The 2020 Covid-19 pandemic and global value chains

This paper considers the impact of the Covid-19 pandemic on firm strategies and, in particular, the configuration of firms’ global value chains (GVCs) once the pandemic has been brought under control. The merits of alternative location strategies (international diversification vs reshoring) are compared, as are the merits of different governance arrangements (internalization vs externalization) for GVC activities. The possibility of fire-sale foreign direct investment is raised, and the wider geopolitical context is emphasized. The widespread human tragedy is noted, as is the dilemma facing national governments around the world in balancing lives and livelihoods

Maternal Intake of Methyl‐Donor Nutrients and Child Cognition at 3 Years of Age

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91325/1/j.1365-3016.2012.01264.x.pd

Clinical Evaluation of Targeted Arterial Infusion of Verapamil in the Interventional Chemotherapy of Primary Hepatocellular Carcinoma

This study evaluates the clinical effectiveness of targeted arterial infusion of verapamil in interventional treatment of primary hepatocellular carcinoma. For this purpose, in 273 patients with middle- or late-stage primary hepatocellular carcinoma, verapamil, IL-2, and chemotherapeutic agents were infused into the target tumor vasculature through femoral artery using Seldinger technique. The medications were infused as serial dilutions, and effectiveness was evaluated after two treatment cycles. Among these 273 patients, 76 cases showed clinical cure or significant improvement, 119 cases improved, 64 cases stabilized, while 14 cases progressed or deteriorated. In 238 patients, KPS score and body weights were stabilized. Regarding side effects, 99 patients (36.3%) developed leukopenia; 160 patients had gastrointestinal reactions (58.6%); 80 patients (29.3%) presented with elevated ALT/AST profile; and 65 cases (23.8%) had pyrexia; however, these side effects abated quickly. No elevations in BUN/Cr and/or allergic reactions were observed. Pre- and post-intervention cardiac function did not change in all the patients. No significant change was observed in ECG. Liver function was also improved after two cycles of treatment. It was concluded that verapamil management via targeted arterial infusion could effectively reverse the multidrug resistance in cancer cells in primary hepatocellular carcinoma patients and therefore enhanced the efficacy of chemotherapy

Anticipation and Reaction to Going Concern Modified Audit Opinions by Sophisticated Investors

The purpose of this paper is to examine whether institutional investors (i) anticipate a distressed firm\u27s receipt of a first‐time going‐concern modified audit opinion, and (ii) react to a first‐time going‐concern modified opinion by engaging in abnormal net selling of firm shares. Using a proprietary database of US institutional investor trades, we find that institutional investors are net sellers of first‐time going‐concern opinion firms beginning 6 months before the release of the report and remain net sellers through the subsequent 3 months. We also find that the severity of the reasons auditors modify their opinions is associated with increased trading activity, but only after the opinion is publicly available. Our results support the position that an auditor\u27s going‐concern modified opinion is influential in the marketplace by documenting that institutional investors anticipate this price‐relevant information and react through increased selling. The finding of increased net selling of firms with more severe reasons for report modifications provides evidence of the incremental informational value of the wording in the modified opinion

Annual trend patterns of phytoplankton species abundance belie homogeneous taxonomical group responses to climate in the NE Atlantic upwelling

Phytoplankton is a sentinel of marine ecosystem change. Composed by many species with different life-history strategies, it rapidly responds to environment changes. An analysis of the abundance of 54 phytoplankton species in Galicia (NW Spain) between 1989 and 2008 to determine the main components of temporal variability in relation to climate and upwelling showed that most of this variability was stochastic, as seasonality and long term trends contributed to relatively small fractions of the series. In general, trends appeared as non linear, and species clustered in 4 groups according to the trend pattern but there was no defined pattern for diatoms, dinoflagellates or other groups. While, in general, total abundance increased, no clear trend was found for 23 species, 14 species decreased, 4 species increased during the early 1990s, and only 13 species showed a general increase through the series. In contrast, series of local environmental conditions (temperature, stratification, nutrients) and climate-related variables (atmospheric pressure indices, upwelling winds) showed a high fraction of their variability in deterministic seasonality and trends. As a result, each species responded independently to environmental and climate variability, measured by generalized additive models. Most species showed a positive relationship with nutrient concentrations but only a few showed a direct relationship with stratification and upwelling. Climate variables had only measurable effects on some species but no common response emerged. Because its adaptation to frequent disturbances, phytoplankton communities in upwelling ecosystems appear less sensitive to changes in regional climate than other communities characterized by short and well defined productive periods.Versión del editor1,953

Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts

Although circulating DNA (ctDNA) could be an attractive tool for early cancer detection, diagnosis, prognosis, monitoring or prediction of response to therapies, knowledge on its origin, form and rate of release is poor and often contradictory. Here, we describe an experimental system to systematically examine these aspects. Nude mice were xenografted with human HT29 or SW620 colorectal carcinoma (CRC) cells and ctDNA was analyzed by Q–PCR with highly specific and sensitive primer sets at different times post-graft. We could discriminate ctDNA from normal (murine) cells and from mutated and non-mutated tumor (human) cells by using species-specific KRAS or PSAT1 primers and by assessing the presence of the BRAF V600E mutation. The concentration of human (mutated and non-mutated) ctDNA increased significantly with tumor growth. Conversely, and differently from previous studies, low, constant level of mouse ctDNA was observed, thus facilitating the study of mutated and non-mutated tumor derived ctDNA. Finally, analysis of ctDNA fragmentation confirmed the predominance of low-size fragments among tumor ctDNA from mice with bigger tumors. Higher ctDNA fragmentation was also observed in plasma samples from three metastatic CRC patients in comparison to healthy individuals. Our data confirm the predominance of mononucleosome-derived fragments in plasma from xenografted animals and, as a consequence, of apoptosis as a source of ctDNA, in particular for tumor-derived ctDNA. Altogether, our results suggest that ctDNA features vary during CRC tumor development and our experimental system might be a useful tool to follow such variations

Context-dependent regulation of endothelial cell metabolism: differential effects of the PPARβ/δ agonist GW0742 and VEGF-A

Peroxisome proliferator activated receptor β/δ (PPARβ/δ) has pro-angiogenic functions, but whether PPARβ/δ modulates endothelial cell metabolism to support the dynamic phenotype remains to be established. This study characterised the metabolic response of HUVEC to the PPARβ/δ agonist, GW0742, and compared these effects with those induced by VEGF-A. In HUVEC monolayers, flux analysis revealed that VEGF-A promoted glycolysis at the expense of fatty acid oxidation (FAO), whereas GW0742 reduced both glycolysis and FAO. Only VEGF-A stimulated HUVEC migration and proliferation whereas both GW0742 and VEGF-A promoted tubulogenesis. Studies using inhibitors of PPARβ/δ or sirtuin-1 showed that the tubulogenic effect of GW0742, but not VEGF-A, was PPARβ/δ- and sirtuin-1-dependent. HUVEC were reliant on glycolysis and FAO, and inhibition of either pathway disrupted cell growth and proliferation. VEGF-A was a potent inducer of glycolysis in tubulogenic HUVEC, while FAO was maintained. In contrast, GW0742-induced tubulogenesis was associated with enhanced FAO and a modest increase in glycolysis. These novel data reveal a context-dependent regulation of endothelial metabolism by GW0742, where metabolic activity is reduced in monolayers but enhanced during tubulogenesis. These findings expand our understanding of PPARβ/δ in the endothelium and support the targeting of PPARβ/δ in regulating EC behaviour and boosting tissue maintenance and repair

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Advances in Auctions

As a selling mechanism, auctions have acquired a central position in the free market economy all over the globe. This development has deepened, broadened, and expanded the theory of auctions in new directions. This chapter is intended as a selective update of some of the developments and applications of auction theory in the two decades since Wilson (1992) wrote the previous Handbook chapter on this topic