Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

Murine norovirus (MNV) is endemic in mouse research facilities in the United States and Europe, with a prevalence as high as 58% to 64%. Because of MNV's orofecal route of infection, clinically silent persistent infections in some mouse strains, and proclivity for macrophage and dendritic cells, its presence in mouse colonies has potential to alter phenotypes in experimental mouse models, particularly those involving inflammation and immunologic responses. Although MNV is subclinical, not causing overt disease in immunocompetent mice, we found that MNV infection can accelerate bacteria-induced inflammatory bowel disease (IBD) progression in Mdr1a^(-/-) mice. The studies presented here examined whether MNV infection also affects the phenotype of a bacterially driven mouse model of inflammation-associated colon cancer in genetically susceptible Smad3^(-/-) mice. In vitro culture of bone-marrow—derived macrophages (BMDM) was used to determine whether MNV4 influenced macrophage cytokine production. For in vivo studies, Smad3-/- mice were infected with MNV4 one week prior to infection with Helicobacter. Mice were monitored for 17 to 32 wk for development of IBD and colon cancer, and tissues were analyzed histopathologically. Although in vitro infection of BMDM with MNV4 led to increased inflammatory cytokine production, infection with MNV4 in vivo did not result in any statistically significant differences in survival, IBD scores, tumor incidence, or tumor phenotype in Smad3^(-/-) mice. In addition, MNV infection alone did not result in IBD or colon cancer. Therefore MNV infection alone or in conjunction with Helicobacter does not alter the development or progression of IBD or colon cancer in Smad3^(-/-) mice

Visualization Tools for Clustering, Trees and Ordered Trees

Consider the situation of a set of individuals visiting a library and browsing through a collection. Each individual will, of course, select different books to browse depending on the original purpose of the visit. In addition, the order in which they search through a catalog will differ. The order is often ignored, yet might provide interesting cues as to the importance of certain books or topics. This scenario is not limited to browsing physical collections, but rather is repeated almost continually in other information-seeking behaviors including searching of on-line databases and hypenext/hypermedia systems

P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission

Background: Natural variations in IL-15 concentration have not been investigated for an association with an immune-protection against HIV. Given IL-15's central role in anti-HIV immunity, we hypothesized that higher concentrations of IL-15 in breast milk may protect against postnatal mother-to-child HIV transmission. Methods: In a case-control study nested within a clinical trial in Zambia, we compared IL-15 concentrations in breast milk of 22 HIV-infected women who transmitted HIV to their infants through breastfeeding with those of 72 who did not, as well as 18 HIV-uninfected women. Breast milk HIV RNA quantity, sodium, CXCL12, CCL5, and IL-8 concentrations were measured as well as maternal plasma HIV RNA concentrations and CD4 cell count. We used logistic regression modeling to adjust for potential confounders. Results: Higher concentrations of IL-15 in breast milk (adjusted odds ratio [AOR]: 0.01 per log10 pg/ml increase, 95% confidence interval [CI]: <0.001 to 0.3) were associated with protection against postnatal HIV transmission in univariate analysis and after adjusting for maternal CD4 cell counts, breast milk HIV RNA, CCL5, CXCL12, and IL-8 concentrations. Breast milk IL-15 concentration correlated with breast milk sodium, the other cytokines and HIV RNA concentration. It was inversely correlated with infant birth weight and tended to be higher in 1 week than in 1 month post-partum samples. Breast milk CCL5 concentrations were associated with increased risk of HIV transmission (AOR: 12.7 95% CI: 1.6 to 102.0) in adjusted analysis. Breast milk CXCL12 and IL-8 concentrations were not independently associated with transmission. Conclusion: High concentration of IL-15 were associated with a protection against breastfeeding HIV transmission after adjusting for other pro-inflammatory cytokines, HIV RNA in breast milk, and maternal CD4 cell count. These results corroborate a protective role of IL-15-mediated cellular immunity against HIV transmission during breastfeeding. They are informative for vaccination studies using IL-15 as an adjuvant

Biosecurity and readiness of smallholder pig farmers against potential African Swine Fever outbreak and other pig diseases in Baybay City, Leyte, Philippines

Preventing African Swine Fever (ASF) outbreaks require an active involvement of pig growers as they are in the frontline of detection, notification, and the application of strict biosecurity measures. The Eastern Visayas (Region VIII) in Central Philippines is still free of ASF but the risk can be remarkable given the high volume of pigs that enter in this region as a market hub to large pig producers both coming from Luzon (north) and Mindanao (south). This study was conducted to better understand the readiness and biosecurity practices of smallholder pig farmers who comprise most of the pig growers in the City of Baybay, Leyte. Using multiple correspondence analysis (MCA) and agglomerative hierarchical clustering (AHC) technique of data from 350 pig farmer-respondents, our study found several areas in pig raising activities that need to be highlighted. While pig farmers were generally aware of the threat posed by ASF and have relatively good biosecurity practices, only 32.90% were convinced that the City of Baybay is prepared in the case of an ASF outbreak. Moreover, the importance of vaccination, footbath, and controlling swill feeding need to be emphasized (Cluster 2, 58.29%).  More efforts should be directed towards preparing and training pig farmers on disease monitoring and surveillance and improving further its biosecurity practices with special focus on bioexclusion. Similar studies should be conducted to nearby local government units particularly those located near entry and exit borders of the Eastern Visayas region

The ebb and flow of adaptive co-management: a longitudinal evaluation of a conservation conflict

Adaptive co-management (ACM) is an emerging approach to the governance of social-ecological systems, but there are few long-term assessments of its efficacy. This is especially true in conservation conflicts, where ACM can mitigate disputes between polarised stakeholders. We evaluated ACM that emerged in 2005 to address conflict between seal conservation and fisheries interests in the Moray Firth, Scotland. We interviewed 20 stakeholders in 2015, repeating a survey carried out in 2011 which applied an indicator framework to measure outcomes and pre-conditions for ACM to continue. In 2015, all but one of the 12 outcome indicators were positive, the exception being the conservation status of salmon. However, pre-conditions for ACM’s continuation had weakened, with declines between 2005, 2011 and 2015. These were most marked for three indicators: leaders prepared to champion the process, presence of a bridging organisation or individual, and participation of all impacted stakeholders. The results show that ACM in this conservation conflict is dynamic. Perceived declines in salmon abundance and increases in seal numbers have renewed tensions amongst stakeholders, triggering a ‘revival’ phase of ACM initiated by fishery interests. Our study provides empirical evidence of ACM’s fluid nature, and how resource crises can reignite ACM. We suggest that participatory evaluation is a potentially important early-warning mechanism that can identify remedial action and galvanise stakeholders to respond to the re-emergence of conflict

The role of aerodynamic drag in propagation of interplanetary coronal mass ejections

Context. The propagation of interplanetary coronal mass ejections (ICMEs) and the forecast of their arrival on Earth is one of the central issues of space weather studies. Aims. We investigate to which degree various ICME parameters (mass, size, take-off speed) and the ambient solar-wind parameters (density and velocity) affect the ICME Sun-Earth transit time. Methods. We study solutions of a drag-based equation of motion by systematically varying the input parameters. The analysis is focused on ICME transit times and 1 AU velocities. Results. The model results reveal that wide ICMEs of low masses adjust to the solar-wind speed already close to the sun, so the transit time is determined primarily by the solar-wind speed. The shortest transit times and accordingly the highest 1 AU velocities are related to narrow and massive ICMEs (i.e. high-density eruptions) propagating in high-speed solar wind streams. We apply the model to the Sun-Earth event associated with the CME of 25 July 2004 and compare the results with the outcome of the numerical MHD modeling

Social acceptance of green hydrogen in Germany: building trust through responsible innovation

Background Social acceptance presents a major challenge for Germany’s transition to green energy. As a power-to-x technology, green hydrogen is set to become a key component of a future sustainable energy system. With a view to averting conflicts like those surrounding wind energy, we have investigated social acceptance of green hydrogen at an early stage in its implementation, before wider rollout. Our study uses a mixed-method approach, wherein semi-structured interviews (n = 24) and two participatory workshops (n = 51) in a selected region in central Germany serve alongside a representative survey (n = 2054) as the basis for both understanding social attitudes and reaching generalisable conclusions. Results Overall, it is possible to observe both a marked lack of knowledge and a large degree of openness towards green hydrogen and its local use, along with high expectations regarding environmental and climate protection. We reach three key conclusions. First, acceptance of green hydrogen relies on trust in science, government, the media, and institutions that uphold distributive justice, with consideration for regional values playing a vital role in establishing said trust. Second, methodologically sound participatory processes can promote acceptance, and active support in particular. Third, recurrent positive participatory experiences can effectively foster trust. Conclusions Accordingly, we argue that trust should be strengthened on a structural level, and that green hydrogen acceptance should be understood as a matter of responsible innovation. As the first empirical investigation into social acceptance of green hydrogen, and by conceptually interlinking acceptance research and responsible innovation, this study constitutes an important contribution to existing research

Controlled Release of Multiple Therapeutics From Silicone Hydrogel Contact Lenses for Post-Cataract/Post-Refractive Surgery and Uveitis Treatment.

PURPOSE: This work demonstrates seven-day controlled and extended in vitro physiological flow dual release of multiple post-ocular surgery therapeutics from extended-wear contact lenses as a dropless alternative for treatment of uveitis and corneal inflammation, pain, and infection. Lens replacement each week optimizes treatment matching patient recall time with the ability to increase or decrease dosage. METHODS: Lenses were synthesized using molecular imprinting to create lenses with macromolecular memory for diclofenac sodium (DS) and dexamethasone sodium phosphate (DMSP), as well as bromfenac sodium (BS) and moxifloxacin (MOX). Drug uptake and release were analyzed, and physical properties were measured and compared to commercial standards. RESULTS: DS + DMSP-loaded lenses demonstrated seven-days-plus release of each, whereas controls released more than 85% of their payload within the first day. Lenses loaded with BS + MOX demonstrated release of BS and MOX for 11 and eight days, respectively. Structural analysis demonstrated statistically similar mesh size and average molecular weight between crosslinks between imprinted lenses and controls, suggesting that release extension was due to formation of macromolecular memory sites rather than a tighter polymer architecture. CONCLUSIONS: Lenses demonstrated in this work have significant clinical applications as an eye drop alternative, possessing the ability to be worn continuously for one week while delivering a consistent amount of therapeutic for the duration of wear. TRANSLATIONAL RELEVANCE: In vitro physiological flow release results demonstrate the clinical potential of therapeutic contact lenses as a dropless vehicle for ocular drug delivery