ISECG Mission Scenarios and Their Role in Informing Next Steps for Human Exploration Beyond Low Earth Orbit

The International Space Exploration Coordination Group (ISECG) was established in response to The Global Exploration Strategy (GES): The Framework for Coordination developed by fourteen space agencies* and released in May 2007. This GES Framework Document recognizes that preparing for human space exploration is a stepwise process, starting with basic knowledge and culminating in a sustained human presence in deep space. ISECG has developed several optional global exploration mission scenarios enabling the phased transition from human operations in Low Earth Orbit (LEO) and utilization of the International Space Station (ISS) to human missions beyond LEO leading ultimately to human missions to cis-lunar space, the Moon, Near Earth Asteroids, Mars and its environs. Mission scenarios provide the opportunity for judging various exploration approaches in a manner consistent with agreed international goals and strategies. Each ISECG notional mission scenario reflects a series of coordinated human and robotic exploration missions over a 25-year horizon. Mission scenarios are intended to provide insights into next steps for agency investments, following on the success of the ISS. They also provide a framework for advancing the definition of Design Reference Missions (DRMs) and the concepts for capabilities contained within. Each of the human missions contained in the scenarios has been characterized by a DRM which is a top level definition of mission sequence and the capabilities needed to execute that mission. While DRMs are generally destination focused, they will comprise capabilities which are reused or evolved from capabilities used at other destinations. In this way, an evolutionary approach to developing a robust set of capabilities to sustainably explore our solar system is defined. Agencies also recognize that jointly planning for our next steps, building on the accomplishments of ISS, is important to ensuring the robustness and sustainability of any human exploration plan. Developing a shared long-term vision is important, but agencies recognize this is an evolutionary process and requires consideration of many strategic factors. Strategic factors such as the implications of an emerging commercial space industry in LEO, the opportunity provided by extending ISS lifetime to at least 2020, and the importance of defining a plan which is sustainable in light of inevitable domestic policy shifts are timely for agency consideration

Trends in Loss to Follow-Up among Migrant Workers on Antiretroviral Therapy in a Community Cohort in Lesotho

BACKGROUND: The provision of antiretroviral therapy (ART) to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. DESIGN: All adult patients (≥18 years) initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. RESULTS: Our cohort comprised 1185 people, among whom 12% (148) were migrant workers. Among the migrant workers, median age was 36.1 (29.6-45.9) and the majority (55%) were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15-6.73); between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18-4.73), whereas after 1 year the rate was 6.69 times greater (95%CI 3.18-14.09). CONCLUSIONS: Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations

Targeting early changes in the synovial microenvironment:a new class of immunomodulatory therapy?

Objectives: Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA). Methods: Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed. Results: Tenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. Conclusions: Early changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Housing development erodes avian community structure in U.S. protected areas

Protected areas are a cornerstone for biodiversity conservation, but they also provide amenities that attract housing development on inholdings and adjacent private lands. We explored how this development affects biodiversity within and near protected areas among six ecological regions throughout the United States. We quantified the effect of housing density within, at the boundary, and outside protected areas, and natural land cover within protected areas, on the proportional abundance and proportional richness of three avian guilds within protected areas. We developed three guilds from the North American Breeding Bird Survey, which included Species of Greatest Conservation Need, land cover affiliates (e.g., forest breeders), and synanthropic species associated with urban environments. We gathered housing density data for the year 2000 from the U.S. Census Bureau, and centered the bird data on this year. We obtained land cover data from the 2001 National Land Cover Database, and we used single- and multiple-variable analyses to address our research question. In all regions, housing density within protected areas was positively associated with the proportional abundance or proportional richness of synanthropes, and negatively associated with the proportional abundance or proportional richness of Species of Greatest Conservation Need. These relationships were strongest in the eastern forested regions and the central grasslands, where more than 70% and 45%, respectively, of the variation in the proportional abundance of synanthropes and Species of Greatest Conservation Need were explained by housing within protected areas. Furthermore, in most regions, housing density outside protected areas was positively associated with the proportional abundance or proportional richness of synanthropes and negatively associated with the proportional abundance of land cover affiliates and Species of Greatest Conservation Need within protected areas. However, these effects were weaker than housing within protected areas. Natural land cover was high with little variability within protected areas, and consequently, was less influential than housing density within or outside protected areas explaining the proportional abundance or proportional richness of the avian guilds. Our results indicate that housing development within, at the boundary, and outside protected areas impacts avian community structure within protected areas throughout the United States

Data from: Long-term avian community response to housing development at the boundary of U.S. protected areas: effect size increases with time

1. Biodiversity conservation is a primary function of protected areas. However, protected areas also attract people, and therefore, land use has intensified at the boundaries of these lands globally. In the USA, since the 1970s, housing growth at the boundaries (<1 km) of protected areas has increased at a rate far higher than on more distant private lands. Here, we designed our analyses to address our central hypothesis that increasing housing density in and near protected areas will increasingly alter their avian communities. 2. We quantified the relationship between abundance and richness of protected-area avian species of greatest conservation need, land-cover affiliates (e.g. species associated with natural land cover such as forest breeders) and synanthropes (e.g. species associated with humans) with housing density on the boundary of protected areas and on more distant private lands from 1970 to 2010 in three ecoregions of the USA. We accomplished this using linear mixed-model analyses, data from the US Census Bureau and 90 routes of the North American Breeding Bird Survey. 3. Housing density at the boundary of protected areas tended to be strongly negatively related with the abundance and richness of species of greatest conservation need and land-cover affiliates (upwards of 88% of variance explained) and strongly positively related with synanthropes (upwards of 83% of variance explained). The effect size of these relationships increased in most cases from 1970 to 2010 and was greatest in the densely developed eastern forests. In the more sparsely populated West, we found similar, though weaker, associations. 4. Housing density on private lands more distant from protected areas had similar, but more muted negative effects. 5. Synthesis and applications. Our results illustrate that as housing density has increased along the boundary of protected areas, the conservation benefit of these lands has likely diminished. We urge conservation planners to prioritize the purchase of private-land inholdings in order to maximize the extent of unfragmented natural lands within protected areas. Further, we strongly recommend that land-use planners implement boundary management strategies to alter the pattern of human access to protected areas, cluster development to concentrate the footprint of rural housing, and establish conservation agreements through local land trusts to buffer protected areas from the effects of development along protected-area boundaries. To maximize the conservation benefit of protected areas, we suggest that housing development should be restricted within 1 km of their boundaries