Dream capitalism

John Tomasi’s Free Market Fairness represents an heroic attempt to bridge the gap between Rawlsian ‘high liberals’ and the advocates of classical liberalism/contemporary libertarianism. I argue that Tomasi’s project fails, above all because it cannot give a compelling account of contemporary (American) capitalism or of its capacity to deliver free market fairness

Chronic Mechanical Circulatory Support for Inotrope-Dependent Heart Failure Patients Who Are Not Transplant Candidates Results of the INTrEPID Trial

ObjectivesThis study evaluated the impact of left ventricular assist device (LVAD) support on survival and quality of life in inotrope-dependent heart failure patients ineligible for cardiac transplantation.BackgroundThe role for LVADs as a bridge to cardiac transplantation has been established, but data supporting their role as permanent therapy in nontransplant candidates are limited.MethodsThe INTrEPID (Investigation of Nontransplant-Eligible Patients Who Are Inotrope Dependent) trial was a prospective, nonrandomized clinical trial comparing LVAD with optimal medical therapy (OMT). Fifty-five patients with New York Heart Association functional class IV symptoms who failed weaning from inotropic support were offered a Novacor LVAD. Eighteen of these patients did not receive an LVAD owing to patient preference (n = 14) or unavailability of the device (n = 4) but consented to follow-up and constitute a contemporaneous control group.ResultsThe LVAD and OMT patients were well matched for demographic and disease severity measures, except OMT patients had a lower mean serum sodium (128 mg/dl vs. 134 mg/dl; p = 0.001) and a higher mean blood urea nitrogen concentration (59 vs. 40; p = 0.02). The LVAD-treated patients had superior survival rates at 6 months (46% vs. 22%; p = 0.03) and 12 months (27% vs. 11%; p = 0.02). Adverse event rates were higher in the OMT group. Eighty-five percent of the LVAD-treated patients had minimal or no heart failure symptoms. Five LVAD patients and 1 OMT patient improved sufficiently while on therapy to qualify for cardiac transplantation.ConclusionsInotrope-dependent heart failure patients who are ineligible for transplantation have a high short-term mortality rate and derive a significant survival advantage from “destination” mechanical circulatory support

Selection of patients for heart transplantationin the current era of heart failure therapy

AbstractObjectivesWe sought to assess the relationship between survival, peak exercise oxygen consumption (Vo2), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy.BackgroundBased on predicted survival, HF patients with peak Vo2<14 ml/min/kg or medium- to high-risk HFSS are currently considered eligible for heart transplantation. However, these criteria were developed before the widespread use of beta-blockers, spironolactone, and defibrillators—interventions known to improve the survival of HF patients.MethodsPeak Vo2and HFSS were assessed in 320 patients followed from 1994 to 1997 (past era) and in 187 patients followed from 1999 to 2001 (current era). Outcomes were compared between these two groups of patients and those who underwent heart transplantation from 1993 to 2000.ResultsSurvival in the past era was 78% at one year and 67% at two years, as compared with 88% and 79%, respectively, in the current era (both p < 0.01). One-year event-free survival (without urgent transplantation or left ventricular assist device) was improved in the current era, regardless of initial peak Vo2: 64% vs. 48% for peak Vo2<10 ml/min/kg (p = 0.09), 81% vs. 70% for 10 to 14 ml/min/kg (p = 0.05), and 93% vs. 82% for >14 ml/min/kg (p = 0.04). Of the patients with peak Vo2of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000.ConclusionsSurvival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation

Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A&gt;G), while the other variant (c.157+3G&gt;C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency

Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125 days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4(+) TEM cells were decreased in peripheral blood (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model

Joint IAEA/NNSA International Workshop Nuclear Forensics Methodologies for Practitioners 2013 Scenario Based Exercise – Version 4.0 Instructor’s Manual

[Participants will serve as border guards for Reimerland. They will be given brief instruction on the operation of hand‐held RadioIsotope DetectorS (RIDS) and be provided an intelligence briefing that tells them to be on the lookout for suspicious activity at their post. Their instruction will include directing suspicious vehicles to a location for secondary screening. If, after secondary screening, suspicions of a criminal act involving nuclear and or radioactive materials remain, participants have been instructed to request assistance from the NLEA, who will then setup and manage a radiological crime scene. Participants will watch a demonstration of two vehicles containing radioactive materials driving through and setting off a portal monitor. The first vehicle, a semi‐tractor trailer, sets off only a gamma alarm. After the driver provides a shipping manifest of fertilizer, participants, posing as border guards, are expected to waive this vehicle through inspection. The second vehicle, an SUV, set off both gamma and 2 neutron alarms. The alarming of the neutron monitor should prompt participants to set up a secondary inspection of the vehicle immediately. The driver of the vehicle indicates he is in legal possession of an industrial instrument containing an old 133Ba source that has decayed to a level no longer requiring official paperwork according to the IAEA and internationally accepted transportation regulations. Authorities have verified that the industrial source does fit the description of one that is sold commercially. However, upon setting up a secondary screening, participants will use hand‐held detectors to locate several other radioactive sources emanating from a black duffle bag in the rear of the vehicle (Figure 1). Hand held detectors detect the presence of 133Ba, and Pu. Upon questioning, the driver only commits to having the 133Ba industrial source and cannot account for the detection of neutrons within his vehicle. Since neutron alarms also sounded, participants should indicate that a neutron alarm would be inconsistent with a 133Ba source alone and should therefore conclude further investigation is warranted. This will prompt participants to call in a response team from the NLEA to set up a radiological crime scene around the vehicle in question. The response team is able to shoot a 3‐D X‐ray radiograph of the duffle bag without moving it to ensure it is rendered safe and moveable without disturbing the contents in the field (Figure 2). At this point, the duffle bag is entered into inventory as evidence and a chain of custody form is initiated. Swipes are taken from the outer bag to confirm there is no dispersible contamination. The bag and its contents are considered valuable for the investigation by the lead investigator. He determines the duffle bag is safe to transport to RRL for evidence inventory and analysis. The duffle bag and its contents are packaged and sent off to the RRL.

Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and alpha CD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed alpha CD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of aCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days

Physiological models of body composition and human obesity

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Non-existence of the Labor Demand/Supply Diagram, and Other Theorems of Institutional Economics

The most famous and influential diagram in modern (neoclassical) labor economics is the model of wage determination by supply and demand. Using concepts and ideas from institutional economics, I argue that the theory of a perfectly competitive labor market is logically contradictory and, hence, the demand/supply diagram cannot exist on the plane of pure theory. Four other fundamental theorems concerning labor markets are also derived, as are implications about the theoretical foundation of the field of industrial relations and the economic evaluation of labor and employment policy. In this article I accomplish four things of significance. The first is to demonstrate that the core diagram of neoclassical labor economics - the diagram of wage determination by demand and supply (D/S) - does not have logical coherence and thus has no existence on the plane of pure theory. The second is to deduce this conclusion using a core concept of institutional economics (i.e., transaction cost), thus demonstrating that the institutional approach to labor economics has theoretical explanatory power. The third is to use the transaction cost idea to also deduce four fundamental theorems concerning labor markets and wage determination. The fourth is to identify the core theoretical foundation of the field of industrial relations. This discussion also yields important implications for the economic evaluation of labor and employment policy, as well as interesting insights on the history of thought in labor economics. Working Paper 07-2