Pilot study of a culturally adapted psychoeducation (CaPE) intervention for bipolar disorder in Pakistan.

Background: Despite the use of maintenance medication, recurrence rates in bipolar affective disorder (BPAD) are high. To date, there are no clinical trials that have investigated the use of psychological interventions in bipolar disorder in Pakistan. / Aim: The purpose of the study was to assess the feasibility and acceptability of a culturally adapted bipolar psychoeducation programme (CaPE) in Pakistan. / Methods: Thirty-four euthymic bipolar I and II outpatients were randomized to either 12 weekly sessions of individual psychoeducation plus Treatment As Usual (Intervention) or Treatment As Usual (TAU) (Control). Outcomes were assessed using the Young Mania Rating Scale (YMRS), Beck Depression Inventory (BDI), EuroQoL (EQ-5D), Bipolar Knowledge and Attitudes and Questionnaire (BKAQ), and a self-reported measure of medication adherence (Morisky Medication Adherence Scale-4 items, MMAS-4). Effect sizes were derived from baseline adjusted standardized regression coefficients. / Results: Retention in the study was good, 80% of patients in the TAU follow-up assessment and 100% of patients in the CaPE group attended all 12 sessions. Patient satisfaction was higher in the CaPE group relative to control (ES = 1.41). Further, there were large effect sizes shown for CaPE versus TAU for medication adherence (MMAS-4: ES = 0.81), knowledge and attitudes towards bipolar (BKAQ: ES = 0.68), mania (YMRS: ES = 1.18), depression (BDI: ES = 1.17) and quality of life measures (EQ-5D: ES ⇒ 0.88). / Conclusions: Culturally adapted psychoeducation intervention is acceptable and feasible, and can be effective in improving mood symptoms and knowledge and attitudes to BPAD when compared with TAU. Larger scale studies are needed to confirm our findings. / Trial registration. Clinicaltrials.gov identifier NCT0221039

An early warning risk prediction tool (RECAP-V1) for patients diagnosed with COVID-19: the protocol for a statistical analysis plan

Background: Since the start of the Covid-19 pandemic efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalisation. The RECAP (Remote COVID Assessment in Primary Care) study investigates the predictive risk of hospitalisation, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process done by clinicians. The study aims to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of a number of general practices across the UK to construct accurate predictive models that will use pre-existing conditions and monitoring data of a patient’s clinical parameters such as blood oxygen saturation to make reliable predictions as to the patient’s risk of hospital admission, deterioration, and death. Objective: We outline the statistical methods to build the prediction model to be used in the prioritisation of patients in the primary care setting. The statistical analysis plan for the RECAP study includes as primary outcome the development and validation of the RECAP-V1 prediction model. Such prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected covid-19. The model will predict risk of deterioration, hospitalisation, and death. Methods: After the data has been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine learning approaches to impute the missing data for the final analysis. For predictive model development we will use multiple logistic regressions to construct the model on a training dataset, as well as validating the model on an independent dataset. The model will also be applied for multiple different datasets to assess both its performance in different patient groups, and applicability for different methods of data collection. Results: As of 5th of May 2021 we have recruited 2280 patients for the main dataset for model development, as well as a further 1741 patients for the validation dataset. Final analysis will commence as soon as data for 2880 are collected. Conclusions: We believe that the methodology for the development of the RECAP V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritise Covid-19 patients. Clinical Trial: Trial registration number: NCT0443504

A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia

Differential effects of exogenous and endogenous cueing in multi-stream RSVP: implications for theories of attentional blink

The attentional blink (AB) refers to the finding that performance on the second of two targets (T1 and T2) in a rapid serial visual presentation (RSVP) stream is impaired when the targets are presented within 200–500 ms. To explore the possible interaction between spatial attentional orienting and temporary attentional deficits, this study used central (endogenous) and peripheral (exogenous) cues in a multi-stream RSVP task and compared the endogenous and exogenous cueing effects inside and outside of the AB period. While the endogenous cueing effect was constant in magnitude over time, the exogenous cueing effect was significantly larger inside than outside of the AB period. Theoretical implications of these findings for the interaction between attention mechanisms in spatial and temporal domains are discussed

Modelling Visual Neglect: Computational Insights into Conscious Perception

Background: Visual neglect is an attentional deficit typically resulting from parietal cortex lesion and sometimes frontal lesion. Patients fail to attend to objects and events in the visual hemifield contralateral to their lesion during visual search. Methodology/Principal Finding: The aim of this work was to examine the effects of parietal and frontal lesion in an existing computational model of visual attention and search and simulate visual search behaviour under lesion conditions. We find that unilateral parietal lesion in this model leads to symptoms of visual neglect in simulated search scan paths, including an inhibition of return (IOR) deficit, while frontal lesion leads to milder neglect and to more severe deficits in IOR and perseveration in the scan path. During simulations of search under unilateral parietal lesion, the model’s extrastriate ventral stream area exhibits lower activity for stimuli in the neglected hemifield compared to that for stimuli in the normally perceived hemifield. This could represent a computational correlate of differences observed in neuroimaging for unconscious versus conscious perception following parietal lesion. Conclusions/Significance: Our results lead to the prediction, supported by effective connectivity evidence, that connections between the dorsal and ventral visual streams may be an important factor in the explanation of perceptua

Expanded phenotype of AARS1-related white matter disease.

Purpose Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. Methods A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. Results We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile–onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile–onset and late-onset phenotypes. Conclusion We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile–onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions

Growth and characterization of gold catalyzed SiGe nanowires and alternative metal-catalyzed Si nanowires

The growth of semiconductor (SC) nanowires (NW) by CVD using Au-catalyzed VLS process has been widely studied over the past few years. Among others SC, it is possible to grow pure Si or SiGe NW thanks to these techniques. Nevertheless, Au could deteriorate the electric properties of SC and the use of other metal catalysts will be mandatory if NW are to be designed for innovating electronic. First, this article's focus will be on SiGe NW's growth using Au catalyst. The authors managed to grow SiGe NW between 350 and 400°C. Ge concentration (x) in Si1-xGex NW has been successfully varied by modifying the gas flow ratio: R = GeH4/(SiH4 + GeH4). Characterization (by Raman spectroscopy and XRD) revealed concentrations varying from 0.2 to 0.46 on NW grown at 375°C, with R varying from 0.05 to 0.15. Second, the results of Si NW growths by CVD using alternatives catalysts such as platinum-, palladium- and nickel-silicides are presented. This study, carried out on a LPCVD furnace, aimed at defining Si NW growth conditions when using such catalysts. Since the growth temperatures investigated are lower than the eutectic temperatures of these Si-metal alloys, VSS growth is expected and observed. Different temperatures and HCl flow rates have been tested with the aim of minimizing 2D growth which induces an important tapering of the NW. Finally, mechanical characterization of single NW has been carried out using an AFM method developed at the LTM. It consists in measuring the deflection of an AFM tip while performing approach-retract curves at various positions along the length of a cantilevered NW. This approach allows the measurement of as-grown single NW's Young modulus and spring constant, and alleviates uncertainties inherent in single point measurement

New approaches to the study of human brain networks underlying spatial attention and related processes

Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brain

Active Inference, Novelty and Neglect

In this chapter, we provide an overview of the principles of active inference. We illustrate how different forms of short-term memory are expressed formally (mathematically) through appealing to beliefs about the causes of our sensations and about the actions we pursue. This is used to motivate an approach to active vision that depends upon inferences about the causes of 'what I have seen' and learning about 'what I would see if I were to look there'. The former could manifest as persistent 'delay-period' activity - of the sort associated with working memory, while the latter is better suited to changes in synaptic efficacy - of the sort that underlies short-term learning and adaptation. We review formulations of these ideas in terms of active inference, their role in directing visual exploration and the consequences - for active vision - of their failures. To illustrate the latter, we draw upon some of our recent work on the computational anatomy of visual neglect