Festschrift Symposium: Honoring Professor Samuel Pillsbury

The Loyola of Los Angeles Law Review is pleased to publish this Festschrift Symposium Honoring Professor Samuel Pillsbury. The following is an edited transcript of the live symposium held at LMU Loyola Law School on Friday, March 25, 2022

Expanding NEON biodiversity surveys with new instrumentation and machine learning approaches

A core goal of the National Ecological Observatory Network (NEON) is to measure changes in biodiversity across the 30-yr horizon of the network. In contrast to NEON’s extensive use of automated instruments to collect environmental data, NEON’s biodiversity surveys are almost entirely conducted using traditional human-centric field methods. We believe that the combination of instrumentation for remote data collection and machine learning models to process such data represents an important opportunity for NEON to expand the scope, scale, and usability of its biodiversity data collection while potentially reducing long-term costs. In this manuscript, we first review the current status of instrument-based biodiversity surveys within the NEON project and previous research at the intersection of biodiversity, instrumentation, and machine learning at NEON sites. We then survey methods that have been developed at other locations but could potentially be employed at NEON sites in future. Finally, we expand on these ideas in five case studies that we believe suggest particularly fruitful future paths for automated biodiversity measurement at NEON sites: acoustic recorders for sound-producing taxa, camera traps for medium and large mammals, hydroacoustic and remote imagery for aquatic diversity, expanded remote and ground-based measurements for plant biodiversity, and laboratory-based imaging for physical specimens and samples in the NEON biorepository. Through its data science-literate staff and user community, NEON has a unique role to play in supporting the growth of such automated biodiversity survey methods, as well as demonstrating their ability to help answer key ecological questions that cannot be answered at the more limited spatiotemporal scales of human-driven surveys

Optimization of a pericyte therapy to improve muscle recovery following hindlimb immobilization

Extended bed rest or single limb immobilization can significantly reduce skeletal muscle mass and function. Recovery may be severely delayed or incomplete due to the inability to effectively engage in physical therapy. Thus, alternative strategies are needed to enhance recovery and prevent long-term disability, particularly in individuals prone to muscle loss (older adults, neuromuscular disease). Our lab recently demonstrated that pericyte quantity is decreased in skeletal muscle following immobilization and appropriate replacement via intramuscular transplantation can effectively recover myofiber size in mice. These data suggest that pericytes positively influence skeletal muscle growth and may represent a novel approach to the prevention and treatment of disability following disuse. However, one of the challenges in developing a pericyte therapy is the lack of a unique marker for identification and isolation of pericytes. Investigators have established that pericytes express a wide variety of cell surface markers, such as neural/glial antigen 2 (Cspg4/NG2), melanoma cell adhesion molecule (Mcam/CD146), and platelet-derived growth factor receptor β (PDGFRβ). Currently, none of these markers are uniquely expressed by pericytes; therefore, cell heterogeneity likely exists when isolating based on one pericyte marker. Tbx18 (T-box18) was recently proposed as a transcription factor uniquely expressed in pericytes, providing the opportunity to examine surface marker expression using the Tbx18CreERT2;Rosa26:tdTomato(Ai9) mouse line. PURPOSE: Aim 1: To compare the capacity for NG2+ and CD146+ pericytes to recover skeletal muscle mass following a period of disuse. Aim 2: To characterize cell surface marker expression of muscle-resident Tbx18+ cells using multiplex flow cytometry. METHODS: Adult, 4-month-old C57BL/6 mice (n=24) were randomly divided into four groups (n=6/group). Mice hindlimbs were immobilized in full dorsiflexion via a surgical staple inserted through the center of the foot and body of the gastrocnemius for 2 weeks. At 2 weeks post immobilization, staples were removed and either pericytes (NG2+CD45-CD31-[Lin-], CD146+Lin-, or CD146+NG2-Lin-) or saline (control) were injected into the tibialis anterior (TA) muscle. TA muscles were excised for analysis after 2 weeks of remobilization and the extent of recovery was assessed. To characterize Tbx18+ cells, 5-month-old, Tbx18CreERT2:Ai9 mice (n=4) were injected with tamoxifen, and tdTomato expressing cells from the TA muscle were assessed for CD146 and NG2 using multiplex flow cytometry. Lineage tracing was also performed to determine pericyte fate following a period of immobilization, as well as following a period of immobilization and remobilization. RESULTS: There was no difference between myofiber CSA or muscle wet weight between groups; however, CD146+Lin-pericytes demonstrated the greatest capacity for recovery based on a trend toward an increase in myofiber cross-sectional area (p=0.071), increased collagen remodeling (p=0.048), and significant improvements in capillarization (p=0.043). CD146+NG2-Lin- also improved capillarization (p=0.012) and a trend toward an increase in collagen remodeling (p=0.053) compared to the saline control group. There were no significant benefits to NG2+Lin- pericyte transplantation in any measure. In adult mice, the total relative percentage of Tbx18+ cells was unexpectedly low (~2%), yet the majority of cells expressed CD146 (>95%). Tbx18+ cells were present in the interstitium between muscle fibers following immobilization and remobilization, and no evidence of Tbx18+ cell contribution to myogenesis was observed. CONCLUSION: CD146+Lin- and CD146+NG2-Lin- pericyte transplantation effectively recovered capillary quantity and collagen remodeling following a period disuse compared to controls, with a trend in myofiber size also observed. NG2+Lin- pericytes likely do not contribute to regrowth following a period of disuse. The relatively low percentage of Tbx18+ pericytes in adult muscle suggest that Tbx18 is a developmentally regulated transcription factor that is suppressed during the postnatal period.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste

Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy

BACKGROUND: Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. METHODS AND RESULTS: This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.status: publishe

Measurement of the CP violating asymmetry amplitude sin 2beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.034 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.030 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes.Comment: 7 pages, 2 postscript figures, submitted to PR