Indexing disease progression at study entry with individuals at‐risk for Huntington disease

The identification of clinical and biological markers of disease in persons at risk for Huntington disease (HD) has increased in efforts to better quantify and characterize the epoch of prodrome prior to clinical diagnosis. Such efforts are critical in the design and implementation of clinical trials for HD so that interventions can occur at a time most likely to increase neuronal survival and maximize daily functioning. A prime consideration in the examination of prodromal individuals is their proximity to diagnosis. It is necessary to quantify proximity so that individual differences in key marker variables can be properly interpreted. We take a data‐driven approach to develop an index that can be viewed as a proxy for time to HD diagnosis known as the CAG‐Age Product Scaled or CAP_S. CAP_S is an observed utility variable computed for all genetically at‐risk individuals based on age at study entry and CAG repeat length. Results of a longitudinal receiver operating characteristic (ROC) analysis showed that CAP_S had a relatively strong ability to predict individuals who became diagnosed, especially in the first 2 years. Bootstrap validation provided evidence that CAP_S computed on a new sample from the same population could have similar discriminatory power. Cutoffs for the empirical CAP_S distribution can be used to create a classification for mutation‐positive individuals (Low–Med–High), which is, useful for comparison with the naturally occurring mutation‐negative Control group. The classification is an improvement over the one currently in use as it is based on observed data rather than model‐based estimated values. © 2011 Wiley‐Liss, Inc.     

A principal components approach to parent-to-newborn body composition associations in South India

Background  

Size at birth is influenced by environmental factors, like maternal nutrition and parity, and by genes. Birth weight is a composite measure, encompassing bone, fat and lean mass. These may have different determinants. The main purpose of this paper was to use anthropometry and principal components analysis (PCA) to describe maternal and newborn body composition, and associations between them, in an Indian population. We also compared maternal and paternal measurements (body mass index (BMI) and height) as predictors of newborn body composition.     

The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.     

Psychometric Properties of a Hurricane Coping Self-Efficacy Measure

This brief report describes the psychometric properties of an instrument designed to measure Hurricane Coping Self-Efficacy (HCSE). Survivors of Hurricane Andrew (n = 165) and Hurricane Opal (n = 63) completed the HCSE and assessments of optimism, social support, distress, and resource loss. Principal components factor analyses revealed a unidimensional structure for the HCSE. Internal consistency of the HCSE was strong. In both samples, HCSE was positively associated with optimism and social support, but negatively associated with general psychological distress, trauma related distress, and resource loss. Finally, hierarchical regression analyses demonstrated that the HCSE explained a significant amount of experimental variance for intrusive thoughts and avoidance after controlling for social support, lost resources, and optimism.     

Induction of Chimerism in Rhesus Macaques through Stem Cell Transplant and Costimulation Blockade-Based Immunosuppression

A strategy for producing high-level hematopoietic chimerism after non-myeloablative conditioning has been established in the rhesus macaque. This strategy relies on hematopoietic stem cell transplantation after induction with a non-myeloablative dose of busulfan and blockade of the IL2-receptor in the setting of mTOR inhibition with sirolimus and combined CD28/CD154 costimulation blockade. Hematopoietic stem cells derived from bone marrow and leukopheresis products both were found to be successful in inducing high-level chimerism. Mean peripheral blood peak donor chimerism was 81% with a median chimerism duration of 145 days. Additional immune modulation strategies, such as pre-transplant CD8 depletion, donor-specific transfusion, recipient thymectomy or peritransplant deoxyspergualin treatment did not improve the level or durability of chimerism. Recipient immunologic assessment suggested that chimerism occurred amidst donor-specific down-regulation of alloreactive T cells, and the reappearance of vigorous T-mediated alloreactivity accompanied rejection of the transplants. Furthermore, viral reactivation constituted a significant transplant-related toxicity and may have negatively impacted the ability to achieve indefinite survival of transplanted stem cells. Nevertheless, this chimerism-induction regimen induced amongst the longest-lived stem cell chimerism reported to date for non-human primates and thus represents a platform upon which to evaluate emerging tolerance-induction strategies.