Is there really "nothing you can do"? Pathways to enhanced flood-risk preparedness

Whilst policy makers have tended to adopt an ‘information-deficit model’ to bolster levels of flood-risk preparedness primarily though communication strategies promoting awareness, the assumed causal relation between awareness and preparedness is empirically weak. As such, there is a growing interest amongst scholars and policy makers alike to better understand why at-risk individuals are underprepared. In this vein, empirical studies, typically employing quantitative methods, have tended to focus on exploring the extent to which flood-risk preparedness levels vary depending not only on socio-demographic variables, but also (and increasingly so) the perceptual factors that influence flood risk preparedness. This study builds upon and extends this body of research by offering a more solution-focused approach that seeks to identify how pathways to flood-risk preparedness can be opened up. Specifically, through application of a qualitative methodology, we seek to explore how the factors that negatively influence flood-risk preparedness can be addressed to foster a shift towards greater levels of mitigation behaviour. In doing so, we focus our analysis on an urban community in Ireland that is identified as ‘at risk’ of flash flooding and is currently undergoing significant flood relief works. In this regard, the case study offers an interesting laboratory to explore how attitudes towards flood-risk preparedness at the individual level are being influenced within the context of a flood relief scheme that is only partially constructed. In order to redress the dearth of theoretically informed qualitative studies in this field, we draw on Protection Motivation Theory (PMT) to help guide our analysis and make sense of our results. Our findings demonstrate that flood-risk preparedness can be undermined by low levels of efficacy amongst individuals in terms of the preparedness measures available to them and their own personal capacity to implement them. We also elucidate that the ‘levee effect’ can occur before engineered flood defences are fully constructed as the flood relief works within our case study are beginning to affect people’s perception of flood risk in the case study area. We conclude by arguing that 1) individuals’ coping appraisals need to be enhanced through communication strategies and other interventions which highlight that future floods may not replicate past events; and 2) the concept of residual risk needs to be communicated at all stages of a flood relief scheme, not just upon completion

A Combination of Sulindac and Antimicrobial Eradication of H. pylori Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice

Author Manuscript: 2010 October 15Helicobacter pylori infection causes severe dysplasia manifested as gastrointestinal intraepithelial neoplasia (GIN) after 28 weeks post–H. pylori infection (WPI) in cancer-prone, hypergastrinemic male INS-GAS mice. We examined the efficacy of the nonsteroidal anti-inflammatory drug sulindac (400 ppm in drinking water) alone, the CCK2/gastrin receptor antagonist YM022 (45 mg/kg/wk) alone, and sulindac or YM022 combined with H. pylori eradication therapy to prevent H. pylori–associated gastric cancer in male INS-GAS mice. Treatments started at 22 WPI, and mice were euthanized at 28 WPI. In uninfected mice, all treatments significantly delayed development of spontaneous GIN (P < 0.05). In H. pylori–infected mice, sulindac alone or YM022 alone had no protective effect on H. pylori–associated GIN. Importantly, sulindac exacerbated the severity of H. pylori–associated gastritis despite decreased gastric prostaglandin E2 levels. However, sulindac combined with H. pylori antimicrobial eradication reduced the incidence of GIN (P < 0.05), whereas YM022 combined with antimicrobial eradication did not reduce GIN. In infected mice, sulindac or YM022 treatment did not alter gastric expression of the proinflammatory cytokines Ifn-γ and Tnf-α and mucosal cell proliferation. Sulindac or YM022 combined with antimicrobial eradication down-regulated mRNA levels of Ifn-γ and Tnf-α and mucosal cell proliferation (P < 0.05). We conclude that sulindac enhances H. pylori gastritis and may promote inflammation-mediated gastric carcinogenesis. The combination of sulindac and antimicrobial H. pylori eradication was beneficial for reducing proinflammatory cytokine mRNA in the stomach and preventing progression from severe dysplasia to gastric cancer in H. pylori–infected INS-GAS mice. [Cancer Res 2009;69(20):8166–74]National Institutes of Health (U.S.) (Grant R01AI37750)National Institutes of Health (U.S.) (Grant P01CA26731)National Institutes of Health (U.S.) (Grant P30ES02109)National Institutes of Health (U.S.) (Grant R01CA093405-07A1

Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice

Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal exposure to major risk factors, such as hepatitis B or C virus infection. Female resistance is hormone-dependent, as evidenced by the sharp increase in HCC incidence in postmenopausal women who do not take hormone replacement therapy. In rodent models sex-dimorphic HCC phenotypes are pituitary-dependent, suggesting that sex hormones act via the gonadal-hypophyseal axis. We found that the estrogen-responsive pituitary hormone prolactin (PRL), signaling through hepatocyte-predominant short-form prolactin receptors (PRLR-S), constrained TNF receptor-associated factor (TRAF)-dependent innate immune responses invoked by IL-1β, TNF-α, and LPS/Toll-like receptor 4 (TLR4), but not TRIF-dependent poly(I:C)/TLR3. PRL ubiquitinated and accelerated poststimulatory decay of a “trafasome” comprised of IRAK1, TRAF6, and MAP3K proteins, abrogating downstream activation of c-Myc–interacting pathways, including PI3K/AKT, mTORC1, p38 MAPK, and NF-κB. Consistent with this finding, we documented exaggerated male liver responses to immune stimuli in mice and humans. Tumor promotion through, but regulation above, the level of c-Myc was demonstrated by sex-independent HCC eruption in Alb-Myc transgenic mice. PRL deficiency accelerated liver carcinogenesis in Prl[superscript −/−] mice of both sexes. Conversely, pharmacologic PRL mobilization using the dopamine D2 receptor antagonist domperidone prevented HCC in tumor-prone C3H/HeN males. Viewed together, our results demonstrate that PRL constrains tumor-promoting liver inflammation by inhibiting MAP3K-dependent activation of c-Myc at the level of the trafasome. PRL-targeted therapy may hold promise for reducing the burden of liver cancer in high-risk men and women.National Institutes of Health (U.S.) (Grant CA067529

Helicobacter cinaedi Induced Typhlocolitis in Rag-2-Deficient Mice

Background Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase-activating gene (Rag)-2-deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2[superscript −/−] mouse model. Materials and Methods Sixty 129SvEv Rag2[superscript −/−] mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice. Results H. cinaedi induced typhlocolitis in Rag2[superscript −/−] mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon-γ, tumor-necrosis factor-α, IL-1β, IL-10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL-4, IL-6, Cox-2, and c-myc mRNA expressions were not detected. Conclusions Our results indicated that the Rag2[superscript −/−] mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS.United States. National Institutes of Health (R01-0D011141)United States. National Institutes of Health (R01-CA067529)United States. National Institutes of Health (P30-ES002109)United States. National Institutes of Health (P01-CA026731

The effects of a mindfulness-based program on the incidence of injuries in young male soccer players

We tested the effectiveness of a mindfulness-based program in reducing sport injury incidence. 168 young male elite soccer players were randomly assigned to mindfulness (MG) and control (CG) groups. The MG consisted of 7 sessions based on the Mindfulness-Acceptance-Commitment approach while the CG consisted of 7 presentations on sport injury psychology. Athlete-exposure and injury data were recorded during one season. State and trait mindfulness, sport anxiety, stress, and attention control of participants were assessed. Number of injuries, average of injuries per team, and days lost to injury in the MG weresignificantly lower than in the CG. Mindfulness and attention control werelower and sport anxiety and stress were higher in injured players than innon-injured players. Psychological variables were associated with injury. Mindfulness training may reduce the injury risk of young soccer players due to improved mindfulness and attention control and reduced sport anxiety

Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota

Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3[superscript +] cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3[superscript +] cells in the corpus and reduced H. pylori-associated gastric atrophy (p < 0.04), dysplasia (p < 0.02) and prevented H. pylori-induced changes in the gastric flora (p < 0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans.RO1-CA67529R01DK052413PO1CA26731P01 CA028842P30ESO2109R01DK06507

Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Species

Background: Wiskott–Aldrich syndrome protein–deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in Wiskott–Aldrich syndrome protein–deficient (WKO) mice. Methods: Feces from WKO mice raised under specific pathogen-free conditions were evaluated for the presence of Helicobacter spp., after which a subset of mice were rederived in Helicobacter spp.–free conditions. Helicobacter spp.–free WKO animals were subsequently infected with Helicobacter bilis. Results: Helicobacter spp. were detected in feces from WKO mice. After rederivation in Helicobacter spp.–free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on Wiskott–Aldrich syndrome protein–deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis–infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. Conclusions: Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.–free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa.National Institutes of Health (U.S.) (R01OD011141)National Institutes of Health (U.S.) (R01CA067529)National Institutes of Health (U.S.) (P01CA026731)National Institutes of Health (U.S.) (P30ES02109

Insulin Resistance and Metabolic Hepatocarcinogenesis with Parent-of-Origin Effects in A×B Mice

Insulin resistance is a defining feature of metabolic syndrome and type 2 diabetes mellitus but also may occur independently of these conditions. Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of these disorders, increases the risk of hepatocellular carcinoma (HCC). However, mechanisms linking hyperinsulinemia to NAFLD and HCC require clarification. We describe a novel model of primary insulin resistance and HCC with strong parent-of-origin effects. Male AB6F1 (A/JCr dam × C57BL/6 sire) but not B6AF1 (B6 dam × A/J sire) mice developed spontaneous insulin resistance, NAFLD, and HCC without obesity or diabetes. A survey of mitochondrial, imprinted, and sex-linked traits revealed modest associations with X-linked genes. However, a diet-induced obesity study, including B6.A chromosome substitution–strain (consomic) mice, showed no segregation by sex chromosome. Thus, parent-of-origin effects were specified within the autosomal genome. Next, we interrogated mechanisms of insulin-associated hepatocarcinogenesis. Steatotic hepatocytes exhibited adipogenic transition characterized by vacuolar metaplasia and up-regulation of vimentin, adipsin, fatty acid translocase (CD36), peroxisome proliferator–activated receptor-γ, and related products. This profile was largely recapitulated in insulin-supplemented primary mouse hepatocyte cultures. Importantly, pyruvate kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was activated by insulin in vivo and in vitro. Thus, our study reveals parent-of-origin effects in heritable insulin resistance, implicating adipogenic transition with acquired anabolic metabolism in the progression from NAFLD to HCC.National Institutes of Health (U.S.) (NIH grant AA016563)National Institutes of Health (U.S.) (NIH grant CA067529)National Institutes of Health (U.S.) (NIH grant P01CA0267)National Institutes of Health (U.S.) (NIH grant P30ES02109)National Institutes of Health (U.S.) (NIH grant RR007036)National Institutes of Health (U.S.) (NIH grant CA158661)National Institutes of Health (U.S.) (NIH grant CA016086

Host switching in a generalist parasitoid: Contrasting transient and transgenerational costs associated with novel and original host species

Parasitoids face challenges by switching between host species that influence survival and fitness, determine their role in structuring communities, influence species invasions, and affect their importance as biocontrol agents. In the generalist parasitoid, Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae), we investigated the costs in encapsulation, survival, and body size on juveniles when adult parasitoids switched from their original host, Plodia interpunctella (Hübner) (Lepidotera, Pyralidae) to a novel host, Ephestia kuehniella (Zeller) (Lepidoptera, Pyralidae), over multiple generations. Switching had an initial survival cost for juvenile parasitoids in the novel host, but increased survival occurred within two generations. Conversely, mortality in the original host increased. Body size, a proxy for fecundity, also increased with the number of generations in the novel host species, reflecting adaptation or maternal effects due to the larger size of the novel host, and therefore greater resources available to the developing parasitoid. Switching to a novel host appears to have initial costs for a parasitoid, even when the novel host may be better quality, but the costs rapidly diminish. We predict that the net cost of switching to a novel host for parasitoids will be complex and will depend on the initial reduction in fitness from parasitizing a novel host versus local adaptations against parasitoids in the original host