Human-centered Electric Prosthetic (HELP) Hand

Through a partnership with Indian non-profit Bhagwan Mahaveer Viklang Sahayata Samiti, we designed a functional, robust, and and low cost electrically powered prosthetic hand that communicates with unilateral, transradial, urban Indian amputees through a biointerface. The device uses compliant tendon actuation, a small linear servo, and a wearable garment outfitted with flex sensors to produce a device that, once placed inside a prosthetic glove, is anthropomorphic in both look and feel. The prosthesis was developed such that future groups can design for manufacturing and distribution in India

For hospitalized dementia patients, do nonpharmacological interventions reduce agitation?

https://digitalcommons.psjhealth.org/stvincent-bootcamp/1035/thumbnail.jp

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission.

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.This work was supported by the Wellcome Trust Senior Research Fellowships 108070/Z/15/Z to MPW, 215515/Z/19/Z to SGB and 207498/Z/17/Z to IGG; Collaborative award 206298/B/17/Z to IGG; Principal Research Fellowship 210688/Z/18/Z to PJL; Investigator Award 200871/Z/16/Z to KGCS; Addenbrooke’s Charitable Trust (to MPW, SGB, IGG and PJL); the Medical Research Council (CSF MR/P008801/1 to NJM); NHS Blood and Transfusion (WPA15-02 to NJM); National Institute for Health Research (Cambridge Biomedical Research Centre at CUHNFT), to JRB, MET, AC and GD, Academy of Medical Sciences and the Health Foundation (Clinician Scientist Fellowship to MET), Engineering and Physical Sciences Research Council (EP/P031447/1 and EP/N031938/1 to RS),Cancer Research UK (PRECISION Grand Challenge C38317/A24043 award to JY). Components of this work were supported by the COVID-19 Genomics UK Consortium, (COG-UK), which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institut

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

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

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

Advancing Inertial Sensors for Performance Quantification: Applications in Balance Rehabilitation and Distance Running

Wearable sensors in the form of inertial measurement units (IMUs) enable the unobtrusive quantification of human movement during daily life. As a result, IMUs ubiquitously appear in smart devices such as phones and watches. Substantial research has explored the use of inertial data in performance assessment and feedback systems with applications spanning from biomedical monitoring to athlete training. However, the algorithms required to generate useful insights vary between movement types and user populations. Continued work is required to fully leverage these wearable devices for their potential benefits to human health and performance. This dissertation advances the use of inertial data in two application areas, balance rehabilitation and distance running. Part I of this dissertation advances IMU-driven feedback systems for use during remote balance rehabilitation programs. Balance rehabilitation is traditionally performed in a clinical setting with the instruction of a physical therapist. However, cost and availability limit access to balance therapy. Technologies improving balance telerehabilitation may therefore improve access to quality care. Inertial sensors can be used to support balance telerehabilitation; training effects can be monitored via automated clinical balance tests, training programs can be automatically or remotely optimized via performance assessments, and the efficacy of training can be improved via feedback. Two studies herein advance the use of IMUs to support remote balance rehabilitation. In the first study, the effects of IMU-driven terminal (i.e., post-task) visual feedback on sway magnitude and velocity were found to be comparable to those of established concurrent (i.e., real-time) feedback methods during a single session of training. Because IMU-based terminal feedback is possible via a single smartphone, it may further support simple, affordable, and accessible balance training devices. In the second study, self-assessments and IMU-driven kinematic measurements were significantly but imperfectly correlated with expert physical therapist intensity assessments. They may therefore be useful during telerehabilitation when expert visual assessment is difficult. Together, these studies on balance rehabilitation suggest that IMU-based systems may support high-quality home-based care. Part II of this dissertation advances the use of IMUs for “real-world” distance running assessment. While analyses of running gait have traditionally been performed in a laboratory, running biomechanics, physiology, and psychology all differ between laboratory and “real-world” settings. IMU-based assessments of “real-world” distance running may therefore capture “real-world” performance determinants, injury etiology, and training or intervention effects. Additionally, IMU-based systems may be less expensive and more accessible than traditional laboratory-based systems. However, additional research is required to expand the set of metrics available via IMUs and to establish relationships between inertial data and important aspects of running performance. Two studies in the dissertation advance the use of IMUs to assess “real-world” distance running. In the first study, an error-state Kalman filter (ErKF) algorithm for the estimation of three-dimensional lower-body running kinematics resulted in joint angle estimates of comparable accuracies to existing methods. ErKF algorithms may also support adaptation to experimental design (e.g., speed, running surface) and should therefore be further advanced for kinematic estimation during “real-world” running. In the second study, numerous biomechanical measures including peak acceleration attenuation and stability were associated with positive running experiences during long, outdoor training runs. These relationships should be additionally explored as means of supporting positive running experiences. Together, these studies on distance running demonstrate that wearable sensors can provide meaningful measures of performance during “real-world” running.PhDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/178026/1/jcferris_1.pd

A Pilot Study Comparing the Effects of Concurrent and Terminal Visual Feedback on Standing Balance in Older Adults

While balance training with concurrent feedback has been shown to improve real-time balance in older adults, terminal feedback may simplify implementation outside of clinical settings. Similarly, visual feedback is particularly well-suited for use outside the clinic as it is relatively easily understood and accessible via ubiquitous mobile devices (e.g., smartphones) with little additional peripheral equipment. However, differences in the effects of concurrent and terminal visual feedback are not yet well understood. We therefore performed a pilot study that directly compared the immediate effects of concurrent and terminal visual feedback as a first and necessary step in the future design of visual feedback technologies for balance training outside of clinical settings. Nineteen healthy older adults participated in a single balance training session during which they performed 38 trials of a single balance exercise including trials with concurrent, terminal or no visual feedback. Analysis of trunk angular position and velocity features recorded via an inertial measurement unit indicated that sway angles decreased with training regardless of feedback type, but sway velocity increased with concurrent feedback and decreased with terminal feedback. After removing feedback, training with either feedback type yielded decreased mean velocity, but only terminal feedback yielded decreased sway angles. Consequently, this study suggests that, for older adults, terminal visual feedback may be a viable alternative to concurrent visual feedback for short duration single-task balance training. Terminal feedback provided using ubiquitous devices should be further explored for balance training outside of clinical settings