Migrating medical communications software to a multi-tenant cloud environment

The rise of cloud computing has paved the way for many new applications. Many of these new cloud applications are also multi-tenant, ensuring multiple end users can make use of the same application instance. While these technologies make it possible to create many new applications, many legacy applications can also benefit from the added flexibility and cost-savings of cloud computing and multi-tenancy. In this paper, we describe the steps required to migrate a. NET-based medical communications application to the Windows Azure public cloud environment, and the steps required to add multi-tenancy to the application. We then discuss the advantages and disadvantages of our migration approach. We found that the migration to the cloud itself requires only a limited amount of changes to the application, but that this also limited the benefits, as individual instances would only be partially used. Adding multi-tenancy requires more changes, but when this is done, it has the potential to greatly reduce the cost of running the application

Assessment of the food available to cape anchovy during their spawning season

The Cape anchovy Engraulis capensis spawns serially between September and February each year on the western Agulhas Bank, South Africa. Food availability in terms of copepod biomass is important for successfulspawning and subsequent recruitment. This note investigates the variability within a spawning season (1993/94 and 1994/95) of copepod biomass on the western Bank and demonstrates that the food available to the Capeanchovy cannot be adequately assessed by a single mid-season estimate, as was the previous sampling strategy. The mid-season estimate of food availability failed to reveal important fluctuations, such as the small biomass of copepods in January 1994, which contributed to the early cessation of spawning and subsequent poor recruitment in 1994. A strategy, based on monthly sampling, is recommended for future sampling programmes

Identifying global synchronies in marine zooplankton populations: issues and opportunities

Analyses of the influences of climate variability on local zooplankton populations and those within ocean basins are relatively recent (past 5–10 years). What is lacking are comparisons of zooplankton population variability among the world's oceans, in contrast to such global comparisons of fish populations. This article examines the key questions, capabilities, and impediments for global comparisons of zooplankton populations using long-term (>10 year) data sets. The key question is whether global synchronies in zooplankton populations exist. If yes, then (i) to what extent are they driven by “bottom-up” (productivity) or “top-down” (predation) forcing; (ii) are they initiated by persistent forcing or by episodic events whose effects propagate through the system with different time-lags; and (iii) what proportion of the biological variance is caused directly by physical forcing and what proportion might be caused by non-linear instabilities in the biological dynamics (e.g. through trophodynamic links)? The capabilities are improving quickly that will enable global comparisons of zooplankton populations. Several long-term sampling programmes and data sets exist in many ocean basins, and the data are becoming more available. In addition, there has been a major philosophical change recently that now recognizes the value of continuing long-term zooplankton observation programmes. Understanding of life-history characteristics and the ecosystem roles of zooplankton are also improving. A first and critical step in exploring possible synchrony among zooplankton from geographically diverse regions is to recognize the limitations of the various data sets. There exist several impediments that must be surmounted before global comparisons of zooplankton populations can be realized. Methodological issues concerned with the diverse spatial and temporal scales of “monitored” planktonic populations are one example. Other problems include data access issues, structural constraints regarding funding of international comparisons, and lack of understanding by decision-makers of the value of zooplankton as indicators of ecosystem change. We provide recommendations for alleviating some of these impediments, and suggest a need for an easily understood example of global synchrony in zooplankton populations and the relation of those signals to large-scale climate drivers

Characteristics of survivors: growth and nutritional condition of early stages of the hake species Merluccius paradoxus and M. capensis in the southern Benguela ecosystem

Larval mortality in marine fish is strongly linked to characteristic traits such as growth and condition, but the variability in these traits is poorly understood. We tried to identify the variability in growth in relation to conditions leading to greater survival chances for early stages of Cape hake, Merluccius paradoxus and M. capensis, in the Benguela upwelling ecosystem. During two cruises in 2007 and one cruise in 2008, hake larvae and juveniles were caught. Otolith microstructures revealed a larval age ranging from 2 to 29 days post-hatching (dph), whereas juvenile age was 67–152 dph. RNA:DNA ratios, used to evaluate nutritional condition, were above the relevant threshold level for growth. No strong coupling between growth and condition was detected, indicating a complex relationship between these factors in the southern Benguela ecosystem. Merluccius paradoxus juveniles caught in 2007 (the surviving larvae of 2006) had significantly higher larval growth rates than larvae hatched in 2007 and 2008, possibly indicating selection for fast growth in 2006. High selection pressure on growth could be linked to predation avoidance, including cannibalism

Residual plaque burden in patients with acute coronary syndromes after successful percutaneous coronary intervention

Objectives: The aim of this study was to characterize and evaluate the clinical impact of untreated atherosclerotic disease after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). Background: Residual atherosclerotic disease after successful PCI may predispose future major adverse cardiovascular events (MACE). Compared with intravascular ultrasound (IVUS), angiography underestimates the presence and severity of coronary artery disease. Methods: Following successful PCI of all clinically significant lesions in 697 patients with ACS, 3-vessel grayscale and radiofrequency IVUS was performed. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. A total of 3,229 untreated lesions (4.89 ± 1.98 lesions/patient) were identified by IVUS, with mean plaque burden (PB) of 49.6 ± 4.2%. Results: By angiography these nonculprit lesions were mild, with mean diameter stenosis of 38.9 ± 15.3%. At least 1 lesion with a PB <70% (PB70 lesion) was found in 220 (33%) patients. By multivariable analysis, a history of prior PCI and angiographic 3-vessel disease were independent predictors of PB70 lesions. Patients with PB70 lesions had greater total percent plaque volume, normalized PB, fibroatheromas, thin-cap fibroatheromas, and normalized volumes of necrotic core and dense calcium. Patients with PB70 lesions had greater 3-year rates of MACE due to untreated nonculprit lesions (20.8% vs. 7.7%, p < 0.0001). Among imaged nonculprit lesions, the proportion of PB70 lesions causing MACE was significantly greater than non-PB70 lesions (8.7% vs. 1.0%, p < 0.0001). Conclusions: After successful PCI of all angiographically significant lesions, overall untreated atherosclerotic burden remains high, and PB70 lesions are frequently present in the proximal and mid-coronary tree. Patients with PB70 lesions have greater atherosclerosis throughout the coronary tree, have more thin-cap fibroatheromas, and are at increased risk for future cardiovascular events. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466

Addressing quality and usability of surface water bodies in semi-arid regions with mining influences

Water resources management has considerable importance, specifically in the context of climate change. This subject has introduced new challenges in semi-arid regions with water quality problems, such as the Iberian Pyrite Belt, which is one of the largest metallogenetic provinces in the world and one of the driest regions in Europe. Positioned in the Mediterranean context, the region has a high density of polymetallic sulphide mines that promote the degradation of water systems. The present study aims to assess the water quality in the Pyrite Belt, considering a total of 34 surface water bodies, including constructed reservoirs, permanent and ephemeral streams, and mining facilities with accumulated water (e.g., pit lakes and mining dams). The water samples were analysed for physico-chemical properties, including field parameters (pH, electrical conductivity), alkalinity/acidity, hardness, anions, and potential toxic elements. The results were used for hydrochemical classifications and the assessment of suitability for public uses. Statistical methods, such as hierarchical cluster analysis and nearest centroid classifier, were used for grouping and evaluating the similarity between water bodies. Two groups were generated from the analysis: i) constructed lakes with alkaline and sodium signatures; and ii) waters suffering from the influence of mining wastes, e.g., showing high acidity, sulphate and metal contents. Therefore, the loss of water quality in the vicinity of mines reflects the impact of acid mine drainage. The methodological approach used may be applied to the integrated management of water resources in regions with mining influences and where it is necessary to combat drought and water scarcity scenarios.Patricia Gomes acknowledge FCT (Science and Technology Foundation, Portugal) by the research fellowship under the POCH (Programa Operacional Capital Humano) supported by the European Social Fund and National Funds of MCTES (Ministerio da Ciencia, Tecnologia e Ensino Superior) with reference SFRH/BD/108887/2015. This work was co-funded by the European Union through the European Regional Development Fund, based on COMPETE 2020 (Programa Operacional da Competitividade e Internacionalizacao) - project ICT (UID/GEO/04683/2013) with reference POCI-01-0145-FEDER-007690 and project Nano-MINENV number 029259

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma

Background: Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment. Methods: We analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models. Results: Tasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+ cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo. Conclusion: Our study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients

Self-maintaining or continuously refreshed? The genetic structure of Euphausia lucens populations in the Benguela upwelling ecosystem

Populations of Euphausia lucens over the shelf of the southern Benguela upwelling region could be self-maintaining. Alternatively, they could be continually refreshed by expatriates from the SW Atlantic that enter the system via South Atlantic Central Water in the south, before developing and then being lost through advection off Namibia. These two hypotheses are investigated here by examining geographic heterogeneity and molecular variation (cox1 and ND1) of the species across its distributional range in the Southern Hemisphere. Comparisons are made with E. vallentini, which is assumed to show panmixia associated with its circumglobal distribution between 50 and 60°S. Phylogenetic analysis with mitochondrial 16S ribosomal RNA and cytochrome oxidase 1 (cox1) confirmed that E. lucens and E. vallentinirepresent sister taxa. Strong geographic structuring of cox1 and ND1 mtDNA genetic variation by ocean basin was recorded in E. lucens, indicating that neritic populations off South Africa are likely self-maintaining. This contrasts with the results for E. vallentini, which appears to occur as a single panmictic population across its distributional range. These differences are likely related to the habitats (neritic, E. lucens; oceanic, E. vallentini) occupied by each species. The results of the neutrality tests are consistent with demographic processes and suggest growth in E. lucens and equilibrium or shrinkage in E. vallentini. Although purifying selection cannot be ruled out in the former, the very few haplotypes recovered from E. vallentini could indicate that any population expansion following a crash is not yet reflected in the relatively slowly evolving mtDNA markers used here. Further work using other methods is recommended.Web of Scienc

Revascularization for Unprotected Left Main Coronary Artery Disease: An Evolution in Clinical Decision Making

Coronary artery bypass grafting (CABG) has been considered the standard therapy for unprotected (nonrevascularized) left main coronary disease (ULM). However, increasing experience with ULM percutaneous coronary intervention (PCI) has resulted in high procedural success and favorable early and late clinical outcomes. In particular, reduction in clinical restenosis with drug-eluting stents, evolution of procedural technique, and demonstration of favorable outcomes from comparative trials with CABG have promoted consideration of PCI as an alternative revascularization strategy in selected patients with ULM disease. This review summarizes the results from comparative studies examining PCI versus CABG for ULM disease, discusses changing indications for ULM PCI and identifies outstanding issues that must be considered before further advancing treatment recommendations

Environmental-dependent proline accumulation in plants living on gypsum soils

[EN] Biosynthesis of proline¿or other compatible solutes¿is a conserved response of all organisms to different abiotic stress conditions leading to cellular dehydration. However, the biological relevance of this reaction for plant stress tolerance mechanisms remains largely unknown, since there are very few available data on proline levels in stress-tolerant plants under natural conditions. The aim of this work was to establish the relationship between proline levels and different environmental stress factors in plants living on gypsum soils. During the 2-year study (2009¿2010), soil parameters and climatic data were monitored, and proline contents were determined, in six successive samplings, in ten taxa present in selected experimental plots, three in a gypsum area and one in a semiarid zone, both located in the province of Valencia, in south-east Spain. Mean proline values varied significantly between species; however, seasonal variations within species were in many cases even wider, with the most extreme differences registered in Helianthemum syriacum (almost 30 lmol g-1 of DW in summer 2009, as compared to ca. 0.5 in spring, in one of the plots of the gypsum zone). Higher proline contents in plants were generally observed under lower soil humidity conditions, especially in the 2009 summer sampling preceded by a severe drought period. Our results clearly show a positive correlation between the degree of environmental stress and the proline level in most of the taxa included in this study, supporting a functional role of proline in stress tolerance mechanisms of plants adapted to gypsum. However, the main trigger of proline biosynthesis in this type of habitat, as in arid or semiarid zones, is water deficit, while the component of ¿salt stress¿ due to the presence of gypsum in the soil only plays a secondary role.This work has been supported by the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund.Boscaiu, M.; Bautista Carrascosa, I.; Lidón Cerezuela, AL.; Llinares Palacios, JV.; Lull, C.; Donat-Torres, M.; Mayoral García-Berlanga, O.... (2013). Environmental-dependent proline accumulation in plants living on gypsum soils. Acta Physiologiae Plantarum. 35:2193-2204. https://doi.org/10.1007/s11738-013-1256-3S2193220435Alvarado JJ, Ruiz JM, López-Cantarero I, Molero J, Romero L (2000) Nitrogen metabolism in five plant species characteristic of gypsiferous soils. J Plant Physiol 156:612–616Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59:206–216Bates LS, Waldren RP, Teare ID (1973) Rapid determination of free proline for water stress studies. Plant Soil 39:205–207Briens M, Larher F (1982) Osmoregulation in halophytic higher plants: a comparative study of soluble carbohydrates, polyols, betaines and free proline. Plant, Cell Environ 5:287–292Burriel F, Hernando V (1947) Nuevo método para determinar el fósforo asimilable en los suelos. Anales de Edafología y Fisiología Vegetal 9:611–622Caballero I, Olano JM, Loidi J, Escudero A (2003) Seed bank structure along a semi-arid gypsum gradient in Central Spain. J Arid Environ 55:287–299Escudero A, Carnes LF, Pérez García F (1997) Seed germination of gypsophytes and gypsovags in semi-arid central Spain. J Arid Environ 36:487–497Escudero A, Somolinos RC, Olano JM, Rubio A (1999) Factors controlling the establishment of Helianthemum squamatum, an endemic gypsophite of semi-arid Spain. J Ecol 87:290–302FAO (1990) Management of gypsiferous soils. FAO Soils Bull 62Ferriol M, Pérez I, Merle H, Boira H (2006) Ecological germination requirements of the aggregate species Teucrium pumilum (Labiatae) endemic to Spain. Plant Soil 284:205–216Flowers TJ, Colmer TD (2008) Salinity tolerance in halophytes. New Phytol 179:945–963Flowers TJ, Troke PF, Yeo AR (1977) The mechanism of salt tolerance in halophytes. Ann Rev Plant Physiol 28:89–121Gil R, Lull C, Boscaiu M, Bautista I, Lidón A, Vicente O (2011) Soluble carbohydrates as osmolytes in several halophytes from a Mediterranean salt marsh. Not Bot Horti Agrobo 39(2):9–17Grigore MN, Boscaiu M, Vicente O (2011) Assessment of the relevance of osmolyte biosynthesis for salt tolerance of halophytes under natural conditions. Eur J Plant Sci Biotech 5:12–19Hare PD, Cress WA, Van Standen J (1998) Dissecting the roles of osmolyte accumulation during stress. Plant Cell Environ 21:535–553Keeney DR, Nelson DW (1982) Nitrogen inorganic forms. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 643–698Knudsen D, Peterson GA, Pratt PF (1982) Lithium, Sodium and Potassium. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 225–246Kuo S (1996) Phosphorus. In: Spark DL (ed) Methods of soil analysis: chemical methods, part 3. Soil Science Society of America, Madison, pp 869–919Martens H, Maes T (1989) Multivariate calibration. Wiley, New York, pp 97–108Martínez-Duro E, Ferrandis P, Escudero A, Luzuriaga AL, Herranz JM (2010) Secondary old-field succession in an ecosystem with restrictive soils: does time from abandonment matter? Appl Veg Sci 13:234–248Meyer SE (1986) The ecology of gypsophile endemism in the eastern Mojave desert. Ecology 67:1303–1313Meyer SE, García-Moya E (1989) Plant community patterns and soil moisture regime in gypsum grasslands of north central Mexico. J Arid Environ 16:147–155Meyer SE, García-Moya E, Lagunes-Espinoza LC (1992) Topographic and soil surface effects on gypsophile plant community patterns in central Mexico. J Veg Sci 3:429–438Moruno F, Soriano P, Vicente O, Boscaiu M, Estrelles E (2011) Opportunistic germination behaviour of Gypsophila (Caryophyllaceae) in two priority habitats from semi-arid Mediterranean steppes. Not Bot Horti Agrobo 39(1):18–23Mota JF, Sánchez Gómez P, Merlo Calvente ME, Catalán Rodríguez P, Laguna Lumbreras E, de la Cruz Rot M, Navarro Reyes FB, Marchal Gallardo F, Bartolomé Esteban C, Martínez Labarga JM, Sainz Ollero H, Valle Tendero F, Serra Laliga L, Martínez Hernández F, Garrido Becerra JA, Pérez García FJ (2009) Aproximación a la checklist de los gipsófitos ibéricos. Anales de Biología 31:71–80Murakeözy ÉP, Nagy Z, Duhazé C, Bouchereau A, Tuba Z (2003) Seasonal changes in the levels of compatible osmolytes in three halophytic species of inland saline vegetation in Hungary. J Plant Physiol 160:395–401Nelson DW, Sommers LE (1982) Total carbon, organic carbon, and organic matter. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 539–577Palacio S, Escudero A, Montserrat-Martí G, Maestro M, Milla R, Albert M (2007) Plants living on gypsum: beyond the specialist model. Ann Bot 99:333–343Parsons RF (1977) Gypsophily in plants—a review. Am Midl Nat 96:1–20Pueyo Y, Alados CL, Maestro M, Komac B (2007) Gypsophile vegetation patterns under a range of soil properties induced by topographical position. Plant Ecol 189:301–311Rivas-Martínez S, Rivas-Sáenz S (2009) Worldwide Bioclimatic Classification System. Phytosociological Research Center, Complutense University of Madrid, Spain. http://www.globalbioclimatics.org/ . Accessed 15 Nov 2012Romão RL, Escudero A (2005) Gypsum physical soil crusts and the existence of gypsophytes in semi-arid central Spain. Plant Ecol 181:127–137Rubio A, Escudero A (2000) Small-scale spatial soil-plant relationship in semi-arid gypsum environment. Plant Soil 220:139–150Ruíz JM, López-Cantarero I, Rivero RM, Romero L (2003) Sulphur phytoaccumulation in plant species characteristic of gypsiferous soils. Int J Phytorem 5:203–210Szabados L, Savouré A (2010) Proline: a multifunctional amino acid. Trends Plant Sci 15:89–97Szabados L, Kovács H, Zilberstein A, Bouchereau A (2011) Plants in extreme environments: importance of protective compounds in stress tolerance. Adv Bot Res 57:105–150Tecator Application Note (1984) AN 5226: Determination of ammonium in 2 M KCl soil extracts by FIAstar 5000. AN 5201: Determination of the sum of nitrate and nitrite in water by FIAstar 5000. (Adapted for 2 M KCl soil extracts)Tipirdamaz R, Gagneul D, Duhazé C, Aïnouche A, Monnier C, Özkum D, Larher F (2006) Clustering of halophytes from an inland salt marsh in Turkey according to their ability to accumulate sodium and nitrogenous osmolytes. Environ Exp Bot 57:139–153Verheye WH, Boyadgiev TG (1997) Evaluating the land use potential of gypsiferous soils from field pedogenic characteristics. Soil Use Manage 13:97–103Vicente O, Boscaiu M, Naranjo MA, Estrelles E, Bellés JM, Soriano P (2004) Responses to salt stress in the halophyte Plantago crassifolia (Plantaginaceae). J Arid Environ 58:463–481Yancey PH (2005) Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 208:2819–283