865 research outputs found

    The 1912 Iceland earthquake rupture: Growth and development of a nascent transform system

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    We have mapped in detail surface ruptures of the 1912 magnitude 7.0 strike-slip earthquake in south Iceland. This earthquake ruptured fresh basalt flows that had covered the pre-existing fault. The observed style of surface fracturing closely matches both theoretical predictions of the first stages of shear fracture development and microscopic-scale observations from laboratory experiments. The shear offset distributed across the zone of surface fractures produced by this earthquake is right-lateral and is in the range of 1 to 3 m. Total mapped rupture length is 9 km, but total rupture length is probably at least ∌ 20 km. This interplate earthquake had an exceptionally high ratio of slip to fault length and, by inference, stress drop. The north-south trending rupture of the 1912 earthquake is part of the “bookshelf” faulting in the east-west trending South Iceland Seismic Zone. We ascribe the “bookshelf” faulting in the South Iceland Seismic Zone to a combination of the early development stage of the transform and regional strength anisotropy of the crust.This research was supported by the National Science Foundation, the Icelandic National Power Authority (Landsvirkjun), and the Department of Geological Sciences of Columbia University. Lamont-Dohert Contribution 5036.Peer Reviewe

    Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study

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    <p>Abstract</p> <p>Background</p> <p>It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also.</p> <p>Methods</p> <p>By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit<sup>© </sup>L30D-55.</p> <p>Results</p> <p>Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022–0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035–0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033–0.065)) nor adenosine (0.050 (0.030–0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant.</p> <p>Conclusion</p> <p>In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.</p

    Improving Requirements-Test Alignment by Prescribing Practices that Mitigate Communication Gaps

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    The communication of requirements within software development is vital for project success. Requirements engineering and testing are two processes that when aligned can enable the discovery of issues and misunderstandings earlier, rather than later, and avoid costly and time-consuming rework and delays. There are a number of practices that support requirements-test alignment. However, each organisation and project is different and there is no one-fits-all set of practices. The software process improvement method called Gap Finder is designed to increase requirements-test alignment. The method contains two parts: an assessment part and a prescriptive part. It detects potential communication gaps between people and between artefacts (the assessment part), and identifies practices for mitigating these gaps (the prescriptive part). This paper presents the design and formative evaluation of the prescriptive part; an evaluation of the assessment part was published previously. The Gap Finder method was constructed using a design science research approach and is built on the Theory of Distances for Software Engineering, which in turn is grounded in empirical evidence from five case companies. The formative evaluation was performed through a case study in which Gap Finder was applied to an on-going development project. A qualitative and mixed-method approach was taken in the evaluation, including ethnographically-informed observations. The results show that Gap Finder can detect relevant communication gaps and seven of the nine prescribed practices were deemed practically relevant for mitigating these gaps. The project team found the method to be useful and supported joint reflection and improvement of their requirements communication. Our findings demonstrate that an empirically-based theory can be used to improve software development practices and provide a foundation for further research on factors that affect requirements communicatio

    Transepithelial Transport and Enzymatic Detoxification of Gluten in Gluten-Sensitive Rhesus Macaques

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    In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness

    Navigating overgrazing and cultural values through narratives and participatory mapping : a socio-cultural analysis of sheep grazing in the Faroe Islands

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    Long-term livestock grazing has shaped landscapes, biodiversity, societies, cultures, and economies in the North Atlantic over time. However, overgrazing has become a major environmental sustainability challenge for this region, covering the Faroe Islands, Greenland, Iceland, Norway, and Scotland. The objective of this study was to elicit narratives and spatial patterns of local people's management preferences for sheep grazing in the Faroe Islands through a socio-cultural lens. We collected data via a Public Participation Geographic Information Systems (PPGIS) survey with an open question about hopes and concerns for sheep management in the Faroe Islands and a mapping exercise for expressing spatial preferences for sheep management. Four distinct narratives emerged from a qualitative analysis of responses to the open question (n = 184): (1) Sustainable sheep management, (2) Nature without sheep, (3) Sheep as part of Faroese culture, and (4) Sheep as nuisance. Visual inspection of narrative-specific maps with locations where either no or fewer sheep were preferred indicated that sheep management is not simply a 'sheep vs. no sheep' issue but embedded in a more nuanced consideration of the place of sheep in the landscape and society. For example, for some residents sheep-farming is not a commercial enterprise but a social activity and local source of food. Our combined methodological approach using qualitative and spatial data can help researchers in other fields identify the interplay between place-specific areas of grazing management concern and socio-cultural values, enabling more targeted land-use management policies or plans.Peer reviewe

    Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

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    Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

    Imaging the mantle beneath Iceland using integrated seismological techniques

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    Using a combination of body wave and surface wave data sets to reveal the mantle plume and plume head, this study presents a tomographic image of the mantle structure beneath Iceland to 400 km depth. Data comes primarily from the PASSCAL-HOTSPOT deployment of 30 broadband instruments over a period of 2 years, and is supplemented by data from the SIL and ICEMELT networks. Three sets of relative teleseismic body wave arrival times are generated through cross correlation: S and SKS arrivals at 0.03–0.1 Hz, and P and PKIKP arrivals at 0.03–0.1 and 0.8–2.0 Hz. Prior to inversion the crustal portion of the travel time anomalies is removed using the crustal model ICECRTb. This step has a significant effect on the mantle velocity variations imaged down to a depth of ∌250 km. Inversion of relative arrival times only provides information on lateral velocity variations. Surface waves are therefore used to provide absolute velocity information for the uppermost mantle beneath Iceland. The average wave number for the Love wave fundamental mode at 0.020 and 0.024 Hz is measured and used to invert for the average S velocity. Combination of the body wave and surface wave information reveals a predominantly horizontal low-velocity anomaly extending from the Moho down to ∌250 km depth, interpreted as a plume head. Below the plume head a near-cylindrical low-velocity anomaly with a radius of ∌100 km and peak VP and VS anomalies of −2% and −4%, respectively, extends down to the maximum depth of resolution at 400 km. Within the plume head, in the uppermost mantle above the core of the plume, there is a relatively high velocity with a maximum VP and VS anomaly of +2%. This high-velocity anomaly may be the result of the extreme degree of melt extraction necessary to generate the thick (46 km) crust in central Iceland. Comparison of the plume volumetric flux implied by our images, the crustal generation rate, and the degree of melting suggested by rare earth element inversions, suggests that (1) mantle material must be flowing horizontally away from the plume core faster than the overlying lithosphere and (2) the bulk of the plume material does not participate in melting beneath Iceland

    Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium

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    BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised. OBJECTIVE: To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]). DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≀3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by &gt;3-12 mo, &gt;1-2 yr, &gt;2-7 yr, and &gt;7 yr intervals). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors. RESULTS AND LIMITATIONS: Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status &lt;80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals &gt;3-12 mo, &gt;1-2 yr, &gt;2-7 yr, and &gt;7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p &lt;  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p &lt;  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p &lt;  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p &lt;  0.0001). Data were collected retrospectively. CONCLUSIONS: Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC. PATIENT SUMMARY: We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome
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