Advancing Brain-Computer Interface System Performance in Hand Trajectory Estimation with NeuroKinect

Brain-computer interface (BCI) technology enables direct communication between the brain and external devices, allowing individuals to control their environment using brain signals. However, existing BCI approaches face three critical challenges that hinder their practicality and effectiveness: a) time-consuming preprocessing algorithms, b) inappropriate loss function utilization, and c) less intuitive hyperparameter settings. To address these limitations, we present \textit{NeuroKinect}, an innovative deep-learning model for accurate reconstruction of hand kinematics using electroencephalography (EEG) signals. \textit{NeuroKinect} model is trained on the Grasp and Lift (GAL) tasks data with minimal preprocessing pipelines, subsequently improving the computational efficiency. A notable improvement introduced by \textit{NeuroKinect} is the utilization of a novel loss function, denoted as $\mathcal{L}_{\text{Stat}}$. This loss function addresses the discrepancy between correlation and mean square error in hand kinematics prediction. Furthermore, our study emphasizes the scientific intuition behind parameter selection to enhance accuracy. We analyze the spatial and temporal dynamics of the motor movement task by employing event-related potential and brain source localization (BSL) results. This approach provides valuable insights into the optimal parameter selection, improving the overall performance and accuracy of the \textit{NeuroKinect} model. Our model demonstrates strong correlations between predicted and actual hand movements, with mean Pearson correlation coefficients of 0.92 ($\pm$0.015), 0.93 ($\pm$0.019), and 0.83 ($\pm$0.018) for the X, Y, and Z dimensions. The precision of \textit{NeuroKinect} is evidenced by low mean squared errors (MSE) of 0.016 ($\pm$0.001), 0.015 ($\pm$0.002), and 0.017 ($\pm$0.005) for the X, Y, and Z dimensions, respectively

An F-ratio-Based Method for Estimating the Number of Active Sources in MEG

Magnetoencephalography (MEG) is a powerful technique for studying the human brain function. However, accurately estimating the number of sources that contribute to the MEG recordings remains a challenging problem due to the low signal-to-noise ratio (SNR), the presence of correlated sources, inaccuracies in head modeling, and variations in individual anatomy. To address these issues, our study introduces a robust method for accurately estimating the number of active sources in the brain based on the F-ratio statistical approach, which allows for a comparison between a full model with a higher number of sources and a reduced model with fewer sources. Using this approach, we developed a formal statistical procedure that sequentially increases the number of sources in the multiple dipole localization problem until all sources are found. Our results revealed that the selection of thresholds plays a critical role in determining the method`s overall performance, and appropriate thresholds needed to be adjusted for the number of sources and SNR levels, while they remained largely invariant to different inter-source correlations, modeling inaccuracies, and different cortical anatomies. By identifying optimal thresholds and validating our F-ratio-based method in simulated, real phantom, and human MEG data, we demonstrated the superiority of our F-ratio-based method over existing state-of-the-art statistical approaches, such as the Akaike Information Criterion (AIC) and Minimum Description Length (MDL). Overall, when tuned for optimal selection of thresholds, our method offers researchers a precise tool to estimate the true number of active brain sources and accurately model brain function

An F-ratio-based method for estimating the number of active sources in MEG

IntroductionMagnetoencephalography (MEG) is a powerful technique for studying the human brain function. However, accurately estimating the number of sources that contribute to the MEG recordings remains a challenging problem due to the low signal-to-noise ratio (SNR), the presence of correlated sources, inaccuracies in head modeling, and variations in individual anatomy.MethodsTo address these issues, our study introduces a robust method for accurately estimating the number of active sources in the brain based on the F-ratio statistical approach, which allows for a comparison between a full model with a higher number of sources and a reduced model with fewer sources. Using this approach, we developed a formal statistical procedure that sequentially increases the number of sources in the multiple dipole localization problem until all sources are found.ResultsOur results revealed that the selection of thresholds plays a critical role in determining the method's overall performance, and appropriate thresholds needed to be adjusted for the number of sources and SNR levels, while they remained largely invariant to different inter-source correlations, translational modeling inaccuracies, and different cortical anatomies. By identifying optimal thresholds and validating our F-ratio-based method in simulated, real phantom, and human MEG data, we demonstrated the superiority of our F-ratio-based method over existing state-of-the-art statistical approaches, such as the Akaike Information Criterion (AIC) and Minimum Description Length (MDL).DiscussionOverall, when tuned for optimal selection of thresholds, our method offers researchers a precise tool to estimate the true number of active brain sources and accurately model brain function

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

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

Cytologic diagnosis of undifferentiated high grade pleomorphic sarcoma of breast presenting with brain metastasis

Primary sarcoma of breast are rare. Diagnosis by aspiration cytology is difficult due to nonspecific cytomorphologic features. An initial presentation with neurological symptoms due to metastasis of breast sarcoma to the brain has not been previously reported. Here, we describe a case of a 60‑year-old female who presented with headache, dizziness and convulsion and was subsequently diagnosed with undifferentiated high grade pleomorphic sarcoma of breast with cerebellar metastasis