An mHealth Intervention to Improve Pre-Exposure Prophylaxis Knowledge Among Young Black Women in Family Planning Clinics: Development and Usability Study.

BACKGROUND: Young Black women between the ages of 18 and 24 years are disproportionately impacted by HIV, yet they have a low self-perception of HIV risk and limited exposure to prevention strategies. Pre-exposure prophylaxis (PrEP) is a safe and effective biomedical HIV prevention strategy for those at risk for HIV infection, but uptake has been slow among cisgender women. Family planning clinics are a primary source of health care access for young women, providing an ideal opportunity to integrate PrEP information and care into existing clinic practices. OBJECTIVE: The aim of this study was to use a multistage, community-engaged process to develop a mobile health app and to evaluate the feasibility and acceptability of the app. METHODS: Using user-centered design, the In the Loop app was developed in collaboration with a community advisory board of young Black women. This study employed a multistage design, which included community-engaged app development, user testing, and evaluation of the app's feasibility and acceptability. A pre- and postdesign was used to assess the impact of the app on PrEP knowledge immediately after app use. Descriptive statistics (eg, mean, SD, and percentage values) were used to describe the sample, and Wilcoxon matched-pairs signed-ranks test was used to detect changes in PrEP knowledge before and immediately after using the app. RESULTS: A total of 50 sexually active, young Black women, aged 18-24 (mean 21, SD 1.9) years, were enrolled in this study. Analysis comparing scores before and immediately after use of the app revealed a significant increase in PrEP content knowledge scores on a 7-item true or false scale (z=-6.04, P<.001). Overall, participants considered the In the Loop app feasible and acceptable to use while waiting for a family planning visit. The majority of participants (n=46, 92%) agreed that they would recommend In the Loop to friends to learn more about PrEP. Participants rated the overall quality of the app 4.3 on a 1-5 scale (1=very poor and 5=very good). Of 50 participants, 40 (80%) agreed that the app was easy to use, and 48 (96%) agreed that they found the information in the app easy to understand. Finally, 40 (80%) agreed that they had enjoyed using the app while waiting for their family planning visit. CONCLUSIONS: Our findings suggest that young Black women waiting for family planning visits found the In the Loop app to be feasible and acceptable. This study demonstrates the value of engaging young Black women in the app design process. As family planning clinics are a primary source of health care access for young women, they provide an ideal setting to integrate PrEP information and care into existing clinic practices. Next steps in the development of the In the Loop app include implementing user-suggested improvements and conducting efficacy testing in a randomized controlled trial to determine the app's impact on PrEP uptake

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented.EEA BarilocheFil: Haider, Sylvia. German Centre for Integrative Biodiversity Research; AlemaniaFil: Haider, Sylvia. Martin Luther University. Institute of Biology. Geobotany and Botanical Garden; AlemaniaFil: Lembrechts, Jonas Johan. University of Antwerp. Centre of Excellence Plants and Ecosystems (PLECO); BélgicaFil: McDougall, Keith. Department of Planning, Industry and Environment; AustraliaFil: Pauchard, Aníbal. Universidad de Concepción. Facultad de Ciencias Forestales. Laboratorio de Invasiones Biológicas; ChileFil: Pauchard, Aníbal. Institute of Ecology and Biodiversity (IEB); ChileFil: Alexander, Jake M. Institute of Integrative Biology; SuizaFil: Barros, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Instituto Argentino de Nivología y Glaciología y Ciencias Ambientales (IANIGLA); ArgentinaFil: Cavieres, Lohengrin A. Universidad de Concepción. Facultad de Ciencias Naturales y Oceanográficas. Departamento de Botánica; ChileFil: Cavieres, Lohengrin A. Institute of Ecology and Biodiversity (IEB); ChileFil: Rashid, Irfan. University of Kashmir. Department of Botany; IndiaFil: Rew, Lisa J. Montana State University. Department of Land Resource and Environmental Sciences; Estados UnidosFil: Aleksanyan, Alla. Institute of Botany aft. A.L. Takhtajyan NAS RA. Department of Geobotany and Plant Ecophysiology; ArmeniaFil: Aleksanyan, Alla. Armenian National Agrarian University. Chair of Biology and Biotechnologies; ArmeniaFil: Dimarco, Romina Daniela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. Grupo de Ecología de Poblaciones de Insectos; ArgentinaFil: Dimarco, Romina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. Grupo de Ecología de Poblaciones de Insectos; ArgentinaFil: Dimarco, Romina Daniela. University of Houston. Department of Biology and Biochemistry; Estados UnidosFil: Seipel, Tim. Montana State University. Department of Land Resource and Environmental Sciences; Estados Unido

High-Dose Ipilimumab and High-Dose Interleukin-2 for Patients With Advanced Melanoma.

High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved agents for metastatic melanoma, but the efficacy and safety of the combination are unknown. The objective of this study was to evaluate the feasibility, safety, and efficacy of combination high-dose IPI and high-dose IL-2 in patients with histologically confirmed advanced unresectable stage III and IV melanoma. This Phase II, multicenter, open-label, single-arm trial was conducted in nine patients enrolled between 12/2014 and 12/2015. Subjects were treated with high-dose IPI 10 mg/kg intravenous (IV) every 3 weeks for four doses starting at week 1 and high-dose IL-2 (600,000 IU/kg IV bolus every 8 h for up to 14 doses) concurrently with IPI at weeks 4 and 7. After the first 12 weeks of combination therapy, maintenance IPI (10 mg/kg IV) monotherapy was administered every 12 weeks for up to 1 year. No patient had received prior PD-1 blockade, and only one received prior vemurafenib. Confirmed partial response was achieved in one (11%), stable disease in four (44%), and progressive disease in four (44%) of nine patients. Two patients achieved durable disease control of 44+ and 50+ months at the most recent follow-up without subsequent therapy. The median overall survival was not reached after a minimum 24 months of follow-up time. One-year and 2-year survival rates were 89 and 67%, respectively. Seven patients (78%) experienced grade 3 or 4 adverse events related to the study therapy, three of which were attributed to both agents. One patient discontinued the treatment due to liver and kidney toxicity. While toxicity was significant, all events were reversible, and there was no treatment-related mortality. In peripheral blood of patients with decreasing tumor burden, the ratio of the non-classical MHC-II proteins HLA-DM to HLA-DO increased 2-fold, raising the possibility of the ratio of HLA-DM:HLA-DO as a novel biomarker of response to treatment. Although the sample size was limited, combination therapy with high-dose IPI and high-dose IL-2 was feasible and associated with clinical benefit. IL-2-based compounds in combination with CTLA-4 blockade should be studied in advanced melanoma patients who fail to benefit from first-line PD-1 blockade

Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.

Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect

Choosing a genome browser for a Model Organism Database: surveying the Maize community

As the B73 maize genome sequencing project neared completion, MaizeGDB began to integrate a graphical genome browser with its existing web interface and database. To ensure that maize researchers would optimally benefit from the potential addition of a genome browser to the existing MaizeGDB resource, personnel at MaizeGDB surveyed researchers’ needs. Collected data indicate that existing genome browsers for maize were inadequate and suggest implementation of a browser with quick interface and intuitive tools would meet most researchers’ needs. Here, we document the survey’s outcomes, review functionalities of available genome browser software platforms and offer our rationale for choosing the GBrowse software suite for MaizeGDB. Because the genome as represented within the MaizeGDB Genome Browser is tied to detailed phenotypic data, molecular marker information, available stocks, etc., the MaizeGDB Genome Browser represents a novel mechanism by which the researchers can leverage maize sequence information toward crop improvement directly

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery