Consumer e-health education in HIV/AIDS: a pilot study of a web-based video workshop

BACKGROUND: Members of the HIV/AIDS community are known to use web-based tools to support learning about treatment issues. Initial research indicated components such as message forums or web-based documentation were effectively used by persons with HIV/AIDS. Video has also shown promise as a technology to aid consumer health education. However, no research has been published thus far investigating the impact of web-based environments combining these components in an educational workshop format. METHODS: In this qualitative study HIV/AIDS community members provided feedback on an integrated web-based consumer health education environment. Participants were recruited through organizations that serve the HIV/AIDS community located in Toronto, Canada. Demographics, data on Internet use, including messages exchanged in the study environment were collected. A group interview provided feedback on usability of the study environment, preferences for information formats, use of the message forum, and other sources for learning about treatment information. RESULTS: In this pilot study analysis of the posted messages did not demonstrate use for learning of the workshop content. Participants did not generally find the environment of value for learning about treatment information. However, participants did share how they were meeting these needs. It was indicated that a combination of resources are being used to find and discuss treatment information, including in-person sources. CONCLUSION: More research on the ways in which treatment information needs are being met by HIV/AIDS community members and how technology fits in this process is necessary before investing large amounts of money into web-based interventions. Although this study had a limited number of participants, the findings were unexpected and, therefore, of interest to those who intend to implement online consumer health education initiatives or interventions

XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results

BACKGROUND: We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer. METHODS: NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 x 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed. RESULTS: The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n = 634; 2 x 2 factorial portion, n 1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85-1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83-1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4. CONCLUSION: Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer

Sustainable Financing of Innovative Therapies: A Review of Approaches

The process of innovation is inherently complex, and it occurs within an even more complex institutional environment characterized by incomplete information, market power, and externalities. There are therefore different competing approaches to supporting and financing innovation in medical technologies, which bring their own advantages and disadvantages. This article reviews value- and cost-based pricing, as well direct government funding, and cross-cutting institutional structures. It argues that performance-based risk-sharing agreements are likely to have little effect on the sustainability of financing; that there is a role for cost-based pricing models in some situations; and that the push towards longer exclusivity periods is likely contrary to the interests of industry

CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope

Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine (Q9VF/5N). We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes

A review of the benefits and drawbacks to virtual field guides in today’s Geoscience higher education environment

Virtual Field Guides are a way for educators to tackle the growing issue of funding pressures in areas of higher education, such as geography. Virtual Field Guides are however underutilised and can offer students a different way of learning. Virtual Field Guides have many benefits to students, such as being more inclusive, building student skills and confidence in a controlled environment pre fieldtrip and can increase engagement in the topic studied. There are also benefits to the educator, such as reduced cost, more efficient students on fieldwork tasks and the ability to tailor and update their field guides to suit their needs. However there are drawbacks in the challenge of creation and their outcome as educational standalone tools. This paper reviews the literature around the benefits and draw backs to the creation and incorporation of virtual field guides in geoscience education. © 2017, The Author(s)

AhR transcriptional activity in serum of Inuits across Greenlandic districts

<p>Abstract</p> <p>Background</p> <p>Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-<it>p</it>-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.</p> <p>Methods</p> <p>The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.</p> <p>Results</p> <p>In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.</p> <p>Conclusion</p> <p>i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.</p

The role of DNA microarrays in Toxoplasma gondii research, the causative agent of ocular toxoplasmosis

Ocular toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii, is the leading cause of retinochoroiditis. Toxoplasma is an obligate intracellular pathogen that replicates within a parasitophorous vacuole. Infections are initiated by digestion of parasites deposited in cat feces or in undercooked meat. Parasites then disseminate to target tissues that include the retina where they then develop into long-lived asymptomatic tissue cysts. Occasionally, cysts reactivate and growth of newly emerged parasites must be controlled by the host’s immune system or disease will occur. The mechanisms by which Toxoplasma grows within its host cell, encysts, and interacts with the host’s immune system are important questions. Here, we will discuss how the use of DNA microarrays in transcriptional profiling, genotyping, and epigenetic experiments has impacted our understanding of these processes. Finally, we will discuss how these advances relate to ocular toxoplasmosis and how future research on ocular toxoplasmosis can benefit from DNA microarrays

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500&nbsp;years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview