444 research outputs found

    Long term storage test of titanium material with liquid fluorine propellant

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    The compatibility of 6AL-4V Ti with propellant grade GF2 and LF2 at 77 K for up to 3 years was investigated. Titanium double coupons, annealed or heat treated, with 16 or 64 RMS finishes, were immersed in F2 in individual Pyrex capsules and stored under LN2 for 29 and 39 months. Pre and post immersion tests were performed on the propellant and coupons. Chemical analysis of the propellant did not reveal any significant changes due to titanium corrosion. Gravimetric, visual, microscopic, and metallurgical examination with pitting analysis did not reveal gross corrosion of the titanium although pitting appears to be greater after 39 months exposure. The increase in pit size and number raises the possibility of unpredictable crack propagation instability. Fracture toughness tests are necessary to define this possibility

    The Treatment-Naive Microbiome in New-Onset Crohn\u27s Disease

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    Inflammatory bowel diseases (IBDs), including Crohn\u27s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD

    Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.

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    Long noncoding RNAs (lncRNA) are key regulators of gene transcription and many show tissue-specific expression. We previously defined a novel inflammatory and metabolic ileal gene signature in treatment-naive pediatric Crohn disease (CD). We now extend our analyses to include potential regulatory lncRNA.Using RNAseq, we systematically profiled lncRNAs and protein-coding gene expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RNA in situ hybridization was used to validate expression. Real-time polymerase chain reaction was used to test lncRNA regulation by IL-1Ξ² in Caco-2 enterocytes.We characterize widespread dysregulation of 459 lncRNAs in the ileum of CD patients. Using only the lncRNA in discovery and independent validation cohorts showed patient classification as accurate as the protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types 1showed that the upregulated LINC01272 is associated with a myeloid pro-inflammatory signature, whereas the downregulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We confirmed tissue-specific expression in biopsies using in situ hybridization, and validated regulation of prioritized lncRNA upon IL-1Ξ² exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury.We systematically define differentially expressed lncRNA in the ileum of newly diagnosed pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNAs, after mechanistic exploration, may serve as potential new tissue-specific targets for RNA-based interventions

    Rapid local anesthesia in humans using minimally invasive microneedles

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    Objective: This study tested the hypothesis that minimally invasive microneedles cause less pain during injection of lidocaine, but induce local anesthesia in humans with the same rapid onset and efficacy as intradermal lidocaine injection using hypodermic needles. Methods: This study was a randomized, single-blinded, within participants, controlled design. Hollow, 500-mm long microneedles were used to inject lidocaine to the forearm of 15 human participants. The associated pain was recorded using a visual analog (VAS) scale. The area and depth of numbness were determined at 0, 7.5, and 15 minutes after injection. Lidocaine was also injected to the dorsum of the hand near a vein, followed by placement of an intravenous catheter and measurement of associated pain. A 26-gauge intradermal bevel hypodermic needle similarly administered lidocaine on the opposite forearm/hand to serve as the positive control. Results: VAS pain scores revealed that injection using microneedles was significantly less painful than hypodermic needles for both the forearm and dorsum of the hand injections. However, there was no significant difference in the area or depth of the resulting numbness between the 2 treatment methods at any time point (0, 7.5, and 15 min) indicating that microneedles had immediate onset and were as effective as hypodermic needles in inducing dermal anesthesia. Moreover, insertion of an intravenous catheter immediately after lidocaine injection on the dorsum of the hand led to comparable pain scores for the microneedle and hypodermic needle treated sites, further confirming efficacy of microneedles in inducing rapid local anesthesia. Lastly, 77% of the participants preferred microneedles and 80% indicated that they did not consider microneedles to be painful. Discussion: This study demonstrates for the first time that microneedle-based lidocaine injection is as rapid and as effective as hypodermic injection in inducing local anesthesia while resulting in significantly less pain during injection

    Partitioning of Mg, Sr, Ba and U into a subaqueous calcite speleothem

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    The trace-element geochemistry of speleothems is becoming increasingly used for reconstructing palaeoclimate, with a particular emphasis on elements whose concentrations vary according to hydrological conditions at the cave site (e.g. Mg, Sr, Ba and U). An important step in interpreting trace-element abundances is understanding the underlying processes of their incorporation. This includes quantifying the fractionation between the solution and speleothem carbonate via partition coefficients (where the partitioning (D) of element X (DX) is the molar ratio [X/Ca] in the calcite divided by the molar ratio [X/Ca] in the parent water) and evaluating the degree of spatial variability across time-constant speleothem layers. Previous studies of how these elements are incorporated into speleothems have focused primarily on stalagmites and their source waters in natural cave settings, or have used synthetic solutions under cave-analogue laboratory conditions to produce similar dripstones. However, dripstones are not the only speleothem types capable of yielding useful palaeoclimate information. In this study, we investigate the incorporation of Mg, Sr, Ba and U into a subaqueous calcite speleothem (CD3) growing in a natural cave pool in Italy. Pool-water measurements extending back 15 years reveal a remarkably stable geochemical environment owing to the deep cave setting, enabling the calculation of precise solution [X/Ca]. We determine the trace element variability of β€˜modern’ subaqueous calcite from a drill core taken through CD3 to derive DMg, DSr, DBa and DU then compare these with published cave, cave-analogue and seawater-analogue studies. The DMg for CD3 is anomalously high (0.042 Β± 0.002) compared to previous estimates at similar temperatures (∼8 Β°C). The DSr (0.100 Β± 0.007) is similar to previously reported values, but data from this study as well as those from Tremaine and Froelich (2013) and Day and Henderson (2013) suggest that [Na/Sr] might play an important role in Sr incorporation through the potential for Na to outcompete Sr for calcite non-lattice sites. DBa in CD3 (0.086 Β± 0.008) is similar to values derived by Day and Henderson (2013) under cave-analogue conditions, whilst DU (0.013 Β± 0.002) is almost an order of magnitude lower, possibly due to the unusually slow speleothem growth rates (<1 ΞΌm aβˆ’1), which could expose the crystal surfaces to leaching of uranyl carbonate. Finally, laser-ablation ICP-MS analysis of the upper 7 ΞΌm of CD3, regarded as β€˜modern’ for the purposes of this study, reveals considerable heterogeneity, particularly for Sr, Ba and U, which is potentially indicative of compositional zoning. This reinforces the need to conduct 2D mapping and/or multiple laser passes to capture the range of time-equivalent elemental variations prior to palaeoclimate interpretation

    Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

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    Copyright: Β© 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)

    Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study

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    Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. // Methods: Data were extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). // Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6–21), group B (49 days, 39–64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. // Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence

    Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients

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    Inflammatory bowel disease (IBD) is a group of chronic digestive tract inflammatory conditions whose genetic etiology is still poorly understood. The incidence of IBD is particularly high among Ashkenazi Jews. Here, we identify 8 novel and plausible IBD-causing genes from the exomes of 4453 genetically identified Ashkenazi Jewish IBD cases (1734) and controls (2719). Various biological pathway analyses are performed, along with bulk and single-cell RNA sequencing, to demonstrate the likely physiological relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of Ashkenazi Jewish adult IBD displays significant overlap with very early onset-IBD genetics. Moreover, by performing biobank phenome-wide analyses, we find that IBD genes have pleiotropic effects that involve other immune responses. Finally, we show that polygenic risk score analyses based on genome-wide high impact variants have high power to predict IBD susceptibility
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