Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors

Background: Accelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30 min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues. Methods: Forty-four patients with a history of focal seizures were tested at 30 min and 7 day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30 min or intact memory performance. Results: The incidence of ALF in the epilepsy patients (18%) was > 3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF. Conclusions: Many patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints

Coordinating Development of the SWARM-EX CubeSat Swarm Across Multiple Institutions

The Space Weather Atmospheric Reconfigurable Multiscale Experiment (SWARM-EX) is a National Science Foundation (NSF) sponsored CubeSat mission distributed across six colleges and universities in the United States. The project has three primary goals: (1) contributing to aeronomy and space weather knowledge, (2) demonstrating novel engineering technology, and (3) advancing higher education. The scientific focus of SWARM-EX is to study the spatial and temporal variability of ion-neutral interactions in the equatorial Ionosphere-Thermosphere (I-T) region. Since the mission consists of three spacecraft operating in a swarm, SWARM-EX will take in-situ measurements of the neutral and ion composition on timescales of less than an orbital period to study the persistence and correlation between different phenomena in the I-T region. The engineering objectives of SWARM-EX are focused on advancing the state of the art in spacecraft formation flying. In addition to being the first passively safe, autonomous formation of more than two spacecraft, SWARM-EX will demonstrate several other key innovations. These include a novel hybrid propulsive/differential drag control scheme and the realization of a distributed aeronomy sensor. Asa project selected by the NSF for its broader impacts as well as its intellectual merit, SWARM-EX aims to use CubeSat development as a vehicle for education. The six collaborating institutions have varying levels of CubeSat experience and involve students who range from first-year undergraduates to Ph.D. candidates. These differences in knowledge, as well as the distributed nature of the program, present a tremendous educational opportunity, but also raise challenges such as cross-institutional communication and coordination, document sharing and file management, and hardware development. By detailing its procedures for overcoming these challenges, the SWARM-EX team believes that it may serve as a case study for the coordination of a successful CubeSat program distributed across multiple institutions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Cerebral processes during visuo-motor imagery of hands

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Examining factors related to accelerated long-term forgetting in epilepsy using ambulatory EEG monitoring

Summary Purpose Some patients with epilepsy demonstrate normal memory when this is tested at relatively short intervals (e.g., 30 min), but substantial loss over longer delay periods (e.g., days or weeks) when compared to healthy control subjects. This pattern of "accelerated long-term forgetting" (ALF) affects the everyday lives of patients, yet goes undetected by standard neuropsychological memory tests, and its pathophysiologic basis is poorly understood. By testing memory over a period of concurrent ambulatory electroencephalography (EEG), the current study aimed to investigate possible factors contributing to ALF. Methods Thirty-nine patients diagnosed with epilepsy or probable epilepsy underwent 5 days of continuous ambulatory EEG: 18 had normal EEG studies, 10 had focal epileptic discharges, 5 had generalized epileptic discharges, and 6 had one or more seizures. Fifteen matched healthy control subjects also participated, but did not undergo EEG. Subjects were taught 13-item word and design lists to criterion, and recall was tested at 30 min, 24 h, and 4 days. Subjects also completed questionnaires pertaining to everyday memory and mood. Key Findings Group analyses (excluding patients who experienced seizures during monitoring) indicated that patients who experienced generalized discharges during the 24-h to 4-day delay intervals showed higher rates of forgetting for nonverbal information. Those with focal discharges showed ALF between 30 min and 4 days for verbal information, whereas those with normal EEGs over the 4 days recording had no evidence of ALF. Surprisingly, mood and epilepsy variables (such as duration of disease or number of anticonvulsant medications) showed no significant correlation with ALF. Although no aspect of nighttime sleep architecture was found to be related to recall after the first 24 h, daytime naps were associated with better retention. Self-report of everyday memory functioning was related to recall at longer delays, but not at 30 min. Significance The present findings indicated that ALF in epilepsy is associated with subclinical discharges rather than antiepileptic drugs (AEDs), mood or sleep disturbance. Measures of longer-term recall can reveal correlations with subjective everyday memory complaints that are not evident when recall is only tested at a standard (30 min) delay interval. These findings have the potential to improve treatment strategies for patients who complain of memory difficulties.9 page(s

Impairments in the perception of odor-induced tastes and their relationship to impairments in taste perception

Certain odors have tastelike qualities when sniffed. To the extent that these qualities are akin to real taste experiences, impairment in perception of odor-induced tastes should be accompanied by taste impairment, and vice versa. Twelve patients were selected with possible odor-induced taste impairments or general taste impairments via a screening test, along with a further 6 patients with a probable taste impairment (insular lesion). These 18 patients, along with 19 normal controls, completed a battery of odor, taste, visual control, and neuropsychological tests to assess impairments in odor-induced taste perception and general taste perception. Four patients had an odor-induced taste impairment and were also impaired on taste perception. A further analysis, using regression on the whole sample, indicated that taste impairments were associated with odor-induced taste abnormalities independent of other predictors. This pattern also held for the patient group alone. The insular patients also exhibited both taste and odor-induced taste impairments. This study is the first to demonstrate a relationship between impaired taste perception and the perception of odor-induced tastes and suggests that both may rely on certain common neural substrates.15 page(s

Old dogs with new tricks : detecting accelerated long-term forgetting by extending traditional measures

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18–60 years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30 min and 7 days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30 min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.7 page(s

Improving memory in outpatients with neurological disorders using a group-based training program

Memory problems are common in patients with a range of neurological conditions, but there have been few attempts to provide and evaluate the usefulness of memory training for groups of neurological outpatients. We used a waitlist-controlled trial design to assess the effectiveness of a newly created, 6-session intervention, which involved training in the use of compensatory strategies as well as education regarding memory function, neurological damage, sleep and lifestyle factors that have an impact on memory. Fifty-six patients with neurological conditions (e.g., stroke, epilepsy) and memory complaints completed the training and assessments. Outcomes were evaluated in terms of reported strategy use as well as objective and subjective measures of anterograde and prospective memory. Training resulted in significant improvements on number of strategies used, scores on the Rey Auditory Verbal Learning Test (total learning and delayed recall) and self-report on the Comprehensive Assessment of Prospective Memory. Improvements were stable at 3-month follow-up. Better individual outcomes were related to lower baseline memory scores, fewer symptoms of depression and greater self-awareness of memory function. Overall the study provides encouraging results to indicate that patients with neurological conditions such as stroke and epilepsy can show improvements in memory after a relatively short group-based intervention.11 page(s