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Background & Aims Hepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. However, the overall contribution of T cells to the control of HAV and the pathogenesis of hepatitis A is unclear and has been impeded by a historic lack of small animal models. Methods Ifnar1-/- mice are highly permissive for HAV and develop pathogenesis that recapitulates many features of hepatitis A. Using this model, we identified HAV-specific CD8+ and CD4+ T cells by epitope mapping, and then used tetramers and functional assays to quantify T cells in the liver at multiple times after infection. We assessed the relationships between HAV-specific T cell frequency, viral RNA amounts, and liver pathogenesis. Results A large population of virus-specific T cells accumulated within the livers of Ifnar1-/- mice during the first 1-2 weeks of infection and persisted over time. HAV replication was enhanced and liver disease exacerbated when mice were depleted of T cells. Conversely, immunization with a peptide vaccine increased virus-specific CD8+ T cell frequencies in the liver, reduced viral RNA abundance, and lessened liver injury. Conclusion These data show that T cells protect against HAV-mediated liver injury and can be targeted to improve liver health. Lay summary Hepatitis A virus is a leading cause of acute viral hepatitis worldwide. T cells were thought to contribute to liver injury during acute infection. We now show that virus-specific T cells protect against infection and limit liver injury.

Objective To describe and illustrate a novel technique of uretero-ileal anastomosis for use in urinary diversion – the Pull-through Anastomosis of Ureter To Enteric Conduit (PAUTEC). A second objective was to evaluate the surgical outcomes of the PAUTEC anastomosis. Materials and Methods Our novel anastomotic technique was described step-by-step and visually depicted with illustrations and the accompanying narrated video. Additionally, to evaluate safety and efficacy, a retrospective review of a prospectively maintained database was performed. Patients who underwent radical cystectomy alone or during pelvic exenteration, with ileal conduit diversion incorporating PAUTEC, 2016-2020 with ≥6 months follow-up were included. Surgical outcomes and renal function were analysed. Results PAUTEC anastomosis was performed on 43 ureters in 23 patients. Mean age was 66 years [50-80] and 21 of 23 patients were male. One patient had a conservatively-managed small urine leak. No ureteric strictures have been identified to date. Mean serum creatinine was 1.15 mg/dL [0.69-2.08] (102umol/L, range 61-184 umol/L) preoperatively, and 1.09 mg/dL [0.61-2.59] (96.3 umol/L, range 54-229 umol/L) at follow-up, demonstrating no significant change (P= .26, paired t-test). Mean follow-up was 15 months [6-44]. Conclusion A PAUTEC technique of uretero-ileal anastomosis is feasible and technically straightforward, with satisfactory outcomes observed to date.

Background Traceability of food products, ingredients and associated operations are important requirements for improving food safety and consumer confidence. Food traceability systems (FTSs) often suffer from inefficiency in either material or information flow within an enterprise or between supply chain partners. Modelling of system architecture is a visualisation approach that allows multiple parties to collaborate in a system design process, identify its inefficiencies and propose improvements. However, there is little academic research on the ability to use a standard visualisation tool that supports collaborative design and considers both material and information flow for a given food traceability system. Scope & approach The aim of this research is to propose a new visualisation approach that allows supply chain operators to collaborate effectively in the design process of FTSs capable of maintaining streamlined information flow, minimising information loss, and improving supply chain performance. Key findings & conclusion Food traceability systems are complex, encompassing processes, material flow, information flow, techniques, infrastructure, people and control strategies. Screening of literature demonstrates that model-based system engineering (MBSE) offers a sound way for visualisation of such complex systems. However, in the food traceability literature, an MBSE-based standardised traceability system modelling approach is absent. This study makes a strong contribution to existing literature by proposing a novel, material and information flow modelling technique (MIFMT), to visualise FTS architecture. MIFMT can support common understanding and iterative implementation of effective FTSs that contextualise food supply chains at multiple levels and provides opportunity to identify points at where inefficiencies can occur so that actions can be taken to mitigate them.

There are limited data to inform risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical resection of osteosarcoma. We retrospectively reviewed patients (n = 5293) following surgical resection of primary osteosarcoma in the National Cancer Database (2004–2015). Univariate and multivariate methods were used to correlate variables with readmission and short-term mortality. Of 210 readmissions (3.97%), risk factors independently associated with unplanned 30-day readmission included comorbidity burden (odds ratio [OR] 2.4, p = 0.042), Medicare insurance (OR 1.9, p = 0.021), and axial skeleton location (OR 1.5, p = 0.029). A total of 91 patients died within 90 days of their surgery (1.84%). Risk factors independently associated with mortality included age (hazard ratio 1.1, p < 0.001), increasing comorbidity burden (OR 6.6, p = 0.001), higher grade (OR 1.7, p = 0.007), increasing tumor size (OR 2.2, p = 0.03), metastatic disease at presentation (OR 8.5, p < 0.001), and amputation (OR 2.0, p = 0.04). Chemotherapy was associated with a decreased risk of short-term mortality (p < 0.001). Several trends were clear: insurance status, tumor location and comorbidity burden were independently associated with readmission rates, while age, amputation, grade, tumor size, metastatic disease, and comorbidity burden were independently associated with short-term mortality.

Management of infants with OEIS complex is challenging and not standardized. Expeditious surgery after birth has been recommended to limit soilage of the urinary tract and optimize intestinal function. However, clinical instability secondary to comorbidities is common in this population and early operation carries risk. We sought to define the risk/benefit profile of delaying repair. All newborn patients with OEIS managed by our institution between Sep 2017 and Oct 2019 were reviewed. Comorbidities were evaluated, including cardiopulmonary pathologies and associated malformations. Ten patients with OEIS were managed. Patients underwent early (2 patients, repair at 0–2 days) or delayed (6 patients, repair at 6–87 days) first-stage exstrophy repair. Two patients died prior to repair (progressive respiratory failure, severe genetic anomalies). Repairs were delayed secondary to cardiac conditions, neurosurgical interventions, medical disease, and/or delayed transfer. Delayed repair patients had longer lengths of stay and use of parenteral nutrition. No patients experienced urinary tract infections prior to repair. Delaying first-stage exstrophy repair to allow physiologic optimization is safe. All repaired patients were discharged home, without parenteral nutrition or supplemental oxygen.

Aims Gender bias and sexual discrimination (GBSD) have been widely recognized across a range of fields and are now part of the wider social consciousness. Such conduct can occur in the medical workplace, with detrimental effects on recipients. The aim of this review was to identify the prevalence and impact of GBSD in orthopaedic surgery, and to investigate interventions countering such behaviours. Methods A systematic review was conducted by searching Medline, EMCARE, CINAHL, PsycINFO, and the Cochrane Library Database in April 2020, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to which we adhered. Original research papers pertaining to the prevalence and impact of GBSD, or mitigating strategies, within orthopaedics were included for review. Results Of 570 papers, 27 were eligible for inclusion. These were published between 1998 and 2020. A narrative review was performed in light of the significant heterogeneity displayed by the eligible studies. A total of 13 papers discussed the prevalence of GBSD, while 13 related to the impact of these behaviours, and six discussed mitigating strategies. GBSD was found to be common in the orthopaedic workplace, with all sources showing women to be the subjects. The impact of this includes poor workforce representation, lower salaries, and less career success, including in academia, for women in orthopaedics. Mitigating strategies in the literature are focused on providing female role models, mentors, and educational interventions. Conclusion GBSD is common in orthopaedic surgery, with a substantial impact on sufferers. A small number of mitigating strategies have been tested but these are limited in their scope. As such, the orthopaedic community is obliged to participate in more thoughtful and proactive strategies that mitigate against GBSD, by improving female recruitment and retention within the specialty. Cite this article: Bone Joint J 2020;102-B(11):1446–1456.

Limitations in workforce size and access to resources remain perennial challenges to greater progress in academic veterinary medicine and engagement between human and veterinary medicine (One Health). Ongoing resource constraints occur in part due to limited public understanding of the role veterinarians play in improving human health. One Health interactions, particularly through interdisciplinary collaborations in biomedical research, present constructive opportunities to inform resource policies and advance health care. To this end, inter-institutional partnerships between individual veterinary medical education programs (VMEPs) and several National Institutes of Health (NIH) intramural research programs have created synergies beyond those provided by individual programs. In the NIH Comparative Biomedical Scientist Training Program (CBSTP), interdisciplinary cross-training of veterinarians consisting of specialty veterinary medicine coupled with training in human disease research leading to a PhD, occurs collaboratively on both VMEP and NIH campuses. Pre-doctoral veterinary student research opportunities have also been made available. Through the CBSTP, NIH investigators and national biomedical science policy makers gain access to veterinary perspective and expertise, while veterinarians obtain additional opportunities for NIH-funded research training. CBSTP Fellows serve as de facto ambassadors enhancing visibility for the profession while in residence at NIH, and subsequently through a variety of university, industry, and government research appointments, as graduates. Thus, the CBSTP represents an inter-institutional opportunity that not only addresses critical needs for veterinarian-scientists in the biomedical workforce, but also simultaneously exposes national policy makers to veterinarian-scientists’ specialized training, leading to more effective realization of One Health goals to benefit human and animal health.

GenX is an alternative to environmentally persistent long-chain perfluoroalkyl and polyfluoroalkyl substances. Mice exposed to GenX exhibit liver hypertrophy, elevated peroxisomal enzyme activity, and other apical endpoints consistent with peroxisome proliferators. To investigate the potential role of peroxisome proliferator-activated receptor alpha (PPARα) activation in mice, and other molecular signals potentially related to observed liver changes, RNA sequencing was conducted on paraffin-embedded liver sections from a 90-day subchronic toxicity study of GenX conducted in mice. Differentially expressed genes were identified for each treatment group, and gene set enrichment analysis was conducted using gene sets that represent biological processes and known canonical pathways. Peroxisome signaling and fatty acid metabolism were among the most significantly enriched gene sets in both sexes at 0.5 and 5 mg/kg GenX; no pathways were enriched at 0.1 mg/kg. Gene sets specific to the PPARα subtype were significantly enriched. These findings were phenotypically anchored to histopathological changes in the same tissue blocks: hypertrophy, mitoses, and apoptosis. In vitro PPARα transactivation assays indicated that GenX activates mouse PPARα. These results indicate that the liver changes observed in GenX-treated mice occur via a mode of action (MOA) involving PPARα, an important finding for human health risk assessment as this MOA has limited relevance to humans.

INTRODUCTION AND OBJECTIVE:Penile cancer is a rare cancer with an incidence of 1/100,000 cases in the EU and USA. Recent Irish data reports an incidence of 1.45/100,000 cases per year. Approximatel...

Introduction Gender bias and sexual discrimination (GBSD) have been widely recognized across a range of fields and are now part of the wider social consciousness. Such conduct can occur in the medical workplace, with detrimental effects on recipients. The aim of this review was to identify the prevalence and impact of GBSD in orthopaedic surgery, as well as mitigating strategies. Method A systematic review was conducted by searching Medline, EMCARE, CINAHL, PsycINFO, and the Cochrane Library Database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Original research papers pertaining to the prevalence and impact of GBSD, or mitigating strategies, within orthopaedics were reviewed. Result Of 570 papers, 27 were eligible for inclusion. These were published between 1998 and 2020. 13 papers discussed the prevalence of GBSD, 13 related to the impact of these behaviours, and six discussed mitigating strategies. GBSD was found to be common in the orthopaedic workplace, with all sources showing women to be the subjects. Effects include poor workforce representation, lower salaries, and less career success for women in orthopaedics. Mitigating strategies in the literature are focused on providing female role models, mentors, and educational interventions. Conclusion GBSD is common in orthopaedic surgery, with a substantial impact on sufferers. A small number of mitigating strategies have been tested but these are limited in their scope. As such, the orthopaedic community is obliged to participate in more thoughtful and proactive strategies that mitigate against GBSD, by improving female recruitment and retention within the specialty. Take-home Message Gender bias and sexual discrimination remain common within orthopaedics. The international orthopaedic community is obliged to do more to tackle this problem.

Cerebrovascular pathology is common in aging and Alzheimer's disease (AD). The microvasculature is particularly vulnerable, with capillary-level microhemorrhages coinciding with amyloid beta deposits in senile plaques. In the current analysis, we assessed the relationship between cerebral microvessels and the neuritic component of the plaque in cortical and hippocampal 50- to 200-μm sections from 11 AD, 3 Down syndrome, and 7 nondemented cases in neuritic disease stages 0-VI. We report that 77%-97% of neuritic plaques are perivascular, independently of disease stage or dementia diagnosis. Within neuritic plaques, dystrophic hyperphosphorylated tau-positive neurites appear as clusters of punctate, bulbous, and thread-like structures focused around capillaries and colocalize with iron deposits characteristic of microhemorrhage. Microvessels within the neuritic plaque are narrowed by 1.0 ± 1.0 μm-4.4 ± 2.0 μm, a difference of 16%-65% compared to blood vessel segments with diameters 7.9 ± 2.0-6.4 ± 0.8 μm (p0.01) outside the plaque domain. The reduced capacity of microvessels within plaques, frequently below patency, likely compromises normal microlocal cerebrovascular perfusion. These data link the neuritic and amyloid beta components of the plaque directly to microvascular degeneration. Strategies focused on cerebrovascular antecedents to neuritic dystrophy in AD have immediate potential for prevention, detection, and therapeutic intervention.

OBJECTIVE To determine associations between geographic accessibility, delivery volume, and obstetric outcomes. METHODS Population-based cohort study of linked hospital administrative, census, and geospatial data (2006-2009) from all Canadian jurisdictions except Quebec. Perinatal mortality and major maternal morbidity/mortality were compared across categories of road distance and hospital delivery volume. RESULTS Among 820 761 mothers delivering 827 504 neonates, travel distance had minimal effect on perinatal mortality. Compared with mothers travelling 0-9 km, the odds of adverse maternal outcomes was decreased for women travelling modest distances (20-49 km, odds ratio, 0.80 [95% confidence interval, 0.75-0.86]), and increased thereafter (50-99 km, 0.99 [0.89-1.10]; 200-299 km, 1.44 [1.10-1.87]; >400 km, 2.22 [1.06-4.63]). Relative to high-volume hospitals (>2500 deliveries/year), adverse maternal outcomes were less likely for hospitals with 1000-2499 (0.90 [0.86-0.95]), and roughly equivalent for hospitals with 200-499 (1.34 [1.22-1.48]) and 500-999 (1.27 [1.17-1.39]) deliveries/year. Odds of perinatal mortality ranged from 1.04 (0.73-1.49; 100-199 deliveries/year) to 1.50 (1.04-2.16; 50-99 deliveries/year); the pattern did not suggest causality. CONCLUSION Maternal outcomes worsen when travel distance is greater than 200 km, and improve when delivery volume exceeds 1000 deliveries per year.

OBJECTIVE To investigate whether there was an association between chronic periodontitis (CP) and reduced respiratory function. METHODS A group of dentate 58- to 72-year-old men in Northern Ireland had a comprehensive periodontal examination. Parallel to the periodontal examination, participants completed questionnaires gathering information on their medical history, social circumstances, demographic background and tobacco use. A physical examination assessed anthropometric measures. Fasting blood samples were obtained and analysed for high-sensitivity C-reactive protein (hs-CRP). Spirometry measures were performed using a wedge bellows spirometer (Vitalograph S Model). The primary outcome variable of interest was the percentage predicted forced expiratory volume in one-second (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders and a regression-based mediation analysis. RESULTS A total of 1,380 men were included in the analysis. The mean age was 63.7 years (SD 3.0). Multiple linear regression analysis showed that a doubling in mean clinical attachment loss (CAL) equated to a -3.33% (95% CI: -4.80, -1.86), p

Background The aim of this systematic review was to outline the prevalence and impact of Gender bias and sexual discrimination (GBSD) in orthopaedics, and to investigate interventions countering such behaviours. Method Original research papers pertaining to the prevalence and impact of gender bias or sexual discrimination, or mitigating strategies in orthopaedics, were suitable for inclusion. PRISMA guidelines were adhered to in this review. Results Of 570 papers, 27 were eligible for inclusion. A total of 13 papers discussed the prevalence of GBSD, whilst 13 related to the impact of these behaviours, and 6 discussed mitigating strategies. GBSD were found to be prevalent in the orthopaedic workplace, with all sources showing females to be the victims. The impact of GBSD includes poor workforce representation, lower salaries, barriers to career progression, and reduced academic output for females in orthopaedics. Mitigating strategies in the literature are focussed on encouraging females to apply for orthopaedic training programmes, by providing female role models, mentors, and educational interventions. Conclusions GBSD are highly prevalent in orthopaedic surgery, impacting females at all stages of their careers. Mitigating strategies have been tested but are limited in their scope. As such, the orthopaedic community as a whole is obliged to do more to tackle GBSD.

Modern society requires large amounts of materials which lead to emissions of greenhouse gases. Effective climate policy should focus on not just energy efficiency but material efficiency as well. Exergy analysis is a powerful metric used to identify opportunities for efficiency improvement in industrial resource flow systems. Exergy offers a single unified measure of energy and material resources and indicates the real thermodynamic value of these resources, but the method suffers from a lack of comprehensive specific material chemical exergy datasets. The variety of different materials used in the global resource supply chain necessitates a combination of exergy calculation approaches. These approaches are combined into a single exergy calculator tool with over 1400 substances in the dataset. The chemical exergy values computed for key materials typically differ by less than 10% from values estimated in literature. The calculator is used in a case study of the upstream global material supply chain in 2013. The exergy resource map is visualized in a Sankey diagram and is found to be 72% resource efficient with 170 EJ of combined exergy losses and destruction. Further analysis is conducted on the refining, utilities, and industry sectors which are found to be 72%, 44%, and 50% resource efficient, respectively. Their combined losses and destruction are 15, 101, and 54 EJ, respectively. This study and the calculator developed provide a comprehensive dataset of chemical exergy values for a wide range of materials and can be applied in a variety of studies using exergy analysis.

Background: Microdissection testicular sperm extraction (mTESE) is the gold standard approach in sperm retrieval in men with non-obstructive azoospermia (NOA). The purpose of the study was to assess the outcomes for Irish men who have undergone mTESE with a single surgeon. Methods: This is a retrospective, single cohort study. Thirty-four patients underwent mTESE between September 2015 and June 2019. A p

Global glass production grew to 150 million tonnes (Mt) in 2014, equating to approximately 21 kg per person. Producing this glass is energy intensive and contributes annual CO2 emissions of some 86Mt. An accurate map of the global glass supply chain is needed to help identify emissions mitigation options from across the supply chain, including process energy efficiency and material efficiency options. This map does not yet exist, so we address this knowledge gap by tracing the production chain from raw materials to end of life and producing a global Sankey diagram of container and flat glass making for 2014. To understand future demand for flat glass we also model the stocks of glass in vehicles and buildings. The analysis shows the relative scale of glass flows and stocks worldwide and provides a baseline for future study of the emission mitigation potential of energy and material efficiency of manufacturing with glass.

Case A 72-year-old man underwent intramedullary nailing of a humeral diaphysis fracture with passage through an unrecognized pathologic fracture. Four months later, a biopsy of a soft-tissue mass in the arm revealed pleomorphic undifferentiated sarcoma. Only after local recurrence and forequarter amputation was the story of a pathologic fracture through undifferentiated pleomorphic sarcomas of bone clear. The patient developed metastatic disease and died after 2 years postoperatively. Discussion Orthopaedic surgeons should consider sarcoma when assessing patients with fractures of unknown etiology and an inappropriate mechanism because the placement of an intramedullary device through a sarcoma of bone has consequences.

Introduction Focused TUS guidance is considered essential when undertaking invasive pleural procedures as it has been proven to improve safety and reduce complications. There is a need for robust assessment methods to assess competence in TUS to facilitate safe pleural intervention. We aimed to develop and validate a bespoke assessment tool corresponding to those skills associated with the most basic level of practice, recently defined as an emergency level operator in the BTS Training Standards for TUS.1 Method The assessment tool allowed comprehensive, multimodal assessment of competence by undertaking an ultrasound examination of a patient followed by identification of ultrasound images and clips. Candidates were enrolled from two distinct groups – trainees with a workplace based assessment of competence in a pleural procedure but with no formal ultrasound training, and those who had undertaken some TUS training without yet having been entrusted to perform TUS unsupervised provided an acceptable surrogate for an emergency level operator. Results Twenty-seven candidates were enrolled by two examiners based in Belfast and Oxford between February and November 2019. This included twelve candidates in the inexperienced and fifteen in the experienced group. Mean score of the inexperienced group was 44.3 (95% CI 39.2–49.4) versus 74.9 (95% CI 72.8–77) in the experienced group. Mean difference was 30.7 (95% CI 24.7–36.7; p Standard setting using a borderline regression method for the first section of the assessment tool and a modified Angoff method for the second resulted in a pass mark of 61. Discussion This assessment tool has the potential to discriminate appropriate TUS performance at the level of an emergency operator and requires further evaluation. It is unlikely that this tool can define competence in isolation but could form part of a broader, multifaceted assessment including mentorship, a logbook and regular assessment of skill application by way of directly observed procedures (DOPs). Further work may delineate the minimum number of TUS scans that correlates with successful exam performance for a majority of candidates, however this has not yet been identified as learning curves exhibit significant variation amongst individuals and the project was not adequately powered to address this.

Numerous studies have been performed in food traceability, but there is no common, clear understanding of its theoretical concepts which are scattered and disjointed across the literature. Existing studies are mainly concerned with practical implementation and the theoretical concepts derive from that approach. As a result, various definitions, classifications and inconsistent principles have been proposed which hamper clear understanding and further development of the field. Thus, this study aims to coalesce the proposed and emergent fundamental concepts of food traceability in a generic theoretical framework. To this end, we have used an iterative approach to review and synthesize the papers in the field most relevant to our enquiry, consolidate proposed drivers and beneficiaries, highlight the main typologies, and as a result, propose a revised definition of food traceability and four associated principles. Different information is recorded in a traceability system, depending on the underlying drivers, for example, legislation, food safety, sustainability, or consumer satisfaction. In this paper traceability approaches are categorised by an iterative typology, as internal or external and the implementation of traceability systems is organised according to four consolidated principles: identification, data recording, data integration and accessibility. It is proposed that the collation of existing approaches into a cohesive theoretical framework will improve understanding and the effective implementation of food traceability systems.

Objective To assess patient-reported outcomes of oncoplastic penile reconstruction using standardized questionnaires. Whilst organ-preserving penile cancer surgery has evolved, aiming to preserve genital function, reduce psychological morbidity of radical penectomy, and maximise patient quality of life, few studies have evaluated patients’ final perceptions. Methods Following ethical approval, patients post partial/radical glansectomy with reconstruction 2016-2019, under a single surgeon, were identified. Patients were posted a modified Index of Male Genital Image, the IIEF-5, a customised questionnaire exploring outcomes of urinary and sensory function and the EORTC QLQ-C30 to complete and return. Questionnaires were nonidentifiable, however study ID linked responses to the procedure performed. Results A total of 130 questionnaires were received from 35 patients post penile reconstruction, giving a response rate of 71.4% (35/49). Mean time from surgery was 22 months (4-51), and mean age 61 years (31–79). The majority (82.4%, n = 28) were satisfied or felt neutral about the appearance of their genitalia. High satisfaction with postprocedure urinary function was reported; 85.3% (29/34) could void from a standing position and 79.4% (27/34) reported little or no spraying of urine. Nineteen patients (55.89%) were sexually active, with mean IIEF-5 scores of 14.9 (5-25) (partial glansectomy) and 15.8 (5-25) (radical glansectomy). Mean QoL over past week on 7-point EORTC QLQ-C30 scale was 5.88 (3-7). Conclusion We report good aesthetic and functional outcomes in a unique study exploring penile cancer surgery patient-reported outcome measures. These results strongly support phallus-preserving phallic-preserving strategies as the standard of care in eligible patients undergoing penile cancer surgery.

A future energy system for road transport requires optimised energy use and primary energy decarbonisation to achieve global CO2 reduction goals. Simultaneously decarbonising transport with other sectors of the economy places additional demands on limited low-carbon energy sources, requiring efficient processes within a fuel pathway from energy source to -energy use. Battery electric vehicles (BEVs) and fuel-cell electric vehicles (FCEVs) are low-carbon options that reduce tailpipe emissions, but differ in overall efficiency, associated carbon intensity, and cost. Current commercialised technologies, as well as theoretical maximums, are aggregated in a stochastic analysis to quantify the energy efficiency and CO2 differences for BEV and FCEV energy systems. Carbon capture and storage improves source-to-wheels CO2 intensity for hydrogen produced from steam methane reformation (27 gCO2/km with carbon capture and store and 140 gCO2/km without for light-duty FCEVs). Light-duty BEVs have a lower CO2 intensity (11 gCO2/km) using decarbonised grid electricity and are 65% more efficient than light-duty FCEVs using grid energy. These effects translate to heavy-good vehicles but with added complexity. In a maximised trailer volume scenario, electric and fuel-cell heavy-good vehicles have similar projected carbon intensities from a natural gas primary energy source, but electric heavy-good vehicle using conventional battery systems or an electric road system are able to achieve a 55% and 67% carbon reduction (gCO2/m3 km) compared to fuel-cell heavy-goods vehicles, respectively.

Small intestinal (SI) tumors are relatively uncommon outcomes in rodent cancer bioassays, and limited information regarding chemical-induced SI tumorigenesis has been reported in the published literature. Herein, we propose a cytotoxicity-mediated adverse outcome pathway (AOP) for SI tumors by leveraging extensive target species- and site-specific molecular, cellular, and histological mode of action (MOA) research for three reference chemicals, the fungicides captan and folpet and the transition metal hexavalent chromium (Cr(VI)). The gut barrier functions through highly efficient homeostatic regulation of SI epithelial cell sloughing, regenerative proliferation, and repair, which involves the replacement of up to 1011 cells per day. This dynamic turnover in the SI provides a unique local environment for a cytotoxicity mediated AOP/MOA. Upon entering the duodenum, cytotoxicity to the villous epithelium is the molecular initiating event, as indicated by crypt elongation, villous atrophy/blunting, and other morphologic changes. Over time, the regenerative capacity of the gut epithelium to compensate declines as epithelial loss accelerates, especially at higher exposures. The first key event (KE), sustained regenerative crypt proliferation/hyperplasia, requires sufficient durations, likely exceeding 6 or 12 months, due to extensive repair capacity, to create more opportunities for the second KE, spontaneous mutation/transformation, ultimately leading to proximal SI tumors. Per OECD guidance, biological plausibility, essentiality, and empirical support were assessed using modified Bradford Hill considerations. The weight-of-evidence also included a lack of induced mutations in the duodenum after up to 90 days of Cr(VI) or captan exposure. The extensive evidence for this AOP, along with the knowledge that human exposures are orders of magnitude below those associated with KEs in this AOP, supports its use for regulatory applications, including hazard identification and risk assessment.

PurposeOsteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease.Experimental designTo overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline.ResultsCouplingin vitrohigh-throughput drug screens on low-passage and established cell lines within vivovalidation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity.ConclusionsThese collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.

The advancement of intracytoplasmic sperm injection (ICSI) has allowed azoospermic men previously deemed infertile to father their own biological offspring provided that sperm can be retrieved from the testicles. Although a number of surgical sperm retrieval techniques can be utilized to obtain sperm for the ICSI cycle, the specific technique used depends on the underlying cause of azoospermia.

Objective: The objective of this study was to evaluate the rising trend in the incidence and mortality of renal cell carcinoma in Ireland. Methods: Data from the National Cancer Registry of Ireland on primary adenocarcinomas of the kidney from 2003 to 2013 were evaluated. Statistical analysis was performed on the data using IBM SPSS statistics V24 software package and Microsoft Excel Software. Results: There were 3801 cases of adenocarcinoma of the kidney with 29% of tumours (n=1103) being found incidentally. The age-adjusted incidence rate of renal cell carcinoma in 2003 was 4.66 per 100,000 women and 8.78 per 100,000 men. These figures have risen to 5.78 and 13.14 in 2013, respectively. There was an annual percentage change of +2.2% for women and +4.1% for men from the years 2003 to 2013. For both sexes the age-standardised all-cause mortality rate for renal adenocarcinoma increased from 1.07 per 100,000 in 2003 to 4.32 ± 0.06 per 100,000 in 2013, an annual percentage change of +15%. Age-adjusted mortality rates in the female population in Ireland increased from 0.78 to 2.66, an annual percentage change of +13.1% and from 1.41 to 6.04 in men, an annual percentage change of +15.8%. Conclusion: There is a paradox emerging in Ireland, with both rising survival rates for renal cell carcinoma and rising mortality rates. While the increased incidence of renal cell carcinoma in Ireland can be attributed somewhat to the increased use of various imaging modalities, it may also be attributed to the significant rise in modifiable risk factors as seen in other developed countries, namely hypertension, obesity, and smoking. Level of evidence: 2c

In 1963, the corporation of the city of Glasgow approved plans for 96 km of motorways. To date, 2017, 48 km have been constructed. These are on a grand scale, with 5 km of dual five-lane, 2 km of dual four-lane and over 25 km of dual three-lane motorways. Traffic flows as high as 198 000 vehicles/d have been recorded. Savings of time, accidents and fuel have been realised as a result. The main focus of this briefing paper is the geometric design of the motorways. Scott Wilson Kirkpatrick and Partners, consulting engineers, were responsible for this work. Much emphasis is placed on motorway traffic volumes. This is because road user benefits are directly related to the amount of traffic diverted to the motorways. Also, predicted traffic was a primary factor in the outline design of the motorways.

Resource efficiency is an instrumental mitigation option in the steel industry but, existing studies have failed to provide a global analysis of the sector's energy and material use. Despite the interactions between energy and materials in steelmaking, recent studies investigate each of these resources in isolation, providing only partial insight into resource efficiency. This study analyses the latest, most comprehensive resource data on the global steel industry and quantifies the savings associated with reducing this through energy- and material-saving measures. Three production routes are investigated for 2010, namely the blast furnace/basic oxygen furnace (ore-based); direct reduction/electric arc furnace; scrap-based electric arc furnace routes (secondary). The sector's resource efficiency – accounting for energy and materials – is expressed in exergy and measured at two levels, that of production routes and plants. The results show that the sector is 32.9% resource-efficient and that secondary steelmaking is twice as efficient (65.7%) as ore-based production (29.1%). Energy-saving options, such as the recovery of off-gases, can save about 4 EJ/year (exergy). Materialsaving options, such as yield improvements, can deliver just under 1 EJ/year extra. A global shift from average ore-based production to best available operation can save up to 6.4 EJ/year; a 26% reduction in global exergy input to steelmaking. Shifting to secondary steelmaking can save 8 EJ/year, limited only by the need to still produce half of steel from ore in 2050. Resource efficiency, measured in exergy, provides stakeholders with an instrument that treats energy and material efficiency measures on an equal footing.

Testicular torsion is the most concerning underlying cause of acute scrotal pain that can lead to loss of the affected testicle. Whether a torted testicle can be salvaged surgically is directly affected by prompt presentation and diagnosis. This study aims to evaluate the awareness of testicular torsion amongst Irish parents and evaluate their response to a potential torsion. An anonymous questionnaire was distributed to parents attending general paediatric clinics and an acute paediatric unit in two paediatric tertiary referral centres. SPSS statistical analysis software was used to perform multivariant analysis of the data. There were 242 completed surveys. Fifty-six percent of responders had an awareness of torsion. In the event of an episode of severe testicular pain parents who were aware of testicular torsion were 4 times more likely to present immediately than those who had no awareness of torsion (OR 4.2, 95% CI 1.4–12.2, P

Training locomotor central pattern-generating networks (CPGs) through arm and leg cycling improves walking in chronic stroke. These outcomes are presumed to result from enhanced interlimb connectivity and CPG function. The extent to which rhythmic arm training activates interlimb CPG networks for locomotion remains unclear and was assessed by studying chronic stroke participants before and after 5 wk of arm cycling training. Strength was assessed bilaterally via maximal voluntary isometric contractions in the legs and hands. Muscle activation during arm cycling and transfer to treadmill walking were assessed in the more affected (MA) and less affected (LA) sides via surface electromyography. Changes to interlimb coupling during rhythmic movement were evaluated using modulation of cutaneous reflexes elicited by electrical stimulation of the superficial radial nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Clinical function tests assessed walking, balance, and motor function. Results show significant changes in function and neurophysiological integrity. Training increased bilateral grip strength, force during MA plantarflexion, and muscle activation. “Normalization” of cutaneous reflex modulation was found during arm cycling. There was enhanced activity in the dorsiflexor muscles on the MA side during the swing phase of walking. Enhanced interlimb coupling was shown by increased modulation of MA soleus stretch reflex amplitudes during arm cycling after training. Clinical evaluations showed enhanced walking ability and balance. These results are consistent with training-induced changes in CPG function and interlimb connectivity and underscore the need for arm training in the functional rehabilitation of walking after neurotrauma.NEW & NOTEWORTHY It has been suggested but not tested that training the arms may influence rehabilitation of walking due to activation of interneuronal patterning networks after stroke. We show that arm cycling training improves strength, clinical function, coordination of muscle activity during walking, and neurological connectivity between the arms and the legs. The arms can, in fact, give the legs a helping hand in rehabilitation of walking after stroke.

Background Serum interleukin 6 (IL-6), chemokine ligand 2 (CCL2), C-reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies. Hypothesis/objectives To determine whether increases in serum IL-6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies. Animals Forty-four client-owned dogs with clinical evidence of liver disease and 10 healthy purpose-bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy. Methods Measurement of serum IL-6, CCL2, CRP, AST, and ALT before scheduled liver biopsy and evaluation of liver histopathology using the METAVIR scoring system used in human medicine, blinded to clinical presentation. Results Median serum IL-6 was approximately twice as high in dogs with high fibrosis scores (15.5 pg/mL; range, 1.4 to 235 pg/mL) compared to dogs with low fibrosis scores (7.6 pg/mL; range, 1.4 to 148.1 pg/mL), with marginal significance (P = .05). Median serum CCL2 was significantly higher in dogs with active necroinflammation (444 pg/mL; range, 144 to 896 pg/mL) compared to dogs without detectable necroinflammation (326 pg/mL; range, 59 to 1692 pg/mL; P = .008), but with considerable overlap between groups. Neither serum CRP nor AST:ALT ratios were significantly different based on fibrosis or necroinflammatory scores. Conclusions and clinical importance Because of substantial variability among dogs, single measurements of IL-6 and CCL2 have limited diagnostic utility for identifying fibrosis or necroinflammation, respectively, in dogs with various chronic liver diseases. The value of these biomarkers should be explored further in monitoring response to treatment in individual dogs with chronic hepatopathies.

This project quantified the impact that voluntary reformulation efforts of the food industry had on the Irish population's nutrient intake. Nutrient composition data on reformulated products were collected from 14 major food companies for two years, 2005 and 2012. Probabilistic intake assessments were performed using the Irish national food consumption surveys as dietary intake data. The nutrient data were weighted by market shares replacing existing food composition data for these products. The reformulation efforts assessed, significantly reduced mean energy intakes by up to 12 kcal/d (adults), 15 kcal/d (teens), 19 kcal/d (children) and 9 kcal/d (pre-schoolers). Mean daily fat intakes were reduced by up to 1.3 g/d, 1.3 g/d, 0.9 g/d and 0.6 g/d, saturated fat intakes by up to 1.7 g/d, 2.3 g/d, 1.8 g/d and 1 g/d, sugar intakes by up to 1 g/d, 2 g/d, 3.5 g/d and 1 g/d and sodium intakes by up to 0.6 g/d, 0.5 g/d, 0.2 g/d, 0.3 g/d for adults, teenagers, children and pre-school children, respectively. This model enables to assess the impact of industry reformulation amongst Irish consumers' nutrient intakes, using consumption, food composition and market share data.

Objective:Otitis externa is a common presentation to secondary care otolaryngology clinics. Despite this, few studies have investigated the microbiology and antimicrobial resistance of otitis externa. This study aimed to examine these issues.Methods:Analysis identified 302 swabs taken from 217 patients (100 male, 117 female), between 1 January 2015 and 30 March 2016, at our rapid access otolaryngology clinic.Results:In total, 315 organisms were isolated; the most frequent was Pseudomonas aeruginosa (31.1 per cent), followed by candida species (22.9 per cent) and Staphylococcus aureus (11.7 per cent). P aeruginosa was sensitive to ciprofloxacin in 97.7 per cent of cases and to gentamicin in 78.4 per cent.Conclusion:Compared with studies worldwide, the relative proportions of different organisms causing otitis externa and the patterns of antimicrobial resistance differ. Increasing resistance of P aeruginosa to aminoglycosides demonstrates a changing pattern of antimicrobial resistance that has not been previously reported. Reassuringly, quinolone antibiotics remain highly effective when treating P aeruginosa.

Chemical products are ubiquitous in modern society. The chemical sector is the largest industrial energy consumer and the third largest industrial emitter of carbon dioxide. The current portfolio of mitigation options for the chemical sector emphasizes upstream "supply side" solutions, whereas downstream mitigation options, such as material efficiency, are given comparatively short shrift. Key reasons for this are the scarcity of data on the sector's material flows, and the highly intertwined nature of its complex supply chains. We provide the most up to date, comprehensive and transparent data set available publicly, on virgin production routes in the chemical sector: from fossil fuel feedstocks to chemical products. We map global mass flows for the year 2013 through a complex network of transformation processes, and by taking account of secondary reactants and by-products, we maintain a full mass balance throughout. The resulting data set partially addresses the dearth of publicly available information on the chemical sector's supply chain, and can be used to prioritise downstream mitigation options.

Basal cell carcinoma is the most commonly occurring cancer worldwide but it is rarely seen in non-sun-exposed areas of the body such as the scrotum.1 Basal cell carcinomas account for 5–10% of all scrotal tumours.2,3 Scrotal basal cell carcinoma is considered more aggressive with higher rates of metastasis versus non-scrotal basal cell carcinoma.1 Gorlin syndrome or nevoid basal cell carcinoma syndrome is an autosomal dominant condition characterised by the development of multiple basal cell carcinomas at a young age.4,5 Prevalence of nevoid basal cell carcinoma syndrome is reported to range from 1 in 57,000 to 1 in 164,000.5 We present the case of a 58-year-old gentleman with a 3-month history of bleeding scrotal and penile lesions. These lesions were excised with 2 cm margins and without complication. Histology showed surface ulceration with basaloid infiltrating tumour extending into the dermis. Given the potential for a very high rate of tumour occurrence within individuals, surgical management of basal cell carcinomas can result in significant, lifestyle-limiting disfigurement.5 As understanding of the pathogenesis of nevoid basal cell carcinoma syndrome has advanced, a number of targeted therapies have been developed.5 Vismodegib targets the Hedgehog signalling pathway and is used in the treatment of locally advanced and metastatic basal cell carcinomas. This represents a rare case of basal cell carcinoma of the scrotum associated with nevoid basal cell carcinoma syndrome caused by a de novo mutation. It is not clear from the literature whether incidence of scrotal tumours is increased in Gorlin syndrome but given the increased risk of basal cell carcinoma elsewhere, it may be prudent for those with known Gorlin syndrome to regularly examine the scrotal skin along with recommended frequent dermatologic surveillance. Level of evidence: 5.

In this study, we explored the effects of a longer term application, up to 12 weeks, of photobiomodulation in normal, naïve macaque monkeys. Monkeys (n = 5) were implanted intracranially with an optical fibre device delivering photobiomodulation (red light, 670 nm) to a midline midbrain region. Animals were then aldehyde-fixed and their brains were processed for immunohistochemistry. In general, our results showed that longer term intracranial application of photobiomodulation had no adverse effects on the surrounding brain parenchyma or on the nearby dopaminergic cell system. We found no evidence for photobiomodulation generating an inflammatory glial response or neuronal degeneration near the implant site; further, photobiomodulation did not induce an abnormal activation or mitochondrial stress in nearby cells, nor did it cause an abnormal arrangement of the surrounding vasculature (endothelial basement membrane). Finally, because of our interest in Parkinson's disease, we noted that photobiomodulation had no impact on the number of midbrain dopaminergic cells and the density of their terminations in the striatum. In summary, we found no histological basis for any major biosafety concerns associated with photobiomodulation delivered by our intracranial approach and our findings set a key template for progress onto clinical trial on patients with Parkinson's disease.

The Refugio Oil Spill occurred on May 19, 2015, due to the failure of an underground pipeline, owned and operated by a subsidiary of Plains All-American Pipeline near Highway 101 in Santa Barbara County. The Responsible Party initially estimated the amount of crude oil released at about 104,000 gallons, with 21,000 gallons reaching the ocean. A Unified Command (UC) was established consisting of Incident Commanders from the U.S. Coast Guard (USCG), California Department of Fish and Wildlife (CDFW) Office of Spill Prevention and Response (OSPR), Santa Barbara County, and Plains Pipeline with additional participation by the U.S. Environmental Protection Agency and California State Parks. Within hours, the CDFW closed fisheries and the following day Governor Brown declared a state of emergency for Santa Barbara County. The released oil caused heavy oiling of both on and offshore areas at Refugio State Beach and impacted other areas of Santa Barbara and Ventura. A number of factors created unique challenges for the management of this response. In addition to direct natural resource impacts, the closure of beaches and fisheries occurred days before the Memorial Day weekend resulting in losses for local businesses and lost opportunities for the public. The Santa Barbara community, with its history with oil spills and environmental activism, was extremely concerned and interested in involvement, including the use of volunteers on beaches. Also this area of the coast has significant tribal and archeologic resources that required sensitive handling and coordination. Finally, this area of California’s coast is a known natural seep area which created the need to distinguish spilled from ‘naturally occurring’ oil. Most emergency responses, including oil spills, follow a similar pattern of command establishment, response and cleanup phases, followed by non-response phase monitoring, cleanup and restoration. This paper will analyze the Refugio oil spill response in three primary focus areas: 1) identify the ways in which this spill response was unique and required innovative and novel solutions; 2) identify the ways in which this response benefited from the ‘lessons’ learned from both the Deepwater Horizon and Cosco Busan oil spills; and 3) provide a summary of OSPR’s response evaluation report for Refugio, with specific focus on how the lessons learned and best practices will inform future planning efforts within California.

We agree with Zedan that sudden sensorineural hearing loss is an ear, nose, and throat emergency, and we emphasised this in our article.12 Such patients should be dealt with promptly with the aim of preserving cochlear function. Additional treatments are warranted for this devastating condition. New drugs are currently …

A 9 mo old female intact golden retriever presented for evaluation of chronic lethargy and decreased appetite. The serum biochemistry profile revealed increased liver enzymes consistent with a mixed hepatocellular and cholestatic pattern. A multiphase computed tomography angiography was performed to evaluate for a portosystemic shunt. Numerous hyperattenuating nodules were identified throughout the liver on the noncontrast-enhanced series. Histologic evaluation of percutaneous needle biopsy samples of a liver nodule showed a rare form of hepatitis called lobular dissecting hepatitis. Lobular dissecting hepatitis should be considered as a differential in young dogs with precontrast hyperattenuating hepatic nodules on noncontrast-enhanced computed tomography.

Squamous cell carcinoma has been reported in a variety of bird species, most commonly psittacine and gallinaceous birds. The long-term prognosis in nongallinaceous birds is generally poor if complete surgical excision is not possible. Squamous cell carcinoma of the rhinotheca was diagnosed in a 34-year-old timneh African grey parrot (Psittacus timneh) with a 2-year history of beak abnormalities. No evidence of metastasis or local invasion were found on results of radiographs or computed tomography scan. The bird was treated with surgical debulking and palliative megavoltage radiation therapy. After 4 radiation treatments, the affected tissue was necrotic and was debrided to reveal healthy granulation tissue. The bird died approximately 7 months after diagnosis and 4 months after cessation of radiation treatment. At the time of death, a small scab lesion remained at the left oral commissure, but no visible tumor regrowth was evident. A postmortem examination was not performed, however, and tumor recurrence could not be ruled out in this bird.