High-consequence infectious diseases: the conception and development of a multi-disciplinary, interprofessional simulation training programme.

BACKGROUND: High-consequence infectious diseases (HCIDs) represent a group of acute infectious diseases with the potential to impact healthcare systems and public health profoundly. Effective management requires a system-based strategy focused on early detection, initiation of infection prevention and control measures, and appropriate use of personal protective equipment (PPE). Inadequate training in the safe use of HCID PPE, and lack of familiarity with key processes such as HCID waste and spills management, exacerbates the risk posed to healthcare workers (HCWs). Enhanced training opportunities are required to ensure that staff are equipped with the necessary knowledge and capabilities to protect themselves from pathogen exposure and infection. AIM: To create a bespoke interprofessional HCID simulation training programme. METHODS: A detailed learning needs analysis was undertaken, which identified multiple areas amenable to educational intervention. A full-day HCID simulation programme was developed, providing HCWs the opportunity to practice and gain proficiency in various domains. FINDINGS: Six interprofessional participants took part in the HCID simulation programme pilot. All six (100%) participants felt that the stated learning objectives had been achieved, and five and one participants found the programme to be extremely useful (83%) or very useful (17%), respectively. Following refinement based on pilot feedback, a further six courses have been run for 38 participants, of whom 97% found the programme to be extremely useful or very useful. CONCLUSION: The development of a training intervention in the low-frequency, high-risk field of HCIDs had a positive impact. Given the disproportionate impact on HCWs at times of HCID outbreaks, more investment is needed to keep the workforce upskilled.

In Vitro Clot Trapping Efficiency of the FDA Generic Inferior Vena Cava Filter in an Anatomical Model: An Experimental Fluid-Structure Interaction Benchmark.

PURPOSE: Robust experimental data for performing validation of fluid-structure interaction (FSI) simulations of the transport of deformable solid bodies in internal flow are currently lacking. This in vitro experimental study characterizes the clot trapping efficiency of a new generic conical-type inferior vena cava (IVC) filter in a rigid anatomical model of the IVC with carefully characterized test conditions, fluid rheological properties, and clot mechanical properties. METHODS: Various sizes of spherical and cylindrical clots made of synthetic materials (nylon and polyacrylamide gel) and bovine blood are serially injected into the anatomical IVC model under worst-case exercise flow conditions. Clot trapping efficiencies and their uncertainties are then quantified for each combination of clot shape, size, and material. RESULTS: Experiments reveal the clot trapping efficiency increases with increasing clot diameter and length, with trapping efficiencies ranging from as low as approximately 42% for small 3.2 mm diameter spherical clots up to 100% for larger clot sizes. Because of the asymmetry of the anatomical IVC model, the data also reveal the iliac vein of clot origin influences the clot trapping efficiency, with the trapping efficiency for clots injected into the left iliac vein up to a factor of 7.5 times greater than that for clots injected into the right iliac (trapping efficiencies of approximately 10% versus 75%, respectively). CONCLUSION: Overall, this data set provides a benchmark for validating simulations predicting IVC filter clot trapping efficiency and, more generally, low-Reynolds number FSI modeling.

'What research was carried out on this vaginal mesh?' Health-related concerns in women following mesh-augmented prolapse surgery: a thematic analysis.

OBJECTIVE: To understand health-related issues in women following mesh-augmented prolapse surgery. DESIGN: Inductive thematic analysis of free-text comments from participants in a cross-sectional study of laparoscopic mesh sacrohysteropexy. SETTING: Tertiary urogynaecology centres, United Kingdom. POPULATION: Women who underwent laparoscopic mesh sacrohysteropexy by surgeons based at two tertiary urogynaecology centres between 2010 and 2018. METHODS: A total of 1766 potential participants were contacted by post and invited to complete paper, online or telephone questionnaires containing a free-text comments section. Of 1121 participants (response proportion 63.5%), 752 (67.1%) provided such comments. These were analysed with a six-stage inductive thematic analysis, using NVivo 11® software. MAIN OUTCOME MEASURES: Themes developed from free-text comments. RESULTS: Following familiarisation, 29 codes and 189 sub-codes were identified. These defined six themes: pelvic floor symptoms, health status, treatment success, mesh, pain and care received. The majority of comments centred on the first of these six themes. There were concerns about mesh use and a desire for more information. A range of pain symptoms were mentioned, often associated with pelvic floor symptoms, prolapse surgery or mesh. CONCLUSIONS: Despite the mesh controversy, pelvic floor symptoms and their impact on quality of life remain the principle concern of women following mesh-augmented prolapse surgery. There is a need for quality, accessible and evidence-based information sources for those women with concerns, and for those considering such surgery in the future, particularly regarding mesh safety and postoperative recovery. The relationships between pain, prolapse, mesh and pelvic floor surgery require further study. TWEETABLE ABSTRACT: Following mesh-augmented prolapse surgery, pelvic floor symptoms remain women's main focus; pain deserves further research.

Possible control of acute outbreaks of a marine fungal pathogen by nominally herbivorous tropical reef fish.

Primary producers in terrestrial and marine systems can be affected by fungal pathogens threatening the provision of critical ecosystem services. Crustose coralline algae (CCA) are ecologically important members of tropical reef systems and are impacted by coralline fungal disease (CFD) which manifests as overgrowth of the CCA crust by fungal lesions causing partial to complete mortality of the CCA host. No natural controls for CFD have been identified, but nominally herbivorous fish could play a role by consuming pathogenic fungi. We documented preferential grazing on fungal lesions by adults of six common reef-dwelling species of herbivorous Acanthuridae and Labridae, (surgeonfish and parrotfish) which collectively demonstrated an ~ 80-fold higher grazing rate on fungal lesions relative to their proportionate benthic coverage, and a preference for lesions over other palatable substrata (e.g. live scleractinian coral, CCA, or algae). Furthermore, we recorded a ~ 600% increase in live CFD lesion size over an approximately 2-week period when grazing by herbivorous fish was experimentally excluded suggesting that herbivorous reef fish could control CFD progression by directly reducing biomass of the fungal pathogen. Removal rates may be sufficient to allow CCA to recover from infection and explain historically observed natural waning behaviour after an outbreak. Thus, in addition to their well-known role as determinants of macroalgal overgrowth of reefs, herbivorous fish could thus also be important in control of diseases affecting crustose coralline algae that stabilize the foundation of coral reef substrata.

Development of a QSAR model to predict hepatic steatosis using freely available machine learning tools.

There are various types of hepatic steatosis of which non-alcoholic fatty liver disease, which may be caused by exposure to chemicals and environmental pollutants is the most prevalent, representing a potential major health risk. QSAR modelling has the potential to provide a rapid and cost-effective method to identify compounds which may trigger steatosis. Although models exist to predict key molecular initiating events of steatosis such as nuclear receptor binding, we are aware of no models to predict the apical effect steatosis. In this study, we describe the development of a QSAR model to predict steatosis using freely available machine learning tools. It was built using a dataset of 207 pharmaceuticals and pesticides which were identified as steatotic or non-steatotic from existing data from in vivo human and animal studies. The best performing model developed using the linear discriminant analysis module in TANAGRA, based on four chemical descriptors, had an accuracy of 70%, a sensitivity of 66% and a specificity of 74%. The expansion of the steatosis dataset to other chemical types, to enable the development of further models, would be of benefit in the identification of compounds with a range of mechanisms of action contributing to steatosis.

Cystoscopic transurethral incision in simplex and duplex ureteroceles-is it the definitive procedure?

OBJECTIVE: The aim of this study is to evaluate the efficacy of primary cystoscopic transurethral incision (CTUI) in the management of paediatric ureteroceles. The secondary aim is to compare the efficacy of CTUI between simplex and duplex systems. PATIENTS AND METHODS: This is a retrospective review of consecutive paediatric patients requiring surgical intervention for ureterocele. Data collected for analysis included demographics, diagnostic, pre-operative investigations, operative interventions and postoperative variables. RESULTS: Over a 19-year period, 79 consecutive cases were identified, and 42 were male (53.2%). The mean follow-up was 6.7 years. Seventy-three (92.4%) cases underwent primary CTUI; 50 of these cases (68.5%) required no further procedures during the study period. Sixty-one cases were treated by endoscopic intervention alone (77.2%). Forty-one (51.9%) cases had a simplex system, and 38 (48.1%), a duplex system. There was no statistically significant difference in the efficacy of primary CTUI in simplex vs duplex systems. Of the 20 patients who had pre-operative and postoperative micturating cystourethrograms performed, seven (35%) developed de-novo postoperative vesicoureteric reflux after CTUI. CONCLUSION: Primary CTUI is a safe, minimally invasive procedure that is definitive in the majority of children presenting with a ureterocele that requires intervention. There was no difference in success of primary CTUI between simplex or duplex systems.

Predicting estrogen receptor binding of chemicals using a suite of in silico methods - Complementary approaches of (Q)SAR, molecular docking and molecular dynamics.

With the aim of obtaining reliable estimates of Estrogen Receptor (ER) binding for diverse classes of compounds, a weight of evidence approach using estimates from a suite of in silico models was assessed. The predictivity of a simple Majority Consensus of (Q)SAR models was assessed using a test set of compounds with experimental Relative Binding Affinity (RBA) data. Molecular docking was also carried out and the binding energies of these compounds to the ERα receptor were determined. For a few selected compounds, including a known full agonist and antagonist, the intrinsic activity was determined using low-mode molecular dynamics methods. Individual (Q)SAR model predictivity varied, as expected, with some models showing high sensitivity, others higher specificity. However, the Majority Consensus (Q)SAR prediction showed a high accuracy and reasonably balanced sensitivity and specificity. Molecular docking provided quantitative information on strength of binding to the ERα receptor. For the 50 highest binding affinity compounds with positive RBA experimental values, just 5 of them were predicted to be non-binders by the Majority QSAR Consensus. Furthermore, agonist-specific assay experimental values for these 5 compounds were negative, which indicates that they may be ER antagonists. We also showed different scenarios of combining (Q)SAR results with Molecular docking classification of ER binding based on cut-off values of binding energies, providing a rational combined strategy to maximize terms of toxicological interest.

Correction to: The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

PURPOSE: This study aims to propose and validate a new unified "Risser+" grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The "Risser+ " grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. METHODS: Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1-16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff's alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. RESULTS: Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81-0.90]) compared to the first reading (0.72 [0.63-0.79]) while combined readings was close to target agreement (0.79 [0.74-0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95-0.97]) including the first (0.94 [0.92-0.95]) and second (0.97 [0.97-0.98]) reads, independently. CONCLUSIONS: The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

The 'clicky hip': to refer or not to refer?

Aims: The significance of the 'clicky hip' in neonatal and infant examination remains controversial with recent conflicting papers reigniting the debate. We aimed to quantify rates of developmental dysplasia of the hip (DDH) in babies referred with 'clicky hips' to our dedicated DDH clinic. Patients and Methods: A three-year prospective cohort study was undertaken between 2014 and 2016 assessing the diagnosis and treatment outcomes of all children referred specifically with 'clicky hips' as the primary reason for referral to our dedicated DDH clinic. Depending on their age, they were all imaged with either ultrasound scan or radiographs. Results: There were 69 'clicky hip' referrals over the three-year period. This represented 26.9% of the total 257 referrals received in that time. The mean age at presentation was 13.6 weeks (1 to 84). A total of 19 children (28%) referred as 'clicky hips' were noted to have hip abnormalities on ultrasound scan, including 15 with Graf Type II hips (7 bilateral), one Graf Type III hip, and three Graf Type IV hips. Of these, ten children were treated with a Pavlik harness, with two requiring subsequent closed reduction in theatre; one child was treated primarily with a closed reduction and adductor tenotomy. In total, 11 (15.9%) of the 69 'clicky hip' referrals required intervention with either harness or surgery. Conclusion: Our study provides further evidence that the 'clicky hip' referral can represent an underlying diagnosis of DDH and should, in our opinion, always lead to further clinical and radiological assessment. In the absence of universal ultrasound screening, we would encourage individual units to carefully assess their own outcomes and protocols for 'clicky hip' referrals and tailor ongoing service provision to local populations and local referral practices. Cite this article: Bone Joint J 2018;100-B:1249-52.

Observation of magnetic vortex pairs at room temperature in a planar α-Fe2O3/Co heterostructure.

Vortices, occurring whenever a flow field 'whirls' around a one-dimensional core, are among the simplest topological structures, ubiquitous to many branches of physics. In the crystalline state, vortex formation is rare, since it is generally hampered by long-range interactions: in ferroic materials (ferromagnetic and ferroelectric), vortices are observed only when the effects of the dipole-dipole interaction are modified by confinement at the nanoscale1-3, or when the parameter associated with the vorticity does not couple directly with strain 4 . Here, we observe an unprecedented form of vortices in antiferromagnetic haematite (α-Fe2O3) epitaxial films, in which the primary whirling parameter is the staggered magnetization. Remarkably, ferromagnetic topological objects with the same vorticity and winding number as the α-Fe2O3 vortices are imprinted onto an ultra-thin Co ferromagnetic over-layer by interfacial exchange. Our data suggest that the ferromagnetic vortices may be merons (half-skyrmions, carrying an out-of plane core magnetization), and indicate that the vortex/meron pairs can be manipulated by the application of an in-plane magnetic field, giving rise to large-scale vortex-antivortex annihilation.

Newborn and infant physical examination standards in a dedicated clinic for developmental dysplasia of the hip.

Introduction In 2014 our centre started a dedicated clinic for developmental dysplasia of the hip (DDH). The aim of the clinic was to streamline DDH referrals, enabling timely review, imaging and multidisciplinary treatment. Ongoing audit has been carried out based on the UK National Screening Committee newborn and infant physical examination (NIPE) guidelines, first published in 2008. Methods A three-year prospective audit was undertaken between 2014 and 2016 assessing compliance with NIPE standards (ST2b and ST2d) relating to timeliness of expert consultation following positive ultrasonography findings of DDH with positive examination or risk factors. Results A total of 257 babies born between January 2014 and December 2016 were seen in our dedicated DDH clinic, with 106 with abnormalities on ultrasonography and 54 requiring treatment. Compliance with 'expert consultation within 4 weeks of age for babies with an abnormality detected on clinical examination and positive ultrasonography' improved from 50% in 2014 to 53% in 2015 and 71% in 2016. Compliance with 'expert consultation within 8 weeks of age for babies with positive risk factors, negative examination and positive ultrasonography' improved from 65% in 2014 to 93% in 2015 and 100% in 2016. Conclusions This prospective audit assessing timeliness of expert consultation has demonstrated ongoing improvements between 2014 and 2016. A greater proportion of babies with ultrasonography evidence of DDH have been seen at the appropriate time. In the majority of cases, this has enabled timely non-invasive treatment with a Pavlik harness rather than surgery.

Coherent Magnetoelastic Domains in Multiferroic BiFeO_{3} Films.

The physical properties of epitaxial films can fundamentally differ from those of bulk single crystals even above the critical thickness. By a combination of nonresonant x-ray magnetic scattering, neutron diffraction and vector-mapped x-ray magnetic linear dichroism photoemission electron microscopy, we show that epitaxial (111)-BiFeO_{3} films support submicron antiferromagnetic domains, which are magnetoelastically coupled to a coherent crystallographic monoclinic twin structure. This unique texture, which is absent in bulk single crystals, should enable control of magnetism in BiFeO_{3} film devices via epitaxial strain.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

The selective outpatient treatment of adults with imported falciparum malaria: a prospective cohort study.

BACKGROUND: Current UK malaria treatment guidelines recommend admission for all patients diagnosed with falciparum malaria. However, evidence suggests that certain patients are at lower risk of severe malaria and death and may be managed as outpatients. AIM: To prospectively assess the risk of post-treatment severe falciparum malaria in selected cases managed as outpatients. The readmission rate and treatment tolerability were assessed as secondary outcomes. DESIGN: Prospective cohort study. METHODS: Adults (>15 years old) diagnosed with falciparum malaria between May 2008 and July 2012 were selected for outpatient treatment using locally defined clinical and laboratory indicators based on known risk factors for severity and death. Treatment outcomes were assessed in clinic or by telephone 4-6 weeks after treatment. RESULTS: 269 adults were diagnosed with falciparum malaria on blood film between May 2008 and July 2012. Of 255 eligible participants, 106 patients were offered ambulatory treatment, of which 95 completed the study. The severe malaria rate was 0% (95% confidence interval (CI) 0-3.8%) and the readmission rate was 5.3% (95% CI 1.7-11.9) in the outpatient group. In addition, 10.6% (95% CI 5.2-18.7%) of outpatients reported drug-related side effects. CONCLUSIONS: The outpatient treatment of selected cases of falciparum malaria is effective in our high volume UK setting. We recommend adopting a similar approach to managing this infection in other non-endemic settings where immediate access to specialist advice is available.

Cross-sectional study of Ebola virus disease preparedness among National Health Service hospital trusts in England.

BACKGROUND: The largest outbreak of Ebola virus disease (EVD) is ongoing in West Africa. Air-travel data indicate that outside Africa, the UK is among the countries at greatest risk of importing a case of EVD. Hospitals in England were therefore instructed to prepare for the assessment and early management of suspected cases. However, the response of hospitals across England is undetermined. AIM: To evaluate the readiness of acute hospitals in England, and to describe the challenges experienced in preparing for suspected cases of EVD. METHODS: A cross-sectional study using semi-structured telephone interviews and online surveys of all acute National Health Service (NHS) hospital trusts in England (hospital trusts are the vehicle by which one or more NHS hospitals in a geographical area are managed). FINDINGS: In total, 112 hospital trusts completed the survey. All interviewed hospital trusts reported undertaking preparedness activities for suspected cases of EVD, and 97% reported that they were ready to assess suspected cases. Most hospital trusts had considered scenarios in accident & emergency (97%). However, fewer hospital trusts had considered specific obstetric (61%) and paediatric scenarios (79%), the provision of ventilatory and renal support (75%), or resuscitation in the event of cardiorespiratory arrest (56%). Thirty-four hospital trusts reported issues with timely access to category A couriers for sample transportation. Challenges included the choice, use and procurement of personal protective equipment (71%), national guidance interpretation (62%) and resource allocation/management support (38%). CONCLUSION: English hospital trusts have engaged well with EVD preparedness. Although subsequent national guidance has addressed some issues identified in this study, there remains further scope for improvement, particularly in a practical direction, for acute care services encountering suspected cases of EVD.

Aggression is associated with aerobic glycolysis in the honey bee brain(1).

Aerobic glycolysis involves increased glycolysis and decreased oxidative catabolism of glucose even in the presence of an ample oxygen supply. Aerobic glycolysis, a common metabolic pattern in cancer cells, was recently discovered in both the healthy and diseased human brain, but its functional significance is not understood. This metabolic pattern in the brain is surprising because it results in decreased efficiency of adenosine triphosphate (ATP) production in a tissue with high energetic demands. We report that highly aggressive honey bees (Apis mellifera) show a brain transcriptomic and metabolic state consistent with aerobic glycolysis, i.e. increased glycolysis in combination with decreased oxidative phosphorylation. Furthermore, exposure to alarm pheromone, which provokes aggression, causes a metabolic shift to aerobic glycolysis in the bee brain. We hypothesize that this metabolic state, which is associated with altered neurotransmitter levels, increased glycolytically derived ATP and a reduced cellular redox state, may lead to increased neuronal excitability and oxidative stress in the brain. Our analysis provides evidence for a robust, distinct and persistent brain metabolic response to aggression-inducing social cues. This finding for the first time associates aerobic glycolysis with naturally occurring behavioral plasticity, which has important implications for understanding both healthy and diseased brain function.

Motion perception correlates with volitional but not reflexive eye movements.

Visually-driven actions and perception are traditionally ascribed to the dorsal and ventral visual streams of the cortical processing hierarchy. However, motion perception and the control of tracking eye movements both depend on sensory motion analysis by neurons in the dorsal stream, suggesting that the same sensory circuits may underlie both action and perception. Previous studies have suggested that multiple sensory modules may be responsible for the perception of low- and high-level motion, or the detection versus identification of motion direction. However, it remains unclear whether the sensory processing systems that contribute to direction perception and the control of eye movements have the same neuronal constraints. To address this, we examined inter-individual variability across 36 observers, using two tasks that simultaneously assessed the precision of eye movements and direction perception: in the smooth pursuit task, observers volitionally tracked a small moving target and reported its direction; in the ocular following task, observers reflexively tracked a large moving stimulus and reported its direction. We determined perceptual-oculomotor correlations across observers, defined as the correlation between each observer's mean perceptual precision and mean oculomotor precision. Across observers, we found that: (i) mean perceptual precision was correlated between the two tasks; (ii) mean oculomotor precision was correlated between the tasks, and (iii) oculomotor and perceptual precision were correlated for volitional smooth pursuit, but not reflexive ocular following. Collectively, these results demonstrate that sensory circuits with common neuronal constraints subserve motion perception and volitional, but not reflexive eye movements.