Upper gastrointestinal bleeding in Scotland 2000-2010: Improved outcomes but a significant weekend effect

Aim: To assess numbers and case fatality of patients with upper gastrointestinal bleeding (UGIB), effects of deprivation and whether weekend presentation affected outcomes. Methods: Data was obtained from Information Services Division (ISD) Scotland and National Records of Scotland (NRS) death records for a ten year period between 2000-2001 and 2009-2010. We obtained data from the ISD Scottish Morbidity Records (SMR01) database which holds data on inpatient and day-case hospital discharges from non-obstetric and non-psychiatric hospitals in Scotland. The mortality data was obtained from NRS and linked with the ISD SMR01 database to obtain 30-d case fatality. We used 23 ICD-10 (International Classification of diseases) codes which identify UGIB to interrogate database. We analysed these data for trends in number of hospital admissions with UGIB, 30-d mortality over time and assessed effects of social deprivation. We compared weekend and weekday admissions for differences in 30-d mortality and length of hospital stay. We determined comorbidities for each admission to establish if comorbidities contributed to patient outcome. Results: A total of 60643 Scottish residents were admitted with UGIH during January, 2000 and October, 2009. There was no significant change in annual number of admissions over time, but there was a statistically significant reduction in 30-d case fatality from 10.3% to 8.8% (P < 0.001) over these 10 years. Number of admissions with UGIB was higher for the patients from most deprived category (P < 0.05), although case fatality was higher for the patients from the least deprived category (P < 0.05). There was no statistically significant change in this trend between 2000/01-2009/10. Patients admitted with UGIB at weekends had higher 30-d case fatality compared with those admitted on weekdays (P < 0.001). Thirty day mortality remained significantly higher for patients admitted with UGIB at weekends after adjusting for comorbidities. Length of hospital stay was also higher overall for patients admitted at the weekend when compared to weekdays, although only reached statistical significance for the last year of study 2009/10 (P < 0.0005). Conclusion: Despite reduction in mortality for UGIB in Scotland during 2000-2010, weekend admissions show a consistently higher mortality and greater lengths of stay compared with weekdays

Inhibition of delta-like ligand 4 induces luteal hypervascularization followed by functional and structural luteolysis in the primate ovary

Using specific inhibitors established that angiogenesis in the ovarian follicle and corpus luteum is driven by vascular endothelial growth factor. Recently, it has been demonstrated that the Notch ligand, delta-like ligand 4 (Dll4) negatively regulates vascular endothelial growth factor-mediated vessel sprouting and branching. To investigate the role of Dll4 in regulation of the ovarian vasculature, we administered a neutralizing antibody to Dll4 to marmosets at the periovulatory period. The vasculature was examined on luteal d 3 or d 10: angiogenesis was determined by incorporation of bromodeoxyuridine, staining for CD31 and cell death by staining for activated caspase-3. Ovulatory progesterone rises were monitored to determine effects of treatment on luteal function and time to recover normal cycles in a separate group of animals. Additionally, animals were treated in the follicular or midluteal phase to determine effects of Dll4 inhibition on follicular development and luteal function. Controls were treated with human IgG (Fc). Corpora lutea from marmosets treated during the periovulatory period exhibited increased angiogenesis and increased vascular density on luteal d 3, but plasma progesterone was significantly suppressed. By luteal d 10, corpora lutea in treated ovaries were significantly reduced in size, with involution of luteal cells, increased cell death, and suppressed plasma progesterone concentrations. In contrast, initiation of anti-Dll4 treatment during the midluteal phase produced only a slight suppression of progesterone for the remainder of the cycle. Moreover, Dll4 inhibition had no appreciable effect on follicular development. These results show that Dll4 has a specific and critical role in the development of the normal luteal vasculature

Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection

<p>Abstract</p> <p>Background</p> <p>Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease.</p> <p>Results</p> <p>We have predicted the protein interaction network of <it>Leishmania major </it>by using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets.</p> <p>Conclusion</p> <p>We have constructed the first protein interaction network of the <it>Leishmania major </it>parasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.</p

Single stage repair of a complex pathology: end stage ischaemic cardiomyopathy, ascending aortic aneurysm and thoracic coarctation

The not uncommon combination of ascending aortic pathology with late presenting coarctation is a difficult surgical challenge. The two stage approach is usually adopted. The necessity for cardiac transplantation adds to the complexity: a trans-sternal approach and single stage repair become mandatory

Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes.

BACKGROUND: Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. RESULTS: A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. CONCLUSION: The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Manual / Issue 13 / Storage

Manual, a journal about art and its making. Storage. Manual 13 opens with an introduction by Fred Wilson, who confides, “You can look at all the opulence on display in a museum and begin to understand that something nefarious might be behind it. Storage, for me, is where the action is.” Museums usually make choices for viewers, their curators presenting what they think most important within a category. They can be so good at doing this that visitors sometimes don’t realize there’s anything else to see: they don’t realize the nature of the decisions behind an exhibition, and they accept that the elites have made a judgment about which shoe is the shoe to see. Visitors can learn about what’s great, but they don’t necessarily consider the process of discernment. –– Fred Wilson The RISD Museum’s thirteenth issue of Manual unpacks the idea and reality of storage—objects museums don’t put on view, works made as containers of various sorts, and more metaphorical considerations about how meanings and narratives are stored. This issue serves as a companion to the Raid the Icebox Now series of exhibitions on view at the RISD Museum through November 2020, in which nine contemporary artists and design collectives use the museum and its collections as a site for critical creative production and presentation. Raid the Icebox Now marks the 50th anniversary of Raid the Icebox 1 with Andy Warhol, held in 1970 at the RISD Museum. Softcover, 120 pages. Published Fall/Winter 2019 by the RISD Museum. Manual 13 (Storage) contributors include: Christina Alderman, Issac M. Alderman, A.H. Jerriod Avant, Hannah Carlson, Wai Yee Chiong, John Dunnigan, Maria Morris Hambourg, David Hartt, Elaine Tyler May, Claire McCardell, Denise Murrell, Ingrid Schaffner, Holly Shaffer, Tanya Sheehan, John W. Smith, Mimi Smith, Sassan Tabatabai, Allen Wexler, and Fred Wilson.https://digitalcommons.risd.edu/risdmuseum_journals/1039/thumbnail.jp

Silicic volcanism on Mars evidenced by tridymite in high-SiO2 sedimentary rock at Gale crater

Tridymite, a SiO2 mineral that crystallizes at low pressures and high temperatures (>870 °C) from high-SiO2 materials, was detected at high concentrations in a sedimentary mudstone in Gale crater, Mars. Mineralogy and abundance were determined by X-ray diffraction using the Chemistry and Mineralogy instrument on the Mars Science Laboratory rover Curiosity. Terrestrial tridymite is commonly associated with silicic volcanism where high temperatures and high-silica magmas prevail, so this occurrence is the first in situ mineralogical evidence for martian silicic volcanism. Multistep processes, including high-temperature alteration of silica-rich residues of acid sulfate leaching, are alternate formation pathways for martian tridymite but are less likely. The unexpected discovery of tridymite is further evidence of the complexity of igneous petrogenesis on Mars, with igneous evolution to high-SiO2 compositions

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P &lt; 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes