Exploring the shell-based taxonomy of the Sri Lankan land snail Corilla H. and A. Adams, 1855 (Pulmonata: Corillidae) using mitochondrial DNA

The land-snail genus Corilla is endemic to Sri Lanka and India’s Western Ghats. The ten extant Sri Lankan species belong to two distinct shell forms that are associated respectively with lowland and montane rainforest. We here present the first molecular phylogenetic analysis for Corilla. Our dataset includes nine nominal Sri Lankan species and is based on three mitochondrial genes (CO1, ND1 and 16S). Although the deeper nodes in the trees are not fully resolved, the results do suggest speciation in Corilla has involved repeated, ecologically-driven convergence in shell form. The mtDNA data agree with the current shell-based taxonomy for C. adamsi, C. beddomeae, C. carabinata, C. humberti and C. colletti, consistently supporting the first four as monophyletic, and supporting the last also as monophyletic in nearly all analyses. Corilla adamsi, C. beddomeae and C. colletti may each contain at least one additional, previously undescribed species. The relationship between northern and eastern C. odontophora couldn’t be reliably resolved, but our results suggest that they are distinct species and that there is further species-level or intraspecific (geographical) differentiation within eastern C. odontophora. The current, morphologically-defined species limits of the three remaining nominal species, C. gudei, C. erronea and C. fryae, are inconsistent with the mtDNA sequence data. Northern and southern C. gudei appear to be distinct species: the sister taxon of southern C. gudei is C. humberti, and most analyses showed that the sister taxon of northern C. gudei is the lowland C. carabinata. Corilla erronea and C. fryae constitute a well supported clade in which both nominal species are paraphyletic. While most intra-clade CO1 p-distances are moderate to relatively large, the phylogenetic structuring within the clade does not seem to correspond to any obvious morphological, elevational or geographical patterns. These results are difficult to interpret, and further detailed study is needed before the taxonomic status of C. erronea and C. fryae can be resolved

Incorporating patient partner scores into high stakes assessment : an observational study into opinions and attitudes

Peer reviewedPublisher PD

A New Determination of the High Redshift Type Ia Supernova Rates with the Hubble Space Telescope Advanced Camera for Surveys

We present a new measurement of the volumetric rate of Type Ia supernova up to a redshift of 1.7, using the Hubble Space Telescope (HST) GOODS data combined with an additional HST dataset covering the North GOODS field collected in 2004. We employ a novel technique that does not require spectroscopic data for identifying Type Ia supernovae (although spectroscopic measurements of redshifts are used for over half the sample); instead we employ a Bayesian approach using only photometric data to calculate the probability that an object is a Type Ia supernova. This Bayesian technique can easily be modified to incorporate improved priors on supernova properties, and it is well-suited for future high-statistics supernovae searches in which spectroscopic follow up of all candidates will be impractical. Here, the method is validated on both ground- and space-based supernova data having some spectroscopic follow up. We combine our volumetric rate measurements with low redshift supernova data, and fit to a number of possible models for the evolution of the Type Ia supernova rate as a function of redshift. The data do not distinguish between a flat rate at redshift > 0.5 and a previously proposed model, in which the Type Ia rate peaks at redshift >1 due to a significant delay from star-formation to the supernova explosion. Except for the highest redshifts, where the signal to noise ratio is generally too low to apply this technique, this approach yields smaller or comparable uncertainties than previous work.Comment: Accepted for publication in Ap

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

The predictive value of depression in the years after heart transplantation for mortality during long-term follow-up

Objective Current understanding of the prognostic impact of depression on mortality after heart transplantation (HTx) is limited. We examined whether depression after HTx is a predictor of mortality during extended follow-up. Subsequently, we explored whether different symptom dimensions of depression could be identified and whether they were differentially associated with mortality. Methods Survival analyses were performed in a sample of 141 HTx recipients assessed for depression, measured by self-report of depressive symptoms (Beck Depression Inventory – version 1A [BDI-1A]), at median 5.0 years after HTx, and followed thereafter for survival status for up to 18.6 years. We used uni- and multivariate Cox proportional hazard models to examine the association of clinically significant depression (BDI-1A total score ≥10), as well as the cognitive-affective and the somatic subscales of the BDI-1A (resulting from principal component analysis) with mortality. In the multivariate analyses, we adjusted for relevant sociodemographic and clinical variables. Results Clinically significant depression was a significant predictor of mortality (hazard ratio = 2.088; 95% confidence interval = 1.366–3.192; p = .001). Clinically significant depression also was an independent predictor of mortality in the multivariate analysis (hazard ratio = 1.982; 95% confidence interval = 1.220–3.217; p = .006). The somatic subscale, but not the cognitive-affective subscale, was significantly associated with increased mortality in univariate analyses, whereas neither of the two subscales was an independent predictor of mortality in the multivariate analysis. Conclusions Depression measured by self-report after HTx is associated with increased mortality during extended follow-up. Clinical utility and predictive validity of specific depression components require further study.acceptedVersio

Observed communication skills: how do they relate to the consultation content? A nation-wide study of graduate medical students seeing a standardized patient for a first-time consultation in a general practice setting

<p>Abstract</p> <p>Background</p> <p>In this study, we wanted to investigate the relationship between background variables, communication skills, and the bio-psychosocial content of a medical consultation in a general practice setting with a standardized patient.</p> <p>Methods</p> <p>Final-year medical school students (N = 111) carried out a consultation with an actor playing the role of a patient with a specific somatic complaint, psychosocial stressors, and concerns about cancer. Based on videotapes, communication skills and consultation content were scored separately.</p> <p>Results</p> <p>The mean level of overall communication skills had a significant impact upon the counts of psychosocial issues, the patient's concerns about cancer, and the information and planning parts of the consultation content being addressed. Gender and age had no influence upon the relationship between communication skills and consultation content.</p> <p>Conclusion</p> <p>Communication skills seem to be important for final-year students' competence in addressing sensitive psychosocial issues and patients' concerns as well as informing and planning with patients being representative for a fairly complex case in general practice. This result should be considered in the design and incorporation of communication skills training as part of the curriculum of medical schools.</p

The Hubble Space Telescope Cluster Supernova Survey: V. Improving the Dark Energy Constraints Above z>1 and Building an Early-Type-Hosted Supernova Sample

We present ACS, NICMOS, and Keck AO-assisted photometry of 20 Type Ia supernovae SNe Ia from the HST Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 < z < 1.415. Fourteen of these SNe Ia pass our strict selection cuts and are used in combination with the world's sample of SNe Ia to derive the best current constraints on dark energy. Ten of our new SNe Ia are beyond redshift $z=1$, thereby nearly doubling the statistical weight of HST-discovered SNe Ia beyond this redshift. Our detailed analysis corrects for the recently identified correlation between SN Ia luminosity and host galaxy mass and corrects the NICMOS zeropoint at the count rates appropriate for very distant SNe Ia. Adding these supernovae improves the best combined constraint on the dark energy density \rho_{DE}(z) at redshifts 1.0 < z < 1.6 by 18% (including systematic errors). For a LambdaCDM universe, we find \Omega_\Lambda = 0.724 +0.015/-0.016 (68% CL including systematic errors). For a flat wCDM model, we measure a constant dark energy equation-of-state parameter w = -0.985 +0.071/-0.077 (68% CL). Curvature is constrained to ~0.7% in the owCDM model and to ~2% in a model in which dark energy is allowed to vary with parameters w_0 and w_a. Tightening further the constraints on the time evolution of dark energy will require several improvements, including high-quality multi-passband photometry of a sample of several dozen z>1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on HST.Comment: 27 pages, 11 figures. Submitted to ApJ. This first posting includes updates in response to comments from the referee. See http://www.supernova.lbl.gov for other papers in the series pertaining to the HST Cluster SN Survey. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Unio

Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension

Introduction: Systemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21. Materials and methods: To investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS). Results: By IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p<0.001). Serum levels of anti-CCL21 antibodies were higher in SSc patients than in healthy controls (p<0.001), but only 5% of the SSc population were positive for anti-CCL21 antibodies in SSc, and we found no correlation between anti-CCl21 and serum levels of CCL21. By MS, we only identified peptides located within amino acid (aa) 23-102 of CCL21, indicating that CCL21 in SSc circulate as a truncated protein without the C-terminal tail. Conclusion: This study demonstrates expression of CCL21 in epithelial lung tissue from SSc patients with PAH, and indicate that CCL21 in SSc circulates as a truncated protein. We extend previous observations indicating biomarker potential of CCL21, but find that Luminex is not suitable as platform for biomarker analyses. Finally, in vivo generated anti-CCL21 antibodies exist in SSc, but do not appear to modify serum CCL21 levels in patients with SSc-PAH