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Background: Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. Methods: A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1–2 months after completing a 6–8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. Results: Five themes were identified in the qualitative data: (1) 'Encouraging entry and supporting exit' (e.g. recognising and managing participants' varied motives and expectations, including around weight loss and symptom alleviation); (2) 'Challenging but potentially transformational,' which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) 'Intervention facilitators,' including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) 'Intervention barriers' (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) 'The wider context' (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. Conclusion: We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. Trial registration: Study registration number: ISRCTN61613198 (02/03/22). [ABSTRACT FROM AUTHOR]

Purpose: Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. Methods: Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. Primary objective: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3–6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). Results: There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54–70), yielding 10,100 (median, 12.5/person, IQR 5.2–19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0–4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46–0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79–1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45–0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84–1.16, P = 0.874). Conclusion: Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. Methods: Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. Primary objective: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3–6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). Results: There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54–70), yielding 10,100 (median, 12.5/person, IQR 5.2–19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0–4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46–0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79–1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45–0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84–1.16, P = 0.874). Conclusion: Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes. [ABSTRACT FROM AUTHOR]

Introduction In contrast to other monogenic causes of neurodegeneration such as mitochondrial and peroxisomal disease (1, 2), the majority of fatal lysosomal storage disorders (LSDs) are caused by a deficiency [...], CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoylprotein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice ([Cln1.sup.-/-]) and CLN1rr15x sheep to assess how to potentially scale up for translation. In [Cln1.sup.-/-]mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In [CLN1.sup.R151X] sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.

Background Short-course partial brain radiotherapy ± chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy-related side effects. Methods This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL). Results 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The median OS was 10.7 months. After accounting for age, sex, treatment, and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI −3.24 to −0.19 P  = .027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow-up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P  = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P  < .001). Conclusions This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy. [ABSTRACT FROM AUTHOR]

In 2015, a groundswell of brain tumour patient, carer and charity activism compelled the UK Minister for Life Sciences to form a brain tumour research task and finish group. This resulted, in 2018, with the UK government pledging £20m of funding, to be paralleled with £25m from Cancer Research UK, specifically for neuro‐oncology research over the subsequent 5 years. Herein, we review if and how the adult brain tumour research landscape in the United Kingdom has changed over that time and what challenges and bottlenecks remain. We have identified seven universal brain tumour research priorities and three cross‐cutting themes, which span the research spectrum from bench to bedside and back again. We discuss the status, challenges and recommendations for each one, specific to the United Kingdom. [ABSTRACT FROM AUTHOR]

In a recent paper, a new method was proposed to find the common invariant subspaces of a set of matrices. This paper investigates the more general problem of putting a set of matrices into block triangular or block-diagonal form simultaneously. Based on common invariant subspaces, two algorithms for simultaneous block triangularization and block diagonalization of sets of matrices are presented. As an alternate approach for simultaneous block diagonalization of sets of matrices by an invertible matrix, a new algorithm is developed based on the generalized eigenvectors of a commuting matrix. Moreover, a new characterization for the simultaneous block diagonalization by an invertible matrix is provided. The algorithms are applied to concrete examples using the symbolic manipulation system Maple. [ABSTRACT FROM AUTHOR]

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models. [ABSTRACT FROM AUTHOR]

Purpose - This study aims to find all subalgebras up to conjugacy in the real simple Lie algebra so(3; 1). Design/methodology/approach - The authors use Lie Algebra techniques to find all inequivalent subalgebras of so(3; 1) in all dimensions. Findings - The authors find all subalgebras up to conjugacy in the real simple Lie algebra so(3; 1). Originality/value - This paper is an original research idea. It will be a main reference for many applications such as solving partial differential equations. If so(3; 1) is part of the symmetry Lie algebra, then the subalgebras listed in this paper will be used to reduce the order of the partial differential equation (PDE) and produce non-equivalent solutions. [ABSTRACT FROM AUTHOR]

This article points out some of the shortcomings of a paper by Ceballos et al. In particular, representations of the indecomposable six‐dimensional complex nilpotent Lie algebras are corrected. In addition, the class of representations is extended so as to include all the indecomposable six‐dimensional real nilpotent Lie algebras. A test case is studied in detail in which it is shown that there is no representation of one of the six‐dimensional real nilpotent Lie algebras using 5 × 5 matrices. This test case points up some of the severe difficulties that one will encounter when implementing an algorithm such as the one developed by Ceballos et al. The case of the seven‐dimensional complex nilpotent Lie algebras is briefly touched upon and several representations are corrected. [ABSTRACT FROM AUTHOR]

Objective: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics. Methods: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed. Results: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value. Conclusion: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management. [ABSTRACT FROM AUTHOR]

For each of the six-dimensional indecomposable nilpotent Lie algebras, the geodesic equations of the associated canonical Lie group connection are given. In each case, a basis for the associated Lie algebra of symmetries is constructed and analyzed. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast media are widely used in cardiovascular MRI to identify and to highlight the intravascular and extracellular space. After gadolinium, manganese has the second highest paramagnetic moment and was one of the first MRI contrast agents assessed in humans. Over the last 50 years, manganese-enhanced MRI (MEMRI) has emerged as a complementary approach enabling intracellular myocardial contrast imaging that can identify functional myocardium through its ability to act as a calcium analogue. Early progress was limited by its potential to cause myocardial depression. To overcome this problem, two clinical formulations of manganese were developed using either chelation (manganese dipyridoxyl diphosphate) or coadministration with a calcium compound (EVP1001-1, Eagle Vision Pharmaceuticals). Preclinical studies have demonstrated the efficacy of MEMRI in quantifying myocardial infarction and detecting myocardial viability as well as tracking altered contractility and calcium handling in cardiomyopathy. Recent clinical data suggest that MEMRI has exciting potential in the quantification of myocardial viability in ischaemic cardiomyopathy, the early detection of abnormalities in myocardial calcium handling, and ultimately, in the development of novel therapies for myocardial infarction or heart failure by actively quantifying viable myocardium. The stage is now set for wider clinical translational study of this novel and promising non-invasive imaging modality. [ABSTRACT FROM AUTHOR]

Introduction: Incidental findings are common in presumed healthy volunteers but are infrequently studied in patients in a clinical context. Objective: To determine the prevalence, nature, and management implications of incidental findings on head MRI in patients presenting with cognitive symptoms, and to quantify and describe unexpected MRI abnormalities that are of uncertain relevance to the patient's cognitive symptoms. Methods: A single-centre retrospective review of patients attending a regional early-onset cognitive disorders clinic between March 2012 and October 2018. Medical records of consecutive patients who underwent head MRI were reviewed. Unexpected MRI findings were classified according to their severity and likelihood of being incidental. Markers of small vessel disease and cerebral atrophy were excluded. Results: Records of 694 patients were reviewed (median age 60 years, 49.9% female), of whom 514 (74.1%) underwent head MRI. 54% of the patients received a diagnosis of a neurodegenerative disorder. Overall 111 incidental findings were identified in 100 patients of whom 18 patients (3.5%, 95% CI 2.2–5.6%) had 18 incidental findings classified as requiring additional medical evaluation. 82 patients (16%, 95% CI 13.0–19.5%) had 93 incidental findings without clearly defined diagnostic consequences. 17 patients (3.3%) underwent further investigations, 14 patients (2.7%) were referred to another specialist clinic and 3 patients (0.6%) were treated surgically. Two patients had MRI findings of uncertain relevance to their cognitive symptoms, necessitating prolonged clinic follow-up. Conclusion: Incidental findings are common in patients with cognitive impairment from this large clinic-based series; however, few required additional medical evaluation. These data could help inform discussions between clinicians and people with cognitive symptoms regarding the likelihood and potential implications of incidental imaging findings. [ABSTRACT FROM AUTHOR]

Index formulas for the curvature tensors of an invariant metric on a Lie group are obtained. The results are applied to the case of solvable Lie algebras that have a codimension one Abelian nilradical. It is argued that such algebras are associated to Einstein metrics only when the metric is of constant negative or zero curvature. Thereafter, all of the four- dimensional Lie algebras are examined with regard to the question of whether they correspond to Einstein metrics. For algebras that are not of the type solvable with codimension one Abelian nilradical, the space of derivations is found and used to reduce the metric and the Ricci tensor is calculated. It is then possible to say precisely which metrics are Einstein spaces. In the indecomposable case precisely four such Einstein spaces are obtained. Two of them are spaces of constant curvature. No examples are found in the decomposable case. [ABSTRACT FROM AUTHOR]

Index formulas for the curvature tensors of an invariant metric on a Lie group are obtained. The results are applied to the problem of characterizing invariant metrics of zero and non-zero constant curvature. Killing vector fields for such metrics are constructed and play an important role in the case of at metrics. [ABSTRACT FROM AUTHOR]

We solve the problem of finding a simultaneous matrix normal form for an element of the Lie algebra o(p, q) and the underlying indefinite inner product. The results are used to determine several classes of classical Hamiltonian dynamical systems which possess a first integral linear in the momentum variables. [ABSTRACT FROM PUBLISHER]

In this investigation, we present symmetry algebras of the canonical geodesic equations of the indecomposable solvable Lie groups of dimension five, confined to algebras A 5 , 7 a b c to A 18 a . For each algebra, the related system of geodesics is provided. Moreover, a basis for the associated Lie algebra of the symmetry vector fields, as well as the corresponding nonzero brackets, are constructed and categorized. [ABSTRACT FROM AUTHOR]