Histopathological diagnosis and surgical complications following bilateral anal sacculectomy for the treatment of unilateral canine apocrine gland anal sac adenocarcinoma: 35 cases (2019-2023).

OBJECTIVES: To report the histopathological diagnosis of both anal sacs in dogs undergoing bilateral anal sacculectomy for the treatment of unilateral apocrine gland anal sac adenocarcinoma and to compare the surgical complication rate associated with this procedure in this population with previously published literature. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent bilateral anal sacculectomy for the treatment of apparently unilateral apocrine gland anal sac adenocarcinoma, at a single institute between 2019 and 2023. Clinical staging, surgical treatment, histological findings, intra- and postoperative complications were evaluated. RESULTS: Thirty-five dogs were included. Only five of 35 (14%) dogs were found to have histologically normal contralateral anal sacs. Non-neoplastic anal sac disease was found in 23 of 35 (66%) dogs and bilateral apocrine gland anal sac adenocarcinoma was seen in seven of 35 (20%) dogs. None of the dogs diagnosed with bilateral neoplasia had evidence of bilateral neoplasia before surgery despite a thorough work-up. Complications attributable to the primary tumour removal were seen in 9% of dogs intraoperatively and 14% of dogs postoperatively, commonly tumour capsule disruption and surgical site infection, respectively. CLINICAL SIGNIFICANCE: Bilateral anal sac disease was diagnosed histologically in the majority of presumed normal anal sacs, with 20% of cases being found to have bilateral apocrine gland anal sac adenocarcinoma. The surgical complication rates of this cohort were comparable to those reported for unilateral anal sacculectomy alone. These findings promote and encourage the use of bilateral anal sacculectomy in cases of suspected unilateral anal sac neoplasia.

Cleft Laterality Dental Arch Relationship Outcomes for Children with Unilateral Cleft Lip and Palate in New Zealand.

OBJECTIVES: To investigate cleft laterality dental arch relationship outcomes of children with non-syndromic complete unilateral cleft lip and palate (UCLP) in New Zealand. DESIGN: A retrospective nationwide study. SETTINGS: Virtual 3D orthodontic study models collected prior to undertaking secondary alveolar bone grafting. PARTICIPANTS: A total of 104 patients with UCLP (L = 80: R = 24). OUTCOME MEASURES: Four calibrated assessors used the GOSLON Yardstick and 100 mm Visual Analogue Scale (VAS) to score the randomised models on 2 separate assessment sessions. Weighted Kappa were used to determine the intra/inter-rater reliability for the GOSLON and correlations for the VAS. RESULTS: Intra-rater reliability ranged from 0.57-0.88 (GOSLON) and 0.45-0.93 (VAS). Inter-rater reliability ranged from 0.62-0.86 (GOSLON) and 0.64-0.93 (VAS).GOSLON scores for the left UCLP were 31.2% for good/very good; 26.3% for fair; 42.5% for poor/very poor while the right UCLP scored 8.3% for good/very good; 37.5% for fair; 54.2% for poor/very poor. The mean VAS for left and right UCLP were 53.4 (sd 22.5) and 44.6 (sd 17.1) respectively. Neither the GOSLON nor VAS differences reached statistical significance (both P = .08). CONCLUSIONS: From a clinical perspective right UCLP had worse dental arch relationship outcomes, however, these differences failed to reach statistical significance. Further studies using larger sample sizes are required to determine if cleft laterality is an important consideration when investigating UCLP dental arch outcomes.

Suture Augmentation of a Four-Strand Semitendinosus Graft Improves Time-Zero Biomechanical Properties.

PURPOSE: To compare the time-zero biomechanical properties of hamstring graft preparations with or without suture augmentation for anterior cruciate ligament reconstruction (ACLR) in a full-construct cadaveric model. METHODS: Hamstring grafts were harvested from 24 fresh frozen human cadavers and prepared in 1 of 3 ways: quadrupled SemiTendinosus (SemiT), and quadrupled SemiT with suture augmentation (SemiT+2.0-mm tape or SemiT+1.3-mm tape; n = 8 per group). Adjustable loop suspensory implants and cortical buttons were used for fixation on a porcine tibia and acrylic block. Testing included force-controlled cyclic loading at 250 N and 400 N followed by load to failure. RESULTS: The 2 suture augmentation groups had less total elongation and increased stiffness compared to the nonsuture-augmented group (P = .025). The SemiT+2.0-mm tape group had 36% less total elongation and 34% increased stiffness compared to SemiT+1.3mm tape (P < .001). CONCLUSIONS: Suture augmentation improves construct biomechanics at time zero following hamstring tendon ACLR. Augmentation with 2.0-mm tape suture improves construct biomechanics compared to 1.3-mm tape suture. CLINICAL RELEVANCE: Independent suture augmentation of a quadrupled SemiT graft improves ACLR construct biomechanics. Outcomes were improved with augmentation using 2.0-mm tape suture compared to 1.3-mm tape suture.

Managing the risks associated with technological disruption in the road transport system: a control structure modelling approach.

Road transport is experiencing disruptive change from new first-of-a-kind technologies. While such technologies offer safety and operational benefits, they also pose new risks. It is critical to proactively identify risks during the design, development and testing of new technologies. The Systems Theoretic Accident Model and Processes (STAMP) method analyses the dynamic structure in place to manage safety risks. This study applied STAMP to develop a control structure model for emerging technologies in the Australian road transport system and identified control gaps. The control structure shows the actors responsible for managing risks associated with first-of-a-kind technologies and the existing control and feedback mechanisms. Gaps identified related to controls (e.g. legislation) and feedback mechanisms (e.g. monitoring for behavioural adaptation). The study provides an example of how STAMP can be used to identify control structure gaps requiring attention to support the safe introduction of new technologies.

This paper considers emerging risks associated with new technologies in the road transport system. It demonstrates a novel approach using STAMP to identify gaps in control and feedback mechanisms within the existing control structure which should be addressed to mitigate risk.

Absence of Spontaneous Magnetic Fields due to Time-Reversal Symmetry Breaking in Bulk Superconducting UTe_{2}.

We have investigated the low-temperature local magnetic properties in the bulk of molten salt-flux (MSF)-grown single crystals of the candidate odd-parity superconductor UTe_{2} by zero-field muon spin relaxation (µSR). In contrast to previous µSR studies of UTe_{2} single crystals grown by a chemical vapor transport method, we find no evidence of magnetic clusters or electronic moments fluctuating slow enough to cause a discernible relaxation of the zero-field µSR asymmetry spectrum. Consequently, our measurements on MSF-grown single crystals rule out the generation of spontaneous magnetic fields in the bulk that would occur near impurities or lattice defects if the superconducting state of UTe_{2} breaks time-reversal symmetry. This result suggests that UTe_{2} is characterized by a single-component superconducting order parameter.

Forecasting emergent risks in advanced AI systems: an analysis of a future road transport management system.

Artificial Intelligence (AI) is being increasingly implemented within road transport systems worldwide. Next generation of AI, Artificial General Intelligence (AGI) is imminent, and is anticipated to be more powerful than current AI. AGI systems will have a broad range of abilities and be able to perform multiple cognitive tasks akin to humans that will likely produce many expected benefits, but also potential risks. This study applied the EAST Broken Links approach to forecast the functioning of an AGI system tasked with managing a road transport system and identify potential risks. In total, 363 risks were identified that could have adverse impacts on the stated goals of safety, efficiency, environmental sustainability, and economic performance of the road system. Further, risks beyond the stated goals were identified; removal from human control, mismanaging public relations, and self-preservation. A diverse set of systemic controls will be required when designing, implementing, and operating future advanced technologies.Practitioner summary: This study demonstrated the utility of HFE methods for formally considering risks associated with the design, implementation, and operation of future technologies. This study has implications for AGI research, design, and development to ensure safe and ethical AGI implementation.

Molecular evidence of anteroposterior patterning in adult echinoderms.

The origin of the pentaradial body plan of echinoderms from a bilateral ancestor is one of the most enduring zoological puzzles1,2. Because echinoderms are defined by morphological novelty, even the most basic axial comparisons with their bilaterian relatives are problematic. To revisit this classical question, we used conserved anteroposterior axial molecular markers to determine whether the highly derived adult body plan of echinoderms masks underlying patterning similarities with other deuterostomes. We investigated the expression of a suite of conserved transcription factors with well-established roles in the establishment of anteroposterior polarity in deuterostomes3-5 and other bilaterians6-8 using RNA tomography and in situ hybridization in the sea star Patiria miniata. The relative spatial expression of these markers in P. miniata ambulacral ectoderm shows similarity with other deuterostomes, with the midline of each ray representing the most anterior territory and the most lateral parts exhibiting a more posterior identity. Strikingly, there is no ectodermal territory in the sea star that expresses the characteristic bilaterian trunk genetic patterning programme. This finding suggests that from the perspective of ectoderm patterning, echinoderms are mostly head-like animals and provides a developmental rationale for the re-evaluation of the events that led to the evolution of the derived adult body plan of echinoderms.

Harold Gillies, pioneer of modern plastic surgery, and Donald Morton, pioneer of modern surgical oncology: Master problem-solvers and surgical role models.

Harold Gillies, plastic surgeon, and Donald Morton, surgical oncologist, were iconic pioneers in their respective fields. Both of them made their mark by identifying crucial practical problems and finding innovative ways of solving them. Gillies grappled with the challenge of restoring form and function to British military personnel injured in World War I, and he set up a dedicated facility for performing this work. He introduced many new reconstructive techniques that became the foundation of the modern specialty of plastic and reconstructive surgery, which he established and nurtured. Morton, in the United States, applied his problem-solving skills to the long-debated question of the best way to manage regional lymph nodes in patients with melanoma. He developed the innovative technique of sentinel lymph node biopsy and initiated large-scale international clinical trials to establish its validity and clinical value. This and other important contributions to the emerging field of surgical oncology earned Morton his reputation as a pioneer and leader of that specialty. The problems that confronted Gillies and Morton were completely different, but both demonstrated remarkable skills as master problem-solvers in their respective fields and made extraordinary contributions to the body of knowledge and welfare of patients. All surgeons must be problem-solvers because every patient who presents for surgical management represents a new problem (or set of problems) to be addressed. As surgeons, we would do well to consider individuals such as Gillies and Morton as role models for our own problem-solving activities in day-to-day clinical practice.

20-αHydroxycholesterol, an oxysterol in human breast milk, reverses mouse neonatal white matter injury through Gli-dependent oligodendrogenesis.

White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth.

Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection.

Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.

Bayesian estimation of potential outcomes for mediation analysis of racial disparity for infant mortality.

Background: There is a need for novel methods to determine preventable causes of racial health disparities. This need has been met with the development of improved methods for mediation modeling. Current mediational analysis methods call for an evaluation of statistical interaction or effect modification between the investigated cause and mediator. For racial disparity, this approach facilitates the estimation of racially specific risks for infant mortality. However, current methods for evaluating multiple interacting mediators are inadequate. The first objective of the study was to compare Bayesian estimation of potential outcomes to other approaches to mediation analysis that included interaction. The second objective was to evaluate three potentially interacting mediators of racial disparity for infant mortality by modeling the large dataset from the National Natality Database using Bayesian estimation of potential outcomes. Methods: A random sample of observations from the 2003 National Natality Database was used to compare the currently promoted methods for mediation modeling. Racial disparity was modeled as a separate function for each of three potential mediators, (i) maternal smoking, (ii) low birth weight and (iii) teenage maternity. As a second objective, direct Bayesian estimation of potential outcomes modeled infant mortality as function of the interactions among the three mediators and race using the full National Natality Database for the years 2016 to 2018. Results: The counterfactual model was inaccurate in estimating the proportion of racial disparity that was attributable to either maternal smoking or teenage maternity. The counterfactual approach did not accurately estimate the probabilities defined by counterfactual definitions. The error was a result of modeling the excess relative risk instead of the risk probabilities. Bayesian approaches did estimate the probabilities of the counterfactual definitions. Results showed that 73% of the racial disparity for infant mortality was attributed to infants born with low birth weight. Conclusions: Bayesian estimation of potential outcomes could evaluate whether proposed public health programs would affect races differently and decisions could include consideration of the causal effect the program may have on racial disparity. The large contribution of low birth weight to racial disparity for infant mortality should be further investigated to identify preventable factors for low birth weight.

Haemostatic resuscitation in practice: a descriptive analysis of blood products administered during Operation HERRICK, Afghanistan.

INTRODUCTION: Life-threatening haemorrhage is the leading cause of potentially survivable injury in battlefield casualties. During Operation HERRICK (Afghanistan), mortality rates improved year on year due to a number of advances in trauma care, including haemostatic resuscitation. Blood transfusion practice has not previously been reported in detail during this period. METHODS: A retrospective analysis of blood transfusion at the UK role 3 medical treatment facility (MTF) at Camp Bastion between March 2006 and September 2014 was performed. Data were extracted from two sources: the UK Joint Theatre Trauma Registry (JTTR) and the newly established Deployed Blood Transfusion Database (DBTD). RESULTS: 3840 casualties were transfused 72 138 units of blood and blood products. 2709 adult casualties (71%) were fully linked with JTTR data and were transfused a total of 59 842 units. Casualties received between 1 unit and 264 units of blood product with a median of 13 units per patient. Casualties wounded by explosion required almost twice the volume of blood product transfusion as those wounded by small arms fire or in a motor vehicle collision (18 units, 9 units, and 10 units, respectively). More than half of blood products were transfused within the first 2 hours following arrival at the MTF. There was a trend towards balanced resuscitation with more equal ratios of blood and blood products being used over time. CONCLUSION: This study has defined the epidemiology of blood transfusion practice during Operation HERRICK. The DBTD is the largest combined trauma database of its kind. It will ensure that lessons learnt during this period are defined and not forgotten; it should also allow further research questions to be answered in this important area of resuscitation practice.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RESULTS: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38). CONCLUSION: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Examining factors for the adoption of silvopastoral agroforestry in the Colombian Amazon.

Current land use systems in the Amazon largely consist of extensive conventional productivist livestock operations that drive deforestation. Silvopastoral systems (SPS) support a transition to low carbon production if they intensify in sympathy with the needs of biophysical and socio-economic contexts. SPS have been promoted for decades as an alternative livestock production system but widespread uptake has yet to be seen. We provide a schema of associating factors for adoption of SPS based on past literature in tropical agriculture and apply this to a bespoke survey of 172 farms in the Caquetá region of the Colombian Amazon. We find a number of factors which do not apply to this region and argue for a context specific approach. The impact of managing increased market access and opportunities for SPS producers are crucial to avoiding additional deforestation. Further understanding of the underlying antecedents of common factors, such as perceptions of silvopastoral systems, would reduce the risk of perverse policy outcomes.

Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome.

Mitochondrial diseases represent a spectrum of disorders caused by impaired mitochondrial function, ranging in severity from mortality during infancy to progressive adult-onset disease. Mitochondrial dysfunction is also recognized as a molecular hallmark of the biological ageing process. Rapamycin, a drug that increases lifespan and health during normative ageing, also increases survival and reduces neurological symptoms in a mouse model of the severe mitochondrial disease Leigh syndrome. The Ndufs4 knockout (Ndufs4-/-) mouse lacks the complex I subunit NDUFS4 and shows rapid onset and progression of neurodegeneration mimicking patients with Leigh syndrome. Here we show that another drug that extends lifespan and delays normative ageing in mice, acarbose, also suppresses symptoms of disease and improves survival of Ndufs4-/- mice. Unlike rapamycin, acarbose rescues disease phenotypes independently of inhibition of the mechanistic target of rapamycin. Furthermore, rapamycin and acarbose have additive effects in delaying neurological symptoms and increasing maximum lifespan in Ndufs4-/- mice. We find that acarbose remodels the intestinal microbiome and alters the production of short-chain fatty acids. Supplementation with tributyrin, a source of butyric acid, recapitulates some effects of acarbose on lifespan and disease progression, while depletion of the endogenous microbiome in Ndufs4-/- mice appears to fully recapitulate the effects of acarbose on healthspan and lifespan in these animals. To our knowledge, this study provides the first evidence that alteration of the gut microbiome plays a significant role in severe mitochondrial disease and provides further support for the model that biological ageing and severe mitochondrial disorders share underlying common mechanisms.

Regional long-term analysis of dietary isotopes in Neolithic southeastern Italy: new patterns and research directions.

Isotopic analyses of prehistoric diet have only recently reached the threshold of going beyond site-focused reports to provide regional syntheses showing larger trends. In this work we present the first regional analysis for Neolithic southeastern Italy as a whole, including both substantial original data and a review of the available published data. The results show that dietary isotopes can shed new light on a number of traditional and important questions about Neolithic foodways. First, we observe regional variations in the distribution of stable isotope values across the area, suggesting variability in the Neolithic diet. Secondly, we show that, although the plant food calorific intake was primary for these communities, animal products were also important, representing on average 40% of the total calories. Third, we note that marine fish was only minorly consumed, but that this could be an underestimation, and we observe some variability in the regions considered, suggesting differences in local human-environment interactions. People in different regions of southeastern Italy may have consumed different versions of a common Neolithic diet. Regional synthesis also allows us to take stock of gaps and new directions in the field, suggesting an agenda for Neolithic isotopic research for the 2020s.

External validation of the Oldham composite Covid-19 associated mortality model (OCCAM), a prognostic model for death in patients hospitalised with Covid-19.

OBJECTIVE: External validation of the Oldham Composite Covid-19 associated Mortality Model (OCCAM), a prognostic model for Covid-19 mortality in hospitalised patients comprised of age, history of hypertension, current or previous malignancy, admission platelet count < 150 × 103/µL, admission CRP ≥ 100 µg/mL, acute kidney injury (AKI), and radiographic evidence of > 50% total lung field infiltrates. PATIENTS AND METHODS: Retrospective study assessing discrimination (c-statistic) and calibration of OCCAM for death in hospital or within 30 days of discharge. 300 adults admitted to six district general and teaching hospitals in North West England for treatment of Covid-19 between September 2020 and February 2021 were included. RESULTS: Two hundred and ninety-seven patients were included in the validation cohort analysis, with a mortality rate of 32.8%. The c-statistic was 0.794 (95% confidence interval 0.742-0.847) vs. 0.805 (95% confidence interval 0.766 - 0.844) in the development cohort. Visual inspection of calibration plots demonstrate excellent calibration across risk groups, with a calibration slope for the external validation cohort of 0.963. CONCLUSION: The OCCAM model is an effective prognostic tool that can be utilised at the time of initial patient assessment to aid decisions around admission and discharge, use of therapeutics, and shared decision-making with patients. Clinicians should remain aware of the need for ongoing validation of all Covid-19 prognostic models in light of changes in host immunity and emerging variants.

A comparison of perceived image quality between computer display monitors and augmented reality smart glasses.

INTRODUCTION: Augmented-reality (AR) smart glasses provide an alternative to standard computer display monitors (CDM). AR smart glasses may provide an opportunity to improve visualisation during fluoroscopy and interventional radiology (IR) procedures when there can be difficulty in viewing intra-procedural images on a CDM. The aim of this study was to evaluate radiographer perception of image quality (IQ) when comparing CDM and AR smart glasses. METHODS: 38 radiographers attending an international congress evaluated ten fluoroscopic-guided surgery and IR images on both a CDM (1920 × 1200 pixels) and a set of Epson Moverio BT-40 AR smart glasses (1920 × 1080 pixels). Participants provided oral responses to pre-defined IQ questions generated by study researchers. Summative IQ scores for each participant/image were compared between CDM and AR smart glasses. RESULTS: Of the 38 participants, the mean age was 39 ± 1 years. 23 (60.5%) participants required corrective glasses. In terms of generalisability, participants were from 12 different countries, the majority (n = 9, 23.7%) from the United Kingdom. For eight out of ten images, the AR smart glasses demonstrated a statistically significant increase in perceived IQ (median [IQR] 2.0 [-1.0 to 7.0] points) when compared to the CDM. CONCLUSION: AR smart glasses appear to show improvements in perceived IQ when compared to a CDM. AR smart glasses could provide an option for improving the experiences of radiographers involved in image-guided procedures and should be subject to further clinical evaluations. IMPLICATIONS FOR PRACTICE: Opportunities exist to improve perceived IQ for radiographers when reviewing fluoroscopy and IR images. AR smart glasses should be further evaluated as a potential opportunity to improve practice when visual attention is split between positioning equipment and image review.