significant advancement in sensor design involves creating composite materials consisting of redox enzymes and metal nanoparticles (or nanotubes) on the electrode surface. This approach not only addresses the fundamental issue of efficient electrical communication between redox proteins and the electrode but also opens up exciting possibilities for developing miniaturized and implantable amperometric sensors. These developments hold great potential for further improving glucose sensor technology and expanding its applications in the field of biomedical devices. These advanced sensor configurations have the potential to revolutionize glucose monitoring for individuals with diabetes, offering greater convenience and accuracy in managing their blood glucose levels. A crucial component in these composite materials is reduced graphene oxide, a form of graphene with oxygen-containing functional groups removed. It provides a larger surface area, allowing for the accommodation of more Au-CuO nanoparticles. Furthermore, the inclusion of rGO, as demonstrated in previous studies , or the The one-pot synthesis method is a versatile technique in which multiple reactions are carried out sequentially within a single reaction environment, resulting in enhanced reaction efficiency. This approach has gained widespread popularity due to its ability to streamline complex separation and purification processes during post-treatment, ultimately saving time and resources . The suc2O3.CuO@rGO nanocomposite as the active substance to enhance the glassy carbon working electrode. This approach was employed to create a highly sensitive and selective electrochemical sensor for the efficient detection of ascorbic acid [To ensure robustness and stability, we have selected PET  as the substrate material for the non-enzymatic glucose sensor. PET’s excellent mechanical properties make it an ideal choice for providing a durable and reliable sensor platform. Recently, Dou and Qu efficiently synthesized rGO-AuNPs-MWCNTs through a straightforward process . They thbic acid . So far,The concentration of glucose in the blood is typically quantified in millimoles per liter (mM), which is equivalent to milligrams per deciliter (mg/dL), rather than in the micromoles (μM) range. Under normal circumstances, blood glucose concentration falls within the range of 3.9 to 6.1 millimoles per liter (or 70 to 110 milligrams per deciliter). Micromoles (μM) are usually employed for measuring substances at lower concentrations, whereas blood glucose exhibits a relatively higher concentration, making millimoles the more commonly used unit of measurement. However, certain laboratory tests or specific research endeavors may necessitate more precise concentration measurements, and in such cases, the μM range may be employed. As a result, the Au-CuO-rGO-MWCNTs compositions were printed as the electrode to investigate for their glucose detection ability across a wide range of concentrations. The study also investigates the influence of incorporating nanotubes on the glucose sensing characteristics during the fabrication process. These findings suggest that the inclusion of MWCNTs at specific levels can enhance the performance of the flexible non-enzymatic glucose sensor for detecting low concentrations of glucose. The results of the study significantly contribute to the development of more efficient and versatile glucose sensing technologies, holding great potential for advancing glucose monitoring in various applications, including medical diagnostics and personalized healthcare. This study would also demonstrate that when using Au-CuO-rGO and Au-CuO-rGO-MWCNTs nanocomposites as carriers, the tested concentration range of non-enzymatic glucose would vary from 1 mM to 0.1 μM. The results of this research would also reveal our successful fabrication of flexible non-enzymatic glucose sensors on a PET substrate, thereby advancing the goal of creating wearable devices in the future.3)2∙3H2O), 99.5% tetrachloroauric(III) acid trihydrate (HAuCl4∙3H2O), 99.3% sodium borohydride (NaBH4), and graphite oxide powder. The oxidized graphene powder had an average thickness of approximately 1 nm, with single-layer sheets ranging from 0.2 to 10 μm in diameter. Additionally, the sheet diameter varied between 500 nm and 40 μm. To facilitate the experiments, other substances were also used, including 99% glucose (glucose powder), 99% polymethyl methacrylate (PMMA), and 99% dimethylformamide (DMF). Deionized water was used consistently throughout all experimental procedures. The screen printing method was employed in this experiment to fabricate electrode and carrier materials on a flexible PET substrate, with the conductive layer comprising silver covered with carbon electrodes. Subsequently, an insulating layer was applied to cover all exposed areas, leaving only the required sensing and measurement regions exposed, as illustrated in (1)Working electrode : This electrode was printed with the nanocomposites Au-CuO-rGO or Au-CuO-rGO-MWCNTs for sensing purposes;(2)Reference electrode: The silver/silver chloride (Ag/AgCl) glue was printed to serve as a reference electrode during sensing measurements;(3)Auxiliary electrode: The original carbon electrode was used to assist in the electrochemical process.The materials used in this study were sourced from Ultimate Materials Technology Co., Ltd.  and included high-purity substances. The key components consisted of 98% pure copper nitrate-trihydrate  acid trihydrate to the GO dispersion and continued stirring for at least 30 min. For the incorporation of nanotubes, the weight ratio between GO and MWCNTs was adjusted while maintaining a concentration of 0.5 g mL−1, using the same experimental procedures employed for producing the GO dispersion. The ratios used for the nanocomposite synthesis were as follows: 0 wt% corresponded to 100 wt% of GO, while the 60 wt% component consisted of 40 wt% GO and 60 wt% MWCNTs. After this, 50 mL of sodium borohydride with a concentration of 0.79 M was slowly introduced into the reaction mixture and stirring at room temperature was maintained for several hours (at least 2 h). It is important to note that during this step, the solution exhibited a vigorous reaction, resulting in the production of a significant amount of gas. This process facilitated the reduction of GO to rGO while simultaneously synthesizing the desired Au-CuO-rGO nanocomposites. If MWCNTs were added, it was essential to maintain vigorous stirring throughout the entire experimental process. This is because the MWCNTs do not participate in the reaction and have a tendency to agglomerate, making it challenging to disperse them evenly throughout the reaction mixture.To synthesize the target nanocomposite Au-CuO-rGO, we utilized a one-pot synthesis method. Initially, we subjected 200 mL of GO dispersion with a concentration of 0.5 mg mL−1) using an ultrasonic oscillator. Before each use, the nanocomposite needed to be treated with an ultrasonic oscillator for more than 10 min to address the issue of precipitation. In this experiment, we utilized a D8 SSS X-ray diffractometer  to analyze the structure of the nanocomposites. The surface morphology of the working electrode was examined using a S-4800 field emission scanning electron microscope . This microscope confirmed the surface morphology of the nanocomposite materials, namely Au-CuO, rGO, and MWCNTs, produced during this study.After the reaction, the resulting precipitate was filtered using filter paper and washed two to three times with deionized water to remove any unreacted reactants. The obtained product was then dried in an oven at 90 °C overnight (12 h). Subsequently, the dried product was annealed in the atmosphere at 300 °C for 4 h in a furnace tube. To disperse the product obtained after annealing, it was stirred for over 3 h (300 rpm) using a magnetic stirrer to break up any agglomeration. Once it was confirmed that there were no noticeable large lumpy particles, the nanocomposite was dispersed in DMF  was conducted using the ULVAC-PHI, PHI 5000 VersaProbe model. The experiment focused on scanning four specific elements—C, O, Au, and Cu—on each test piece. The aim was to analyze the chemical bonding composition of these elements, providing valuable insights into the characteristics of the synthesized rGO. Linear sweep voltammetry (LSV) was used as a measurement technique in which the potential varies linearly with time, enabling the quantification of the current variation with voltage . During LSV was utilized to evaluate changes in the glucose oxidation peak currents of two types of test specimens: Au-CuO-rGO and Au-CuO-rGO-MWCNTs, with varying proportions of MWCNTs ranging from 15 wt% to 75 wt%. The glucose concentration range covered values from 0.1 μM to 10 mM, with a concentration step of 10 times for the measurements. The primary objective was to identify the concentration range in which the oxidation peak current (Ip) exhibits significant variations for different proportions of MWCNTs across the broad spectrum of glucose concentrations. Subsequently, small-scale measurements were conducted in regions with higher sensitivity, focusing on concentration ranges of 0.1 μM to 1 μM and 1 μM to 10 μM. For selective measurements, LSV was utilized to evaluate and compare the oxidation peak current for various substances, including sodium hydroxide, sodium chloride, potassium ion, urea, and glucose. The experiments were conducted in a 0.1 M sodium hydroxide solution with a glucose concentration of 1 μM. For the ampere response measurements, the CHI627D instrument was used, and a Au-CuO-40 wt% rGO-60 wt% MWCNTs test piece was employed in a 0.1 M NaOH environment. The choice of 0.1 M NaOH as the supporting electrolyte was based on its capacity to establish a stable and precisely defined electrochemical environment. The alkaline properties of NaOH guarantee a consistent pH level that is well-suited for the electrochemical reactions essential for our sensor’s operation. Two sets of measurements were performed at (a) a wide-range measurement with a 10-fold concentration increase, spanning from 0.1 μM to 1 mM and (b) amperometric response measurements within the concentration range of 0.2 mM to 1 mM.XRD is an effective technique for material analyses and, therefore, XRD analyses were first performed on the processed materials to characterize their structures and compositions . Figure −1 and a G band at 1593 cm−1, while for MWCNTs, the bands were located at 1328 cm−1 and 1567 cm−1. For the Au-CuO-rGO nanocomposite, the spectral peaks were observed at 1328 cm−1 and 1584 cm−1, and for the Au-CuO-rGO-MWCNTs composite showed Raman bands at 1333 cm−1 and 1580 cm−1. The blue shift of the G band observed in these materials can be attributed to the reduction in oxygen functionalities during the reduction process. Notably, the Raman spectrum of Au-CuO-rGO exhibited an increased ID/IG ratio (ID and IG are the intensities at D band and G band), which suggests that the formation of rGO led to a further increase in defects. Furthermore, the incorporation of MWCNTs in the Au-CuO-rGO-MWCNTs composite contributed to an additional blue shift of the G band. The specific ID/IG ratios for GO, MWCNTs, Au-CuO-rGO, and Au-CuO-40 wt% rGO-60 wt% MWCNTs were 1.09, 0.594, 1.25, and 0.760, respectively. The observed variations in the Raman spectra and the calculated ID/IG ratios provide valuable insights into the structural and chemical changes occurring in the graphene-based materials due to different processing methods and the incorporation of nanotubes. Such information can be crucial for tailoring the properties of graphene-based composites for various applications, such as electronics, energy storage, and catalysis. However, further comprehensive analysis and characterization are necessary to fully understand the underlying mechanisms responsible for these spectral shifts and their impact on the material’s performance.Raman spectroscopy is a powerful technique widely used to investigate the vibrational properties of graphene . It ofteXPS is a valuable analytical technique employed for studying the elemental composition and chemical states of materials . Togethe2+ species, confirming the successful synthesis of CuO. 7/2 and Au 4f5/2, respectively, which indicate the presence of gold in the sample. These results prove that with the addition of MWCNTs, the emission intensity of the Cu-O bond in the O1 peak spectrum significantly increases, further validating that the addition of MWCNTs enhances the successful synthesis of CuO. This suggests that the addition of MWCNTs plays a crucial role in improving the characteristics of the CuO composite, potentially leading to enhance the performance of the Au-CuO-rGO-MWCNTs in the application of sensing the non-enzymatic glucose.To further investigate the influence of the materials used on their properties, we conducted X-ray photoelectron spectroscopy (XPS) analysis to determine the oxygen chemical bonding state, and The study utilized the LSV method ranging from 0 V to 1.5 V to investigate the electrochemical response of glucose in different concentrations, without and with the different contents of MWCNTs addition. The measurements were conducted under a 0.1 M NaOH environment, and the detection limit is the concentration at which the sensor can reliably detect the presence of glucose and provide a measurable signal. From The trends of the change in peak current slope with increasing glucose concentration in a wide range of measurements are observed, and the results are shown in The possible reason for the higher sensing efficiency of the Au-CuO-40 wt% rGO-60 wt% MWCNTs sample is that MWCNTs have a higher surface area. The surface area of MWCNTs plays a crucial role in their sensing performance, particularly in non-enzymatic glucose detection. MWCNTs possess a unique cylindrical nanostructure, which results in a high surface area providing numerous active sites for glucose molecules to adsorb and react. As the surface area increases, the capacity to accommodate glucose molecules also rises, leading to heightened sensitivity. Moreover, the elevated surface area allows MWCNTs to adsorb a larger quantity of glucose molecules, promoting enhanced electron transfer between the glucose molecules and the MWCNT surface. This improved electron transfer significantly boosts the sensitivity of glucose detection. Additionally, the abundance of available sites on a larger surface area facilitates glucose oxidation reactions, leading to a lower detection limit for the sensor. Consequently, the sensor becomes more sensitive, capable of detecting even lower concentrations of glucose. Although higher surface area generally improves sensitivity, it also contributes to increased stability and reusability of MWCNT-based sensors. The surplus of active sites enables repeated glucose sensing without experiencing a significant loss in performance. This potential for extended use enhances the practical applicability of MWCNT-based glucose sensors.(a)Hindered mass transport: When the content of MWCNTs in the composition of Au-CuO-rGO-MWCNTs is too high, it can result in a densely packed and compacted structure, which hinders the diffusion of glucose molecules to the active sensing sites on the MWCNTs. As a consequence, this reduced mass transport restricts the number of glucose molecules that can interact with the sensor’s surface, thereby decreasing its sensitivity to glucose detection.(b)Limited surface area: An elevated MWCNTs content in the composition of Au-CuO-rGO-MWCNTs can result in a reduced effective surface area available for glucose molecules to interact with. Consequently, fewer glucose molecules can be captured and detected by the sensor, leading to a decrease in sensitivity.(c)Electron transfer inefficiency: In glucose sensors, the efficient interaction between glucose and MWCNTs depends on smooth electron transfer between them. An excessive amount of MWCNTs in the composition of Au-CuO-rGO-MWCNTs can disrupt this electron transfer process, resulting in a diminished response to changes in glucose concentration.(d)Non-specific binding: A high content in the composition of Au-CuO-rGO-MWCNTs may increase the likelihood of non-specific binding with other interfering substances present in the sample. This non-specific binding can lead to inaccurate readings and diminish the sensor’s sensitivity and selectivity to glucose.On the other hand, the power sensing characteristics of the Au-CuO-25 wt% rGO-75 wt% MWCNTs sample may be attributed to the excessive addition of MWCNTs. An excessive amount of MWCNTs can lead to a decrease in sensitivity in a glucose sensor made with MWCNTs due to several factors:To maintain optimal sensitivity in a glucose sensor made with the composition of Au-CuO-rGO-MWCNTs, it is crucial to carefully optimize the proportion of MWCNTs to strike a balance between surface area, electron transfer efficiency, and mass transport, while minimizing non-specific interactions with other substances. As a result, at a glucose concentration of 0.1 µM, the sample exhibits the maximum Ip value. However, with increasing glucose concentration, there is no significant increase in the Ip value.−1 cm−2 was obtained. In the range of 0.02 mM to 0.1 mM, although there was a clear oxidation peak, the linearity was poor, preventing further analysis (not shown here). As depicted in −1 cm−2. In −1 cm−2.Sensitivity and selectivity were measured using linear sweep voltammetry (LSV) on samples with the additions of 0 wt% and 60 wt% MWCNTs, and the ability to detect glucose was determined based on peak current. The scan range for LSV measurements ranged from 100 mV/s to 1000 mV/s, with a 0.1 M sodium hydroxide solution. For each type of sample, we prepared five replicates, and each of these samples underwent two separate tests. The average results of these tests are depicted in 2) value, commonly referred to as R squared. In the context of this study, various sensors were employed to detect different glucose concentrations, and their corresponding R-squared values for the results in One crucial evaluation parameter is the coefficient of determination, represented by the R-squared , making it less accurate in detecting glucose at such low levels. On the other hand, the Au-CuO-40 wt% rGO-60 wt% MWCNTs samples demonstrated higher sensitivity within the concentration range of 0.1 μM to 1 μM and lower sensitivity within the range of 1 μM to 10 μM, suggesting an improvement due to the addition of appropriate MWCNTs. This study shows that the sensor is most effective for glucose concentrations within the micromolar range (0.1 μM to 1 μM), with excellent linearity and sensitivity. Additionally, the sensitivity of the Au-CuO-40 wt% rGO-60 wt% MWCNTs sample is significantly higher than that of the Au-CuO-rGO sample. The variation in peak current with glucose concentration and the achieved sensitivities provide valuable information on the detection capability of the fabricated sensors. However, as the glucose concentration increases beyond this range (up to 10 μM), the change in peak current becomes less pronounced, although the sensor still maintains reasonable linearity and sensitivity. Overall, this study highlights the glucose concentration and the use of different proportions of MWCNTs in determining the performance of the sensors for glucose detection. These findings contribute to the development of glucose biosensors and other electrochemical sensing applications.−1 cm−2.Due to the electrode containing 60 wt% MWCNTs exhibiting a significantly higher response compared to other electrodes, it was selected for the selective analysis. The measurements were carried out for substances like sodium hydroxide, sodium chloride, potassium ions, urea, and glucose by sequentially adding them one by one. The variation of current with voltage for different compositions on Ag/AgCl is illustrated in (a)High surface area: MWCNTs offer a large surface area, providing numerous active sites for glucose molecules to interact with the sensor. This increased surface area enables a higher number of glucose molecules to be adsorbed, leading to improved sensitivity and detection capabilities.(b)Excellent electrical conductivity: MWCNTs exhibit outstanding electrical conductivity, facilitating efficient electron transfer during the glucose sensing process. This enhanced electron transfer ensures the faster and more accurate response of the sensor to changes in glucose concentration. As a result, the sensor can rapidly detect variations in glucose levels with greater precision.(c)Synergistic effects: The incorporation of Au-CuO along with both rGO and MWCNTs creates synergistic effects that enhance the overall performance of the sensor. The Au-CuO nanoparticles can enhance the catalytic activity towards glucose oxidation, while rGO and MWCNTs improve the electrical properties and stability of the sensor, resulting in more efficient and reliable glucose detection.(d)Enhanced stability and durability: MWCNTs are known for their exceptional mechanical strength and chemical stability, which significantly improves the sensor’s overall stability and durability. As a result, the sensor can maintain its sensing capabilities over an extended period without experiencing degradation.(e)Versatility: MWCNTs can be easily functionalized with various chemical groups, allowing for the modification of surface properties and the customization of the sensor’s selectivity towards glucose. This versatility enables the detection of glucose in complex biological samples without interference from other substances, making the sensor highly adaptable and practical.The use of MWCNTs instead of rGO in Au-CuO-rGO-MWCNTs glucose sensors can significantly enhance the sensing effect for several reasons:(a)Heightened Sensitivity: these nanocomposites exhibit the capacity to significantly enhance the sensitivity of non-enzymatic glucose sensors. The inclusion of Au, CuO, rGO, and MWCNTs results in an exceptionally conductive and catalytically active surface for glucose oxidation, thereby leading to improved sensor performance.(b)Swift Response Time: the distinctive properties of these nanocomposites facilitate the rapid detection of glucose, yielding a swift response time. This characteristic is particularly vital for applications that necessitate real-time monitoring.(c)Adaptability: the capability to fabricate these sensors on flexible substrates endows them with adaptability and versatility, rendering them suitable for various shapes and applications, such as wearable devices and biomedical sensors.(d)Interference Mitigation: non-enzymatic sensors constructed with these nanocomposites demonstrate reduced susceptibility to interference from substances other than glucose, resulting in more precise measurements, even within complex sample matrices.(e)Broad Detection Range: non-enzymatic glucose sensors employing Au-CuO-rGO-MWCNTs nanocomposites as carriers may boast a wide detection range for glucose concentrations when compared to enzymatic sensors.In comparison to other studies on glucose sensors, the use of Au-CuO-rGO and Au-CuO-rGO-MWCNTs nanocomposites as carriers in the fabrication of flexible non-enzymatic glucose sensors offers several distinct advantages:(a)Cost Factor: the fabrication of Au-CuO-rGO and Au-CuO-rGO-MWCNTs nanocomposites can be relatively costly due to the incorporation of precious metals like gold and additional materials such as carbon nanotubes. This expense may pose a limitation on their widespread adoption.(b)Technical Complexity: the synthesis and integration of these nanocomposites can be technically intricate and demand specialized equipment and expertise.Nevertheless, certain disadvantages should be considered:D/IG ratios for GO, MWCNTs, Au-CuO-rGO, and Au-CuO-40 wt% rGO-60 wt% MWCNTs were 1.09, 0.594, 1.25, and 0.760, respectively. The analysis results of XPS spectroscopy showed that the addition of MWCNTs plays a crucial role in improving the characteristics of the CuO composite and leading to enhance the sensing performance of the Au-CuO-rGO-MWCNTs in the non-enzymatic glucose. The detection limit of the Au-CuO-rGO sample was achieved at approximately 1 mM concentration, and falling, and it had a sensitivity of 127.8 μA nM−1 cm−2 within the range of 0.2 mM to 0.8 mM. When the Au-CuO-40 wt% rGO-60 wt% MWCNTs sample was used, the high sensitivity of 61,111 μA nM−1 cm−2 was observed within the glucose concentration range of 0.1 μM to 1 μM and the high sensitivity of 1570 μA nM−1 cm−2 was observed within the glucose concentration range of 1 μM to 10 μM. When the content of MWCNTs increases from 0 to 60 wt%, it is evident that the sensitivity of the fabricated Au-CuO-rGO-MWCNTs non-enzymatic glucose sensor is significantly enhanced. In other words, it allows for the detection of concentrations in the micromolar (μM) range, as opposed to the millimolar (mM) range. This improvement in sensitivity suggests that the sensor becomes more capable of detecting lower concentrations of glucose in a sample, making it more suitable for applications requiring high precision and detection of trace amounts of glucose. The sample containing Au-CuO-40 wt% rGO-60 wt% MWCNTs also exhibited strong selectivity in detecting glucose, even in the presence of interfering substances such as sodium hydroxide, sodium chloride, potassium ions, and urea. This indicates that the sensor can accurately distinguish glucose from other compounds, making it reliable for practical applications where such interferences might occur. In summary, the addition of MWCNTs to the Au-CuO-rGO-MWCNTs glucose sensors brings about significant enhancements in sensitivity, stability, and versatility. These improvements make the sensors more effective in their ability to detect glucose accurately and with high precision, even in complex sample matrices.The analysis results of Raman spectroscopy showed that the incorporation of MWCNTs in the Au-CuO-rGO-MWCNT composite contributed to a blue shift of the G band, and the specific I


Body Project is the most effective ED prevention program for at-risk women according to several meta-analyses, but reach is limited since delivery, traditionally, has been in-person. Moreover, peer-led Body Project groups have been reported to produce stronger effects than clinician-led Body Project groups when delivered in-person. This has not yet been examined for virtually delivered Body Project groups. This study therefore seeks to investigate the effect of virtual Body Project groups delivered by peers versus clinicians on ED risk factors, ED symptoms, and prospective ED onset.Eating disorders (EDs) are a group of mental illnesses associated with significant psychological and physiological consequences. Overall, only about one-fifth of individuals with EDs receive treatment and treatment is effective for only about one-third for those who receive care. The development and implementation of effective prevention approaches for those at risk is therefore pivotal. The Body Project groups led by clinicians; (ii) virtually delivered Body Project groups led by peers; and (iii) psychoeducational control group. Participants will complete assessments at five timepoints over two years .Young women with body image concerns aged 16–25 years (N = 441) will be included in the study and randomized to three conditions: (i) virtually delivered Body Project could markedly expand the reach for young women at risk. If findings confirm that peers can deliver virtual Body Project groups as effectively as clinicians, this will further enhance the implementation potential.Further research is needed to examine approaches to increase the potential for broad implementation of prevention of EDs. The virtual modality of the Trial registration: The present study has been registered on clinicaltrials.gov (NCT05993728). EDs affect approximately 13% of women and 5% of males , and areBody Project, a selective 4-hour group-based program designed specifically for young women at risk for EDs, has the strongest evidence of effectiveness in reducing ED risk factors  and ED symptoms [Body Project is strong and based on over 20 controlled trials including assessment-only controls [Body Project have shown a 60% reduction in future onset of EDs relative to assessment-only control participants [Body Project was originally designed as a face-to-face intervention, limiting availability to those who could attend in person. To reduce barriers to access, Ghaderi et al. [Body Project groups (1 h a week over four consecutive weeks), through Google Hangouts, among young women (N = 443) aged 15–20 years. The participants were randomized to three conditions; (i) virtually delivered Body Project groups; (ii) expressive writing; and (iii) wait-list control group. Groups were facilitated by psychology undergraduates. The wait-list group received the Body Project after the 6-month follow-up. At two-year follow-up, Body Project participants compared to control participants showed a 77% lower incidence of ED onset and significantly greater reductions in ED symptoms and risk factors. This suggests that virtual Body Project groups may be an effective prevention strategy for individuals at risk of EDs, with an increased outreach. Moreover, in-person Body Project groups led by peer group facilitators produced a 58% greater reduction in future onset of EDs over 4-year follow-up when implemented by peer educators versus clinicians [Body Project groups is unclear. Peer-led groups demand fewer resources to carry out than clinician-led groups, which may facilitate broader implementation.The symptoms , as wellsymptoms . The evicontrols –13 and acontrols , 15. Paricipants  and a 54i et al.  examinedBody Project has a strong evidence-base, it is important to confirm that interventions affect objectively measured (as opposed to self-reported) outcomes. The Body Project has previously been found to affect four objective outcomes, including reductions in cardiac risk [Body Project affects objective (implicit) outcomes when implemented virtually. More insight into such implicit and explicit mechanisms of change after Body Project participation may inform refinements of the script that will improve the effectiveness of the Body Project.Finally, though the effect of the iac risk , brain riac risk , attentiiac risk , and posiac risk . HoweverBody Project has consistently demonstrated its effectiveness in reducing ED risk factors, symptoms, and future ED onset across several independent research teams and countries, including England [Body Project in a virtual format [In sum, the  England , USA [15 England , Saudi A England , Mexico  England , and Bra England . However England  especiall format  will be Body Project. Specifically, the following hypotheses will be tested:The overall objective of this study is to evaluate the effectiveness of the Body Project groups will show significantly greater reductions in ED risk factors and symptoms compared to controls.Participants in both peer-led or clinician-led virtually delivered Body Project groups will show a significantly lower rates of ED onset over the 2-year follow-up than controls.Participants in both peer-led or clinician-led virtually delivered Body Project groups will show significant reductions in positive implicit attitudes towards the thin ideal compared to controls.Participants in both peer-led or clinician-led virtually delivered Body Project groups will show significantly greater improvements in outcomes than participants in clinician-led virtually delivered Body Project groups.Participants in peer-led  virtually delivered Body Project groups; (ii) peer-led virtual Body Project groups; and (iii) psychoeducational control group.This is a randomized controlled trial (RCT) with three arms; (i) clinician-led virtual Body Project is a group-based ED prevention program based on the principles of cognitive dissonance. According to Festinger [Body Project, participants collectively critique the thin beauty ideal through a series of verbal, written, and behavioral exercises. Engaging in these activities prompts participants to align their attitudes with their publicly displayed behaviors, which results in a reduction in pursuit of the thin beauty ideal, which in turn is theorized to reduce body dissatisfaction and ED symptoms. Consistent with this theory, reductions in pursuit of the thin beauty ideal mediated the effects of the Body Project on ED symptom reduction [Body Project script [Body Project study [Body Project is largely participant-driven given the Socratic open questions in line with dissonance-theory, which may explain why minimal changes are required to obtain efficacy in different countries. For example, in session 1 group facilitators ask what the society tells us that young women should ideally look like, by which the participants themselves define the appearance ideal in their own cultural context.The estinger , cognitieduction . During eduction  and socit script  to Norwet script . No furtct study . The BodBody Project d = 0.71 vs. 0.17) [A total of 441 young women will be included in the study. Inclusion criteria are being female, age between 16 and 25 years, and at least some level of self-reported body dissatisfaction verbally confirmed by the participant in the screening call, following procedures used in previous trials , 15, 31.s. 0.17) . Exclusiwww.bodyproject.no) has been designed to facilitate recruitment and project profiles are posted on Facebook and Instagram. The link will be shared via our online platforms, including Facebook, Instagram, and TikTok. Also, advertisement campaigns on social media will be run nationally. Individuals express interest by sending an e-mail to a Body Project mailbox hosted by Oslo University Hospital, which leads to a screening phone call to determine eligibility based on the inclusion criteria described above. In this screening call eligible participants verbally confirm to experience at least some body dissatisfaction. After providing informed consent, participants will complete baseline assessment (pretest) before being randomized into one of three arms: (i) peer-led virtual Body Project groups; (ii) clinician-led virtual Body Project groups; and (iii) educational video control group. Assessment will be repeated post intervention (posttest) and follow-up assessment after 6-months, 1-year, and 2-years. ED diagnostic interviews are conducted at baseline, 1-year, and 2-year assessments by research staff who are masked to the condition to which each participant will be randomized. Online assessment will be conducted via an online survey (Viedoc) hosted by Clinical Trials Unit (CTU), Oslo University Hospital. Randomization will be conducted by Viedoc once baseline assessment is completed. Virtually delivered Body Project group sessions will be implemented by use of Microsoft Teams, administered by Oslo University Hospital. Adaptations required for virtual script delivery include administration of home exercises via e-mail and using the chat function for summarizing themes during in-session group discussions rather than white boards or flip-charts used for in-person Body Project groups. This study is funded by the Norwegian Health Authority Region South-East .A Norwegian website , clinical dietitians, and a social worker, who are licensed health care personnel associated with the Regional Department for Eating Disorders at Oslo Universal Hospital. Peer group facilitators are recruited through acquaintances of our research team, and includes university and college-level students  and maximum four years older than the participants.Body Project, and contains a detailed intervention script. Facilitators will then attend an 8-hour virtual workshop, where the conceptual rationale and supporting evidence for the Body Project are presented, facilitators role-play delivery of the intervention using the scripted manual, and process issues are discussed . All Body Project sessions will be videotaped, and all sessions from the first group implemented by facilitators will be rated for intervention fidelity and therapeutic competence (see below for psychometrics); supervision based on these ratings will be provided to facilitators via e-mail , which has been found to significantly increase intervention effects compared to trials that did not provide this type of ongoing supervision [Body Project trials [Facilitators (both clinicians and peer educators) will read the intervention manual that outlines the theoretical rational of the intervention, reviews the evidence-base for the ervision . This stt trials , 33.Body Project have utilized such educational videos as the control condition [Body Project participants than for control participants. Adherence to watching the videos will be recorded by self-report at posttest assessment. In a previous trial participants showed similar adherence to attending Body Project group sessions versus watching the educational videos  [An educational control condition was selected to control for expectancy effects and demand characteristics. Pre-existing freely available videos allow participants to view them over the Internet to match the virtual delivery modality (1 h per week over 4 consecutive weeks). The videos contain information about how to promote a positive body image, costs associated with EDs, and how to seek help if they experience concerns related to body image, eating, body pressures, and weight. Past trials of the ondition , 33, 34.ver 80%) .All measures are translated to Norwegian. Only the Eating Disorder Examination Questionnaire (EDE-Q) and Eating Disorder Assessment for DSM-5 (EDA-5) are validated in Norwegian, while the psychometric properties of the remaining measures are validated in English. See details below:Thin-ideal internalization: the 8-item Ideal-Body Stereotype Scale-Revised (IBSS-R) [r = .80), predictive validity for future ED onset, and sensitivity to detecting intervention effects [(IBSS-R)  to asses effects .Body dissatisfaction: ten items from the Body Parts Scale [r = .90), predictive validity for future ED onset, and sensitivity to detecting intervention effects [ts Scale  to asses effects .Negative affect: 20 negative items from the Positive and Negative Affect Schedule – Revised (PANAS-X) [PANAS-X)  to measuPANAS-X) .ED symptoms: The Eating Disorder Examination Questionnaire (EDE-Q) [eating restraint, eating concern, shape concern, and weight concern and is previously translated and validated in Norwegian men and women [ (EDE-Q)  is a sel (EDE-Q) . Reponsend women , 42.Appearance ideal internalization and pressures: the Social Attitudes Towards Appearance Questionnaire 4 – Revised (SATAQ-4R) for women [or women  consistsImplicit attitudes: the Implicit Association Test (IAT) [st (IAT)  measuresst (IAT) . ParticiED diagnoses: the Eating Disorder Assessment for DSM-5 (EDA-5). The EDA-5 [he EDA-5  is as a he EDA-5  and is she EDA-5 , 48. A rBody Project [All sessions will be recorded and key elements of a randomly selected subset of sessions will be rated for degree of fidelity . Facilitator competence will be rated with 12 items  using a 100-point scale with anchors for each item . Fidelity ratings and competence ratings have shown inter-rater agreement  for the original  Project . The PI Model building. Intent-to-treat (ITT) analyses of condition effects will be evaluated using mixed effects growth models fit with SAS 9.2 PROC MIXED [d [Body Project trials have replicated in 22 controlled trials from independent teams [OC MIXED . IndividOC MIXED , when coMIXED [d . We willMIXED [d . MissingMIXED [d , we willMIXED [d  and implMIXED [d  will tesMIXED [d ) are pront teams , we willBody Project RCT [Sample size calculation was made for incidence of EDs assessed over a 2-year follow up via diagnostic interviews as the primary endpoint. Incidence rates were obtained from the previous Swedish virtual ject RCT . Based oBody Project groups we have conducted, this problem has never come to our attention); (iii) participants may experience mental health deterioration that requires additional care; and (iv) participants may experience a dangerous ED-related medical risk. Our team is not providing any medical treatment or guidance, however participants are offered a phone call with a therapist for advice on local treatment options if necessary. Based on past experience with other studies in our team, a few participants have accepted this invitation, which has worked well.The study is registered in clinicaltrials.gov (NCT05993728) and approved by the data protection department at Oslo University Hospital  and the Regional Ethics Committee  in Norway. Informed consent will be gathered, and data will be handled and stored according to requirements. Potential ethical concerns include (i) participants could somehow be identified in the video-recorded sessions or research records might be obtained by someone not authorized to hear/view them. Although this could be moderately distressing due to the personal nature of the data, the likelihood of this risk is very low given our plans for protection against risks, in collaboration with the CTU at Oslo University Hospital who will help with safety and quality monitoring of the study. A data safety and monitoring board (DSMB) will be formed to provide monitoring on a regular basis. Participant data will be identified by their assigned ID number rather than by name, and efforts will be made to ensure participants’ full names are not used in the sessions; (ii) participants might discuss confidential information about another group member outside the group. This could be distressing but also appears unlikely based on our previous experience and our plans for protection (of the over 150 a) the effectiveness of virtually-delivered Body Project on ED risk factors and symptoms compared to controls; b) the effectiveness of virtually-delivered peer-led versus clinician-led Body Project groups on ED risk factors and symptoms; and c) incidence of EDs at 2-year follow-up among participants receiving virtual Body Project versus control condition.Research process and outcomes will be shared at national and international conferences, health nurses at high schools, user organizations, and on social media. Academic papers arising from this project will be published in international peer-review journals and working titles include: Body Project groups, this would increase the implementation potential even further. Thus, the opportunities for generalization and broad application of knowledge are considered significant with the proposed study. The Body Project is brief in nature and requires few resources to carry out, including training of group facilitators. The Body Project has already been successfully implemented by a range of different research groups in a variety of countries and settings and is even effective when implemented by peers/students, reducing implementation expenses [Body Project could markedly expand the reach of the ED prevention program for young women at risk, who often do not reside near clinics or other in-person Body Project sites.A documented effect of virtually delivered brief ED prevention program, which requires little time to train group-facilitators, may be important for health nurses at high-schools, and for their students, which represents the age group with the peak onset of EDs. Thus, this is a critical window for effective prevention. We would offer to freely share the manual and provide training to implement this in high schools. Moreover, if the proposed study finds that peers are as effective as clinicians in delivering virtual expenses . The novBody Project is a broader project at the Regional Department for Eating Disorders at Oslo University Hospital, consisting of ongoing and future sub studies within our project group. Current Body Project studies include: (i)Diabetes Body Project; the JDRF-funded multi-site RCT is recently initiated and will run broadly parallel processes with the current study; (ii)Young Athlete Body Project; a pilot study among young athletes at sports junior high schools, in collaboration with the Norwegian School of Sport Sciences (NIH) and Østfold University College; and (iii) Body Project Treatment, a novel 8-hour transdiagnostic outpatient treatment for individuals with an established DSM-5 ED diagnosis, which is an extension of the Body Project prevention program. Finally, we are in the process of seeking financial support to develop and evaluate a version of the Body Project specifically targeting young men.The