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Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.
Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.
Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.
These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the ‘dysconnectivity hypothesis’ of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.
Energy policy making is complex, and policy makers have traditionally relied on evidence and assessments dominated by a handful of disciplines from the natural and physical sciences. These assessments have often focused on technological solutions with the implicit message that the answer to policy needs lies in identifying and developing the right technology. Historically, however, problems arise in the implementation process of new technologies. These obstacles may be better understood, and either alleviated or avoided, through a more holistic analysis of energy policy requirements that includes multidisciplinary approaches from the social sciences and humanities. This chapter introduces the main ideas of the book, including an overview of each chapter and the most important arguments of the book.
In this chapter, we discuss the evolution of the field of ‘ethics of nuclear energy’, regarding its past, present and future. We will first review the history of this field in the previous four decades, focusing on new and emerging challenges of nuclear energy production and waste disposal, in light of several important developments. Four of the most pressing ethical challenges will be further reviewed in the chapter. First, what is a morally ‘acceptable’ nuclear energy production method, if we consider the existing and possible new technologies? Second, provided a new tendency to consider nuclear waste disposal with several countries, what would be the new ethical and governance challenges of these multinational collaborations? Third, how should we deal with the (safety) challenges of the new geographic distribution of nuclear energy, tilting towards emerging economies with less experience with nuclear technology? Fourth, nuclear energy projects engender highly emotional controversies. Neither ignoring the emotions of the public nor taking them as a reason to prohibit or restrict a technology – we call them technocratic populist pitfalls respectively – seem to be able to guide responsible policy making.
The final chapter presents responses to the content of the entire book by policy practitioners who have dealt with the realities of constructing and implementing policies. They include essays by Emily Shuckburgh, OBE, deputy head of the Polar Oceans Team at the British Antarctic Survey; John Deutch, currently Institute Professor at the Massachusetts Institute of Technology and former Deputy Secretary of Energy in the United States; and Lord Ronald Oxburgh, who is a British parliamentarian, member of the House of Lords, a former chairman of Shell and himself a geologist and geophysicist. These ‘technologists’ offer three different perspectives on the topic of ‘good energy policy’. Finally the editors provide the main lessons learned from the book and offer suggestions for future directions of multidisciplinary research in energy policy.
The aim of this chapter is two-fold. First, the authors present a practical application of multidisciplinary research based on the experience of editing a book comprised of multidisciplinary cases and focusing on two chapter cases. There are many theoretical accounts of how one may approach multidisciplinary research, but here the authors aim to offer a practical account of how the theoretical goal of multidisciplinary research can play out in the ‘real world’. After addressing the current conceptual understanding of multidisciplinary versus interdisciplinary research, the authors will explain how useful these concepts, in fact, are when applied to the typical constraints that many academics face today in conducting joint research. The authors, who are both editors of the book, will provide lessons for future multidisciplinary collaboration and suggestions for developing methods of multidisciplinary research.
Political science does not offer a distinct subdiscipline to address the subject of energy. Insofar as political science has addressed energy, it has focused on issues often neglected by other disciplines, notably the role of geopolitics and international relations, and the domestic politics of resource-rich states. Apart from the different subfields, we examine different approaches including realism, constructivism, liberalism and Marxism. The rise and fall and rise again of academic articles on energy in leading political science journals is reviewed and linked to exogenous forces such as the price of oil. Two distinct energy topics which have received attention are nuclear power and the oil crises of 1973–79 because of their wider geopolitical ramifications. Perhaps the most prominent or consistent thread through studies of the politics of energy is the question of energy security or energy independence. Finally, in recent years, energy has increasingly emerged as a focus for study in environmental politics and climate change politics in particular.
Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.
All paediatric heart transplant recipients (2004–2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.
A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (−18.2 versus −14.1), global circumferential strain (−24.1 versus −19.6), longitudinal strain rate (−1 versus −0.8), circumferential strain rate (−1.3 versus −1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.
Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.
We consider the steady flow of a granular current over a uniformly sloped surface that is smooth upstream (allowing slip for
) but rough downstream (imposing a no-slip condition on
), with a sharp transition at
. This problem is similar to the classical Blasius problem, which considers the growth of a boundary layer over a flat plate in a Newtonian fluid that is subject to a similar step change in boundary conditions. Our discrete particle model simulations show that a comparable boundary-layer phenomenon occurs for the granular problem: the effects of basal roughness are initially localised at the base but gradually spread throughout the depth of the current. A rheological model can be used to investigate the changing internal velocity profile. The boundary layer is a region of high shear rate and therefore high inertial number
; its dynamics is governed by the asymptotic behaviour of the granular rheology for high values of the inertial number. The
rheology (Jop et al., Nature, vol. 441 (7094), 2006, pp. 727–730) asserts that
, but current experimental evidence is insufficient to confirm this. We show that this rheology does not admit a self-similar boundary layer, but that there exist generalisations of the
rheology, with different dependencies of
, for which such self-similar solutions do exist. These solutions show good quantitative agreement with the results of our discrete particle model simulations.
Drawing on political science, economics, philosophy, theology, social anthropology, history, management studies, law, and other subject areas, In Search of Good Energy Policy brings together leading academics from across the social sciences and humanities to offer an innovative look at why science and technology, and the type of quantification they champion, cannot alone meet the needs of energy policy making in the future. Featuring world-class researchers from the University of Cambridge and other leading universities around the world, this innovative book presents an interdisciplinary dialogue in which scientists and practitioners reach across institutional divides to offer their perspectives on the relevance of multi-disciplinary research for 'real world' application. This work should be read by anyone interested in understanding how multidisciplinary research and collaboration is essential to crafting good energy policy.