C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

Context In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. Objective To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. Design, Setting, and Participants A prospective phase 1/2 study of 23 patients with type 1 DM(aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. Main Outcome Measures C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA1c. Results During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P<.001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P=.001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P=.001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. Conclusion After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. Trial Registration clinicaltrials.gov Identifier: NCT00315133

Open-economy central banking: Explaining Australia's recommitment to central bank independence

Why do governments offload major instruments such as monetary policy to an independent central bank? This article answers this question in relation to the Australian case, a case which reflects wider global developments. The article challenges the methodology of quantitative approaches to explaining central bank independence and instead argues that a model of 'embedded statism' is the most fruitful explanatory approach.

Auditor independence and fee dependence

This study investigates whether fee dependence within the audit firms' offices jeopardises auditor independence. Fee dependence is examined at both the national audit firm level as well as the local office level and in a setting where public disclosure of fees is mandatory. We focus our tests on audit fee dependence and at the same time we control for the effects of non-audit service fee dependence post the 1989 mergers. We operationalise the exercise of independent judgement in auditing by the propensity to issue qualified audit opinions. If fee dependence affects auditors' independent judgement, then auditors are less likely to qualify the accounts. The study's results show that the level of auditor fee dependence does not affect auditor propensity to issue unqualified audit opinions. The findings remain robust to a number of sensitivity tests including the analyses controlling for the effects of non-audit service fee dependence and other settings in which there is heightened pressure on auditors to confront the effects of fee dependence on exercising independent audit judgement. (C) 2002 Elsevier Science B.V. All rights reserved.

Projeto visita virtual e videoconfer??ncia judicial

Este projeto nasceu de uma parceria entre o Departamento Penitenci??rio Nacional e a Defensoria P??blica da Uni??o (DPU). Apresenta duas importantes vertentes no ??mbito da execu????o penal. A primeira relaciona-se ao direito de manuten????o dos v??nculos afetivos dos presidi??rios, possibilitando o contato deles com seus familiares e amigos; e a segunda refere-se ?? realiza????o de audi??ncias judiciais por videoconfer??ncia. Desde a implanta????o do Projeto Visita Virtual e Videoconfer??ncia Judicial, em maio de 2010, 509 presos participaram da visita virtual e puderam conversar e visualizar seus familiares e amigos por meio desse recurso, conferindo, assim, um resultado extremamente satisfat??rio, visto que h?? pelo menos um ano n??o recebiam visitas. De mar??o de 2011 at?? julho deste ano, foram realizadas 160 videoconfer??ncias

Reformas pr??-mercado, rigidez constitucional e revis??o judicial: Brasil, Argentina e Uruguai em perspectiva comparada

Este artigo aborda a import??ncia da distribui????o de poderes de agenda e de veto dos cidad??os e dos Poderes Executivo, Legislativo e Judici??rio para viabilizar a implementa????o de reformas pr??-mercado no Brasil, na Argentina e no Uruguai em perspectiva comparada. Nesse sentido, o artigo aborda os temas da flexibilidade constitucional, da din??mica de forma????o das leis e da presen??a ou aus??ncia de revis??o judicial. A hip??tese subjacente a este artigo ?? a de que quanto mais r??gida a Constitui????o ??? vari??vel que envolve o poder de agenda e de veto dos cidad??os, do Executivo, do Legislativo e do Judici??rio ??? mais bem desenhado deve ser o jogo pol??tico para a viabiliza????o de implementa????o das reformas. Para exemplificar este artigo, foram analisadas as reformas previdenci??rias implantadas nos pa??ses em estudo.