Intrinsic Inter-Subject Variability in Functional Neuroimaging: Verification Using Blind Source Separation Features

The holy grail of brain imaging is the identification of a biomarker, which can identify an abnormality that can be used to diagnose disease and track the effectiveness of treatment and disease progression. Typically approaches that search for biomarkers start by identifying mean differences between groups of patients and healthy controls. However, combining data from different subjects and groups to be able to make meaningful inferences is not trivial. The structure of the brain in each individual is unique in size and shape as well as in the relative location of anatomical landmarks (e.g. sulci and gyri). When looking for mean differences in functional images, this issue is exacerbated by the presence of variability in functional localization, i.e. variability in the location of functional regions in the brain. This is notably an important reason to focus on looking for inter-individual differences or variability. Inter-subject variability in neuroimaging experiments is often viewed as noise. The analyses are setup in a manner to ignore this variability assuming that a global spatial normalization brings the data into the same space. Nonetheless, functional activation patterns can be impacted by variability in multiple ways for e.g., there could be spatial variability of the maps or variability in the spectral composition of the timecourses or variability in the connectivity between the activation patterns identified. The overarching problem this thesis seeks to contribute to, is seeking improved measures to quantify biologically significant spatial, spectral and connectivity based variability and to identify associated cognitive or behavioral differences in the distribution of brain networks. We have successfully shown that different (spatial and spectral) measures of variability in blind source separated functional activation patterns underline previously unexplained characteristics that help in discerning schizophrenia patients from healthy controls. Additionally, we show that variance measures in dynamic connectivity between networks in healthy controls can justify relationship between connectivity patterns and executive functioning abilities

Rapid pulsation growth at quasi-parallel collisionless shocks.

M.Phil.The bow shock is a shock wave that forms ahead of the Earth's magnetosphere in the collisionless supersonic flow of the solar wind. The quasi-parallel shock forms when the interplanetary magnetic field makes an angle of less than 45 degrees with the shock normal. Observations show the presence of magnetic pulsations, energetic diffuse ions and cooler, denser specularly reflected ions at the shock. Shock reformation involving the growth of magnetic pulsations is a key component of the structure of Earths quasi-parallel bow shock. This thesis aims to explore the rapid growth mechanism of these pulsations and hence increase our understanding of the structure of the quasi- parallel shock, which is generally less well understood than quasi-perpendicular shock. Using a hybrid simulation model of the interaction between shock reflected ions and upstream waves we study the effect of varying the parameters which control the growth of waves into large amplitude pulsations. A number of features are observed providing an insight into the growth mechanisms. Reflected ion beams can cause strong coupling with the pulse due to nonlinear cyclotron effects, and cause a narrow feature to develop. On the other hand, the diffuse ions show a relatively weaker interaction with the pulse and no narrow feature is generated. A strong interaction with the diffuse ions requires an unrealistically high density. However, in both cases, it is clear that the ULF wave does not simply just grow, as the pulse does not remain with the ions that cause the interaction. Instead the pulse splits and launches a new beamward (i.e., in the beam direction) wave in the simulation frame. This result may explain the spacecraft observation that pulsations appear to slow down in the spacecraft frame. The newly launched propagating wave seems to have some of the same properties as solitons. Comparisons are made with observations from the Cluster spacecraft. Hence, the results give us a greater insight into the wave-particle dynamics in the reformation process and implications for particle acceleration at the quasi-parallel shock.STFC studentship

Electroconvulsive Therapy Response in Major Depressive Disorder: a Pilot Functional Network Connectivity Resting State FMRI Investigation

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treat- ment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case–control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and func- tional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treat- ment.The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode

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

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

Sonic Therapeutic Intervention: A Better Medicine for the Future

Sonic Therapeutic Intervention (STI) is, in essence, a method of healing and self-improvement based on the regular administration of particular sound vibrations. Based on the fundamental principle that various types of sounds have particular effects on the mind and body, Sonic Therapeutic Intervention seeks to take advantage of those sounds that are most beneficial to the mind, in order to create various positive effects — including decreased anger and anxiety, more developed cognitive function, improved decision-making ability, and increased self-control. With regular practice, Sonic Therapeutic Intervention is effectively able to enact these beneficial effects, thus destroying the root causes of a variety of social and psychological problems

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Children's preferences for different kinds of dental attires: The concept of psychological modulation of children's behavior by different kinds of attires in dental clinics

Context: Psychologists highlight the importance of appearance and its effect upon first impressions and the development of interpersonal relationship. How a dental surgeon dresses may be important in determining the success of dental surgeon–patient relationship. Different dental attires may evoke different feelings according to their appearances. Knowing the children's preferences for different kinds of dental attire, a dental surgeon may determine the most child-friendly attire and the care provided by dental surgeons can be, further, improved. Aims: The aim of the present study was to assess children's preferences for different kinds of dental attire and to investigate and relate the influence of age, socioeconomic status, effect of media, and the previous exposure to a dental setup on children's preferences. Materials and Methods: A total of 2500 schoolchildren in the age group of 9–14 years were interviewed on their preferences individually for different kinds of dental attire followed by a questionnaire. Ten photographs of five male and five female dental surgeons in different modes of attire were shown to children and asked to give their preferences. The completely answered questionnaires by children were collected on the same day from the children and by parents the next day. Statistical Analysis Used: Collected data were compiled and analyzed. Statistical analysis was performed with SPSS (version 13, SPSS Inc., Chicago, USA) package. The statistical tests used for the analysis were Chi-square test, Fisher's exact test, and linear association. Results: The results obtained revealed that 35.6% of children preferred white coat the most followed by the attire-scrubs with cartoon (21.8%) for male dental surgeons while 38.2% of children preferred white coat followed by formal attire (28.4%) for the female dental surgeons. Conclusion: White coat is the most preferred attire by children followed by scrubs with cartoons and formal attire. Plain scrub was the least preferred. Age and socioeconomic status have definite influence on the preferences of children as lower class and higher age groups showed more inclination toward white coat. Past dental experiences and effect of media showed no significant effect on children's preferences