Assessment of geometrical characteristics of dental endodontic micro-instruments utilizing X-ray micro computed tomography

OBJECTIVE: The aim of this study was to quantify the surface area, volume and specific surface area of endodontic files employing quantitative X-ray micro computed tomography (mXCT). MATERIAL AND METHODS: Three sets (six files each) of the Flex-Master Ni-Ti system (Nº 20, 25 and 30, taper .04) were utilized in this study. The files were scanned by mXCT. The surface area and volume of all files were determined from the cutting tip up to 16 mm. The data from the surface area, volume and specific area were statistically evaluated using the one-way ANOVA and SNK multiple comparison tests at α=0.05, employing the file size as a discriminating variable. The correlation between the surface area and volume with nominal ISO sizes were tested employing linear regression analysis. RESULTS: The surface area and volume of Nº 30 files showed the highest value followed by Nº 25 and Nº 20 and the differences were statistically significant. The Nº 20 files showed a significantly higher specific surface area compared to Nº 25 and Nº 30. The increase in surface and volume towards higher file sizes follows a linear relationship with the nominal ISO sizes (r²=0.930 for surface area and r²=0.974 for volume respectively). Results indicated that the surface area and volume demonstrated an almost linear increase while the specific surface area exhibited an abrupt decrease towards higher sizes. CONCLUSIONS: This study demonstrates that mXCT can be effectively applied to discriminate very small differences in the geometrical features of endodontic micro-instruments, while providing quantitative information for their geometrical properties

Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest

The enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging from the dorsal neural tube between somites 1 and 7. Defects in the development and function of the ENS cause a range of enteric neuropathies, including Hirschsprung disease. Little is known about the signals that specify early ENS progenitors, limiting progress in the generation of enteric neurons from human pluripotent stem cells (hPSCs) to provide tools for disease modeling and regenerative medicine for enteric neuropathies. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neurons in vitro and, following in vivo transplantation, achieved long-term colonization of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS. In this article, Frith and colleagues show that retinoic acid (RA) signaling alters the axial identity of hPSC-derived neural crest cells in a time- and dose-dependent manner. They utilized this to derive enteric nervous system (ENS) proge

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial

Background Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. Methods PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0–2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1–2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. Findings We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI –1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference –1·3% [95% CI –3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. Interpretation In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

WORLDSOILS-Monitoring Topsoil Organic Carbon at Continental Scale Using Earth Observation Data

The adoption of multidimensional and integrated approaches is crucial to support relevant economic operators with sustainable soil related policies and services. The combination of innovative technologies based on Earth Observation (EO), Artificial Intelligence (AI), and cloud computing has been identified as a game changer for operational and cost-effective soil organic carbon (SOC) monitoring, reporting and verification approaches. In close collaboration with users and stakeholders, the European Space Agency funded WORLDSOILS project aims to develop an EO-driven soil monitoring system on a suitable cloud environment, utilizing open-source EO data, additional variables, and indices derived from EO sources, along with reference data from the European LUCAS soil data archive. The system focuses on monitoring top SOC using AI techniques and is designed in a modular manner to allow future extension to additional soil indices. With a grid resolution of 50m over Europe, it enables the assessment of temporal changes in the topsoil layer at least once a year, even at the intra-field level. At the outset, the system prepares the EO database for SOC retrievals by utilizing per-pixel reflectance composites from satellite imagery, using a novel histogram separation thresholding approach. This allows the collection of exposed soil spectra expanding the analyzable area and eliminating the effect of ambient factors, such as soil moisture, for subsequent modeling steps. The composites are then segmented into exposed soil (croplands) and permanently vegetated pixels. For exposed soils, SOC estimation relies on multi-input 1-D convolutional neural networks using Sentinel-2 spectral bands, while digital soil mapping techniques based on quantile random forest are effectively employed to generate a SOC product for vegetated areas, utilizing environmental covariates from various sources and spectral composites. Three pilot regions in Belgium, Czech Republic and Greece have been identified for validation purposes, representing different bioclimatic European territories, vegetation types, land uses, and soil compositions

Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer

Purpose: Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods: We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score # 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason # 6, and PSA # 20 ng/mL; or T1 to 2, Gleason = 7, and PSA # 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio,, 1.32). Results: Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion: The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer

Axial progenitors generate trunk neural crest cells at a high efficiency in vitro

Expression profiling by array. Gene expression profiling utilised total RNA extracted from ES cells (N=3); hPSC derived Cranial neural crest precursors (N=3); hPSC derived Cranial neural crest cells (N=3); hPSC derived Cranial neural crest cells after RA treatment to posteriorise (N=3); hPSC derived Neuromesodermal progenitors (N=3); hPSC derived Trunk neural crest progenitors (N=3); hPSC derived trunk neural crest cells (N=3)The in vitro generation of neural crest (NC) cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology and isolate NC derivatives for disease modelling/regenerative medicine applications. However, conventional differentiation protocols induce only a modest yield of NC cells corresponding to the trunk level. Here we show that trunk NC cells and, their downstream derivatives, sympathoadrenal progenitors, can be produced at a high efficiency from hPSC-derived axial progenitors, the in vitro counterparts of the posteriorly-located drivers of embryonic axis elongation. Moreover, using transcriptome analysis, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities. Collectively, our findings indicate that a post-cranial NC state is achieved through two different routes: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas a trunk fate relies on a posterior axial progenitor intermediate.Frith TJ, Granata I, Stout E, Wind M, Thompson O, Stavish D, Heath PR, Hackland JO, Anastassiadis K, Gouti M, Briscoe J, Wilson V, Guarracino MR, Andrews PW, Tsakridis A, 2018, Axial progenitors generate trunk neural crest cells at a high efficiency in vitro, Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10926