Innovative programmatic approaches to HIV prevention and care services for gay men, other men who have sex with men (MSM) and transgender persons using information and communication technology (ICT)

This Special Issue of Digital Culture & Education (DCE) provides innovative programmatic approaches to HIV prevention and care services for gay men, other men that have sex with men (MSM) and transgender persons using information and communication technology (ICT) at a time when these same populations are experiencing an alarming upward trend of new HIV infections. During a successful participatory consultation in Washington D.C. in May 2013 hosted by the U.S. Agency for International Development (USAID) and co-supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), amfAR, the Foundation for AIDS Research, and the National Institutes of Mental Health (NIMH), representatives from Africa, Asia, the Caribbean, Latin America, Europe, Australia and the United States shared innovative uses of communication technology across HIV research, programs, outreach, advocacy and public-private partnerships. Believing it crucial to share their innovations more widely—through open-access channels—led us to working in partnership with these frontline workers, activists, researchers and educators to further document and share their technological innovations in different global contexts. Importantly, we prioritised working with frontline workers and activists by providing cyclical and targeted writing mentoring to assist them in writing about their successful digital interventions. Disseminating this timely work through open-access channels, like Digital Culture & Education (DCE) means that researchers in less resourced institutions, practitioners and activists in the field and the general public can better understand how ICT, particularly mobile technologies, provides unprecedented opportunities to more effectively reach and engage gay men, other MSM and transgender populations across the HIV prevention, testing, treatment and care cascade

Panel 2: ATP/CTP Experience Report & New Ideas In Flight Education

Provider and employer reports on current results, compliance success, affiliations/partnerships meeting FOQ ATP/CTP requirements. FAA Adams Collegiate & Flight Academy Educators Byrnes (ERAU), Morrison (CAE), Hibler (FSI) Employers: Airlines Greubel (ExpressJet), Haugaard (Horizon Air), Buyer (United), Dee (Republic), Winter (JetBlue), Panhans (Allegiant) New Idea in U.S. Flight Education; JetBlue Gateway 7 Program (G7) Winte

Uncovering Tropical Eiversity: Six Sympatric Cryptic Species of Blepharoneura (Diptera: Tephritidae) in Flowers of Gurania spinulosa (Cucurbitaceae) in Eastern Ecuador

Diversification of phytophagous insects is often associated with changes in the use of host taxa and host parts. We focus on a group of newly discovered Neotropical tephritids in the genus Blepharoneura, and report the discovery of an extraordinary number of sympatric, morphologically cryptic species, all feeding as larvae on calyces of flowers of a single functionally dioecious and highly sexually dimorphic host species (Gurania spinulosa) in eastern Ecuador. Molecular analyses of the mitochondrial cytochrome oxidase-I gene from flies reared from flowers of G. spinulosa reveal six distinct haplotype groups that differ by 7.2-10.1% bp (uncorrected pairwise distances; N = 624 bp). Haplotype groups correspond to six distinct and well-supported clades. Members of five clades specialize on the calyces of flowers of a particular sex: three clades comprise male flower specialists; two clades comprise female flower specialists; the sixth clade comprises generalists reared from male and female flowers. The six clades occupy significantly different morphological spaces defined by wing pigmentation patterns; however, diagnostic morphological characters were not discovered. Behavioural observations suggest specific courtship behaviours may play a role in maintaining reproductive isolation among sympatric species

A cross-sectional assessment of population demographics, HIV risks and human rights contexts among men who have sex with men in Lesotho

<p>Abstract</p> <p>Background</p> <p>Evidence is increasing of high HIV risks among southern African men who have sex with men (MSM). This represents the first study of HIV risks and human rights contexts among MSM in Lesotho.</p> <p>Methods</p> <p>Two hundred and fifty-two men who reported ever having anal sex with another man were accrued with snowball sampling and were administered a structured quantitative instrument in October and November 2009.</p> <p>Results</p> <p>Of the participants, 96.4% (240/249) were ethnic Basotho with a mean age of 26.3 years (range 18-56), 49.6% (124/250) were currently employed, and 95.2% (238/250) had at least a secondary-level education. Self-reported HIV prevalence was 11.6% (22/190); 54.5% (128/235) reported being tested for HIV in the last year. HIV knowledge was low; only 3.7% (8/212) of MSM knew that receptive anal intercourse was the highest risk for HIV and that a water-based lubricant was most appropriate to use with condoms.</p> <p>Bivariate associations of wearing condoms during last intercourse with men include: having easy access to condoms (OR 3.1, 95% CI 1.2-8.5, p < 0.05); being older than 26 years (OR 2.3, 95% CI 1.3-4.2, p < 0.01); knowing that receptive anal intercourse is higher risk than insertive anal intercourse (OR 2.6, 95% CI 1.2-5.9, p < 0.05); wearing condoms with female sexual partners (OR 3.5, 95% 1.4-8.3, p < 0.01); using water-based lubricants (OR 2.8, 95% CI 1.4-5.5, p < 0.01); being less likely to report having been diagnosed with a sexually transmitted infecton (OR 0.21, 95% CI 0.06-0.76, p < 0.05); and being more likely to have been tested for HIV in the last year (OR 2.0, 95% CI 1.2-3.6, p > 0.05).</p> <p>Human rights abuses were common: 76.2% (170/223) reported at least one abuse, including rape (9.8%, 22/225), blackmail (21.3%, 47/221), fear of seeking healthcare (22.2%, 49/221), police discrimination (16.4%, 36/219), verbal or physical harassment (59.8%, 140/234), or having been beaten (18.9%, 43/228).</p> <p>Conclusions</p> <p>MSM in Lesotho are at high risk for HIV infection and human rights abuses. Evidence-based and rights-affirming HIV prevention programmes supporting the needs of MSM should be developed and implemented.</p

Droplet Size Impact on Efficacy of a Dicamba-plus-Glyphosate Mixture

Chemical weed control remains a widely used component of integrated weed management strategies because of its cost-effectiveness and rapid removal of crop pests. Additionally, dicamba-plus-glyphosate mixtures are a commonly recommended herbicide combination to combat herbicide resistance, specifically in recently commercially released dicamba-tolerant soybean and cotton. However, increased spray drift concerns and antagonistic interactions require that the application process be optimized to maximize biological efficacy while minimizing environmental contamination potential. Field research was conducted in 2016, 2017, and 2018 across three locations (Mississippi, Nebraska, and North Dakota) for a total of six site-years. The objectives were to characterize the efficacy of a range of droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)] using a dicamba-plus-glyphosate mixture and to create novel weed management recommendations utilizing pulse-width modulation (PWM) sprayer technology. Results across pooled site-years indicated that a droplet size of 395 μm (Coarse) maximized weed mortality from a dicamba-plus-glyphosate mixture at 94 L ha–1. However, droplet size could be increased to 620 μm (Extremely Coarse) to maintain 90% of the maximum weed mortality while further mitigating particle drift potential. Although generalized droplet size recommendations could be created across site-years, optimum droplet sizes within each site-year varied considerably and may be dependent on weed species, geographic location, weather conditions, and herbicide resistance(s) present in the field. The precise, site-specific application of a dicamba-plus-glyphosate mixture using the results of this research will allow applicators to more effectively utilize PWM sprayers, reduce particle drift potential, maintain biological efficacy, and reduce the selection pressure for the evolution of herbicide-resistant weeds

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts