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Integration of brain structural information into prognostic and treatment formulation is key for achieving an all-encompassing biopsychosocial approach in psychiatry. Uncovering biological markers of specific mental illnesses, specific illness stages and of remission, may help further our understanding of the aetiology and precipitators of certain types of psychopathologies, identify central neurobiological processes as distinct from epiphenomena, validate boundaries of clinical groups, and potentially aid in predicting response to treatment. This book chapter reviewed the current structural neuroimaging evidence in three prominent mental illness domains: schizophrenia-spectrum, bipolar and depressive disorders. The large degree of overlap in abnormal neuropathology across the broad mental illness groups, which is no doubt partially due to within-group heterogeneity, makes the discovery of sets or networks of localized diagnosis-specific neural biomarkers unlikely. However, this is not to say that subtle distinctions in neural abnormalities do not exist, but rather challenges the usefulness of traditional diagnostic categories in the context of brain imaging being applied within a clinical staging model. A focus on identifying and characterising microscale circuits that are dysfunctional and which map onto symptomatology in a transdiagnostic manner, may have the greatest implications for clinical translation in the near future.
We establish the first global results for groups definable in tame expansions of o-minimal structures. Let
be an expansion of an o-minimal structure
that admits a good dimension theory. The setting includes dense pairs of o-minimal structures, expansions of
by a Mann group, or by a subgroup of an elliptic curve, or a dense independent set. We prove: (1) a Weil’s group chunk theorem that guarantees a definable group with an o-minimal group chunk is o-minimal, (2) a full characterization of those definable groups that are o-minimal as those groups that have maximal dimension; namely, their dimension equals the dimension of their topological closure, (3) as an application, if
by a dense independent set, then every definable group is o-minimal.
In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain–cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness.
Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR.
Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients.
In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure – cognition outcomes in the extant literature.
Objectives: The Wisconsin Card Sorting Test (WCST) is a complex measure of executive function that is frequently employed to investigate the schizophrenia spectrum. The successful completion of the task requires the interaction of multiple intact executive processes, including attention, inhibition, cognitive flexibility, and concept formation. Considerable cognitive heterogeneity exists among the schizophrenia spectrum population, with substantive evidence to support the existence of distinct cognitive phenotypes. The within-group performance heterogeneity of individuals with schizophrenia spectrum disorder (SSD) on the WCST has yet to be investigated. A data-driven cluster analysis was performed to characterise WCST performance heterogeneity. Methods: Hierarchical cluster analysis with k-means optimisation was employed to identify homogenous subgroups in a sample of 210 schizophrenia spectrum participants. Emergent clusters were then compared to each other and a group of 194 healthy controls (HC) on WCST performance and demographic/clinical variables. Results: Three clusters emerged and were validated via altered design iterations. Clusters were deemed to reflect a relatively intact patient subgroup, a moderately impaired patient subgroup, and a severely impaired patient subgroup. Conclusions: Considerable within-group heterogeneity exists on the WCST. Identification of subgroups of patients who exhibit homogenous performance on measures of executive functioning may assist in optimising cognitive interventions. Previous associations found using the WCST among schizophrenia spectrum participants should be reappraised. (JINS, 2019, 25, 750–760)
Foreign policies of nations do not alter radically with changes in governments, but with the backing of the Indian electorate's decisive mandate, the Narendra Modi government which came to office in May 2014 underlined that it was keen to bring about a realignment of Indian foreign policy priorities and goals. Ever since the end of the Cold War, the changing structural imperatives have been shaping the trajectory of Indian foreign policy. As a rising economic power, India has been gradually moving from the periphery to the centre of global politics, generating new demands on the conduct of Indian diplomacy. Yet, change in Indian foreign policy is also emanating from within: new constituencies with stakes in India's external relations have in the past quarter of a century become important to its foreign policy. Given these constellation of influences on Indian foreign policy, the agency of Narendra Modi's prime ministership adds another dimension to understanding India's external behaviour. On the one hand, Modi seems to exude an understanding of power and interests, thereby appearing ready for a realpolitik approach, while on the other, his emergence also underscores the changing identity of the Indian state itself. There is a vigorous debate in the emerging literature on whether Modi's foreign policy represents a transformation or merely an evolution in Indian foreign policy approach. Yet it is also evident that because of a range of structural and domestic political and unit level factors, new dimensions have emerged in the study and conduct of Indian foreign policy. Modi's prime ministership is just one of them.
The Modi factor
In his first few years, Modi has defied many expectations and confounded his detractors and supporters alike. On the foreign policy front, remarkably for a politician who was considered provincial before elections, Modi hit the ground running from the very first day. On the security front, there has been a new purposeful response against China with a focus on more efficient border management and defence acquisitions. Modi also reached out to the US immediately after his election, despite his personal grievances over visa denial by Washington when he was the Chief Minister of Gujarat, and there has been a focus on immediate neighbours, though not without setbacks.
Harsh V. Pant, Director of Research at Observer Research Foundation, New Delhi, and Professor of International Relations at King's College London.,
Avinash Paliwal, diplomacy and public policy at the School of Oriental and African Studies (SOAS), University of London, UK.
In a town-hall type address to citizens in August 2016, Prime Minister Narendra Modi stated that India's foreign policy was all about ‘India First’. Though this can be inferred in myriad ways, the statement underlined two well-known assumptions about Indian foreign policy. First, as noted in the first such study by J. Bandyopadhyaya, Prime Ministers play a critical role in steering the direction of Indian foreign policy. This has been evident in the articulation of doctrines around the persona and political temperament of different Prime Ministers. If foreign policy ‘emerged whole from the head and heart’ of Jawaharlal Nehru, Indira and Rajiv Gandhi overshadowed, if not stepped upon, the bureaucracy in charting India's relationship with the world. More recently, terms such as Rao Doctrine, Gujral Doctrine, Manmohan Doctrine, and Modi Doctrine typify the diplomatic style and policy substance of different Indian Prime Ministers. Second, external affairs are a policy domain wherein both the Indian public and policymakers seek – and believe there exists – consensus. Even during periods of extreme political polarisation, few would disagree that India should indeed focus on ‘India First’ when it comes to international politics. For it underlines the basic tenet of political realism in an anarchic world. It can be argued that Nehru's Non-Alignment, Narasimha Rao's pragmatism and Modi's assertiveness are all manifestations of this deep realist foundation of India's foreign policy outlook.
Most existing scholarly analyses of India's foreign policy revolves around these two broad facets. Be it debates around the role of institution or about the drivers of India's foreign policy, the issue is assessed by focusing on what policy output looks like rather than how it is formulated. Both India's position in the world and its shifting policy pronouncements in the context of a constantly evolving world order are aspects that have been well researched, and shall continue to elicit vibrant debate and discussion. Similar to works on other rising powers, studies on India's foreign policy address a diverse set of questions. What are the ideological underpinnings of Indian foreign policy? Does India offer a vision to the world? What is the state of India's relationships with major global powers? Why does India continue to have problems in emerging as a ‘benign’ regional power in South Asia?
The study of Indian foreign policy has been undergoing a significant shift in recent years with new themes and new theoretical approaches emerging and newer voices adding their vibrancy to the field. This project was commissioned by Cambridge University Press (CUP) to specifically examine the impact of the emergence of Narendra Modi as India's Prime Minister in 2014 on the study and practice of Indian foreign policy. As we thought about the project more, we concluded that though the debates about the impact of Modi on the study of Indian foreign policy would continue, the field has been undergoing an evolution of its own. So this volume turned out to be not about Narendra Modi's impact on Indian foreign policy per se but about the key debates in Indian foreign policy as they have evolved over the last few years. In some cases, Modi's personality and convictions have had a role to play but in others, underlying institutional, structural and ideational factors beyond Modi have been powerful drivers of Indian foreign policy's trajectory.
I would like to thank CUP for giving me this opportunity, allowing me to relook at the state of the field. The whole team at the CUP – Qudsiya Ahmed, Sohini Ghosh, Aniruddha De – was very encouraging even as the project took much more time than was earlier anticipated. The contributors to this volume have been extremely cooperative and their patience in seeing this volume through to publication is much appreciated. I would also like to thank the two institutions I am associated with – the Observer Research Foundation, New Delhi, and King's College London – for giving me time and space to conclude this project. Finally, thanks are due to my family members who make sure that I remain insulated to concentrate on my projects.
This book is dedicated to the emerging new voices in the study of Indian foreign policy who, slowly but surely, are transforming the subject. More power to them!
Harsh V. Pant, Director of Research at Observer Research Foundation, New Delhi, and Professor of International Relations at King's College London.,
Julie M. Super, PhD student at George Mason University's Schar School of Policy and Government, with a focus on comparative politics and international relations.
The release of a report titled Nonalignment 2.0 in 2012 brought a seemingly antiquated debate back to the forefront of Indian policy circles. Yet as any close examination of Indian foreign policy over the past six decades will underscore, Indian policymakers’ fixation with non-alignment never truly petered out. It has remained a central component of Indian identity in global politics that is manifest in continuities: India has been in pursuit of strategic autonomy since Independence, which in practice has led to semi-alliances fashioned under the cover of non-alignment and shaped by regional dynamics. In this setting, the rise of China now raises an interesting conundrum for Indian policymakers as New Delhi seeks to balance the benefits and risks of an increasingly assertive neighbour and a network of alliances with like-minded countries.
This chapter provides an overview of what non-alignment has meant in practice for India, from the early roots of the policy, through the Cold War era, and into the modern day international system. The focus of the chapter is narrowed primarily to the role of external factors in shaping Indian policy, especially the ongoing challenges posed by Pakistan and China and the role of power politics in the global system. Though domestic factors have had a significant influence on the trajectory of Indian foreign policy, the continuities of non-alignment have prevailed through changes in leadership and domestic vicissitudes. By exploring the foundation of non-alignment and how India has operationalized the policy through time, this chapter maintains that to some extent continuity has persisted into the twenty-first century: despite the revival of non-alignment rhetoric with the 2012 policy prescription, India moved closer to the West and its allies in practice. Yet, amid China's growing influence, the success of India's modern-day pursuit of strategic autonomy may well rest on a strong foundation of strategic partnerships that move beyond the limited commitments of non-alignment. The coming to office of the NDA government led by Narendra Modi in May 2014 has signaled a move away from even the rhetoric of non-alignment with significant implications for the future of Indian foreign policy.
Many factors contributed to the development of non-alignment in India, but the origins of non-alignment can be traced to three main factors, drawn from nationalist leanings, proximity to the Soviet Union, and economic troubles on the eve of independence.
To summarize risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) in hospitalized pediatric patients as determined by previous observational studies.
Meta-analysis and systematic review.
Studies evaluating risk factors for CDI in pediatric inpatients were eligible for inclusion.
We systematically searched MEDLINE, Web of Science, Scopus, and EMBASE for subject headings and text words related to CDI and pediatrics from 1975 to 2017. Two of the investigators independently screened studies, extracted and compiled data, assessed study quality, and performed the meta-analysis.
Of the 2,033 articles screened, 14 studies reporting 10,531,669 children met the inclusion criteria. Prior antibiotic exposure (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31–3.52) and proton pump inhibitor (PPI) use (OR, 1.33; 95% CI, 1.07–1.64) were associated with an increased risk of CDI in children. Subgroup analyses using studies reporting only adjusted results suggested that prior antibiotic exposure is not a significant risk factor for CDI. H2 receptor antagonist (H2RA) use (OR, 1.36; 95% CI, 0.31–5.98) and that female gender (OR, 0.87; 95% CI, 0.74–1.03) did not play a significant role as a risk factor for developing CDI.
Prior antibiotic exposure appears to be an important risk factor for CDI based on the combined analysis but not significant using adjusted studies. PPI use was associated with an increased risk of CDI. Judicious and appropriate use of antibiotics and PPIs may help reduce the risk of CDI in this vulnerable population.
It is unclear how individual differences in parenting and brain development interact to influence adolescent mental health outcomes. This study examined interactions between structural brain development and observed maternal parenting behavior in the prediction of adolescent depressive symptoms and psychological well-being. Whether findings supported diathesis-stress or differential susceptibility frameworks was tested. Participants completed observed interactions with their mothers during early adolescence (age 13), and the frequency of positive and aggressive maternal behavior were coded. Adolescents also completed structural magnetic resonance imaging scans at three time points: mean ages 13, 17, and 19. Regression models analyzed interactions between maternal behavior and longitudinal brain development in the prediction of late adolescent (age 19) outcomes. Indices designed to distinguish between diathesis-stress and differential susceptibility effects were employed. Results supported differential susceptibility: less thinning of frontal regions was associated with higher well-being in the context of low levels of aggressive maternal behavior, and lower well-being in the context of high levels of aggressive maternal behavior. Findings suggest that reduced frontal cortical thinning during adolescence may underlie increased sensitivity to maternal aggressive behavior for better and worse and highlight the importance of investigating biological vulnerability versus susceptibility.
North America is facing a public health epidemic – the opioid crisis – part of which is attributed to the inappropriate use of opioids in pain management. As such, the 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain recommends optimizing non-opioid pharmacotherapy or non-pharmacological therapy to treat chronic pain, before a trial of opioids. However, the Guideline itself is not designed to provide evidence on the effectiveness of these non-opioid alternatives, leaving a gap for those attempting to put the recommendation into practice.
In collaboration with its partners, including clinicians and policymakers, the Canadian Agency for Drugs and Technologies (CADTH) identified the gaps in evidence, and developed an action plan to bridge the evidence gaps to support the optimization of non-opioid alternatives in pain management.
Since the release of the Guideline, CADTH produced over 20 Rapid Response reports that synthesize and appraise evidence on non-opioid alternatives in the management of a wide range of pain, both acute and chronic. Additionally, CADTH has also reviewed evidence on multidisciplinary pain treatment programs, and is developing environmental scan reports on the availability and access to non-pharmacological treatments for pain in Canada, and on drugs for emerging non-opioid pain. Further, CADTH developed knowledge mobilization tools based on the evidence reviews. The evidence reviews and tools are used as a resource by CADTH partners, including the Coalition of Safe and Effective Pain Management and McMaster University National Pain Center.
This presentation will discuss the role of HTA and CADTH to fill the gaps in evidence for a crucial clinical practice guideline recommendation in a time of public health crisis, and help put the evidence into action. It will present the evidence synthesized by CADTH on various non-opioid alternatives for pain management, while highlighting the remaining gaps in evidence. Understanding the evidence on non-opioid alternatives will inform clinical and policy decisions and potentially reduce inappropriate use of opioids in pain management.
While previous studies have identified relationships between hippocampal volumes and memory performance in schizophrenia, these relationships are not apparent in healthy individuals. Further, few studies have examined the role of hippocampal subfields in illness-related memory deficits, and no study has examined potential differences across varying illness stages. The current study aimed to investigate whether individuals with early and established psychosis exhibited differential relationships between visuospatial associative memory and hippocampal subfield volumes.
Measurements of visuospatial associative memory performance and grey matter volume were obtained from 52 individuals with a chronic schizophrenia-spectrum disorder, 28 youth with recent-onset psychosis, 52 older healthy controls, and 28 younger healthy controls.
Both chronic and recent-onset patients had impaired visuospatial associative memory performance, however, only chronic patients showed hippocampal subfield volume loss. Both chronic and recent-onset patients demonstrated relationships between visuospatial associative memory performance and hippocampal subfield volumes in the CA4/dentate gyrus and the stratum that were not observed in older healthy controls. There were no group by volume interactions when chronic and recent-onset patients were compared.
The current study extends the findings of previous studies by identifying particular hippocampal subfields, including the hippocampal stratum layers and the dentate gyrus, that appear to be related to visuospatial associative memory ability in individuals with both chronic and first-episode psychosis.