Management of Severe Aortic Stenosis in Cardiogenic Shock: Early Percutaneous Mechanical Circulatory Support or Emergent Transcatheter Aortic Valve Replacement?

Aortic stenosis (AS) affects an estimated 1.5 million patients in the United States, with 250,000 patients or more suffering severe, symptomatic aortic stenosis. A subset of these patients also have unrevascularized coronary artery disease and left ventricular dysfunction, representing an extreme risk population of AS patients. Cardiogenic shock (CS) complicates a small minority of AS presentations and/or patients referred for transcatheter aortic valve replacement (TAVR) but is responsible in these cases for a disproportionately high rate of morbidity and mortality. Indeed, CS results in a 4-fold increase in TAVR mortality, proportional to shock severity and largely independent of procedural complications. All patients undergoing TAVR should undergo an assessment of hemodynamics and vascular access as well as an estimation of risk for conduction system abnormalities, coronary occlusion, landing zone rupture, and stroke. In patients with pre-procedural CS or at a high risk of hemodynamic deterioration, preemptive or carefully planned, provisional use of mechanical circulatory support (MCS) helps ensure the best possible outcomes during TAVR

Cooperative Enterprise as an Antimonopoly Strategy

After decades of neglect, antitrust is once again a topic of public debate. Proponents of reviving antitrust have called for abandoning the narrow consumer welfare objective and embracing a broader set of objectives. One essential element that has been overlooked thus far is the ownership structure of the firm itself. The dominant model of investor-owned business and associated philosophy of shareholder wealth maximization exacerbate the pernicious effects of market power. In contrast, cooperative ownership models can mitigate the effects of monopoly and oligopoly, as well as advance the interests of consumers, workers, small business owners, and citizens. The promotion of fair competition among large firms should be paired with support for democratic cooperation within firms. Antitrust law has had a complicated history and relationship with cooperative enterprise. Corporations threatened by cooperatives have used the antitrust laws to frustrate the growth of these alternative businesses. To insulate cooperatives from the antitrust threat, Congress has enacted exemptions to protect cooperative entities, notably a general immunity for farm cooperatives in the 1922 Capper-Volstead Act. As part of an agenda to tame corporate monopoly, all three branches of the federal government and the states should revisit these ideas and seek to protect and enable the cooperative model across the economy. Although protections that farmers fought for a century ago may seem obsolete in an era of big-box retail and online platforms, matters of ownership design have at least as much relevance today and should be a part of the antimonopoly arsenal

Multiple Foci Drill-Down through Tuple and Attribute Polyarchies in Tabular Data.

Information analysis often involves decomposing data into sub-groups to allow for comparison and identification of relationships. Breakdown Visualization provides a mechanism to support this analysis through user guided drill-down of polyarchical metadata. This metadata describes multiple hierarchical structures for organizing tuple aggregation and table attributes. This structure is seen in sport statistics, financial data, organizational structures, and other fields. A spreadsheet format enables comparison of visualizations at each level of the hierarchy. Breakdown Visualization allows users to drill-down a single hierarchy then pivot into another hierarchy within the same view. We utilize a fix and move technique that allows users to select multiple foci for drill-down. We present an analysis scenario that demonstrates how Breakdown Visualization can be used to perform financial statement analysi

Structural phylogeny by profile extraction and multiple superimposition using electrostatic congruence as a discriminator

Phylogenetic analysis of proteins using multiple sequence alignment (MSA) assumes an underlying evolutionary relationship in these proteins which occasionally remains undetected due to considerable sequence divergence. Structural alignment programs have been developed to unravel such fuzzy relationships. However, none of these structure based methods have used electrostatic properties to discriminate between spatially equivalent residues. We present a methodology for MSA of a set of related proteins with known structures using electrostatic properties as an additional discriminator (STEEP). STEEP first extracts a profile, then generates a multiple structural superimposition providing a consolidated spatial framework for comparing residues and finally emits the MSA. Residues that are aligned differently by including or excluding electrostatic properties can be targeted by directed evolution experiments to transform the enzymatic properties of one protein into another. We have compared STEEP results to those obtained from a MSA program (ClustalW) and a structural alignment method (MUSTANG) for chymotrypsin serine proteases. Subsequently, we used PhyML to generate phylogenetic trees for the serine and metallo-β-lactamase superfamilies from the STEEP generated MSA, and corroborated the accepted relationships in these superfamilies. We have observed that STEEP acts as a functional classifier when electrostatic congruence is used as a discriminator, and thus identifies potential targets for directed evolution experiments. In summary, STEEP is unique among phylogenetic methods for its ability to use electrostatic congruence to specify mutations that might be the source of the functional divergence in a protein family. Based on our results, we also hypothesize that the active site and its close vicinity contains enough information to infer the correct phylogeny for related proteins

Hypersparse Traffic Matrix Construction using GraphBLAS on a DPU

Low-power small form factor data processing units (DPUs) enable offloading and acceleration of a broad range of networking and security services. DPUs have accelerated the transition to programmable networking by enabling the replacement of FPGAs/ASICs in a wide range of network oriented devices. The GraphBLAS sparse matrix graph open standard math library is well-suited for constructing anonymized hypersparse traffic matrices of network traffic which can enable a wide range of network analytics. This paper measures the performance of the GraphBLAS on an ARM based NVIDIA DPU (BlueField 2) and, to the best of our knowledge, represents the first reported GraphBLAS results on a DPU and/or ARM based system. Anonymized hypersparse traffic matrices were constructed at a rate of over 18 million packets per second

Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey

IntroductionThe classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited.MethodsThis prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1–3 days after, 2–4 weeks after, and 2–3 months after psilocybin use.ResultsA sample of 2,833 respondents completed all baseline assessments approximately 2 weeks before psilocybin use, 1,182 completed the 2–4 week post-use survey, and 657 completed the final follow-up survey 2–3 months after psilocybin use. Participants were primarily college-educated White men residing in the United States with a prior history of psychedelic use; mean age = 40 years. Participants primarily used dried psilocybin mushrooms (mean dose = 3.1 grams) for “self-exploration” purposes. Prospective longitudinal data collected before and after a planned psilocybin experience on average showed persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and reduced neuroticism and burnout after psilocybin use. However, a minority of participants (11% at 2–4 weeks and 7% at 2–3 months) reported persisting negative effects after psilocybin use (e.g., mood fluctuations, depressive symptoms).DiscussionResults from this study, the largest prospective survey of naturalistic psilocybin use to date, support the potential for psilocybin to produce lasting improvements in mental health symptoms and general wellbeing

Myeloablative vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era