A (Running) Bolt for New Reasons

We construct a four-parameter family of smooth, horizonless, stationary solutions of ungauged five-dimensional supergravity by using the four-dimensional Euclidean Schwarzschild metric as a base space and "magnetizing" its bolt. We then generalize this to a five-parameter family based upon the Euclidean Kerr-Taub-Bolt. These "running Bolt" solutions are necessarily non-static. They also have the same charges and mass as a non-extremal black hole with a classically-large horizon area. Moreover, in a certain regime their mass can decrease as their charges increase. The existence of these solutions supports the idea that the singularities of non-extremal black holes are resolved by low-mass modes that correct the singularity of the classical black hole solution on large (horizon-sized) scales.Comment: 25 pages, 3 figures, LaTeX; v2: minor changes, references adde

Holography and Quaternionic Taub-NUT

As a concrete application of the holographic correspondence to manifolds which are only asymptotically Anti-de Sitter, we take a closer look at the quaternionic Taub-NUT space. This is a four dimensional, non-compact, inhomogeneous, riemannian manifold with the interesting property of smoothly interpolating between two symmetric spaces, AdS_4 itself and the coset SU(2,1)/U(2). Even more interesting is the fact that the scalar curvature of the induced conformal structure at the boundary (corresponding to a squashed three-sphere) changes sign as we interpolate between these two limiting cases. Using twistor methods, we construct the bulk-to-bulk and bulk-to-boundary propagators for conformally coupled scalars on quaternionic Taub-NUT. This may eventually enable us to calculate correlation functions in the dual strongly coupled CFT on a squashed S^3 using the standard AdS/CFT prescription.Comment: 1+36 pages, no figures. Some minor typos correcte

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Body growth, mitochondrial enzymatic capacities and aspects of the antioxidant system and redox balance under calorie restriction in young turbot (Scophthalmus maximus, L.).

Caloric reduction (cr) without undernutrition has been found to enhance stress resistance and life span in endotherms and ectotherms. We investigated the effect of 30% reduction in food offering on growth, aerobic capacities and oxidative stress parameters in young turbot (Scophthalmus maximus, L.).No differences in body weight, length and hepatosomatic index between the ad libitum fed (AL) and the calorie reduced (CR) group occurred after 55 days of diet application. Of the mitochondrial marker enzymes, only citrate synthase activity in liver was reduced under CR, whereas muscle CS activity and cytochrome oxidase activity in both tissues remained the same in both feeding groups. The concentration of reduced glutathione increased significantly during feeding in muscle of CR fish, resulting in a more reduced glutathione redox ratio (GSH/GSSG) compared to AL fish muscle. TBARS (lipid peroxidation) but not protein carbonyl content (protein oxidation) was significantly reduced in CR fish muscle. Liver oxidative stress parameters did not vary significantly between experimental feeding groups.We conclude that 30% calorie reduction over 8 weeks has no adverse effect on young turbot. On the contrary, cr supports a reduced tissue oxidation state and reduces accumulation of lipid peroxidation products in muscle at sustained muscular aerobic capacity

Neuroimaging correlates of brain injury in Wilson’s disease: a multimodal, whole-brain MRI study

Wilson’s disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to ‘de-copper’ patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focused on specific sequences or regions of interest, often stratifying chronically treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively recruited patients with Wilson’s disease (age range 16–68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding 6 months as having ‘active’ disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound (‘free’) copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson’s disease

Neuroimaging correlates of cognitive deficits in Wilson's disease

Background Cognitive impairment is common in neurological presentations of Wilson's disease (WD). Various domains can be affected, and subclinical deficits have been reported in patients with hepatic presentations. Associations with imaging abnormalities have not been systematically tested. Objective The aim was to determine the neuroanatomical basis for cognitive deficits in WD. Methods We performed a 16-item neuropsychological test battery and magnetic resonance brain imaging in 40 patients with WD. The scores for each test were compared between patients with neurological and hepatic presentations and with normative data. Associations with Unified Wilson's Disease Rating Scale neurological examination subscores were examined. Quantitative, whole-brain, multimodal imaging analyses were used to identify associations with neuroimaging abnormalities in chronically treated stable patients. Results Abstract reasoning, executive function, processing speed, calculation, and visuospatial function scores were lower in patients with neurological presentations than in those with hepatic presentations and correlated with neurological examination subscores. Deficits in abstract reasoning and phonemic fluency were associated with lower putamen volumes even after controlling for neurological severity. About half of patients with hepatic presentations had poor performance in memory for faces, cognitive flexibility, or associative learning relative to normative data. These deficits were associated with widespread cortical atrophy and/or white matter diffusion abnormalities. Conclusions Subtle cognitive deficits in patients with seemingly hepatic presentations represent a distinct neurological phenotype associated with diffuse cortical and white matter pathology. This may precede the classical neurological phenotype characterized by movement disorders and executive dysfunction and be associated with basal ganglia damage. A binary phenotypic classification for WD may no longer be appropriate. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Dystonia rating scales: critique and recommendations

Item does not contain fulltextMany rating scales have been applied to the evaluation of dystonia, but only few have been assessed for clinimetric properties. The Movement Disorders Society commissioned this task force to critique existing dystonia rating scales and place them in the clinical and clinimetric context. A systematic literature review was conducted to identify rating scales that have either been validated or used in dystonia. Thirty-six potential scales were identified. Eight were excluded because they did not meet review criteria, leaving 28 scales that were critiqued and rated by the task force. Seven scales were found to meet criteria to be "recommended": the Blepharospasm Disability Index is recommended for rating blepharospasm; the Cervical Dystonia Impact Scale and the Toronto Western Spasmodic Torticollis Rating Scale for rating cervical dystonia; the Craniocervical Dystonia Questionnaire for blepharospasm and cervical dystonia; the Voice Handicap Index (VHI) and the Vocal Performance Questionnaire (VPQ) for laryngeal dystonia; and the Fahn-Marsden Dystonia Rating Scale for rating generalized dystonia. Two "recommended" scales (VHI and VPQ) are generic scales validated on few patients with laryngeal dystonia, whereas the others are disease-specific scales. Twelve scales met criteria for "suggested" and 7 scales met criteria for "listed." All the scales are individually reviewed in the online information. The task force recommends 5 specific dystonia scales and suggests to further validate 2 recommended generic voice-disorder scales in dystonia. Existing scales for oromandibular, arm, and task-specific dystonia should be refined and fully assessed. Scales should be developed for body regions for which no scales are available, such as lower limbs and trunk

Investigation and management of Wilson's disease: a practical guide from the British Association for the Study of the Liver

Wilson's disease is an autosomal-recessive disorder of copper metabolism with hepatic, neurological, psychiatric, ophthalmological, haematological, renal, and rheumatological manifestations. Making a diagnosis can be challenging given that no single test can confirm or exclude the disease, and diagnostic delays are common. Treatment protocols vary and adverse effects, including paradoxical neurological worsening, can occur. In this Review, we provide a practical guide to the diagnosis of Wilson's disease. We include recommendations on indications for testing, how to interpret results, and when additional investigations are required. We also cover treatment initiation, ideally under the guidance of a specialist centre for Wilson's disease, and the principles behind long-term management. This guidance was developed by a multidisciplinary group of Wilson's disease experts formed through the British Association for the Study of the Liver. The guidance has been endorsed by the British Society of Gastroenterology and approved by the Association of British Neurologists