Paediatric mass casualty response through the lens of Functional Resonance Analytical Methodology- lessons learned.

BACKGROUND: Mass Casualty Incidents are rare but can significantly stress healthcare systems. Functional Resonance Analytical Methodology (FRAM) is a systematic approach to model and explore how complex systems adapt to variations and to understand resilient properties in the face of perturbations. The aim of this study was to use FRAM to create a model of a paediatric trauma system during the initial response to the Manchester Arena Attack to provide resilience-based insights for the management of future Mass Casualty Incidents (MCI). METHODS: Qualitative interviews in the immediate aftermath of a terrorist bombing, were followed up with further in-depth probing of subject matter experts to create a validated and verified FRAM model. This model was compared with real incident data, then simplified for future studies. RESULTS: A Work As Imagined (WAI) model of how a paediatric emergency department provided resilient healthcare for MCI patients from reception and resuscitation to definitive care is presented. A focused model exploring the pathway for the most severely injured patients that will facilitate the simulation of a myriad of potential emergency preparedness resilience response scenarios is also presented. CONCLUSIONS: The systematic approach undertaken in this study has produced a model of a paediatric trauma system during the initial response to the Manchester Arena Attack, providing key insights on how a resilient performance was sustained. This modelling may provide an important step forward in the preparedness and planning for future MCIs.

Ultrasound-Guided Continuous Radiofrequency Ablation Of Painful Residual Limb Neuroma In Individuals With Limb Amputation-A Retrospective Case Series.

BACKGROUND: Residual limb neuromas are a significant cause of post-amputation pain. There is little knowledge concerning ultrasound-guided (US) radiofrequency ablation (RFA) as treatment. OBJECTIVE: To investigate US-guided RFA for neuroma associated pain in individuals with limb amputation. METHODOLOGY: The notes of nine consecutive patients were retrospectively reviewed. Information obtained included neuroma size and nerve, RFA duration/temperature, pain scores, analgesic requirements and ease/comfort of prosthetic use. Eight patients had lower-limb amputations and one had a trans-radial amputation. All except one, underwent diagnostic US-guided steroid injection to confirm the neuroma as the source of pain, prior to RFA. RESULTS: Six patients reported significant reduction in pain scores (defined as at least 50% reduction) and an improvement in comfort/ease of wearing their prosthetic limb, with no adverse effects. Three of these six patients also reported a reduction in analgesic requirements. Of the three remaining patients - one had a large sciatic nerve neuroma that was eventually surgically excised, another had confounding pain from an adjacent bony spur, whilst the third patient did not receive a routine diagnostic steroid injection prior to RFA. CONCLUSIONS: Our findings suggest that US-guided RFA is safe and effective for small to medium-sized residual limb neuroma associated pain in individuals with limb amputation. It can reduce pain and analgesic requirements, improve comfort/ease of wearing the prosthesis and potentially avoid surgical excision. We recommend patients should undergo a diagnostic steroid injection prior to RFA to confirm that the neuroma is the source of pain.

Linear response of east Greenland's tidewater glaciers to ocean/atmosphere warming.

Predicting the retreat of tidewater outlet glaciers forms a major obstacle to forecasting the rate of mass loss from the Greenland Ice Sheet. This reflects the challenges of modeling the highly dynamic, topographically complex, and data-poor environment of the glacier-fjord systems that link the ice sheet to the ocean. To avoid these difficulties, we investigate the extent to which tidewater glacier retreat can be explained by simple variables: air temperature, meltwater runoff, ocean temperature, and two simple parameterizations of "ocean/atmosphere" forcing based on the combined influence of runoff and ocean temperature. Over a 20-y period at 10 large tidewater outlet glaciers along the east coast of Greenland, we find that ocean/atmosphere forcing can explain up to 76% of the variability in terminus position at individual glaciers and 54% of variation in terminus position across all 10 glaciers. Our findings indicate that (i) the retreat of east Greenland's tidewater glaciers is best explained as a product of both oceanic and atmospheric warming and (ii) despite the complexity of tidewater glacier behavior, over multiyear timescales a significant proportion of terminus position change can be explained as a simple function of this forcing. These findings thus demonstrate that simple parameterizations can play an important role in predicting the response of the ice sheet to future climate warming.

The new 8th edition of TNM staging and its implications for skin cancer: a review by the British Association of Dermatologists and the Royal College of Pathologists, U.K.

The 8th edition of TNM (tumour, node and metastasis) has numerous and important changes compared with the 7th edition. Public Health England and the Royal College of Pathologists, U.K., have adopted the 8th edition of TNM (TNM8) published by the Union for International Cancer Control for skin cancer staging. These changes will have an impact on the management and commissioning of melanoma and nonmelanoma skin cancer (NMSC). The T1-T3 categories for NMSC staging require the clinician to measure the maximum dimension (usually diameter) of every potential invasive cancer. For squamous, basal and adnexal carcinomas, but not Merkel cell carcinoma (MCC), the T1-T3 categories are defined by new 20-mm and 40-mm divisions based on the maximum dimension of the lesion. In addition, new risk factors upstage T1 or T2 to T3. For melanoma, mitotic index no longer influences separation of pathological stage (pT1). There is a new, additional stratification level at 0·8-mm Breslow thickness. Subdivision pT1b, with a negative sentinel lymph node biopsy (SLNB) of pN0, is now stage IA compared with the previous IB. For MCC, SLNB is now included specifically in the pN staging system. The pT1 subdivision requires clinical information as to whether histologically involved nodes were clinically occult or detectable. For both melanoma and MCC the clinician must state whether the lymph nodes are occult or clinically detectable. Eyelid carcinoma continues to have a staging system different from that in general skin and the system is substantially revised in TNM8.

A retrospective 3-year study of salivary gland FNAC with categorisation using the Milan reporting system.

INTRODUCTION: To assess our practice using the recently developed standardised classification system designated The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and to ascertain the rates of malignancy for each category by means of a retrospective study. METHODS: All salivary gland FNAC samples received between 1 January 2013 and 31 December 2015 were retrospectively assigned a diagnostic category code from the MSRSGC. Cytology results were correlated with subsequent histology (where available), and clinical and radiological follow up. RESULTS: A total of 287 salivary gland FNA samples were received from 272 patients. The specimens were classified as non-diagnostic (21.3%), non-neoplastic (22%), atypia of undetermined significance (2.4%), neoplasm benign (36.9%), neoplasm of uncertain malignant potential (5.2%), suspicious for malignancy (1.7%) and malignant (10.5%; low grade 1.4% and high grade 9.1%). Histological and clinical/radiological follow up was available for 138 (48.1%) specimens, clinical/radiological follow up only for 145 (50.5%) and no follow up for the remaining four (1.4%) samples. The risk of malignancy for each category was non-diagnostic (8.5%), non-neoplastic (1.6%), atypia of undetermined significance (0%), neoplasm benign (1.9%), neoplasm of uncertain malignant potential (26.7%), suspicious for malignancy (100%) and malignant (100%). CONCLUSIONS: The MSRSGC appears to be a useful tool to guide clinical management and provide an indication of possible risk of malignancy. We favour implementing use of these categories in our reporting practice with a future re-evaluation to assess maintenance of service quality as well as the clinical utility of this reporting system.

Outcomes of endoscopic ultrasound-guided pancreatic FNAC diagnosis for solid and cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme.

OBJECTIVE: To compare endoscopic ultrasound (EUS)-FNAC diagnosis of pancreatic lesions with patient outcome based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme diagnostic categories: Panc 1 (non-diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3 (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5 (suspicious of malignancy); and Panc 6 (positive/malignant). METHODS: All EUS-FNA pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively classified according to the above scheme at the time of cytology reporting and data recorded prospectively. Subsequently, outcomes based on clinical follow-up or histopathology diagnosis were compared with the cytology diagnosis. RESULTS: 120 EUS-FNA pancreas specimens from 111 patients were received, of which 112 (93.3%) specimens had follow-up data. There were 79 and 41 EUS-FNA pancreas specimens from solid and cystic lesions, respectively. Based on the cytology diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3 (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The performance indicators for diagnosis of malignancy or neoplasia with malignant potential, included sensitivity (95.4%), specificity (100%), positive predictive value (100%), negative predictive value (92.3%), false positive rate (0%) and false negative rate (4.6%). CONCLUSIONS: The Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme is a logical system that can easily be introduced in a diagnostic cytopathology service. This classification scheme acts as an aid to diagnostic reporting, clear communication of significant results including risk of neoplasia/malignancy to clinicians, clinical audit and comparison of results with other centres.

The uterine myocyte as a target for prevention of preterm birth.

Preterm birth (PTB) remains the most common cause of neonatal morbidity and mortality as well as long-term disability. Current strategies to prevent or arrest spontaneous preterm labor (SPTL) have limited success. For almost three decades, there have been no novel pharmacological agents used clinically to address this important obstetrical complication. In this review, we focus on the uterine myocyte as a target for prevention of spontaneous PTB. After presenting an overview of intracellular signaling pathways that are important in regulation of smooth muscle contractility, we discuss previous and current pharmacological approaches to manage SPTL. We also present recent evidence from our own laboratories suggesting a potentially novel and uterine-specific approach to maintain or impose uterine relaxation. Finally, we briefly discuss extrinsic systems that might affect uterine activity and reinforce the concept that SPTL represents a syndrome that is the end result of a variety of pathophysiologic etiologies leading to PTB. We conclude by emphasizing the need for much more research to provide sufficient understanding of the mechanisms of SPTL and to make inroads towards reducing the incidence and adverse consequences of this common and serious syndrome.

A preliminary evaluation of pre-treatment hypodontia patients using the Dental Aesthetic Index: how does it compare with other commonly used indices?

There is currently no specific occlusal index related to hypodontia and there is a paucity of published literature on this subject. The aim of this study was to determine the relationship, if any, between the Peer Assessment Rating (PAR) Index, the Index of Complexity, Outcome and Need (ICON), and the Dental Aesthetic Index (DAI) score and the severity of hypodontia. All new patients attending the Newcastle Dental Hospital hypodontia clinic between February 2002 and March 2003 were included in the study. Of the 60 patients, two were excluded as the models were unavailable and one because they were predominantly in the primary dentition, making scoring impractical. The patient casts were scored with respect to PAR, ICON, and DAI. The mean patient age at presentation was 12 years, with a standard deviation of 1.89 and a range of 9-16 years, and a female to male ratio of 1.1:1. A significant positive correlation, using Kendall tau b, was found between the number of missing teeth, excluding third molars, and the DAI score (tau = 0.215, P = 0.027). There was no significant positive correlation between PAR (tau = -0.186, P = 0.056) and ICON (tau = 0.017, P = 0.861) score and the number of missing teeth. The results of this investigation indicate that further research is required in order to assess if the DAI could be used to determine whether or not to refer hypodontia patients for specialist advice.

Io's atmospheric response to eclipse: UV aurorae observations.

The New Horizons (NH) spacecraft observed Io's aurora in eclipse on four occasions during spring 2007. NH Alice ultraviolet spectroscopy and concurrent Hubble Space Telescope ultraviolet imaging in eclipse investigate the relative contribution of volcanoes to Io's atmosphere and its interaction with Jupiter's magnetosphere. Auroral brightness and morphology variations after eclipse ingress and egress reveal changes in the relative contribution of sublimation and volcanic sources to the atmosphere. Brightnesses viewed at different geometries are best explained by a dramatic difference between the dayside and nightside atmospheric density. Far-ultraviolet aurora morphology reveals the influence of plumes on Io's electrodynamic interaction with Jupiter's magnetosphere. Comparisons to detailed simulations of Io's aurora indicate that volcanoes supply 1 to 3% of the dayside atmosphere.

An alloantibody to a high-prevalence MNS antigen in a person with a GP.JL/Mk phenotype.

The low-prevalence MNS blood group antigenTSEN is located at the junction of glycophorin A (GPA) to glycophorin B (GPB) in several hybrid glycophorin molecules. Extremely rare people have RBCs with a double dose of the TSEN antigen and have made an antibody to a high-prevalence MNS antigen. We report the first patient who is heterozygous for GYP.JL and Mk. During prenatal tests,an alloantibody to a high-prevalence antigen was detected in the serum of a 21-year-old Hispanic woman. The antibody detected an antigen resistant to treatment by papain, trypsin, alpha-chymotrypsin, or DTT. The antibody was strongly reactive by the IAT with all RBCs tested except those having the MkMk, GP.Hil/GP.Hil, or GP.JL/GP.JL phenotypes. The patient's RBCs typed M+N-S+/-s-U+, En(a+/-), Hut-, Mi(a-), Mur-, Vw-, Wr(a-b-), and were TSEN+, MINY+. Reactivity with Glycine soja suggested that her RBCs had a decreased level of sialic acid. Immunoblotting showed the presence of monomer and dimer forms of a GP(A-B) hybrid and an absence of GPA and GPB. Sequencing of DNA and PCR-RFLP using the restriction enzyme RsaI confirmed the presence of a hybrid GYP(AB). The patient's antibody was determined to be anti-EnaFR. She is the first person reported with the GP.JL phenotype associated with a deletion of GYPA and GYPB in trans to GYP.JL.

Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour.

Since the controversies regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase (COX)-2 antagonists for the treatment of preterm labour (PTL), more emphasis has been placed on investigating the terminal synthases involved in the production of prostaglandins (PGs) to allow more targeted therapy in PTL. Prostaglandin E(2) (PGE(2)) is synthesized by one of three enzymes, cytosolic prostaglandin E synthase (cPGES), microsomal PGES-1 (mPGES-1) and microsomal PGES-2 (mPGES-2). We have determined (i) the immuno-localization of all three PGES enzymes in lower segment pregnant human myometrium, (ii) the expression of PGES and COX-2 mRNA expression at term and preterm gestation with and without labour and (iii) the effect of interleukin (IL)-1beta on COX-2 and PGES mRNA and protein expression in human myometrial smooth muscle (HMSM) cell cultures. We show mPGES-1 protein located predominantly in myometrial and vascular smooth muscle cells (SMCs), whilst mPGES-2 protein is largely in stromal cells surrounding the SMC and cPGES is diffusely located throughout the myometrium. Expression of mPGES-2 mRNA increased with term labour and PTL and expression of COX-2 and mPGES-1 mRNA with term labour, whereas cPGES expression did not change. IL-1beta stimulated release of PGE(2) by HMSM cells and increased COX-2 and mPGES-1 mRNA and protein expression. Thus, COX-2 expression and mPGES-1 expression are co-ordinately up-regulated in lower segment myometrium with term labour and with IL-1beta treatment in HMSM cells.