"Let's Not Have the Perfect Be the Enemy of the Good": Social Impact Bonds, Randomized Controlled Trials, and the Valuation of Social Programs.

This article uses the case of "social impact bonds" (SIBs) to explore the role of social science methods in new markets in "social investment." Pioneered in the UK in 2010, SIBs use private capital to fund social programs with governments paying returns for successful outcomes. Central to the SIB model is the question of evaluation and the method to be used in determining program outcomes and investor returns.

Econometrics as evidence? Examining the 'causal' connections between financial speculation and commodities prices.

One of the lasting legacies of the financial crisis of 2008, and the legislative energies that followed from it, is the growing reliance on econometrics as part of the rulemaking process. Financial regulators are increasingly expected to rationalize proposed rules using available econometric techniques, and the courts have vacated several key rules emanating from Dodd-Frank on the grounds of alleged deficiencies in this evidentiary effort. The turn toward such econometric tools is seen as a significant constraint on and challenge to regulators as they endeavor to engage with such essential policy questions as the impact of financial speculation on food security.

A77 1726, the active metabolite of leflunomide, attenuates lupus nephritis by promoting the development of regulatory T cells and inhibiting IL-17-producing double negative T cells.

Lupus nephritis (LN) is a challenging problem that affects 50% of patients with systemic lupus erythematosus (SLE) without effective therapy. Here, we report that A77 1726, the active metabolite of leflunomide, effectively inhibits development of LN and attenuates the generalized autoimmune features. A77 1726 suppresses the expansion of double negative (DN) T cells, and inhibits T and B cell activation.

Inhibition of p70 S6 kinase (S6K1) activity by A77 1726 and its effect on cell proliferation and cell cycle progress.

Leflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid arthritis. It inhibits the activity of protein tyrosine kinases and dihydroorotate dehydrogenase, a rate-limiting enzyme in the pyrimidine nucleotide synthesis pathway. Here, we report that A77 1726, the active metabolite of leflunomide, inhibited the phosphorylation of ribosomal protein S6 and two other substrates of S6K1, insulin receptor substrate-1 and carbamoyl phosphate synthetase 2, in an A375 melanoma cell line.

Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection.

The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis.

Natural history of post-liver transplantation hepatitis C: A review of factors that may influence its course.

Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected.

Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression.

Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied.

Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab.

Vitamin A toxicity: when one a day doesn't keep the doctor away.

Vitamin A toxicity has been reported to cause severe liver disease and, occasionally, liver failure. Herein we present the case of a 60-year-old male with symptoms of muscle soreness, alopecia, nail dystrophy, and ascites. He continued to deteriorate with the development of refractory ascites, renal insufficiency, encephalopathy, and failure to thrive.

Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: the "hepatitis C 3" multi-institutional trial experience.

Context: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials.

Objective: To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the "Hepatitis C 3" trial.

Design: The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV.

Living donor liver transplantation for hepatitis C-related cirrhosis: no difference in histological recurrence when compared to deceased donor liver transplantation recipients.

The question of possible earlier and more aggressive recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT) remains unanswered. To address this issue we retrospectively reviewed virological, histological, and clinical data in 67 patients (52 DDLT and 15 LDLT) who underwent liver transplant for their HCV-related cirrhosis since April 2001. Our data indicate that there is no statistical difference between LDLT and DDLT groups in mean age, Child-Turcotte-Pugh score, model for end-stage liver disease score, and gender distribution.

Telepathy: maximizing resident exposure to surgical pathology decision making.

Background: General surgery residents are often not present for the critical intraoperative discussion between surgeon and pathologist regarding surgical pathology findings.

Methods: A prospective pilot study analyzed general surgery resident exposure to surgical pathology. Thereafter, an operating room was equipped to view frozen section images in real time and verbally communicate with the pathologist (TelePATHy).

Auto-Rejection of Renal Donor-Origin Metastatic Melanoma.

We report a case of metastatic malignant melanoma discovered in a living related donor shortly after renal transplant and subsequently diagnosed in the recipient. The recipient hepatic metastases were followed with serial computed tomography (CT) during regression/rejection of tumor after cessation of immunosuppression and allograft removal. Correlation made with serial liver mass biopsies.

Polyoma virus infection of renal allografts: relationships of the distribution of viral infection, tubulointerstitial inflammation, and fibrosis suggesting viral interstitial nephritis in untreated disease.

Whether polyoma virus (PV) infection of renal allografts induces an antiviral or antigraft immune reaction is unclear. By examination of the relationships of tubular PV to graft inflammation and scarring, this study sought histological evidence of viral interstitial nephritis in allograft biopsies with untreated PV infection and compared the inflammatory indices to controls with acute rejection (AR). Morphological features including viral cytopathic changes (VCCs) and modified Banff 97 histological indices were evaluated in sections of 28 diagnostic biopsies from a group of patients receiving prednisone, tacrolimus, and mycophenolate mofetil at constant dosage before biopsy.

Mechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV infection in rats.

Background: FK778 is a malononitrilamide, a class of immune suppressive compounds with antiviral features and experimental activity in chronic rejection, a potentially interesting combination for organ transplantation. The goal of this project was to study the tolerability, immune suppressive efficacy, and anti-cytomegalovirus (CMV) activity of FK778 and to assess the in vivo relevance of its previously described inhibition of de novo pyrimidine synthesis.

Methods: Heart transplants were performed in rats (Brown Norway [BN] to Lewis) and treated with varying doses of FK778 or leflunomide for 28 days.

Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: an open-label series.

Background: Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal. We aimed to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) and ribavirin (RIB) in the treatment of post-OLT HCV recurrence.

Methods: Thirty-seven patients with recurrent HCV after OLT were screened and began treatment.