Light on! Real world evaluation of a P300-based brain-computer interface (BCI) for environment control in a smart home

Brain-computer interface (BCI) systems aim to enable interaction with other people and the environment without muscular activation by the exploitation of changes in brain signals due to the execution of cognitive tasks. In this context, the visual P300 potential appears suited to control smart homes through BCI spellers. The aim of this work is to evaluate whether the widely used character-speller is more sustainable than an icon-based one, designed to operate smart home environment or to communicate moods and needs. Nine subjects with neurodegenerative diseases and no BCI experience used both speller types in a real smart home environment. User experience during BCI tasks was evaluated recording concurrent physiological signals. Usability was assessed for each speller type immediately after use. Classification accuracy was lower for the icon-speller, which was also more attention demanding. However, in subjective evaluations, the effect of a real feedback partially counterbalanced the difficulty in BCI use. PRACTITIONER SUMMARY: Since inclusive BCIs require to consider interface sustainability, we evaluated different ergonomic aspects of the interaction of disabled users with a character-speller (goal: word spelling) and an icon-speller (goal: operating a real smart home). We found the first one as more sustainable in terms of accuracy and cognitive effort.     

Finite-tree analysis for constraint logic-based languages

Logic languages based on the theory of rational, possibly infinite, trees have much appeal in that rational trees allow for faster unification (due to the safe omission of the occurs-check) and increased expressivity (cyclic terms can provide very efficient representations of grammars and other useful objects). Unfortunately, the use of infinite rational trees has problems. For instance, many of the built-in and library predicates are ill-defined for such trees and need to be supplemented by run-time checks whose cost may be significant. Moreover, some widely used program analysis and manipulation techniques are correct only for those parts of programs working over finite trees. It is thus important to obtain, automatically, a knowledge of the program variables (the finite variables) that, at the program points of interest, will always be bound to finite terms. For these reasons, we propose here a new data-flow analysis, based on abstract interpretation, that captures such information. We present a parametric domain where a simple component for recording finite variables is coupled, in the style of the open product construction of Cortesi et al., with a generic domain (the parameter of the construction) providing sharing information. The sharing domain is abstractly specified so as to guarantee the correctness of the combined domain and the generality of the approach. This finite-tree analysis domain is further enhanced by coupling it with a domain of Boolean functions, called finite-tree dependencies, that precisely captures how the finiteness of some variables influences the finiteness of other variables. We also summarize our experimental results showing how finite-tree analysis, enhanced with finite-tree dependencies, is a practical means of obtaining precise finiteness information.     

An integer goal programming model for determining capital expenditures for correctional facilities

The selection of capital expenditure projects for the construction of state correctional facilities is often complicated by the existence of multiple and conflicting objectives on the part of the various interest groups involved in the decision-making process. While some groups view the limited availability of state funds to construct such facilities as the paramount consideration, others might consider having adequate capacity to house prisoners in a satisfactory manner, and the effect of prison overcrowding on prisoner sentencing as the primary factors in the decision to construct new facilities. As such. it is imperative that the limited funds available for constructing correctional facilities be allocated in the most efficient and satisfactory manner possible. In this paper, integer goal programming is demonstrated via a case example as a means for allocating funds for capital expenditures for new and renovated correctional facilities. Sensitivity analysis is performed using the model in order to demonstrate its capability for testing various planning scenarios including alternative priority structures, goal constraints and goal levels.     

Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic–tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.     

Iron,Neuroinflammation and Neurodegeneration

Disturbance of the brain homeostasis, either directly via the formation of abnormal proteins or cerebral hypo-perfusion, or indirectly via peripheral inflammation, will activate microglia to synthesise a variety of pro-inflammatory agents which may lead to inflammation and cell death. The pro-inflammatory cytokines will induce changes in the iron proteins responsible for maintaining iron homeostasis, such that increased amounts of iron will be deposited in cells in the brain. The generation of reactive oxygen and nitrogen species, which is directly involved in the inflammatory process, can significantly affect iron metabolism via their interaction with iron-regulatory proteins (IRPs). This underlies the importance of ensuring that iron is maintained in a form that can be kept under control; hence, the elegant mechanisms which have become increasingly well understood for regulating iron homeostasis. Therapeutic approaches to minimise the toxicity of iron include N-acetyl cysteine, non-steroidal anti-inflammatory compounds and iron chelation.     

ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.     

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.     

Mechanisms of Sensitivity and Resistance of Primary Effusion Lymphoma to Dimethyl Fumarate (DMF)

PEL is a rare B cell lymphoma associated with KSHV that mainly arises in immune-deficient individuals. The search for new drugs to treat this cancer is still ongoing given its aggressiveness and the poor response to chemotherapies. In this study, we found that DMF, a drug known for its anti-inflammatory properties which is registered for the treatment of psoriasis and relapsing–remitting MS, could be a promising therapeutic strategy against PEL. Indeed, although some mechanisms of resistance were induced, DMF activated NRF2, reduced ROS and inhibited the phosphorylation of STAT3 and the release of the pro-inflammatory and immune suppressive cytokines IL-6 and IL-10, which are known to sustain PEL survival. Interestingly, we observed that DMF displayed a stronger cytotoxic effect against fresh PEL cells in comparison to PEL cell lines, due to the activation of ERK1/2 and autophagy in the latter cells. This finding further encourages the possibility of using DMF for the treatment of PEL.