107 research outputs found

    Prevalence And Predictors Of Attention Deficit Hyperactivity Disorder In Adolescent And Adult Males With Fragile X Syndrome And Autism Spectrum Disorder

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    Individuals with fragile X syndrome (FXS) experience disproportionate rates of diagnoses of attention-deficit/hyperactivity disorder (ADHD) when compared to the general population. Exact prevalence rates and outcomes for individuals with a diagnosis of FXS and ADHD is not well known. The current study assesses rates of ADHD diagnosis in individuals with FXS as well as tests the prediction of a diagnosis of ADHD from levels of autism spectrum disorder (ASD) symptom presentation. The present study included 30 individuals with FXS aged 13-25 and were assessed using a structured diagnostic interview. Interviews were conducted with individual’s parents’ due to low cognitive ability found in individuals with FXS. ASD symptoms were not found to be a significant predictor of ADHD in our sample. Diagnostic prevalence rates of ADHD were found to be 45% for the FXS sample. Individuals with FXS experience diagnostic rates of ADHD significantly higher than those found in the general population. The presence of ASD does not appear to account for the differences found in these rates

    Discharge Identity of Medullary Inspiratory Neurons is Altered during Repetitive Fictive Cough

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    This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing

    Semiclassical Theory of Coulomb Blockade Peak Heights in Chaotic Quantum Dots

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    We develop a semiclassical theory of Coulomb blockade peak heights in chaotic quantum dots. Using Berry's conjecture, we calculate the peak height distributions and the correlation functions. We demonstrate that the corrections to the corresponding results of the standard statistical theory are non-universal and can be expressed in terms of the classical periodic orbits of the dot that are well coupled to the leads. The main effect is an oscillatory dependence of the peak heights on any parameter which is varied; it is substantial for both symmetric and asymmetric lead placement. Surprisingly, these dynamical effects do not influence the full distribution of peak heights, but are clearly seen in the correlation function or power spectrum. For non-zero temperature, the correlation function obtained theoretically is in good agreement with that measured experimentally.Comment: 5 color eps figure

    Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework

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    © 2019 Author(s). As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often nonintuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline various efforts to extend immersive technologies to the molecular sciences, and we introduce "Narupa," a flexible, open-source, multiperson iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn potential energy functions, biomolecular conformational sampling, protein-ligand binding, reaction discovery using "on-the-fly" quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances and outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures

    Anomalies and Vector Space Search: Tools for S-Box Analysis

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    International audienceS-boxes are functions with an input so small that the simplest way to specify them is their lookup table (LUT). How can we quantify the distance between the behavior of a given S-box and that of an S-box picked uniformly at random? To answer this question, we introduce various "anomalies". These real numbers are such that a property with an anomaly equal to should be found roughly once in a set of 2a2^a random S-boxes. First, we present statistical anomalies based on the distribution of the coefficients in the difference distribution table, linear approximation table, and for the first time, the boomerang connectivity table. We then count the number of S-boxes that have block-cipher like structures to estimate the anomaly associated to those. In order to recover these structures, we show that the most general tool for decomposing S-boxes is an algorithm efficiently listing all the vector spaces of a given dimension contained in a given set, and we present such an algorithm. Combining these approaches, we conclude that all permutations that are actually picked uniformly at random always have essentially the same cryptographic properties and the same lack of structure

    Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic

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    BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients.ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result

    Exploring knowledge, perception of risk and biosecurity practices among researchers in the UK: a quantitative survey

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    Accidental introduction and/or spread of Invasive Non-Native Species (INNS) can result from a range of activities including agriculture, transport, trade and recreation. Researchers represent an important group of stakeholders who undertake activities in the field that could potentially facilitate the spread of INNS. Biosecurity is key to preventing the introduction and spread of INNS. Risk perceptions are a fundamental component in determining behaviour, so understanding how researchers perceive the risks associated with their activities can help us understand some of the drivers of biosecurity behaviour in the field. The aim of this study was to investigate researchers’ perceptions of risk in relation to their field activities and whether risk perceptions influenced behaviour. We gathered quantitative data on perceptions of risk and biosecurity practices using an online questionnaire. Only 35% of all respondents considered their field activities to pose some risk in terms of spreading INNS. Higher risk perception was found in those who undertook high risk activities or where INNS were known/expected to be present. However, whilst respondents with experience of INNS were more likely to report consciously employing biosecurity in the field, this did not translate into better actual biosecurity practices. Awareness of biosecurity campaigns did in fact increase perception of risk, perceived and actual biosecurity behaviour. However, there remains a disconnect between reported and actual biosecurity practices, including a lack of understanding about what constitutes good biosecurity practice. These findings should be used to improve targeted awareness raising campaigns and help create directed training on biosecurity practices

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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