Early Results Research Articles

HIV Vaccine Development at a Crossroads: New B and T Cell Approaches.

Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of HIV and its ability to escape from antiviral adaptive immune responses. In recent years, several phase 3 efficacy trials have been conducted, testing a similar hypothesis, e.g., that non-neutralizing antibodies and classical cellular immune responses could prevent HIV-1 acquisition. These studies were not successful. As a result, the field has now pivoted to bold novel approaches, including sequential immunization strategies to drive the generation of broadly neutralizing antibodies and human CMV-vectored vaccines to elicit MHC-E-restricted CD8+ T cell responses. Many of these vaccine candidates are now in phase 1 trials, with early promising results.

Early and Mid-Term Results of Endovascular Aneurysm Repair with the Cordis Incraft Ultra-Low Profile Endograft: A High-Volume Center Experience.

Background/Objectives: In recent years, manufacturers have developed new low-profile stent grafts to allow endovascular treatment of abdominal aortic aneurysms (AAA) in patients with small access vessels. We evaluated the early and mid-term outcomes of the Incraft (Cordis Corp, Bridgewater, NJ, USA) ultra-low profile endograft implantation in a high-volume single center. Methods: Between 2014 and 2023, 133 consecutive endovascular aneurysm repair (EVAR) procedures performed using the Incraft endograft were recorded in a prospective database. Indications included infrarenal aortic aneurysms, common iliac aneurysms, and infrarenal penetrating aortic ulcers. Mid-term results were analyzed using the Kaplan-Meier method. Results: During the study period, 133 patients were treated with the Cordis Incraft endograft, in both elective and urgent settings. The Incraft graft was the first choice for patients with hostile iliac accesses, a feature characterizing at least one side in 90.2% of the patients in the study cohort. The immediate technical success rate was 78.2%. The intraoperative endoleak rate was 51.9% (20.3% type 1 A, 0.8% type 1 B, and 30.8% type 2 endoleak). Within 30 days, technical and clinical success rates were both 99.3%; all type 1A and 1B endoleaks were resolved at the 30-day follow-up CT-angiogram. After a mean follow-up of 35.4 months, the actuarial freedom from the re-intervention rate was 96.0%, 91.1%, and 84.0% at 1, 3, and 5 years, respectively. The iliac leg patency rate was 97.1%, 94.1%, and 93.1% at 1, 3, and 5 years, respectively. No statistically significant differences were observed between hostile and non-hostile access groups, nor between the groups with grade 1, grade 2, and grade 3 access hostility. Conclusions: The ultra-low profile Cordis Incraft endograft represents a valid option for the endovascular treatment of AAA in patients with hostile iliac accesses. The procedure can be performed with high rates of technical and clinical success at 30 days and the rates of iliac branch occlusion observed during the follow-up period appear acceptable in patients with poor aorto-iliac outflow.

Early experience using vacuum-assisted closure for managing soft tissue injuries in open type IIIB tibial fractures, a non-randomised controlled trial from a North African level one trauma centre

Purpose: The primary objective was to investigate our early results of using vacuum-assisted closure (VAC) for wound management in patients with open IIIB tibial fractures and compare the results with a group subjected to conventional daily dressing. Methods: A prospective non-randomised clinical trial (NRCT) with a parallel design and allocation ratio of 1:1 was conducted after obtaining ethical committee approval. Forty skeletally mature patients with unilateral type IIIB open tibia fractures were included over two years, starting from April 2019. In group A, patients were treated with VAC, which was changed every four days if needed, and in group B, patients had daily conventional dressings. Results: Both groups had no differences in the basic demographic, comorbidities, injury mechanism, and associated injuries. The need for secondary debridement surgeries was significantly lower in Group A than in Group B, 1 ± 0.50 versus 2.50 ± 0.85, respectively ( P < 0.001). The time till definitive coverage was significantly lower in Group A than in Group B, 12.22 ± 2.90 versus 23.56 ± 8.68 (days); P < 0.001. All coverage procedures succeeded in Group A, while four (20%) failed in Group B, P = 0.04. Infection was higher in Group B, with six (30%) patients compared to one (5%) in Group A, P = 0.01. Conclusion: Reports on VAC's role in managing severe open fracture wounds are rare in our area, and the initial results we obtained are encouraging, with lower infection rates and less cumbersome reconstruction procedures; however, further evaluation of the procedure's cost-effectiveness is mandatory.

MIGHTEE-H i: deep spectral line observations of the COSMOS field

ABSTRACT The MIGHTEE survey utilizes the South African MeerKAT radio telescope to observe four extragalactic deep fields, with the aim of advancing our understanding of the formation and evolution of galaxies across cosmic time. MIGHTEE’s frequency coverage encompasses the $\textrm {H}\scriptstyle \mathrm{I}$ line to a redshift of z $\simeq$ 0.58, and OH megamasers to z $\simeq$ 0.9. We present the MIGHTEE-$\textrm {H}\scriptstyle \mathrm{I}$ imaging products for the COSMOS field, using a total of 94.2 h on-target and a close-packed mosaic of 15 individual pointings. The spectral imaging covers two broad, relatively interference-free regions (960–1150 and 1290–1520 MHz) within MeerKAT’s L-band, with up to 26 kHz spectral resolution (5.5 km s$^{-1}$ at z = 0). The median noise in the highest spectral resolution data is 74 μJy beam$^{-1}$, corresponding to a 5$\sigma$$\textrm {H}\scriptstyle \mathrm{I}$ mass limit of 10$^{8.5}$ M$_{\odot }$ for a 300 km s$^{-1}$ line at z = 0.07. The mosaics cover $\gt $4 deg$^{2}$, provided at multiple angular resolution / sensitivity pairings, with an angular resolution for $\textrm {H}\scriptstyle \mathrm{I}$ at z = 0 of 12 arcsec. We describe the spectral line processing workflow that will be the basis for future MIGHTEE-$\textrm {H}\scriptstyle \mathrm{I}$ products, and validation of, and some early results from, the spectral imaging of the COSMOS field. We find no evidence for line emission at the position of the z = 0.376 $\textrm {H}\scriptstyle \mathrm{I}$ line reported from the CHILES survey at a $\gt $94 per cent confidence level, placing a 3$\sigma$ upper limit of 8.1 $\times$ 10$^{9}$ M$_{\odot }$ on $M_{\mathrm{HI}}$ for this galaxy. A public data release accompanies this article.

Double-Cut Tibial Plateau Leveling Osteotomy for the Management of Cranial Cruciate Ligament Insufficiency in Dogs with an Excessive Plateau Angle: Early Clinical Results in 16 Dogs.

To describe a modification of the tibial plateau leveling osteotomy technique wherein a double cut is made in the same plane to level the tibial plateau (double-cut tibial plateau leveling osteotomy [DCTPLO]) for treating dogs with cranial cruciate ligament (CrCL) and excessive tibial plateau angle (eTPA) diseases. The DCTPLO technique was performed on 18 stifles in dogs with CrCL and an eTPA (>34°). This study evaluated the accuracy of preoperative planning, feasibility of the technique, postoperative clinical outcomes, radiographic examinations at the postoperative follow-up for the first 120 days, evolution of the tibial plateau angle (TPA), time of union of the osteotomy, apposition of the implants, and possible complications. The described technique proved to be feasible for clinical application, with reproducibility from preoperative planning. An effective reduction in the eTPA levels was observed. The mean preoperative and postoperative TPA values were 39.4° (36°-43.5°) and 6.3° (3°-13°), respectively. Radiographic healing time was 60 days in 17/18 of stifles. Minor complications (not requiring surgical review or clinical treatment) were observed in 4/18 of stifles. The DCTPLO technique was effective for treating CrCL disease with TPA of up to 43.5° in dogs.

Reinforced tension-line suture after laparotomy: early results of the Rein4CeTo1 randomized clinical trial.

The aim was to investigate whether adding a reinforced tension-line (RTL) suture to a standard 4 : 1 small-bite closure would reduce the incidence of incisional hernia after colorectal cancer surgery. Patients aged at least 18 years, who were scheduled for elective colorectal cancer surgery through a midline incision at two Swedish hospitals (2017-2021), were randomized in a 1 : 1 ratio to either fascial closure with RTL and 4 : 1 small-bite closure with polypropylene sutures (RTL group) or 4 : 1 small-bite closure with polydioxanone suture alone (PDS group). The primary outcome was CT-detected incisional hernia 1 year after surgery. CT interpreters were blinded regarding treatment group. In all, 160 patients were randomized, 80 in each group. The study closed early to recruitment and follow-up. Some 134 patients were analysed at 1 year: 63 in the RTL group and 71 in the PDS group. Nineteen patients were found to have an incisional hernia: 4 (6%) in the RTL group and 15 (21%) in the PDS group (OR 3.95, 95% c.i. 1.24 to 12.60; P = 0.014). No unintended effects were found in either group. Adding an RTL suture at fascial closure decreased the incidence of incisional hernia in patients undergoing surgery for colorectal cancer. Trial registration: NCT03390764 (https://clinicaltrials.gov).

THE PLACE OF ACELLULAR COLLAGEN MATRIX IN THE TREATMENT OF CARTILAGE DAMAGE OF THE KNEE JOINT

The collagen matrix has established itself as the standard in the treatment of chondral and osteochondral injuries of the knee joint. Purpose: The application of this surgical technique aims at the restoration and regeneration of the defect with hyaline cartilage, which is the basis for achieving good early and long-term clinical results. Material and Methods: We present 36 patients who are surgically treated with this technique. Patients are divided into two groups according to the etiological principle. Results: Results are defined as good and very good and are comparable to the results of other similar retrospective studies. Conclusions: The method is applicable in selected cases of a traumatic and degenerative nature and is an alternative to early knee arthroplasty.

Improving parenting and healthy nutrition for stunted toddler mothers through community service programs

Stunting is a significant public health problem, especially among toddlers, caused by chronic malnutrition and suboptimal parenting. This community service program aims to overcome these problems by providing relevant education and interventions to mothers of toddlers who experience stunting. This program aims to improve the knowledge and skills of mothers under five in terms of parenting and healthy nutrition, as well as encourage behavioral changes that support optimal child growth and development. This program is carried out through a series of educational activities, including training on balanced nutrition, how to serve nutritious food, and parenting techniques that support children's health. In addition, this activity also involves direct counseling and the provision of educational materials that are easy to understand by mothers of toddlers. The evaluation was carried out to measure the improvement of parenting knowledge, skills, and practices and their impact on the nutritional status of children. Early results showed a significant increase in maternal knowledge about the importance of balanced nutrition and healthy parenting. Practical skills in the presentation of nutritious food have also improved. Further evaluation showed that there was an improvement in the nutritional status of toddlers and a decrease in the prevalence of stunting in the target community. This community service program has succeeded in improving parenting and healthy nutrition knowledge for mothers of stunted toddlers. This intervention is expected to be a model for similar programs in other regions and make a positive contribution to reducing stunting rates more broadly

The development of a cognitive screening protocol for Aboriginal and/or Torres Strait Islander peoples: the Guddi Way screen.

Background Many Aboriginal and/or Torres Strait Islander peoples are exposed to risk factors for cognitive impairment. However, culturally appropriate methods for identifying potential cognitive impairment are lacking. This paper reports on the development of a screen and interview protocol designed to flag possible cognitive impairments and psychosocial disability in Aboriginal and/or Torres Strait Islander adults over the age of 16years. Methods The Guddi Way screen includes items relating to cognition and mental functions across multiple cognitive domains. The screen is straightforward, brief, and able to be administered by non-clinicians with training. Results Early results suggest the Guddi Way screen is reliable and culturally acceptable, and correctly flags cognitive dysfunction among Aboriginal and/or Torres Strait Islander adults. Conclusions The screen shows promise as a culturally appropriate and culturally developed method to identify the possibility of cognitive impairments and psychosocial disability in Aboriginal and/or Torres Strait Islander adults. A flag on the Guddi Way screen indicates the need for referral to an experienced neuropsychologist or neuropsychiatrist for further assessment and can also assist in guiding support services.

Early results from the pivotal trial substudy of the GORE EXCLUDER conformable endoprosthesis in angulated necks

ObjectiveTo report the investigational device exemption study 1-year clinical outcomes of the high neck angulation (HNA) substudy of the GORE EXCLUDER Conformable AAA Endoprosthesis (EXCC) for treatment of infrarenal abdominal aortic aneurysms (AAAs). MethodsThis study is a prospective, multicenter clinical trial conducted in the United States and included core laboratory assessment of imaging and independent event adjudication. Anatomical criteria for enrollment in the HNA substudy included infrarenal aortic neck angulation >60° and ≤90° with aortic neck length ≥10 mm. Primary safety end points included estimated blood loss of >1000 mL, death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, and thromboembolic events. Primary effectiveness end points included technical success, absence from type I and III endoleaks, migration (≥10 mm), sac enlargement (≥5 mm), sac rupture, and conversion to open repair. ResultsBetween January 2018 and February 2022, 95 patients were enrolled in the HNA substudy across 35 sites. Of the 95 patients, 71 (74.7%) were male and the cohort average age was 74.4 years. The mean infrarenal proximal aortic neck angle was 71.6° and the mean AAA size was 62.9 mm. Overall technical success was achieved in 93 patients (97.9%). Freedom from a primary safety end point through 30 days was 96.7%; 3 (3.3%) patients had an estimated blood loss of >1000 mL. Freedom from the primary effectiveness at 12 months was achieved in 94.8%. Four patients (4.3%) had a type IA endoleak; intervention after the procedure was not required and no subsequent interventions or sac enlargement were noted in these patients. At 12 months, 29 patients (39.7%) experienced a type II endoleak and 1 (1.3%) patient experienced AAA sac expansion of ≥5 mm. Through 12 months, 1 patient (1.3%) had a conversion to open surgical repair. There were no aneurysm-related deaths, ruptures, or migration through 12 months. ConclusionsThe investigational device exemption study demonstrates safety and effectiveness of the GORE EXCLUDER Conformable AAA Endoprosthesis device in AAA with highly angulated necks (>60° and ≤90°) are preserved at the 12-month follow-up.

Data-driven analysis that integrates bioinformatics and machine learning uncovers PANoptosis-related diagnostic genes in early pediatric septic shock

ObjectivesSepsis is one of the leading causes of death for children worldwide. Additionally, refractory septic shock is one of the most significant groups that contributes to a high death rate. The interaction of pyroptosis, apoptosis, and necroptosis results in a unique inflammatory cell death mechanism known as PANoptosis. An increasing amount of evidence suggests that PANoptosis can be brought on by several stimuli, including cytokine storms, malignancy, and bacterial or viral infections. The goal of this study is to improve the diagnostic significance of the PANoptosis-related gene signature in early pediatric septic shock. Design and methodsWe examined children with septic shock from the GSE66099 discovery cohort and looked at differentially expressed genes (DEGs). To filter the important modules, weighted gene co-expression network analysis (WCGNA) was employed. In the end, random forest analysis and the least absolute shrinkage and selection operator (LASSO) were used to determine the PANoptosis diagnostic signature genes. To determine the PANoptosis signature genes, we also found four validation cohorts: GSE26378, GSE26440, GSE8121, and GSE13904. The area under the curve (AUC) of the receiver operating characteristic curves (ROCs), along with sensitivity, specificity, positive predictive value, and negative predictive value, were used to assess the diagnostic efficacy of these signature genes. ResultsFrom GSE66099, 1142 DEGs in total were tested. Following the WGCNA clustering of the data into 16 modules, the MEgrey module showed a significant correlation with pediatric septic shock (p < 0.0001). Following the use of LASSO and random forest algorithms to identify the PANoptosis-related signature genes, which include ANXA3, S100A9, TXN, CLEC5A, and TMEM263. These signature genes' receiver operating characteristic curves (ROCs) were confirmed in the external dataset from GSE26378, GSE26440, GSE8121, and GSE13904, and were 0.994 (95 % CI 0.987–0.999), 0.987 (95 % CI 0.974–0.997), 0.957 (95 % CI 0.927–0.981), 0.974 (95 % CI 0.954–0.988), 0.897 (95 % CI 0.846–0.941), respectively. ConclusionIn summary, the discovery of PANoptosis genes, ANXA3, S100A9, TXN, CLEC5A, and TMEM263 proved to be quite helpful in the early detection of pediatric septic shock patients. These early results, which need to be further confirmed in basic and clinical research, are extremely important for understanding immune cell infiltration in the pathophysiology of pediatric septic shock.

PJY02 Retzius sparing robotic-assisted radical prostatectomy; single center, single surgeon and our early results

PJY02 Retzius sparing robotic-assisted radical prostatectomy; single center, single surgeon and our early results

Integrating Maternity Care Through Bundled Payments In The Netherlands: Early Results And Policy Lessons.

Bundled payments are increasingly used globally to move health care delivery in a value-based direction. However, evidence remains scant in key clinical areas. We evaluated bundled payments for maternity care in the Netherlands during the period 2016-18. We used a quasi-experimental difference-in-differences design to measure the association between the bundled payment model and changes in key clinical and economic outcomes. Bundled payments were associated with an increase in outpatient, midwife-led births and a reduction in in-hospital, obstetrician-led births, along with changes in the use of labor inductions and planned versus emergency cesarean deliveries. Total spending on maternity care decreased by US$328 (5percent) per pregnancy. No changes in maternal or neonatal health outcomes were observed. Several policy lessons emerged. First, bundled payments appeared to help affect providers' behavior in the maternity care setting. Second, bundled payments seemed to exert heterogeneous effects across participating maternity care networks, as the same financial incentive translated into different changes in clinical practices and outcomes. Third, alternative payment models should be designed with clear goals and definitions of success to guide evaluation and implementation.

1 PSMA MRI Guided Prostate Sbrt: Acute Toxicity and Early Results from the Argos-Climber Phase I/II Trial

1 PSMA MRI Guided Prostate Sbrt: Acute Toxicity and Early Results from the Argos-Climber Phase I/II Trial

1565P Improving lung cancer screening selection: Hunt Lung Cancer Model (HUNT LCM) versus PLCOm2012, early results after two rounds of screening in a prospective screening pilot study in Norway (TIDL)

1565P Improving lung cancer screening selection: Hunt Lung Cancer Model (HUNT LCM) versus PLCOm2012, early results after two rounds of screening in a prospective screening pilot study in Norway (TIDL)

Innovative solutions to frontier exploration in Eastern Mediterranean salt basins

The Eastern Mediterranean region is expected to hold large undiscovered natural gas resources that could address critical energy supply needs of the surrounding countries. However, exploration is challenged due to regional geologic complexities. The combination of Messinian salt structures and diapiric shales in offshore Cyprus and Egypt often causes strong attenuation of seismic energy and severe seismic imaging illumination shadows, which lead to large uncertainty regarding subsalt reservoir presence and the underlying petroleum system assessment. As part of the efforts to solve these imaging challenges, we present innovative seismic acquisition solutions to address key exploration risks such as reservoir presence. A one-sided wide-azimuth configuration consisting of one streamer vessel and one dedicated source vessel operating under the simultaneous-source mode was used to acquire data in a cost-effective way. An 8000 in3 low-frequency source was used on both vessels to provide higher energy output in the low-frequency bands of less than approximately 4 Hz. Our preliminary results show evidence of seismic image uplift due to enhanced acquisition and processing, leading to greater confidence in interpretation, which is critical for positioning wells in future drilling campaigns. This paper highlights seismic testing results undertaken to design a large exploration-scale seismic survey in the Eastern Mediterranean and early results from the execution of that program. This will help better refine optimal design criteria for future acquisition, signal processing, and imaging in order to unlock additional resources beneath complex salt provinces and identify where additional imaging needs still exist.

Commentator Discussion: A novel hybrid prosthesis for open repair of acute DeBakey type I dissection with malperfusion: Early results from the Prospective, Single Arm, Multi-center Clinical Investigation to Evaluate the Safety and Effectiveness of AMDS in the Treatment of acute DeBakey Type I Dissection trial

Commentator Discussion: A novel hybrid prosthesis for open repair of acute DeBakey type I dissection with malperfusion: Early results from the Prospective, Single Arm, Multi-center Clinical Investigation to Evaluate the Safety and Effectiveness of AMDS in the Treatment of acute DeBakey Type I Dissection trial

The early and medium-term results of the Ross procedure in pediatric patients

Introduction and objectivesThe Ross method is the preferred surgical treatment for pediatric aortic valve diseases, and its long-term outcomes have been extensively documented. This article presents the results of the Ross and Ross–Konno procedures performed on pediatric patients in our center. MethodsRoss and Ross–Konno procedures were performed on 20 patients in our center between January 2015 and January 2019. ResultsThe patients’ mean age was 10.6 years (range: 23 days to 18 years) and mean weight was 37.6 kg (range: 3–63 kg). Thirteen had aortic valve stenosis, four had aortic valve insufficiency, and three had a mixed disease. The Ross–Konno procedure was used for four patients. The mean cardiopulmonary bypass time was 184.68±60.1 min and the mean cross time was 149±67.8 min. One neonatal patient died in the early postoperative phase due to low cardiac output. The mean follow-up time was 60.15±24.45 months. One patient later underwent reoperation due to conduit stenosis. One patient is being monitored for moderately serious conduit stenosis. At present, of those who underwent the procedure, one has moderate aortic regurgitation, two have mild or moderate aortic regurgitation, and others have minimal aortic regurgitation. No patients required intervention for left ventricular outflow tract obstruction and mortality was not observed in the long term. Conclusion(s)The reintervention rates for autograft and conduit-related cases were low in early and medium-term follow-up, and no significant autograft insufficiency was observed. Ross or Ross–Konno surgery is preferred for aortic diseases in pediatric patients due to its low mortality and satisfactory long-term results.

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

Topography-guided Anatomical Reassembly for Distal Penile Hypospadias Without Chordee: A Comprehensive Illustration and Midterm Results of a Novel Approach

ObjectivesTo provide a comprehensive illustration of the newly introduced ‘topography-guided anatomical reassembly’ approach, which has shown promising early results, and to report the mid-term outcomes of an extended series. MethodsThis is a prospective cohort study of all patients presenting to the author’s facility with distal penile hypospadias without chordee between June 2018 and January 2023. Redo cases, circumcised cases, and cases with non-preservable plates are excluded. The procedure follows the most recently introduced principle of the topography-guided anatomical reassembly approach for distal penile hypospadias, that is, the exclusive zipping-up of the unfolded spongiosal plate. ResultsA subset of 97 boys met the enrolment criteria. The hypospadias meatus was coronal or sub-coronal in 35 boys, distal penile in 45 boys, and mid-penile in 17 boys. The mean age at the time of surgical correction was 8.11 months. The mean operative time was 66.7 min. After a mean follow-up of 27 months, five urethrocutaneous fistulae were reported: three glanular and two sub-coronal. Meatal disfigurement with downward stream deviation was reported in two more patients. Two more occurrences of meatal recession were identified, yet surgical correction was not necessary. The overall reoperation rate settled at 7%. ConclusionsThe proposed topography-guided anatomical reassembly technique for distal hypospadias is simple, effective, and highly feasible at mid-term follow-up of the given series. Maintaining the integrity of well-developed penile tissues eliminates the possibility of unforgivable tissue damage and avoids the need for challenging revision procedures.