Orbitally forced ice sheet fluctuations during the Marinoan Snowball Earth glaciation

Two global glaciations occurred during the Neoproterozoic. Snowball Earth theory posits that these were terminated after millions of years of frigidity when initial warming from rising atmospheric CO2 concentrations was amplified by the reduction of ice cover and hence a reduction in planetary albedo. This scenario implies that most of the geological record of ice cover was deposited in a brief period of melt-back. However, deposits in low palaeo-latitudes show evidence of glacial–interglacial cycles. Here we analyse the sedimentology and oxygen and sulphur isotopic signatures of Marinoan Snowball glaciation deposits from Svalbard, in the Norwegian High Arctic. The deposits preserve a record of oscillations in glacier extent and hydrologic conditions under uniformly high atmospheric CO2 concentrations. We use simulations from a coupled three-dimensional ice sheet and atmospheric general circulation model to show that such oscillations can be explained by orbital forcing in the late stages of a Snowball glaciation. The simulations suggest that while atmospheric CO2 concentrations were rising, but not yet at the threshold required for complete melt-back, the ice sheets would have been sensitive to orbital forcing. We conclude that a similar dynamic can potentially explain the complex successions observed at other localities

Finite Element Analysis to model ischemia experienced in the development of device related pressure ulcers.

Pressure ulcers are a common occurrence of damage to skin. Severity ranges from slightly discoloured skin to full thickness tissue damage which can be fatal in some cases. Engineering effort, typically developing computational models had made significant progress in the understanding and demonstration of the formation mechanism of pressure ulcers with the aetiology of excessive stress however relatively limited attempts had been made to develop relevant models for pressure ulcers caused by ischemia. The aim of this paper is to present evidence of a computational model developed to simulate ischemic pressure ulcer formation and demonstrate the established relationship between the computational data and the acquired clinically relevant experimental data by utilising laser Doppler velocimetry. The application of the presented computational model and the established relationship allows the evaluation of the effect of a mechanical loading to the cutaneous blood flow velocity which is a step closing to understand and evaluate a mechanical load to the formation of pressure ulcers caused by ischemia

Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage

[EN] As a well established discipline and profession, project management has its distinctive tools and techniques. One of them that has been considered the embodiment of the core principles of project management is the Earned Value Management (EVM). In managing construction projects, the EVM has been considered as a suitable tool and hence, has been implemented in various construction industry but absent in some others. Taking into account the dynamic environment where construction companies have to operate, particularly in turbulence environments as the direct result of recent global economic downturn, this paper explores the potential implementation of EVM in one of the construction industry, the Spanish construction industry. The outcomes confirm the needs for and feasibility of implementing EVM as a structured approach in the industry to reposition the Spanish construction industry with the long term view to increase its project management maturity level as a pathway to gaining competitive advantage.Universitat Politecnica de Valencia [grant number 19701344]Sutrisna, M.; Pellicer, E.; Torres-Machí, C.; Picornell, M. (2018). Exploring earned value management in the Spanish construction industry as a pathway to competitive advantage. International Journal of Construction Management. 20(1):1-12. https://doi.org/10.1080/15623599.2018.1459155S112201Anbari, F. T. (2004). Earned value project management method and extensions. IEEE Engineering Management Review, 32(3), 97-97. doi:10.1109/emr.2004.25113Aram, J. D., & Walochik, K. (1996). Improvisation and the Spanish Manager. International Studies of Management & Organization, 26(4), 73-89. doi:10.1080/00208825.1996.11656695Brandon, D. M. (1998). Implementing Earned Value Easily and Effectively. Project Management Journal, 29(2), 11-18. doi:10.1177/875697289802900204Brown, A., & Adams, J. (2000). Measuring the effect of project management on construction outputs: a new approach. International Journal of Project Management, 18(5), 327-335. doi:10.1016/s0263-7863(99)00026-5Bryde, D. J. (2003). Modelling project management performance. International Journal of Quality & Reliability Management, 20(2), 229-254. doi:10.1108/02656710310456635Chen, H. L., Chen, W. T., & Lin, Y. L. (2016). Earned value project management: Improving the predictive power of planned value. International Journal of Project Management, 34(1), 22-29. doi:10.1016/j.ijproman.2015.09.008De la Cruz, M. P., del Caño, A., & de la Cruz, E. (2006). Downside Risks in Construction Projects Developed by the Civil Service: The Case of Spain. Journal of Construction Engineering and Management, 132(8), 844-852. doi:10.1061/(asce)0733-9364(2006)132:8(844)Din, S., Abd-Hamid, Z., & Bryde, D. J. (2011). ISO 9000 certification and construction project performance: The Malaysian experience. International Journal of Project Management, 29(8), 1044-1056. doi:10.1016/j.ijproman.2010.11.001Eldin, N. N. (1989). Measurement of Work Progress: Quantitative Technique. Journal of Construction Engineering and Management, 115(3), 462-474. doi:10.1061/(asce)0733-9364(1989)115:3(462)Gidado, K. I. (1996). Project complexity: The focal point of construction production planning. Construction Management and Economics, 14(3), 213-225. doi:10.1080/014461996373476Hastak, M., Halpin, D. W., & Vanegas, J. (1996). COMPASS—New Paradigm for Project Cost Control Strategy and Planning. Journal of Construction Engineering and Management, 122(3), 254-264. doi:10.1061/(asce)0733-9364(1996)122:3(254)D. Holt, G., & S. Goulding, J. (2014). Conceptualisation of ambiguous-mixed-methods within building and construction research. Journal of Engineering, Design and Technology, 12(2), 244-262. doi:10.1108/jedt-02-2013-0020Ibbs, C. W., & Kwak, Y. H. (2000). Assessing Project Management Maturity. Project Management Journal, 31(1), 32-43. doi:10.1177/875697280003100106Jugdev, K., & Thomas, J. (2002). 2002 Student Paper Award Winner: Project Management Maturity Models: The Silver Bullets of Competitive Advantage? Project Management Journal, 33(4), 4-14. doi:10.1177/875697280203300402Kim, E., Wells, W. G., & Duffey, M. R. (2003). A model for effective implementation of Earned Value Management methodology. International Journal of Project Management, 21(5), 375-382. doi:10.1016/s0263-7863(02)00049-2Kim, T., Kim, Y.-W., & Cho, H. (2016). Customer Earned Value: Performance Indicator from Flow and Value Generation View. Journal of Management in Engineering, 32(1), 04015017. doi:10.1061/(asce)me.1943-5479.0000377Laufer, A., & Tucker, R. L. (1987). Is construction project planning really doing its job? A critical examination of focus, role and process. Construction Management and Economics, 5(3), 243-266. doi:10.1080/01446198700000023Liberatore, M. J., Pollack-Johnson, B., & Smith, C. A. (2001). Project Management in Construction: Software Use and Research Directions. Journal of Construction Engineering and Management, 127(2), 101-107. doi:10.1061/(asce)0733-9364(2001)127:2(101)Mir, F. A., & Pinnington, A. H. (2014). Exploring the value of project management: Linking Project Management Performance and Project Success. International Journal of Project Management, 32(2), 202-217. doi:10.1016/j.ijproman.2013.05.012Navon, R., & Haskaya, I. (2006). Is detailed progress monitoring possible without designated manual data collection? Construction Management and Economics, 24(12), 1225-1229. doi:10.1080/01446190600999097Onwuegbuzie, A. J., & Leech, N. L. (2005). Taking the «Q» Out of Research: Teaching Research Methodology Courses Without the Divide Between Quantitative and Qualitative Paradigms. Quality & Quantity, 39(3), 267-295. doi:10.1007/s11135-004-1670-0Oviedo-Haito, R. J., Jiménez, J., Cardoso, F. F., & Pellicer, E. (2014). Survival Factors for Subcontractors in Economic Downturns. Journal of Construction Engineering and Management, 140(3), 04013056. doi:10.1061/(asce)co.1943-7862.0000811Pellicer, E., Sanz, M. A., Esmaeili, B., & Molenaar, K. R. (2016). Exploration of Team Integration in Spanish Multifamily Residential Building Construction. Journal of Management in Engineering, 32(5), 05016012. doi:10.1061/(asce)me.1943-5479.0000438Potts, K., & Ankrah, N. (2008). Construction Cost Management. doi:10.4324/9780203933015Vanhoucke, M. (2012). Project Management with Dynamic Scheduling. doi:10.1007/978-3-642-25175-7Yazici, H. J. (2009). The Role of Project Management Maturity and Organizational Culture in Perceived Performance. Project Management Journal, 40(3), 14-33. doi:10.1002/pmj.20121Yu, A. G., Flett, P. D., & Bowers, J. A. (2005). Developing a value-centred proposal for assessing project success. International Journal of Project Management, 23(6), 428-436. doi:10.1016/j.ijproman.2005.01.00

Nitric Oxide-Induced Activation of the AMP-Activated Protein Kinase α2 Subunit Attenuates IκB Kinase Activity and Inflammatory Responses in Endothelial Cells

BACKGROUND: In endothelial cells, activation of the AMP-activated protein kinase (AMPK) has been linked with anti-inflammatory actions but the events downstream of kinase activation are not well understood. Here, we addressed the effects of AMPK activation/deletion on the activation of NFκB and determined whether the AMPK could contribute to the anti-inflammatory actions of nitric oxide (NO). METHODOLOGY/PRINCIPAL FINDINGS: Overexpression of a dominant negative AMPKα2 mutant in tumor necrosis factor-α-stimulated human endothelial cells resulted in increased NFκB activity, E-selectin expression and monocyte adhesion. In endothelial cells from AMPKα2(-/-) mice the interleukin (IL)-1β induced expression of E-selectin was significantly increased. DETA-NO activated the AMPK and attenuated NFκB activation/E-selectin expression, effects not observed in human endothelial cells in the presence of the dominant negative AMPK, or in endothelial cells from AMPKα2(-/-) mice. Mechanistically, overexpression of constitutively active AMPK decreased the phosphorylation of IκB and p65, indicating a link between AMPK and the IκB kinase (IKK). Indeed, IKK (more specifically residues Ser177 and Ser181) was found to be a direct substrate of AMPKα2 in vitro. The hyper-phosphorylation of the IKK, which is known to result in its inhibition, was also apparent in endothelial cells from AMPKα2(+/+) versus AMPKα2(-/-) mice. CONCLUSIONS: These results demonstrate that the IKK is a direct substrate of AMPKα2 and that its phosphorylation on Ser177 and Ser181 results in the inhibition of the kinase and decreased NFκB activation. Moreover, as NO potently activates AMPK in endothelial cells, a portion of the anti-inflammatory effects of NO are mediated by AMPK

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95%; CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95%; CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC

The extramural metastasis might be categorized in lymph node staging for colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The objective of this study is to assess the clinical significance and prognostic impact of extramural metastasis in colorectal carcinoma and establish an optimal categorization in the staging system.</p> <p>Methods</p> <p>To determine the frequency and prognostic significance of extramural metastasis, from 2000 to 2005, a total of 1,215 patients with colorectal cancer who underwent surgical resection were recruited into this study. Individual demographic and clinicopathologic data were collected including tumor stage, nodal stage, tumor histology, degree of tumor differentiation, and presence of lymphovascular invasion. After surgery, all patients received standard treatments and follow-up, which were closed in April 2010.</p> <p>Results</p> <p>EM was detected in 167 (13.7%) patients and in 230 (1.8%) of the 12,534 nodules retrieved as 'lymph nodes'. The incidence of extramural metastasis was significantly higher in patients with large tumors, deeper invasive depth and more lymph node metastasis (P < 0.001). After curative operation, overall survival was significantly worse for patients with extramural metastasis than those without (P < 0.001). Multivariate analysis identified extramural metastasis as an independent prognostic factor (RR = 2.1, 95%CI:1.5-3.0). By using the Akaike information criterion (AIC), N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and extramural metastasis were treated together as N factors(AIC = 1025.3).</p> <p>Conclusion</p> <p>Extramural metastasis might be diagnosed as replaced lymph nodes in the process of classification, thus forming a new categorization.</p

The wood from the trees: The use of timber in construction

Trees, and their derivative products, have been used by societies around the world for thousands of years. Contemporary construction of tall buildings from timber, in whole or in part, suggests a growing interest in the potential for building with wood at a scale not previously attainable. As wood is the only significant building material that is grown, we have a natural inclination that building in wood is good for the environment. But under what conditions is this really the case? The environmental benefits of using timber are not straightforward; although it is a natural product, a large amount of energy is used to dry and process it. Much of this can come from the biomass of the tree itself, but that requires investment in plant, which is not always possible in an industry that is widely distributed among many small producers. And what should we build with wood? Are skyscrapers in timber a good use of this natural resource, or are there other aspects of civil and structural engineering, or large-scale infrastructure, that would be a better use of wood? Here, we consider a holistic picture ranging in scale from the science of the cell wall to the engineering and global policies that could maximise forestry and timber construction as a boon to both people and the planet.This work was funded in major part by a Leverhulme Trust Programme Grant. Additional support comes from the EPSRC (UK)EP/K011774/1 (Allwood and Densley-Tingley) and NSERC (Canada) (Fleming).This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.rser.2016.09.10

The search for the 'next' euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

Purpose: A detailed review on the chemistry and pharmacology of non-fentanil novel synthetic opioid receptor agonists, particularly N-substituted benzamides and acetamides (known colloquially as U-drugs) and 4-aminocyclohexanols, developed at the Upjohn Company in the 1970s and 1980s is presentedMethod: Peer-reviewed literature, patents, professional literature, data from international early warning systems and drug user fora discussion threads have been used to track their emergence as substances of abuse.Results: In terms of impact on drug markets, prevalence and harm, the most significant compound of this class to date has been U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide), reported by users to give short-lasting euphoric effects and a desire to re-dose. Since U-47700 was internationally controlled in 2017, a range of related compounds with similar chemical structures, adapted from the original patented compounds, have appeared on the illicit drugs market. Interest in a structurally unrelated opioid developed by the Upjohn Company and now known as BDPC/bromadol appears to be increasing and should be closely monitored.Conclusions: International early warning systems are an essential part of tracking emerging psychoactive substances and allow responsive action to be taken to facilitate the gathering of relevant data for detailed risk assessments. Pre-emptive research on the most likely compounds to emerge next, so providing drug metabolism and pharmacokinetic data to ensure that new substances are detected early in toxicological samples is recommended. As these compounds are chiral compounds and stereochemistry has a large effect on their potency, it is recommended that detection methods consider the determination of configuration

Phylogenetic analysis of Croatian orf viruses isolated from sheep and goats

<p>Abstract</p> <p>Background</p> <p>The <it>Orf virus </it>(ORFV) is the prototype of the parapoxvirus genus and it primarily causes contagious ecthyma in goats, sheep, and other ruminants worldwide. In this paper, we described the sequence and phylogenetic analysis of the B2L gene of ORFV from two natural outbreaks: i) in autochthonous Croatian Cres-breed sheep and ii) on small family goat farm.</p> <p>Results</p> <p>Sequence and phylogenetic analyses of the ORFV B2L gene showed that the Cro-Cres-12446/09 and Cro-Goat-11727/10 were not clustered together. Cro-Cres-12446/09 shared the highest similarity with ORFV NZ2 from New Zealand, and Ena from Japan; Cro-Goat-11727/10 was closest to the HuB from China and Taiping and Hoping from Taiwan.</p> <p>Conclusion</p> <p>Distinct ORFV strains are circulating in Croatia. Although ORFV infections are found ubiquitously wherever sheep and goats are farmed in Croatia, this is the first information on genetic relatedness of any Croatian ORFV with other isolates around the world.</p