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A springtime source of toxic Pseudo-nitzschia cells on razor clam beaches in the Pacific Northwest
Concentrations of domoic acid (DA) above the regulatory limit in Washington coast razor clams are usually higher on northern beaches from summer to fall. Recent field studies have confirmed that the primary source of toxic Pseudo-nitzschia (PN) cells in those seasons is a semi-retentive topographically trapped seasonal eddy located offshore and north of the clamming beaches. Another semi-retentive coastal feature, Heceta Bank, that has been shown to support toxic PN cells in summer, is located south of Washington's clamming beaches. In this paper we present evidence to demonstrate that Heceta Bank, although not a likely source of toxic cells to Washington in summer due to the prevailing southward seasonal currents, may be a source of cells in springtime before the southward currents develop. In contrast to summer and fall seasons, concentrations of DA in razor clams are typically higher at southern beaches in spring. The likelihood of a southern source is explored using biological and transport data surrounding a period of toxic razor clams in April 2005. In particular, satellite-derived chlorophyll data confirm that a bloom occurred over Heceta Bank in March of that year, just prior to a period of strong storm-driven northward transport. PN cells of the same species observed in the April bloom on Washington beaches and in offshore waters were documented in Oregon offshore waters on the northern edge of Heceta Bank. That species, P. australis, has been shown to be highly toxic in this region; shore-based data show that razor clams on Oregon beaches were also toxic at the time when P. australis was observed offshore. Both measured and modeled currents show that transport was more than sufficient to move cells from the vicinity of Heceta Bank, Oregon to southern Washington beaches by the time the toxic cells were observed on those beaches. The rapid transport was due in part to the presence of the buoyant plume from the Columbia River, a common feature in winter and spring in nearshore waters of the U.S. Pacific Northwest. (c) 2013 Elsevier B.V. All rights reserved.Keywords: Coastal currents, Heceta Bank, Domoic acid, HAB, Pseudo-nitzschia, Juan de Fuca edd
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Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema
<p>Abstract</p> <p>Background</p> <p>Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.</p> <p>Methods</p> <p>Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.</p> <p>Results</p> <p>Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.</p> <p>Conclusions</p> <p>The results confirm and quantify the causal relationships with smoking.</p
A Springtime Source of Toxic \u3cem\u3ePseudo-nitzschia\u3c/em\u3e Cells on Razor Clam Beaches in the Pacific Northwest
Concentrations of domoic acid (DA) above the regulatory limit in Washington coast razor clams are usually higher on northern beaches from summer to fall. Recent field studies have confirmed that the primary source of toxic Pseudo-nitzschia (PN) cells in those seasons is a semi-retentive topographically trapped seasonal eddy located offshore and north of the clamming beaches. Another semi-retentive coastal feature, Heceta Bank, that has been shown to support toxic PN cells in summer, is located south of Washington’s clamming beaches. In this paper we present evidence to demonstrate that Heceta Bank, although not a likely source of toxic cells to Washington in summer due to the prevailing southward seasonal currents, may be a source of cells in springtime before the southward currents develop. In contrast to summer and fall seasons, concentrations of DA in razor clams are typically higher at southern beaches in spring. The likelihood of a southern source is explored using biological and transport data surrounding a period of toxic razor clams in April 2005. In particular, satellite-derived chlorophyll data confirm that a bloom occurred over Heceta Bank in March of that year, just prior to a period of strong storm-driven northward transport. PN cells of the same species observed in the April bloom on Washington beaches and in offshore waters were documented in Oregon offshore waters on the northern edge of Heceta Bank. That species, P. australis, has been shown to be highly toxic in this region; shore-based data show that razor clams on Oregon beaches were also toxic at the time when P. australis was observed offshore. Both measured and modeled currents show that transport was more than sufficient to move cells from the vicinity of Heceta Bank, Oregon to southern Washington beaches by the time the toxic cells were observed on those beaches. The rapid transport was due in part to the presence of the buoyant plume from the Columbia River, a common feature in winter and spring in nearshore waters of the U.S. Pacific Northwest
Ketones and lactate “fuel” tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism
Previously, we proposed a new model for understanding the “Warburg effect” in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm “The Reverse Warburg Effect.” Here, we directly evaluate whether the end-products of aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More specifically, we show that administration of 3-hydroxy-butyrate (a ketone body) increases tumor growth by ∼2.5-fold, without any measurable increases in tumor vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as chemo-attractants, stimulating the migration of epithelial cancer cells. Although L-lactate did not increase primary tumor growth, it stimulated the formation of lung metastases by ∼10-fold. Thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the “reverse Warburg effect.” Moreover, we discuss the possibility that it may be unwise to use lactate-containing i.v. solutions (such as lactated Ringer's or Hartmann's solution) in cancer patients, given the dramatic metastasis-promoting properties of L-lactate. Also, we provide evidence for the upregulation of oxidative mitochondrial metabolism and the TCA cycle in human breast cancer cells in vivo, via an informatics analysis of the existing raw transcriptional profiles of epithelial breast cancer cells and adjacent stromal cells. Lastly, our findings may explain why diabetic patients have an increased incidence of cancer, due to increased ketone production, and a tendency towards autophagy/mitophagy in their adipose tissue