Controlling chaotic maps using next-generation reservoir computing.

In this work, we combine nonlinear system control techniques with next-generation reservoir computing, a best-in-class machine learning approach for predicting the behavior of dynamical systems. We demonstrate the performance of the controller in a series of control tasks for the chaotic Hénon map, including controlling the system between unstable fixed points, stabilizing the system to higher order periodic orbits, and to an arbitrary desired state. We show that our controller succeeds in these tasks, requires only ten data points for training, can control the system to a desired trajectory in a single iteration, and is robust to noise and modeling error.

The Encyclopedia of Proteome Dynamics: a big data ecosystem for (prote)omics.

Driven by improvements in speed and resolution of mass spectrometers (MS), the field of proteomics, which involves the large-scale detection and analysis of proteins in cells, tissues and organisms, continues to expand in scale and complexity. There is a resulting growth in datasets of both raw MS files and processed peptide and protein identifications. MS-based proteomics technology is also used increasingly to measure additional protein properties affecting cellular function and disease mechanisms, including post-translational modifications, protein-protein interactions, subcellular and tissue distributions. Consequently, biologists and clinicians need innovative tools to conveniently analyse, visualize and explore such large, complex proteomics data and to integrate it with genomics and other related large-scale datasets. We have created the Encyclopedia of Proteome Dynamics (EPD) to meet this need (https://peptracker.com/epd/). The EPD combines a polyglot persistent database and web-application that provides open access to integrated proteomics data for >30 000 proteins from published studies on human cells and model organisms. It is designed to provide a user-friendly interface, featuring graphical navigation with interactive visualizations that facilitate powerful data exploration in an intuitive manner. The EPD offers a flexible and scalable ecosystem to integrate proteomics data with genomics information, RNA expression and other related, large-scale datasets.

Status and trends of orthophosphate concentrations in groundwater used for public supply in California.

Phosphorus is a necessary nutrient for all organisms. However excessive phosphorus can cause eutrophication in surface water. Groundwater can be an important nonpoint contributor of phosphorus to surface water bodies. Most groundwater phosphorus is in the form of orthophosphate and orthophosphate concentrations in California groundwater vary temporally and geographically. This study quantifies orthophosphate concentrations in water samples from public supply wells in California, evaluates temporal trends (both step and monotonic trends) in orthophosphate concentration for different areas of the state, and explores potential explanatory factors for the trends observed. Orthophosphate concentrations are low in 42 percent of the groundwater used for public supply in California, moderate in 43 percent, and high in 15 percent of this groundwater relative to reference conditions and a goal expressed by the USEPA for streams overlying the aquifers. The findings also suggest that orthophosphate concentrations increased in approximately one-third of this groundwater during the study period (2000 to 2018). The timing of orthophosphate increases observed in time-series evaluations coincided approximately with the timing of increases observed in step-trend evaluations, with both suggesting that the increasing trend occurred mostly before 2011. Principal component analysis (PCA) of the statewide dataset indicates that orthophosphate concentrations are antithetically related to dissolved oxygen (DO), and weakly associated with boron, arsenic, and fluoride. Step trend and time-series trend analyses using PCA were inconclusive.

Global Proteomics Analysis of the Response to Starvation in C. elegans.

Periodic starvation of animals induces large shifts in metabolism but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass-spectrometry-based quantitative proteomics to identify global changes in the Caenorhabditis elegans proteome due to acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin-associated proteins, including specific linker histones, histone variants, and histone posttranslational modifications associated with the epigenetic control of gene expression. To maximize community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/).

High Interspecimen Variability in Engagement of the Anterolateral Ligament: An In Vitro Cadaveric Study.

BACKGROUND: Anterolateral ligament (ALL) reconstruction as an adjunct to anterior cruciate ligament (ACL) reconstruction remains a subject of clinical debate. This uncertainty may be driven in part by a lack of knowledge regarding where, within the range of knee motion, the ALL begins to carry force (engages). QUESTIONS/PURPOSES: (1) Does the ALL engage in the ACL-intact knee; and (2) where within the range of anterior tibial translation occurring in the ACL-sectioned knee does the ALL engage? METHODS: A robotic manipulator was used to measure anterior tibial translation, ACL forces, and ALL forces in 10 fresh-frozen cadaveric knees (10 donors; mean age, 41 ± 16 years; range, 20-64 years; eight male) in response to applied multiplanar torques. The engagement point of the ALL was defined as the anterior tibial translation at which the ALL began to carry at least 15% of the force carried by the native ACL; a threshold of 15% minimized the sensitivity of the engagement point of the ALL. This engagement point was compared with the maximum anterior tibial translation permitted in the ACL-intact condition using a paired Wilcoxon signed-rank test (p < 0.05). Normality of each outcome measure was confirmed using Kolmogorov-Smirnov tests (p < 0.05). RESULTS: The ALL engaged in five and four of 10 ACL-intact knees in response to multiplanar torques at 15° and 30° of flexion, respectively. Among the nine of 10 knees in which the ALL engaged with the ACL sectioned, the ACL-intact motion limit, and ALL engagement point, respectively, averaged 1.5 ± 1.1 mm and 5.4 ± 4.1 mm at 15° of flexion and 2.0 ± 1.3 mm and 5.7 ± 2.7 mm at 30° of flexion. Thus, the ALL engaged 3.8 ± 3.1 mm (95% confidence interval [CI], 1.4-6.3 mm; p = 0.027) and 3.7 ± 2.4 mm (95% CI, 2.1-5.3 mm; p = 0.008) beyond the maximum anterior tibial translation of the ACL-intact knee at 15° and 30° of flexion, respectively. CONCLUSIONS: In this in vitro, cadaveric study, the ALL engaged in up to half of the ACL-intact knees. In the ACL-sectioned knees, the ALL engaged beyond the ACL-intact limit of anterior subluxation on average in response to multiplanar torques, albeit with variability that likely reflects interspecimen heterogeneity in ALL anatomy. CLINICAL RELEVANCE: The findings suggest that surgical variables such as the joint position and tension at which lateral extraarticular grafts and tenodeses are fixed might be able to be tuned to control where within the range of knee motion the graft tissue is engaged to restrain joint motion on a patient-specific basis.

Triennial changes in groundwater quality in aquifers used for public supply in California: utility as indicators of temporal trends.

From 2004 to 2011, the U.S. Geological Survey collected samples from 1686 wells across the State of California as part of the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Priority Basin Project (PBP). From 2007 to 2013, 224 of these wells were resampled to assess temporal trends in water quality. The samples were analyzed for 216 water-quality constituents, including inorganic and organic compounds as well as isotopic tracers. The resampled wells were grouped into five hydrogeologic zones. A nonparametric hypothesis test was used to test the differences between initial sampling and resampling results to evaluate possible step trends in water-quality, statewide, and within each hydrogeologic zone. The hypothesis tests were performed on the 79 constituents that were detected in more than 5 % of the samples collected during either sampling period in at least one hydrogeologic zone. Step trends were detected for 17 constituents. Increasing trends were detected for alkalinity, aluminum, beryllium, boron, lithium, orthophosphate, perchlorate, sodium, and specific conductance. Decreasing trends were detected for atrazine, cobalt, dissolved oxygen, lead, nickel, pH, simazine, and tritium. Tritium was expected to decrease due to decreasing values in precipitation, and the detection of decreases indicates that the method is capable of resolving temporal trends.

Social Relationships and Sleep Quality.

BACKGROUND: The quality of social relationships and social support appears to be associated with physical health outcomes and sleep quality. Almost all previous research in this area focuses on positive aspects of relationships. PURPOSE: The present study thus intended to examine the links between supportive, aversive, ambivalent, and indifferent network ties and sleep quality. METHODS: Relationship data, Pittsburgh Sleep Quality Index (PSQI)-assessed sleep quality, and depression were examined in 175 middle-aged and older adults. RESULTS: Consistent with hypotheses, supportive ties were positively related to sleep quality, while aversive ties predicted worse sleep quality, associations that were primarily seen for close relationships. Ambivalent and indifferent ties were not significant predictors of sleep quality. Importantly, depression was found to mediate the link between relationship quality and sleep quality. CONCLUSIONS: These data suggest the more specific types of social relationships that may be linked to poor sleep quality and that depression appears to underlie these associations.

Comparison of an Electronic and Paper-based Montreal Cognitive Assessment Tool.

This pilot study compared a novel electronic Montreal Cognitive Assessment (eMoCA) tool to the original paper-based MoCA. Potential participants were approached at primary care practices, a geriatric day hospital, and a university campus. Each of the 401 participants were randomly assigned to either the eMoCA (N=182) or MoCA (N=219). Scores were adjusted by self-reported demographic and health information using regression analysis. The difference in average scores (26.21±3.11 for the MoCA group and 24.84±4.21 for the eMoCA group) was found to be statistically significant. Controlling for the effect of potential covariate factors with regression analyses, the adjusted difference is -0.90 (95% confidence interval, -1.45 to -0.35). This difference may be due to factors related to use of the electronic device or software usability. However, the standardized, self-administered eMoCA may offer an opportunity for health systems to screen for early changes in cognitive function in primary care settings and offer greater access to assessment for rural or remote communities. Population-level research may be required to identify whether the score difference between test versions requires a downward adjustment to the eMoCA score taken as indicative of cognitive impairment.

Controlling chaos using edge computing hardware.

Machine learning provides a data-driven approach for creating a digital twin of a system - a digital model used to predict the system behavior. Having an accurate digital twin can drive many applications, such as controlling autonomous systems. Often, the size, weight, and power consumption of the digital twin or related controller must be minimized, ideally realized on embedded computing hardware that can operate without a cloud-computing connection. Here, we show that a nonlinear controller based on next-generation reservoir computing can tackle a difficult control problem: controlling a chaotic system to an arbitrary time-dependent state. The model is accurate, yet it is small enough to be evaluated on a field-programmable gate array typically found in embedded devices. Furthermore, the model only requires 25.0 ± 7.0 nJ per evaluation, well below other algorithms, even without systematic power optimization. Our work represents the first step in deploying efficient machine learning algorithms to the computing "edge."

Engineered Microenvironmental Cues from Fiber-Reinforced Hydrogel Composites Drive Tenogenesis and Aligned Collagen Deposition.

Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber-reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber-reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor ß3 drives a cell fate switch toward pro-regenerative or pro-fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber-reinforced hydrogels critically mediates the alignment of de novo collagen fibrils, reflecting native tendon architecture. These findings inform the design of cell-free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load-bearing connective tissues.

Degree of Tendon Retraction and Younger Age Are Associated With Functional Decline Following Nonoperative Management of Complete Proximal Hamstring Ruptures.

Purpose: To characterize functional outcomes of patients with complete proximal hamstring tendon ruptures who were treated nonoperatively and determine whether there are patient characteristics associated with unfavorable outcomes. Methods: We retrospectively identified patients aged 18-80 (treated 1/2000-12/2019) who received nonoperative management of complete rupture of the hamstring tendon origin. Participants completed the Lower Extremity Functional Scale (LEFS), as well as Tegner Activity Scale (TAS), and a chart review was conducted to obtain demographic and medical information. Preinjury and postinjury TAS scores were compared, and additional models quantified associations between LEFS scores or changes in TAS scores (ΔTAS) and patient characteristics. Results: Twenty-eight subjects (mean age: 61.5 ± 1.5 years; 10 male) were included. The mean follow-up time was 5.8 ± 0.8 years (range: 2-22 years). Mean preinjury and postinjury TAS scores were 5.3 ± 0.4 and 3.7 ± 0.4, respectively, with a change of 1.5 ± 0.3 (P = .0002). Degree of tendon retraction showed a negative correlation with LEFS score (P = .003) and ΔTAS (P = .005). Increased follow-up time (P = .015) and body mass index (P = .018) were associated with lower LEFS scores. Moreover, increased follow-up time (P = .002) and younger age at injury (P = .035) were associated with more negative ΔTAS. Patients classified with an American Society of Anesthesiologists (ASA) score of 2 had a median LEFS score that was 20 points (95% CI: 6.9-33.6) lower than those classified as ASA 1 (P = .015). Conclusions: In this study, we found that increased degree of tendon retraction, increased follow-up time, and younger age at initial injury were associated with significantly worse self-reported functional outcomes. Level of Evidence: Level IV, prognostic case series.

Early Outcomes Following Plantar Condylectomy and Imbrication of Plantar Plate to Metatarsal Neck for Metatarsalgia and Grade 0 Lesser Toe Metatarsophalangeal Joint Instability.

Background: Metatarsalgia and plantar plate tears are characterized by forefoot pain and toe deformity in severe cases. Conservative management may slow progression of symptoms; however, definitive treatment often requires operative intervention. The purpose of this observational study was to evaluate the combination of plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck to repair grade 0 plantar plate injuries. Methods: We retrospectively identified 22 patients with metatarsalgia and low-grade plantar plate lesions (grade 0), operated between 2018 and 2021, who underwent operative repair involving plantar metatarsal condylectomy and proximal surgical imbrication of the plantar plate to the metatarsal neck. Fourteen patients underwent concomitant hallux valgus correction. Data collection was performed preoperatively and postoperatively and included Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores. Paired Wilcoxon signed-rank tests compared PROMIS PF and PI scores at patients' preoperative, 6-9-week, 3-4-month, 5-6-month, and ≥9-month follow-up evaluations (P < .05). Results: Compared to their preoperative visit, patients demonstrated modest improvement in their PROMIS (pain and physical function) scores over the first ≥9 months postoperatively (median 13.0 months). Median preoperative and most recent PROMIS physical function scores were 40.5 (95% CI: 36-49) and 44.5 (95% CI: 40-52), respectively. Median PROMIS pain interference scores changed from 62.5 (95% CI: 56-67) to 56.0 (95% CI: 51-62). Improvement in pain and function was sustained in patients available for postoperative follow-up. Conclusion: In this small, early follow-up series, we found that plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck was modestly helpful to treat metatarsalgia and grade 0 plantar plate injuries. Level of Evidence: Level IV, retrospective case series.

Building-Block Size Mediates Microporous Annealed Particle Hydrogel Tube Microenvironment Following Spinal Cord Injury.

Spinal cord injury (SCI) is a life-altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre-constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery. MAP tubes prepared from 20-, 40-, and 60-micron polyethylene glycol (PEG) beads are generated and implanted in a T9-10 murine hemisection model of SCI. Tubes attenuate glial and fibrotic scarring, increase innate immune cell density, and reduce inflammatory phenotypes in a bead size-dependent manner. Tubes composed of 60-micron beads increase the cell density of the chronic macrophage response, while neutrophil infiltration and phenotypes do not deviate from those seen in controls. At 8 weeks postinjury, implantation of tubes composed of 60-micron beads results in enhanced locomotor function, robust axonal ingrowth, and remyelination through both lumens and the inter-tube space. Collectively, these studies demonstrate the importance of bead size in MAP construction and highlight PEG tubes as a biomaterial therapy to promote regeneration and functional recovery in SCI.

Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization.

Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear. Using time course transcriptomic and proteomic analyses, we identified discoidin domain receptor 2 (DDR2), a cell surface receptor for fibrillar collagen, as a key MLin cell regulator in HO formation. Inhibition of DDR2 signaling, through either constitutive or conditional Ddr2 deletion or pharmaceutical inhibition, reduced HO formation in mice. Mechanistically, DDR2 perturbation alters focal adhesion orientation and subsequent matrix organization, modulating Focal Adhesion Kinase (FAK) and Yes1 Associated Transcriptional Regulator and WW Domain Containing Transcription Regulator 1 (YAP/TAZ)-mediated MLin cell signaling. Hence, ECM-DDR2 interactions are critical in driving HO and could serve as a previously unknown therapeutic target for treating this disease process.

Entrapment of Hydrophilic and Hydrophobic Molecules in Beads Prepared from Isolated Denatured Whey Protein.

The oral route of administration is by far the most convenient route, especially in the treatment of chronic conditions. However, many therapeutics present formulation difficulties which make them unsuitable for oral delivery. Recently, we synthesized a denatured whey protein isolate (dWPI) bead entrapped with insulin. Our present goal was to assess the suitability of this delivery system to the delivery of other potential molecules, both hydrophilic and hydrophobic. Beads of 1.2-1.5 mm in diameter were entrapped with four payloads representing a range of solubilities. The water-soluble payloads were sodium fluorescein (SF) and FITC dextran 4000 Da (FD4), while the hydrophobic ones were Fast Green and curcumin. Encapsulation efficiency (EE) was 73%, 84%, 70%, and 83% for SF, FD4, Fast Green, and curcumin-loaded beads, respectively. The corresponding loading capacity for each bead was 0.07%, 1.1%, 0.75%, and 1.1%, respectively. Each payload produced different release profiles in simulated gastric fluid (SGF) and simulated intestinal fluids (SIF). SF released steadily in both SGF and SIF. FD4 and curcumin release was not substantial in any buffers, while Fast Green release was low in SGF and high in SIF. The differences in release behaviour were likely due to the varying properties of the payloads. The effect of proteolysis on beads suggested that enzymatic degradation of the whey bead may promote payload release. The beads swelled rapidly in SGF compared to SIF, which likely contributed to the release from the beads, which was largely governed by solvent diffusion and polymer relaxation. Our results offer a systematic examination of the behaviour of hydrophilic and hydrophobic payloads in a dWPI delivery system. These beads may be further designed to orally deliver poorly permeable macromolecules and poorly soluble small molecules of pharmaceutical interest.

Magnetic Alignment of Electrospun Fiber Segments Within a Hydrogel Composite Guides Cell Spreading and Migration Phenotype Switching.

Fibrous extracellular matrix (ECM) proteins provide mechanical structure and adhesive scaffolding to resident cells within stromal tissues. Aligned ECM fibers play an important role in directing morphogenetic processes, supporting mechanical loads, and facilitating cell migration. Various methods have been developed to align matrix fibers in purified biopolymer hydrogels, such as type I collagen, including flow-induced alignment, uniaxial tensile deformation, and magnetic particles. However, purified biopolymers have limited orthogonal tunability of biophysical cues including stiffness, fiber density, and fiber alignment. Here, we generate synthetic, cell-adhesive fiber segments of the same length-scale as stromal fibrous proteins through electrospinning. Superparamagnetic iron oxide nanoparticles (SPIONs) embedded in synthetic fiber segments enable magnetic field induced alignment of fibers within an amorphous bulk hydrogel. We find that SPION density and magnetic field strength jointly influence fiber alignment and identify conditions to control the degree of alignment. Tuning fiber length allowed the alignment of dense fibrous hydrogel composites without fiber entanglement or regional variation in the degree of alignment. Functionalization of fiber segments with cell adhesive peptides induced tendon fibroblasts to adopt a uniaxial morphology akin to within native tendon. Furthermore, we demonstrate the utility of this hydrogel composite to direct multicellular migration from MCF10A spheroids and find that fiber alignment prompts invading multicellular strands to separate into disconnected single cells and multicellular clusters. These magnetic fiber segments can be readily incorporated into other natural and synthetic hydrogels and aligned with inexpensive and easily accessible rare earth magnets, without the need for specialized equipment. 3D hydrogel composites where stiffness/crosslinking, fiber density, and fiber alignment can be orthogonally tuned may provide insights into morphogenetic and pathogenic processes that involve matrix fiber alignment and can enable systematic investigation of the individual contribution of each biophysical cue to cell behavior.

Synthesis and In Vivo Evaluation of Insulin-Loaded Whey Beads as an Oral Peptide Delivery System.

For many diabetics, daily, lifelong insulin injections are required to effectively manage blood glucose levels and the complications associated with the disease. This can be a burden and reduces patient quality of life. Our goal was to develop a more convenient oral delivery system that may be suitable for insulin and other peptides. Insulin was entrapped in 1.5-mm beads made from denatured whey protein isolate (dWPI) using gelation. Beads were then air-dried with fumed silica, Aerosil®. The encapsulation efficiency was ~61% and the insulin loading was ~25 µg/mg. Dissolution in simulated gastric-, and simulated intestinal fluids (SGF, SIF) showed that ~50% of the insulin was released from beads in SGF, followed by an additional ~10% release in SIF. The omission of Aerosil® allowed greater insulin release, suggesting that it formed a barrier on the bead surface. Circular dichroism analysis of bead-released insulin revealed an unaltered secondary structure, and insulin bioactivity was retained in HepG2 cells transfected to assess activation of the endogenous insulin receptors. Insulin-entrapped beads were found to provide partial protection against pancreatin for at least 60 min. A prototype bead construct was then synthesised using an encapsulator system and tested in vivo using a rat intestinal instillation bioassay. It was found that 50 IU/kg of entrapped insulin reduced plasma glucose levels by 55% in 60 min, similar to that induced by subcutaneously (s.c.)-administered insulin (1 IU/kg). The instilled insulin-entrapped beads produced a relative bioavailability of 2.2%. In conclusion, when optimised, dWPI-based beads may have potential as an oral peptide delivery system.

Implementation of a Coronavirus Disease 2019 Vaccination Condition of Employment in a Community Nursing Home.

The rate of coronavirus disease 2019 (COVID-19) vaccination uptake by US nursing home staff remains low despite the increased risks of viral transmission and related morbidity and mortality in this setting. This study describes vaccine uptake activities including a COVID-19 vaccination condition of employment (COE) policy in one community nursing home. This case study summarizes the timeline of vaccination uptake activities, staff vaccination rates over time, and stakeholder perspectives around the implementation of a COVID-19 vaccination COE. Organizational data were used to calculate vaccination rates from January 1, 2021 until May 1, 2021 among all nursing home staff. Interviews were held with the executive leadership team, human resources leadership, and nursing home staff to understand the process of implementation. During a 4-month period, nursing home leaders provided 8 written handouts about COVID-19 to all staff, hosted 5 on-site vaccination clinics in partnership with area pharmacies, conducted 2 virtual presentations for staff in addition to individual outreach and internal communications. Fewer than one-half of the staff were vaccinated prior to the decision to pursue a vaccine COE on February 9, 2021. The decision to pursue a COVID-19 vaccination COE was supported by executive leadership and nursing home staff to protect the health and safety of each other and their residents. By May 1, 2021 a total of 221 of the 246 (89.8%) nursing home staff members received a COVID-19 vaccination. The facility reached 100% compliance with the vaccination COE policy with 18 people who chose to resign and 7 people who were exempt or on a leave of absence. In combination with frequent, personalized outreach, a COVID-19 vaccination COE resulted in high staff vaccination rates and minimal staff turnover. This case study provides a detailed summary of vaccination uptake activities within an organizational context to inform efforts at other healthcare facilities.

Anterior cruciate ligament graft forces are sensitive to fixation angle and tunnel position within the native femoral footprint during passive flexion.

BACKGROUND: Anterior cruciate ligament (ACL) graft position within the anatomic femoral footprint of the native ACL and the flexion angle at which the graft is fixed (i.e., fixation angle) are important considerations in ACL reconstruction surgery. However, their combined effect on ACL graft force remains less well understood. HYPOTHESIS: During passive flexion, grafts placed high within the femoral footprint carry lower forces than grafts placed low within the femoral footprint (i.e., high and low grafts, respectively). Forces carried by high grafts are independent of fixation angle. All reconstructions impart higher forces on the graft than those carried by the native ACL. STUDY DESIGN: Controlled laboratory study. METHODS: Five fresh-frozen cadaveric knees were mounted to a robotic manipulator and flexed from full extension to 90° of flexion. The ACL was sectioned and ACL force was calculated via superposition. ACL reconstructions were then performed using a patellar tendon autograft. For each knee, four different reconstruction permutations were tested: high and low femoral graft positions fixed at 15° and at 30° of flexion. Graft forces were calculated from full extension to 90° of flexion for each combination of femoral graft position and fixation angle again via superposition. Native ACL and ACL graft forces were compared through early flexion (by averaging tissue force from 0 to 30° of flexion) and in 5° increments from full extension to 90° of flexion. RESULTS: When fixed at 30° of flexion, high grafts carried less force than low grafts through early flexion bearing a respective 64 ± 19 N and 88 ± 11 N (p = 0.02). Increasing fixation angle from 15° to 30° caused graft forces through early flexion to increase 40 ± 13 N in low grafts and 23 ± 6 N in high grafts (p < 0.001). Low grafts fixed at 30° of flexion differed most from the native ACL, carrying 67 ± 9 N more force through early flexion (p < 0.001). CONCLUSION: ACL grafts placed high within the femoral footprint and fixed at a lower flexion angle carried less force through passive flexion compared to grafts placed lower within the femoral footprint and fixed at a higher flexion angle. At the prescribed pretensions, all grafts carried higher forces than the native ACL through passive flexion. CLINICAL RELEVANCE: Both fixation angle and femoral graft location within the anatomic ACL footprint influence graft forces and, therefore, should be considered when performing ACL reconstruction.