Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples

In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research.     

Estimating maize production in Kenya using NDVI: Some statistical considerations

A regression model approach using a normalized difference vegetation index (NDVI) has the potential for estimating crop production in East Africa. However, before production estimation can become a reality, the underlying model assumptions and statistical nature of the sample data (NDVI and crop production) must be examined rigorously. Annual maize production statistics from 1982-90 for 36 agricultural districts within Kenya were used as the dependent variable; median area NDVI (independent variable) values from each agricultural district and year were extracted from the annual maximum NDVI data set. The input data and the statistical association of NDVI with maize production for Kenya were tested systematically for the following items: (1) homogeneity of the data when pooling the sample, (2) gross data errors and influence points, (3) serial (time) correlation, (4) spatial autocorrelation and (5) stability of the regression coefficients. The results of using a simple regression model with NDVI as the only independent variable are encouraging (r 0.75, p 0.05) and illustrate that NDVI can be a responsive indicator of maize production, especially in areas of high NDVI spatial variability, which coincide with areas of production variability in Kenya.     

Individual differences in drivers’ cognitive processing of road safety messages

Using Gray and McNaughton's (2000) revised reinforcement sensitivity theory (r-RST), we examined the influence of personality on processing of words presented in gain-framed and loss-framed anti-speeding messages and how the processing biases associated with personality influenced message acceptance. The r-RST predicts that the nervous system regulates personality and that behaviour is dependent upon the activation of the behavioural activation system (BAS), activated by reward cues and the fight-flight-freeze system (FFFS), activated by punishment cues. According to r-RST, individuals differ in the sensitivities of their BAS and FFFS (i.e., weak to strong), which in turn leads to stable patterns of behaviour in the presence of rewards and punishments, respectively. It was hypothesised that individual differences in personality (i.e., strength of the BAS and the FFFS) would influence the degree of both message processing (as measured by reaction time to previously viewed message words) and message acceptance (measured three ways by perceived message effectiveness, behavioural intentions, and attitudes). Specifically, it was anticipated that, individuals with a stronger BAS would process the words presented in the gain-frame messages faster than those with a weaker BAS and individuals with a stronger FFFS would process the words presented in the loss-frame messages faster than those with a weaker FFFS. Further, it was expected that greater processing (faster reaction times) would be associated with greater acceptance for that message. Driver licence holding students (N = 108) were recruited to view one of four anti-speeding messages (i.e., social gain-frame, social loss-frame, physical gain-frame, and physical loss-frame). A computerised lexical decision task assessed participants’ subsequent reaction times to message words, as an indicator of the extent of processing of the previously viewed message. Self-report measures assessed personality and the three message acceptance measures. As predicted, the degree of initial processing of the content of the social gain-framed message mediated the relationship between the reward sensitive trait and message effectiveness. Initial processing of the physical loss-framed message partially mediated the relationship between the punishment sensitive trait and both message effectiveness and behavioural intention ratings. These results show that reward sensitivity and punishment sensitivity traits influence cognitive processing of gain-framed and loss-framed message content, respectively, and subsequently, message effectiveness and behavioural intention ratings. Specifically, a range of road safety messages (i.e., gain-frame and loss-frame messages) could be designed which align with the processing biases associated with personality and which would target those individuals who are sensitive to rewards and those who are sensitive to punishments.     

Contemporary challenges of soot build-up in IC engine and their tribological implications

Confronted with the contemporary challenges of maximising energy efficiency with minimal impact on the environment, the automotive industry has developed various technologies to tackle them. Most of these technologies, however, have wider implications on the tribological performance of the automotive engines due to resultant soot build-up. This paper reviews the effects that attempts by stakeholders to satisfy requirements for reduced fuel consumption, reduced emissions and extended service intervals have had on increasing soot levels to an extent that can lead to engine component failure. Three areas have been identified that have either not been explored or not widely explored in the study of automotive soot namely: numerical simulation and modelling of soot wear, soot effects on wear of actual engine components and the wear and friction performance of non-metallic materials used in internal combustion engines. A paper-grading system is also utilised to present an overview of how sooty oil-related research covers various areas.     

“Thank heavens for the lease”: histories of shared ownership

Drawing on and developing Kingdon’s multiple streams analysis, this article examines the development of one aspect of the UK’s low cost home ownership programme: shared ownership. We demonstrate how key human and non-human policy entrepreneurs were able to set the agenda from 1973–1983 in favour of shared ownership; they neutralized the alternatives, while retaining some of their instruments; and solved a number of early problems by bringing key players into the programme. Our data-sets include a range of archival material and elite interviews. The policy entrepreneurs included John Stanley (who was the housing minister in the First Thatcher government), the National Federation of Housing Associations, and the Building Societies Association. Our development of the multiple streams analysis is to argue that documents, including the lease, act as policy entrepreneurs in their own right. The lease was central to the development of shared ownership and its transformation into a model lease enrolled other organizations, most critically the building societies.     

Understanding the Friction Mechanisms Between the Human Finger and Flat Contacting Surfaces in Moist Conditions

Human hands sweat in different circumstances and the presence of sweat can alter the friction between the hand and contacting surface. It is, therefore, important to understand how hand moisture varies between people, during different activities and the effect of this on friction. In this study, a survey of fingertip moisture was done. Friction tests were then carried out to investigate the effect of moisture. Moisture was added to the surface of the finger, the finger was soaked in water, and water was added to the counter-surface; the friction of the contact was then measured. It was found that the friction increased, up until a certain level of moisture and then decreased. The increase in friction has previously been explained by viscous shearing, water absorption and capillary adhesion. The results from the experiments enabled the mechanisms to be investigated analytically. This study found that water absorption is the principle mechanism responsible for the increase in friction, followed by capillary adhesion, although it was not conclusively proved that this contributes significantly. Both these mechanisms increase friction by increasing the area of contact and therefore adhesion. Viscous shearing in the liquid bridges has negligible effect. There are, however, many limitations in the modelling that need further exploration.     

Transparent ceramics for high-energy laser systems

We demonstrate that transparent magnesium aluminate spinel ceramic possesses excellent thermo-optical properties, a record low absorption loss of 6 ppm/cm, and superior ruggedness which position it as a prime candidate for an exit window aperture for high energy laser systems, especially in hostile environments. We also demonstrate lasing with an efficiency of about 45% in transparent Yb³⁺:Y₂O₃ ceramic made by hot pressing high purity submicron co-precipitated powder. This paves the way forward for high power solid state lasers exploiting hosts with higher thermal conductivity than YAG.     

In Situ Characterization of Lattice Structure Evolution during Phase Transformation of Zr‐2.5Nb

The α–β phase transformation behavior of Zr‐2.5Nb (in mass%) has been characterized in real time during an in situ neutron diffraction experiment. The Zr‐2.5Nb material in the current study consists, at room temperature, of α‐Zr phase (hcp) and two β phases (bcc), a Nb rich β‐Nb phase and retained, Zr rich, β‐Zr(Nb) phase. It is suggested that this is related to a quench off the equilibrium solubility of Nb atoms in the Zr bcc unit cells. Vegard's law combined with thermal expansion is applied to calculate the composition of the β‐phase, which is compared with the phase diagram, revealing the system's kinetic behavior for approaching equilibrium.     

Review of high temperature thermochemical properties and application in phase-field modelling of incipient melting in defective fuel

In a defective fuel element, fuel oxidation may occur that may affect the thermal performance of the fuel element thereby increasing the potential for centreline melting. A review of UO_2+x material properties is presented, and methods of extrapolation to melting conditions are, where necessary, recommended based on mechanistic considerations and self-consistency among the properties. These properties are implemented in a phase-field model derived through the theory of irreversible processes to simulate coupled heat and mass transport in the presence of a dynamic, non-congruent phase change. Simulation results are presented for centreline melting in operational, defective nuclear fuel showing that centreline melting is a self-regulating process.