ACCERT: Auckland's cancer cachexia evaluating resistance training study

Background: Cancer Cachexia (CC) is a common problem seen in many advanced malignancies including Non- Small-Cell Lung Cancer (NSCLC). In CC there is a significant loss of adipose tissue and skeletal muscle mass. Muscle wasting is the main cause of impaired function, leading to respiratory complications and fatigue. The optimal treatment for CC is the complete removal of the tumour; unfortunately with advanced NSCLC this is unachievable. The next best options are to increase nutritional intake to counteract weight loss, address the anorexia, inflammation, and metabolic alterations i.e. loss of body fat and the skeletal muscle wasting. This requires the need to utilise a multi-targeted approach to decrease the inflammation and to stimulate the skeletal anabolic pathways with the use of progressive resistance training (PRT). PRT has shown acceptability and benefits in other cancer populations. This study aims to identify a novel multi-targeted treatment regimen that will alleviate and/or stabilise CC weight loss. Methods: This is a randomised, open-label study to investigate whether 2 sessions each week of PRT followed by essential amino acids (EAA's) high in leucine, when administered in addition to Eicosapentaenoic Acid (EPA) and a Cox-2 inhibitor is acceptable to NSCLC cachectic patients for a period of 20 weeks (primary endpoint). Secondary endpoints include Lean Body Mass, MRI thigh skeletal muscle values, QoL and Fatigue questionnaires, serum pro-inflammatory cytokine profiles, and hand and leg strength. Safety data will also be collected. Outcome measures to power a future study will be determined from the trend in difference between the two groups. 21 patients are planned to be randomised in a 1:2 ratio Arm A EPA and Cox-2 inhibitor vs. Arm B EPA, Cox-2 inhibitor, PRT followed by EAA's. All patients are offered to continue with the study medications and/or PRT sessions on compassionate use. Main inclusion criteria include: histological proven NSCLC patients who have at least 5% weight loss and fulfil the following cachectic definition (Evans Clin Nut 2008 27). A guest patient was enrolled in May 2012, followed by study participants in June 201

Menus for Feeding Black Holes

Black holes are the ultimate prisons of the Universe, regions of spacetime where the enormous gravity prohibits matter or even light to escape to infinity. Yet, matter falling toward the black holes may shine spectacularly, generating the strongest source of radiation. These sources provide us with astrophysical laboratories of extreme physical conditions that cannot be realized on Earth. This chapter offers a review of the basic menus for feeding matter onto black holes and discusses their observational implications.Comment: 27 pages. Accepted for publication in Space Science Reviews. Also to appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

Utility of the Hebb–Williams maze paradigm for translational research in Fragile X syndrome: A direct comparison of mice and humans

To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb–Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focuse

Meta-analysis of data from animal studies:A practical guide

AbstractMeta-analyses of data from human studies are invaluable resources in the life sciences and the methods to conduct these are well documented. Similarly there are a number of benefits in conducting meta-analyses on data from animal studies; they can be used to inform clinical trial design, or to try and explain discrepancies between preclinical and clinical trial results. However there are inherit differences between animal and human studies and so applying the same techniques for the meta-analysis of preclinical data is not straightforward. For example preclinical studies are frequently small and there is often substantial heterogeneity between studies. This may have an impact on both the method of calculating an effect size and the method of pooling data. Here we describe a practical guide for the meta-analysis of data from animal studies including methods used to explore sources of heterogeneity

Expedition 369 methods

This chapter documents the procedures and methods used in the shipboard laboratories during International Ocean Discovery Program (IODP) Expedition 369. This introductory section in particular provides a rationale for the site locations and an overview of IODP depth conventions, curatorial procedures, and general core handling/analyses during Expedition 369. Subsequent sections describe specific laboratory procedures and instruments in more detail. This information only applies to shipboard work described in the Proceedings volume; methods used in shore-based analyses of Expedition 369 samples and/or data will be described in various scientific contributions in the open peer-reviewed literature and the Expedition Research Results chapters of this Proceedingsvolume

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele