Multidisciplinary Management of Phyllodes Tumours and Breast Sarcoma: A Cross-sectional Survey of Clinical Practice across the UK and Ireland.

AIMS: Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. MATERIALS AND METHODS: An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. RESULTS: Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14-21% of the MDTs and the most recommended resection margins for breast surgery were 'no tumour on ink' in benign phyllodes (39%) and 10 mm in the remaining subtypes (25-29%). Immediate breast reconstruction was supported by 11-18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. CONCLUSION: The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres.

Direct Verification of the Kinetic Description of Wave Turbulence for Finite-Size Systems Dominated by Interactions among Groups of Six Waves.

The present work considers systems whose dynamics are governed by the nonlinear interactions among groups of 6 nonlinear waves, such as those described by the unforced quintic nonlinear Schrödinger equation. Specific parameter regimes in which ensemble-averaged dynamics of such systems with finite size are accurately described by a wave kinetic equation, as used in wave turbulence theory, are theoretically predicted. In addition, the underlying reasons that the wave kinetic equation may be a poor predictor of wave dynamics outside these regimes are also discussed. These theoretical predictions are directly verified by comparing ensemble averages of solutions to the dynamical equation with corresponding solutions of the wave kinetic equation.

Small bowel obstruction caused by a fibrotic bow-string appendix: a consequence of non-operative management of acute appendicitis.

A 73-year-old woman presented with small bowel obstruction that failed to settle with conservative management. Over the previous 2 years she had presented twice with computed tomography scan-proven acute appendicitis with localised perforation of the appendix tip. In view of medical comorbidities, she was treated non-operatively with clinical and radiological resolution on each occasion, but on the third presentation laparoscopy was undertaken for non-resolving small bowel obstruction and the non-inflamed appendix itself was identified as a fibrous band causing compression of the distal ileum and complete small bowel obstruction. Following division and appendicectomy, the patient made an uneventful recovery. This case illustrates the potential consequence of repeated appendiceal inflammation and non-operative management and may be seen increasingly as this approach is widely adopted during the COVID-19 pandemic.

Urine thebaine determination by liquid chromatography tandem mass spectrometry after poppy seed consumption.

Laboratories are challenged to distinguish whether a positive urine morphine result is due to heroin use or possible poppy seed consumption. Thebaine is an opium alkaloid that has been shown to be present in the urine of individuals who have consumed poppy seeds, as well as those who have used opium. It is not present in heroin. We present a sensitive, specific liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for thebaine. We show that thebaine is detectable after consumption of two different poppy seed-containing products for up to 72 h in urine. We discuss limitations of the assay and suggest how the test might best be used.

Legalisation of e-scooters in the UK: the injury rate and pattern is similar to those of bicycles in an inner city metropolitan area.

INTRODUCTION: Rental electric scooters (e-scooters) have become more available to the UK public following amendments to legislation in 2020 affecting rideshare schemes. Existing literature from outside the UK demonstrates a worrying trend of increasing injuries related to their use and non-compliance with suggested safety precautions. An e-scooter rideshare scheme trial began in Liverpool in October 2020. We intended to identify the musculoskeletal injury rate and describe the injuries sustained during this pilot. METHODS: Data were collected retrospectively from electronic patient records on all patients at a major trauma centre covering the whole of the Liverpool rideshare trial site presenting with e-scooter and bicycle musculoskeletal injuries between the trial start on 6th October 2020 and 5th May 2021 and between 6th March 2020 and 5th October 2020. Data on rental e-scooter use were obtained from the rideshare operator. RESULTS: Fifty-one patients sustained musculoskeletal injuries involving e-scooters during the trial period and six injuries before the trial. Two-thirds of injuries were on rental e-scooters. We calculate an orthopaedic injury rate of 26.1 injuries per million km on e-scooters and 24.1 injuries per million km on bicycles. Over 70% of e-scooter patients had upper limb injuries, over 50% had lower limb injuries and 15.7% of patients required surgery. CONCLUSIONS: We observed an increase in musculoskeletal injuries presenting to hospital during the e-scooter pilot. Rates of musculoskeletal injuries were comparable to rates of injuries sustained on bicycles. E-scooters should be regulated closely and further safety measures introduced to minimise the rate of injuries.

The experimental methodology and comparators used for in vivo hernia mesh testing: a 10-year scoping review.

PURPOSE: Before being marketed, hernia mesh must undergo in vivo testing, which often includes biomechanical and histological assessment. Currently, there are no universal standards for this testing and methods vary greatly within the literature. A scoping review of relevant studies was undertaken to analyse the methodologies used for in vivo mesh testing. METHODS: Medline and Embase databases were searched for relevant studies. 513 articles were identified and 231 duplicates excluded. 126 papers were included after abstract and full text review. The data extraction was undertaken using standardised forms. RESULTS: Mesh is most commonly tested in rats (53%). 78% of studies involve the formation of a defect; in 52% of which the fascia is not opposed. The most common hernia models use mesh to bridge an acute defect (50%). Tensile strength testing is the commonest form of mechanical testing (63%). Testing strip widths and test speeds vary greatly (4-30 mm and 1.625-240 mm/min, respectively). There is little consensus on which units to use for tensile strength testing. Collagen is assessed for its abundance (54 studies) more than its alignment (18 studies). Alignment is not measured quantitatively. At least 21 histological scoring systems are used for in vivo mesh testing. CONCLUSIONS: The current practice of in vivo mesh testing lacks standardisation. There is significant inconsistency in every category of testing, both in methodology and comparators. We would call upon hernia organisations and materials testing institutions to discuss the need for a standardised approach to this field.

Breast Angiosarcoma Surveillance Study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall.

BACKGROUND: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort. METHODS: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres. RESULTS: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort. CONCLUSION: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study.

Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Lethal and sublethal effects of toxicants on bumble bee populations: a modelling approach.

Pollinator decline worldwide is well-documented; globally, chemical pesticides (especially the class of pesticides known as neonicotinoids) have been implicated in hymenopteran decline, but the mechanics and drivers of population trends and dynamics of wild bees is poorly understood. Declines and shifts in community composition of bumble bees (Bombus spp.) have been documented in North America and Europe, with a suite of lethal and sub-lethal effects of pesticides on bumble bee populations documented. We employ a mathematical model parameterized with values taken from the literature that uses differential equations to track bumble bee populations through time in order to attain a better understanding of toxicant effects on a developing colony of bumble bees. We use a delay differential equation (DDE) model, which requires fewer parameter estimations than agent-based models while affording us the ability to explicitly describe the effect of larval incubation and colony history on population outcomes. We explore how both lethal and sublethal effects such as reduced foraging ability may combine to affect population outcomes, and discuss the implications for the protection and conservation of ecosystem services.

Carfentanil Use in a Patient Undergoing Treatment for Substance Use Disorder.

Carfentanil is a synthetic opioid approximately 10,000 times as powerful as morphine. It is not approved for human use. However, cases of death associated with carfentanil have become more frequent in recent years. In this report, the case of a patient with a positive urine test for norcarfentanil (a metabolite of carfentanil) is described. The analytical method leading to the detection is summarized. This is a rarely reported case of survival of carfentanil use. It is unique in the published literature of an account of a norcarfentanil-positive patient concurrently enrolled in a substance use disorder treatment program. To the authors' knowledge, this is the first documented case of a carfentanil exposure in the state of New York.

Trainee experience of 'out of hours' surgical working in the UK: A cross-sectional analysis.

BACKGROUND: Changes to working practices and increasing service demand have contributed to low morale amongst UK surgical trainees, with pressures particularly acute 'out of hours' (OOH). Surgeons may be expected to be 'on call' for multiple hospitals, or to provide remote consultations, yet healthcare systems may undermine their professional safety and patient care. This cross-sectional study sought to define the perceptions of UK-based Royal College of Surgeons of Edinburgh (RCSEd) affiliated trainees of OOH surgical care and training. METHODS: The RCSEd Trainees' Committee conducted a design-thinking exercise to produce an online questionnaire. Non-consultant grade RCSEd Members and Fellows were invited to participate. Quantitative data was analysed using descriptive statistics, and qualitative data was coded to identify emergent themes. RESULTS: One hundred and fifty-five surgeons participated. Of those surgeons working in multiple hospitals OOH (n = 16), many did not receive access cards (12[75%]) or site-specific induction (13[81%]), and 8(50%) were not confident in using local electronic investigation and records systems. Only 14/114 (12%) of the surgeons providing remote opinion had access to a consultation record system, and most perceived dissatisfaction with the system. Emergent themes from qualitative data revealed that trainee surgeons desire specific training in OOH working, concerns that OOH work experience is diminishing, and that hospital infrastructure such as IT and communications, rest facilities and catering were inadequate in facilitating safe care. CONCLUSIONS: The participants perceived that the systems supporting delivery of safe surgical care OOH were inadequate. Hospital leaders should ensure that systems minimise risk to staff and patients.

Effective dispersion in the focusing nonlinear Schrödinger equation.

For waves described by the focusing nonlinear Schrödinger equation (FNLS), we present an effective dispersion relation (EDR) that arises dynamically from the interplay between the linear dispersion and the nonlinearity. The form of this EDR is parabolic for a robust family of "generic" FNLS waves and equals the linear dispersion relation less twice the total wave action of the wave in question multiplied by the square of the nonlinearity parameter. We derive an approximate form of this EDR explicitly in the limit of small nonlinearity and confirm it using the wave-number-frequency spectral (WFS) analysis, a Fourier-transform based method used for determining dispersion relations of observed waves. We also show that it extends to the FNLS the universal EDR formula for the defocusing Majda-McLaughlin-Tabak (MMT) model of weak turbulence. In addition, unexpectedly, even for some spatially periodic versions of multisolitonlike waves, the EDR is still a downward shifted linear-dispersion parabola, but the shift does not have a clear relation to the total wave action. Using WFS analysis and heuristic derivations, we present examples of parabolic and nonparabolic EDRs for FNLS waves and also waves for which no EDR exists.

Optimal design for dynamical modeling of pest populations.

We apply SE-optimal design methodology to investigate optimal data collection procedures as a first step in investigating information content in ecoinformatics data sets. To illustrate ideas we use a simple phenomenological citrus red mite population model for pest dynamics. First the optimal sampling distributions for a varying number of data points are determined. We then analyze these optimal distributions by comparing the standard errors of parameter estimates corresponding to each distribution. This allows us to investigate how many data are required to have confidence in model parameter estimates in order to employ dynamical modeling to infer population dynamics. Our results suggest that a field researcher should collect at least 12 data points at the optimal times. Data collected according to this procedure along with dynamical modeling will allow us to estimate population dynamics from presence/absence-based data sets through the development of a scaling relationship. These Likert-type data sets are commonly collected by agricultural pest management consultants and are increasingly being used in ecoinformatics studies. By applying mathematical modeling with the relationship scale from the new data, we can then explore important integrated pest management questions using past and future presence/absence data sets.

Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008.

H5 and H7 subtypes of low pathogenicity avian influenza viruses (LPAIVs) have the potential to evolve into highly pathogenic avian influenza viruses (HPAIVs), causing high mortality in galliforme poultry with substantial economic losses for the poultry industry. This study provides direct evidence of H7N7 LPAIV mutation to HPAIV on a single poultry premises during an outbreak that occurred in June 2008 in free range laying hens in Oxfordshire, UK. We report the first detection of a rare di-basic cleavage site (CS) motif (PEIPKKRGLF), unique to galliformes, that has previously been associated with a LPAIV phenotype. Three distinct HPAIV CS sequences (PEIPKRKKRGLF, PEIPKKKKRGLF and PEIPKKKKKKRGLF) were identified in the infected sheds suggesting molecular evolution at the outbreak premises. Further evidence for H7N7 LPAIV preceding mutation to HPAIV was derived by examining clinical signs, epidemiological descriptions and analysing laboratory results on the timing and proportions of seroconversion and virus shedding at each infected shed on the premises. In addition to describing how the outbreak was diagnosed and managed via statutory laboratory testing, phylogenetic analysis revealed reassortant events during 2006-2008 that suggested likely incursion of a wild bird origin LPAIV precursor to the H7N7 HPAIV outbreak. Identifying a precursor LPAIV is important for understanding the molecular changes and mechanisms involved in the emergence of HPAIV. This information can lead to understanding how and why only some H7 LPAIVs appear to readily mutate to HPAIV.

From theory to experimental design-Quantifying a trait-based theory of predator-prey dynamics.

Successfully applying theoretical models to natural communities and predicting ecosystem behavior under changing conditions is the backbone of predictive ecology. However, the experiments required to test these models are dictated by practical constraints, and models are often opportunistically validated against data for which they were never intended. Alternatively, we can inform and improve experimental design by an in-depth pre-experimental analysis of the model, generating experiments better targeted at testing the validity of a theory. Here, we describe this process for a specific experiment. Starting from food web ecological theory, we formulate a model and design an experiment to optimally test the validity of the theory, supplementing traditional design considerations with model analysis. The experiment itself will be run and described in a separate paper. The theory we test is that trophic population dynamics are dictated by species traits, and we study this in a community of terrestrial arthropods. We depart from the Allometric Trophic Network (ATN) model and hypothesize that including habitat use, in addition to body mass, is necessary to better model trophic interactions. We therefore formulate new terms which account for micro-habitat use as well as intra- and interspecific interference in the ATN model. We design an experiment and an effective sampling regime to test this model and the underlying assumptions about the traits dominating trophic interactions. We arrive at a detailed sampling protocol to maximize information content in the empirical data obtained from the experiment and, relying on theoretical analysis of the proposed model, explore potential shortcomings of our design. Consequently, since this is a "pre-experimental" exercise aimed at improving the links between hypothesis formulation, model construction, experimental design and data collection, we hasten to publish our findings before analyzing data from the actual experiment, thus setting the stage for strong inference.

Identification of delirium and dementia in older medical inpatients in Tanzania: A comparison of screening and diagnostic methods.

BACKGROUND: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults. This study assesses clinical utility of two instruments, the IDEA cognitive screen and the Confusion Assessment Method (CAM) for identification of delirium in older adults admitted to medical wards of a tertiary referral hospital in Tanzania. METHOD: The IDEA cognitive screen and CAM were administered to a consecutive cohort of older individuals on admission to Kilimanjaro Christian Medical Centre using a blinded protocol. Consensus diagnosis for delirium was established against DSM-5 criteria and dementia by DSM-IV criteria. RESULTS: Of 507 admission assessments, 95 (18.7%) had DSM-5 delirium and 95 (18.7%) had DSM-IV dementia (33 (6.5%) delirium superimposed on dementia). The CAM and IDEA cognitive screen had very good diagnostic accuracy for delirium (AUROC curve 0.94 and 0.87 respectively). However, a number of participants (10.5% and 16.4% respectively) were unable to complete these screening assessments due to reduced consciousness, or other causes of reduced verbal response and were excluded from this analysis; many of whom met DSM-5 criteria for delirium. Secondary analysis suggests that selected cognitive and observational items from the CAM and IDEA cognitive screen may be as effective as the full screening tools in identifying delirium even in unresponsive patients. CONCLUSION: Both instruments appeared useful for delirium screening in this inpatient setting, but had significant limitations. The combination of assessment items identified may form the basis of a brief, simple delirium screening tool suitable for use by non-specialist clinicians. Further development work is needed.

Dynamic sex chromosomes in Old World chameleons (Squamata: Chamaeleonidae).

Much of our current state of knowledge concerning sex chromosome evolution is based on a handful of 'exceptional' taxa with heteromorphic sex chromosomes. However, classifying the sex chromosome systems of additional species lacking easily identifiable, heteromorphic sex chromosomes is indispensable if we wish to fully understand the genesis, degeneration and turnover of vertebrate sex chromosomes. Squamate reptiles (lizards and snakes) are a potential model clade for studying sex chromosome evolution as they exhibit a suite of sex-determining modes yet most species lack heteromorphic sex chromosomes. Only three (of 203) chameleon species have identified sex chromosome systems (all with female heterogamety, ZZ/ZW). This study uses a recently developed method to identify sex-specific genetic markers from restriction site-associated DNA sequence (RADseq) data, which enables the identification of sex chromosome systems in species lacking heteromorphic sex chromosomes. We used RADseq and subsequent PCR validation to identify an XX/XY sex chromosome system in the veiled chameleon (Chamaeleo calyptratus), revealing a novel transition in sex chromosome systems within the Chamaeleonidae. The sex-specific genetic markers identified here will be essential in research focused on sex-specific, comparative, functional and developmental evolutionary questions, further promoting C. calyptratus' utility as an emerging model organism.

Longitudinal and Transverse Instability of Ion Acoustic Waves.

Ion acoustic waves are found to be susceptible to at least two distinct decay processes. Which process dominates depends on the parameters. In the cases examined, the decay channel where daughter modes propagate parallel to the mother mode is found to dominate at larger amplitudes, while the decay channel where the daughter modes propagate at angles to the mother mode dominates at smaller amplitudes. Both decay processes may occur simultaneously and with onset thresholds below those suggested by fluid theory, resulting in the eventual multidimensional collapse of the mother mode to a turbulent state.

Coronal Knee Alignment 40 Years after Total Meniscectomy in Adolescents: A Prospective Cohort Study.

INTRODUCTION: Meniscectomies result in altered knee biomechanics and increase contact forces on the operated knee joint. METHODS: We assessed coronal knee alignment in relation to radiological osteoarthritis grading, clinical range of movement and patient reported outcome measures 40 years after total open meniscectomies in adolescence. Thirty eight knees (30 patients) that underwent total open meniscectomy were assessed on standardised weight-bearing anteroposterior radiographs for deviation from 'physiological valgus angle' in either direction (magnitude of malalignment). These values were analysed as per site of meniscectomy for correlations with radiographic scoring systems, range of motion and patient reported outcome measures. RESULTS: Tibiofemoral angle was significantly more varus, and the magnitude of malalignment was significantly higher for the medial meniscectomy patients. The range of flexion was lower for those patients who underwent medial and lateral meniscectomies of the same knee. The patients who underwent meniscectomies of both knees had worse scores for IKDC and KOOS quality of life. Tibiofemoral angle, magnitude of malalignment and range of flexion strongly correlated with Ahlback, and Kellgren and Laurence scores, but patient reported that outcome measures did not correlate. CONCLUSION: Meniscectomy induced malalignment corresponds to the site of meniscectomy and the radiographic degree of osteoarthritis. While malalignment and reduced range of movement correlate well with worsening radiographic signs of arthritis, patient reported outcome measures do not correlate.