Label-free in vitro assays predict the potency of anti-disialoganglioside chimeric antigen receptor T-cell products.

BACKGROUND AIMS: Chimeric antigen receptor (CAR) T cells have demonstrated remarkable efficacy against hematological malignancies; however, they have not experienced the same success against solid tumors such as glioblastoma (GBM). There is a growing need for high-throughput functional screening platforms to measure CAR T-cell potency against solid tumor cells. METHODS: We used real-time, label-free cellular impedance sensing to evaluate the potency of anti-disialoganglioside (GD2) targeting CAR T-cell products against GD2+ patient-derived GBM stem cells over a period of 2 days and 7 days in vitro. We compared CAR T products using two different modes of gene transfer: retroviral transduction and virus-free CRISPR-editing. Endpoint flow cytometry, cytokine analysis and metabolomics data were acquired and integrated to create a predictive model of CAR T-cell potency. RESULTS: Results indicated faster cytolysis by virus-free CRISPR-edited CAR T cells compared with retrovirally transduced CAR T cells, accompanied by increased inflammatory cytokine release, CD8+ CAR T-cell presence in co-culture conditions and CAR T-cell infiltration into three-dimensional GBM spheroids. Computational modeling identified increased tumor necrosis factor α concentrations with decreased glutamine, lactate and formate as being most predictive of short-term (2 days) and long-term (7 days) CAR T cell potency against GBM stem cells. CONCLUSIONS: These studies establish impedance sensing as a high-throughput, label-free assay for preclinical potency testing of CAR T cells against solid tumors.

Approaches for peptide and protein cyclisation.

The cyclisation of polypeptides can play a crucial role in exerting biological functions, maintaining stability under harsh conditions and conferring proteolytic resistance, as demonstrated both in nature and in the laboratory. To date, various approaches have been reported for polypeptide cyclisation. These approaches range from the direct linkage of N- and C- termini to the connection of amino acid side chains, which can be applied both in reaction vessels and in living systems. In this review, we categorise the cyclisation approaches into chemical methods (e.g. direct backbone cyclisation, native chemical ligation, aldehyde-based ligations, bioorthogonal reactions, disulphide formation), enzymatic methods (e.g. subtiligase variants, sortases, asparaginyl endopeptidases, transglutaminases, non-ribosomal peptide synthetases) and protein tags (e.g. inteins, engineered protein domains for isopeptide bond formation). The features of each approach and the considerations for selecting an appropriate method of cyclisation are discussed.

Combining the AM-PAC "6-Clicks" and the Morse Fall Scale to Predict Individuals at Risk for Falls in an Inpatient Rehabilitation Hospital.

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.

Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol.

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 (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury. 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.

Modified dynamic gait index and limits of stability in myotonic dystrophy type 1.

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.

Stepping Activity in Children With Congenital Myotonic Dystrophy.

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.

Modulation of hand aperture during reaching in persons with incomplete cervical spinal cord injury.

The intact neuromotor system prepares for object grasp by first opening the hand to an aperture that is scaled according to object size and then closing the hand around the object. After cervical spinal cord injury (SCI), hand function is significantly impaired, but the degree to which object-specific hand aperture scaling is affected remains unknown. Here, we hypothesized that persons with incomplete cervical SCI have a reduced maximum hand opening capacity but exhibit novel neuromuscular coordination strategies that permit object-specific hand aperture scaling during reaching. To test this hypothesis, we measured hand kinematics and surface electromyography from seven muscles of the hand and wrist during attempts at maximum hand opening as well as reaching for four balls of different diameters. Our results showed that persons with SCI exhibited significantly reduced maximum hand aperture compared to able-bodied (AB) controls. However, persons with SCI preserved the ability to scale peak hand aperture with ball size during reaching. Persons with SCI also used distinct muscle coordination patterns that included increased co-activity of flexors and extensors at the wrist and hand compared to AB controls. These results suggest that motor planning for aperture modulation is preserved even though execution is limited by constraints on hand opening capacity and altered muscle co-activity. Thus, persons with incomplete cervical SCI may benefit from rehabilitation aimed at increasing hand opening capacity and reducing flexor-extensor co-activity at the wrist and hand.

A 21-year retrospective outcome study of New South Wales forensic patients granted conditional and unconditional release.

AIM: To retrospectively examine the outcomes of forensic patients found not guilty by reason of mental illness (NGMI) in New South Wales (NSW) and subsequently released into the community, as measured by reoffending, conditional release revocation and psychiatric hospital readmission. METHOD: Data were collected from the NSW Mental Health Review Tribunal (MHRT) files for all patients who received an NGMI verdict between January 1990 and December 2010, and who were released into the community during this period. The outcome measures of conditional release revocation and psychiatric hospital readmission were extracted from these files. Information about subsequent criminal charges, convictions and penalties were obtained from the Bureau of Crime Statistics and Research's reoffending database. RESULTS: During the 21-year period studied, 364 offenders received an NGMI verdict and were placed under the supervision of the MHRT. Of these, 197 were released into the community, including 85 who were granted unconditional release. Over a follow-up period averaging 8.4 years, 18% of conditionally released patients reoffended, 11.8% were convicted of a further offence, 8.7% were charged with a violent offence, 3.1% were convicted of a violent offence and 3.7% were sentenced to a term of imprisonment. Five (3.1%) conditionally released forensic patients received a further NGMI verdict. One-quarter of the conditionally released patients had their conditional release revoked and half were readmitted to hospital. Of the forensic patients granted unconditional release, 12.5% were charged with an offence, 9.4% received convictions for an offence, 6.3% were charged with a violent offence and 4.7% were convicted of a violent offence, in a mean follow-up period of 7.6 years. None committed a further serious offence resulting in a term of imprisonment, nor a second NGMI verdict. CONCLUSIONS: The results of this study suggest that the treatment and rehabilitation of forensic patients in NSW, together with the decision-making procedures of the MHRT, is effective in protecting the community from further offending by forensic patients.

Coverage of physical therapy assessments in the Observational Medical Outcomes Partnership Model common data model.

BACKGROUND: High-value care aims to enhance meaningful patient outcomes while reducing costs and is accelerated by curating data across healthcare systems through common data models (CDMs), such as Observational Medical Outcomes Partnership Model (OMOP). Meaningful patient outcomes, such as physical function, must be included in these CDMs. However, the extent that physical therapy assessments are covered in the OMOP CDM is unclear. OBJECTIVE: Examine the extent that physical therapy assessments used in neurologic and orthopaedic conditions are in the OMOP CDM. METHODS: After identifying assessments, two reviewer teams independently mapped the neurologic and orthopaedic assessments into the OMOP CDM. We quantified agreement within the reviewer team by the number of assessments mapped by both reviewers, one reviewer but not the other, or neither reviewer. The reviewer teams then reconciled disagreements, after which we examined agreement and the average number of concept ID numbers per assessment. RESULTS: Of the 81 neurologic assessments, 48.1% (39/81) were initially mapped by both reviewers, 9.9% (8/81) were mapped by one reviewer but not the other, and 42% (34/81) were unmapped. After reconciliation, 46.9% (38/81) were mapped by both reviewers and 53.1% (43/81) were unmapped. Of the 79 orthopaedic assessments, 46.8% (37/79) were initially mapped by both reviewers, 12.7% (10/79) were mapped by one reviewer but not the other, and 48.1% (38/79) were unmapped. After reconciliation, 48.1% (38/79) were mapped by both reviewers and 51.9% (41/79) were unmapped. Most assessments that were mapped had more than one concept ID number (2.2±1.3 and 4.3±4.4 concept IDs per neurologic and orthopaedic assessment, respectively). CONCLUSIONS: The OMOP CDM includes some assessments recommended for use in neurologic and orthopaedic conditions, but many have multiple concept IDs. Including more functional assessments in the OMOP CDM and creating guidelines for mapping would improve our ability to include functional data in large datasets.

The effect of post-acute rehabilitation setting on 90-day mobility after stroke: A difference-in-difference analysis.

Background: After discharged from the hospital for acute stroke, individuals typically receive rehabilitation in one of three settings: inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), or home with community services (i.e., home health or outpatient clinics). The initial setting of post-acute care (i.e., discharge location) is related to mortality and hospital readmission; however, the impact of this setting on the change in functional mobility at 90-days after discharge is still poorly understood. The purpose of this work was to examine the impact of discharge location on the change in functional mobility between hospital discharge and 90-days post-discharge. Methods: In this retrospective cohort study, we used the electronic health record to identify individuals admitted to Johns Hopkins Medicine with an acute stroke and who had measurements of mobility [Activity Measure for Post Acute Care Basic Mobility (AM-PAC BM)] at discharge from the acute hospital and 90-days post-discharge. Individuals were grouped by discharge location (IRF=190 [40%], SNF=103 [22%], Home with community services=182 [(38%]). We compared the change in mobility from time of discharge to 90-days post-discharge in each group using a difference-in-differences analysis and controlling for demographics, clinical characteristics, and social determinants of health. Results: We included 475 individuals (age 64.4 [14.8] years; female: 248 [52.2%]). After adjusting for covariates, individuals who were discharged to an IRF had a significantly greater improvement in AM-PAC BM from time of discharge to 90-days post-discharge compared to individuals discharged to a SNF or home with community services (ß=-3.5 (1.4), p=0.01 and ß=-8.2 (1.3), p=<0.001, respectively). Conclusions: These findings suggest that the initial post-acute rehabilitation setting impacts the magnitude of functional recovery at 90-days after discharge from the acute hospital. These findings support the need for high-intensity rehabilitation and for policies that facilitate the delivery of high-intensity rehabilitation after stroke.

Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

Investigating the effects of cyclic topology on the performance of a plastic degrading enzyme for polyethylene terephthalate degradation.

Agitation is a commonly encountered stress for enzymes during all stages of production and application, but investigations that aim to improve their tolerance using topological engineering have yet to be reported. Here, the plastic-degrading enzyme IsPETase was cyclized in a range of topologies including a cyclic monomer, cyclic dimer and catenane using SpyTag/SpyCatcher technologies, and their tolerance towards different stresses including mechanical agitation was investigated. The cyclic dimer and catenane topologies were less susceptible to agitation-induced inactivation resulting in enhancement of polyethylene terephthalate (PET) degradation. While contrary to conventional belief, cyclic topologies did not improve tolerance of IsPETase towards heat or proteolytic treatment, the close proximity of active sites in the dimeric and catenane variants was found to enhance PET conversion into small soluble products. Together, these findings illustrate that it is worthwhile to explore the topology engineering of enzymes used in heterogeneous catalysis as it improves factors that are often overlooked in homogeneous catalysis studies.

Medicare Advantage Patterns of Poststroke Discharge to an Inpatient Rehabilitation or Skilled Nursing Facility: A Consideration of Demographic, Functional, and Payer Factors.

OBJECTIVE: The purpose of this study was to determine the factors influencing the discharge to an inpatient rehabilitation facility (IRF) or a skilled nursing facility (SNF) of people poststroke with Medicare Advantage plans. METHODS: A retrospective cohort study was conducted with data from naviHealth, a company that manages postacute care discharge placement on behalf of Medicare Advantage organizations. The dependent variable was discharge destination (IRF or SNF). Variables included age, sex, prior living setting, functional status (Activity Measure for Post-Acute Care [AM-PAC]), acute hospital length of stay, comorbidities, and payers (health plans). Analysis estimated relative risk (RR) of discharge to SNF, while controlling for regional variation. RESULTS: Individuals discharged to an SNF were older (RR = 1.17), women (RR = 1.05), lived at home alone or in assisted living (RR = 1.13 and 1.39, respectively), had comorbidities impacting their function "some" or "severely" (RR = 1.43 and 1.81, respectively), and had a length of stay greater than 5 days (RR = 1.16). Individuals with better AM-PAC Basic Mobility (RR = 0.95) went to an IRF, and individuals with better Daily Activity (RR = 1.01) scores went to an SNF. There was a substantial, significant variation in discharge of individuals to SNF by payer group (RR range = 1.12-1.92). CONCLUSIONS: The results of this study show that individuals poststroke are more likely to be discharged to an SNF than to an IRF. This study did not find a different discharge decision-making picture for those with Medicare Advantage plans than previously described for other insurance programs. IMPACT: Medicare Advantage payers have varied patterns in discharge placement to an IRF or SNF for patients poststroke.

Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion.

Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord-hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations.

Is the Activity Measure for Postacute Care "6-Clicks" Tool Associated With Discharge Destination Postacute Stroke?

Objective: To investigate the association of poststroke physical function, measured within 24 hours prior to discharge from the acute care hospital using Activity Measure for Postacute Care (AM-PAC) Inpatient "6-Clicks" scores and discharge destination (home vs facility and inpatient rehabilitation facility [IRF] vs skilled nursing facility [SNF]). Design: Retrospective cross-sectional cohort study. Setting: Acute care, University Hospital. Participants: Individuals post acute ischemic stroke, N=721, 51.3% male, mean age 63.6±16.4 years. Interventions: Not applicable. Main Outcome Measures: AM-PAC "6-Clicks" 3 domains: basic mobility, daily activity, and applied cognition. Results: AM-PAC basic mobility and daily activity were significant predictors of discharge. Those in the home discharge group had AM-PAC basic mobility mean t scale score of 48.5 compared with a score of 34.8 for individuals sent to a facility and daily activity score of 47.2 compared with 32.7 for individuals sent to a facility. The AM-PAC variables accounted for an additional 24% of the variance in the discharge destination, with basic mobility and daily activity accounting for most of the variance.The AM-PAC scores were not statistically different and were not able to discriminate between placement in an IRF vs SNF. The mean basic mobility t scale score for individuals going to an IRF was 34.9 compared with 34.6 for those going to an SNF. The daily activity score for IRF was 32.8 compared with 32.6 for SNF. The AM-PAC accounted for no additional variance in discharge destination to an IRF or SNF. Conclusions: The AM-PAC Inpatient "6-Clicks" 3 domains are able to distinguish individuals with stroke being discharged to home from postacute care (PAC) but not for differentiating between PAC facilities (IRF vs SNF) in this cohort of individuals post stroke.

Personalized practice dosages may improve motor learning in older adults compared to "standard of care" practice dosages: A randomized controlled trial.

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [practice to plateau (PtP) and overpractice (OVP)] improve retention and transfer of a motor task, compared to low dose [LD] practice that mimics standard clinical dosages. In this pilot randomized controlled trial (NCT02898701, ClinicalTrials.gov), community-dwelling older adults (n = 41, 25 female, mean age 68.9 years) with a range of balance ability performed a standing serial reaction time task in which they stepped to specific targets. Presented stimuli included random sequences and a blinded repeating sequence. Participants were randomly assigned to one of three groups: LD (n = 15, 6 practice trials equaling 144 steps), PtP (n = 14, practice until reaching an estimated personal plateau in performance), or OVP (n = 12, practice 100% more trials after reaching an estimated plateau in performance). Measures of task-specific learning (i.e., faster speed on retention tests) and transfer of learning were performed after 2-4 days of no practice. Learning of the random sequence was greater for the OVP group compared to the LD group (p = 0.020). The OVP (p = 0.004) and PtP (p = 0.010) groups learned the repeated sequence more than the LD group, although the number of practice trials across groups more strongly predicted learning (p = 0.020) than did group assignment (OVP vs. PtP, p = 0.270). No group effect was observed for transfer, although significant transfer was observed in this study as a whole (p < 0.001). Overall, high and personalized dosages of postural training were well-tolerated by older adults, suggesting that this approach is clinically feasible. Practicing well-beyond standard dosages also improved motor learning. Further research should determine the clinical benefit of this personalized approach, and if one of the personalized approaches (PtP vs. OVP) is more beneficial than the other for older patients.

Reading, writing, and phonological processing skills of adolescents with 10 or more years of cochlear implant experience.

OBJECTIVES: This study had three goals: (1) to document the literacy skills of deaf adolescents who received cochlear implants (CIs) as preschoolers; (2) to examine reading growth from elementary grades to high school; (3) to assess the contribution of early literacy levels and phonological processing skills, among other factors, to literacy levels in high school. DESIGN: A battery of reading, spelling, expository writing, and phonological processing assessments were administered to 112 high school (CI-HS) students, ages 15.5 to 18.5 yrs, who had participated in a reading assessment battery in early elementary grades (CI-E), ages 8.0 to 9.9 yrs. The CI-HS students' performance was compared with either a control group of hearing peers (N = 46) or hearing norms provided by the assessment developer. RESULTS: Many of the CI-HS students (47 to 66%) performed within or above the average range for hearing peers on reading tests. When compared with their CI-E performance, good early readers were also good readers in high school. Importantly, the majority of CI-HS students maintained their reading levels over time compared with hearing peers, indicating that the gap in performance was, at the very least, not widening for most students. Written expression and phonological processing tasks posed a great deal of difficulty for the CI-HS students. They were poorer spellers, poorer expository writers, and displayed poorer phonological knowledge than hearing age-mates. Phonological processing skills were a critical predictor of high school literacy skills (reading, spelling, and expository writing), accounting for 39% of variance remaining after controlling for child, family, and implant characteristics. CONCLUSIONS: Many children who receive CIs as preschoolers achieve age-appropriate literacy levels as adolescents. However, significant delays in spelling and written expression are evident compared with hearing peers. For children with CIs, the development of phonological processing skills is not just important for early reading skills, such as decoding, but is critical for later literacy success as well.

Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.

BACKGROUND AND PURPOSE: Resistance exercise via negative, eccentrically induced work (RENEW) has been shown to be associated with improvements in strength, mobility, and balance in multiple clinical populations. However, RENEW has not been reported for individuals with multiple sclerosis (MS). METHODS: Nineteen individuals with MS (8 men, 11 women; age mean = 49 ± 11 years; Expanded Disability Status Scale [EDSS] mean = 5.2 ± 0.9) were randomized into either standard exercise (STAND) or standard exercise and RENEW training (RENEW) for 3×/week for 12 weeks. Outcome measures were lower extremity strength (hip/knee flexion and extension, ankle plantar and dorsiflexion, and the sum of these individual values [sum strength]); Timed Up and Go (TUG), 10-m walk, self-selected pace (TMWSS) and maximal-pace (TMWMP), stair ascent (S-A) and descent (S-D) and 6-Minute Walk Test (6MWT), Berg Balance Scale (BBS), Fatigue Severity Scale (FSS). RESULTS: No significant time effects or interactions were observed for strength, TUG, TMWSS, TMWMP, or 6MWT. However, the mean difference in sum strength in the RENEW group was 38.60 (representing a 15% increase) compared to the sum strength observed in the STAND group with a mean difference of 5.58 (a 2% increase). A significant interaction was observed for S-A, S-D, and BBS as the STAND group improved whereas the RENEW group did not improve in these measures. DISCUSSION AND CONCLUSIONS: Contrary to results in other populations, the addition of eccentric training to standard exercises did not result in significantly greater lower extremity strength gains in this group of individuals with MS. Further this training was not as effective as standard exercise alone in improving balance or the ability to ascend and descend stairs. Following data collection, reassessment of required sample size indicates we were likely underpowered to detect strength differences between groups.