Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

Mycosis fungoides (MF) and Sezary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin`s lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. J Clin Oncol 29:2598-2607. (C) 2011 by American Society of Clinical Oncology

Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as `benign cytochrome c oxidase deficiency myopathy` is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T > C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

The Alzheimer`s Association external quality control program for cerebrospinal fluid biomarkers

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer`s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer`s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. (C) 2011 The Alzheimer`s Association. All rights reserved.

Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative

Context: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods. Objectives: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. Design, Setting, and Participants: Crosssectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview. Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment. Results: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system. Conclusions: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.

A Randomized Clinical Trial to Examine Enhancing Cognitive-Behavioral Group Therapy for Obsessive-Compulsive Disorder with Motivational Interviewing and Thought Mapping

Background: Obsessive-compulsive disorder (OCD) is characterized by repeated and persistent attempts to control thoughts and actions with rituals. These rituals are used in order to prevent feared or personally distressing outcomes. Cognitive behavioral group therapy (CBGT) has been reported to be effective for treating OCD patients. However, about one-third (30%) of patients do not benefit from CBGT. Some of these patients do not show significant improvement and continue to use rituals following CBGT, partially because they fail to complete the exposure and ritual prevention (ERP) exercises. Consequently, it is important to motivate patients to fully engage in CBGT treatment and complete the ERP exercises. Aims: A randomized behavioral trial examined 12 weeks of manual directed CBGT, with the addition of individual sessions of Motivational Interviewing (MI) and Thought Mapping (TM), and compared treatment outcome to the effectiveness of CBGT group alone. Method: Subjects were randomized (n = 93) into a CBGT group or a CBGT group with MI+TM. Results: When the two groups were compared, both groups reduced OCD symptoms. However, symptom reduction and remission were significantly higher in the MI+TM CBGT group. Positive outcomes were also maintained, with additional symptom reduction at the 3-month follow-up for the MI TM CBGT group. Conclusions: Adding two individual sessions of MI and TM before CBGT successfully reduced OCD symptoms and was more effective than using CBGT group alone.

Rapid-cycling bipolar disorder: cross-national community study

Background The epidemiology of rapid-cycling bipolar disorder in the community is largely unknown. Aims To investigate the epidemiological characteristics of rapid cycling and non-rapid-cycling bipolar disorder in a large cross-national community sample. Method The Composite International Diagnostic interview (CIDI version 3.0) was used to examine the prevalence, severity, comorbidity, impairment, suicidality, sociodemographics, childhood adversity and treatment of rapid-cycling and non-rapid-cycling bipolar disorder in ten countries (n=54257). Results The 12-month prevalence of rapid-cycling bipolar disorder was 0.3%. Roughly a third and two-fifths of participants with lifetime and 12-month bipolar disorder respectively met criteria for rapid cycling. Compared with the non-rapid-cycling, rapid-cycling bipolar disorder was associated with younger age at onset, higher persistence, more severe depressive symptoms, greater impairment from depressive symptoms, more out-of-role days from mania/hypomania, more anxiety disorders and an increased likelihood of using health services. Associations regarding childhood, family and other sociodemographic correlates were less clear cut. Conclusions The community epidemiological profile of rapid-cycling bipolar disorder confirms most but not all current clinically based knowledge about the illness. Declaration of interest R.C.K. has been a consultant for GlaxoSmithKline Inc, Kaiser Permanente, Pfizer Inc, Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst, and has had research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc, Pfizer Inc and Sanofi-Avertis.

Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms

Familial hypertrophic cardiomyopathy (FHC) is frequently caused by cardiac myosin-binding protein C (cMyBP-C) gene mutations, which should result in C-terminal truncated mutants. However, truncated mutants were not detected in myocardial tissue of FHC patients and were rapidly degraded by the ubiquitin-proteasome system (UPS) after gene transfer in cardiac myocytes. Since the diversity and specificity of UPS regulation lie in E3 ubiquitin ligases, we investigated whether the muscle-specific E3 ligases atrogin-1 or muscle ring finger protein-1 (MuRF1) mediate degradation of truncated cMyBP-C. Human wild-type (WT) and truncated (M7t, resulting from a human mutation) cMyBP-C species were co-immunoprecipitated with atrogin-1 after adenoviral overexpression in cardiac myocytes, and WT-cMyBP-C was identified as an interaction partner of MuRF1 by yeast two-hybrid screens. Overexpression of atrogin-1 in cardiac myocytes decreased the protein level of M7t-cMyBP-C by 80% and left WT-cMyBP-C level unaffected. This was rescued by proteasome inhibition. In contrast, overexpression of MuRF1 in cardiac myocytes not only reduced the protein level of WT- and M7t-cMyBP-C by > 60%, but also the level of myosin heavy chains (MHCs) by > 40%, which were not rescued by proteasome inhibition. Both exogenous cMyBP-C and endogenous MHC mRNA levels were markedly reduced by MuRF1 overexpression. Similar to cardiac myocytes, MuRF1-overexpressing (TG) mice exhibited 40% lower levels of MHC mRNAs and proteins. Protein levels of cMyBP-C were 29% higher in MuRF1 knockout and 34% lower in TG than in WT, without a corresponding change in mRNA levels. These data suggest that atrogin-1 specifically targets truncated M7t-cMyBP-C, but not WT-cMyBP-C, for proteasomal degradation and that MuRF1 indirectly reduces cMyBP-C levels by regulating the transcription of MHC.

Economic constraints on public policy

Economics is commonly described as "the science of allocating scarce resources." By contrast, a popular description of politics is "the art of the possible." Both of these descriptions refer to the same central feature of human existence: our wants generally exceed our capacity to satisfy them. However, economic and political approaches to the problem of scarcity are quite different. [Extract from Introduction]

Exercise training accelerates the removal from plasma of LDL-like nanoemulsion in moderately hypercholesterolemic subjects

Objective: Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events. Methods: Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with 14C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24h after injection to determine the fractional clearance rate (FCR, in h-1) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period. Results: In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443 +/- 0.0126; 0.0602 +/- 0.0187, p=0.0187 and 0.0503 +/- 0.0203; 0.0686 +/- 0.0216, p=0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation. Conclusion: In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

A estrat??gia de sa??de da fam??lia

A Sa??de da Fam??lia ?? uma estrat??gia de reorienta????o do modelo assistencial, operacionalizada mediante a implanta????o de equipes multiprofissionais em unidades b??sicas de sa??de. Essas equipes s??o respons??veis pelo acompanhamento de um n??mero definido de fam??lias, localizadas em ??rea geogr??fica delimitada. As equipes atuam com a????es de promo????o da sa??de, preven????o, recupera????o, reabilita????o de doen??as e agravos mais frequentes, e na manuten????o da sa??de dessa comunidade. A responsabilidade pelo acompanhamento das fam??lias coloca para as equipes de sa??de da fam??lia a necessidade de ultrapassar os limites classicamente definidos para a aten????o b??sica no Brasil, especialmente no contexto do SUS. A implanta????o da estrat??gia de Sa??de da Fam??lia tem demonstrado significativa melhoria nos indicadores de sa??de do pa??s, em especial na amplia????o do acesso ?? sa??de da popula????o brasileira, tendo se mostrado tamb??m efetiva na redu????o das iniquidades, cumprindo seu papel de porta de entrada do SUS

Preg??o: uma nova modalidade de licita????o

Inseridos no contexto de log??stica globalizada e economia digital e, objetivando minimizar os efeitos burocratizantes das modalidades em uso, o Minist??rio do Planejamento, Or??amento e Gest??o, por interm??dio da Secretaria de Log??stica e Tecnologia da Informa????o/SLTI e, do seu Departamento de Log??stica e Servi??os Gerais/DLSG, gestor das compras e contrata????es do Governo Federal, respons??vel pela formula????o de diretrizes e pol??ticas p??blicas neste segmento, idealizou e direcionou esfor??os para a cria????o de uma nova modalidade de licita????o, que atendesse aos anseios mais emergentes do governo, dos fornecedores e da sociedade em geral. Assim, em 4 de maio de 2000, instituiu-se no ??mbito da Uni??o, nos termos do art. 37 da Constitui????o Federal, a modalidade de licita????o denominada ???Preg??o???, realizada inicialmente de forma presencial, direcionada ??s aquisi????es de bens e servi??os comuns

Gest??o de Pessoas: bases te??ricas e experi??ncias no setor p??blico

Embora haja extensa literatura dedicada ?? gest??o de pessoas nas empresas, poucas obras tomam como foco as especificidades desse tema na administra????o p??blica. Sistematizando reflex??es realizadas no decorrer da primeira edi????o do curso de Especializa????o em Gest??o de Pessoas no Servi??o P??blico, esta obra valoriza a articula????o entre o conhecimento acad??mico, trazido por professores de renomadas universidades brasileiras, e a experi??ncia dos servidores p??blicos, participantes do curso. Ao disseminar os aprendizados gerados, a publica????o busca ampliar o debate sobre os temas em refer??ncia e subsidiar o interc??mbio e a produ????o de conhecimentos inerentes ?? tem??tica no servi??o p??blico, considerando sua centralidade para a sustentabilidade dos programas de governo. Nos textos publicados, professores e alunos tratam de temas, conceitos e experi??ncias que hoje s??o desafios na gest??o de pessoas no setor p??blico. N??o h?? pretens??o de fazer abordagens conclusivas e, sim, trazer indaga????es

Comprasnet: o site da transpar??ncia das compras governamentais

O Site www.comprasnet.gov.br, utilizando recurso da Internet, est?? definindo novas estrat??gias para as Compras Governamentais. Entre as funcionalidades existentes, os usu??rios do governo, fornecedores e a sociedade contam com os seguintes servi??os: Legisla????o: trata dos assuntos legais pertinentes, Publica????es: voltado ??s not??cias de interesse comum entre os usu??rios; Servi??os de Livre Acesso: disponibiliza, entre outros, o SICAFWEB, Preg??o Eletr??nico, Consulta Licita????o; Servi??os por Assinatura: agrega valores para atender necessidades espec??ficas dos usu??rios cadastrados. Exemplo: Consulta Licita????es com acesso a itens e editais, Listas Preferenciais, etc. e, o SIASG que concentra F??rum de Discuss??o, Consultas Gerenciais, Homologa????o de Preg??o Eletr??nico, al??m dos diversos m??dulos que o comp??em

Matriz de aloca????o de recursos financeiros para as unidades acad??micas

A matriz de distribui????o de recursos para as unidades acad??micas promove a transpar??ncia em dois sentidos: por um lado ?? um instrumento que permite a parti????o de recursos de forma mais justa entre as unidades acad??micas da Universidade de Bras??lia; por outro lado, fornece informa????es sobre a destina????o dos recursos e em quais atividades estes foram aplicados

Pr??-equidade de g??nero: incorporando pol??ticas de a????o afirmativa no mundo do trabalho

A institui????o do Programa Pr??-equidade de G??nero ?? o reconhecimento p??blico da desigualdade de tratamento e de oportunidades, que ainda permanece entre mulheres e homens. A implementa????o ?? consolidada com a coloca????o em pr??tica dos planos de a????es firmados entre a Secretaria Especial de Pol??ticas para as Mulheres (SPM) e as organiza????es aderentes. A pesquisa explorat??ria teve como objetivo apresentar o programa e discuti-lo com base no modelo "policy cycle como aprendizado", de Silva e Melo (2000). Os resultados subsidiar??o pesquisa futura sobre a avalia????o do programa. Dentro da estrat??gia adotada, a coleta de dados ocorreu em documentos institucionais e dados bibliogr??ficos em mar??o de 2009, com o seguinte resultado: a avalia????o n??o trata de forma clara da efetividade e da sustentabilidade do programa. Este trabalho est?? dividido em seis partes: descri????o do m??todo utilizado; apresenta????o do Programa Pro-equidade de G??nero; avalia????o de suas duas primeiras edi????es; breve contextualiza????o das pol??ticas p??blicas no Brasil e o modelo "policy cicle como aprendizado"; rela????es entre o programa e o modelo; e considera????es finais.