Phylogeography of the crown-of-thorns starfish in the Indian Ocean

Background: Understanding the limits and population dynamics of closely related sibling species in the marine realm is particularly relevant in organisms that require management. The crown-of-thorns starfish Acanthaster planci, recently shown to be a species complex of at least four closely related species, is a coral predator infamous for its outbreaks that have devastated reefs throughout much of its Indo-Pacific distribution. Methodology/Principal Findings: In this first Indian Ocean-wide genetic study of a marine organism we investigated the genetic structure and inferred the paleohistory of the two Indian Ocean sister-species of Acanthaster planci using mitochondrial DNA sequence analyses. We suggest that the first of two main diversification events led to the formation of a Southern and Northern Indian Ocean sister-species in the late Pliocene-early Pleistocene. The second led to the formation of two internal clades within each species around the onset of the last interglacial. The subsequent demographic history of the two lineages strongly differed, the Southern Indian Ocean sister-species showing a signature of recent population expansion and hardly any regional structure, whereas the Northern Indian Ocean sister-species apparently maintained a constant size with highly differentiated regional groupings that were asymmetrically connected by gene flow. Conclusions/Significance: Past and present surface circulation patterns in conjunction with ocean primary productivity were identified as the processes most likely to have shaped the genetic structure between and within the two Indian Ocean lineages. This knowledge will help to understand the biological or ecological differences of the two sibling species and therefore aid in developing strategies to manage population outbreaks of this coral predator in the Indian Ocean

Assessment of EGFR/HER2 dimerization by FRET-FLIM utilizing Alexa-conjugated secondary antibodies in relation to targeted therapies in cancers

The expression level of the HER family is unreliable as a predictive marker for targeted therapies in cancer. Thus, there is a need to develop other biomarkers, which can be used to accurately select responsive patients for targeted therapies. The HER dimerization status may be more important than HER receptor expression per se in determining sensitivity or resistance to a given therapeutic agent. The aim of the study is to develop a FRET assay using dye conjugated secondary antibodies to assess HER receptor dimerization. Using primary antibodies from different species in conjunction with Alexa488 and Alexa546 conjugated secondary antibodies, we validated our EGFR/HER2 dimerization assay in three cell lines, EGFR positive A431 cells as well as HER2 positive breast cell lines BT474 and SKBR3 cells. Finally, we applied our assay to assess EGFR/HER2 dimerization in paraffin embedded cell pellets. Our results show promise for the assay to be applied to tumor samples in order to assess the prognostic significance and predictive value of HER receptor dimerization in various cancers

Recruitment, growth and mortality of an Antarctic hexactinellid sponge, Anoxycalyx joubini.

Polar ecosystems are sensitive to climate forcing, and we often lack baselines to evaluate changes. Here we report a nearly 50-year study in which a sudden shift in the population dynamics of an ecologically important, structure-forming hexactinellid sponge, Anoxycalyx joubini was observed. This is the largest Antarctic sponge, with individuals growing over two meters tall. In order to investigate life history characteristics of Antarctic marine invertebrates, artificial substrata were deployed at a number of sites in the southern portion of the Ross Sea between 1967 and 1975. Over a 22-year period, no growth or settlement was recorded for A. joubini on these substrata; however, in 2004 and 2010, A. joubini was observed to have settled and grown to large sizes on some but not all artificial substrata. This single settlement and growth event correlates with a region-wide shift in phytoplankton productivity driven by the calving of a massive iceberg. We also report almost complete mortality of large sponges followed over 40 years. Given our warming global climate, similar system-wide changes are expected in the future

Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies

Paul Garner and colleagues conducted a systematic review of 80 studies to compare the quality of private versus public ambulatory health care in low- and middle-income countries

A Pluralistic Theory of Wordhood

What are words and how should we individuate them? There are two main answers on the philosophical market. For some, words are bundles of structural-functional features defining a unique performance profile. For others, words are non-eternal continuants individuated by their causal-historical ancestry. These conceptions offer competing views of the nature of words, and it seems natural to assume that at most one of them can capture the essence of wordhood. This paper makes a case for pluralism about wordhood: the view that there is a plurality of acceptable conceptions of the nature of words, none of which is uniquely entitled to inform us as to what wordhood consists in

The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes

Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing T-bet and GATA3 separately or together in mouse T cells, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. This redistribution of GATA3 is independent of GATA3 DNA binding activity and is instead mediated by the T-bet DNA binding domain, which interacts with the GATA3 DNA binding domain and changes GATA3′s sequence binding preference. This mechanism allows T-bet to drive the TH1 gene expression program in the presence of GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other transcription factors driving alternative differentiation pathways

Development of pseudorandom binary arrays for calibration of surface profile metrology tools

Optical Metrology tools, especially for short wavelength (EUV and X-Ray), must cover a wide range of spatial frequencies from the very low, which affects figure, to the important mid-spatial frequencies and the high spatial frequency range, which produces undesirable scattering. A major difficulty in using surface profilometers arises due to the unknown Point-Spread Function (PSF) of the instruments [1] that is responsible for distortion of the measured surface profile. Generally, the distortion due to the PSF is difficult to account because the PSF is a complex function that comes to the measurement via the convolution operation, while the measured profile is described with a real function. Accounting for instrumental PSF becomes significantly simpler if the result of measurement of a profile is presented in a spatial frequency domain as a Power Spectral Density (PSD) distribution [2]. For example, the measured PSD distributions provide a closed set of data necessary for three-dimensional calculations of scattering of light by the optical surfaces [3], [4]. The distortion of the surface PSD distribution due to the PSF can be modeled with the Modulation Transfer Function (MTF), which is defined over the spatial frequency bandwidth of the instrument [1], [2]. The measured PSD distribution can be presented as a product of the squared MTF and the ideal PSD distribution inherent for the System Under Test (SUT). Therefore, the instrumental MTF can be evaluated by comparing a measured PSD distribution of a known test surface with the corresponding ideal numerically simulated PSD. The square root of the ratio of the measured and simulated PSD distributions gives the MTF of the instrument. In previous work [5], [6] the instrumental MTF of a surface profiler was precisely measured using reference test surfaces based on Binary Pseudo-Random (BPR) gratings. Here, we present results of fabricating and using two-dimensional (2D) BPR arrays that allow for a direct 2D calibration of the instrumental MTF. BPR sequences are widely used in engineering and communication applications such as Global Position System, and wireless communication protocols. The ideal BPR pattern has a flat 'white noise' response over the entire range of spatial frequencies of interest. The BPR array used here is based on the Uniformly Redundant Array prescription [7] initially used for x-ray and gamma ray astronomy applications. The URA's superior imaging capability originates from the fact that its cyclical autocorrelation function very closely approximates a delta function, which produces a flat PSD. Three different size BPR array patterns were fabricated by electron beam lithography and ICP etching of silicon. The basic size unit was 200 nm, 400 nm, and 600 nm. Two different etch processes were used, CF{sub 4}/Ar and HBr, which resulted in undercut and vertical sidewall profiles, respectively. The 2D BPR arrays were used as standard test surfaces for MTF calibration of the MicroMap{trademark}-570 interferometric microscope using all available objectives. The HBr etched two-dimensional BPR arrays have proven to be a very effective calibration standard making possible direct calibration corrections without the need of additional calculation considerations, while departures from the ideal vertical sidewall require an additional correction term for the CF{sub 4}/Ar etched samples. [8] Initial surface roughness of low cost 'prime' wafers limits low magnification calibration but should not be a limitation if better polished samples are used

Quality of medication use in primary care - mapping the problem, working to a solution: a systematic review of the literature

Background: The UK, USA and the World Health Organization have identified improved patient safety in healthcare as a priority. Medication error has been identified as one of the most frequent forms of medical error and is associated with significant medical harm. Errors are the result of the systems that produce them. In industrial settings, a range of systematic techniques have been designed to reduce error and waste. The first stage of these processes is to map out the whole system and its reliability at each stage. However, to date, studies of medication error and solutions have concentrated on individual parts of the whole system. In this paper we wished to conduct a systematic review of the literature, in order to map out the medication system with its associated errors and failures in quality, to assess the strength of the evidence and to use approaches from quality management to identify ways in which the system could be made safer. Methods: We mapped out the medicines management system in primary care in the UK. We conducted a systematic literature review in order to refine our map of the system and to establish the quality of the research and reliability of the system. Results: The map demonstrated that the proportion of errors in the management system for medicines in primary care is very high. Several stages of the process had error rates of 50% or more: repeat prescribing reviews, interface prescribing and communication and patient adherence. When including the efficacy of the medicine in the system, the available evidence suggested that only between 4% and 21% of patients achieved the optimum benefit from their medication. Whilst there were some limitations in the evidence base, including the error rate measurement and the sampling strategies employed, there was sufficient information to indicate the ways in which the system could be improved, using management approaches. The first step to improving the overall quality would be routine monitoring of adherence, clinical effectiveness and hospital admissions. Conclusion: By adopting the whole system approach from a management perspective we have found where failures in quality occur in medication use in primary care in the UK, and where weaknesses occur in the associated evidence base. Quality management approaches have allowed us to develop a coherent change and research agenda in order to tackle these, so far, fairly intractable problems

Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers