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In this chapter, we present some of the common comorbidities frequently encountered in persons with epilepsy (PWE). We begin by examining the cognitive and behavioral issues, then focus on sleep disorders, headaches, and bone health, and end by discussing the topic of sudden unexpected death in epilepsy (SUDEP). We hope that this chapter will assist physicians in providing better care to PWE.
Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity.
We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis.
Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69–410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion.
Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.
This paper reports the molecular organization and mechanical properties of electrospun, post-drawn polyacrylonitrile (PAN) nanofibers. Without post-drawing, the polymer chain was kinked and oriented in hexagonal crystalline structures. Immediate post-drawing in the semi-solid state disrupted the crystal structures and chain kink at maximum draw ratio. Structural re-orientation at maximum draw resulted in a 500% increase in Young's modulus and a 100% increase in ultimate tensile strength. By applying post-drawing to electrospinning it may be possible to obtain PAN fibers and PAN-derived carbon fibers with enhanced mechanical properties compared to available fabrication technologies.
The processes underwriting the acquisition of culture remain unclear. How are shared habits, norms, and expectations learned and maintained with precision and reliability across large-scale sociocultural ensembles? Is there a unifying account of the mechanisms involved in the acquisition of culture? Notions such as ‘shared expectations’, the ‘selective patterning of attention and behaviour’, ‘cultural evolution’, ‘cultural inheritance’, and ‘implicit learning’ are the main candidates to underpin a unifying account of cognition and the acquisition of culture; however, their interactions require greater specification and clarification. In this paper, we integrate these candidates using the variational (free energy) approach to human cognition and culture in theoretical neuroscience. We describe the construction by humans of social niches that afford epistemic resources called cultural affordances. We argue that human agents learn the shared habits, norms, and expectations of their culture through immersive participation in patterned cultural practices that selectively pattern attention and behaviour. We call this process “Thinking through Other Minds” (TTOM) – in effect, the process of inferring other agents’ expectations about the world and how to behave in social context. We argue that for humans, information from and about other people's expectations constitutes the primary domain of statistical regularities that humans leverage to predict and organize behaviour. The integrative model we offer has implications that can advance theories of cognition, enculturation, adaptation, and psychopathology. Crucially, this formal (variational) treatment seeks to resolve key debates in current cognitive science, such as the distinction between internalist and externalist accounts of Theory of Mind abilities and the more fundamental distinction between dynamical and representational accounts of enactivism.
Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8–85.6%) at 36 months and survival without disease progression was 78% (62.6–87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.
Anthropogenic habitat alteration and invasive species are threatening carnivores globally. Understanding the impact of these factors is critical for creating localized, effective conservation programmes. Madagascar's Eupleridae have been described as the least studied and most threatened group of carnivores. We investigated the effects of habitat degradation and the presence of people and exotic species on the modelled occupancy of the endemic fosa Cryptoprocta ferox, conducting camera-trap surveys in two western deciduous forests, Ankarafantsika National Park and Andranomena Special Reserve. Our results indicated no clear patterns between habitat degradation and fosa occupancy but a strong negative association between cats Felis sp. and fosas. Cat occupancy was negatively associated with birds and positively associated with contiguous forest and narrow trails. In contrast, dog Canis lupus familiaris occupancy was best predicted by wide trails, degraded forest and exotic civets. Our results suggest fosas are capable of traversing degraded landscapes and, in the short term, are resilient to contiguous forest disturbance. However, high occupancy of cats and dogs in the landscape leads to resource competition through prey exploitation and interference, increasing the risk of transmission of potentially fatal diseases. Management strategies for exotic carnivores should be considered, to reduce the widespread predation of endemic species and the transmission of disease.
We collected dietary records over the course of nine months to comprehensively characterize the consumption patterns of Malagasy people living in remote rainforest areas of north-eastern Madagascar.
The present study was a prospective longitudinal cohort study to estimate dietary diversity and nutrient intake for a suite of macronutrients, micronutrients and vitamins for 152 randomly selected households in two communities.
Madagascar, with over 25 million people living in an area the size of France, faces a multitude of nutritional challenges. Micronutrient-poor staples, especially rice, roots and tubers, comprise nearly 80 % of the Malagasy diet by weight. The remaining dietary components (including wild foods and animal-source foods) are critical for nutrition. We focus our study in north-eastern Madagascar, characterized by access to rainforest, rice paddies and local agriculture.
We enrolled men, women and children of both sexes and all ages in a randomized sample of households in two communities.
Although the Household Dietary Diversity Score and Food Consumption Score reflect high dietary diversity, the Minimum Dietary Diversity–Women indicator suggests poor micronutrient adequacy. The food intake data confirm a mixed nutritional picture. We found that the median individual consumed less than 50 % of his/her age/sex-specific Estimated Average Requirement (EAR) for vitamins A, B12, D and E, and Ca, and less than 100 % of his/her EAR for energy, riboflavin, folate and Na.
Malnutrition in remote communities of north-eastern Madagascar is pervasive and multidimensional, indicating an urgent need for comprehensive public health and development interventions focused on providing nutritional security.
Aberrant sensitivity to social reward may be an important contributor to abnormal social behavior that is a core feature of schizophrenia. The neuropeptide oxytocin impacts the salience of social information across species, but its effect on social reward in schizophrenia is unknown.
We used a competitive economic game and computational modeling to examine behavioral dynamics and oxytocin effects on sensitivity to social reward among 39 men with schizophrenia and 54 matched healthy controls. In a randomized, double-blind study, participants received one dose of oxytocin (40 IU) or placebo and completed a 35-trial Auction Game that quantifies preferences for monetary v. social reward. We analyzed bidding behavior using multilevel linear mixed models and reinforcement learning models.
Bidding was motivated by preferences for both monetary and social reward in both groups, but bidding dynamics differed: patients initially overbid less compared to controls, and across trials, controls decreased their bids while patients did not. Oxytocin administration was associated with sustained overbidding across trials, particularly in patients. This drug effect was driven by a stronger preference for winning the auction, regardless of monetary consequences. Learning rate and response variability did not differ between groups or drug condition, suggesting that differences in bidding derive primarily from differences in the subjective value of social rewards.
Our findings suggest that schizophrenia is associated with diminished motivation for social reward that may be increased by oxytocin administration.
The relation of the X-ray small-angle scattering parameters to the results of transmission electron microscopy for spherical Guinier-Preston zones was investigated. Experimentally, the Guinier radius is found to equal (<R7>/<R5>1/2) and the Porod radius to equal <R3>/<R2>. These results were theoretically predicted by Baur and Gerold, A log normal distribution was found to be in close agreement with the experimental data. The use of this distribution allowed the size-distribution curve of spherical Guinier-Preston zones to be constructed from the X-ray parameters and from a knowledge of the metastable miscibility gap. This approach is used to follow the evolution of size distribution in both Al-Ag and Al-Zn alloys. The application of this approach to nncleation and growth as well as redistribution processes is discussed. Growth paths are established from the size distribution evolution curves through an Nv> construction. A brief discussion of the technique is included.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children.
Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a reference population of Malawian children.
Children discharged from SAM treatment in 2006 and 2007 (n 320; median age 9·3 years) were compared with controls: siblings closest in age to the SAM survivors and age/sex-matched community children.
SAM survivors were significantly more likely to be in a lower grade at school than controls (adjusted OR = 0·4; 95 % CI 0·3, 0·6; P < 0·0001) and had consistently poorer scores in all CANTAB cognitive tests. Adjusting for HIV and socio-economic status diminished statistically significant differences. There were no significant differences in odds of brain abnormalities and sinusitis between SAM survivors (n 49) and reference children (OR = 1·11; 95 % CI 0·61, 2·03; P = 0·73).
Despite apparent preservation in gross brain structure, persistent impaired school achievement is likely to be detrimental to individual attainment and economic well-being. Understanding the multifactorial causes of lower school achievement is therefore needed to design interventions for SAM survivors to thrive in adulthood. The cognitive and potential economic implications of SAM need further emphasis to better advocate for SAM prevention and early treatment.
Common mental health problems affect a quarter of the population. Online cognitive–behavioural therapy (CBT) is increasingly used, but the factors modulating response to this treatment modality remain unclear.
This study aims to explore the demographic and clinical predictors of response to one-to-one CBT delivered via the internet.
Real-world clinical outcomes data were collected from 2211 NHS England patients completing a course of CBT delivered by a trained clinician via the internet. Logistic regression analyses were performed using patient and service variables to identify significant predictors of response to treatment.
Multiple patient variables were significantly associated with positive response to treatment including older age, absence of long-term physical comorbidities and lower symptom severity at start of treatment. Service variables associated with positive response to treatment included shorter waiting times for initial assessment and longer treatment durations in terms of the number of sessions.
Knowledge of which patient and service variables are associated with good clinical outcomes can be used to develop personalised treatment programmes, as part of a quality improvement cycle aiming to drive up standards in mental healthcare. This study exemplifies translational research put into practice and deployed at scale in the National Health Service, demonstrating the value of technology-enabled treatment delivery not only in facilitating access to care, but in enabling accelerated data capture for clinical research purposes.
Declaration of interest
A.C., S.B., V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety disorders; cognitive behavioural therapies; depressive disorders; individual psychotherapy
One of the more consistent characterizations of both American Fundamentalism and other versions of conservative Evangelicalism is that these groups represent authoritarian religious and social systems. Such characterizations are not entirely without some basis in fact. Fundamentalism will almost always appear authoritarian, and so too will forms of Pentecostalism which, like Fundamentalism, place a heavy emphasis on correct thinking and combine a belief in the infallibility of scripture with a commitment to literal readings. Outsiders are sometimes disconcerted to find that “authoritarian” and related concepts are not assessed negatively in conservative Evangelical circles. Quite the contrary is the case: the Bible, infallible, inerrant, “God-breathed,” is the clear center of Evangelical authority. Many a Fundamentalist sermon has sought to clinch its case with the phrase, “on authority of the holy Word of God.”
OBJECTIVES/SPECIFIC AIMS: As the sole Clinical and Translational Science Award (CTSA) site in Michigan, the Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (UM) is working to develop community networks that drive clinical and translational research on community-identified health priorities. METHODS/STUDY POPULATION: These CBRNs will be modeled from successful work that has been accomplished in Jackson, MI where stakeholders from the local healthcare community, County Health Department, Health Improvement Organization, and grassroots community members created a Community of Solution to address the unmet behavioral health and social needs of community members. The CBRN’s will focus on identifying community health priorities by receiving input from community members in underserved communities using deliberative software called Choosing All Together (CHAT). RESULTS/ANTICIPATED RESULTS: In the fall of 2017, 3 focus groups were held in Northern Michigan to identify community health priorities. The top 5 community health priorities include; (1) mental wellness, (2) long-term illness, (3) alcohol and drugs, (4) air, water, and land, and (5) affording care. Additional focus groups are scheduled for the winter in 2 additional geographic areas. DISCUSSION/SIGNIFICANCE OF IMPACT: Future work for the creation of CBRNs includes building leadership groups comprised of clinicians, community leaders, public health leaders, health system leaders and researchers to inform the leadership groups of community-identified health priorities. In addition, the team is working to identify a platform to connect academic investigators across UM and community partners on shared research priorities in real time. In order to measure and map relationships within the networks, we are planning to utilize Social Network Analysis as an evaluation tool.
Objectives: Concussions affect the processing of emotional stimuli. This study aimed to investigate how sex interacts with concussion effects on early event-related brain potentials (ERP) measures (P1, N1) of emotional facial expressions (EFE) processing in asymptomatic, multi-concussion athletes during an EFE identification task. Methods: Forty control athletes (20 females and 20 males) and 43 multi-concussed athletes (22 females and 21 males), recruited more than 3 months after their last concussion, were tested. Participants completed the Beck Depression Inventory II, the Beck Anxiety Inventory, the Post-Concussion Symptom Scale, and an Emotional Facial Expression Identification Task. Pictures of male and female faces expressing neutral, angry, and happy emotions were randomly presented and the emotion depicted had to be identified as fast as possible during EEG acquisition. Results: Relative to controls, concussed athletes of both sex exhibited a significant suppression of P1 amplitude recorded from the dominant right hemisphere while performing the emotional face expression identification task. The present study also highlighted a sex-specific suppression of the N1 component amplitude after concussion which affected male athletes. Conclusions: These findings suggest that repeated concussions alter the typical pattern of right-hemisphere response dominance to EFE in early stages of EFE processing and that the neurophysiological mechanisms underlying the processing of emotional stimuli are distinctively affected across sex. (JINS, 2018, 24, 1–11)