A JWST/MIRI and NIRCam Analysis of the Young Stellar Object Population in the Spitzer I region of NGC 6822

We present an imaging survey of the Spitzer~I star-forming region in NGC 6822 conducted with the NIRCam and MIRI instruments onboard JWST. Located at a distance of 490 kpc, NGC 6822 is the nearest non-interacting low-metallicity ($\sim$0.2 $Z_{\odot}$) dwarf galaxy. It hosts some of the brightest known HII regions in the local universe, including recently discovered sites of highly-embedded active star formation. Of these, Spitzer I is the youngest and most active, and houses 90 color-selected candidate young stellar objects (YSOs) identified from Spitzer Space Telescope observations. We revisit the YSO population of Spitzer~I with these new JWST observations. By analyzing color-magnitude diagrams (CMDs) constructed with NIRCam and MIRI data, we establish color selection criteria and construct spectral energy distributions (SEDs) to identify candidate YSOs and characterize the full population of young stars, from the most embedded phase to the more evolved stages. In this way, we have identified 129 YSOs in Spitzer I. Comparing to previous Spitzer studies of the NGC 6822 YSO population, we find that the YSOs we identify are fainter and less massive, indicating that the improved resolution of JWST allows us to resolve previously blended sources into individual stars.Comment: 17 pages, 9 figures, 2 tables, to be submitted to ApJ, comments welcom

JWST MIRI and NIRCam Unveil Previously Unseen Infrared Stellar Populations in NGC 6822

NGC 6822 is a nearby (\sim490 kpc) non-interacting low-metallicity (0.2 Z_\odot) dwarf galaxy which hosts several prominent Hii regions, including sites of highly embedded active star formation. In this work, we present an imaging survey of NGC 6822 conducted with the NIRCam and MIRI instruments onboard JWST. We provide a description of the data reduction, source extraction, and stellar population identifications from combined near- and mid-infrared (IR) photometry. Our NIRCam observations reach seven magnitudes deeper than previous JHKs surveys of this galaxy, which were sensitive to just below the tip of the red giant branch (TRGB). These JWST observations thus reveal for the first time in the near-IR the red clump stellar population and extend nearly three magnitudes deeper. In the mid-IR, we observe roughly two magnitudes below the TRGB with the MIRI F770W and F1000W filters. With these improvements in sensitivity, we produce a catalogue of \sim900,000 point sources over an area of \sim 6.0 x 4.3 arcmin2. We present several NIRCam and MIRI colour-magnitude diagrams and discuss which colour combinations provide useful separations of various stellar populations to aid in future JWST observation planning. Finally, we find populations of carbon- and oxygen-rich asymptotic giant branch stars which will assist in improving our understanding of dust production in low-metallicity, early Universe analogue galaxies

Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages.

Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2-/- mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

How do trainers and trainees use formative workplace-based assessments of operative competence to deliver and receive structured feedback?

Objective: The aim of this study is to assess the quality of feedback provided to surgical trainees in the operating theatre, and to further investigate how trainees and trainers use workplace-based assessment in practice with regards to frequency and timing of assessments. Design: A retrospective study of all submitted Supervised Structured Assessments of Operative Performance (SSAOPs) from April 25, 2016 to February 2, 2021 was conducted. Setting: Surgical trainees in the Republic of Ireland across all national surgical training sites submitted SSAOPs through an online platform. Participants: Assessments of operative competence (SSAOPs) from all Core Surgical Trainees (in their first two years of dedicated post-graduate surgical training) were included for analysis, regardless of surgical subspecialty. A total of 2294 assessments were submitted from April 25, 2016 to February 2, 2021 by 330 core surgical trainees and 379 surgeon assessors. Five hundred of these assessments were randomly selected and scored for quality of feedback using a modified "Task, Gap, Action (TGA)" framework. Results: Of all 2294 submitted assessments, 1905 (83.04%) were submitted in the latter 3 months of each rotation, and 803 (35%) were submitted in the last month. Only 51 of 270 (18.89%) of trainees in their first year and 33 of 236 trainees in their second year (13.98%) submitted more than the minimum required number of assessments (6 per year). Of 500 randomly selected assessments, 362 (72.4%) had documented written feedback. The mean 'Gap' and 'Action' scores were low, at 0.44/3 and 0.53/3 respectively. Conclusions: Trainees do not submit more than the required number of operative workplace-based assessments. Assessments are submitted at the end of the trainee's rotation, limiting their formative value. The quality of written feedback is poor and could be improved significantly by encouraging a "Task," "Gap" and "Action" approach.</p

How do trainers and trainees use formative workplace-based assessments of operative competence to deliver and receive structured feedback?

Objective: The aim of this study is to assess the quality of feedback provided to surgical trainees in the operating theatre, and to further investigate how trainees and trainers use workplace-based assessment in practice with regards to frequency and timing of assessments. Design: A retrospective study of all submitted Supervised Structured Assessments of Operative Performance (SSAOPs) from April 25, 2016 to February 2, 2021 was conducted. Setting: Surgical trainees in the Republic of Ireland across all national surgical training sites submitted SSAOPs through an online platform. Participants: Assessments of operative competence (SSAOPs) from all Core Surgical Trainees (in their first two years of dedicated post-graduate surgical training) were included for analysis, regardless of surgical subspecialty. A total of 2294 assessments were submitted from April 25, 2016 to February 2, 2021 by 330 core surgical trainees and 379 surgeon assessors. Five hundred of these assessments were randomly selected and scored for quality of feedback using a modified "Task, Gap, Action (TGA)" framework. Results: Of all 2294 submitted assessments, 1905 (83.04%) were submitted in the latter 3 months of each rotation, and 803 (35%) were submitted in the last month. Only 51 of 270 (18.89%) of trainees in their first year and 33 of 236 trainees in their second year (13.98%) submitted more than the minimum required number of assessments (6 per year). Of 500 randomly selected assessments, 362 (72.4%) had documented written feedback. The mean 'Gap' and 'Action' scores were low, at 0.44/3 and 0.53/3 respectively. Conclusions: Trainees do not submit more than the required number of operative workplace-based assessments. Assessments are submitted at the end of the trainee's rotation, limiting their formative value. The quality of written feedback is poor and could be improved significantly by encouraging a "Task," "Gap" and "Action" approach.</p

Enhancing arginase 2 expression using target site blockers as a strategy to modulate macrophage phenotype

Macrophages are plastic cells playing a crucial role in innate immunity. While fundamental in responding to infections, when persistently maintained in a pro-inflammatory state they can initiate and sustain inflammatory diseases. Therefore, a strategy that reprograms pro-inflammatory macrophages toward an anti-inflammatory phenotype could hold therapeutic potential in that context. We have recently shown that arginase 2 (Arg2), a mitochondrial enzyme involved in arginine metabolism, promotes the resolution of inflammation in macrophages and it is targeted by miR-155. Here, we designed and tested a target site blocker (TSB) that specifically interferes and blocks the interaction between miR-155 and Arg2 mRNA, leading to Arg2 increased expression and activity. In bone marrow-derived macrophages transfected with Arg2 TSB (in the presence or absence of the pro-inflammatory stimulus LPS), we observed an overall shift of the polarization status of macrophages toward an anti-inflammatory phenotype, as shown by significant changes in surface markers (CD80 and CD71), metabolic parameters (mitochondrial oxidative phosphorylation) and cytokines secretion (IL-1β, IL-6, and TNF). Moreover, in an in vivo model of LPS-induced acute inflammation, intraperitoneal administration of Arg2 TSB led to an overall decrease in systemic levels of pro-inflammatory cytokines. Overall, this proof-of-concept strategy represent a promising approach to modulating macrophage phenotype. </p

Enhancing arginase 2 expression using target site blockers as a strategy to modulate macrophage phenotype

Macrophages are plastic cells playing a crucial role in innate immunity. While fundamental in responding to infections, when persistently maintained in a pro-inflammatory state they can initiate and sustain inflammatory diseases. Therefore, a strategy that reprograms pro-inflammatory macrophages toward an anti-inflammatory phenotype could hold therapeutic potential in that context. We have recently shown that arginase 2 (Arg2), a mitochondrial enzyme involved in arginine metabolism, promotes the resolution of inflammation in macrophages and it is targeted by miR-155. Here, we designed and tested a target site blocker (TSB) that specifically interferes and blocks the interaction between miR-155 and Arg2 mRNA, leading to Arg2 increased expression and activity. In bone marrow-derived macrophages transfected with Arg2 TSB (in the presence or absence of the pro-inflammatory stimulus LPS), we observed an overall shift of the polarization status of macrophages toward an anti-inflammatory phenotype, as shown by significant changes in surface markers (CD80 and CD71), metabolic parameters (mitochondrial oxidative phosphorylation) and cytokines secretion (IL-1β, IL-6, and TNF). Moreover, in an in vivo model of LPS-induced acute inflammation, intraperitoneal administration of Arg2 TSB led to an overall decrease in systemic levels of pro-inflammatory cytokines. Overall, this proof-of-concept strategy represent a promising approach to modulating macrophage phenotype. </p