General Muscle Torque Generator Model for a Two Degree-of-Freedom Shoulder Joint.

Muscle torque generators (MTGs) have been developed as an alternative to muscle-force models, reducing the muscle-force model complexity to a single torque at the joint. Current MTGs can only be applied to single Degree-of-freedom (DoF) joints, leading to complications in modeling joints with multiple-DoFs such as the shoulder. This study aimed to develop an MTG model that accounts for the coupling between 2-DoF at the shoulder joint: shoulder plane of elevation (horizontal abduction/adduction) and shoulder elevation (flexion/extension). Three different 2-DoF MTG equations were developed to model the coupling between these two movements. Net joint torques at the shoulder were determined for 20 participants (10 females and 10 males) in isometric, isokinetic, and passive tests. Curve and surface polynomial fitting were used to find the best general fit for the experimental data in terms of the different degrees of coupling. The models were validated against experimental isokinetic torque data. It was determined that implicit coupling that used interpolation between single-DoF MTGs resulted in the lowest root-mean-square percent error of 8.5%. The work demonstrated that general MTG models can predict torque results that are dependent on multiple-DoFs of the shoulder.

Community advisory board members' perspectives on their contributions to a large multistate cluster RCT: a mixed methods study.

Background: Community advisory boards (CABs) are an established approach to ensuring research reflects community priorities. This paper examines two CABs that are part of the HEALing Communities Study which aims to reduce overdose mortality. This analysis aimed to understand CAB members' expectations, experiences, and perspectives on CAB structure, communication, facilitation, and effectiveness during the first year of an almost fully remote CAB implementation. Current literature exploring these perspectives is limited. Methods: We collected qualitative and survey data simultaneously from members (n = 53) of two sites' CABs in the first 9 months of CAB development. The survey assessed trust, communication, and relations; we also conducted 32 semi-structured interviews. We analyzed the survey results descriptively. The qualitative data were analyzed using a deductive codebook based on the RE-AIM PRISM framework. Themes were drawn from the combined qualitative data and triangulated with survey results to further enrich the findings. Results: CAB members expressed strong commitment to overall study goals and valued the representation of occupational sectors. The qualitative data described a dissonance between CAB members' commitment to the mission and unmet expectations for influencing the study within an advisory role. Survey results indicated lower satisfaction with the research teams' ability to create a mutually beneficial process, clear communication, and sharing of power. Conclusion: Building a CAB on a remote platform, within a study utilizing a community engagement strategy, still presents challenges to fully realizing the potential of a CAB. These findings can inform more effective operationalizing of community-engaged research through enhanced CAB engagement.

The prodomain of Arabidopsis metacaspase 2 positively regulates immune signaling mediated by pattern-recognition receptors.

Metacaspases (MCs) are structural homologs of mammalian caspases found in plants, fungi, and protozoa. Type-I MCs carry an N-terminal prodomain, the function of which is unclear. Through genetic analysis of Arabidopsis mc2-1, a T-DNA insertion mutant of MC2, we demonstrated that the prodomain of metacaspase 2 (MC2) promotes immune signaling mediated by pattern-recognition receptors (PRRs). In mc2-1, immune responses are constitutively activated. The receptor-like kinases (RLKs) BAK1/BKK1 and SOBIR1 are required for the autoimmune phenotype of mc2-1, suggesting that immune signaling mediated by the receptor-like protein (RLP)-type PRRs is activated in mc2-1. A suppressor screen identified multiple mutations in the first exon of MC2, which suppress the autoimmunity in mc2-1. Further analysis revealed that the T-DNA insertion at the end of exon 1 of MC2 causes elevated expression of the MC2 prodomain, and overexpression of the MC2 prodomain in wild-type (WT) plants results in the activation of immune responses. The MC2 prodomain interacts with BIR1, which inhibits RLP-mediated immune signaling by interacting with BAK1, suggesting that the MC2 prodomain promotes plant defense responses by interfering with the function of BIR1. Our study uncovers an unexpected function of the prodomain of a MC in plant immunity.

Plant-based, aqueous, water-repellent sprays for coating textiles.

Novel superhydrophobic coatings, that are both biodegradable and biosourced, have the potential to revolutionize the water-repellent coating industry. Here, water-repellent coatings were prepared from commercially unavailable plant waxes, isolated using solvent extraction and characterized using DSC, GC-MS and DLS. In the first stage, a plant survey was conducted to identify an ideal plant source for the final spray, in which Whatman filter paper was submerged in a wax-solvent solution with recrystallization occurring upon air-drying. In the second stage, aqueous, PFC-free wax dispersions were prepared, coated onto textiles (cotton and polyester), and heat-treated with a home drying machine to allow for the spreading and recrystallization of the waxes. In both stages, SEM visualization verified the coating's morphology, and contact angle measurements showed them to be superhydrophobic. It was concluded that, using less coating material than commercial coatings, high-performing petroleum-free coatings could be made and applied onto textiles of various polarities.

Community coalition and key stakeholder perceptions of the community opioid epidemic before an intensive community-level intervention.

INTRODUCTION: Opioid overdoses are a major public health emergency in the United States. Despite effective treatments that can save lives, access to and utilization of such treatments are limited. Community context plays an important role in addressing treatment barriers and increasing access. The HEALing Communities Study (HCS) is a multisite community-level cluster-randomized trial that will study implementation and outcomes of a community coalition-based intervention (Communities that HEAL [CTH]) that implements evidence-based practices (EBPs) to reduce opioid overdose deaths in four states. To examine contextual factors critical to understanding implementation, we assessed the perspectives of community members about their communities, current substance use-related services, and other important issues that could impact intervention implementation. METHODS: Researchers conducted 382 semi-structured qualitative interviews in the HCS communities. Interviews were audio-recorded and transcribed; researchers subsequently analyzed data using directed content analysis based on the constructs of the RE-AIM/PRISM implementation science framework to identify key themes within the external community context. RESULTS: Despite the diversity in states and communities, four similar themes related to the external community context emerged across communities: These themes included the importance of understanding: 1) community risk perceptions, 2) levels of stigma, 3) the health services environment and the availability of substance use services, and 4) funding for substance use services. CONCLUSION: Understanding and addressing the external community context in which the CTH intervention and EBPs are implemented are crucial for successful health services-related and community engaged interventions. While implementing EBPs is a challenging undertaking, doing so will help us to understand if and how a community-based intervention can successfully reduce opioid overdose deaths and influence both community beliefs and the community treatment landscape.

MuscleNET: mapping electromyography to kinematic and dynamic biomechanical variables by machine learning.

Objective.This paper proposes machine learning models for mapping surface electromyography (sEMG) signals to regression of joint angle, joint velocity, joint acceleration, joint torque, and activation torque.Approach.The regression models, collectively known as MuscleNET, take one of four forms: ANN (forward artificial neural network), RNN (recurrent neural network), CNN (convolutional neural network), and RCNN (recurrent convolutional neural network). Inspired by conventional biomechanical muscle models, delayed kinematic signals were used along with sEMG signals as the machine learning model's input; specifically, the CNN and RCNN were modeled with novel configurations for these input conditions. The models' inputs contain either raw or filtered sEMG signals, which allowed evaluation of the filtering capabilities of the models. The models were trained using human experimental data and evaluated with different individual data.Main results.Results were compared in terms of regression error (using the root-mean-square) and model computation delay. The results indicate that the RNN (with filtered sEMG signals) and RCNN (with raw sEMG signals) models, both with delayed kinematic data, can extract underlying motor control information (such as joint activation torque or joint angle) from sEMG signals in pick-and-place tasks. The CNNs and RCNNs were able to filter raw sEMG signals.Significance.All forms of MuscleNET were found to map sEMG signals within 2 ms, fast enough for real-time applications such as the control of exoskeletons or active prostheses. The RNN model with filtered sEMG and delayed kinematic signals is particularly appropriate for applications in musculoskeletal simulation and biomechatronic device control.

InverseMuscleNET: Alternative Machine Learning Solution to Static Optimization and Inverse Muscle Modeling.

InverseMuscleNET, a machine learning model, is proposed as an alternative to static optimization for resolving the redundancy issue in inverse muscle models. A recurrent neural network (RNN) was optimally configured, trained, and tested to estimate the pattern of muscle activation signals. Five biomechanical variables (joint angle, joint velocity, joint acceleration, joint torque, and activation torque) were used as inputs to the RNN. A set of surface electromyography (EMG) signals, experimentally measured around the shoulder joint for flexion/extension, were used to train and validate the RNN model. The obtained machine learning model yields a normalized regression in the range of 88-91% between experimental data and estimated muscle activation. A sequential backward selection algorithm was used as a sensitivity analysis to discover the less dominant inputs. The order of most essential signals to least dominant ones was as follows: joint angle, activation torque, joint torque, joint velocity, and joint acceleration. The RNN model required 0.06 s of the previous biomechanical input signals and 0.01 s of the predicted feedback EMG signals, demonstrating the dynamic temporal relationships of the muscle activation profiles. The proposed approach permits a fast and direct estimation ability instead of iterative solutions for the inverse muscle model. It raises the possibility of integrating such a model in a real-time device for functional rehabilitation and sports evaluation devices with real-time estimation and tracking. This method provides clinicians with a means of estimating EMG activity without an invasive electrode setup.

A Systematic Review of Surveys for Measuring Patient-centered Care in the Hospital Setting.

BACKGROUND: Patient-centered care (PCC) is a core component of quality care and its measurement is fundamental for research and improvement efforts. However, an inventory of surveys for measuring PCC in hospitals, a core care setting, is not available. OBJECTIVE: To identify surveys for assessing PCC in hospitals, assess PCC dimensions that they capture, report their psychometric properties, and evaluate applicability to individual and/or dyadic (eg, mother-infant pairs in pregnancy) patients. RESEARCH DESIGN: We conducted a systematic review of articles published before January 2019 available on PubMed, Web of Science, and EBSCO Host and references of extracted papers to identify surveys used to measure "patient-centered care" or "family-centered care." Surveys used in hospitals and capturing at least 3 dimensions of PCC, as articulated by the Picker Institute, were included and reviewed in full. Surveys' descriptions, subscales, PCC dimensions, psychometric properties, and applicability to individual and dyadic patients were assessed. RESULTS: Thirteen of 614 articles met inclusion criteria. Nine surveys were identified, which were designed to obtain assessments from patients/families (n=5), hospital staff (n=2), and both patients/families and hospital staff (n=2). No survey captured all 8 Picker dimensions of PCC [median=6 (range, 5-7)]. Psychometric properties were reported infrequently. All surveys applied to individual patients, none to dyadic patients. CONCLUSIONS: Multiple surveys for measuring PCC in hospitals are available. Opportunities exist to improve survey comprehensiveness regarding dimensions of PCC, reporting of psychometric properties, and development of measures to capture PCC for dyadic patients.

Prospects, challenges and current status of RNAi through insect feeding.

RNA interference is a phenomenon in which the introduction of double-stranded RNA (dsRNA) into cells triggers the degradation of the complementary messenger RNA in a sequence-specific manner. Suppressing expression of vital genes could lead to insect death, therefore this technology has been considered as a potential strategy for insect pest control. There are three main routes of dsRNA administration into insects: (i) injections to the hemolymph, (ii) topical, and (iii) feeding. In this review, we focus on dsRNA administration through feeding. We summarize novel strategies that have been developed to improve the efficacy of this method, such as the use of nano-based formulations, engineered microorganisms, and transgenic plants. We also expose the hurdles that have to be overcome in order to use this technique as a reliable pest management method. © 2019 Society of Chemical Industry.

High-Throughput Synthesis, Analysis, and Optimization of Injectable Hydrogels for Protein Delivery.

The development of in situ-gelling hydrogels that can enable prolonged protein release is increasingly important due to the emergence of a growing number of protein-based therapeutics. Herein, we describe a high-throughput strategy to fabricate, characterize, and subsequently optimize hydrazone-cross-linked in situ-gelling hydrogels for protein delivery. Hydrogels are fabricated using an automated high-throughput robot to mix a variety of thermoresponsive, nonthermoresponsive, charged, neutral, naturally sourced, and synthetic polymers functionalized with hydrazide or aldehyde groups, generating in situ-gelling hydrogels with well-defined compositions within a 96-well plate. High-throughput characterization strategies are subsequently developed to enable on-plate analysis of hydrogel swelling, mechanics, degradation, transparency, and protein (ovalbumin) release kinetics that yield results consistent with those collected using traditional bulk hydrogel analysis techniques. Dynamic regression and latent variable modeling are then applied to fit performance statistics to the collected data set; subsequently, numerical optimization is used to identify mixtures of precursor polymers that exhibit targeted combinations of minimal burst release, maximum total protein release, minimum release rate, and maximum transparency (the latter of particular relevance for ophthalmic protein delivery applications). Given the rapid throughput of the protocols developed (i.e., 126 hydrogels can be synthesized and screened in quadruplicate within hours), this approach offers particular promise for accelerating the identification of injectable hydrogel compositions relevant for both protein delivery as well as other biomedical applications for which clearly predefined materials properties are required.

AKT1, LKB1, and YAP1 Revealed as MYC Interactors with NanoLuc-Based Protein-Fragment Complementation Assay.

The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the development of a NanoLuc-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2. Importantly, NanoPCA allows the study of PPI dynamics with reversible interactions. To demonstrate its utility for large-scale PPI detection in mammalian intracellular environment, we have used NanoPCA to examine MYC interaction with 83 cancer-associated proteins in live cancer cell lines. Our new MYC PPI data confirmed known MYC-interacting proteins, such as MAX, GSK3A, and SMARCA4, and revealed a panel of novel MYC interaction partners, such as RAC-α serine/threonine-protein kinase (AKT)1, liver kinase B (LKB)1, and Yes-associated protein (YAP)1. The MYC interactions with AKT1, LKB1, and YAP1 were confirmed by coimmunoprecipitation of endogenous proteins. Importantly, AKT1, LKB1, and YAP1 were able to activate MYC in a transcriptional reporter assay. Thus, these vital growth control proteins may represent promising MYC regulators, suggesting new mechanisms that couple energetic and metabolic pathways and developmental signaling to MYC-regulated cellular programs.

Development of an internal amplification control system for a real-time PCR assay for detection of Neisseria meningitidis in CSF and EDTA blood.

The aim of this study was to assemble and assess a non-competitive internal amplification control (IAC) system targeting the Escherichia coli alanine racemase (alr) gene to include in a real-time polymerase chain reaction (PCR) assay for Neisseria meningitidis. Primers and hybridisation probes specific for the IAC were designed and assessed for specificity. Amplification efficiency and limit of detection for the assembled assay was extrapolated using standard curves constructed with serial dilutions of N. meningitidis in saline, pooled cerebrospinal fluid (CSF) and EDTA blood. The 95% confidence limits (CI) were calculated for IAC crossing-points recorded for assays for N. meningitidis ctrA in saline (negative blank), and N. meningitides-negative samples of CSF and EDTA blood. These limits served as a reference range against which the IAC crossing-points recorded for prospective assays are compared to detect sample inhibition. This system was used in testing consecutive EDTA blood samples from two cases of meningococcal disease. The IAC system is specific for Escherichia coli and Shigella species. The amplification efficiency of the assembled assay for N. meningitidis and ability to detect low target DNA levels was not compromised with the inclusion of the IAC system. The IAC crossing-points varied in clinical samples of CSF and EDTA blood. The elucidated reference range for EDTA blood was used to detect sample inhibition in one of the two clinical cases investigated.The IAC system monitors the performance of all processes in the assembled assay for N. meningitidis. Measuring IAC crossing-points serves as an indicator of sample stability and inhibitory properties when testing single or multiple samples from the same patient. Specificity for E. coli and Shigella species enables inclusion in assays of different targets within the same laboratory. Reporting PCR assay results in the context of the IAC crossing-points and reference ranges validates against sample inhibition and suitability for detection of low levels of target DNA in random and multiple samples.

Limited diversity in the gene pool allows prediction of third-generation cephalosporin and aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae.

Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ≥ 2 µg/mL were collected from seven major hospitals in Sydney (Australia) in 2008-2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC ≥ 2 µg/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC ≥ 8 µg/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5-10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations.

Antibiotic susceptibility patterns of Staphylococcus aureus isolates from Australian children.

AIM: Staphylococcus aureus is an important cause of serious illness in children. Antibiotic resistance is an international problem and affects initial antibiotic choice. We aimed to describe susceptibility patterns of S. aureus isolates from Australian children to inform optimal empiric treatment of staphylococcal infections in this population. METHODS: We analysed susceptibility data for all S. aureus isolates from children at Australian tertiary paediatric hospitals in 2006. Susceptibility rates were compared between hospitals and states, and with published studies of S. aureus isolates from Australian adults. RESULTS: Overall, the proportion of methicillin-resistant S. aureus (MRSA) in Australian children was low (9.8%), and in each state it was less than for the comparable adult population. There were significant differences in susceptibility patterns between different states. Most MRSA isolates were susceptible to clindamycin (73%) and all isolates were reported as susceptible to vancomycin. Susceptibility patterns for isolates from bacteraemic patients were similar to those for isolates from all patients. CONCLUSIONS: These data support current Australian recommendations for the use of flucloxacillin or a first-generation cephalosporin as initial treatment of non-life-threatening staphylococcal infections. However, broad spectrum antibiotic therapy including agents that are effective against MRSA should be considered for more serious infections. Appropriate specimens should be collected for susceptibility testing to enable directed treatment for MRSA and other resistant organisms. This study highlights the importance of using local, age-specific data in planning antibiotic treatment guidelines, as results vary substantially from city to city and between adults and children.

Surgical site marking does not affect sterility.

BACKGROUND: In 2005, surgical site marking became mandatory in Australia, with the introduction of the first Australian guidelines to prevent wrong site surgery. It has been our experience that most surgical site marking occurs with the use of a non-sterile marking pen, which has been used on multiple patients and there is little information in the published work about the effects of surgical site marking carried out in this fashion. Our aim was to determine whether the sterility of a surgical site was affected by surgical site marking with a non-sterile surgical marking pen. METHODS: Both forearms of 20 volunteers would simulate surgical sites. Surgical site marking was carried out on right forearms with the same non-sterile surgical marking pen, whereas left forearms were unmarked controls. Microbiology swabs were taken from both forearms before, and after, skin sterilization with 10% povidone-iodine. Routine cultures were carried out on the swabs after sodium thiosulphate was used to deactivate residual iodine. Cultures were assessed for growth after 5 days. RESULTS: One of the 20 marked forearms and 15 of the 20 unmarked forearms had bacterial growth on cultures before skin sterilization (P < 0.1). After sterilization with iodine, no bacterial growth occurred in the cultures of the swabs taken from the marked or control arms. CONCLUSION: Surgical site marking carried out with a non-sterile surgical marking pen did not contaminate the surgical site. We recommend the practice of surgical site marking.

Bacteria commonly isolated from keratitis specimens retain antibiotic susceptibility to fluoroquinolones and gentamicin plus cephalothin.

PURPOSE: Patients presenting with presumed infective keratitis were studied to determine predisposing factors, the current susceptibilities of the bacterial isolates to a range of relevant antibiotics, the success rate of topical antibiotic treatment of keratitis and predictors of failure of topical therapy. METHODS: Corneal scrapings taken from patients who presented between January 2002 and December 2003 to the Sydney Eye Hospital Emergency Department with keratitis were cultured. The minimum inhibitory concentration of selected antibiotics was determined for each bacterial isolate using an agar dilution technique. RESULTS: One hundred and twelve consecutive patients presented with corneal ulcers. Forty-seven of the 112 (42%) patients had a growth from the corneal scraping. Potential predisposing factors were identified in 64% of patients, most frequently contact lens wear (36% of patients). Coagulase-negative staphylococci were the most common species isolated. Other common organisms isolated include Pseudomonas aeruginosa, Corynebacterium spp., Staphylococcus aureus and Streptococcus spp. CONCLUSIONS: Most microorganisms isolated from patients with bacterial keratitis showed susceptibility to ciprofloxacin and aminoglycosides. Cephalothin plus aminoglycoside constituted an effective initial broad-spectrum antibiotic combination. The success rate of topical antibiotic treatment of corneal abscess is 89%. Predictors of failure include older age group, medium or large ulcer, culture-negative keratitis, hypopyon and poor visual acuity.