Imaginative Representations of Two- and Three-Dimensional Matrices in Children with Nonverbal Learning Disabilities

Children with non-verbal learning disabilities (NLD) are characterized by high verbal and poor non-verbal intelligence, poor cognitive abilities, school difficulties, and—sometimes—depressive symptoms. NLD children lack visuospatial working memory, but it is not clear whether they encounter difficulties in mental imagery tasks. In the present study, NLD adolescents without depressive symptoms, depressed adolescents without NLD symptoms, and a control group were administered a mental imagery task requiring them to imagine to move along the cells of a 2-D (5 × 5) or 3-D (3 × 3 × 3) matrix. Results showed that NLD adolescents had difficulty at performing the imagery task when a 3-D pattern was involved. It is suggested that 3-D mental imagery tasks tap visuospatial processes which are weak in NLD individuals. In addition, their poor cognitive performance cannot be attributed to a depressive state, as the depressed group had a performance similar to that of controls

Understanding uncertainty in self-adaptive systems

Ensuring that systems achieve their goals under uncertainty is a key driver for self-adaptation. Nevertheless, the concept of uncertainty in self-adaptive systems (SAS) is still insufficiently understood. Although several taxonomies of uncertainty have been proposed, taxonomies alone cannot convey the SAS research community's perception of uncertainty. To explore and to learn from this perception, we conducted a survey focused on the SAS ability to deal with unanticipated change and to model uncertainty, and on the major challenges that limit this ability. In this paper, we analyse the responses provided by the 51 participants in our survey. The insights gained from this analysis include the view - held by 71% of our participants - that SAS can be engineered to cope with unanticipated change, e.g., through evolving their actions, synthesising new actions, or using default actions to deal with such changes. To handle uncertainties that affect SAS models, the participants recommended the use of confidence intervals and probabilities for parametric uncertainty, and the use of multiple models with model averaging or selection for structural uncertainty. Notwithstanding this positive outlook, the provision of assurances for safety-critical SAS continues to pose major challenges according to our respondents. We detail these findings in the paper, in the hope that they will inspire valuable future research on self-adaptive systems

HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy

The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naïve CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure. In silico analysis showed spatial proximity of some of the newly-identified, mutated RT residues to the RT catalytic centre while most S-substitutions caused alteration in epitope hydrophobicity. TDF administration resulted in virological response in 60% of LMV-failed patients at 24-week but non-response in 40% of patients even after 48-weeks. Significantly high frequencies of 6 S-substitutions and one novel RT-substitution, rtH124N with 6.5-fold-reduced susceptibility to TDF in vitro, were noted at baseline in TDF non-responders than responders. Follow-up studies depicted greater evolutionary drift of HBV quasispecies and significant decline in frequencies of 3 RT and 6 S-substitutions in responder-subgroup after 24-week TDF-therapy while most variants persisted in non-responders. Thus, we identified the HBV-RT/S variants that could potentially predict unfavorable response to LMV/TDF-therapy and impede immune-mediated viral clearance

Identifying confidentiality violations in architectural design using palladio

Meeting confidentiality requirements in software systems is vital for organizations. Considering confidentiality in early development phases such as the architectural design phase is beneficial compared to late phases such as the implementation because fixing design issues is more cost-efficient in early phases. This tutorial introduces an approach for modeling and statically analyzing confidentiality in software architectures within the Palladio tool suite. Besides foundational knowledge, the tutorial provides a practical hands-on session using the tool. The goal is to show that it is already possible to consider confidentiality in the early design process and that this consideration can be integrated into existing architectural design tools

Temporal Lobe Spikes Affect Distant Intrinsic Connectivity Networks

Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE). Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE. Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus. Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level

ROS in platelet biology: Functional aspects and methodological insights

© 2020 by the authors. Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Physical activity and redox balance in the elderly: Signal transduction mechanisms

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy