Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

Cutting Edge: Bach2 Integrates Cytokine Signals to Arbitrate Differentiation Decisions between T Follicular Helper and Th17 Lineages.

CXCR5 is a hallmark of T follicular helper (Tfh) cells. The mechanism of CXCR5 induction, however, is still incompletely understood. In this study, we report that in mice with the absence of transcription factor Bach2, the Th17-inducing cytokines IL-6 and TGF-ß together induced CXCR5 expression in vitro. Mechanistically, IL-6/STAT3 drove Cxcr5 promoter activity via the upstream site 1 regulatory element, whereas TGF-ß enhanced permissive histone modifications, and the STAT3 binding to the site 1 regulatory element was higher in the absence of Bach2. Subsequently, despite previous studies showing enhanced Th17 cell differentiation in the absence of Bach2 in vitro, we found that in vivo, the Bach2 deficiency led to an enhanced Tfh cell response at the expense of the Th17 cell response. These findings suggest that Bach2 helps integrate cytokine signals to arbitrate differentiation decisions between Tfh and Th17 lineages.

Wildfire Threat to Inpatient Health Care Facilities in California, 2022.

Objectives. To assess wildfire risks to California inpatient health care facilities in 2022. Methods. Locations of inpatient facilities and associated inpatient bed capacities were mapped in relation to California Department of Forestry and Fire Protection fire threat zones (FTZs), which combine expected fire frequency with potential fire behavior. We computed the distances of each facility to the nearest high, very high, and extreme FTZs. Results. Half (107 290 beds) of California's total inpatient capacity is within 0.87 miles of a high FTZ and 95% (203 665 beds) is within 3.7 miles of a high FTZ. Half of the total inpatient capacity is within 3.3 miles of a very high FTZ and 15.5 miles of an extreme FTZ. Conclusions. Wildfires threaten a large number of inpatient health care facilities in California. In many counties, all health care facilities may be at risk. Public Health Implications. Wildfires in California are rapid-onset disasters with short preimpact phases. Policies should address facility-level preparedness including smoke mitigation, sheltering measures, evacuation procedures, and resource allocation. Regional evacuation needs, including access to emergency medical services and patient transportation, must also be considered. (Am J Public Health. 2023;113(5):555-558. https://doi.org/10.2105/AJPH.2023.307236).

Multiplexed droplet single-cell sequencing (Mux-Seq) of normal and transplant kidney.

Maintenance of systemic homeostasis by kidney requires the coordinated response of diverse cell types. The use of single-cell RNA sequencing (scRNAseq) for patient tissue samples remains fraught with difficulties with cell isolation, purity, and experimental bias. The ability to characterize immune and parenchymal cells during transplant rejection will be invaluable in defining transplant pathology where tissue availability is restricted to needle biopsy fragments. Herein, we present feasibility data for multiplexing approach for droplet scRNAseq (Mux-Seq). Mux-Seq has the potential to minimize experimental batch bias and variation even with very small sample input. In this first proof-of-concept study for this approach, explant tissues from six normal and two transplant recipients after multiple early post-transplant rejection episodes leading to nephrectomy due to aggressive antibody mediated rejection, were pooled for Mux-Seq. A computational tool, Demuxlet was applied for demultiplexing the individual cells from the pooled experiment. Each sample was also applied individually in a single microfluidic run (singleplex) to correlate results with the pooled data from the same sample. Our applied protocol demonstrated that data from Mux-Seq correlated highly with singleplex (Pearson coefficient 0.982) sequencing results, with the ability to identify many known and novel kidney cell types including different infiltrating immune cells. Trajectory analysis of proximal tubule and endothelial cells demonstrated separation between healthy and injured kidney from transplant explant suggesting evolving stages of cell- specific differentiation in alloimmune injury. This study provides the technical groundwork for understanding the pathogenesis of alloimmune injury and host tissue response in transplant rejection and normal human kidney and provides a protocol for optimized processing precious and low input human kidney biopsy tissue for larger scale studies.

Multi-institutional patterns of clopidogrel response among patients undergoing transcarotid artery revascularization.

OBJECTIVE: Current guidelines recommend dual antiplatelet therapy (DAPT) in patients undergoing carotid artery stenting. The most common DAPT regimen is aspirin and clopidogrel, a P2Y12 receptor antagonist; however, the prevalence of clopidogrel resistance (CR) in patients undergoing percutaneous coronary interventions may exceed 60%. Few studies have investigated the prevalence and impact of CR in patients undergoing extracranial carotid artery stenting, particularly transcarotid artery revascularization (TCAR). METHODS: Consecutive high-risk patients ≥ 18 years who underwent TCAR for high grade (≥70%) and/or symptomatic (≥50%) carotid stenosis with preoperative P2Y12 testing between August 2019 and December 2021 were identified across five institutions. Preoperative platelet reactivity was measured with the VerifyNow P2Y12 Reaction Unit (PRU) Test (Instrumentation Laboratory, Bedford, MA), with CR defined as PRU ≥ 194 and hyper-response as PRU <70. Patients without preoperative P2Y12 testing within 30 days prior to TCAR or those on a non-clopidogrel P2Y12 inhibitor preoperatively were excluded. The primary outcome of interest was prevalence of CR. Secondary outcomes of interest included the incidence of ischemic and hemorrhagic complications. RESULTS: Of 92 patients identified, the majority were male (59%) and Caucasian (75%) with a mean age of 75 years (±8, range 56-92). Preoperatively, 93% of patients were on aspirin, 100% on clopidogrel, and 13% on therapeutic anticoagulation. At presentation, 36% were symptomatic. The mean preoperative P2Y12 was 156 PRU (±76, range 6-349). In total, 30 (33%) patients met criteria for CR (mean PRU 240 ± 37; range 197-349), and 15 (16%) met criteria for hyper-responder (mean PRU 38 ± 20; range 6-68). There was no significant difference by clopidogrel response phenotype in terms of sex (p = 0.246), race (p = 0.384), or symptomatic presentation (p = 0.956). Postoperatively, the cumulative incidence of stroke and MI was 2.1%, with no statistically significant difference in the incidence of in-hospital stroke (PRU 238, p = 0.489) or MI (PRU 168, p = 1) between clopidogrel phenotypes. Three (3.3%) patients, one CR (PRU 240) and two responders (PRU 119 and PRU 189), experienced postoperative access site hematomas that required no subsequent intervention. No other index hospitalization hemorrhagic complications occurred. CONCLUSIONS: Using preoperative P2Y12 testing with a threshold PRU ≥ 194 to define CR, we identified a high prevalence of CR in patients undergoing TCAR similar to that in the pre-existing coronary literature. We found no significant differences in postoperative ischemic or hemorrhagic complications by clopidogrel response phenotype, although complication rates in the overall study cohort were low. CR may be a spectrum from responder to partial responder to complete non-responder, and this may account for the differences in our CR cohort compared to the ROADSTER 2 protocol deviation cohort. Further investigation is warranted to determine if a quantitative assessment of CR is sufficient to identify patients at risk of developing secondary cerebrovascular ischemic events in this patient population.

A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project.

Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and personalized therapies for diseases. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate three-dimensional (3-D) molecular atlases of healthy and diseased kidney biopsies by using multiple state-of-the-art omics and imaging technologies across several institutions. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single-cell level or in 3-D space is a significant challenge that can be a futile exercise if not well controlled. We describe a "follow the tissue" pipeline for generating a reliable and authentic single-cell/region 3-D molecular atlas of human adult kidney. Our approach emphasizes quality assurance, quality control, validation, and harmonization across different omics and imaging technologies from sample procurement, processing, storage, shipping to data generation, analysis, and sharing. We established benchmarks for quality control, rigor, reproducibility, and feasibility across multiple technologies through a pilot experiment using common source tissue that was processed and analyzed at different institutions and different technologies. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before their being approved to interrogate clinical biopsy specimens. The process established economizes the use of valuable biopsy tissue for multiomics and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and serves as a model for precision medicine projects across laboratories, institutions and consortia.

Regional Variation in Usage of Ultrasound-Guided Femoral Access in the Vascular Quality Initiative.

BACKGROUND: Access site complications are among the most common complications following peripheral vascular interventions. Previous studies have demonstrated a reduced rate of complications with ultrasound-guided vascular access (UGVA). The objective of this study is to evaluate the regional use of UGVA within the Vascular Quality Initiative (VQI). METHODS: The VQI peripheral intervention module between 2010 and 2018 was evaluated. Regional ID was used to compare distribution of ultrasound usage. Regions were grouped into terciles based on the rate of ultrasound use. Patients were categorized based on type of access. Primary outcome was use of ultrasound across regions. Secondary outcomes were access site complications. RESULTS: Over 43,000 cases across the 18 VQI regions were evaluated. The average rate of ultrasound usage was 71% across the regions with a wide variation (range 38-97%). There is a significant difference in utilization among the top third (87%), middle third (79%), and bottom third (58%) (P < 0.001). Average sheath size was similar across all 3 groups. A higher use of ultrasound-guided access was associated with significantly fewer access site complications (top third 1.96% vs. bottom third 3.04%, P < 0.001), the most significant of which was a decreased rate of access site hematoma (top third 1.37% vs. bottom third 2.35%, P < 0.001). CONCLUSIONS: This is the first study to evaluate ultrasound-guided access across VQI regions. Our results demonstrate that despite strong evidence supporting the utilization of UGVA, there remains a wide variation in ultrasound usage across VQI regions. This is also the first study to show that the prevalence of ultrasound use in peripheral vascular interventions (PVI) is inversely related to access site complications. Given all of the data supporting the usage of UGVA across numerous specialties, our findings encourage the consideration of an ultrasound-first approach for vascular access in PVI and the implementation of targeted strategies and evidence-based guidelines to enhance UGVA utilization in PVI.

The role of the inferior mesenteric artery in predicting secondary intervention for type II endoleak following endovascular aneurysm repair.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is associated with a greater risk of graft-related complications and need for secondary interventions compared with open repair. Type II endoleak (EL-2) is the most common complication. We examined the hypothesis that a functionally occluded inferior mesenteric artery (IMA) before EVAR was associated with fewer secondary interventions for EL-2. METHODS: All nonruptured abdominal aortic aneurysms (AAA) treated by EVAR using U.S. Food and Drug Administration-approved endografts from January 2005 to December 2017 were retrospectively reviewed, including computed tomography angiograms. Preoperative patency of the IMA and any secondary interventions performed after the index EVAR procedure were recorded. A functionally occluded IMA was defined as one that was (1) chronically occluded or severely stenosed on preoperative imaging or (2) coil embolized before EVAR. Secondary interventions for persistent EL-2 were indicated when AAA sac diameter increased by more than 5 mm. RESULTS: The study cohort comprised 490 patients (84 women) with a mean age of 74.8 ± 8.2 years. The mean preoperative AAA diameter was 5.6 ± 0.9 cm. One hundred twenty-nine patients (26.3%) died during follow-up. The mean follow-up of survivors was 38 months. Types (prevalence) of endoleak were I (2.4%), II (18.9%), III (0.7%), IV (0.5%), and V (0.2%). Patients with a functionally occluded IMA underwent significantly fewer secondary interventions for EL-2 compared with patients with a patent IMA (2.6% vs 7.1%; P = .020). All secondary interventions in the functionally occluded IMA group involved the lumbar arteries (LA). When the IMA was patent, secondary interventions were equally distributed between the LA and IMA. Logistic regression confirmed that a functionally patent IMA was associated with a greater number of secondary interventions for EL-2 (odds ratio, 3.0; 95% confidence interval, 1.2-7.5; P = .025). CONCLUSIONS: Patients with a functionally occluded IMA required significantly fewer secondary interventions for EL-2 after EVAR. In addition, the type of vessels intervened on were primarily LA. Among patients with a patent IMA, preoperative coil embolization may decrease secondary interventions and improve the long-term durability of EVAR.

TREO Aortic Endograft Demonstrates Significant Aneurysmal Sac Shrinkage.

BACKGROUND: Aneurysmal sac shrinkage is associated with successful aneurysm repair after endovascular aortic repair (EVAR). There are a variety of approved aortic endografts, with a recent study demonstrating increased sac shrinkage in certain endografts compared with others. The TREO endograft (Terumo Aortic Ltd, Renfrewshire, Scotland, UK) is being evaluated for use in EVAR, with preliminary data demonstrating high rates of success. The objective of this study is to evaluate sac shrinkage of the TREO endograft. METHODS: This is a retrospective analysis of EVARs at a single institution by a high-volume surgeon over a 1-year period in which the TREO graft was used. The change in sac size and rate of sac shrinkage (mm/mo) were evaluated between TREO and non-TREO grafts. All TREO grafts were included in the analysis. Non-TREO grafts were matched a priori for TREO indications for use anatomic specifications. Non-TREO grafts were also excluded for traumatic or emergent cases. The primary outcome was sac shrinkage, and secondary outcomes were composite complication profile within 30 d of operation. RESULTS: Six TREO grafts and 16 non-TREO grafts were included for analysis. The groups were similar in age, gender, and race. The groups were also similar in aortic anatomy before EVAR. The aneurysm sac shrinkage rate (mm/mo) is significantly greater in the TREO group than in the non-TREO group (0.484 ± 0.107 versus 0.018 ± 0.112, P = 0.033). The total average size of sac shrinkage was also greater for the TREO group (-0.688 ± 2.262 versus 12.00 ± 2.78, P < 0.001). The composite complication profile of stroke, myocardial infarction, death, and respiratory complications was not different between groups. CONCLUSIONS: TREO aortic endografts for aneurysm repair are being used in Europe. However, their application in the United States is limited. Our data demonstrate the significant advantage the TREO graft has with increased sac shrinkage and minimal complications, compared with other grafts. This study adds to the growing body of literature supporting TREO graft use for EVAR.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

FlyBase at 25: looking to the future.

Since 1992, FlyBase (flybase.org) has been an essential online resource for the Drosophila research community. Concentrating on the most extensively studied species, Drosophila melanogaster, FlyBase includes information on genes (molecular and genetic), transgenic constructs, phenotypes, genetic and physical interactions, and reagents such as stocks and cDNAs. Access to data is provided through a number of tools, reports, and bulk-data downloads. Looking to the future, FlyBase is expanding its focus to serve a broader scientific community. In this update, we describe new features, datasets, reagent collections, and data presentations that address this goal, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, a portal for external resources, video tutorials and the FlyBase Community Advisory Group.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point of care coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, has increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has declined only modestly over the last decade, remaining at 50% or greater in high-risk patients. Given these limitations and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists has formed the Blood Conservation in Cardiac Surgery Working Group in order to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

FlyBase: introduction of the Drosophila melanogaster Release 6 reference genome assembly and large-scale migration of genome annotations.

Release 6, the latest reference genome assembly of the fruit fly Drosophila melanogaster, was released by the Berkeley Drosophila Genome Project in 2014; it replaces their previous Release 5 genome assembly, which had been the reference genome assembly for over 7 years. With the enormous amount of information now attached to the D. melanogaster genome in public repositories and individual laboratories, the replacement of the previous assembly by the new one is a major event requiring careful migration of annotations and genome-anchored data to the new, improved assembly. In this report, we describe the attributes of the new Release 6 reference genome assembly, the migration of FlyBase genome annotations to this new assembly, how genome features on this new assembly can be viewed in FlyBase (http://flybase.org) and how users can convert coordinates for their own data to the corresponding Release 6 coordinates.

Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study.

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for covariates, low hemoglobin (<8 g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97-2.41]) and aHR = 1.84, [0.91-3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10-11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (a HR = 1.43 [0.84-2.43]) or doxorubicin (a HR = 1.25, [0.66-2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.

Active Monitoring of Travelers Arriving from Ebola-Affected Countries - New York City, October 2014-April 2015.

The Ebola virus disease (Ebola) outbreak in West Africa has claimed approximately 11,300 lives (1), and the magnitude and course of the epidemic prompted many nonaffected countries to prepare for Ebola cases imported from affected countries. In October 2014, CDC and the Department of Homeland Security (DHS) implemented enhanced entry risk assessment and management at five U.S. airports: John F. Kennedy (JFK) International Airport in New York City (NYC), O'Hare International Airport in Chicago, Newark Liberty International Airport in New Jersey, Hartsfield-Jackson International Airport in Atlanta, and Dulles International Airport in Virginia (2). Enhanced entry risk assessment began at JFK on October 11, 2014, and at the remaining airports on October 16 (3). On October 21, DHS exercised its authority to direct all travelers flying into the United States from an Ebola-affected country to arrive at one of the five participating airports. At the time, the Ebola-affected countries included Guinea, Liberia, Mali, and Sierra Leone. On October 27, CDC issued updated guidance for monitoring persons with potential Ebola virus exposure (4), including recommending daily monitoring of such persons to ascertain the presence of fever or symptoms for a period of 21 days (the maximum incubation period of Ebola virus) after the last potential exposure; this was termed "active monitoring." CDC also recommended "direct active monitoring" of persons with a higher risk for Ebola virus exposure, including health care workers who had provided direct patient care in Ebola-affected countries. Direct active monitoring required direct observation of the person being monitored by the local health authority at least once daily (5). This report describes the operational structure of the NYC Department of Health and Mental Hygiene's (DOHMH) active monitoring program during its first 6 months (October 2014-April 2015) of operation. Data collected on persons who required direct active monitoring are not included in this report.

The Synthesis and Characterization of Highly Fluorescent Polycyclic Azaborine Chromophores.

Six new heteroaromatic polycyclic azaborine chromophores were designed, synthesized, and investigated as easily tunable high-luminescent organic materials. The impact of the nitrogen-boron-hydroxy (N-BOH) unit in the azaborines was investigated by comparison with their N-carbonyl analogs. Insertion of the N-B(OH)-C unit into heteroaromatic polycyclic compounds resulted in strong visible absorption and sharp fluorescence with efficient quantum yields. The solid-state fluorescence of the heteroaromatic polycyclic compounds displayed a large Stokes shift compared to being in solution. The large Stokes shifts observed offset the self-quench effect in the solid state.

Aortic valve replacement reduces valvuloarterial impedance but does not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet aortic valve stenosis.

OBJECTIVE: Standard methods of quantifying aortic valve stenosis (AS), which focus entirely on the valve itself, do not adequately characterize the magnitude, predict the onset, progression, and severity of symptoms, or identify the incidence of subsequent adverse events. Valvuloarterial impedance (Z(va)) is an index of global left ventricular (LV) afterload that incorporates valvular and arterial loads. The authors tested the hypothesis that aortic valve replacement (AVR) reduces Z(va) but does not affect the arterial component of LV afterload in elderly patients with degenerative calcific trileaflet AS. DESIGN: Observational study. SETTING: Veterans affairs medical center. PARTICIPANTS: Eight elderly (age, 79 ± 4 years) men with moderate-to-severe AS and normal preoperative LV function (ejection fraction, 61% ± 9%) scheduled for AVR with or without coronary artery bypass graft surgery were studied after institutional review board approval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A comprehensive TEE examination was performed during isoflurane-fentanyl-rocuronium anesthesia. Doppler echocardiography was used to measure pressure gradients across the aortic valve, stroke volume (continuity equation), and aortic valve area using standard techniques. Z(va) was determined as (systolic arterial pressure+mean gradient)/stroke volume index. Energy loss index was calculated as (aortic area × aortic valve area)/([aortic area--aortic valve area]× body surface area). The stroke work loss was obtained as (mean gradient × 100/[systolic arterial pressure+mean gradient]). The ratio of stroke volume index to pulse pressure was used to measure systemic arterial compliance. Z(va), energy loss index, stroke work loss, and systemic arterial compliance were assessed before and 15 minutes after cardiopulmonary bypass. Systemic and pulmonary hemodynamics (invasive catheters) were similar after versus before AVR. Aortic valve area increased significantly (p<0.05) with AVR (0.92 ± 0.26 cm(2) to 1.94 ± 0.35 cm(2)), concomitant with decreases in peak and mean gradients (60 ± 17 mmHg to 15 ± 8 mmHg and 38 ± 11 mmHg to 8 ± 5 mmHg, respectively) and peak blood flow velocity (3.9 ± 0.5 m · s(-1) to 1.9 ± 0.5 m · s(-1)). AVR reduced Z(va) (4.6 ± 1.0 mmHg · mL(-1) · m(-2) to 3.5 ± 0.3 mmHg · mL(-1) · m(-2)) and improved energy loss index (0.55 ± 0.16 cm(2) · m(-2) to 1.58 ± 0.48 cm(2) · m(-2)) concomitant with a decline in stroke work loss (25% ± 6% to 7% ± 4%), but systemic arterial compliance remained unchanged (0.63 ± 0.13 compared with 0.70 ± 0.12 mL · mmHg(-1)· m(-2)). CONCLUSION: The current results showed that AVR acutely reduced Zva, improved energy loss index, and decreased stroke work loss, but did not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet AS.

A standardised differential privacy framework for epidemiological modeling with mobile phone data.

During the COVID-19 pandemic, the use of mobile phone data for monitoring human mobility patterns has become increasingly common, both to study the impact of travel restrictions on population movement and epidemiological modeling. Despite the importance of these data, the use of location information to guide public policy can raise issues of privacy and ethical use. Studies have shown that simple aggregation does not protect the privacy of an individual, and there are no universal standards for aggregation that guarantee anonymity. Newer methods, such as differential privacy, can provide statistically verifiable protection against identifiability but have been largely untested as inputs for compartment models used in infectious disease epidemiology. Our study examines the application of differential privacy as an anonymisation tool in epidemiological models, studying the impact of adding quantifiable statistical noise to mobile phone-based location data on the bias of ten common epidemiological metrics. We find that many epidemiological metrics are preserved and remain close to their non-private values when the true noise state is less than 20, in a count transition matrix, which corresponds to a privacy-less parameter ϵ = 0.05 per release. We show that differential privacy offers a robust approach to preserving individual privacy in mobility data while providing useful population-level insights for public health. Importantly, we have built a modular software pipeline to facilitate the replication and expansion of our framework.