Unit of analysis issues in laboratory-based research

Many studies in the biomedical research literature report analyses that fail to recognise important data dependencies from multilevel or complex experimental designs. Statistical inferences resulting from such analyses are unlikely to be valid and are often potentially highly misleading. Failure to recognise this as a problem is often referred to in the statistical literature as a unit of analysis (UoA) issue. Here, by analysing two example datasets in a simulation study, we demonstrate the impact of UoA issues on study efficiency and estimation bias, and highlight where errors in analysis can occur. We also provide code (written in R) as a resource to help researchers undertake their own statistical analyses

A review of the principles of turbidity measurement

Turbidity of water due to the presence of suspended sediment is measured and interpreted in a variety of ways, which can lead to the misinterpretation of data. This paper re-examines the physics of light scattering in water, and exposes the extent to which the reporting of turbidity data is inconsistent. It is proposed that the cause of this inconsistency is the fact that the accepted turbidity standards USEPA Method 180.1, ISO 7027 and GLI Method 2 are mutually inconsistent, as these standards give rise to a large number of measurement units that are not based on the optical properties of light absorption and scattering by suspensions in water, but by the arbitrary definition of the degree of turbidity being due to a concentration of formazin or other similar polymer-based calibration standard. It is then proposed that all turbidity-measuring devices should be calibrated with precise optical attenuators such as neutral density filters. Such calibration would allow for the definition of a beam attenuation coefficient for every turbidity-measuring instrument which would be cross-comparable with any other instrument calibrated in the same way. The units for turbidity measurements should be based on attenuation and reported as dB m−1. It is also proposed that a new standard should be drafted according to this attenuation-based method, and this new standard should also define the nomenclature for reporting data collected at any specific scattering angle in terms of an attenuation in dB m−1. The importance of multi-parameter turbidity measurements for the improvement of the quality of turbidity data and the application of parameter-rich data sets to new methods of sediment characterization are discussed. It is suggested that more research into multi-parameter turbidity measurements is needed, as these new methods will facilitate an increase in parity between turbidity and suspended sediment concentration, a relationship that is subjective

Skull morphology diverges between urban and rural populations of red foxes mirroring patterns of domestication and macroevolution

Human activity is drastically altering the habitat use of natural populations. This has been documented as a driver of phenotypic divergence in a number of wild animal populations. Here, we show that urban and rural populations of red foxes (Vulpes vulpes) from London and surrounding boroughs are divergent in skull traits. These changes are primarily found to be involved with snout length, with urban individuals tending to have shorter and wider muzzles relative to rural individuals, smaller braincases and reduced sexual dimorphism. Changes were widespread and related to muscle attachment sites and thus are likely driven by differing biomechanical demands of feeding or cognition between habitats. Through extensive sampling of the genus Vulpes, we found no support for phylogenetic effects on skull morphology, but patterns of divergence found between urban and rural habitats in V. vulpes quantitatively aligned with macroevolutionary divergence between species. The patterns of skull divergence between urban and rural habitats matched the description of morphological changes that can occur during domestication. Specifically, urban populations of foxes show variation consistent with ‘domestication syndrome’. Therefore, we suggest that occurrences of phenotypic divergence in relation to human activity, while interesting themselves, also have the potential to inform us of the conditions and mechanisms that could initiate domestication. Finally, this also suggests that patterns of domestication may be developmentally biased towards larger patterns of interspecific divergence

Sticky stuff : redefining bedform prediction in modern and ancient environments

This work was funded by the UK Natural Environment Research Council (NERC) under the COHBED project (NE/1027223/1). Paterson was funded by the Marine Alliance for Science and Technology for Scotland (MASTS).The dimensions and dynamics of subaqueous bedforms are well known for cohesionless sediments. However, the effect of physical cohesion imparted by cohesive clay within mixed sand-mud substrates has not been examined, despite its recognized influence on sediment stability. Here we present a series of controlled laboratory experiments to establish the influence of substrate clay content on subaqueous bedform dynamics within mixtures of sand and clay exposed to unidirectional flow. The results show that bedform dimensions and steepness decrease linearly with clay content, and comparison with existing predictors of bedform dimensions, established within cohesionless sediments, reveals significant over-prediction of bedform size for all but the lowermost clay contents examined. The profound effect substrate clay content has on bedform dimensions has a number of important implications for interpretation in a range of modern and ancient environments, including reduced roughness and bedform heights in estuarine systems and the often cited lack of large dune cross-sets in turbidites. The results therefore offer a step change in our understanding of bedform formation and dynamics in these, and many other, sedimentary environments.Publisher PDFPeer reviewe

On the formation of sand ramps: A case study from the Mojave Desert

Sand ramps are dune-scale sedimentary accumulations found at mountain fronts and consist of a combination of aeolian sands and the deposits of other geomorphological processes associated with hillslope and fluvial activity. Their complexity and their construction by wind, water and mass movement means that sand ramps potentially hold a very rich store of palaeoenvironmental information. However, before this potential can be realised a full understanding of their formation is necessary. This paper aims to provide a better understanding of the principal factors influencing the development of sand ramps. It reviews the stratigraphic, chronometric and sedimentological evidence relating to the past development of sand ramps, focussing particularly on Soldier Mountain sand ramp in the Mojave Desert, as well as using observations of the modern movement of slope material to elucidate the formation of stone horizons within sand ramps. Findings show that sand ramps cannot easily be interpreted in terms of a simple model of fluctuating palaeoenvironmental phases from aeolian dominated to soil/fluvial dominated episodes. They accumulate quickly (perhaps in < 5 ka), probably in a single phase before becoming relict. Based on the evidence from Soldier Mountain, they appear strongly controlled by a ‘window of opportunity’ when sediment supply is plentiful and cease to develop when this sediment supply diminishes and/or the accommodation space is filled up. Contemporary observations of stone movement both on rock and sandy sloping surfaces in the Mojave region indicate movement rates in the order of 0.6 and 11 mm yr− 1, which is insufficiently fast to explain how stone horizons could have been moved across and been incorporated into sand ramps on multiple occasions. Stone horizons found within the aeolian sediments lack evidence for soil development and are interpreted as very short-term events in which small streams moved and splayed discontinuous stone horizons across the sand ramp surface before aeolian deposition resumed. Surface stone horizons may form by creep from mountain slope sources across sand ramps but require enhanced speed compared to measured rates of runoff creep. We propose the mechanism of fluvio-aeolian creep. Our study suggests that current models of alternating aeolian and colluvial deposition within sand ramps, their palaeoenvironmental significance and indeed how sand ramps are distinguished from other dune forms require amendment

A pulsating white dwarf in an eclipsing binary

White dwarfs are the burnt-out cores of Sun-like stars and are the fate of 97 per cent of the stars in our Galaxy. The internal structure and composition of white dwarfs are hidden by their high gravities, which causes all elements apart from the lightest ones to settle out of their atmospheres. The most direct method of probing the inner structure of stars and white dwarfs in detail is via asteroseismology. Here we present a pulsating white dwarf in an eclipsing binary system, enabling us to place extremely precise constraints on the mass and radius of the white dwarf from the lightcurve, independent of the pulsations. This 0.325-solar-mass white dwarf—one member of the SDSS J115219.99+024814.4 system—will serve as a powerful benchmark with which to constrain empirically the core composition of low-mass stellar remnants and to investigate the effects of close binary evolution on the internal structure of white dwarfs

Cytocompatibility, degradation, mechanical property retention and ion release profiles for phosphate glass fibre reinforced composite rods

Fibre reinforced composites have recently received much attention as potential bone fracture fixation applications. Bioresorbable composites based on poly lactic acid (PLA) and phosphate based glass fibre were investigated according to ion release, degradation, biocompatibility and mechanical retention profiles. The phosphate based glass fibres used in this study had the composition of 40P2O5-24MgO-16CaO-16Na2O-4Fe2O3 in mol% (P40). The degradation and ion release profiles for the composites showed similar trends with the amount of sodium and orthophosphate ions released being greater than the other cations and anions investigated. This was attributed to low Dietzal's field strength for the Na(+) in comparison with Mg(2+) and Ca(2+) and breakdown of longer chain polyphosphates into orthophosphate ions. P40 composites exhibited good biocompatibility to human mesenchymal stem cells (MSCs), which was suggested to be due to the low degradation rate of P40 fibres. After 63 days immersion in PBS at 37 °C, the P40 composite rods lost ~1.1% of mass. The wet flexural, shear and compressive strengths for P40 UD rods were ~70%, ~80% and ~50% of their initial dry values after 3 days of degradation, whereas the flexural modulus, shear and compressive strengths were ~70%, ~80%, and ~65% respectively. Subsequently, the mechanical properties remained stable for the duration of the study at 63 days. The initial decrease in mechanical properties was attributed to a combination of the plasticisation effect of water and degradation of the fibre-matrix interface, with the subsequent linear behaviour being attributed to the chemical durability of P40 fibres. P40 composite rods showed low degradation and ion release rates, good biocompatibility and maintained mechanical properties similar to cortical bone for the duration of the study. Therefore, P40 composite rods have huge potential as resorbable intramedullary nails or rods

Mid-crustal deformation of the Annapurna-Dhaulagiri Himalaya, central Nepal: An atypical example of channel flow during the Himalayan orogeny

The channel-flow model for the Greater Himalayan Sequence (GHS) of the Himalayan orogen involves a partially molten, rheologically weak, mid-crustal layer “flowing” southward relative to the upper and lower crust during late Oligocene–Miocene. Flow was driven by topographic overburden, underthrusting, and focused erosion. We present new structural and thermobarometric analyses from the GHS in the Annapurna-Dhaulagiri Hima­laya, central Nepal; these data suggest that during exhumation, the GHS cooled, strengthened, and transformed from a weak “active channel” to a strong “channel plug” at greater depths than elsewhere in the Himalaya. After strengthening, continued convergence resulted in localized top-southwest (top-SW) shortening on the South Tibetan detachment system (STDS). The GHS in the Annapurna-Dhaulagiri Himalaya displays several geological features that distinguish it from other Himalayan regions. These include reduced volumes of leucogranite and migmatite, no evidence for partial melting within the sillimanite stability field, reduced structural thickness, and late-stage top-southwest shortening in the STDS. New and previously published structural and thermobarometric constraints suggest that the channel-flow model can be applied to mid-Eocene–early Miocene mid-crustal evolution of the GHS in the Annapurna-Dhaulagiri Himalaya. However, pressure-temperature-time (PTt) constraints indicate that following peak conditions, the GHS in this region did not undergo rapid isothermal exhumation and widespread sillima­nite-grade decompression melting, as commonly recorded elsewhere in the Hima­laya. Instead, lower-than-typical structural thickness and melt volumes suggest that the upper part of the GHS (Upper Greater Himalayan Sequence [UGHS]—the proposed channel) had a greater viscosity than in other Hima­layan regions. We suggest that viscosity-limited, subdued channel flow prevented exhumation on an isothermal trajectory and forced the UGHS to exhume slowly. These findings are distinct from other regions in the Himalaya. As such, we describe the mid-crustal evolution of the GHS in the Annapurna-­Dhaulagiri Himalaya as an atypical example of channel flow during the Himalayan orogeny

Kindlin-1 regulates epidermal growth factor receptor signalling

Kindler syndrome (KS) is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding kindlin-1. Kindlin-1 localises to focal adhesion and is known to contribute to the activation of integrin receptors. Most cases of KS show a reduction or complete absence of kindlin-1 in keratinocytes, resulting in defective integrin activation, cell adhesion and migration. However, roles for kindlin-1 beyond integrin activation remain poorly defined. In the current study we show that skin and keratinocytes from KS patients have significantly reduced expression levels of the epidermal growth factor receptor (EGFR), resulting in defective EGF-dependent signalling and cell migration. Mechanistically, we demonstrate that kindlin-1 can associate directly with EGFR in vitro and in keratinocytes in an EGF-dependent, integrin-independent manner and that formation of this complex is required for EGF-dependent migration. We further demonstrate that kindlin-1 acts to protect EGFR from lysosomal-mediated degradation. This reveals a new role for kindlin-1 that has implications for understanding KS disease pathology