Search

The QLX is a low-profile automatic powered wheelchair docking system (WDS) prototype developed to improve the securement and discomfort of wheelchair users when riding in vehicles. The study evaluates the whole-body vibration effects between the proposed QLX and another WDS (4-point tiedown system) following ISO 2631-1 standards and a systematic usability evaluation. Whole-body vibration analysis was evaluated in wheelchairs using both WDS to dock in a vehicle while riding on real-world surfaces. Also, participants rated the usability of each WDS while driving a wheelchair and while riding in a vehicle in driving tasks. Both WDSs showed similar vibration results within the vibration health-risk margins; but shock values below health-risk margins. Fifteen powered wheelchair users reported low task load demand to operate both WDS; but better performance to dock in vehicles with the QLX (p = 0.03). Also, the QLX showed better usability (p < 0.01), less discomfort (p’s < 0.05), and greater security compared to the 4-point tiedown while riding in a vehicle (p’s < 0.05). Study findings indicate that both WDS maintain low shock exposure for wheelchair users while riding vehicles, but a better performance overall to operate the QLX compared to the 4-point tiedown system; hence enhancing user’s autonomy to dock in vehicles independently.

Despite advances in wearable robots across various fields, there is no consensus definition or design framework for the application of this technology in rehabilitation or musculoskeletal (MSK) injury prevention. This paper aims to define wearable robots and explore their applications and challenges for military rehabilitation and force protection for MSK injury prevention. We conducted a modified Delphi method, including a steering group and 14 panelists with 10+ years of expertise in wearable robots. Panelists presented current wearable robots currently in use or in development for rehabilitation or assistance use in the military workforce and healthcare. The steering group and panelists met to obtain a consensus on the wearable robot definition applicable for rehabilitation or primary injury prevention. Panelists unanimously agreed that wearable robots can be grouped into three main applications, as follows: (1) primary and secondary MSK injury prevention, (2) enhancement of military activities and tasks, and (3) rehabilitation and reintegration. Each application was presented within the context of its target population and state-of-the-art technology currently in use or under development. Capturing expert opinions, this study defines wearable robots for military rehabilitation and MSK injury prevention, identifies health outcomes and assessment tools, and outlines design requirements for future advancements.

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates.

Caregivers that assist with wheelchair transfers are susceptible to back pain and occupational injuries. The study describes a prototype of the powered personal transfer system (PPTS) consisting of a novel powered hospital bed and a customized Medicare Group 2 electric powered wheelchair (EPW) working together to provide a no-lift solution for transfers. The study follows a participatory action design and engineering (PADE) process and describes the design, kinematics, and control system of the PPTS and end-users’ perception to provide qualitative guidance and feedback about the PPTS. Thirty-six participants (wheelchair users (n = 18) and caregivers (n = 18)) included in the focus groups reported an overall positive impression of the system. Caregivers reported that the PPTS would reduce the risk of injuries and make transfers easier. Feedback revealed limitations and unmet needs of mobility device users, including a lack of power seat functions in the Group-2 wheelchair, a need for no-caregiver assistance/capability for independent transfers, and a need for a more ergonomic touchscreen. These limitations may be mitigated with design modifications in future prototypes. The PPTS is a promising robotic transfer system that may aid in the higher independence of powered wheelchair users and provide a safer solution for transfers.

IntroductionTransorbital sonographic measurement of optic nerve sheath diameter (ONSD) is an emerging non-invasive technique for the identification and monitoring of intracranial hypertension. In recent years, new pocket ultrasound devices have become available, and it is uncertain if they have the resolution to measure such small structures appropriately as compared to their predecessors. In this study, we measure the performance of three ultrasound units on a simulation model to establish their precision and accuracy.MethodsONSD was measured by three expert point-of-care sonographers using ultrasound machines three times on each of seven discrete ONS model sizes ranging from 3.5 to 7.9 mm. Two pocket ultrasounds (IVIZ, Sonosite, and Lumify, Philips) and one standard-sized portable ultrasound (M-Turbo, Sonosite) were used. Measurements were analyzed for mean error and variance and tested for significance using blocked covariance matrix regression analyses.ResultsThe devices differed in their variances (Lumify: 0.19 mm2, M-Turbo: 0.26 mm2, IVIZ: 0.34 mm2) and their mean error (Lumify: −0.05 mm, M-Turbo: 0.10 mm, IVIZ: −0.10 mm). The difference in mean error between users is not significant (p = 0.45), but there is a significant difference in mean error between devices (p = 0.02).ConclusionsAccurate ONSD measurement is possible utilizing pocket-sized ultrasound, and in some cases, may be more accurate than larger portable ultrasound units. While the differences in these devices were statistically significant, all three were highly accurate, with one pocket device (Lumify) outperforming the rest. Further study in human subjects should be conducted prior to using pocket ultrasound devices for in vivo diagnosis of intracranial hypertension.

Abstract Background Ultrasound measurement of optic nerve sheath diameter (ONSD) appears to be a promising, rapid, non-invasive bedside tool for identification of elevated intra-cranial pressure. With improvements in ultrasound technology, machines are becoming smaller; however, it is unclear if these ultra-portable handheld units have the resolution to make these measurements precisely. In this study, we estimate the accuracy of ONSD measurement in a pocket-sized ultrasound unit. Methods Utilizing a locally developed, previously validated model of the eye, ONSD was measured by two expert observers, three times with two machines and on five models with different optic nerve sheath sizes. A pocket ultrasound (Vscan, GE Healthcare) and a standard portable ultrasound (M-Turbo, SonoSite) were used to measure the models. Data was analyzed by Bland–Altman plot and intra-class correlation coefficient (ICC). Results The ICC between raters for the SonoSite was 0.878, and for the Vscan was 0.826. The between-machine agreement ICC was 0.752. Bland–Altman agreement analysis between the two ultrasound methods showed an even spread across the range of sheath sizes, and that the Vscan tended to read on average 0.33 mm higher than the SonoSite for each measurement, with a standard deviation of 0.65 mm. Conclusions Accurate ONSD measurement may be possible utilizing pocket-sized, handheld ultrasound devices despite their small screen size, lower resolution, and lower probe frequencies. Further study in human subjects is warranted for all newer handheld ultrasound models as they become available on the market.

Background. New sonographic quality criteria to optimize optic nerve sheath diameter (ONSD) measurements were suggested. The latter were correlated to elevated intracranial pressure (ICP) in traumatic brain injury (TBI). Aim. We investigated whether ONSD measurements were correlated to simultaneous ICP measurements in severe TBI. Methods. Forty patients with severe TBI (Marshall Scale ≥II and GCS ≤8) participated in the study. All patients had an intraparenchymal ICP catheter inserted, while ONSD was measured bilaterally, upon admission and over the next 48 hours, based on the new sonographic criteria. A total of 400 ONSD measurements were performed, while mean ONSD values of both eyes were used in the analysis. Results. ONSD measurements were strongly correlated to ICP values (r=0.74, p

The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.

The Amyloid Precursor Protein (APP) undergoes sequential proteolytic cleavages through the action of beta- and gamma-secretase, which result in the generation of toxic beta-amyloid (Abeta) peptides and a C-terminal fragment consisting of the intracellular domain of APP (AICD). Mutations leading to increased APP levels or alterations in APP cleavage cause familial Alzheimer's disease (AD). Thus, identification of factors that regulate APP steady state levels and/or APP cleavage by gamma-secretase is likely to provide insight into AD pathogenesis. Here, using transgenic flies that act as reporters for endogenous gamma-secretase activity and/or APP levels (GAMAREP), and for the APP intracellular domain (AICDREP), we identified mutations in X11L and ubiquilin (ubqn) as genetic modifiers of APP. Human homologs of both X11L (X11/Mint) and Ubqn (UBQLN1) have been implicated in AD pathogenesis. In contrast to previous reports, we show that overexpression of X11L or human X11 does not alter gamma-secretase cleavage of APP or Notch, another gamma-secretase substrate. Instead, expression of either X11L or human X11 regulates APP at the level of the AICD, and this activity requires the phosphotyrosine binding (PTB) domain of X11. In contrast, Ubqn regulates the levels of APP: loss of ubqn function leads to a decrease in the steady state levels of APP, while increased ubqn expression results in an increase in APP levels. Ubqn physically binds to APP, an interaction that depends on its ubiquitin-associated (UBA) domain, suggesting that direct physical interactions may underlie Ubqn-dependent regulation of APP. Together, our studies identify X11L and Ubqn as in vivo regulators of APP. Since increased expression of X11 attenuates Abeta production and/or secretion in APP transgenic mice, but does not act on gamma-secretase directly, X11 may represent an attractive therapeutic target for AD.

Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures.We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively.We conclude that PB gene expression profiles can be identified in mice and humans that are accurate in predicting medical conditions, are specific to each condition and remain highly accurate over time.

The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans.We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.

Time-resolved cathodoluminescence using 30 keV ultrafast electron pulses has been used to perform direct measurements of the minority hole lifetime τ h as a function of 3.7 MeV α -particle fluence in high-quality free-standing n-type GaN substrates. The lifetime damage factor K calculated from these measurements was found to monotonically decrease from 6.9 × 10−2 to 6.4 × 10−4 cm2 s−1 ion−1 with increasing α -fluence from 108 to 1012 cm−2, implying a reduction in trap cross section and/or an aggregation of α -induced traps. The small, ∼ 200–300 nm, hole diffusion length estimated from the minority hole lifetime for the highest α -fluence necessitates the deployment of α -voltaic device strategies and architectures that emphasize depletion and drift over diffusion for effective charge collection and optimal power conversion efficiency. [ABSTRACT FROM AUTHOR]

Despite advances in wearable robots across various fields, there is no consensus definition or design framework for the application of this technology in rehabilitation or musculoskeletal (MSK) injury prevention. This paper aims to define wearable robots and explore their applications and challenges for military rehabilitation and force protection for MSK injury prevention. We conducted a modified Delphi method, including a steering group and 14 panelists with 10+ years of expertise in wearable robots. Panelists presented current wearable robots currently in use or in development for rehabilitation or assistance use in the military workforce and healthcare. The steering group and panelists met to obtain a consensus on the wearable robot definition applicable for rehabilitation or primary injury prevention. Panelists unanimously agreed that wearable robots can be grouped into three main applications, as follows: (1) primary and secondary MSK injury prevention, (2) enhancement of military activities and tasks, and (3) rehabilitation and reintegration. Each application was presented within the context of its target population and state-of-the-art technology currently in use or under development. Capturing expert opinions, this study defines wearable robots for military rehabilitation and MSK injury prevention, identifies health outcomes and assessment tools, and outlines design requirements for future advancements. [ABSTRACT FROM AUTHOR]