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On any given day, we make countless reaching movements to objects around us. While such ubiquity may suggest uniformity, each movement is unique in the speed with which it is made. Some movements are slow, while others are fast. These variations in reach speed have long been known to be influenced by accuracy constraints; we slow down when accuracy demands are high. However, in other forms of movement like walking, metabolic cost is the primary determinant of movement speed. Here we ask, how do metabolic cost and accuracy interact to determine speed of reaching movements? First we systematically measure the effect of increasing mass on the metabolic cost of reaching across a range of movement speeds. Next, in a sequence of three experiments, we examine how added mass affects preferred movement speeds in a simple reaching task with increasing accuracy requirements. We find that mass consistently increased metabolic cost and led to slower movements. Yet, intriguingly, preferred reach speeds were slower than metabolically optimal. We then demonstrate how a single model that, critically, considers both accuracy and metabolic cost can explain preferred movement speeds across the range of accuracy and effort requirements tested. Together, these findings provide a unifying framework to explain the combined effects of metabolic cost and accuracy on movement speed, and also highlight the integral role metabolic cost plays in determining reach speed.

Introduction: Difficulty swallowing (dysphagia) occurs frequently in patients with neurological disorders and can lead to aspiration, choking, and malnutrition. Dysphagia is typically diagnosed using costly, invasive imaging procedures or subjective, qualitative bedside examinations. Wearable sensors are a promising alternative to noninvasively and objectively measure physiological signals relevant to swallowing. An ongoing challenge with this approach is consolidating these complex signals into sensitive, clinically meaningful metrics of swallowing performance. To address this gap, we propose 2 novel, digital monitoring tools to evaluate swallows using wearable sensor data and machine learning. Methods: Biometric swallowing and respiration signals from wearable, mechano-acoustic sensors were compared between patients with poststroke dysphagia and nondysphagic controls while swallowing foods and liquids of different consistencies, in accordance with the Mann Assessment of Swallowing Ability (MASA). Two machine learning approaches were developed to (1) classify the severity of impairment for each swallow, with model confidence ratings for transparent clinical decision support, and (2) compute a similarity measure of each swallow to nondysphagic performance. Task-specific models were trained using swallow kinematics and respiratory features from 505 swallows (321 from patients and 184 from controls). Results: These models provide sensitive metrics to gauge impairment on a per-swallow basis. Both approaches demonstrate intrasubject swallow variability and patient-specific changes which were not captured by the MASA alone. Sensor measures encoding respiratory-swallow coordination were important features relating to dysphagia presence and severity. Puree swallows exhibited greater differences from controls than saliva swallows or liquid sips (p < 0.037). Discussion: Developing interpretable tools is critical to optimize the clinical utility of novel, sensor-based measurement techniques. The proof-of-concept models proposed here provide concrete, communicable evidence to track dysphagia recovery over time. With refined training schemes and real-world validation, these tools can be deployed to automatically measure and monitor swallowing in the clinic and community for patients across the impairment spectrum.

BackgroundIn clinical practice, therapists often rely on clinical outcome measures to quantify a patient’s impairment and function. Predicting a patient’s discharge outcome using baseline clinical information may help clinicians design more targeted treatment strategies and better anticipate the patient’s assistive needs and discharge care plan. The objective of this study was to develop predictive models for four standardized clinical outcome measures (Functional Independence Measure, Ten-Meter Walk Test, Six-Minute Walk Test, Berg Balance Scale) during inpatient rehabilitation.MethodsFifty stroke survivors admitted to a United States inpatient rehabilitation hospital participated in this study. Predictors chosen for the clinical discharge scores included demographics, stroke characteristics, and scores of clinical tests at admission. We used the Pearson product-moment and Spearman’s rank correlation coefficients to calculate correlations among clinical outcome measures and predictors, a cross-validated Lasso regression to develop predictive equations for discharge scores of each clinical outcome measure, and a Random Forest based permutation analysis to compare the relative importance of the predictors.ResultsThe predictive equations explained 70–77% of the variance in discharge scores and resulted in a normalized error of 13–15% for predicting the outcomes of new patients. The most important predictors were clinical test scores at admission. Additional variables that affected the discharge score of at least one clinical outcome were time from stroke onset to rehabilitation admission, age, sex, body mass index, race, and diagnosis of dysphasia or speech impairment.ConclusionsThe models presented in this study could help clinicians and researchers to predict the discharge scores of clinical outcomes for individuals enrolled in an inpatient stroke rehabilitation program that adheres to U.S. Medicare standards.

Significance Early detection of infant neuromotor pathologies is critical for timely therapeutic interventions that rely on early-life neuroplasticity. Traditional assessments rely on subjective expert evaluations or specialized medical facilities, making them challenging to scale in remote and/or resource-constrained settings. The results presented here aim to democratize these evaluations using wireless networks of miniaturized, skin-integrated sensors that digitize movement behaviors and vital signs of infants in a cost-effective manner. The resulting data yield full-body motion reconstructions in the form of deidentified infant avatars, along with a range of important cardiopulmonary information. This technology approach enables rapid, routine evaluations of infants at any age via an engineering platform that has potential for use in nearly any setting across developed and developing countries alike., Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

Children with abdominal pain are frequently seen in emergency departments. Physicians and parents worry about appendicitis; physicians are also concerned about intussusception and bowel obstruction in patients with previous surgical procedures. Sometimes the patient is ill, and the diagnosis is elusive. In a 6-month period at our pediatric emergency department with an annual census of 57,400 patients, we cared for 4 patients who presented with abdominal pain due to complications of Meckel's diverticulum. None presented with painless rectal bleeding, the complication of which physicians are most aware. We are reporting these patients to raise awareness of Meckel's diverticulum as a cause of acute abdomen in children. Meckel's diverticulum may masquerade as appendicitis, an abdominal mass, intussusception, or a complication of severe constipation.

A role for vitamin D in the immune system is emerging from human research but data in the bovine is limited. In the current study, 48 Holstein–Friesian calves were randomly assigned to one of 4 groups designed to expose calves to divergent vitamin D levels for a 7 month period and to determine its effects on circulating immunity in young calves. Concentrations of circulating 25-hydroxyvitamin D (25OHD) was measured in serum using a commercial ELISA with validated bovine standards. Results showed that mean circulating concentrations of 25OHD at birth was 7.64 ± 3.21 ng/ml indicating vitamin D deficiency. Neither the injection of Vit D3 at birth nor the elevated levels in milk replacer yield discernible changes to pre-weaning circulating concentration of 25OHD. No calf reached the recommended level of vitamin D immune sufficiencyof 30 ng/ml of 25OHD until at least 3 months of age (T4). Increasing dietary Vit D3 via ration in the post-weaning period significantly elevated 25OHD concentrations in serum in VitD-In calves. Maximal levels of circulating 25OHD were achieved in VitD-Out calves, reaching 60.86 ± 7.32 ng/ml at 5 months of age (T7). Greatest divergence in haematology profile was observed between Ctl-In vs VitD-In groups with Ctl-In calves showing an elevated count of neutrophils, eosinophils, and basophils associated with reduced 25OHD concentrations. Neither IL-8 expression nor ROS production in serum were significantly different between calves with high and low 25OHD, indicating that other vitamin D-dependent mechanisms may contribute to the divergent circulating cellular profiles observed. This novel data on the vitamin D status of neonatal calves identifies a significant window of vitamin D insufficiency which is associated with significant differences in circulating immune cell profiles. Vitamin D insufficiency may therefore exacerbate pre-weaning disease susceptibility, and further work in now warranted.

Even though ownership of a Children’s Savings Account (CSA), children’s academic achievement, and parental college expectations are potentially key components for closing the inequality gap in education, the interdependence of these elements is not yet fully understood. Guided by the Theory of Planned Behavior, we utilize structural equation modeling (SEM) in this cross-sectional study to examine the mediating role of parental college expectations on the relationship between ownership of a Harold Alfond College Challenge (HACC) account and parents’ perception of children’s math and reading abilities by the level of household income. Although it is currently a universal, opt-out CSA program available to all babies born in Maine, HACC started in 2008 as an opt-in program, and it is this timeframe that is the focus of the current study. SEM models utilizing survey data from a sample of Maine parents reveal a positive association between the Alfond Grant enrollment and parental college expectations among low-to-moderate income families. Moreover, parental expectations are found to be a complete mediator between having a HACC account and parental perceptions of children’s math ability (but not reading ability) among low-to-moderate income students. No findings were significant for high income families. Correlational evidence from this study suggests that HACC may complement schools’ academic objectives in Maine, particularly about improving parents’ perceptions of their child’s math performance among low-to-moderate income families. This study highlights the need for more rigorous research on HACC and its potential effects on children’s educational attainment.

Interleukin 8 (IL8) is a major mediator of the innate immune response. Polymorphisms in this gene are associated with susceptibility to inflammatory disease in humans. Two major promoter polymorphic haplotypes (IL8-h1 and IL8-h2) segregating in cattle populations have shown a significant effect on the immune response profile in calves but their implications for transition cow immunity have not been established. The aims of this study were to assess functional relevance of the IL8 haplotypes on the immunological traits of periparturient cows (n = 32) belonging to three genetic groups: Holstein (HO), Simmental (SI) and their crosses (CR) and to evaluate the frequency of IL8 haplotypes in the HO (dairy) and SI (dual purpose) pure breeds. IL8 haplotypes showed a significant effect on circulating number of both T helper lymphocytes (P = 0.0133) and T cytotoxic lymphocytes (P = 0.0024). Differences in percentage of CD14+ monocytes and T lymphocyte subsets were found between haplotype groups at different time points. Plasma concentrations of Serum Amyloid A (SAA) and Haptoglobin (Hp) were enhanced at calving in IL8-h2 (P = 0.0019, P = 0.0029) and IL8-het (P = 0.050 and P = 0.052) respectively, compared with IL8-h1 cows. In contrast, significantly lower levels of reactive oxygen metabolites (d-ROMs) activation were identified in IL8-h2 and IL8-het cows after calving compared with IL8-h1 cows. Furthermore, genotyping results showed that SI cows have a high frequency of the homozygous IL8-h2 haplotype compared to the HO cows (87.5 % vs 40 %) which reflects the different selective pressure between the two pure breeds. In conclusion, our preliminary data suggests that IL8 promoter haplotype is associated with significant and dynamic changes in immunological traits during peripartum and early lactation period. Future work will focus on a more comprehensive assessment of immune changes in additional cows.

Interleukin-8 (IL-8) is a potent inflammatory chemokine, and two gene promoter haplotypes have been previously reported to segregate in cattle populations. Our earlier work showed how these divergent IL8 genotypes influence IL-8 expression and other immune response parameters at a systemic level. Here we extend that work to characterise the influence of haplotype on the local immune response - in primary bovine dermal fibroblasts. Furthermore, we also investigated how this response is modulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Significant induction of IL8 expression was observed in cells from both haplotypes at 3 and 24 h post-stimulation with the TLR1/2 ligand, Pam3CSK4 and with the TLR4 ligand, LPS. IL8 expression was elevated in response to both LPS and Pam3CSK4 in fibroblasts carrying the IL8-h1 haplotype and this result was supported by significantly enhanced IL-8 protein secretion. Gene expression profiles for other known fibroblast immune mediators (SAA3 and CCL20) did not show significant differences between haplotypes but NOS2 gene expression was significantly elevated in response to vitamin D, even above the level detected in response to both TLR ligands. In conclusion, this work has demonstrated that the IL-8 response of dermal fibroblasts is dependent on IL8 haplotype and that the immune response profile in these cells is significantly differentially regulated by 1,25(OH)2D3. Fibroblasts have important immune response capacity and their function in driving inflammatory responses (including iNOS) is underappreciated. Understanding the relationship between cattle genotype and immune function is critically important for uncovering sustainable solutions for animal disease.

To compare the impacts of yoga-based physical therapy versus a seated rest within the context of standard rehabilitation practice on sleep, heart rate variability (HRV), anxiety, and fatigue during acute traumatic brain injury (TBI) rehabilitation.Eleven individuals participated in this crossover study involving the following interventions in a randomized order: group yoga-based physical therapy (YPT), conventional physical therapy (CPT), and group seated rest in a relaxing environment (SR). HRV and self-reported anxiety and fatigue were measured immediately before and after each group, and sleep after each condition and at baseline. Data was analyzed using generalized linear mixed models with repeated measures.The interaction between time and treatment was statistically significant (Yoga-based physical therapy is feasible and safe in the inpatient rehabilitation setting following TBI. Sleep quality improved following the addition of a one-hour seated rest in a relaxing environment to a standard rehabilitation daily schedule, suggesting that structured rest time may be beneficial to sleep hygiene during inpatient rehabilitation following TBI. ClinicalTrials.Gov Registration Number: NCT03701594.

The faecal-oral route is a predominant mode of infectious disease transmission and yet the immunology of the bovine oral cavity is poorly understood. The objectives of this study were to develop an in vitro cell model of bovine salivary gland cells and to characterize the role of vitamin D on the expression of innate immune genes induced by stimulation with bacterial and viral pathogen-associated molecular patterns (PAMPs). Submandibular glandular tissue was excised post-mortem, processed, cells isolated and cultured until confluency after which cells were incubated with the active form of vitamin D (1,25(OH)D) for 18 h before stimulation with lipopolysaccharide (LPS μg/ml), lipoteichoic acid (LTA μg/ml) or polyinosinic:polycytidylic acid (poly I:C-20 μg/ml) PAMPs for 6 h and immune gene expression was assessed by Quantitative Real-Time PCR (RT-qPCR). RT-qPCR analysis of vimentin expression in cells derived from the bovine submandibular gland shows that cultured cells were fibroblast in origin. These cells significantly induce the pro-inflammatory cytokine IL1B, β-defensin and cathelicidin genes but these were not significantly altered in response to 1,25(OH)D. In contrast, 1,25(OH)D significantly up-regulates the expression of the NOS2 gene encoding iNOS in bovine submandibular stromal cells compared to EtOH (vehicle) control and this is a maintained response to all three bacterial and viral ligands. We have developed a new in vitro model to allow detailed investigations of mechanisms to enhance oral immunity in cattle. We show that these cells are fibroblast in nature, immunologically competent and vitamin D responsive. Their vitamin D-mediated enhancement of NOS2 expression warrants further investigation in saliva as a potential mechanism to boost oral immunity against infectious agents.

The study conducts an initial examination of the associations between participation and saving in the Promise Indiana Children's Savings Account (CSA) program and school administrative data on attendance and standardized math and reading scores. The primary research questions guiding this analysis are whether or not having a CSA is associated with lower absenteeism and/or higher reading and math scores and, for those who have a CSA, whether being a saver or the amount saved in the account is associated with better academic outcomes. Given the importance of family income to savings behaviors and academic achievement, analyses were conducted for the full sample as well as for the subsample of low-income students, defined by free/reduced lunch status. Among the low-income subsample, having a CSA is positively associated with both reading and math scores; this association is not found in the aggregate sample. The amount contributed to the CSA has a positive association with math and reading scores in the overall sample, but not with the scores of children receiving free/reduced lunch. Being a saver is associated with reading scores for both the overall and free/reduced lunch samples. Student attendance was not associated with any account variables. While more research is needed before policy conclusions can be drawn, these findings suggest that CSA programs may complement schools' academic objectives. Further, this study adds to the literature on children's assets by finding some differences in academic outcomes associated with different engagement with the CSA (e.g. account ownership and saving).

Background: Genetically modified T cells expressing an anti-CD19 murine chimeric antigen receptor (CAR) result in response rates of up to 90% in patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (ALL). Durable remissions are limited by relapses of both CD19+ disease, correlating with loss of persistence, and CD19- disease, due to target antigen loss. The use of humanized CAR T products with improved persistence and dual antigen targeting are strategies that may improve relapse free survival. Methods: Adult patients with r/r ALL were co-administered two humanized autologous CAR T cell products, one targeted to CD19 (huCART19) and the other to CD22 (CART22-65s) after fludarabine and cyclophosphamide lymphodepletion. A three day fractionated adaptive dosing scheme was used in which the second or third huCART19 and CART22-65s infusions could be held for early signs of cytokine release syndrome (CRS). Total planned dose was 2.0x10 6 CART22-65sf2 cells/kg and 2.0x10 6 huCART19 cells/kg. Safety of the novel combination was the primary endpoint of the study; feasibility and efficacy were key secondary endpoints. Results: Of 13 treated patients (median age 46 (range 28-71)), two had received prior murine CART19 cells, 8 had prior blinatumomab, 8 had prior inotuzumab and 10 had a prior allogeneic stem cell transplant (SCT). The two products had distinct peak expansions which correlated with two clinically distinct episodes of CRS in some patients. The median time to peak huCART19 expansion was 9 days versus 16 days for CART22-65s. Eleven patients experienced CRS, all Grade 1 or 2. Two patients had immune effector cell-associated neurotoxicity syndrome (ICANS), one of which was grade 4. Two patients died within 30 days of infusion, one from complications of treatment (Grade 4 ICANS and sepsis) and one from rapidly progressive disease. One patient developed hemophagocytic lymphohistiocytosis-like syndrome that was clinically and temporally distinct from a CRS event; this was characterized by delayed pancytopenia, transaminase elevation and hypofibrinogenemia, similar to events reported in other trials of CART22. This syndrome was refractory to IL6 and IL1beta inhibition but ultimately responded to ruxolitinib. Of the 11 patients evaluable for response, 100% achieved CR with unmeasurable residual disease (uMRD) one month after infusion. One of the 11 had molecular recurrence 9 months post infusion. The other 10 patients are alive and remain in an uMRD remission with a median follow up of 6.2 months (range 0.2 to 25 months) and none have proceeded to consolidative SCT. Three months after infusion, 9/11 patients had detectable huCART19 and 8/11 patients had detectable CART22-65s. At 6 months, 7/8 evaluable patients had detectable huCART19 cells and 4/8 patients had detectable CART22-65s. All three patients with 12 months follow-up had detectable huCART19 and CART22-65s. Conclusion: Co-administration and adaptive dosing of CART22-65s with huCART19 in adult patients with r/r ALL is feasible and effective. The two different products demonstrated differential expansion and persistence kinetics. Despite prior exposure to CD19- and/or CD22-specific immunotherapies, all evaluable patients achieved CR with uMRD; we continue to monitor CAR T cell persistence and its impact on durability of response. Disclosures Frey: Novartis: Research Funding; Sana Biotechnology: Consultancy; Syndax Pharmaceuticals: Consultancy; Kite Pharma: Consultancy. Gill: Interius Biotherapeutics: Current holder of stock options in a privately-held company, Research Funding; Novartis: Other: licensed intellectual property, Research Funding; Carisma Therapeutics: Current holder of stock options in a privately-held company, Research Funding. Luger: Syros: Honoraria; Agios: Honoraria; Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Brystol Myers Squibb: Honoraria; Acceleron: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Onconova: Research Funding; Celgene: Research Funding; Biosight: Research Funding; Hoffman LaRoche: Research Funding; Kura: Research Funding. Pratz: Abbvie: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; Agios: Consultancy; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Perl: AbbVie: Consultancy, Research Funding; Roche: Consultancy; Astellas: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Fujifilm: Research Funding; Arog: Research Funding; BMS/Celgene: Consultancy; Genentech: Consultancy; Actinium: Consultancy; Forma: Consultancy; Syndax: Consultancy; Loxo: Consultancy; Onconova: Consultancy; Sumitomo Dainippon: Consultancy. Ruella: viTToria biotherapeutics: Research Funding; Tmunity: Patents & Royalties; AbClon: Consultancy, Research Funding; BMS, BAYER, GSK: Consultancy; Novartis: Patents & Royalties. Brogdon: Novartis Institutes for Biomedical Research: Current Employment. Engels: Novartis: Current Employment, Current equity holder in publicly-traded company. Levine: In8bio: Membership on an entity's Board of Directors or advisory committees; Ori Biotech: Membership on an entity's Board of Directors or advisory committees; Vycellix: Membership on an entity's Board of Directors or advisory committees; Immusoft: Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Other: Co-Founder and equity holder; Immuneel: Membership on an entity's Board of Directors or advisory committees; Avectas: Membership on an entity's Board of Directors or advisory committees; Akron: Membership on an entity's Board of Directors or advisory committees. June: Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Current equity holder in publicly-traded company; Novartis: Patents & Royalties; AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Consultancy. Porter: American Society for Transplantation and Cellular Therapy: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months; DeCart: Membership on an entity's Board of Directors or advisory committees; ASH: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria. Hexner: Tmunity Therapeutics: Research Funding; Blueprint medicines: Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This trial reports outcomes from investigational products delivered as part of a clinical trial.

Children's savings accounts (CSAs) provide early asset-building opportunities to reduce disparities in children's outcomes, particularly regarding postsecondary education and financial well-being. Promise Indiana (PI) is a state-supported and community-driven CSA program for children in kindergarten through third grade. This study used a mixed methods approach to better understand savings behaviors and perceptions among PI participants. Administrative data showed a substantial 60 percent uptake of 529 savings accounts in the first year. Forty-five percent of PI accounts had deposits from family or champion funds, with an average account balance of $270. These findings suggest that PI is contributing to college savings rates in the 529 plan that exceed what would otherwise be expected for families of young children. Further, results from parental interviews suggested PI activated key components of the identity-based motivation framework, enabling individuals to assert and act on a vision of themselves as someone who saves for college.

This work was supported by the Lilly Endowment Inc. [Grant number 2015-0644] and the Charles Stewart Mott Foundation [Grant number 2012-0059]. These organizations are not responsible for the quality or accuracy of the report, which is the sole responsibility of AEDI, nor do they necessarily agree with any or all of the report’s findings and recommendations.

Objective To examine the immediate effects of a hip-assistive wearable robotic exoskeleton on clinical walking performance, walking energetics, gait kinematics, and corticomotor excitability in individuals with stroke. Design Randomized cross-over trial. Setting Research laboratory of a rehabilitation hospital. Participants Twelve individuals (4F/8M, mean age 57.8±7.2) with chronic hemiparetic stroke. Interventions Honda’s Stride Management Assist (SMA) exoskeleton, which provides torque-based flexion and extension assistance at the hip joints during walking. Main Outcome Measures The primary outcome measure was change in self-selected walking speed with the device off vs. with the device on. Secondary outcome measures included changes in clinical endurance, energy expenditure, kinematics, and corticomotor excitability of lower limb muscles. Results In a single session using the device, participants exhibited adaptations over most outcome measures. Self-selected walking speed and peak treadmill speed increased, while oxygen consumption rate decreased during overground and treadmill endurance tests. More symmetric walking patterns were observed during treadmill walking. Changes in corticomotor excitability were highly variable among participants, with a non-significant increase in excitability for the paretic rectus femoris. Conclusions The SMA hip exoskeleton causes immediate positive adaptations in walking performance in individuals with stroke when the device is in use.

Capturing the phenotypic variation in immune responses holds enormous promise for the development of targeted treatments for disease as well as tailored vaccination schedules. However, accurate detection of true biological variation can be obscured by the lack of standardised immune assays. The TruCulture® whole blood stimulation system has now been extensively used to detect basal and induced immune responses to a range of pathogen-associated molecular patterns (PAMPs) in human peripheral blood. This study demonstrates the optimisation of this commercially available assay for systemic immune phenotyping in cattle. The early immune response in Holstein-Friesian bull calves (n = 10) was assessed by haematology, flow cytometry and cytokine expression profiling after 24 h ex-vivo PAMP (LPS, poly (I:C) and zymosan) stimulation in TruCulture® tubes. A comparative analysis was also performed with a traditional whole blood stimulation assay and cell viability using both systems was also evaluated. Results: Supernatant collected from TruCulture® tubes showed a significant increase in IL-1β and IL-8 expression compared to null stimulated tubes in response to both LPS and zymosan. In contrast, a detectable immune response was not apparent at the standard concentration of poly (I:C). Conventional whole blood cultures yielded similar response profiles, although the magnitude of the response was higher to both LPS and zymosan, which may be attributed to prokaryotic strain-specificity or batch of the stimulant used. Despite being a closed system, HIF1A expression - used as a measure of hypoxia was not increased, suggesting the TruCulture® assay did not negatively affect cell viability. This represents the first reported use of this novel standardised assay in cattle, and indicates that the concentration of poly (I:C) immunogenic in humans is insufficient to induce cytokine responses in cattle. We conclude that the low blood volume and minimally invasive TruCulture® assay system offers a practical and informative technique to assess basal and induced systemic immune responses in cattle.

Interleukin-8 (IL-8) is an inflammatory chemokine released during the primary innate immune response to recruit neutrophils to the site of infection. Two distinct gene promoter haplotypes have been previously reported to segregate in the Holstein-Friesian breed (IL8-h1 and IL8-h2). Our earlier work showed how these divergent IL8 haplotypes influence IL-8 concentration and other immune response parameters at a systemic level. While a close relationship has been established between vitamin D and IL-8 in other species, the role of genetic haplotype on temporal variation in vitamin D concentrations and its impact on immunity remains unexplored in cattle. Therefore this study had two objectives - 1: to establish the temporal variation in IL-8 concentration profile in healthy calves of each IL-8 haplotype (n = 5/6 per group) and 2: to identify the relationship between systemic 25(OH)D concentration and IL8 haplotype in blood at 10 time points across their first year of life. Elevated IL-8 protein concentration profiles were apparent in IL8-h2 calves at multiple time points throughout the year (P < 0.05). In contrast, circulating concentrations of 25(OH) vitamin D were negatively correlated (0.38) with IL-8, with elevated concentrations in calves of the IL8-h1 haplotype. Increased numbers of innate immune cells - specifically monocytes and basophils, were also detected in blood from IL8-h2 calves (P < 0.05). Importantly, circulating concentrations of vitamin D were substantially below recommended concentrations of 30 ng/mL serum for optimal immunity in the first five months of life, indicating a window of potentially heightened disease susceptibility - particularly in calves of the IL8-h1 haplotype. In conclusion, this study has established that IL8 haplotype confers divergent chemokine concentrations and which contrasts with circulating concentrations of vitamin D. Accounting for both IL8 haplotype and vitamin D concentration may be critical to provide dairy calves with optimal immune protection in early life.

Children’s savings account programs are interventions that seek to engage disadvantaged children and their families in early college saving, cultivate college-saver identities, and reduce disparities in educational and economic outcomes. Existing research has revealed positive effects of CSAs on children’s outcomes, but questions remain about how and for whom CSAs facilitate these outcomes. This study uses account data from 493 accountholders and findings from interviews with 50 participants to examine asset accumulation and savings experiences among mostly low income, Latino families in New Mexico’s Prosperity Kids CSA program. One-third of the families made a deposit into their child’s account designated as “savers” with a median total contribution of $123 and a median account balance, including initial seed deposit, of $345. Longer duration of program enrollment and fewer number of unexcused absences predicted savers status. Qualitative findings highlight emerging college-saver identities, viewed through the framework of identity-based motivation, understood to include salience, normalization of difficulty, and group congruence. Qualitative interview data further suggest that initial seed money, deposit incentives, and withdrawal restrictions were important influences on participants’ saving. These findings suggest CSA features that may encourage positive savings outcomes for economically disadvantaged households and, then, that may have implications for future CSA policy development.

Introduction After stroke, upper limb impairment affects independent performance of activities of daily living. We evaluated the usability, functionality, and efficacy of a myoelectric elbow-wrist-hand orthosis to provide support, limit unsafe motion, and enhance the functional motion of paralyzed or weak upper limbs. Methods Individuals with stroke participated in a single-session study to evaluate the device. Ability to activate the device was tested in supported and unsupported shoulder position, as well as the elbow range of motion, ability to maintain elbow position, and ability to lift and hold a range of weights while using the device. Results No adverse events were reported. 71% of users were able to operate the device in all three active myoelectric activation modes (Biceps, Triceps, Dual) during testing. Users were able to hold a range of wrist weights (0.5–2 lbs) for 10–120 seconds, with the largest percentage of participants able to hold weights with the device in Biceps Mode. Conclusions The myoelectric elbow-wrist-hand orthosis improved range of motion during use and was efficacious at remediating upper extremity impairment after stroke. All users could operate the device in at least one mode, and most could lift and hold weights representative of some everyday objects using the device.

ObjectiveTo test the hypothesis that gait training with a hip-assistive robotic exoskeleton improves clinical outcomes and strengthens the descending corticospinal drive to the lower limb muscles in persons with chronic stroke.MethodsFifty participants completed the randomized, single-blind, parallel study. Participants received over-ground gait training with the Honda Stride Management Assist (SMA) exoskeleton or intensity-matched functional gait training, delivered in 18 sessions over 6–8 weeks. Performance-based and self-reported clinical outcomes were measured at baseline, midpoint, and completion, and at a 3-month follow-up. Corticomotor excitability (CME) of 3 bilateral leg muscles was measured using transcranial magnetic stimulation.ResultsThe primary outcome, walking speed, improved for the SMA group by completion of the program (0.24 ± 0.14 m/s difference, p < 0.001). Compared to the functional group, SMA users had greater improvement in walking endurance (46.0% ± 27.4% vs 35.7% ± 20.8%, p = 0.033), took more steps during therapy days (4,366 ± 2,426 vs 3,028 ± 1,510; p = 0.013), and demonstrated larger changes in CME of the paretic rectus femoris (178% ± 75% vs 33% ± 32%, p = 0.010). Participants with hemorrhagic stroke demonstrated greater improvement in balance when using the SMA (24.7% ± 20% vs 6.8% ± 6.7%, p = 0.029).ConclusionsGait training with the SMA improved walking speed in persons with chronic stroke, and may promote greater walking endurance, balance, and CME than functional gait training.Clinicaltrials.gov identifierNCT01994395.Classification of evidenceThis study provides Class I evidence that gait training with a hip-assistive exoskeleton increases clinical outcomes and CME in persons with chronic stroke, but does not significantly improve walking speeds compared to intensity-matched functional gait training.