Monitoring falls in residential aged care facilities: Agreement between falls incident reports and progress notes.

OBJECTIVES: Accurate fall reporting is essential for assessing the effectiveness of fall prevention strategies. This study aimed to investigate the level of agreement between incident reports and resident progress notes as data sources for falls monitoring in residential aged care facilities. METHODS: A retrospective observational study was conducted involving 46 older people from six residential aged care facilities who had consented to join the broader TOP UP trial. Fall events documented in the incident report system and resident progress notes over 12 months before randomisation were extracted by two independent reviewers using a standardised Excel form. Agreement between the two data collection methods was calculated using Cohen's kappa coefficient. RESULTS: A total of 75 falls were recorded from 27 (59%) of the 46 participants who were 65% female, with an average age of 83 [SD 9] years. The incident reports captured 68 (90.7%) falls, while the progress notes captured 73 (97.3%) falls. Overall, there was a 75% agreement between falls recorded in progress notes and incident reports. Perfect agreement was identified for five facilities (n = 35), while one facility had a lower agreement rate of 29% (n = 11), which appeared to be attributable to staff shortages linked to the COVID-19 pandemic. CONCLUSIONS: There was substantial agreement between incident reports and progress records. These findings support the use of incident reports for identifying falls in research or to investigate the effectiveness of fall prevention strategies in residential aged care facilities.

Disruption of Ebola NP0VP35 Inclusion Body-like Structures reduce Viral Infection.

Viral inclusion bodies (IBs) are potential sites of viral replication and assembly. How viral IBs form remains poorly defined. Here we describe a combined biophysical and cellular approach to identify the components necessary for IB formation during Ebola virus (EBOV) infection. We find that the eNP0VP35 complex containing Ebola nucleoprotein (eNP) and viral protein 35 (eVP35), the functional equivalents of nucleoprotein (N) and phosphoprotein (P) in non-segmented negative strand viruses (NNSVs), phase separates to form inclusion bodies. Phase separation of eNP0VP35 is reversible and modulated by ionic strength. The multivalency of eVP35, and not eNP, is also critical for phase separation. Furthermore, overexpression of an eVP35 peptide disrupts eNP0VP35 complex formation, leading to reduced frequency of IB formation and limited viral infection. Together, our results show that upon EBOV infection, the eNP0VP35 complex forms the minimum unit to drive IB formation and viral replication.

Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice.

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice.

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1.

Oropouche orthobunyavirus (OROV; Peribunyaviridae) is a mosquito-transmitted virus that causes widespread human febrile illness in South America, with occasional progression to neurologic effects. Host factors mediating the cellular entry of OROV are undefined. Here, we show that OROV uses the host protein low-density lipoprotein-related protein 1 (Lrp1) for efficient cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. In addition, chimeric vesicular stomatitis virus (VSV) expressing OROV glycoproteins (VSV-OROV) bound to the Lrp1 ectodomain in vitro. Furthermore, we demonstrate the biological relevance of the OROV-Lrp1 interaction in a proof-of-concept mouse study in which treatment of mice with RAP at the time of infection reduced tissue viral load and promoted survival from an otherwise lethal infection. These results with OROV, along with the recent finding of Lrp1 as an entry factor for Rift Valley fever virus, highlight the broader significance of Lrp1 in cellular infection by diverse bunyaviruses. Shared strategies for entry, such as the critical function of Lrp1 defined here, provide a foundation for the development of pan-bunyaviral therapeutics.

Peptide-Antibody Fusions Engineered by Phage Display Exhibit an Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants.

The spread of COVID-19 has been exacerbated by the emergence of variants of concern (VoC). Many VoC contain mutations in the spike protein (S-protein) and are implicated in infection and response to therapeutics. Bivalent neutralizing antibodies (nAbs) targeting the S-protein receptor-binding domain (RBD) are promising therapeutics for COVID-19, but they are limited by low potency and vulnerability to RBD mutations in VoC. To address these issues, we used naïve phage-displayed peptide libraries to isolate and optimize 16-residue peptides that bind to the RBD or the N-terminal domain (NTD) of the S-protein. We fused these peptides to the N-terminus of a moderate-affinity nAb to generate tetravalent peptide-IgG fusions, and we showed that both classes of peptides were able to improve affinities for the S-protein trimer by >100-fold (apparent KD < 1 pM). Critically, cell-based infection assays with a panel of six SARS-CoV-2 variants demonstrated that an RBD-binding peptide was able to enhance the neutralization potency of a high-affinity nAb >100-fold. Moreover, this peptide-IgG was able to neutralize variants that were resistant to the same nAb in the bivalent IgG format, including the dominant B.1.1.529 (Omicron) variant that is resistant to most clinically approved therapeutic nAbs. To show that this approach is general, we fused the same peptide to a clinically approved nAb drug and showed that it enabled the neutralization of a resistant variant. Taken together, these results establish minimal peptide fusions as a modular means to greatly enhance affinities, potencies, and breadth of coverage of nAbs as therapeutics for SARS-CoV-2.

Mobile Robotic Platform for Contactless Vital Sign Monitoring.

The COVID-19 pandemic has accelerated methods to facilitate contactless evaluation of patients in hospital settings. By minimizing in-person contact with individuals who may have COVID-19, healthcare workers can prevent disease transmission and conserve personal protective equipment. Obtaining vital signs is a ubiquitous task that is commonly done in person by healthcare workers. To eliminate the need for in-person contact for vital sign measurement in the hospital setting, we developed Dr. Spot, a mobile quadruped robotic system. The system includes IR and RGB cameras for vital sign monitoring and a tablet computer for face-to-face medical interviewing. Dr. Spot is teleoperated by trained clinical staff to simultaneously measure the skin temperature, respiratory rate, and heart rate while maintaining social distancing from patients and without removing their mask. To enable accurate, contactless measurements on a mobile system without a static black body as reference, we propose novel methods for skin temperature compensation and respiratory rate measurement at various distances between the subject and the cameras, up to 5 m. Without compensation, the skin temperature MAE is 1.3°C. Using the proposed compensation method, the skin temperature MAE is reduced to 0.3°C. The respiratory rate method can provide continuous monitoring with a MAE of 1.6 BPM in 30 s or rapid screening with a MAE of 2.1 BPM in 10 s. For the heart rate estimation, our system is able to achieve a MAE less than 8 BPM in 10 s measured in arbitrary indoor light conditions at any distance below 2 m.

Lrp1 is a host entry factor for Rift Valley fever virus.

Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFV entry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorly defined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-related protein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associated protein (RAP) as critical host factors for RVFV infection. RVFV Gn directly binds to specific Lrp1 clusters and is glycosylation independent. Exogenous addition of murine RAP domain 3 (mRAPD3) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse cell lines. Mice treated with mRAPD3 and infected with pathogenic RVFV are protected from disease and death. A mutant mRAPD3 that binds Lrp1 weakly failed to protect from RVFV infection. Together, these data support Lrp1 as a host entry factor for RVFV infection and define a new target to limit RVFV infections.

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without (p < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.

Assessment of the Acceptability and Feasibility of Using Mobile Robotic Systems for Patient Evaluation.

Importance: Before the widespread implementation of robotic systems to provide patient care during the COVID-19 pandemic occurs, it is important to understand the acceptability of these systems among patients and the economic consequences associated with the adoption of robotics in health care settings. Objective: To assess the acceptability and feasibility of using a mobile robotic system to facilitate health care tasks. Design, Setting, and Participants: This study included 2 components: a national survey to examine the acceptability of using robotic systems to perform health care tasks in a hospital setting and a single-site cohort study of patient experiences and satisfaction with the use of a mobile robotic system to facilitate triage and telehealth tasks in the emergency department (ED). The national survey comprised individuals living in the US who participated in a sampling-based survey via an online analytic platform. Participants completed the national survey between August 18 and August 21, 2020. The single-site cohort study included patients living in the US who presented to the ED of a large urban academic hospital providing quaternary care in Boston, Massachusetts between April and August 2020. All data were analyzed from August to October 2020. Exposures: Participants in the national survey completed an online survey to measure the acceptability of using a mobile robotic system to perform health care tasks (facilitating telehealth interviews, acquiring vital signs, obtaining nasal or oral swabs, placing an intravenous catheter, performing phlebotomy, and turning a patient in bed) in a hospital setting in the contexts of general interaction and interaction during the COVID-19 pandemic. Patients in the cohort study were exposed to a mobile robotic system, which was controlled by an ED clinician and used to facilitate a triage interview. After exposure, patients completed an assessment to measure their satisfaction with the robotic system. Main Outcomes and Measures: Acceptability of the use of a mobile robotic system to facilitate health care tasks in a hospital setting (national survey) and feasibility and patient satisfaction regarding the use of a mobile robotic system in the ED (cohort study). Results: For the national survey, 1154 participants completed all acceptability questions, representing a participation rate of 35%. After sample matching, a nationally representative sample of 1000 participants (mean [SD] age, 48.7 [17.0] years; 535 women [53.5%]) was included in the analysis. With regard to the usefulness of a robotic system to perform specific health care tasks, the response of "somewhat useful" was selected by 373 participants (37.3%) for facilitating telehealth interviews, 350 participants (35.0%) for acquiring vital signs, 307 participants (30.7%) for obtaining nasal or oral swabs, 228 participants (22.8%) for placing an intravenous catheter, 249 participants (24.9%) for performing phlebotomy, and 371 participants (37.1%) for turning a patient in bed. The response of "extremely useful" was selected by 287 participants (28.7%) for facilitating telehealth interviews, 413 participants (41.3%) for acquiring vital signs, 192 participants (19.2%) for obtaining nasal or oral swabs, 159 participants (15.9%) for placing an intravenous catheter, 167 participants (16.7%) for performing phlebotomy, and 371 participants (37.1%) for turning a patient in bed. In the context of the COVID-19 pandemic, the median number of individuals who perceived the application of robotic systems to be acceptable for completing telehealth interviews, obtaining nasal and oral swabs, placing an intravenous catheter, and performing phlebotomy increased. For the ED cohort study, 51 individuals were invited to participate, and 41 participants (80.4%) enrolled. One participant was unable to complete the study procedures because of a signaling malfunction in the robotic system. Forty patients (mean [SD] age, 45.8 [2.7] years; 29 women [72.5%]) completed the mobile robotic system-facilitated triage interview, and 37 patients (92.5%) reported that the interaction was satisfactory. A total of 33 participants (82.5%) reported that their experience of receiving an interview facilitated by a mobile robotic system was as satisfactory as receiving an in-person interview from a clinician. Conclusions and Relevance: In this study, a mobile robotic system was perceived to be acceptable for use in a broad set of health care tasks among survey respondents across the US. The use of a mobile robotic system enabled the facilitation of contactless triage interviews of patients in the ED and was considered acceptable among participants. Most patients in the ED rated the quality of mobile robotic system-facilitated interaction to be equivalent to in-person interaction with a clinician.

Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice.

Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunctions, electrophysiological changes and macroscopic structural changes. However, the underlying mechanisms of this syndrome remain unclear. A possible role of myocardial apoptosis in the pathogenesis has not been previously examined. We hypothesized that dysregulation of apoptotic signalling participates in cardiac dysfunction in the cirrhotic heart. Therefore, we evaluated apoptotic pathways in the hearts of mice with chronic BDL (bile duct ligation). A cirrhotic cardiomyopathy model was induced by BDL in mice. Left ventricular geometry and volumes were evaluated by MRI. Intrinsic and extrinsic apoptotic pathways were evaluated by immunohistochemical staining and Western blot analysis. Fas-mediated apoptosis was inhibited by in vivo administration of an anti-FasL (Fas ligand) monoclonal antibody, and subsequently cardiac contractility was measured in isolated cardiomyocytes. BDL-mice showed significantly more PARP [poly(ADP-ribose) polymerase] staining than sham controls (18.2±11.4 compared with 6.7±5.3; P<0.05). Fas protein expression and PARP cleavage were activated, whereas FLIP (Fas-associated death domain-like interleukin 1ß-converting enzyme-inhibitory protein) was decreased compared with sham controls. The Bcl-2/Bax ratio was increased in BDL-mice compared with sham controls. Anti-FasL monoclonal antibody injection in BDL-mice improved systolic and diastolic dysfunctions in cardiomyocytes, but had no effect in sham controls. A net pro-apoptotic balance exists in BDL hearts, mainly mediated by activation of the extrinsic pathway, and abrogation of apoptosis improved contractility. These results suggest that apoptosis contributes to depressed cardiac contractility in a murine model of cirrhotic cardiomyopathy.

Assessing the value of team science: a study comparing center- and investigator-initiated grants.

BACKGROUND: Large cross-disciplinary scientific teams are becoming increasingly prominent in the conduct of research. PURPOSE: This paper reports on a quasi-experimental longitudinal study conducted to compare bibliometric indicators of scientific collaboration, productivity, and impact of center-based transdisciplinary team science initiatives and traditional investigator-initiated grants in the same field. METHODS: All grants began between 1994 and 2004 and up to 10 years of publication data were collected for each grant. Publication information was compiled and analyzed during the spring and summer of 2010. RESULTS: Following an initial lag period, the transdisciplinary research center grants had higher overall publication rates than the investigator-initiated R01 (NIH Research Project Grant Program) grants. There were relatively uniform publication rates across the research center grants compared to dramatically dispersed publication rates among the R01 grants. On average, publications produced by the research center grants had greater numbers of coauthors but similar journal impact factors compared with publications produced by the R01 grants. CONCLUSIONS: The lag in productivity among the transdisciplinary center grants was offset by their overall higher publication rates and average number of coauthors per publication, relative to investigator-initiated grants, over the 10-year comparison period. The findings suggest that transdisciplinary center grants create benefits for both scientific productivity and collaboration.

Influence of a National Cancer Institute transdisciplinary research and training initiative on trainees' transdisciplinary research competencies and scholarly productivity.

Over the past several decades, there has been burgeoning interest and investment in large transdisciplinary (TD) team science initiatives that aim to address complex societal problems. Despite this trend, TD training opportunities in the health sciences remain limited, and evaluations of these opportunities are even more uncommon due to funding constraints. We had the unique opportunity to conduct an exploratory study to examine the potential outcomes and impacts of TD training in a National Cancer Institute-supported initiative for TD research and training-the Transdisciplinary Research on Energetics and Cancer I (TREC I) initiative. This study used a retrospective mixed-methods approach leveraging secondary analysis of existing data sources to learn about TREC trainees' experiences with TREC training, TD research competencies, changes in scholarly productivity, and the associations among these domains. Results indicated that, on average, TREC trainees were satisfied with their TREC mentoring experiences and believed that TREC training processes were effective, in general. Participation in TREC training was associated with TD research competencies, including TD research orientation, positive general attitude toward TD training, development of scientific skills for TD research, and intrapersonal/interpersonal competencies for collaboration. There was also a significant increase in trainees' scholarly productivity from before to after starting in TREC training, as indicated by average annual number of publications and presentations and average number of coauthors per publication. Perceived effectiveness of TREC training was positively correlated with change in average annual number of research presentations from before to after starting in TREC training (r = 0.65, p < 0.05, N = 12), as well as TD research orientation (r = 0.36, p < 0.05), general attitude toward TD training (0.39, p < 0.05), scientific skills for TD research (r = 0.45-0.48, p < 0.05), and perceived collaborative productivity at one's TREC center (r = 0.47, p < 0.01). Finally, a significant positive correlation was observed between multi-mentoring experiences and both TD research orientation (r = 0.58, p < 0.05) and perceived collaborative productivity at one's TREC center (r = 0.44, p < 0.05). This exploratory study had methodological constraints including the absence of a comparison group and cross-sectional rather than longitudinal data related to TD research competencies. Despite these limitations, the study provided an opportunity to use existing data sources to explore potential outcomes and impacts of TD training and inform development of future rigorous evaluations of TD training. Overall, findings suggest that TD training in the context of a TD research initiative can provide satisfying training opportunities that support the development of TD research competencies and promote scholarly productivity.

Moving the science of team science forward: collaboration and creativity.

Teams of scientists representing diverse disciplines are often brought together for purposes of better understanding and, ultimately, resolving urgent public health and environmental problems. Likewise, the emerging field of the science of team science draws on diverse disciplinary perspectives to better understand and enhance the processes and outcomes of scientific collaboration. In this supplement to the American Journal of Preventive Medicine, leading scholars in the nascent field of team science have come together with a common goal of advancing the field with new models, methods, and measures. This summary article highlights key themes reflected in the supplement and identifies several promising directions for future research organized around the following broad challenges: (1) operationalizing cross-disciplinary team science and training more clearly; (2) conceptualizing the multiple dimensions of readiness for team science; (3) ensuring the sustainability of transdisciplinary team science; (4) developing more effective models and strategies for training transdisciplinary scientists; (5) creating and validating improved models, methods, and measures for evaluating team science; and (6) fostering transdisciplinary cross-sector partnerships. A call to action is made to leaders from the research, funding, and practice sectors to embrace strategies of creativity and innovation in a collective effort to move the field forward, which may not only advance the science of team science but, ultimately, public health science and practice.