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Background: Stroke is a leading cause of long-term disability. Greater rehabilitation therapy after stroke is known to improve functional outcomes. This study examined therapy doses during the first year of stroke recovery and identified factors that predict rehabilitation therapy dose. Methods: Adults with new radiologically confirmed stroke were enrolled 2 to 10 days after stroke onset at 28 acute care hospitals across the United States. Following an initial assessment during acute hospitalization, the number of physical therapy, occupational therapy, and speech therapy sessions were determined at visits occurring 3, 6, and 12 months following stroke. Negative binomial regression examined whether clinical and demographic factors were associated with therapy counts. False discovery rate was used to correct for multiple comparisons. Results: Of 763 patients enrolled during acute stroke admission, 510 were available for follow-up. Therapy counts were low overall, with most therapy delivered within the first 3 months; 35.0% of patients received no physical therapy; 48.8%, no occupational therapy, and 61.7%, no speech therapy. Discharge destination was significantly related to cumulative therapy; the percentage of patients discharged to an inpatient rehabilitation facility varied across sites, from 0% to 71%. Most demographic factors did not predict therapy dose, although Hispanic patients received a lower cumulative amount of physical therapy and occupational therapy. Acutely, the severity of clinical factors (grip strength and National Institutes of Health Stroke Scale score, as well as National Institutes of Health Stroke Scale subscores for aphasia and neglect) predicted higher subsequent therapy doses. Measures of impairment and function (Fugl-Meyer, modified Rankin Scale, and Stroke Impact Scale Activities of Daily Living) assessed 3 months after stroke also predicted subsequent cumulative therapy doses. Conclusions: Rehabilitative therapy doses during the first year poststroke are low in the United States. This is the first US-wide study to demonstrate that behavioral deficits predict therapy dose, with patients having more severe deficits receiving higher doses. Findings suggest directions for identifying groups at risk of receiving disproportionately low rehabilitation doses.

Federal administrations have been addressing the problem of hunger in Brazil since the days of Lula da Silva. An extensive review of the literature shows that the fight against hunger reached its highest level of priority during the Lula da Silva administrations (2003–2010), where it was organized with an institutional structure and seen as an international model for public policy. Every subsequent government since then has given less attention to it, ending in the complete neglect of the issue under the Bolsonaro administration. Governos federais têm abordado o problema da fome no Brasil desde a época de Lula da Silva. Uma revista exhaustiva da literatura aponta que a luta contra a fome atingiu o seu apogeu quando lhe foi atribuída máxima proridade na agenda política federal durante os governos Lula da Silva (2003–2010) onde era organizada com base numa estrutura institucional que é hoje celebrada como modelo internacional de política pública. Desde então, cada governo sucessivo prestou cada vez menos atenção à fome, acabando no descaso completo do assunto sob o governo Bolsonaro.

Assessments, even summative, are part of the learning journey not just for the student, but for the instructors as well. In competency-based education, performance assessments (PAs) are regarded as a highly authentic method of measurement, but their complexity makes them vulnerable to construct-irrelevant variance such as group bias. A differential item functioning (DIF) study was conducted to detect potential bias in a series of information technology PA tasks in which task scenarios were identified (by SMEs) as neutral or potentially controversial, where the latter was hypothesized as more likely to trigger DIF for certain demographics. Given the variety of DIF methods available and their relative strengths and weaknesses, three common statistical methods – Mantel-Haenszel (MH), logistic regression (LR), and Lord's chi-square (LC) - were used followed by a substantive review of DIF items. Hypotheses were largely supported by the analysis and review. Discussion centers on the implication of findings for assessment strategies in education.

The way people communicate — be it verbally, visually, or via text– is indicative of personality traits. In social media the concept of the status update is used for individuals to communicate to their social networks in an always-on fashion. In doing so individuals utilize various kinds of speech acts that, while primarily communicating their content, also leave traces of their personality dimensions behind. We human-coded a set of Facebook status updates from the myPersonality dataset in terms of speech acts label and then experimented with surface level linguistic features including lexical, syntactic, and simple sentiment detection to automatically label status updates as their appropriate speech act. We apply supervised learning to the dataset and using our features are able to classify with high accuracy two dominant kinds of acts that have been found to occur in social media. At the same time we used the coded data to perform a regression analysis to determine which speech acts are significant of certain personality dimensions. The implications of our work allow for automatic large-scale personality identification through social media status updates.

Programs in an online competency-based higher education (OCBHE) institute will focus on a set of skills and competencies that form a theme throughout multiple courses, where one course builds upon another in terms of increasing the strength or depth of competency. Thus, for students within a given program or major, it is ideal for scores from course assessments with overlapping content to correlate and indicate higher-order skills or competencies. The purpose of this study was to use factor analysis to test the internal and structural validity of course-level performance assessment scores for a group of courses taken as part of a data analytics program in an OCBHE institution. Moreover, the presence of program-level competencies was investigated using hierarchical factor analysis for two groups: a faster, shorter course track and a slow, longer course track. Results supported validity at the course level as well as the presence of a higher-order factor (program-level competency) for the fast course track but not the slow track.

Assessment is the cornerstone of competency-based higher education because the outcome of the assessment ultimately determines whether the student has demonstrated competence in a job-related skill and is thus able to advance in one's career. As a result, the assessment development process must be sufficiently thorough and data-driven to produce high quality assessments. To address concerns and changes in higher education, a multi-stage, longitudinal assessment development cycle is proposed. In Stage 1, assessment specifications and design are established. Stage 2 culminates in the building of assessment forms and standard setting. Stage 3 involves administration and scoring of assessments. Stage 4 focuses on evaluating the validity of assessments via several assessment quality indicators (AQIs). Finally, these stages repeat over time due to a variety of factors such as aberrations in the AQI metrics and the results of large-scale validity studies, resulting in continuous quality improvement of assessments.

Objective To determine the effect of adding the Activity Measure for Post-Acute Care (AM-PAC) Inpatient ‘6-Clicks’ Short Forms to the Morse Fall Scale (MFS) to assess fall risk. Falls that occur in a rehabilitation hospital result in increased morbidity and mortality, increased cost, and negatively affect reimbursement. Identifying individuals at high risk for falls would enable targeted fall prevention strategies and facilitate appropriate resource allocation to address this critical patient safety issue. Design We used a retrospective observational design and repeated k-fold cross-validation (10 repeats and 10 folds) of logistic regression models with falls regressed onto: MFS alone, AM-PAC basic mobility and applied cognitive scales alone, and MFS and AM-PAC combined. Setting Inpatient rehabilitation hospital. Participants After exclusions, 2007 patients from an inpatient setting (N=2007; 131 experienced a fall). Primary diagnoses included 602 individuals with stroke (30%), 502 with brain injury (25%), 321 with spinal cord injury (16%), and 582 with other diagnoses (29%). Interventions Not applicable. Main Outcome Measures Experience of a fall during inpatient stay. Results The MFS at admission was associated with falls (area under the curve [AUC], 0.64). Above and beyond the MFS, AM-PAC applied cognitive and basic mobility at admission were also significantly associated with falls (combined model AUC, 0.70). Although MFS and applied cognition showed linear associations, there was evidence for a nonlinear association with AM-PAC basic mobility. Conclusions The AM-PAC basic mobility and AM-PAC applied cognitive scales showed associations with falls above and beyond the MFS. More work is needed to validate model predictions in an independent sample with truly longitudinal data; prediction accuracy would also need to be substantially improved. However, the current data do suggest that the AM-PAC has the potential to reduce the burden of fall management by focusing resources on a smaller cohort of patients identified as having a high fall risk.

The cardiac action potential (AP) is vital for understanding healthy and diseased cardiac biology and drug safety testing. However, techniques for high throughput cardiac AP measurements have been limited. Here, we introduce a novel technique for reliably increasing the coupling of cardiomyocyte syncytium to planar multiwell microelectrode arrays, resulting in a stable, label-free local extracellular action potential (LEAP). We characterized the reliability and stability of LEAP, its relationship to the field potential, and its efficacy for quantifying AP morphology of human induced pluripotent stem cell derived and primary rodent cardiomyocytes. Rise time, action potential duration, beat period, and triangulation were used to quantify compound responses and AP morphology changes induced by genetic modification. LEAP is the first high throughput, non-invasive, label-free, stable method to capture AP morphology from an intact cardiomyocyte syncytium. LEAP can accelerate our understanding of stem cell models, while improving the automation and accuracy of drug testing.

Background Motor learning has been investigated using various paradigms, including serial reaction time tasks (SRTT) that examine upper extremity reaching and pointing while seated. Few studies have used a stepping SRTT, which could offer additional insights into motor learning involving postural demands. For a task to measure motor learning, naive participants must demonstrate a) improved performance with task practice, and b) a dose-response relationship to learning the task. Research question Is a stepping SRTT feasible and efficacious for measuring motor learning? Methods In this prospective study, 20 participants stood on an instrumented mat and were presented with stimuli on a computer screen. They stepped to the corresponding positions on the mat as quickly as possible. Presented stimuli included random sequences and a blinded imbedded repeating sequence. Three days after completing the randomly assigned practice dose [high dose group (n = 10) performed 4320 steps; low dose group (n = 10) performed 144 steps], a retention test of 72 steps was performed. Feasibility was measured as the proportion of participants who completed the assigned practice dose without adverse events. Efficacy was measured as within-group performance improvement on the random sequences and on the repeating sequence (paired t-tests), as well as a dose-response relationship to learning both types of sequences (independent t-tests). Results All participants (mean age 26.8 years) completed all practice sessions without adverse events, indicating feasibility. High dose practice resulted in performance improvement while low dose did not; a dose-response relationship was found, with high dose practice resulting in greater learning of the task than low dose practice, indicating efficacy. Significance This stepping SRTT is a feasible and efficacious way to measure motor learning, which could provide critical insights into anticipatory stepping, postural control, and fall risk. Future research is needed to determine feasibility, efficacy, and optimal practice dosages for older and impaired populations.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor—1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world’s population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index

Background Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI ( Methods To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. Discussion The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. Trial registration ClinicalTrials.gov, NCT02632422. Registered 16 December 2015

Greater consumption of oily fish, and elevated plasma levels of the long-chain marine-derived omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been strongly and consistently associated with a reduced incidence of heart attacks, strokes, cognitive decline, Alzheimer's disease and cancers. Despite international guidelines recommending eating oily fish at least once per week (> 250mg/day DHA and EPA), many people do not eat fish, and only a small minority of the world's population have optimal omega-3-PUFA plasma and tissue levels. Hence, in this project, we studied the bioavailability and blood pressure lowering effects of recently developed alternatives to oily fish, namely chicken-meat and eggs naturally enriched with algae-sourced omega-3-PUFAs.This was a double-blinded, controlled, randomised trial. Using a 2X2 factorial design, 161 healthy participants were randomized to eat at least 3 portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least 3 omega-3-PUFA enriched (or control) eggs/week, for 6 months.Compared to control foods, eating enriched eggs, enriched chicken-meat and the combination for 6 months, resulted in plasma EPA increments (μg/g) of 3.1[2.8], 8.8[2.9]* & 4.7[2.9], plasma DHA increments (μg/g) of 5.1[3.7], 9.3[3.8]* & 13.1[3.9]*, and omega-3-index (sum of EPA + DHA as a percentage of total fatty acids in erythrocytes, %) increments of 0.9[0.3]*, 0.7[0.4]* & 1.5[0.4]*, respectively. Mean 24-hour ambulatory blood pressure (systolic/diastolic, mmHg) declined with the enriched foods 0.3[1.3]/-0.2[1.0], -0.7[1.4]/-1.4[1.0], & -1.9[1.4]/-2.9[1.0]*, respectively. Data provided as mean difference[SEM], and * denotes p < 0.05.Regular consumption of omega-3-PUFA enriched chicken-meat and eggs resulted in statistically significant and clinically relevant increases in plasma and red cell levels of DHA and EPA. Both plasma and red cell bioavailability were similar to those previously described for oily fish. Furthermore, blood pressure, an important biomarker of cardiovascular health, decreased in those eating the omega-3-PUFA enriched foods. Omega-3-PUFA enriched chicken-meat and eggs offers consumers an attractive additional alternative to eating oily fish. Unlike many lifestyle interventions, long-term large population health benefits are not dependent on willingness of people to make long-lasting dietary changes, but on the widespread availability of a range of inexpensive, commonly eaten, naturally enriched foods.

Introduction The purpose of this study was to describe and compare the performance of balance and walking tests in relation to self-reported fall history in adults with myotonic dystrophy type 1 (DM1). Methods Twenty-two (13 male) participants with DM1 completed, a 6-month fall history questionnaire, the modified Dynamic Gait Index (mDGI), limits of stability (LoS) testing, and 10-m walking tests. Results Mean (SD) falls in 6 months was 3.7 (3.1), and 19 (86%) participants reported at least 1 fall. Significant differences in mDGI scores (P = 0.006) and 10-m fast walking gait velocity (P = 0.02) were found between those who had been classified as "fallers" and those who had been classified as "nonfallers." Significant correlations were found between mDGI scores and 10-m walking time. Discussion Falls are common in DM1, and the mDGI may have potential to distinguish fallers from nonfallers, whereas the LoS failed to detect such impairment. Future studies should further explore use of the mDGI in DM1. Muscle Nerve 58: 694-699, 2018.

Background Sequence-specific learning (SSL); the ability to implicitly integrate repeated sequences compared to random sequences during a motor sequence paradigm, is impaired in healthy elders (HE) compared to healthy young (HY). Prior studies have provided limited practice (small repetitions and only 1 to 3 days). Research question Using a standing, postural control task we sought to assess if more practice (7 days) would remediate the differences observed in SSL for HE. Methods We used a continuous tracking task following a sinusoidal path of randomly presented random and repeated patterns. Root mean square error (RMSE) was the primary dependent variable, and the difference in RMSE between the random and repeated sequences was calculated to determine if SSL occurred. Results Improvement in SSL was documented as a decreasing value of the mean repeated sequence and less or no change in the random sequence. Eight HY and 8 HE practiced the repeated sequences 420 times over 7 days. No differences were observed between the groups on cognition, balance, and mobility. HE did not demonstrate the ability to integrate the repeated sequence on day 1, but with increased practice, they integrated the repeated sequence similar to HY by the end of practice. The results of this study suggest that sustained practice over 7 days remediated differences in performance of a standing, implicit, sequence-specific task between HY and HE. Significance Clinically, it is important to provide individuals with sufficient practice amount to achieve integration of a standing task. Results suggest that older adults need more practice to demonstrate SSL.

The National Leadership Consortium in Sensory Disabilities (NLCSD) trained doctoral scholars at universities across the United States to increase the number and quality of professionals specializing in educating children with sensory disabilities. NLCSD produced 40 new doctorates and created a community of learners comprised of scholars, faculty, and leaders in policy and advocacy.

Glioblastoma (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-18 months. Immune effector T cells are a promising therapy due to their innate cytotoxicity. In addition, engineering chimeric antigen receptors (CAR) to target tumor-associated or neo-antigens can lend high specificity. The ability to assess the efficacy and potency of such T cell therapies in vitro at high throughputs is vital for the preclinical development of these promising therapies. Cellular impedance assays offer a sensitive, non-destructive, and label-free method to continuously monitor cancer cell proliferation and immune cell-mediated cytotoxicity in real-time, revealing not only the potency but also the kinetics of T cell killing. Here, we used co-culture to compare the cytolytic potency and kinetics of naïve activated T Cells and targeted GD2 CAR-T cells against glioma stem cells (GSC), a subpopulation of glioblastoma cells. Patient-derived N08 GSCs were plated at 50k cells per well on a PEI and laminin-coated CytoView-Z 96-well plates, and their impedance was continuously monitored on the Maestro Z impedance platform (Axion BioSystems). After 48 hours, human naïve activated T Cells (ImmunoCult CD3/CD28 activation media) or GD2 CAR-T cells were added at varying effector:target ratios ranging from 0.1:1 to 10:1. Impedance and cytolysis were subsequently monitored for up to 7 days. The addition of activated T Cells or GD2 CAR-T Cells resulted in cell swelling, followed by a decrease in impedance consistent with T cell-mediated lysis of GSCs. GD-2 CAR-T Cells resulted in a significantly higher percent cytolysis of GSCs compared to naïve activated T Cells after 7 days of exposure. In addition, the kill time 50, defined as the time to reach 50% cytolysis of target cells, was shorter for GD-2 CAR-T Cells compared to naïve activated T Cells. Cytotoxic function was validated with subsequent flow cytometry and cytokine analysis. After 7 days in co-culture, GD2 CAR-T cells exhibited markers of chronic activation, including greater CD8 expression than CD4, upregulation of CD69 (33% of cells), and induction of GrB (70%). Initial exhaustion was suggested by expression of PD1 (80% cells) and LAG3 (35%), but not TIM3. Overall, both naïve activated T-Cells and GD2 CAR-T Cells were effective for cytolysis of GSCs, with CAR-T exhibiting more efficient killing. CAR-T Cells engineered to target the GD2 antigen exhibited stronger potency and faster kinetics, suggesting greater clinical potential against glioblastoma. Citation Format: Heather Brant Hayes, Meghan T. Logun, Stacie A. Chvatal, Katie Mueller, Nicole Piscopo, Amritava Das, Krishanu Saha, Daniel C. Millard, Lohitash Karumbaiah. Kinetics and potency of T cell and CAR-T cell mediated cytolysis of glioma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1552.

Emerging Issues in Cochlear ImplantationThe American Cochlear Implant Alliance (ACI Alliance) was incorporated in the late 2011 as a non-profit organization of cochlear implant clinicians from acro...

Objective: Herein, we describe the disease burden and age-related changes of congenital-onset myotonic dystrophy (CDM) in childhood. Methods: Children with CDM and age-matched controls aged 0 to 13 years were enrolled. Participants were divided into cohorts based on the following age groups: 0–2, 3–6, and 7–13 years. Each cohort received age-appropriate evaluations including functional testing, oral facial strength testing, neuropsychological testing, quality-of-life measurements, and ECG. Independent-samples t test or Wilcoxon 2-sample test was used to compare the differences between children with CDM and controls. Probability values less than 0.05 are reported as significant. Results: Forty-one participants with CDM and 29 healthy controls were enrolled. The 6-minute walk was significantly different between CDM (258.3 m [SD 176.0]) and control participants (568.2 m [SD 73.2]). The mean lip force strength was significantly different in CDM (2.1 N [SD 2.8)] compared to control participants (17.8 N [SD 7.6]). In participants with CDM, the mean IQ (65.8; SD 18.4) was 3 SDs below the mean compared to standardized norms. Measurements of grip strength, sleep quality, and quality of life were also significantly different. Strength measures (oral facial strength, grip strength, and 6-minute walk) correlated with each other but not with participant IQ. Conclusions: This work identifies important phenotypes associated with CDM during childhood. Several measures of strength and function were significantly different between participants with CDM and controls and may be useful during future therapeutic trials.

BODIPY-based conjugated microporous polymers (BDP_CMP and PHTT_BDP) have been synthesised via two distinct methods of assembly: high-yielding Suzuki–Miyaura cross-coupling of BODIPY-containing building blocks, and post-synthetic conversion of an aldehyde-equipped CMP host that was synthesised in the absence of metal-based catalysts. Both approaches yielded BODIPY-based materials featuring a high BET surface area (484–769 m2 g−1) and a bathochromic shift in the maximum light absorbance (520–550 nm). Singlet oxygen production employing the BODIPY-based materials at 530 nm was carried out heterogeneously in a commercial photochemical flow reactor.

Glioblastoma (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-15 months. Immune system effector T cells are a promising therapy due to their high specificity and innate cytotoxicity. The ability to assess the efficacy and potency of T cell therapies in vitro and with high throughput is vital for the further development of this promising therapy. Cellular impedance-based assays offer a sensitive, label-free, and nondestructive method to continuously monitor cancer cell proliferation and immune cell-mediated cytotoxicity in real-time and at high throughputs, revealing not only the potency but also the kinetics of T cell therapies. Here, we investigated the targeting potency of activated human T cells on human U87MG glioma cell monolayers across multiple cell densities. U87MG cells were plated at 10k, 25k, and 50k cells per well on a PDL-coated CytoView-Z 96-well plate (n=12 wells per density), and their impedance was continuously monitored on the Maestro Z impedance platform. After 24 hours, activated patient-derived T Cells (ImmunoCult CD3/CD28 activation media) were added in a 10:1 effector:target ratio. Impedance and cytolysis were subsequently monitored for another 120 hours. As expected, higher densities proliferated faster and reached a higher impedance level at 24 hours. The addition of activated human T cells resulted in a decrease of the impedance signal consistent with T cell-mediated lysis of the glioma cells. The highest density of T cells (500k) exhibited the fastest rate of U87 cytolysis, with a Kill Time 50 of 35 hours. All densities reached 100% cytolysis by 100 hours. Overall, activated human T cells were highly effective for cytolysis of U87MG glioma cell monolayers of varying densities. The cellular impedance assay revealed high potency, with kinetics that varied across cell densities despite the same effector:target ratios. Citation Format: Stacie A. Chvatal, Meghan T. Logun, Heather B. Hayes, Daniel C. Millard, Lohitash Karumbaiah. Kinetics and potency of T Cell-mediated cytolysis of glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2187.

Background & Aim Glioblastoma is an aggressive brain cancer with no effective treatments and a prognosis of 12-15 months. Immune system effector T cells are a promising therapy due to their high specificity and innate cytotoxicity. Assessing the efficacy and potency of T cell therapies in vitro and with high throughput is vital for development of this promising therapy. Cellular impedance-based assays offer sensitive, label-free, and continuous monitoring of cell proliferation and immune cell-mediated cytotoxicity, revealing both the potency and kinetics of T cell killing. Here, we investigated the targeting potency of activated human T cells on human U87MG glioma and patient-derived glioma cells. Methods, Results & Conclusion U87MG and patient-derived glioma cells were plated at densities ranging from 10k to 50k cells per well on a PDL-coated CytoView-Z 96-well plate (n=12 wells per density). After 24 hours, activated patient-derived T Cells (ImmunoCult CD3/CD28 activation media) were added in a 10:1 effector:target ratio. Impedance and cytolysis were continuously monitored for over 120 hours. As expected, higher densities of glioma cells proliferated faster and reached a higher impedance level at 24 hours. Addition of activated human T cells resulted in a decrease in impedance consistent with T cell-mediated lysis of the glioma cells. The highest density of T cells (500k) exhibited the fastest rate of U87 cytolysis, with a Kill Time 50 of 35 hours. All densities reached 100% cytolysis by 100 hours. Overall, activated human T cells were highly effective for cytolysis of U87MG and patient-derived glioma cells. The cellular impedance assay revealed high potency, with kinetics that varied across cell densities despite the same effector:target ratios.

PURPOSE The purpose of this study was to investigate the physical activity levels in children with congenital myotonic dystrophy (CDM), and to examine whether patient clinical and functional characteristics correlated to physical activity. METHODS Twenty-five children with CDM were assessed on functional measures, clinical measures, and physical activity levels. RESULTS Results support that children with CDM spend the majority of their time inactive. There was a negative correlation between inactivity and cytosine-thymine-guanine repeats, suggesting increased inactivity with increased CDM severity. Age, body mass index, and lean muscle mass may be factors influencing activity levels. CONCLUSIONS Children in this study received one-third the recommended steps per day. The number of steps per day is not correlated with clinical measures.