Reversing factor Xa inhibitors - clinical utility of andexanet alfa

Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications. Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, such as apixaban, edoxaban and rivaroxaban, and indirect FXa inhibitors such as low-molecular-weight heparins. This narrative reviews the development of andexanet alfa and explores its basic science, pharmacokinetics/pharmacodynamics, animal models, and human studies

Charles W. Mahan, SJ Papers

All physical materials associated with the New England Province Archive are currently held by the Jesuit Archives in St. Louis, MO. Any inquiries about these materials should be directed to Jesuit Archives. Electronic versions of some items and the descriptions and finding aids to the Archives, which are hosted in CrossWorks, are provided only as a courtesy. Charles W. Mahan was born in Roxbury, MA on March 3, 1899 to Francis A. and Mary (Cunningham) Mahan. He was educated at St. John’s Preparatory School in Danvers, MA. He briefly studied at Boston College before entering into the Society of Jesus on January 22, 1919 at St. Andrew-on-the-Hudson in Poughkeepsie, NY where he also spent his juniorate from 1921 until 1922. He studied Philosophy at Woodstock College, earning his A.B. in 1924 and his A.M. in 1925. He then spent his regency teaching in the Philippines from 1925 until 1928. In 1928, he returned to New England, studying Theology at Weston College until 1932 and was also ordained at Weston College in 1931. After his ordination, he taught Spanish at St.Georges College, Kingston, Jamaica and served as editor of the Catholic Opinion. In 1934, he completed his tertianship in Belgium. His next assignment was teaching English, Mathematics, Religion, and Economics at Baghdad College in Iraq in 1935. In 1957, he left for a year sabbatical at St. Francis Xavier Chapel in Boston, MA, but returned to Baghdad in 1958. During his 35 years in Iraq, he also was prefect at the boarder’s residence at the college. In 1969, shortly before the Iraqi government expelled all foreign missionaries, he became ill and returned to the United States. He lived at Campion Center until his death on May 22, 1982. The collection consists of sermons, homilies, retreat notes, Baghdad College tests/examinations, diplomas, and a play Ziyaret Il Kulliyye. There is also a scrapbook and one-2.5 inch box of photographs of Baghdad College and Iraq

Elucidation of Beta-Oxidation Pathways in Ralstonia Eutropha H16 by Examination of Global Gene Expression

Ralstonia eutropha H16 is capable of growth and polyhydroxyalkanoate production on plant oils and fatty acids. However, little is known about the triacylglycerol and fatty acid degradation pathways of this bacterium. We compare whole-cell gene expression levels of R. eutropha H16 during growth and polyhydroxyalkanoate production on trioleate and fructose. Trioleate is a triacylglycerol that serves as a model for plant oils. Among the genes of note, two potential fatty acid β-oxidation operons and two putative lipase genes were shown to be upregulated in trioleate cultures. The genes of the glyoxylate bypass also exhibit increased expression during growth on trioleate. We observed that single β-oxidation operon deletion mutants of R. eutropha could grow using palm oil or crude palm kernel oil as the sole carbon source, regardless of which operon was present in the genome, but a double mutant was unable to grow under these conditions. A lipase deletion mutant did not exhibit a growth defect in emulsified oil cultures but did exhibit a phenotype in cultures containing nonemulsified oil. Mutants of the glyoxylate shunt gene for isocitrate lyase were able to grow in the presence of oils, while a malate synthase (aceB) deletion mutant grew more slowly than wild type. Gene expression under polyhydroxyalkanoate storage conditions was also examined. Many findings of this analysis confirm results from previous studies by our group and others. This work represents the first examination of global gene expression involving triacylglycerol and fatty acid catabolism genes in R. eutropha.Malaysia-MIT Biotechnology Partnership Programm

The Photo Essay: A Visual Research Method for Educating Obstetricians and Other Health Care Professionals

When it comes to issues related to low-income women seeking early, adequate, or continuous prenatal ca re, the public health and medical communities continue to tell women to take responsibility for their actions. Rarely are messages aimed at providers. To help physicians see how factors in their offices and clinics can affect service utilization, the photo essay, a visual qualitative research strategy was developed using low- income minority and disenfranchised women who had recently given birth or were near to giving birth. Eight photo essays were completed. Together, the narratives, in collaboration with the photos, provided an opportunity for physicians to hear and observe women, as consumers, as they expanded their descriptions of their prenatal care experience

Control of Josephson current by Aharonov-Casher Phase in a Rashba Ring

We study the interference effect induced by the Aharonov-Casher phase on the Josephson current through a semiconducting ring attached to superconducting leads. Using a 1D model that incorporates spin-orbit coupling in the semiconducting ring, we calculate the Andreev levels analytically and numerically, and predict oscillations of the Josephson current due to the AC phase. This result is valid from the point contact limit to the long channel length limit, as defined by the ratio of the junction length and the BCS healing length. We show in the long channel length limit that the impurity scattering has no effect on the oscillation of the Josephson current, in contrast to the case of conductivity oscillations in a spin-orbit coupled ring system attached to normal leads where impurity scattering reduces the amplitude of oscillations. Our results suggest a new scheme to measure the AC phase with, in principle, higher sensitivity. In addition, this effect allows for control of the Josephson current through the gate voltage tuned AC phase.Comment: 12pages, 8 figure

Cost-of-Illness Analysis of Long-Term Health Care Resource Use and Disease Burden in Patients With Pulmonary Embolism: Insights From the PREFER in VTE Registry

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long-term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost-of-illness analysis with a bottom-up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events-European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12-month follow-up in 2020 Euros. We estimated a disability weight for the 12-month post-PE status and corresponding disability adjusted life years presumably owing to PE. Disease-specific costs in the first year of follow-up after an incident PE case ranged between 9135 Euros and 10 620 Euros. The proportion of indirect costs was 42% to 49% of total costs. Costs were lowest in patients with ongoing cancer, mainly because productivity loss was less evident in this already burdened population. The calculated disability weight for survivors who were cancer free 12 months post-PE was 0.017, and the estimated disability adjusted life years per incident case were 1.17. Conclusions The economic burden imposed by PE to society and affected patients is considerable, and productivity loss is its main driver. The disease burden from PE is remarkable and translates to the loss of roughly 1.2 years of healthy life per incident PE case

High-Field Electrical Transport in Single-Wall Carbon Nanotubes

Using low-resistance electrical contacts, we have measured the intrinsic high-field transport properties of metallic single-wall carbon nanotubes. Individual nanotubes appear to be able to carry currents with a density exceeding 10^9 A/cm^2. As the bias voltage is increased, the conductance drops dramatically due to scattering of electrons. We show that the current-voltage characteristics can be explained by considering optical or zone-boundary phonon emission as the dominant scattering mechanism at high field.Comment: 4 pages, 3 eps figure

Fellows as teachers: a model to enhance pediatric resident education

Pressures on academic faculty to perform beyond their role as educators has stimulated interest in complementary approaches in resident medical education. While fellows are often believed to detract from resident learning and experience, we describe our preliminary investigations utilizing clinical fellows as a positive force in pediatric resident education. Our objectives were to implement a practical approach to engage fellows in resident education, evaluate the impact of a fellow-led education program on pediatric resident and fellow experience, and investigate if growth of a fellowship program detracts from resident procedural experience.This study was conducted in a neonatal intensive care unit (NICU) where fellows designed and implemented an education program consisting of daily didactic teaching sessions before morning clinical rounds. The impact of a fellow-led education program on resident satisfaction with their NICU experience was assessed via anonymous student evaluations. The potential value of the program for participating fellows was also evaluated using an anonymous survey.The online evaluation was completed by 105 residents. Scores were markedly higher after the program was implemented in areas of teaching excellence (4.44 out of 5 versus 4.67, p<0.05) and overall resident learning (3.60 out of 5 versus 4.61, p<0.001). Fellows rated the acquisition of teaching skills and enhanced knowledge of neonatal pathophysiology as the most valuable aspects of their participation in the education program. The anonymous survey revealed that 87.5% of participating residents believed that NICU fellows were very important to their overall training and education.While fellows are often believed to be a detracting factor to residency training, we found that pediatric resident attitudes toward the fellows were generally positive. In our experience, in the specialty of neonatology a fellow-led education program can positively contribute to both resident and fellow learning and satisfaction. Further investigation into the value of utilizing fellows as a positive force in resident education in other medical specialties appears warranted

Effect of elevated CO2 on peanut performance in a semi-arid production region

With the intensification and frequency of heat waves and periods of water deficit stress, along with rising atmospheric carbon dioxide [CO2], understanding the seasonal leaf-gas-exchange responses to combined abiotic factors will be important in predicting crop performance in semi-arid production systems. In peanut (Arachis hypogaea L.), the availability of developmental stage physiological data on the response to repeated water deficit stress periods in an elevated [CO2] (EC) environment is limited and necessary to improve crop model predictions. Here, we investigated the effects of season-long EC (650 µmol CO2 m−2 s−1) on the physiology and productivity of peanut in a semi-arid environment. This study was conducted over two-growing seasons using field-based growth chambers to maintain EC conditions, and impose water-stress at three critical developmental stages. Our results showed that relative to ambient [CO2] (AC), long-term EC during water-stress episodes, increased leaf-level light-saturated CO2 assimilation (Asat), transpiration efficiency (TE), vegetative biomass, and pod yield by 58%, 73%, 58%, and 39%, respectively. Although leaf nitrogen content was reduced by 16%, there was 41% increase in maximum Rubisco carboxylation efficiency in EC, indicating that there was minimal photosynthetic down-regulation. Furthermore, long-term EC modified the short-term physiological response (Asat) to rapid changes in [CO2] during the water-stress episodes, generating a much greater change in EC (54%) compared to AC (10%). Additionally, long-term EC generated a 23% greater Asat compared to the short-term EC during the water-stress episodes. These findings indicate high levels of physiological adjustment in EC, which may increase drought resilience. We concluded that EC may reduce the negative impacts of repeated water-stress events at critical developmental stages on rain-fed peanut in semi-arid regions. These results can inform current models to improve the projections of peanut response to future climates