Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

Molecular approaches to malaria and babesiosis diagnosis.

The development of additional methods for detecting and identifying Babesia and Plasmodium infections may be useful in disease monitoring, management and control efforts. The preliminary evaluate synthetic peptide-based serodiagnosis, a hydrophilic sequence (DDESEFDKEK) was selected from the published BabR gene of B. bovis. Immunization of rabbits and cattle with the hemocyanin-conjugated peptide elicited antibody responses that specifically detected both P. falciparum and B. bovis antigens by immunofluorescence and Western blots. Using a dot-ELISA with this peptide, antisera from immunized and naturally-infected cattle, and immunized rodents, were specifically detected. Reactivity was weak and correlated with peptide immunization or infection. DNA-based detection using repetitive DNA was species-specific in dot-blot formats for B. bovis DNA, and in both dot-blot and in situ formats for P. falciparum; a streamlined enzyme-linked synthetic DNA assay for P. falciparum detected 30 parasites/mm3 from patient blood using either colorimetric (2-15 h color development) or chemiluminescent detection (0.5-6-min exposures). Serodiagnostic and DNA hybridization methods may be complementary in the respective detection of both chronic and acute infections. However, recent improvements in the polymerase chain reaction (PCR) make feasible a more sensitive and uniform approach to the diagnosis of these and other infectious disease complexes, with appropriate primers and processing methods. An analysis of ribosomal DNA genes of Plasmodium and Toxoplasma identified Apicomplexa-conserved sequence regions. Specific and distinctive PCR profiles were obtained for primers spanning the internal transcribed spacer locus for each of several Plasmodium and Babesia species

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

GLAST: Understanding the High Energy Gamma-Ray Sky

We discuss the ability of the GLAST Large Area Telescope (LAT) to identify, resolve, and study the high energy gamma-ray sky. Compared to previous instruments the telescope will have greatly improved sensitivity and ability to localize gamma-ray point sources. The ability to resolve the location and identity of EGRET unidentified sources is described. We summarize the current knowledge of the high energy gamma-ray sky and discuss the astrophysics of known and some prospective classes of gamma-ray emitters. In addition, we also describe the potential of GLAST to resolve old puzzles and to discover new classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by K.S. Cheng and G.E. Romer

Antenatal screening for Group B Streptococcus: A diagnostic cohort study

BACKGROUND: A range of strategies have been adopted to prevent early onset Group B Streptococcal (EOGBS) sepsis, as a consequence of Group B Streptococcal (GBS) vertically acquired infection. This study was designed to provide a scientific basis for optimum timing and method of GBS screening in an Australian setting, to determine whether screening for GBS infection at 35–37 weeks gestation has better predictive values for colonisation at birth than screening at 31–33 weeks, to examine the test characteristics of a risk factor strategy and to determine the test characteristics of low vaginal swabs alone compared with a combination of perianal plus low vaginal swabs per colonisation during labour. METHODS: Consented women received vaginal and perianal swabs at 31–33 weeks gestation, 35–38 weeks gestation and during labour. Swabs were cultured on layered horse blood agar and inoculated into selective broth prior to analysis. Test characteristics were calculated with exact confidence intervals for a high risk strategy and for antenatal screening at 31–33 and 35–37 weeks gestation for vaginal cultures alone, perianal cultures alone and combined low vaginal and perianal cultures. RESULTS: The high risk strategy was not informative in predicting GBS status during labour. There is an unequivocal benefit for the identification of women colonised with GBS during labour associated with delaying screening until 36 weeks however the results for method of screening were less definitive with no clear advantage in using a combined low vaginal and perianal swabbing regimen over the use of a low vaginal swab alone. CONCLUSION: This study can contribute to the development of prevention strategies in that it provides clear evidence for optimal timing of swabs. The addition of a perianal swab does not confer clear benefit. The quantification of advantages and disadvantages provided in this study will facilitate communication with clinicians and pregnant women alike

Using Pre-existing Microarray Datasets to Increase Experimental Power: Application to Insulin Resistance

Although they have become a widely used experimental technique for identifying differentially expressed (DE) genes, DNA microarrays are notorious for generating noisy data. A common strategy for mitigating the effects of noise is to perform many experimental replicates. This approach is often costly and sometimes impossible given limited resources; thus, analytical methods are needed which increase accuracy at no additional cost. One inexpensive source of microarray replicates comes from prior work: to date, data from hundreds of thousands of microarray experiments are in the public domain. Although these data assay a wide range of conditions, they cannot be used directly to inform any particular experiment and are thus ignored by most DE gene methods. We present the SVD Augmented Gene expression Analysis Tool (SAGAT), a mathematically principled, data-driven approach for identifying DE genes. SAGAT increases the power of a microarray experiment by using observed coexpression relationships from publicly available microarray datasets to reduce uncertainty in individual genes' expression measurements. We tested the method on three well-replicated human microarray datasets and demonstrate that use of SAGAT increased effective sample sizes by as many as 2.72 arrays. We applied SAGAT to unpublished data from a microarray study investigating transcriptional responses to insulin resistance, resulting in a 50% increase in the number of significant genes detected. We evaluated 11 (58%) of these genes experimentally using qPCR, confirming the directions of expression change for all 11 and statistical significance for three. Use of SAGAT revealed coherent biological changes in three pathways: inflammation, differentiation, and fatty acid synthesis, furthering our molecular understanding of a type 2 diabetes risk factor. We envision SAGAT as a means to maximize the potential for biological discovery from subtle transcriptional responses, and we provide it as a freely available software package that is immediately applicable to any human microarray study

Knockout mice: Is it just genetics? Effect of enriched housing on fibulin-4+/- mice

Background. Fibulin-4 is an extracellular matrix protein expressed by vascular smooth muscle cells that is essential for maintaining arterial integrity. Fibulin-4-/- mice die just before birth due to arterial hemorrhage, but fibulin-4+/- mice appear to be outwardly normal. Experiments were therefore performed to determine whether fibulin-4+/- mice display arterial pathologies on a microscopic scale. After preliminary experiments were performed, a second purpose developed, which was to test the hypothesis that any observed pathologies would be ameliorated by housing the animals in enriched cages. Methodology. Fibulin-4+/- and wild-type mice were housed either four/cage in standard cages or two per cage in larger cages, each cage containing a tunnel and a wheel. After three weeks the mice were sacrificed, and the aortas perfusion-fixed and excised for light and electron microscopy. Principle Findings. When the mice were in standard cages, localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the fibulin-4+/- mice. In the wild-type mice, the smooth muscle cells were closely connected to each other and the media was more compact. The number of disorganized regions per square mm was significantly greater for fibulin-4+/- mice (172±43 (SEM)) than for wild-type mice (15±8) (p<0.01, n = 8). When the mice were in enriched cages, the fibulin-4+/- mice showed significantly fewer disorganized regions than those in standard cages (35±12) (p<0.05, n = 8). The wild type mice also showed fewer disorganized regions (3±2), but this difference was not significant. Conclusions. These results indicate that arterial pathologies manifested in fibulin-4+/- mice can be reduced by enriching the housing conditions, and imply that appropriate environments may counteract the effects of some genetic deficiencies

Transient pulsed radio emission from a magnetar

Anomalous X-ray pulsars (AXPs) are slowly rotating neutron stars with very bright and highly variable X-ray emission that are believed to be powered by ultra-strong magnetic fields of >1e14 G, according to the 'magnetar' model. The radio pulsations that have been observed from more than 1,700 neutron stars with weaker magnetic fields have never been detected from any of the dozen known magnetars. The X-ray pulsar XTE J1810-197 was revealed (in 2003) as the first AXP with transient emission when its luminosity increased 100-fold from the quiescent level; a coincident radio source of unknown origin was detected one year later. Here we show that XTE J1810-197 emits bright, narrow, highly linearly polarized radio pulses, observed at every rotation, thereby establishing that magnetars can be radio pulsars. There is no evidence of radio emission before the 2003 X-ray outburst (unlike ordinary pulsars, which emit radio pulses all the time), and the flux varies from day to day. The flux at all radio frequencies is approximately equal -- and at >20 GHz XTE J1810-197 is currently the brightest neutron star known. These observations link magnetars to ordinary radio pulsars, rule out alternative accretion models for AXPs, and provide a new window into the coronae of magnetars.Comment: accepted by Nature; some new data and significantly revised discussio