BASiCS: Bayesian Analysis of Single-Cell Sequencing Data

Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants are estimated as part of the model parameters, (ii) technical variability is quantified based on spike-in genes that are artificially introduced to each analysed cell's lysate and (iii) the total variability of the expression counts is decomposed into technical and biological components. BASiCS also provides an intuitive detection criterion for highly (or lowly) variable genes within the population of cells under study. This is formalised by means of tail posterior probabilities associated to high (or low) biological cell-to-cell variance contributions, quantities that can be easily interpreted by users. We demonstrate our method using gene expression measurements from mouse Embryonic Stem Cells. Cross-validation and meaningful enrichment of gene ontology categories within genes classified as highly (or lowly) variable supports the efficacy of our approach

Shade Effects on Athletic Field Playing Characteristics of Overseeded and Non-Overseeded Bermudagrass

In many athletic stadiums around the world, reduced light levels from the stadium structure can significantly reduce turfgrass quality and playing characteristics. In most warm-weather stadiums, the primary surface is bermudagrass which is commonly overseeded with perennial ryegrass to provide a winter and spring playing surface. The objective of this study was to examine the effects of four shade levels on turfgrass quality and playing characteristics of overseeded and non-overseeded bermudagrass (cv. Riviera). Shade levels included a non-shaded control and shade treatments which blocked 30%, 60%, and 90% of ambient light. These shade levels resulted in average daily PAR loads of 45.1, 29.6, 16.7, and 4.7 mol PAR / m2 / day, respectively. Data collection included both quality and playability characteristics. The effects of shading became obvious as the study continued into early summer, with the 90% shade plots losing almost all cover and the 60% shade plots losing up to 40% of coverage through mid-summer. The 30% shade plots had a slight decline in turfgrass coverage, although, still retained close to 90% coverage. Based on these results, a minimum daily light load of approximately 30 mol PAR / m2 / day is needed to sustain Riviera bermudagrass at or near 100% coverage. In the overseeded plots, the only shade treatment that caused a significant reduction in turfgrass coverage was the 90% shade treatment (4.7 mol PAR / m2 / day). There was a significant decrease in the amount of bermudagrass present in the overseeded plots in mid-summer, suggesting that increased shading was causing a shift in population from the warm-season bermudagrass to the cool-season perennial ryegrass. In both overseeded and non-overseeded plots, rotational resistance (traction) decreased even with modest levels of shade , which is likely correlated to a decrease in turfgrass densit

Where is my sink? Reconstruction of landscape development in 1 southwestern Africa since the Late Jurassic

Quantifying the rates and timing of landscape denudation provides a means to constrain sediment flux through time to offshore sedimentary basins. The Late Mesozoic evolution of drainage basins in southern Africa is poorly constrained despite the presence of several onshore and offshore sedimentary basins. A novel approach has been developed to calculate the volume of material eroded since the Late Jurassic at different time steps by constructing structural cross-sections and extrapolating thicknesses of eroded material. Using different assumptions, the calculated volumes of material eroded from southwestern Africa range from 2.52x10⁶ km³ (11.3 km of vertical thickness removed) to 8.87 x10⁵ km³ (4.0 km of vertical thickness removed). For the southward draining systems alone, the calculated removal of 7.81 x10⁵ – 2.60 x10⁵ km³ of material is far greater than the volumes of sediment recorded in offshore sedimentary basins (268 500 km³). Reconstruction of the drainage systems using geomorphic indicators and clast provenance of the Uitenhage Group, as well as extrapolated surface exposure ages, indicate the southern draining systems were active from the Late Jurassic with coeval activity in axial and transverse drainage systems. The calculated volumes are tied to published apatite fission track (AFT) dates to constrain the changes in exhumation rate through time (using multiple scenarios), which indicate a significant amount of Early Cretaceous exhumation (up to 1.26 x10⁶ km³, equivalent to 5.70km of vertical thickness). For the first time, this has permitted long-term landscape evolution to be used to support the interpretation that some of the ‘missing’ sediment was deposited in sedimentary basins on the Falkland Plateau as it moved past southern Africa during the Early Cretaceous. This implies that in this instance, the sinks are separated from their source areas by ~6000 km

What is the impact of giant cell arteritis on patients' lives?: a UK qualitative study

Objectives: Clinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients’ lives. Methods: UK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed. Results: 24 participants were recruited (age: 65–92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and ‘life-changing’ impacts. The overall impact of GCA on patients’ lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision. Conclusions: The impact of GCA in patients’ everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients’ experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success

Damage function for historic paper. Part I: Fitness for use

Background In heritage science literature and in preventive conservation practice, damage functions are used to model material behaviour and specifically damage (unacceptable change), as a result of the presence of a stressor over time. For such functions to be of use in the context of collection management, it is important to define a range of parameters, such as who the stakeholders are (e.g. the public, curators, researchers), the mode of use (e.g. display, storage, manual handling), the long-term planning horizon (i.e. when in the future it is deemed acceptable for an item to become damaged or unfit for use), and what the threshold of damage is, i.e. extent of physical change assessed as damage. Results In this paper, we explore the threshold of fitness for use for archival and library paper documents used for display or reading in the context of access in reading rooms by the general public. Change is considered in the context of discolouration and mechanical deterioration such as tears and missing pieces: forms of physical deterioration that accumulate with time in libraries and archives. We also explore whether the threshold fitness for use is defined differently for objects perceived to be of different value, and for different modes of use. The data were collected in a series of fitness-for-use workshops carried out with readers/visitors in heritage institutions using principles of Design of Experiments. Conclusions The results show that when no particular value is pre-assigned to an archival or library document, missing pieces influenced readers/visitors’ subjective judgements of fitness-for-use to a greater extent than did discolouration and tears (which had little or no influence). This finding was most apparent in the display context in comparison to the reading room context. The finding also best applied when readers/visitors were not given a value scenario (in comparison to when they were asked to think about the document having personal or historic value). It can be estimated that, in general, items become unfit when text is evidently missing. However, if the visitor/reader is prompted to think of a document in terms of its historic value, then change in a document has little impact on fitness for use

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers