Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

Objective. The efficacy of individualized, community-based physical activity as an adjunctive smoking cessation treatment to enhance long-term smoking cessation rates was evaluated for the Lifestyle Enhancement Program (LEAP). Methods. The study was a two-arm, parallel-group, randomized controlled trial. All participants (n = 392) received cessation counseling and a nicotine patch and were randomized to physical activity (n = 199; YMCA membership and personalized exercise programming from a health coach) or an equal contact frequency wellness curriculum (n = 193). Physical activity treatment was individualized and flexible (with each participant selecting types of activities and intensity levels and being encouraged to exercise at the YMCA and at home, as well as to use “lifestyle” activity). The primary outcome (biochemically verified prolonged abstinence at 7-weeks (end of treatment) and 6- and 12-months postcessation) and secondary outcomes (7-day point prevalent tobacco abstinence (PPA), total minutes per week of leisure time physical activity and strength training) were assessed at baseline, 7 weeks, 6 months, and 12 months. Results. Prolonged abstinence in the physical activity and wellness groups was 19.6% and 25.4%, respectively, at 7-weeks, 15.1% and 16.6% at 6-months, and 14.1% and 17.1% at 12 months (all between-group P values >0.18). Similarly, PPA rates did not differ significantly between groups at any follow-up. Change from baseline leisure-time activity plus strength training increased significantly in the physical activity group at 7 weeks (P = 0.04). Across treatment groups, an increase in the number of minutes per week in strength training from baseline to 7 weeks predicted prolonged abstinence at 12 months (P ≤ 0.001). Further analyses revealed that social support, fewer years smoked, and less temptation to smoke were associated with prolonged abstinence over 12 months in both groups. Conclusions. Community-based physical activity programming, delivered as adjunctive treatment with behavioral/pharmacological cessation treatment, did not improve long-term quit rates compared to adjunctive wellness counseling plus behavioral/pharmacological cessation treatment. This trial is registered with https://beta.clinicaltrials.gov/study/NCT00403312, registration no. NCT00403312.

Glioblastomas are the most frequent and aggressive primary brain tumor in adults and despite recent therapeutic advances, they are resistant to treatment. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumor vasculature, leading to insufficient blood supply, hypoxic areas, and ultimately to the formation of necrosis. Hypoxia induces direct or indirect changes in the biology of solid tumor and their microenvironment through the activation of HIF transcription factors, leading to increased aggressiveness and tumor resistance to therapy. Not much is known about the epigenetic alterations induced by hypoxia and how they could alter tumor biology. In the present study, we have utilized PIMO as a specific marker of hypoxia in glioblastoma patients, treated with PIMO preoperatively. We have estimated PIMO positivity in each tumor (5-45%) and determined that it positively correlates with the hypoxia marker CA IX (r=0.57). In addition, 10 surgical PIMO cases were dissociated, immune labeled using PIMO antibody, followed by DNA isolation and methylation profiling. Our analysis of differentially top 4000 differentially methylated probes suggests that PIMO-positive (hypoxic) cells are differentially methylated compared to the PIMO-negative cells and these changes are associated with genes involved in hypoxic cellular response. We will validate these findings in additional glioblastoma cases and assess the mechanism of these epigenetic alterations in vitro in glioma stem cell culture conditions and upon exposure of the cells hypoxic conditions.

Seed of 41 economically important weed species of the Great Plains region of the United States were buried 20 cm deep in soil in eastern and western Nebraska in 1976. The 41 species consisted of 11 annual grass, 14 annual broadleaf, 4 biennial broadleaf, and 12 perennial broadleaf species. Weed seeds were exhumed annually for germination tests the first 9 yr, then after 12 and 17 yr. Germination percentages at the two burial locations averaged over 0, 1 to 4, 5 to 8, and 9 to 17 yr of burial were 57, 28, 9, and 4% for annual grass; 47, 26, 16, and 11 % for annual broadleaf; 52, 49, 44, and 30 % for biennial broadleaf; 36, 18, 13, and 8% for perennial broadleaf; and 47, 26, 16, and 10% for all 41 weed species, respectively. Biennial broadleaf weeds showed the greatest seed germination over years. Annual grass weeds showed less seed germinability over 17 yr of burial than annual broadleaf weeds and perennial broadleaf weed species were intermediate. Weed seed germinability in soil was greater in the reduced rainfall and more moderate soil temperatures of western Nebraska than in the greater rainfall and more fluctuating soil temperatures of eastern Nebraska. The greatest seed survival among the 41 weed species was shown by common mullein, which had 95% germination after 17 yr of burial in western Nebraska. Decay rates of individual weed species in soil will be of most value to weed scientists, agriculturalists, and modelers evaluating past or designing future weed management systems.

The success of scaling out depends on a clear understanding of the factors that affect adoption of grain legumes and account for the dynamism of those factors across heterogeneous contexts of sub-Saharan Africa. We reviewed literature on adoption of grain legumes and other technologies in sub-Saharan Africa and other developing countries. Our review enabled us to define broad factors affecting different components of the scaling out programme of N2Africa and the scales at which those factors were important. We identified three strategies for managing those factors in the N2Africa scaling out programme: (i) testing different technologies and practices; (ii) evaluating the performance of different technologies in different contexts; and (iii) monitoring factors that are difficult to predict. We incorporated the review lessons in a design to appropriately target and evaluate technologies in multiple contexts across scales from that of the farm to whole countries. Our implementation of this design has only been partially successful because of competing reasons for selecting activity sites. Nevertheless, we observe that grain legume species have been successfully targeted for multiple biophysical environments across sub-Saharan Africa, and to social and economic contexts within countries. Rhizobium inoculant and legume specific fertiliser blends have also been targeted to specific contexts, although not in all countries. Relatively fewer input and output marketing models have been tested due to public–private partnerships, which are a key mechanism for dissemination in the N2Africa project.

The Australian Centre for Advanced Photovoltaics (ACAP) co-ordinates the activities of the six Australian research institutions and a group of industrial partners in the Australia-US Institute for Advanced Photovoltaics (AUSIAPV) to develop the next generations of photovoltaic device technology and to provide a pipeline of opportunities for performance increase and cost reduction. AUSIAPV links ACAP with US-based partners. These national and international research collaborations provide a pathway for highly visible, structured photovoltaic research collaboration between Australian and US researchers, institutes and agencies with significant joint programs based on the clear synergies between the participating organizations. The research program is organized in five collaborative Program Packages (PPs). PP1 deals with silicon wafer-based cells, focusing on three main areas: cells from solar grade silicon, rear contact and silicon-based tandem cells. PP2 involves research into a range of organic solar cells, organic/inorganic hybrid cells, "earth abundant" thin-film materials and "third generation" approaches. PP3 is concerned with optics and characterization. PP4 will deliver a substantiated methodology for assessing manufacturing costs of the different technologies and PP5 involves education, training and outreach. The main research topics, results and plans for the future are presented.