Showing papers by "Tulane University published in 2023"

Holographic measurement and quantum teleportation in the SYK thermofield double

Abstract: A bstract According to holography, entanglement is the building block of spacetime; therefore, drastic changes of entanglement will lead to interesting transitions in the dual spacetime. In this paper, we study the effect of projective measurements on the Sachdev-Ye-Kitaev (SYK) model’s thermofield double state, dual to an eternal black hole in Jackiw-Teitelboim (JT) gravity. We calculate the (Renyi-2) mutual information between the two copies of the SYK model upon projective measurement of a subset of fermions in one copy. We propose a dual JT gravity model that can account for the change of entanglement due to measurement, and observe an entanglement wedge phase transition in the von Neumann entropy. The entanglement wedge for the unmeasured side changes from the region outside the horizon to include the entire time reversal invariant slice of the two-sided geometry as the number of measured Majorana fermions increases. Therefore, after the transition, the bulk information stored in the measured subsystem is not entirely lost upon projection in one copy of the SYK model, but rather teleported to the other copy. We further propose a decoding protocol to elucidate the teleportation interpretation, and connect our analysis to the physics of traversable wormholes.

Optimization of Host Cell-Compatible, Antimicrobial Peptides Effective against Biofilms and Clinical Isolates of Drug-Resistant Bacteria

Abstract: Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called d-amino acid CONsensus with Glycine Absent (d-CONGA), which has excellent antimicrobial activities in vitro and in vivo. In this newest generation of rational d-CONGA variants, we tested multiple sequence-structure-function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, d-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, d-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates of Klebsiella pneumoniae, innate resistance to d-CONGA was surprisingly common despite a lack of inducible resistance in Pseudomonas aeruginosa reported previously. Yet, these same isolates were susceptible to d-CONGA-Q7. d-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, d-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.

The Impact of Reimbursement for Non–Face-to-Face Chronic Care Management on Comprehensive Metabolic Biomarkers Among Multimorbid Patients With Type 2 Diabetes

Abstract: Aims: We evaluated the impact of reimbursement for non–face-to-face chronic care management (NFFCCM) on comprehensive metabolic risk factors among multimorbid Medicare beneficiaries with type 2 diabetes in Louisiana. Materials and Methods: We implemented a propensity score method to obtain comparable treatment (n=1501 with NFFCCM) and control (n=17,524 without NFFCCM) groups. Patients with type 2 diabetes were extracted from the electronic health records stored in REACHnet. The study period was from 2013 to February 2020. The comprehensive metabolic risk factors included the primary outcome of glycated hemoglobin (HbA1c) (as the primary outcome) and the secondary outcomes of body mass index (BMI), systolic blood pressure (BP), and low-density lipoprotein cholesterol. Results: Receiving any NFFCCM was associated with improvement in all outcomes measures: a reduction in HbA1c of 0.063% (95% CI: 0.031%–0.094%; P<0.001), a reduction in BMI of 0.155 kg/m2 (95% CI: 0.029–0.282 kg/m2; P=0.016), a reduction in systolic BP of 0.816 mm Hg (95% CI: 0.469–1.163 mm Hg; P<0.001), and a reduction in low-density lipoprotein cholesterol of 1.779 mg/dL (95% CI: 0.988 2.570 mg/dL; P<0.001). Compared with the control group, the treatment group had 1.6% more patients with HbA1c <7% (95% CI: 0.3%–2.9%; P=0.013). Conclusions: Patients with diabetes in Louisiana receiving NFFCCM experienced better control of HbA1c, BMI, BP, and low-density lipoprotein outcomes.

Chromatin-Accessible miRNA Regulons Driving Thyroid Tumorigenesis and Progression

Abstract: Background: While papillary thyroid cancer (PTC) can remain indolent, associated lymph node metastases (LNM) and recurrence rates are approximately 50% and 20%, respectively. Omics-based medicine has led to the discovery of predictive biomarkers that can be used to predict tumor progression and clinical outcomes. We aimed to develop a non-invasive omics-driven blood test to allow accurate risk stratification and help tailor individual patient treatment plans. Study design: RNA-seq and miRNA-seq analysis of TCGA and GEO datasets were employed to identify an epigenetic prognostic panel. Integrated bulk ATAC-seq and RNA-seq experiments confirmed the results. Sixty-two paired tumor and adjacent control thyroid tissues and 67 blood samples (62 PTC and 5 controls) were analyzed for validation using sequencing and RT-PCR and correlated to clinical outcomes. Liposome-exosome fusion CRISPR-FDS miRNA assay was developed. A predictive risk nomogram was generated and tested for performance. Results: Our miRNA panel (miR-146b-5p and miR-221-3p) from tissue and blood was associated with aggressive features and was located within accessible chromatin regions. The miRNA risk score and prognostic nomogram showed higher accuracy in predicting LNM (miR-146b: AUC=0.816, sensitivity=76.9%; miR-221: AUC=0.740, sensitivity=79.5%) and recurrence (miR-146b: AUC=0.921, sensitivity=75.0%; miR-221: AUC=0.756, sensitivity=70.0%) (p<0.001) than staging and ATA risk stratification. CRISPR-based miRNA assays showed upregulation in the blood of cancer cohorts. Conclusion: CRISPR-based detection of miR-146b and miR-221 in the blood of TC patients is a reliable and non-invasive tool for real-time assessment and prognostication that has great potential to provide a direct impact on the care of these patients.

Powered Air-Purifying Respirator (PAPR) and High-Efficiency Particulate Air (HEPA) Buggies to Improve COVID-19 Safety for the Youngest Children: Evaluation of Prototypes

Abstract: Abstract Introduction: Young children are susceptible to COVID-19 infection in high-risk settings because they cannot begin vaccination until at least 6 months old and cannot mask safely until at least 2 years old. During essential activities, parents have attempted to protect children in strollers using rain covers, but these provide limited protection against airborne transmission. The investigator examined various models of rain-covered strollers that used either PAPR or HEPA air cleaning devices to provide safer air, so-called “PAPR buggies” and “HEPA buggies.” Materials and Method The investigation examined six models that varied based on the type of air filter, (PAPR, small/large HEPA), stroller, and rain cover, and the number of children (single or twin). Key outcomes were a qualitative assessment of strengths and limitations, air flow metrics, and sound intensity. Although all models used safe commercially-sold rain covers, the smallest model was also tested for air quality. Results The investigator evaluated each model as acceptable. The PAPR buggies are discrete, whereas the HEPA buggies offer greater flexibility in price and air flow rates. Models had a median of 185.26 air changes per hour, ACH (range of 57.22-951.33), equivalent to 12.35 times the standard for U.S. operating rooms (range of 3.81–63.42). Sound intensity was equivalent to a conversation or office setting (55.5–64.6 dB). Air quality testing revealed no safety concerns. Costs are reasonable for many families. Discussion PAPR and HEPA buggies are additional tools families can use as a part of a multifaceted strategy to improve safety in high-risk settings during the COVID-19 pandemic. The models evaluated were reasonable, provided excellent air flow, and had tolerable sound levels. There were no safety concerns, though parents are cautioned to only use commercially-sold, safe rain covers. The investigator offers suggestions for disseminating the widespread use of PAPR and HEPA buggies.

Persistent Lack of Female Orthopaedic Sports Medicine Fellows

Abstract: PurposeTo evaluate the gender composition of fellows, faculty, and leaders within orthopaedic sports medicine fellowship programs to provide a more complete description of gender diversity within this subspecialty.MethodsOfficial program websites of orthopaedic sports medicine fellowships listed on the Arthroscopy Association of North America fellowship directory were examined. Data collected for analysis included the gender of program directors, fellowship faculty, orthopaedic surgery department faculty, current sports medicine fellows, and fellows who graduated within the last 5 years.ResultsOf the 132 orthopaedic sports medicine fellows in training in the United States in the 2021 to 2022 academic year, 113 (85.6%) were men and 19 (14.4%) were women (P < .001). Within the past 5 years, 419 fellows were listed as completing a sports medicine fellowship, with 375 (89.5%) being men, and 44 (10.5%) being women (P < .001). There was no significant difference in the gender composition of current fellows compared with the composition of fellows within the last 5 years (P = .74). When we examined gender trends in sports medicine faculty, 639 (86.6%) were men and 99 (13.4%) were women (P < .001). There were 14 women (14.4%) orthopaedic sports medicine faculty in leadership positions (i.e., program director or assistant program director) compared with 83 men in such positions (85.6%) (P < .001).ConclusionsOrthopaedic sports medicine fellowships remain heavily male-dominated on all levels, including fellows, faculty, and leadership. There were no differences in the gender composition of current fellows when compared with those who graduated in the last 5 years, suggesting persistent gender disparity and the need for novel initiatives to enhance gender diversity in sports medicine.Level of EvidenceIV, descriptive study. To evaluate the gender composition of fellows, faculty, and leaders within orthopaedic sports medicine fellowship programs to provide a more complete description of gender diversity within this subspecialty. Official program websites of orthopaedic sports medicine fellowships listed on the Arthroscopy Association of North America fellowship directory were examined. Data collected for analysis included the gender of program directors, fellowship faculty, orthopaedic surgery department faculty, current sports medicine fellows, and fellows who graduated within the last 5 years. Of the 132 orthopaedic sports medicine fellows in training in the United States in the 2021 to 2022 academic year, 113 (85.6%) were men and 19 (14.4%) were women (P < .001). Within the past 5 years, 419 fellows were listed as completing a sports medicine fellowship, with 375 (89.5%) being men, and 44 (10.5%) being women (P < .001). There was no significant difference in the gender composition of current fellows compared with the composition of fellows within the last 5 years (P = .74). When we examined gender trends in sports medicine faculty, 639 (86.6%) were men and 99 (13.4%) were women (P < .001). There were 14 women (14.4%) orthopaedic sports medicine faculty in leadership positions (i.e., program director or assistant program director) compared with 83 men in such positions (85.6%) (P < .001). Orthopaedic sports medicine fellowships remain heavily male-dominated on all levels, including fellows, faculty, and leadership. There were no differences in the gender composition of current fellows when compared with those who graduated in the last 5 years, suggesting persistent gender disparity and the need for novel initiatives to enhance gender diversity in sports medicine.

Evidence for Landscape Transformation of Ridgetop Forests in Amazonian Ecuador

Abstract: Abstract The Napo River basin, which is situated within the Upper Amazon archaeological region, is one of the most speciose forests in Greater Amazonia. Standard thinking in scholarship and science holds that these forests are essentially pristine because any Indigenous impacts in the past would have been minimal, seedbanks would have been nearby, and natural forests would have reappeared after the humans left, died out, or dispersed. Inventory research in 2019 on three ridgetop forests in Waorani territory inside the Curaray basin (which drains to the right margin of the Napo River) and a comparable inventory on one control site forest along the Nushiño River (also in the Curaray basin) show human impacts from about the late nineteenth century to about 1960; they occurred during the period of wartime among Waorani themselves and between Wao people and outsiders. The human impacts resulted in the high basal-area presence of two long-lived species with important Waorani cultural uses: cacao ( Theobroma cacao L.) and ungurahua palm ( Oenocarpus bataua Mart.). These species have high frequency and dominance values and do not occur in the control site, which is comparable in terms of elevation above the flood zone of the rivers in the sample. These findings mean that alpha diversity in the right margin sector (or south) of the Napo River basin cannot a priori be explained by reference to traditionally, biologically accepted patterns of ecological succession but may require knowledge of historical patterns of Indigenous land use and secondary landscape transformation over time due to human (specifically Waorani) impacts of the past.

Variance in Autism Prevalence: Links With State-Level Autism Resources

Abstract: The prevalence of autism spectrum disorder (ASD) has varied over time and across the United States. This variability is likely related to external factors, such as regional differences in ASD-related resources. The study reported on here examined the links between ASD prevalence as measured by Individuals with Disabilities Education Act (IDEA) Part B child count data and four aspects of state infrastructure (health care and insurance policies, clinical resources, research infrastructure, and awareness-raising individuals/organizations). This study also investigated whether these constructs varied by geographical region. The data for this study were abstracted from publicly available databases. Information on state infrastructure was gathered from high-quality reports, resource guides, certificant registries, and databases. More comprehensive ASD-relevant insurance and health care policies, more clinical resources, and greater research infrastructure were associated with higher ASD state prevalence rates as measured by the IDEA Part B child count data. Prevalence of ASD was higher in eastern U.S. states compared with southern U.S. states, but state-level ASD resources did not statistically significantly differ across geographic regions. Implications for research, practice, and policy are discussed.

Reply on RC2

Abstract: Abstract. We explore how rock properties and channel morphology vary with rock type in Last Chance canyon, Guadalupe mountains, New Mexico, USA. The rocks here are composed of horizontally to near horizontally interbedded carbonate and sandstone. This study focuses on first and second order channel sections where the streams have a lower channel steepness index (ksn) upstream and transition to a higher ksn downstream. We hypothesize that differences in bed thickness and rock strength influence ksn values, both directly by influencing bulk bedrock strength but also indirectly through the production of coarse sediment. We collected discontinuity intensity data (the length of bedding planes and fractures per unit area), Schmidt hammer rebound measurements, and measured the largest boulder at every 40-foot elevation contour to test this hypothesis. Bedrock and boulder minerology was determined using a lab-based carbonate dissolution method. High resolution orthomosaics and DEMs were generated from drone photos. The orthomosaics were used to map channel sections with exposed bedrock. The high-resolution DEMs were used to measure channel slope and hillslope relief. We find that discontinuity intensity is negatively correlated with Schmidt hammer rebound values. Channel steepness is higher where reaches are primarily incising through more thickly bedded carbonate bedrock. Where there is more thinly bedded sandstone rock exposed, channel steepness tends to be lower. Furthermore, the effect that rock properties have on channel morphology is confounded by sediment input from hillslopes. Thickly bedded rock units on surrounding hillslopes contribute larger sized colluvial sediment to the channels, and these reaches have higher ksn. Larger and more competent carbonate sediment armors both the carbonate and the more erodible sandstone and dampens the negative effect sandstone bedrock has on channel steepness. We believe that in the relatively steep, high ksn downstream channel sections slope is primarily controlled by the coarse alluvial cover. We further posit that the upstream low ksn reaches have a baselevel that is essentially fixed by the steep downstream reaches, resulting in a stable configuration where channel slopes have adjusted to lithologic differences and/or sediment armor.

Marsh induced backwater: the influence of non-fluvial sedimentation on a delta's channel morphology and kinematics

Abstract: Abstract. We investigate the interaction of fluvial and non-fluvial sedimentation on the channel morphology and kinematics of an experimental river delta. We compare two deltas: one that evolved with a proxy for non-fluvial sedimentation (treatment experiment) and one that evolved without the proxy (control). We show that the addition of the non-fluvial sediment proxy alters the delta's channel morphology and kinematics. Notably, the flow outside the channels is significantly reduced in the treatment experiment and the channels are deeper (as a function of radial distance) and longer. We also find that the treatment channels have the same width from the entrance to the shoreline, while the control channels get narrower as they approach the shore. Interestingly, the channel beds in the treatment experiment often exist below sea level in the terrestrial portion of the delta top creating a ~0.7 m reach of steady, nonuniform backwater flow. However, in the control experiment, the channel beds generally exist at or above relative sea level, creating channel movement resembling morphodynamic backwater kinematics and topographic flow expansions. Differences between channel and far-field aggradation produce a longer channel in-filling timescale for the treatment as compared to the control, suggesting that the channel avulsions triggered by a peak in channel sedimentation occur less frequently in the treatment experiment. Despite this difference, the basin-wide timescale of lateral channel mobility remains similar. Ultimately, non-fluvial sedimentation on the delta top plays a key role in the channel morphology and kinematics of an experimental river delta, producing channels which are more analogous to channels in global river deltas, and which cannot be produced solely by increasing cohesion in an experimental river delta.

Exosomes and Microvesicles From Adipose-derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

Abstract: Introduction Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASC) have therapeutic potential in multiple disease states, however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. Methods Exosomes and microvesicles were collected from ASC conditioned media by centrifugation (10,000 g for microvesicles, 100,000 g for exosomes). Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). LPS injured cells (n = 578) were compared to HUVECS with concomitant LPS injury plus 1.0 μg/mL of exosomes (n = 540) or microvesicles (n = 510) for 24 hours. These two cohorts were compared to control HUVECs that received phosphate-buffered saline only (n = 786) and HUVECs exposed to exosomes (n = 505) or microvesicles (n = 500) alone. Cells were fixed and stained with FITC-labelled wheat germ agglutinin (WGA) to quantify EGX. Real-time quantitative reverse-transcription polymerase chain reaction were used on HUVECs cell lystate to quantify Hyaluron Synthase-1 (HAS1) expression. Results Exosomes alone decreased endothelial glycocalyx staining intensity when compared to control (4.94 vs. 6.41 AU, p < 0.001), while microvesicles did not cause a change glycocalyx staining intensity (6.39 vs. 6.41, p = 0.99). LPS injury resulted in decreased glycocalyx intensity as compared to control (5.60 vs. 6.41, p < 0.001). Exosomes (6.85 vs. 5.60, p < 0.001) and microvesicles (6.35 vs. 5.60, p < 0.001) preserved endothelial glycocalyx staining intensity after LPS injury. HAS1 levels were found to be higher in the exosome (1.14 vs. 3.67 RE, p = 0.02) and microvesicle groups (1.14 vs. 3.59 RE, p = 0.02) when compared to LPS injury. Hyaluron Synthase-2 and -3 expression were not different in the various experimental groups. Conclusions Exosomes alone can damage the endothelial glycocalyx. However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect appears to be mediated by HAS1. Level of Evidence Basic Science study

The Adjuvant Combination of dmLT and Monophosphoryl Lipid A Activates the Canonical, Nonpyroptotic NLRP3 Inflammasome in Dendritic Cells and Significantly Interacts to Expand Antigen-Specific CD4 T Cells

Abstract: Abstract Adjuvants are often essential additions to vaccines that enhance the activation of innate immune cells, leading to more potent and protective T and B cell responses. Only a few vaccine adjuvants are currently used in approved vaccine formulations in the United States. Combinations of one or more adjuvants have the potential to increase the efficacy of existing and next-generation vaccines. In this study, we investigated how the nontoxic double mutant Escherichia coli heat-labile toxin R192G/L211A (dmLT), when combined with the TLR4 agonist monophosphoryl lipid A (MPL-A), impacted innate and adaptive immune responses to vaccination in mice. We found that the combination of dmLT and MPL-A induced an expansion of Ag-specific, multifaceted Th1/2/17 CD4 T cells higher than that explained by adding responses to either adjuvant alone. Furthermore, we observed more robust activation of primary mouse bone marrow–derived dendritic cells in the combination adjuvant–treated group via engagement of the canonical NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex. This was marked by a multiplicative increase in the secretion of active IL-1β that was independent of classical gasdermin D–mediated pyroptosis. Moreover, the combination adjuvant increased the production of the secondary messengers cAMP and PGE2 in dendritic cells. These results demonstrate how certain adjuvant combinations could be used to potentiate better vaccine responses to combat a variety of pathogens.