Designing a global assessment of climate change on inland fishes and fisheries: knowns and needs

© 2017, Springer International Publishing Switzerland (outside the USA). To date, there are few comprehensive assessments of how climate change affects inland finfish, fisheries, and aquaculture at a global scale, but one is necessary to identify research needs and commonalities across regions and to help guide decision making and funding priorities. Broadly, the consequences of climate change on inland fishes will impact global food security, the livelihoods of people who depend on inland capture and recreational fisheries. However, understanding how climate change will affect inland fishes and fisheries has lagged behind marine assessments. Building from a North American inland fisheries assessment, we convened an expert panel from seven countries to provide a first-step to a framework for determining how to approach an assessment of how climate change may affect inland fishes, capture fisheries, and aquaculture globally. Starting with the small group helped frame the key questions (e.g., who is the audience? What is the best approach and spatial scale?). Data gaps identified by the group include: the tolerances of inland fisheries to changes in temperature, stream flows, salinity, and other environmental factors linked to climate change, and the adaptive capacity of fishes and fisheries to adjust to these changes. These questions are difficult to address, but long-term and large-scale datasets are becoming more readily available as a means to test hypotheses related to climate change. We hope this perspective will help researchers and decision makers identify research priorities and provide a framework to help sustain inland fish populations and fisheries for the diversity of users around the globe

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

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

Diversity-Production Relationships of Fish Communities in Freshwater Stream Ecosystems

Aim Ecological relationships between species richness and biomass production are increasingly thought to be pervasive across the globe. Yet, diversity-production relationships have not been explored extensively for freshwater fish communities even though fisheries production provides key services to humans. Our aim was to evaluate the diversity-production relationship of fish communities inhabiting freshwater streams across the Appalachian Mountain range and examine how diversity-production relationships varied across streams possessing different thermal signatures. Location Our study area included 25 freshwater stream ecosystems spanning from Vermont to North Carolina in the United States. Twenty sites were located in Maryland south to Tennessee and North Carolina, while five additional higher latitude sites were sampled in Massachusetts and Vermont. Methods We sampled the 25 study streams from June to September 2012 and collected fish population information to calculate biomass, species richness, the Shannon diversity index and annual production for each fish community. Linear mixed effects models were used to analyse the relationship between diversity indices and total community production. We also compared diversity and production relationships across other taxa. Results Across all streams, community fish production, biomass and P/B ratios ranged from 0.15-6.79 g m(-)(2) y(-)(1), 0.61-0.73 g m(-)(2) and 0.21-1.07 y(-1), respectively. Species richness had a significant positive effect (p = .012) on community fish production, while accounting for the thermal signature of the streams as a random effect and other habitat covariates. The Shannon diversity index did not have a significant effect (p = .101) on community production. Main conclusions The diversity-production relationship observed for stream fish communities was similar to other studies but demonstrated one of the highest slopes. Our results demonstrate that effects of biodiversity resonate to influence the production of fishes; thus, management of fisheries is more closely coupled to biodiversity than previously thought

Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study

Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research

Human-Computer Interaction in the School of Computer Science

The SCS faculty interested in Human-Computer Interaction (HCI) presents its position on what role HCI can play in Carnegie Mellon&apos;s School of Computer Science. We present a short description of the need for HCI research and recommend a task/human/computer approach to satisfying that need. After presenting illustrative research scenarios, we draw implications of adopting this approach for our research and educational programs. SCS is well positioned to implement this approach, given the interests and skills of our faculty and faculty in other organizations at CMU. We recommend that the Computer Science Department form a new area in HCI. Human-Computer Interaction in the School of Computer Science Edited by Bonnie E. John, Philip L. Miller, Brad A. Myers, Christine M. Neuwirth, and Steven A. Shafer October 1992 CMU-CS-92-193 Keywords: Human Computer Interaction (HCI), strategic plan, curriculum Executive Summary The Problem. Computers have the potential to revolutionize many areas ..

Optimal therapeutic targeting by HDAC inhibition in biopsy-derived treatment-naïve diffuse midline glioma models

BACKGROUND Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs), have a dismal prognosis with less than 2% surviving 5-years post-diagnosis. The majority of DIPGs and all DMGs harbor mutations altering the epigenetic regulatory histone tail (H3 K27M). Investigations addressing DMG epigenetics have identified few promising drugs, including the HDAC inhibitor (HDACi) panobinostat. Here, we use clinically-relevant DMG models to identify and validate other effective HDACi and their biomarkers of response. METHODS HDACi were tested across biopsy-derived treatment-naïve in vitro and in vivo DMG models with biologically-relevant radiation-resistance. RNA sequencing was performed to define and compare drug efficacy, and to map predictive biomarkers of response. RESULTS Quisinostat and romidepsin showed efficacy with a low nanomolar IC50 values (~50 and ~5 nM, respectively). Comparative transcriptome analyses across quisinostat, romidepsin, and panobinostat showed a greater degree of shared biological effects between quisinostat and panobinostat, and less overlap with romidepsin. However, some transcriptional changes were consistent across all three drugs at similar biologically effective doses, such as overexpression of TNNT1 and downregulation of COL20A1, identifying these as potential vulnerabilities or on-target biomarkers in DMG. Quisinostat and romidepsin significantly (p <0.0001) inhibited in vivo tumor growth. CONCLUSIONS Our data highlights the utility of treatment-naïve biopsy-derived models; establishes quisinostat and romidepsin as effective in vivo; illuminates potential mechanisms and/or biomarkers of DMG cell lethality due to HDAC inhibition; and emphasizes the need for brain-tumor-penetrant versions of potentially efficacious agents

A New Approach to Evaluate and Reduce Uncertainty of Model-Based Biodiversity Projections for Conservation Policy Formulation

Biodiversity projections with uncertainty estimates under different climate, land-use, and policy scenarios are essential to setting and achieving international targets to mitigate biodiversity loss. Evaluating and improving biodiversity predictions to better inform policy decisions remains a central conservation goal and challenge. A comprehensive strategy to evaluate and reduce uncertainty of model outputs against observed measurements and multiple models would help to produce more robust biodiversity predictions. We propose an approach that integrates biodiversity models and emerging remote sensing and in-situ data streams to evaluate and reduce uncertainty with the goal of improving policy-relevant biodiversity predictions. In this article, we describe a multivariate approach to directly and indirectly evaluate and constrain model uncertainty, demonstrate a proof of concept of this approach, embed the concept within the broader context of model evaluation and scenario analysis for conservation policy, and highlight lessons from other modeling communities.NASAPublic domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]