Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women

Objectives To describe the effect of multidisciplinary care on survival in women treated for breast cancer

Developing a Relational View of the Organizing Role of Objects: A study of the innovation process in computer games

Innovation processes create distinctive challenges for coordination. Objects are seen as supporting coordination in such settings by enabling the emergent action needed to deal with a dynamic and uncertain process. Thus, previous work has highlighted the role of different types of objects in coordinating the collaborative tasks undertaken by expert groups, either by motivating the creation of new knowledge or through the translation of understanding. Through an empirical study of innovation processes in the computer games sector, our paper adds to this previous work by finding that the relations between objects, and not the objects alone, help to orchestrate multiple collaborative tasks towards a final outcome within temporal and resource constraints. The relational view which emerges from this study shows how such a ‘system of objects’ is able to stabilize coordination of the process while preserving the emergence and autonomy of games developer practices needed to achieve innovation

Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal

<p>Abstract</p> <p>Background</p> <p>Hormones are critical for early gonadal development in nonmammalian vertebrates, and oestrogen is required for normal ovarian development. In contrast, mammals determine sex by the presence or absence of the <it>SRY </it>gene, and hormones are not thought to play a role in early gonadal development. Despite an XY sex-determining system in marsupial mammals, exposure to oestrogen can override <it>SRY </it>and induce ovarian development of XY gonads if administered early enough. Here we assess the effect of exogenous oestrogen on the molecular pathways of mammalian gonadal development.</p> <p>Results</p> <p>We examined the expression of key testicular (<it>SRY</it>, <it>SOX9</it>, <it>AMH </it>and <it>FGF9</it>) and ovarian (<it>WNT4</it>, <it>RSPO1</it>, <it>FOXL2 </it>and <it>FST</it>) markers during gonadal development in the marsupial tammar wallaby (<it>Macropus eugenii</it>) and used these data to determine the effect of oestrogen exposure on gonadal fate. During normal development, we observed male specific upregulation of <it>AMH </it>and <it>SOX9 </it>as in the mouse and human testis, but this upregulation was initiated before the peak in <it>SRY </it>expression and 4 days before testicular cord formation. Similarly, key genes for ovarian development in mouse and human were also upregulated during ovarian differentiation in the tammar. In particular, there was early sexually dimorphic expression of <it>FOXL2 </it>and <it>WNT4</it>, suggesting that these genes are key regulators of ovarian development in all therian mammals. We next examined the effect of exogenous oestrogen on the development of the mammalian XY gonad. Despite the presence of <it>SRY</it>, exogenous oestrogen blocked the key male transcription factor SOX9 from entering the nuclei of male somatic cells, preventing activation of the testicular pathway and permitting upregulation of key female genes, resulting in ovarian development of the XY gonad.</p> <p>Conclusions</p> <p>We have uncovered a mechanism by which oestrogen can regulate gonadal development through the nucleocytoplasmic shuttling of SOX9. This may represent an underlying ancestral mechanism by which oestrogen promotes ovarian development in the gonads of nonmammalian vertebrates. Furthermore, oestrogen may retain this function in adult female mammals to maintain granulosa cell fate in the differentiated ovary by suppressing nuclear translocation of the SOX9 protein.</p> <p>See commentary: http://www.biomedcentral.com/1741-7007/8/110</p

Ethnicity and the first diagnosis of a wide range of cardiovascular diseases: Associations in a linked electronic health record cohort of 1 million patients

Background: While the association of ethnic group with individual cardiovascular diseases has been studied, little is known about ethnic differences in the initial lifetime presentation of clinical cardiovascular disease in contemporary populations. Methods and results: We studied 1,068,318 people, aged ≥30 years and free from diagnosed CVD at baseline (90.9% White, 3.6% South Asian and 2.9% Black), using English linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry and mortality registry (CALIBER research platform). During 5.7 years median follow-up between 1997-2010, 95,224 people experienced an incident cardiovascular diagnosis. 80.2% (77.7% -82.5%) of initial presentation in South Asian <60 yrs were coronary heart disease presentations compared to 66.2% (65.7-66.7) in White and 56.7% (52.1%-61.2%) in Black patients. Compared to White patients, Black patients had significantly lower age-sex adjusted hazard ratios (HRs) for initial lifetime presentation of all the coronary disease diagnoses (stable angina HR 0.80 (95% CI 0.68-0.93); unstable angina – 0.75 (0.59-0.97); myocardial infarction 0.49 (0.40-0.62)) while South Asian patients had significantly higher HRs (stable angina – 1.67 (1.52-1.84); unstable angina 1.82 (1.56-2.13); myocardial infarction – 1.67 (1.49-1.87). We found no ethnic differences in initial presentation with heart failure (Black 0.97 (0.79-1.20); S Asian 1.04(0.87-1.26)). Compared to White patients, Black patients were more likely to present with ischaemic stroke (1.24 (0.97-1.58)) and intracerebral haemorrhage (1.44 (0.97-2.12)). Presentation with peripheral arterial disease was less likely for Black (0.63 (0.50-0.80)) and South Asian patients (0.70 (0.57-0.86)) compared with White patients. Discussion: While we found the anticipated substantial predominance of coronary heart disease presentations in South Asian and predominance of stroke presentations in Black patients, we found no ethnic differences in presentation with heart failure. We consider the public health and research implications of our findings

Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients

Background: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. Methods and Results: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-American

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

A Joint Fermi-GBM and Swift-BAT Analysis of Gravitational-wave Candidates from the Third Gravitational-wave Observing Run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift- BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

© 2008 Ebert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens