Clinical Utility of Machine-Learning Approaches in Schizophrenia: Improving Diagnostic Confidence for Translational Neuroimaging

Machine-learning approaches are becoming commonplace in the neuroimaging literature as potential diagnostic and prognostic tools for the study of clinical populations. However, very few studies provide clinically informative measures to aid in decision-making and resource allocation. Head-to-head comparison of neuroimaging-based multivariate classifiers is an essential first step to promote translation of these tools to clinical practice. We systematically evaluated the classifier performance using back-to-back structural MRI in two field strengths (3- and 7-T) to discriminate patients with schizophrenia (n = 19) from healthy controls (n = 20). Gray matter (GM) and white matter images were used as inputs into a support vector machine to classify patients and control subjects. Seven Tesla classifiers outperformed the 3-T classifiers with accuracy reaching as high as 77% for the 7-T GM classifier compared to 66.6% for the 3-T GM classifier. Furthermore, diagnostic odds ratio (a measure that is not affected by variations in sample characteristics) and number needed to predict (a measure based on Bayesian certainty of a test result) indicated superior performance of the 7-T classifiers, whereby for each correct diagnosis made, the number of patients that need to be examined using the 7-T GM classifier was one less than the number that need to be examined if a different classifier was used. Using a hypothetical example, we highlight how these findings could have significant implications for clinical decision-making. We encourage the reporting of measures proposed here in future studies utilizing machine-learning approaches. This will not only promote the search for an optimum diagnostic tool but also aid in the translation of neuroimaging to clinical use

Altered connectivity of the right anterior insula drives the pain connectome changes in chronic knee osteoarthritis

Resting-state functional connectivity (FC) has proven a powerful approach to understand the neural underpinnings of chronic pain, reporting altered connectivity in three main networks: the default mode (DMN), central executive (CEN), and the salience network (SN). The interrelation and possible mechanisms of these changes are less well understood in chronic pain. Based on emerging evidence of its role to drive switches between network states, the right anterior insula (rAI, an SN hub) may play a dominant role in network connectivity changes underpinning chronic pain. To test this hypothesis, we used seed-based resting-state FC analysis including dynamic and effective connectivity metrics in 25 people with chronic osteoarthritis (OA) pain and 19 matched healthy volunteers. Compared to controls, participants with painful knee OA presented with increased anticorrelation between the right anterior insula (SN) and DMN regions. Also, the left dorsal prefrontal cortex (CEN hub) showed more negative FC with the right temporal gyrus. Granger causality analysis revealed increased negative influence of the right anterior insula on the posterior cingulate (DMN) in OA patients in line with the observed enhanced anticorrelation. Moreover, dynamic FC was lower in the DMN of patients and thus more similar to temporal dynamics of the SN. Together, these findings evidence a widespread network disruption in patients with persistent osteoarthritis pain, and point toward a driving role of the rAI

Multiplication and Composition in Weighted Modulation Spaces

We study the existence of the product of two weighted modulation spaces. For this purpose we discuss two different strategies. The more simple one allows transparent proofs in various situations. However, our second method allows a closer look onto associated norm inequalities under restrictions in the Fourier image. This will give us the opportunity to treat the boundedness of composition operators.Comment: 49 page

Outside interference or Hong Kong embracing its unique identity? : The Chinese Universities Shakespeare Festival

Ongoing clashes between Hong Kong citizens and its government have foregrounded questions about outside interference in Hong Kong’s politics (largely from the government and media of People’s Public of China), as well as debate about what institutions in Hong Kong are neo-colonial, heavily inflected with nostalgia for British colonialism, or in the process of being ‘colonised’ by the People’s Republic of China. This article looks at Shakespeare in Hong Kong (and, to some extent, greater Chinese) theatre and education as one of those contested institutions, using the particular case of the now-defunct Chinese Universities Shakespeare Festival. The author probes their initial, surface impression of the festival as a simple outpouring of colonial sentiment and impulse, using its sizeable archives to realise a reading of the institution that highlights the complexities of international and intra-regional politics, culture and identity in Hong Kong and greater China. It builds on the Hong Kong literary critic Michael Ingham’s call for attention to Hong Kong’s quest – sometimes overt (as in the demonstrations of 2019), sometimes implicit (in the body of literature Ingham explores in his cultural and literary history) – for a unique, post-colonial identity that is inspired – but, critically, not confined – by its Chinese and British histories. The article briefly outlines the origins and set-up of the festival before juxtaposing the dominance of English language and culture in it with the opportunities it presents (seized by several teams) for intra-regional cooperation, competition and sharing diverse, greater Chinese cultures. The article offers a model for critically appraising other institutions and cultural products in Hong Kong in ways that resist easy binaries of British or Chinese, colonial or indigenous

Association of Genetic Risks with Autism Spectrum Disorder and Early Neurodevelopmental Delays among Children without Intellectual Disability

IMPORTANCE Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. OBJECTIVE To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. MAIN OUTCOMES AND MEASURES Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. RESULTS Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, −1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, −1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, −5.28; SE, 1.40; P \u3c .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, −5.30; SE 1.30; P \u3c .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, −6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, −6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling–associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, −5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, −5.38; SE, 1.74; P = .002). CONCLUSIONS AND RELEVANCE In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills

Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain?

Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10 µg/50 µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1 mg/50 µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7 T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72 mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5 g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats

Scalar-mediated ttˉt\bar t forward-backward asymmetry

A large forward-backward asymmetry in $t\bar t$ production, for large invariant mass of the $t\bar t$ system, has been recently observed by the CDF collaboration. Among the scalar mediated mechanisms that can explain such a large asymmetry, only the t-channel exchange of a color-singlet weak-doublet scalar is consistent with both differential and integrated $t\bar t$ cross section measurements. Constraints from flavor changing processes dictate a very specific structure for the Yukawa couplings of such a new scalar. No sizable deviation in the differential or integrated $t\bar t$ production cross section is expected at the LHC.Comment: 22 pages, 1 figure and 2 tables. v2: Corrected Eqs.(50,51,74), adapted Fig.1, Tab.1 and relevant discussions. Extended discussion of top decay and single to