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Concrete slabs are widely used in modern railways to increase the inherent resilient quality of the tracks, provide safe and smooth rides, and reduce the maintenance frequency. In this paper, the elastic performance of a novel slab trackform for high-speed railways is investigated using three-dimensional finite element modelling in Abaqus. It is then compared to the performance of a ballasted track. First, slab and ballasted track models are developed to replicate the full-scale testing of track sections. Once the models are calibrated with the experimental results, the novel slab model is developed and compared against the calibrated slab track results. The slab and ballasted track models are then extended to create linear dynamic models, considering the track geodynamics, and simulating train passages at various speeds, for which the Ledsgård documented case was used to validate the models. Trains travelling at low and high speeds are analysed to investigate the track deflections and the wave propagation in the soil, considering the issues associated with critical speeds. Various train loading methods are discussed, and the most practical approach is retained and described. Moreover, correlations are made between the geotechnical parameters of modern high-speed rail and conventional standards. It is found that considering the same ground condition, the slab track deflections are considerably smaller than those of the ballasted track at high speeds, while they show similar behaviour at low speeds. [ABSTRACT FROM AUTHOR]

Purpose. Multidisciplinary rehabilitation programmes providing exercise, nutrition support, education, and peer support can effectively meet the rehabilitation needs of upper gastrointestinal (UGI) cancer survivors. This study aimed to explore the experiences of participants who engaged in a telehealth, multidisciplinary rehabilitation programme for UGI cancer survivors. Methods. This single-arm feasibility study recruited participants who completed curative treatment for UGI cancer. Participants (n = 10, male = 9) aged 58–76 years were 5–17 months postsurgery. A 12-week telehealth rehabilitation programme was delivered via video call, consisting of group resistance training, remotely monitored aerobic training, 1 : 1 dietary counselling, 1 : 1 physiotherapy support, and group education sessions. Independent researchers conducted semistructured interviews at postintervention assessments. Transcripts were analysed using reflexive thematic analysis (RTA). Results. RTA of participant transcripts generated three overarching themes: (1) ReStOre@Home impacted psychosocial and physical needs by addressing a broad and meaningful gap in services, (2) paving a pathway towards prosperity, and (3) contrasting experiences with using technology. Participants' preferences and recommendations for future telehealth programmes were discussed. Conclusions. A telehealth multidisciplinary rehabilitation programme supported participants in physical and psychosocial recovery. Qualitative analysis identified an important ongoing need for some in-person care and provided detailed insights into participant experiences during telehealth-delivered rehabilitation. [ABSTRACT FROM AUTHOR]

Objectives: To determine the causative organisms, clinical features and outcome of canine infective endocarditis in the UK. Materials and Methods: Medical records of three veterinary referral hospitals were searched for dogs with infective endocarditis between December 2009 and December 2019. Signalment, clinical signs, causative organism, valve affected, treatment and survival data were recorded. Results: Seventy‐seven cases with possible or definite infective endocarditis (according to the modified Duke criteria) were included. The majority were large breed (40/77 – 51.9%). There were 47 of 77 (61%) male dogs and the mean age was 7.3 ±3 years. A causative organism was identified in 26 of 77 (33.8%) cases. The most common organisms were Escherichia coli (7/27 – 25.9%), Pasteurella spp. (5/27 – 18.5%), Staphylococcus spp. (4/27 – 14.8%) and Corynebacterium spp. (4/27 – 14.8%). Bartonella spp. were not detected in any patients. The mitral valve was most commonly affected (48/77 – 62.3%). Clinical features were non‐specific, with lethargy being the most common clinical sign observed (53/77 – 68.8%). Fifty‐three dogs (68.8%) survived to discharge. The median survival time post discharge was 425 days (2 to 3650 days). The development of congestive heart failure was associated with a poorer outcome. Cardiac troponin concentration, antithrombotic use and the development of thromboembolism or arrhythmias were not significantly associated with outcome. Clinical Significance: Some dogs with infective endocarditis that survive to discharge can have a long lifespan. The inability to detect an underlying organism is common and Bartonella spp. may be a less prevalent cause of canine infective endocarditis in the UK than in the USA. [ABSTRACT FROM AUTHOR]

Introduction: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in β-oxidation of fatty acids and an increased dependence upon glycolysis. Objectives: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. Methods: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. Results: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. Conclusions: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced β-oxidation. This proposed explanation warrants further research. [ABSTRACT FROM AUTHOR]

A novel numerical methodology is presented to solve the dynamic response of railway bridges under the passage of running trains, considering soil–structure interaction. It is advantageous compared to alternative approaches because it permits, (i) consideration of complex geometries for the bridge and foundations, (ii) simulation of stratified soils, and, (iii) solving the train-bridge dynamic problem at minimal computational cost. The approach uses sub-structuring to split the problem into two coupled interaction problems: the soil–foundation, and the soil–foundation–bridge systems. In the former, the foundation and surrounding soil are discretized with Finite Elements (FE), and padded with Perfectly Match Layers to avoid boundary reflections. Considering this domain, the equivalent frequency dependent dynamic stiffness and damping characteristics of the soil–foundation system are computed. For the second sub-system, the dynamic response of the structure under railway traffic is computed using a FE model with spring and dashpot elements at the support locations, which have the equivalent properties determined using the first sub-system. This soil–foundation–bridge model is solved using complex modal superposition, considering the equivalent dynamic stiffness and damping of the soil–foundation corresponding to each natural frequency. The proposed approach is then validated using both experimental measurements and an alternative Finite Element–Boundary Element (FE–BE) methodology. A strong match is found and the results discussed. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread and increasing use of NOACs in Saudi Arabia, there is a lack of contemporary guidance specific to the region. In particular, guidance on NOAC use in high-risk patients who are more likely to experience bleeding with oral anticoagulant therapy is needed. There is an unmet need for a review of contemporary evidence coupled with expert insights on safe and effective NOAC use in high-risk patients with AF in Saudi Arabia.Research Design and Methods: This article provides a detailed review of contemporary literature on NOAC use in high-risk patients with AF. Additionally, key gaps in the literature are identified and expert insights are shared to guide effective management of patients and the significance of local data is evaluated with respect to challenges in optimizing the use of NOACs.Conclusions: This article provides information that complements and expands on existing reviews and guidelines on NOAC use in patients with AF, with a focus on challenges specific to the Saudi Arabian context with the potential to make a positive contribution to the medical community in Saudi Arabia and in other nations. [ABSTRACT FROM AUTHOR]

Neural development requires the orchestration of dynamic changes in gene expression to regulate cell fate decisions. This regulation is heavily influenced by epigenetics, heritable changes in gene expression not directly explained by genomic information alone. An understanding of the complexity of epigenetic regulation is rapidly emerging through the development of novel technologies that can assay various features of epigenetics and gene regulation. Here, we provide a broad overview of several commonly investigated modes of epigenetic regulation, including DNA methylation, histone modifications, noncoding RNAs, as well as epitranscriptomics that describe modifications of RNA, in neurodevelopment and diseases. Rather than functioning in isolation, it is being increasingly appreciated that these various modes of gene regulation are dynamically interactive and coordinate the complex nature of neurodevelopment along multiple axes. Future work investigating these interactions will likely utilize 'multi‐omic' strategies that assay cell fate dynamics in a high‐dimensional and high‐throughput fashion. Novel human neurodevelopmental models including iPSC and cerebral organoid systems may provide further insight into human‐specific features of neurodevelopment and diseases. [ABSTRACT FROM AUTHOR]

In this work we evaluated a novel microreactor prepared using a surface modified, high surface-to-volume ratio multi-lumen fused silica capillary (MLC). The MLC investigated contained 126 parallel channels, each of 4 μm internal diameter. The MLC, along with conventional fused silica capillaries of 25 μm and 50 μm internal diameter, were treated by (3-aminopropyl)triethoxysilane (APTES) and then modified with gold nanoparticles, of ∼20 nm in diameter, to ultimately provide immobilisation sites for the proteolytic enzyme, trypsin. The modified capillaries and MLCs were characterised and profiled using non-invasive scanning capacitively coupled contactless conductivity detection (sC4D). The sC4D profiles confirmed a significantly higher amount of enzyme was immobilised to the MLC when compared to the fused silica capillaries, attributable to the increased surface to volume ratio. The MLC was used for dynamic protein digestion, where peptide fragments were collected and subjected to off-line chromatographic evaluation. The digestion was achieved with the MLC reactor, using a residence time of just 1.26 min, following which the HPLC peak associated with the intact protein decreased by ＞70%. The MLC reactors behaved similarly to the classical in vitro or in-solution approach, but provided a reduction in digestion time, and fewer peaks associated with trypsin auto-digestion, which is common using in-solution digestion. The digestion of cytochrome C using both the MLC-IMER and the in-solution approach, resulted in a sequence coverage of ∼80%. The preparation of the MLC microreactor was reproducible with ＜2.5% RSD between reactors (n = 3) as determined by sC4D. [ABSTRACT FROM AUTHOR]

Purpose: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing.Methods: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach.Results: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention.Conclusions: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery. [ABSTRACT FROM AUTHOR]

Background: Cats with hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) can have resolution of both left ventricular hypertrophy and CHF. Objectives: To describe the clinical characteristics of cats with transient myocardial thickening (TMT) and CHF compared with a control population of cats without resolution of HCM. Animals: A total of 21 cats with TMT, 21 cats with HCM. Methods: Retrospective study. Clinical records at 4 veterinary centers were searched for TMT cases and a control group of cats with HCM and CHF. TMT was defined as initial maximal left ventricular wall thickness (LVWT) ≥6 mm with left‐sided CHF, with subsequent resolution of CHF, reduction in left atrium/aorta (LA/Ao), and LVWT<5.5 mm. HCM was defined as persistent LVWT ≥6 mm. Results: Cats with TMT were younger (2 [0.4–11.4] years) than cats with HCM (8 [1.6–14] years) (P < 0.0001), and antecedent events were more common (15/21 versus 6/21, respectively) (P = 0.01). In cats with TMT, LVWT normalized from 6.8 [6.0–9.7] mm to 4.8 [2.8–5.3] mm and LA/Ao decreased from 1.8 [1.6–2.3] to 1.45 [1.2–1.7] after a mean interval of 3.3 (95% CI: 1.8–4.7) months. CHF recurred in 1 of 21 TMT and 15 of 21 cats with HCM. Cardiac treatment was discontinued in 20 of 21 cats with TMT and 0 of 21 HCM cats. All cats with TMT survived, whereas 8 of 19 cats with HCM died during the study period. Conclusions and Clinical Importance: TMT occurs in younger cats, and antecedent events are common. The prognosis is better in cats with CHF associated with TMT than HCM. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic and clinical contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with abnormalities of the posterior fossa as the only intracranial abnormality recognized on antenatal ultrasound.Methods: This was a subgroup analysis of the MERIDIAN study of fetuses with abnormalities of the posterior fossa (with or without ventriculomegaly) diagnosed on antenatal ultrasound in women who had MRI within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI is reported, as well as indicators of diagnostic confidence and effects on prognosis and clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data.Results: Abnormalities confined to the posterior fossa according to ultrasound were found in 81 fetuses (67 with parenchymal and 14 with cerebrospinal fluid-containing lesions). The overall diagnostic accuracy for detecting an isolated posterior fossa abnormality was 65.4% for ultrasound and 87.7% for MRI (difference, 22.3% (95% CI, 14.0-30.5%); P < 0.0001). There was an improvement in 'appropriate' diagnostic confidence, as assessed by the score-based weighted average method (P < 0.0001), and a three-fold reduction in 'high confidence but incorrect diagnosis' was achieved using MRI. Prognostic information given to the women changed after MRI in 44% of cases, and the overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 35% of cases.Conclusions: Our data suggest that any woman whose fetus has a posterior fossa abnormality as the only intracranial finding on ultrasound should have MRI for further evaluation. This is on the basis of improved diagnostic accuracy and confidence, which impacts substantially on the prognostic information given to women as well as their clinical management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with either agenesis or hypogenesis of the corpus callosum (referred to collectively as failed commissuration) on antenatal ultrasound.Methods: This was a subgroup analysis of the MERIDIAN study of fetuses with failed commissuration (with or without ventriculomegaly) diagnosed on ultrasound in women who had MRI assessment within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was studied, as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data.Results: In the MERIDIAN cohort, 79 fetuses were diagnosed with failed commissuration on ultrasound (55 with agenesis and 24 with hypogenesis of the corpus callosum). The diagnostic accuracy for detecting failed commissuration was 34.2% for ultrasound and 94.9% for MRI (difference, 60.7% (95% CI, 47.6-73.9%), P < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for ultrasound and 87.5% for MRI, and for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for ultrasound and 92.7% for MRI. There was a statistically significant improvement in 'appropriate' diagnostic confidence when using MRI as assessed by the score-based weighted average method (P < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after MRI and its overall effect on clinical management was 'significant', 'major' or 'decisive' in 35/79 cases (44.3%).Conclusions: Our data suggest that any woman whose fetus has failed commissuration as the only intracranial finding detected on ultrasound should have MRI examination for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with ventriculomegaly (VM) as the only abnormal intracranial finding on antenatal ultrasound.Methods: This was a subgroup analysis of the MERIDIAN study of fetuses with only VM diagnosed on ultrasound in women who had a subsequent MRI examination within 2 weeks and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was reported in relation to the severity of VM. The difference in measurements of trigone size on the two imaging methods and the clinical impact of adding MRI to the diagnostic pathway were also studied.Results: In 306 fetuses with VM, ultrasound failed to detect 31 additional brain abnormalities, having an overall diagnostic accuracy of 89.9% for ultrasound, whilst MRI correctly detected 27 of the additional brain abnormalities, having a diagnostic accuracy of 98.7% (P < 0.0001). There were other brain abnormalities in 14/244 fetuses with mild VM on ultrasound (diagnostic accuracy, 94.3%) and MRI correctly diagnosed 12 of these (diagnostic accuracy, 99.2%; P = 0.0005). There was a close agreement between the size of trigones measured on ultrasound and on MRI, with categorical differences in only 16% of cases, showing that MRI did not systematically overestimate or underestimate trigone size. Complete prognostic data were available in 295/306 fetuses and the prognosis category changed after MRI in 69/295 (23.4%) cases. The overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 76/295 (25.8%) cases.Conclusion: Our data suggest that a woman carrying a fetus with VM as the only intracranial finding on ultrasound should be offered an adjuvant investigation by MRI for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The aim in this paper is to evaluate the economic viability of electric vehicles that are supplemented by electric roads (eRoads), instead of using conventional diesel, petrol, and battery electric vehicles (BEVs). The battery is the most expensive component of an electric vehicle, so the premise of this paper is to reduce the size of the battery, and thereby significantly reduce the cost, by installing a series of electric roads for long-distance journeys. Denmark is used here as case study to ensure the assumptions reflect a real-world case when comparing petrol, diesel, BEVs, and eRoads. The results suggest that eRoads are a cheaper method of electrifying road transport than BEVs, which is an important finding, since electrification is widely believed to be the cheapest method for decarbonising the transport sector in the coming decades. Furthermore, if fuel and vehicle prices evolve as predicted between now and 2050, then eRoads are also a cheaper form of road transport than diesel and petrol, primarily due to increasing oil prices and decreasing battery costs. By implementing eRoads, it is also possible to electrify heavy-duty transport such as buses and trucks, which results in even more energy savings and reductions in carbon dioxide emissions. [ABSTRACT FROM AUTHOR]

The article presents comparison of radiologically and histologically determined thickness of the bone overlying superior semicircular canal in sixty-six cadaveric specimens and also discusses about the impact on the diagnosis of Minor's Syndrome. clinical manifestations of superior canal dehiscence (SCD) usually include sound or pressure related symptoms of vertigo and disequilibrium.

Stroke is recognised as an important disease in adults. Paediatric stroke is less understood, yet still an important cause of morbidity and mortality, with an incidence of 5 per 100 000 children and is one of the top 10 leading causes of death in children. In adults the vast majority of strokes are ischaemic, whereas in children haemorrhage makes up half the cases. The incidence of neonatal stroke is much higher, at up to 45 per 100 000 population; however, the underlying causes are less understood. This paper acts as a guide to the different causes of stroke with the key differences on imaging discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVES Echocardiography is used routinely to assess mitral regurgitation severity, but echocardiographic measures of mitral regurgitation in dogs have not been compared with other quantitative methods. The study aim was to compare echocardiographic measures of mitral regurgitation with cardiac magnetic resonance imaging-derived mitral regurgitant fraction in small-breed dogs. METHODS Dogs with myxomatous mitral valve disease scheduled for magnetic resonance imaging assessment of neurological disease were recruited. Correlations were tested between cardiac magnetic resonance imaging-derived mitral regurgitant fraction and the following echocardiographic measures: vena contracta/aortic diameter, transmitral E-wave velocity, amplitude of mitral prolapse/aortic diameter, diastolic left ventricular diameter:aortic diameter, left atrium:aortic diameter, mitral regurgitation jet area ratio and regurgitant fraction calculated using the proximal isovelocity surface area method. RESULTS Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction was attempted in 21 dogs. Twelve consecutive, complete studies were obtained and 10 dogs were included in the final analysis: vena contracta/aortic diameter (r = 0 · 89, p = 0 · 001) and E-wave velocity (r = 0 · 86, p = 0 · 001) had the strongest correlations with cardiac magnetic resonance imaging-derived mitral regurgitant fraction. E velocity had superior repeatability and could be measured in all dogs. The presence of multiple jets precluded vena contracta/aortic diameter measurement in one dog. CLINICAL SIGNIFICANCE Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction is feasible but technically demanding. The echocardiographic measures that correlated most closely with cardiac magnetic resonance imaging-derived mitral regurgitant fraction were vena contracta/aortic diameter and E-wave velocity. [ABSTRACT FROM AUTHOR]

OBJECTIVES Human carriers of hypertrophic cardiomyopathy associated sarcomeric mutations have abnormal collagen metabolism before overt left ventricular hypertrophy is detectable. This study investigated whether differences in collagen biomarkers were present in blood samples of ragdoll cats positive for the MYBPC3: R820W mutation compared with negative controls. MATERIALS AND METHODS Cats were recruited for hypertrophic cardiomyopathy screening using echocardiography and genotyping. Circulating markers of collagen turnover (C-terminal telopeptide of type I collagen [ CITP; type I collagen degradation] and N-terminal propeptide of type III procollagen [type III collagen synthesis]) and cardiac biomarkers (N-terminal B-type natriuretic peptide and cardiac troponin I) were measured. Correlation between concentrations of collagen biomarkers and echocardiographic variables was analysed, and collagen biomarker concentrations were compared between MYBPC3 mutation positive and negative cats, without left ventricular hypertrophy. RESULTS Linear regression analyses showed that genotype was independently associated with CITP concentration. CITP was higher in mutation carriers (25 · 4 µg/L, interquartile range 16 · 0-29 · 2 µg/L) than non-carriers (14 · 6 µg/L, interquartile range 9 · 38-19 · 2 µg/L; P = 0 · 024). CLINICAL SIGNIFICANCE Circulating CITP was higher in MYBPC3-positive ragdoll cats than negative controls and may indicate altered collagen metabolism. Further studies are necessary to determine whether alterations in circulating collagen biomarker concentration relate to an early stage of hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aurora kinase A (AURKA) localizes to centrosomes and mitotic spindles where it mediates mitotic progression and chromosomal stability. Overexpression of AURKA is common in cancer, resulting in acquisition of alternate non-mitotic functions. In the current study, we identified a novel role for AURKA in regulating ovarian cancer cell dissemination and evaluated the efficacy of an AURKA-selective small molecule inhibitor, alisertib (MLN8237), as a single agent and combined with paclitaxel using an orthotopic xenograft model of epithelial ovarian cancer (EOC). Ovarian carcinoma cell lines were used to evaluate the effects of AURKA inhibition and overexpression on migration and adhesion. Pharmacological or RNA interference-mediated inhibition of AURKA significantly reduced ovarian carcinoma cell migration and adhesion and the activation-associated phosphorylation of the cytoskeletal regulatory protein SRC at tyrosine 416 (pSRCY416). Conversely, enforced expression of AURKA resulted in increased migration, adhesion and activation of SRC in cultured cells. In vivo tumor growth and dissemination were inhibited by alisertib treatment as a single agent. Moreover, combination of alisertib with paclitaxel, an agent commonly used in treatment of EOC, resulted in more potent inhibition of tumor growth and dissemination compared with either drug alone. Taken together, these findings support a role for AURKA in EOC dissemination by regulating migration and adhesion. They also point to the potential utility of combining AURKA inhibitors with taxanes as a therapeutic strategy for the treatment of EOC patients. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence and complications of pre-septal (pre-SC) and post-septal (post-SC) cellulitis over 10 years. Pre-SC and post-SC are also known as periorbital and orbital cellulitis, respectively. Methods: Retrospective analysis of CT scans. Data included the presence of pre-SC and post-SC, paranasal sinus disease (PNS) and complications. Results: Among 125 patients scanned for these suspected diagnoses, 67 had both pre-SC and post-SC, 37 had pre-SC and 4 had post-SC: there were 17 normal scans. 110 patients had PNS. 68/71 (96%) patients with post-SC had PNS. Post-SC complications included orbital and/or subperios- teal abscess (50/71: 30 medial orbital, 10 superomedial, 3 lateral, 2 anteromedial, 2 inferomedial, 1 superior, 1 ante- rosuperior and 1 not specified), cavernous sinus thrombosis (CST) (1), superior ophthalmic vein (SOV) thrombosis (4) and subdural frontal empyema (2): 1 patient had SOy and CST and subdural empyema. Conclusion: 71/125 (57%) patients had post-SC. 50/125 (40%) patients imaged for pre-SC/post-SC had orbital abscess: 44/50 (88%) of these involved the medial orbit. Patients can develop solely superior or inferior abscesses that are difficult to identify by axial imaging alone, hence coronal reformatted imaging is essential. 5/125 (4%) patients developed major complications (SOV/CST/ empyema), hence imaging review of the head and cavernous sinus region is essential. A diagnosis of post-SC on CT should alert the radiologist because this diagnosis can be associated with an increased incidence (5/71, 7%) of complications. Advances in knowledge: We recommend that all patients with a suspected diagnosis of post-SC should undergo CT scan (post-contrast orbits and post- contrast head, with multiplanar reformats and a careful review of the SOV and the cavernous sinus). Particular attention should be paid to exclude intracranial complications including subdural empyema and cerebral abscess. As soon as a diagnosis of post-SC is made, in addition to informing the referring clinical team, urgent opinion should be sought from ear, nose and throat (ENT), neurology and ophthalmology with a view to urgently drain of the paranasal sinuses', [ABSTRACT FROM AUTHOR]

Objective To assess whether pleural fluid and urine amino terminal proB-type natriuretic peptide ( NT-proBNP) can distinguish cardiac from non-cardiac causes of pleural effusion. Methods Blood, urine and pleural fluid were prospectively collected from cats presenting with pleural effusion categorised as cardiac or non-cardiac in origin. NT-ProBNP concentrations were measured using a feline-specific enzyme-linked immunosorbent assay. Groups were statistically compared and receiver operating characteristic curves constructed to determine cut-offs to distinguish cardiac from non-cardiac pleural effusion in plasma, pleural fluid and urine. Results Forty cats with pleural effusion (22 cardiac and 18 non-cardiac) were studied. NT-proBNP concentrations in plasma and pleural fluid were strongly correlated. Plasma (P<0·001) and pleural fluid (P<0·001) NT-proBNP concentrations and urinary NT-proBNT/creatinine ratios (P=0·035) were significantly higher in the cardiac group. After receiver operating characteristic curve analysis a plasma NT-proBNP cut-off of 214·3 pmol/ mL was suggested [sensitivity=86·4% (95% CI: 66·7 to 95·3%), specificity=88·9% (95% CI: 67·2 to 96·9%)] and a pleural fluid NT-proBNP cut-off of 322·3 pmol/ mL was suggested [sensitivity=100% (95% CI: 85·1 to 100%), specificity=94·4% (95% CI: 74·2 to 99·0%)]. No cut-off with adequate sensitivity and specificity for urinary NT-proBNP/creatinine ratios was suggested. Clinical Significance Measurement of NT-proBNP in pleural fluid distinguishes cardiac from non-cardiac causes of pleural effusion in cats. [ABSTRACT FROM AUTHOR]

Objective. To assess the natural history of isolated syringomyelia in children. Methods. MRI reports from February 2007 to August 2011 mentioning syrinx were identified on Sheffield Children's PACS database. Scans with syringes having an AP diameter of > 1 mm and extending over at least two vertebral bodies were reviewed. Patients with an identifiable cause such as a Chiari malformation were then excluded. Results. Thirty-nine patients were included with a mean age at diagnosis of 10.6 years. The average syrinx AP diameter was 3.30 mm. The rostrocaudal length of the syringes varied between 2 and 19 vertebral bodies. Twenty-seven out of 39 syringes were thoracic in origin. There were 3 and 6 syringes involving the cervicothoracic and thoracolumbar regions, respectively, with 3 involving the cervical area only. Eleven out of 39 (Group I) patients were found 'incidentally' during work-up for adolescent idiopathic scoliosis and these were considered as a separate group. These patients did not have any significant symptoms and were discharged following their scoliosis correction surgery. Syrinx was incidental in 14 further patients (Group II). Of the 14 patients, 11 remained asymptomatic with no change in syrinx morphology throughout follow up. Of the 14 patients, 3 were lost to follow-up. Of the 39 patients, 14 (Group III) presented with progressive back pain without any obvious clinical cause. Of the 14, 10 either improved or remained the same. Of the14 patients, 3 underwent lumbar puncture, 1/14 having myelography. All 4/14 patients reported significant pain reduction on follow up following intervention. Conclusion. Idiopathic syrinx is a benign pathology, which can be managed expectantly. Most cases remain stable or improve over time. In a small minority who have progressive back pain, we have found that lumbar puncture may be helpful in reducing symptoms. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess the influence of thyroid function on natriuretic peptide concentration in hyperthyroid cats before and after treatment. METHODS Serum natriuretic peptide concentration was measured in 61 hyperthyroid cats recruited from first-opinion clinics before and after treatment. RESULTS Following successful treatment, total thyroxine, heart rate, systolic blood pressure and packed cell volume all decreased and bodyweight and creatinine concentrations increased. Furthermore, a significant (P < 0·001) decline in NT-proBNP concentration but not NT-proANP was identified. CLINICAL SIGNIFICANCE Thyroid function has a modest but significant effect on NT-proBNP concentration. Thyroid status should be taken into account when interpreting NT-proBNP concentrations in cats. [ABSTRACT FROM AUTHOR]

Objectives: Clinical guidelines suggest that all patients diagnosed with localised seizures should be investigated with MRI to identify any epileptogenic structural lesions, as these patients may benefit from surgical resection. There is growing impetus to use higher field strength scanners to image such patients, as some evidence suggests that they improve detection rates. We set out to review the detection rate of radiological abnormalities found by imaging patients with localised seizures using a high-resolution 3.01 epilepsy protocol. Methods: Data were reviewed from 2000 consecutive adult patients with localisation- related epilepsy referred between January 2005 and February 2011, and imaged at 3.0T using a standard epilepsy protocol. Results: An abnormality likely to be related to seizure activity was identified in 403/ 2000(20.2%) patients, with mesial temporal sclerosis diagnosed in 211 patients. 313/ 2000 (15.6%) had lesions potentially amenable to surgery. Abnormalities thought unrelated to seizure activity were found in 324/2000 (16.1%), with 8.9% having evidence of ischaemic disease. Conclusions: Since the introduction of the then National Institute for Clinical Excellence guidelines in 2004, the detection rate of significant pathology using a dedicated 3.01 epilepsy protocol has not fallen, despite the increased numbers of patients being imaged. This is the largest study of epilepsy imaging at 3.0T to date and highlights the detection rates of significant pathology in a clinical setting using a high- strength magnet. The prevalence of ischaemic disease in this population is significantly higher than first thought, and may not be incidental, as is often reported. [ABSTRACT FROM AUTHOR]

Aims: With general practice potentially having an important role in early intervention of mental and substance use disorders among young people, we aim to explore this issue by determining the prevalence of psychological problems and general practice/health service utilization among young people attending general practice. Methods: A retrospective cross-sectional study of patients attending three general practices in Dublin city. Results: Among a sample of young people (mostly women, 44% general medical services (GMS) eligible), we observed considerable contact with general practice, both lifetime and for the 2 years of the study. The mean consultation rate was 3.9 consultations in 2 years and psychosocial issues (most commonly stress/anxiety and depression) were documented in 35% of cases. Identification of psychosocial issues was associated with GMS eligibility, three or more doctor consultations, and documentation of smoking and drinking status. Conclusions: Psychosocial issues are common among young people attending general practice and more work on their epidemiology and further identification in general practice are advocated. [ABSTRACT FROM AUTHOR]

Background: Mental and substance use disorders are a leading cause of morbidity among young people. Policy and clinical services in Ireland are endeavouring to address these twin issues. Aims: To review the emerging literature on the role of general practice in addressing youth mental health and to discuss the implications of this literature for further research, education and service delivery. Methods: We conducted a review of 'PubMed' and a web search of relevant national/international primary/mental healthcare agencies and professional bodies. Results: Although general practice has an important role in addressing youth mental health, there are challenges in how young people seek help. Specifically, young people do not engage with healthcare agencies and many factors which act as barriers and enablers in this regard have been identified. The detection and treatment of mental and substance use disorders by GPs can be improved and implementing interventions to improve screening and early intervention are likely to be valuable. Conclusions: General practice is a central agency in addressing youth mental health and complex multifaceted interventions (education, clinical guidelines, and promoting awareness) are likely to support its role. Further research exploring this issue is a priority. [ABSTRACT FROM AUTHOR]

Increased activity of SRC family kinases promotes tumor invasion and metastasis, and overexpression of the mitotic regulator Aurora kinase A (AURKA) drives tumor aneuploidy and chromosomal instability. These functions nominate SRC and AURKA as valuable therapeutic targets for cancer, and inhibitors for SRC and Aurora kinases are now being used in the clinic. In this study, we demonstrate potent synergy between multiple inhibitors of Aurora and SRC kinases in ovarian and colorectal cancer cell lines, but not in normal ovarian epithelial cell lines. Combination of Aurora and SRC inhibitors selectively killed cells that have undergone a preceding aberrant mitosis, and was associated with a postmitotic reattachment defect, and selective removal of aneuploid cell populations. Combined inhibition of Aurora kinase and SRC potentiated dasatinib-dependent loss of activated (Y416-phosphorylated) SRC. SRC and AURKA share a common interaction partner, NEDD9, which serves as a scaffolding protein with activities in cell attachment and mitotic control, suggesting SRC and AURKA might interact directly. In vitro, we observed physical interaction and mutual cross-phosphorylation between SRC and AURKA that enhanced SRC kinase activity. Together, these findings suggest that combination of SRC and Aurora-targeting inhibitors in the clinic may be a productive strategy. [ABSTRACT FROM AUTHOR]

Encephalopathy is a common paediatric emergency associated with a high risk of morbidity, mortality and long term neurodevelopmental delay in survivors. Prompt diagnosis of the cause of encephalopathy enables the paediatrician to deliver specific medical or surgical treatment that will facilitate a better short and long term outcome. Diagnostic imaging plays a pivotal role in diagnosis. Encephalopathy has many causes. The differential diagnosis includes non accidental injury, trauma, metabolic syndromes, meningo-encephalitis, toxins, hypoxia, demyelination, stroke, haemorrhage and tumours. We describe an approach that helps us formulate an imaging strategy using US, CT and MRI that facilitates patient care. [ABSTRACT FROM AUTHOR]

Head injury from physical abuse is unfortunately a common occurrence in our society. It is a major cause of mortality and long-term physical and psychological disability in children. Diagnosis of non-accidental head injury may be difficult, as most infants present with non-specific clinical findings and without external signs of trauma. Neuroimaging plays a fundamental role both for medical management and medicolegal aspects of child abuse. It is therefore imperative for the radiologist to promptly recognise the radiological findings of various forms of non-accidental head injury to render a more accurate opinion. A standardised imaging protocol and good communication between professionals are essential for optimum management. [ABSTRACT FROM AUTHOR]

PSA levels have shown daily and seasonal variation, although data are conflicting regarding the season with higher PSA levels and the clinical relevance of this. We assessed the correlation of total PSA levels with meteorological data on a daily, weekly, monthly and seasonal basis. Data from 53 224 men aged 45-74 years, with an initial PSA <10.0 ng ml−1 were correlated with temperature (°C), duration of bright sunshine (hours) and rainfall (mm). There was seasonal variation in PSA levels, with median PSA being higher in spring compared with other seasons (1.18 vs 1.10 ng ml−1, P=0.004). Seasonal variation was not apparent when PSA levels were age-adjusted (P=0.112). Total PSA was not correlated with daily, weekly or monthly hours of sunshine, rainfall or mean temperature. In contrast, age-adjusted PSA varied with weekday, with higher PSA levels on Thursday and Friday compared with other days (1.16 vs 1.10 ng ml−1, respectively). On multivariate analysis, only age predicted for PSA levels >3.0 ng ml−1. In conclusion, PSA levels did show seasonal variation, although there was no direct correlation between PSA and any meteorological parameter. The degree of seasonal variation is small and the decision to proceed to prostate biopsy should be independent of season or weather parameters. [ABSTRACT FROM AUTHOR]

To investigate the impact of different PSA testing policies and health-care systems on prostate cancer incidence and mortality in two countries with similar populations, the Republic of Ireland (RoI) and Northern Ireland (NI). Population-level data on PSA tests, prostate biopsies and prostate cancer cases 1993–2005 and prostate cancer deaths 1979–2006 were compiled. Annual percentage change (APC) was estimated by joinpoint regression. Prostate cancer rates were similar in both areas in 1994 but increased rapidly in RoI compared to NI. The PSA testing rate increased sharply in RoI (APC = +23.3%), and to a lesser degree in NI (APC = +9.7%) to reach 412 and 177 tests per 1,000 men in 2004, respectively. Prostatic biopsy rates rose in both countries, but were twofold higher in RoI. Cancer incidence rates rose significantly, mirroring biopsy trends, in both countries reaching 440 per 100,000 men in RoI in 2004 compared to 294 in NI. Median age at diagnosis was lower in RoI (71 years) compared to NI (73 years) ( p < 0.01) and decreased significantly over time in both countries. Mortality rates declined from 1995 in both countries (APC = −1.5% in RoI, −1.3% in NI) at a time when PSA testing was not widespread. Prostatic biopsy rates, rather than PSA testing per se, were the main driver of prostate cancer incidence. Because mortality decreases started before screening became widespread in RoI, and mortality remained low in NI, PSA testing is unlikely to be the explanation for declining mortality. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) affects people's physical capabilities and the lives of people with MS are constantly changing (Finlayson et al 2005), yet how people adapt to the disease from an occupational perspective has received little attention. This study explored the occupational adaptation of women with MS. Seven women with MS were recruited from the Multiple Sclerosis Society of Ireland. Each participant completed the Modified Interest Checklist (Kielhofner and Neville 1983), the Role Checklist (Oakley et al 1985) and the Occupational Questionnaire (Smith et al 1986). Qualitative data were also collected, using the Occupational Performance History Interview - II (Kielhofner et al 2004). The findings from all four tools were amalgamated and analysed. Three main themes emerged: the impact of MS on (i) performance capacity, (ii) roles and (iii) interests. The participants adapted by performing interests and roles differently and developing new meaningful interests and roles that were congruent with their performance capacity. The findings highlight the importance of having an understanding of the impact of different types of MS on the occupational adaptation process. A greater understanding will facilitate occupational therapists in enabling people with MS to adapt to their condition by engaging in meaningful occupations throughout the lifespan. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate reduction of door-to-balloon (DTB) time and its impact on in-hospital mortality of high-risk infarct patients in a collaboration of district general hospitals (DGH) with a physician-to-patient model. Methods: Primary percutaneous coronary interventions (PPCI) with short DTB time offer mortality benefit for ST-segment elevation myocardial infarction but literatures are conflicting on this benefit for high- vs. low-risk patients. In a unique model at Sandwell and West Birmingham Hospitals, five interventional cardiologists provide 24-h PPCI at whichever one of its two DGH that patients present to. A retrospective audit was performed on 3 years (July 2005–June 2008) of PPCI data in the British Cardiovascular Intervention Society database. Data were analysed in four periods corresponding to change from daytime-only to 24-h PPCI. DTB time and in-hospital mortality were the main outcome measures. Results: Of the 459 patients, median DTB time improved from 89 min (interquartile range: 49–120) to 68 min (50–91) (p = 0.005) and proportion of patients achieving target 90-min DTB time increased from 53% (21/40) to 75% (93/124) (p = 0.005). In-hospital mortality was less for short DTB time [4.6% (13/284) vs. 11.5% (20/174); odds ratio (OR) 0.37, 95% confidence interval (CI): 0.18–0.75; p = 0.008]. With the proviso that our study was limited in power, long DTB time (> 90 min vs. ≤ 90 min) was associated with higher in-hospital mortality in high-risk patients [15.6% (20/128) vs. 7.1% (12/168); OR 2.41, 95% CI: 1.14–5.06; p = 0.024] and not in low-risk patients [0% (0/46) vs. 0.9% (1/117); OR 0, 95% CI: 0–9.88; p = 1.000]. Conclusions: A collaboration of DGH with a physician-to-patient model can deliver timely PPCI that appear to translate into mortality benefit more so in high-risk patients. Low-risk patients would therefore probably tolerate delays associated with transfer to large centres while high-risk patients would not and need alternative strategy. A collaboration of smaller hospitals with a pool of mobile interventional cardiologists could be such an alternative. [ABSTRACT FROM AUTHOR]

To examine the practice of repeating an abnormal prostate-specific antigen (PSA) level before proceeding to prostate biopsy, we assessed the pattern of PSA change following an initially raised (4.0 ng ml−1) PSA, and the relationship of this to prostate cancer diagnosis. In 7052 men, 71.2% with initially raised PSA had a reduction in PSA, with values <4.0 ng ml−1 in 37.8%. A total of 43.0% of men with prostate cancer showed a PSA decrease below their baseline level. Short-term decreases in PSA may occur in men with prostate cancer, including high-grade cancer, and so should not influence the decision to proceed to prostate biopsy.Prostate Cancer and Prostatic Diseases (2009) 12, 47–51; doi:10.1038/pcan.2008.37; published online 2 September 2008 [ABSTRACT FROM AUTHOR]

The article describes three cases of seizure-like episodes in cats with intermittent high-grade atrioventricular dysfunction. The first cat is a 12-year-old male neutered domestic shorthaired that was evaluated after 12-seizure-lie episodes in a 24-hour period. The second cat is a 12-year-old femal spayed domestic shorthaired that was presented for collapsing episodes with increasing frequency with up to 20 times. The third cat is a 14-year-old female Birman that was presented for collapsing episodes that lasted 60 seconds.