695 research outputs found

    A new indicator mineral methodology based on a generic Bi-Pb-Te-S mineral inclusion signature in detrital gold from porphyry and low/intermediate sulfidation epithermal environments in Yukon Territory, Canada

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    Porphyry-epithermal and orogenic gold are two of the most important styles of gold-bearing mineralization within orogenic belts. Populations of detrital gold resulting from bulk erosion of such regions may exhibit a compositional continuum wherein Ag, Cu, and Hg in the gold alloy may vary across the full range exhibited by natural gold. This paper describes a new methodology whereby orogenic and porphyry-epithermal gold may be distinguished according to the mineralogy of microscopic inclusions observed within detrital gold particles. A total of 1459 gold grains from hypogene, eluvial, and placer environments around calc-alkaline porphyry deposits in Yukon (Nucleus-Revenue, Casino, Sonora Gulch, and Cyprus-Klaza) have been characterized in terms of their alloy compositions (Au, Ag, Cu, and Hg) and their inclusion mineralogy. Despite differences in the evolution of the different magmatic hydrothermal systems, the gold exhibits a clear Bi-Pb-Te-S mineralogy in the inclusion suite, a signature which is either extremely weak or (most commonly) absent in both Yukon orogenic gold and gold from orogenic settings worldwide. Generic systematic compositional changes in ore mineralogy previously identified across the porphyry-epithermal transition have been identified in the corresponding inclusion suites observed in samples from Yukon. However, the Bi-Te association repeatedly observed in gold from the porphyry mineralization persists into the epithermal environment. Ranges of P-T-X conditions are replicated in the geological environments which define generic styles of mineralization. These parameters influence both gold alloy composition and ore mineralogy, of which inclusion suites are a manifestation. Consequently, we propose that this methodology approach can underpin a widely applicable indicator methodology based on detrital gold

    Current challenges in software solutions for mass spectrometry-based quantitative proteomics

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    This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

    The Future of Rectal Cancer Surgery: A Narrative Review of an International Symposium

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    Surgery remains the mainstay of curative treatment for primary rectal cancer. For mid and low rectal tumors, optimal oncologic surgery requires total mesorectal excision (TME) to ensure the tumor and locoregional lymph nodes are removed. Adequacy of surgery is directly linked to survival outcomes and, in particular, local recurrence. From a technical perspective, the more distal the tumor, the more challenging the surgery and consequently, the risk for oncologically incomplete surgery is higher. TME can be performed by an open, laparoscopic, robotic or transanal approach. There is a lack of consensus on the “gold standard” approach with each of these options offering specific advantages. The International Symposium on the Future of Rectal Cancer Surgery was convened to discuss the current challenges and future pathways of the 4 approaches for TME. This article reviews the findings and discussion from an expert, international panel

    Role of 20-Hydroxyeicosatetraenoic Acid in Mediating Hypertension in Response to Chronic Renal Medullary Endothelin Type B Receptor Blockade

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    BACKGROUND: The renal medullary endothelin (ET-1) system plays an important role in the control of sodium excretion and arterial pressure (AP) through the activation of renal medullary ET-B receptors. We have previously shown that blockade of endothelin type B receptors (ET-B) leads to salt-sensitive hypertension through mechanisms that are not fully understood. One possible mechanism is through a reduction in renal medullary production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a metabolite of arachidonic acid, has natriuretic properties similar to ET-B activation. While these findings suggest a possible interaction between ET-B receptor activation and 20-HETE production, it is unknown whether blockade of medullary ET-B receptors in rats maintained on a high sodium intake leads to reductions in 20-HETE production. METHODOLOGY/PRINCIPAL FINDINGS: The effect of increasing sodium intake from low (NS = .8%) to high (HS = 8%) on renal medullary production of 20-HETE in the presence and absence of renal medullary ET-B receptor antagonism was examined. Renal medullary blockade of ET-B receptors resulted in salt sensitive hypertension. In control rats, blood pressure rose from 112.8±2.4 mmHg (NS) to 120.7±9.3 mmHg (HS). In contrast, when treated with an ET-B receptor blocker, blood pressure was significantly elevated from 123.7±3.2 (NS) to 164.2±7.1 (HS). Furthermore, increasing sodium intake was associated with elevated medullary 20-HETE (5.6±.8 in NS vs. 14.3±3.7 pg/mg in HS), an effect that was completely abolished by renal medullary ET-B receptor blockade (4.9±.8 for NS and 4.5±.6 pg/mg for HS). Finally, the hypertensive response to intramedullary ET-B receptor blockade was blunted in rats pretreated with a specific 20-HETE synthesis inhibitor. CONCLUSION: These data suggest that increases in renal medullary production of 20-HETE associated with elevating salt intake may be, in part, due to ET-B receptor activation within the renal medulla

    Acute Achilles tendon rupture: minimally invasive surgery versus non operative treatment, with immediate full weight bearing. Design of a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>We present the design of an open randomized multi-centre study on surgical versus conservative treatment of acute Achilles tendon ruptures. The study is designed to evaluate the effectiveness of conservative treatment in reducing complications when treating acute Achilles tendon rupture.</p> <p>Methods/Design</p> <p>At least 72 patients with acute Achilles tendon rupture will be randomized to minimally invasive surgical repair followed by functional rehabilitation using tape bandage or conservative treatment followed by functional rehabilitation with use of a functional bracing system. Both treatment arms use a 7 weeks post-rupture rehabilitation protocol. Four hospitals in the Netherlands will participate. Primary end-point will be reduction in complications other than re-rupture. Secondary end-point will be re-rupturing, time off work, sporting activity post rupture, functional outcome by Leppilahti score and patient satisfaction. Patient follow-up will be 12 month.</p> <p>Discussion</p> <p>By making this design study we wish to contribute to more profound research on AT rupture treatment and prevent publication bias for this open-labelled randomized trial.</p> <p>Trial registration</p> <p>ISRCTN50141196</p

    Evaluation of the limitations and methods to improve rapid phage-based detection of viable Mycobacterium avium subsp. paratuberculosis in the blood of experimentally infected cattle

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    Background Disseminated infection and bacteraemia is an underreported and under-researched aspect of Johne’s disease. This is mainly due to the time it takes for Mycobacterium avium subsp. paratuberculosis (MAP) to grow and lack of sensitivity of culture. Viable MAP cells can be detected in the blood of cattle suffering from Johne’s disease within 48 h using peptide-mediated magnetic separation (PMMS) followed by bacteriophage amplification. The aim of this study was to demonstrate the first detection of MAP in the blood of experimentally exposed cattle using the PMMS-bacteriophage assay and to compare these results with the immune response of the animal based on serum ELISA and shedding of MAP by faecal culture. Results Using the PMMS-phage assay, seven out of the 19 (37 %) MAP-exposed animals that were tested were positive for viable MAP cells although very low numbers of MAP were detected. Two of these animals were positive by faecal culture and one was positive by serum ELISA. There was no correlation between PMMS-phage assay results and the faecal and serum ELISA results. None of the control animals (10) were positive for MAP using any of the four detection methods. Investigations carried out into the efficiency of the assay; found that the PMMS step was the limiting factor reducing the sensitivity of the phage assay. A modified method using the phage assay directly on isolated peripheral blood mononuclear cells (without PMMS) was found to be superior to the PMMS isolation step. Conclusions This proof of concept study has shown that viable MAP cells are present in the blood of MAP-exposed cattle prior to the onset of clinical signs. Although only one time point was tested, the ability to detect viable MAP in the blood of subclinically infected animals by the rapid phage-based method has the potential to increase the understanding of the pathogenesis of Johne’s disease progression by warranting further research on the presence of MAP in blood

    Revisiting German labour market reform effects—a panel data analysis for occupational labour markets

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    There is an ongoing discussion that centres on the German labour market reforms (2003- 2005) and the role of these reforms in boosting the German economy. Considering that one of the main objectives of the reforms was to improve the matching process on the labour market, I use rich, high-frequency, and recent administrative panel data to present new details regarding the development of job-matching performance before and after the reform years. The results show that matching productivity increased during all reform stages and slightly deteriorated in 2009 (the year of the financial crisis), even after controlling for the recession. Furthermore, increases in matching productivity have become smaller in recent years. Beyond these findings, the results show detailed differences in the changes in matching productivity on occupational labour markets.Über einen etwaigen Beitrag der deutschen Arbeitsmarktreformen (2003-2005) zur Stabilisierung der deutschen Wirtschaft wird sowohl in Wissenschaft als auch Politik nach wie vor debattiert. Dabei war die Verbesserung der Effizienz des Arbeitsmarktausgleichs eines der erklärten Hauptziele der Reformen. Zur Frage, ob dieses Ziel erreicht wurde, stelle ich präzise und neue detaillierte Befunde auf der Basis von umfangreichen administrativen Daten vor, die auch die Zeit der Wirtschafts- und Finanzkrise (2008/2009) einschließen. Die Effizienz des Arbeitsmarktausgleichs erhöhte sich während und nach den Reformjahren deutlich. Dies lässt sich nun auch für die Einführung der letzten Reformstufe im Jahr 2005 belegen. Jedoch waren die Arbeitsmarktausgleichsprozesse nicht vollständig immun gegen die Wirtschafts- und Finanzkrise; die positive Entwicklung wurde hier unterbrochen und setzte sich danach nicht in dem gleichen Maße fort. Darüber hinaus zeigen die Analysen eine unterschiedliche Entwicklung der Matchingeffizienz in beruflichen Teilarbeitsmärkten auf

    Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

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    Aims/hypothesis This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measurements are applicable to pregnant women with diabetes. Methods CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5–7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA1c measure. In total, 688 average glucose–HbA1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA1c. Results There was a strong association between HbA1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4–7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. Conclusions/interpretation The HbA1c–average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care
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