Case studies

In this chapter, case studies are used as examples of how to gain a better understanding of the risks posed by extreme weather and climate-related events while identifying lessons and best practices from past responses to such occurrences. Using the information in Chapters 1 to 8, it was possible to focus on particular examples to reflect the needs of the whole Special Report. The chosen case studies are illustrative of an important range of disaster risk reduction, disaster risk management, and climate change adaptation issues. They are grouped to examine representative types of extreme events, vulnerable regions, and methodological approaches

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

The atmospheric role in the Arctic water cycle: A review on processes, past and future changes, and their impacts

This is the final version of the article. Available from the publisher via the DOI in this record.Atmospheric humidity, clouds, precipitation, and evapotranspiration are essential components of the Arctic climate system. During recent decades, specific humidity and precipitation have generally increased in the Arctic, but changes in evapotranspiration are poorly known. Trends in clouds vary depending on the region and season. Climate model experiments suggest that increases in precipitation are related to global warming. In turn, feedbacks associated with the increase in atmospheric moisture and decrease in sea ice and snow cover have contributed to the Arctic amplification of global warming. Climate models have captured the overall wetting trend but have limited success in reproducing regional details. For the rest of the 21st century, climate models project strong warming and increasing precipitation, but different models yield different results for changes in cloud cover. The model differences are largest in months of minimum sea ice cover. Evapotranspiration is projected to increase in winter but in summer to decrease over the oceans and increase over land. Increasing net precipitation increases river discharge to the Arctic Ocean. Over sea ice in summer, projected increase in rain and decrease in snowfall decrease the surface albedo and, hence, further amplify snow/ice surface melt. With reducing sea ice, wind forcing on the Arctic Ocean increases with impacts on ocean currents and freshwater transport out of the Arctic. Improvements in observations, process understanding, and modeling capabilities are needed to better quantify the atmospheric role in the Arctic water cycle and its changes.We thank all colleagues involved in the Arctic Freshwater Synthesis (AFS) for fruitful discussions. In particular, John Walsh is acknowledged for his constructive comments on the manuscript. AFS has been sponsored by the World Climate Research Programme’s Climate and the Cryosphere project (WCRP-CliC), the International Arctic Science Committee (IASC), and the Arctic Monitoring and Assessment Programme (AMAP). The work for this paper has been supported by the Academy of Finland (contracts 259537 and 283101), the UK Natural Environment Research Council (grant NE/J019585/1), the US National Science Foundation grant ARC-1023592 and the Program “Arctic” and the Basic Research Program of the Presidium Russian Academy of Sciences. NCAR is supported by the U.S. National Science Foundation. We gratefully acknowledge the project coordination and meeting support of Jenny Baeseman and Gwenaelle Hamon at the CliC International Project Office. No new data were applied in the manuscript. Data applied for Figures 2 and 3 are available from the JRA-55 archive at http://jra. kishou.go.jp/JRA-55/index_en. html#usage

Perinatal Hypoxia-Ischemia Disrupts Striatal High-Affinity [ 3 H]Glutamate Uptake into Synaptosomes

: We examined the impact of hypoxia-ischemia on high-affinity [ 3 H]glutamate uptake into a synaptosomal fraction prepared from immature rat corpus striatum. In 7-day-old pups the right carotid artery was ligated, and pups were exposed to 8% oxygen for 0, 0.5, 1, or 2.5 h, and allowed to recover for up to 24 h before they were killed. High-affinity glutamate uptakes in striatal synaptosomes derived from tissue ipsilateral and contralateral to ligation were compared. After 1 h of hypoxia plus ischemia, high-affinity glutamate uptake in the striatum was reduced by 54 ± 13% compared with values from the opposite (nonischemic) side of the brain (p < 0.01, t test versus ligates not exposed to hypoxia). There were similar declines after 2.5 h of hypoxiaischemia. Activity remained low after a 1 h recovery period in room air, but after 24 h of recovery, high-affinity glutamate uptake was equal bilaterally. Kinetic analysis revealed that loss of activity could be attributed primarily to a 40% reduction in the number of uptake sites. Hypoxia alone had no effect on high-affinity glutamate uptake although it reduced synaptosomal uptake of [ 3 H]3,4-dihydroxyphenyl-ethylamine. Addition of 1 mg/ml of bovine serum albumin to the incubation medium preferentia'ly stimulated high-affinity glutamate uptake in hypoxic-ischemic brain compared with its effects in normal tissue. These studies demonstrate that hypoxia-ischemia reversibly inhibits high-affinity glutamate uptake and this occurs earlier than the time required to produce neuronal damage in the model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66361/1/j.1471-4159.1986.tb00803.x.pd

The xc− cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance

The xc− cystine transporter enhances biosynthesis of glutathione, a tripeptide thiol important in drug resistance and cellular defense against oxidative stress, by enabling cellular uptake of cystine, a rate-limiting precursor. Because it is known to regulate glutathione levels and growth of various cancer cell types, and is expressed in the pancreas, we postulate that it is involved in growth and drug resistance of pancreatic cancer. To examine this, we characterised expression of the xc− transporter in pancreatic cancer cell lines, MIA PaCa-2, PANC-1 and BxPC-3, as subjected to cystine-depletion and oxidative stress. The results indicate that these cell lines depend on xc−-mediated cystine uptake for growth, as well as survival in oxidative stress conditions, and can modulate xc− expression to accommodate growth needs. Immunohistochemical analysis showed that the transporter was differentially expressed in normal pancreatic tissues and overexpressed in pancreatic cancer tissues from two patients. Furthermore, gemcitabine resistance of cells was associated with elevated xc− expression and specific xc− inhibition by monosodium glutamate led to growth arrest. The results suggest that the xc− transporter by enhancing glutathione biosynthesis plays a major role in pancreatic cancer growth, therapy resistance and represents a potential therapeutic target for the disease

Corrigendum to "European contribution to the study of ROS:A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

The lack of effect of market structure on hospice use.

OBJECTIVE: To describe the relative importance of health care market structure and county-level demographics in determining rates of hospice use. DATA SOURCES: Medicare claims data for a cohort of elderly patients newly diagnosed with lung cancer, colon cancer, stroke, or heart attack in 1993, followed for up to five years, and linked to Census and Area Resource File data. STUDY DESIGN: Variation between markets in rates of hospice use by patients with serious illness was examined after taking into account differences in individual-level data using hierarchical linear models. The relative explanatory power of market-level structure and local demographic variables was compared. DATA COLLECTION METHODS: The cohort was defined within the Medicare hospital claims data using validated algorithms to detect incident cases of disease with a three-year lookback. Use of hospice was determined by linkage at an individual level to the Standard Analytic Files for Hospice through 1997. Individual-level data was linked to the Area Resource File using county identifiers present in the Medicare claims. PRINCIPAL FINDINGS: There is substantial variation in hospice use across markets. This variation is not explained by differences in the major components of health care infrastructure: the availability of hospital, nursing home, or skilled nursing facilities, nor by the availability of HMOs, doctors, or generalists. CONCLUSIONS: Intercounty heterogeneity in hospice use is substantial, and may not be related to the set-up of the medical care system. The important local factors may be local preferences, differences in the particular mix of services provided by local hospices, or differences in community leadership on end of life-issues; many of these differences may be amenable to educational efforts.http://deepblue.lib.umich.edu/bitstream/2027.42/61410/1/02.I.Chang.Zhang.C.HSR.pd

Th17 Cytokines and the Gut Mucosal Barrier

Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic sites. Several subsets of T cells in the gut (T-helper 17 cells, γδ T cells, natural killer (NK), and NK-T cells) contribute to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and IL-26. These cytokines induce the secretion of chemokines and antimicrobial proteins, thereby orchestrating the mucosal barrier against gastrointestinal pathogens. While the mucosal barrier prevents bacterial dissemination from the gut, it also promotes colonization by pathogens that are resistant to some of the inducible antimicrobial responses. In this review, we describe the contribution of Th17 cytokines to the gut mucosal barrier during bacterial infections