News from the BSC No. 8

Abstract

In the 8th and following issues of News from the Biological Stain Commission (BSC), under the heading of Regulatory affairs, the BSC's International Affairs Committee will present information from a meeting held in Ghent, Belgium on 15–18 June 2009 concerning the progress achieved by the International Standards Organization Committee ISO/TC 212 Clinical Laboratory Testing and in Vitro Diagnostic Test Systems since the last meeting held in Vancouver, Canada in 2008. A note on the meaning and significance of E numbers found on the labels of foodstuffs and beverages sold for human consumption concludes this edition of News from the Biological Stain Commission.     

Proteomics in translational cancer research: biomarker discovery for clinical applications

This special focus issue of Expert Review of Proteomics invites key opinion leaders to report their recent findings and views on the important topic of translating potential proteomic biomarkers to clinically useful, regulator-approved biomarkers: a challenging journey. The issue also highlights the difficulties associated with and the way forward in the discovery of proteomic cancer biomarkers for clinical applications, as well as presenting recent original research in the field.     

Lab-Scale Treatability Tests for the Thermal Desorption of Hydrocarbon-Contaminated Soils

Within an integrated management plan for contaminated site remediation at a given territorial scale, the performance of treatability tests could be useful and/or expressly requested by the control authority on a site-specific basis to evaluate the overall feasibility of a given remedial option. The thermal desorption process appears to be a favorable treatment technology for organic contaminants. In this context, a particular lab-scale, indirectly heated desorber for treatability tests was originally developed and first applied to natural soils with different textures (silty sand, loam, silt clay, and clayey silt) that were “ad hoc” highly contaminated with diesel oil at various desorption process conditions (heating temperature in the range of 300–390°C, and reactor retention time in the range of 40–120 min). The Italian soil threshold level for heavy hydrocarbons (C > 12) of 50 mg kg^?1 (dry matter) was assumed to be the successful goal of the treatability studies. In addition to the individuation of the favorable desorption process conditions for each soil, also in terms of a composite evaluation of heating temperature and retention time, the comparative experimental results provided useful indications of the possible influence of soil texture, the reduction of initial soil organic matter, and the evaluation of kinetic rate constants.     

32k Da protein improve ovariectomy-induced bone loss in rats

The objective of the present study was to systematically explore the effects of 32K Da protein (32KP) on postmenopausal osteoporosis. Eighty 3-mo-old female Sprague-Dawley rats were employed and randomly divided into one sham-operated group (SHAM) and five ovariectomy (OVX) subgroups as OVX (control), OVX with 17-ethinylestradiol (E2, 25 g/kg/day), OVX with 32KP of graded doses (50, 50, or 150 mg/kg/day). 32KP or E2 diet was fed on week 4 after operation, for 16 weeks. Bone mass, bone turnover and strength were evaluated by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test, respectively. Femur marrow cavity was observed by light microscopy via hematoxylin-eosin staining. It is observed that different dosage treatment of 32KP increased the body weight and prevented the loss of bone mass induced by OVX. The prevention effect against bone loss was presumably due to the altering of the rate of bone remodeling. The bone mineral density and bone calcium content in OVX rats were lower than that in the control group, suggesting that 32KP was able to prevent significant bone loss. In addition, the data from three point bending test and femur sections showed that 32KP treatment enhanced bone strength and reduced the marrow cavity of the femur in OVX rats. In the serum and urine assay, 32KP decreased urinary deoxypyridinoline and calcium concentrations; however, serum alkaline phosphatase activities were not inhibited. It suggested that amelioration of bone loss was changed via inhibition of bone reabsorption. Our findings indicated that 32KP might be a potential alternative drug for the prevention and treatment of postmenopausal osteoporosis.     

Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection: Methods,simulation model and their implementation in R

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development programmes of new drugs, for example, in terms of sample size and/or development time. It is well acknowledged that adaptive designs are more involved from a logistical perspective and require more upfront planning, often in the form of extensive simulation studies, than conventional approaches. Here, we present a framework for adaptive treatment and subgroup selection using the same notation, which links the somewhat disparate literature on treatment selection on one side and on subgroup selection on the other. Furthermore, we introduce a flexible and efficient simulation model that serves both designs. As primary endpoints often take a long time to observe, interim analyses are frequently informed by early outcomes. Therefore, all methods presented accommodate interim analyses informed by either the primary outcome or an early outcome. The R package asd , previously developed to simulate designs with treatment selection, was extended to include subgroup selection (so-called adaptive enrichment designs). Here, we describe the functionality of the R package asd and use it to present some worked-up examples motivated by clinical trials in chronic obstructive pulmonary disease and oncology. The examples both illustrate various features of the R package and provide insights into the operating characteristics of adaptive seamless studies.     

Randomization inference with general interference and censoring

Interference occurs between individuals when the treatment (or exposure) of one individual affects the outcome of another individual. Previous work on causal inference methods in the presence of interference has focused on the setting where it is a priori assumed that there is “partial interference,” in the sense that individuals can be partitioned into groups wherein there is no interference between individuals in different groups. Bowers et al. (2012, Political Anal, 21, 97–124) and Bowers et al. (2016, Political Anal, 24, 395–403) consider randomization-based inferential methods that allow for more general interference structures in the context of randomized experiments. In this paper, extensions of Bowers et al. that allow for failure time outcomes subject to right censoring are proposed. Permitting right-censored outcomes is challenging because standard randomization-based tests of the null hypothesis of no treatment effect assume that whether an individual is censored does not depend on treatment. The proposed extension of Bowers et al. to allow for censoring entails adapting the method of Wang et al. (2010, Biostatistics, 11, 676–692) for two-sample survival comparisons in the presence of unequal censoring. The methods are examined via simulation studies and utilized to assess the effects of cholera vaccination in an individually randomized trial of 73 000 children and women in Matlab, Bangladesh.     

Jumping and gliding rodents: Mitogenomic affinities of Pedetidae and Anomaluridae deduced from an RNA-Seq approach

An RNA-Seq strategy was used to obtain the complete set of protein-coding mitochondrial genes from two rodent taxa. Thanks to the next generation sequencing (NGS) 454 approach, we determined the complete mitochondrial DNA genome from Graphiurus kelleni (Mammalia: Rodentia: Gliridae) and partial mitogenome from Pedetes capensis (Pedetidae), and compared them with published rodent and outgroup mitogenomes. We finished the mitogenome sequencing by a series of amplicons using conserved PCR primers to fill the gaps corresponding to tRNA, rRNA and control regions. Phylogenetic analyses of the mitogenomes suggest a well-supported rodent phylogeny in agreement with nuclear gene trees. Pedetes groups with Anomalurus into the clade Anomaluromorpha, while Graphiurus branches within the squirrel-related clade. Moreover, Pedetes + Anomalurus branch with Castor into the mouse-related clade. Our study demonstrates the utility of NGS for obtaining new mitochondrial genomes as well as the importance of choosing adequate models of sequence evolution to infer the phylogeny of rodents.     

On the Application of Widom's Test Particle Method to Homogeneous and Inhomogeneous Fluids

Abstract

Chemical potentials of a homogeneous and an inhomogeneous Lennard-Jones fluid have been determined by molecular dynamics simulations on the vector computer CYBER 205 by applying essentially the fictitious test particle method of Widom. For the homogeneous fluid we find, contrary to the previous result of Guillot and Guissani, that the simulated chemical potential is independent of the particle number. The crucial point, however, is a sufficiently large cut-off radius in the evaluation of the Boltzmann factor. Comparing with our WCA-type perturbation theory, we get agreement in the chemical potentials within 0.1 kT up to the density n[sgrave]³ = 0.80 and a difference of 0.2 kT at n[sgrave]³ = 0.85. For the inhomogeneous case we consider a fluid in a cylindrical pore and integrate Widom's equation over a certain probe volume as suggested earlier by us. Chemical potentials are then calculated independently in five different probe volumes, which are cylindrical shells. The results agree well from the second to the fourth shell. Inaccuracies in the innermost cylinder can be easily explained by bad statistics. In the shell close to the wall the extremely high local density is responsible for the inaccuracies. Extending the probe volume over all cylindrical shells besides the one closest to the wall is thought to yield rather reliable results for the chemical potential. As a by-product of the simulations we also obtained diffusion coefficients, which are given in an appendix.