Type Ia Supernovae and the Hubble Constant

The focus of this review is the work that has been done during the 1990s on using Type Ia supernovae (SNe Ia) to measure the Hubble constant ($H_0$). SNe Ia are well suited for measuring $H_0$. A straightforward maximum-light color criterion can weed out the minority of observed events that are either intrinsically subluminous or substantially extinguished by dust, leaving a majority subsample that has observational absolute-magnitude dispersions of less than $\sigma_{obs}(M_B) \simeq \sigma_{obs}(M_V) \simeq 0.3$ mag. Correlations between absolute magnitude and one or more distance-independent SN Ia or parent-galaxy observables can be used to further standardize the absolute magnitudes to better than 0.2 mag. The absolute magnitudes can be calibrated in two independent ways --- empirically, using Cepheid-based distances to parent galaxies of SNe Ia, and physically, by light curve and spectrum fitting. At present the empirical and physical calibrations are in agreement at $M_B \simeq M_V \simeq -19.4$ or -19.5. Various ways that have been used to match Cepheid-calibrated SNe Ia or physical models to SNe Ia that have been observed out in the Hubble flow have given values of $H_0$ distributed throughout the range 54 to 67 km/s Mpc$^{-1}$. Astronomers who want a consensus value of $H_0$ from SNe Ia with conservative errors could, for now, use $60 \pm 10$ km/s Mpc^{-1}$.Comment: 46 pages. Hard copies of figures, all from the published literature, can be obtained from the author. With permission, from the Annual Review of Astronomy and Astrophysics, Volume 36, copyright 1998, by Annual Review

How and why are communities of practice established in the healthcare sector? A systematic review of the literature

Background: Communities of Practice (CoPs) are promoted in the healthcare sector as a means of generating and sharing knowledge and improving organisational performance. However CoPs vary considerably in the way they are structured and operate in the sector. If CoPs are to be cultivated to benefit healthcare organisations, there is a need to examine and understand their application to date. To this end, a systematic review of the literature on CoPs was conducted, to examine how and why CoPs have been established and whether they have been shown to improve healthcare practice. Methods. Peer-reviewed empirical research papers on CoPs in the healthcare sector were identified by searching electronic health-databases. Information on the purpose of establishing CoPs, their composition, methods by which members communicate and share information or knowledge, and research methods used to examine effectiveness was extracted and reviewed. Also examined was evidence of whether or not CoPs led to a change in healthcare practice. Results: Thirty-one primary research papers and two systematic reviews were identified and reviewed in detail. There was a trend from descriptive to evaluative research. The focus of CoPs in earlier publications was on learning and exchanging information and knowledge, whereas in more recently published research, CoPs were used more as a tool to improve clinical practice and to facilitate the implementation of evidence-based practice. Means by which members communicated with each other varied, but in none of the primary research studies was the method of communication examined in terms of the CoP achieving its objectives. Researchers are increasing their efforts to assess the effectiveness of CoPs in healthcare, however the interventions have been complex and multifaceted, making it difficult to directly attribute the change to the CoP. Conclusions: In keeping with Wenger and colleagues' description, CoPs in the healthcare sector vary in form and purpose. While researchers are increasing their efforts to examine the impact of CoPs in healthcare, cultivating CoPs to improve healthcare performance requires a greater understanding of how to establish and support CoPs to maximise their potential to improve healthcare

Promoter Methylation in Head and Neck Squamous Cell Carcinoma Cell Lines Is Significantly Different than Methylation in Primary Tumors and Xenografts

Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments

The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences

Simon Chapman and Ross MacKenzie review the evidence and argue that health promotion messages should emphasize that the most successful method used by most ex-smokers is unassisted cessation

Iron Biogeochemistry in the High Latitude North Atlantic Ocean

Iron (Fe) is an essential micronutrient for marine microbial organisms, and low supply controls productivity in large parts of the world’s ocean. The high latitude North Atlantic is seasonally Fe limited, but Fe distributions and source strengths are poorly constrained. Surface ocean dissolved Fe (DFe) concentrations were low in the study region (<0.1 nM) in summer 2010, with significant perturbations during spring 2010 in the Iceland Basin as a result of an eruption of the Eyjafjallajökull volcano (up to 2.5 nM DFe near Iceland) with biogeochemical consequences. Deep water concentrations in the vicinity of the Reykjanes Ridge system were influenced by pronounced sediment resuspension, with indications for additional inputs by hydrothermal vents, with subsequent lateral transport of Fe and manganese plumes of up to 250–300 km. Particulate Fe formed the dominant pool, as evidenced by 4–17 fold higher total dissolvable Fe compared with DFe concentrations, and a dynamic exchange between the fractions appeared to buffer deep water DFe. Here we show that Fe supply associated with deep winter mixing (up to 103 nmol m−2 d−1) was at least ca. 4–10 times higher than atmospheric deposition, diffusive fluxes at the base of the summer mixed layer, and horizontal surface ocean fluxes

Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice

<p>Abstract</p> <p>Background</p> <p>Mutations of the <it>MEN1 </it>gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that <it>Men1 </it>disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the <it>Men1 </it>mutant mice.</p> <p>Methods</p> <p>To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 <it>Men1</it>^+/-mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort.</p> <p>Results</p> <p>Six <it>Men1</it>^+/-mice (12.8%) developed prostate cancer, including two adenocarcinomas and four <it>in situ </it>carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the <it>Men1 </it>gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type <it>Men1 </it>allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a <it>Men1 </it>target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice.</p> <p>Conclusion</p> <p>Our work suggests the possible involvement of <it>Men1 </it>inactivation in the tumorigenesis of the prostate gland.</p

Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins

We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The gentic diversity of H pylori is known to be influenced by these genomic elements including prophages who’s geneomes range from 22.6 to 33.0 Kbp. There was a high conservation of integration site shared in over 50% of cases with greater than 40% or prophage genomes harbouring insertion sequences (IS). Furthermore prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. There was evidence of recombination within the genome of some prophages, which resulted in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Expression of oestrogen receptors, ERα, ERβ, and ERβ variants, in endometrial cancers and evidence that prostaglandin F may play a role in regulating expression of ERα

<p>Abstract</p> <p>Background</p> <p>Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERα and ERβ) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERβ lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors.</p> <p>Methods</p> <p>We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n ≥ 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2α on expression of ERs and PR.</p> <p>Results</p> <p>Full length ERβ (ERβ1) and two ERβ variants (ERβ2, ERβ5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERα^neg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERα. Treatment of adenocarcinoma cells with PGF2α reduced expression of ERα but had no impact on ERβ1. Cells incubated with PGF2α were unable to increase expression of PR mRNA when they were incubated with E2.</p> <p>Conclusion</p> <p>We have demonstrated that ERβ5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERβ variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERβ^pos/ERα^neg. We found evidence of a link between COX-2, its product PGF2α, and expression of ERα and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease.</p