Strengthen causal models for better conservation outcomes for human well-being

This is the final version. Available from the publisher via the DOI in this record.All data files are available on github at www.github.com/scheng87/ toc.Background Understanding how the conservation of nature can lead to improvement in human conditions is a research area with significant growth and attention. Progress towards effective conservation requires understanding mechanisms for achieving impact within complex social-ecological systems. Causal models are useful tools for defining plausible pathways from conservation actions to impacts on nature and people. Evaluating the potential of different strategies for delivering co-benefits for nature and people will require the use and testing of clear causal models that explicitly define the logic and assumptions behind cause and effect relationships. Objectives and methods In this study, we outline criteria for credible causal models and systematically evaluated their use in a broad base of literature (~1,000 peer-reviewed and grey literature articles from a published systematic evidence map) on links between nature-based conservation actions and human well-being impacts. Results Out of 1,027 publications identified, only ~20% of articles used any type of causal models to guide their work, and only 14 total articles fulfilled all criteria for credibility. Articles rarely tested the validity of models with empirical data. Implications Not using causal models risks poorly defined strategies, misunderstanding of potential mechanisms for affecting change, inefficient use of resources, and focusing on implausible efforts for achieving sustainability.Science for Nature and People Partnership (SNAPP)National Institute for Health Research (NIHR

Using machine learning to advance synthesis and use of conservation and environmental evidence

This is the final version. Available from Wiley via the DOI in this record. National Institute for Health ResearchScience for Nature and People Partnershi

Strengthen causal models for better conservation outcomes for human well-being.

BACKGROUND: Understanding how the conservation of nature can lead to improvement in human conditions is a research area with significant growth and attention. Progress towards effective conservation requires understanding mechanisms for achieving impact within complex social-ecological systems. Causal models are useful tools for defining plausible pathways from conservation actions to impacts on nature and people. Evaluating the potential of different strategies for delivering co-benefits for nature and people will require the use and testing of clear causal models that explicitly define the logic and assumptions behind cause and effect relationships. OBJECTIVES AND METHODS: In this study, we outline criteria for credible causal models and systematically evaluated their use in a broad base of literature (~1,000 peer-reviewed and grey literature articles from a published systematic evidence map) on links between nature-based conservation actions and human well-being impacts. RESULTS: Out of 1,027 publications identified, only ~20% of articles used any type of causal models to guide their work, and only 14 total articles fulfilled all criteria for credibility. Articles rarely tested the validity of models with empirical data. IMPLICATIONS: Not using causal models risks poorly defined strategies, misunderstanding of potential mechanisms for affecting change, inefficient use of resources, and focusing on implausible efforts for achieving sustainability

A cross-sectional survey exploring HIV and HCV prevalence among men who purchase sex in Dnipro, Ukraine

BACKGROUND: HIV programming in Ukraine largely targets "key population" groups. Men who purchase sex are not directly reached. The aim of our study was to explore the prevalence of sexually transmitted and blood-borne infections (STBBIs) among men who purchase sex from female sex workers. METHODS: Following geographic mapping and population size estimation at each "hotspot", we conducted a cross-sectional bio-behavioural survey with men who purchase sex between September 2017 and March 2018 in Dnipro, Ukraine. Eligibility criteria included purchasing sex services at a "hotspot" and being ≥ 18 years. Participants completed a structured questionnaire, followed by HIV/HCV rapid testing and a dried blood spot (DBS) sample collection for confirmatory serology. RESULTS: The study enrolled 370 participants. The median age was 32 (interquartile range [IQR] = 27-38) and the median age of first purchase of sexual services was 22 (IQR = 19-27). Over half (56%) of participants reported ever testing for HIV; four participants (2%, N = 206) reported having tested positive for HIV, with three out of the four reporting being on ART. Forty percent of participants had ever tested for HCV, with three (2%, N = 142) having ever tested positive for HCV. In DBS testing, nine participants (2.4%) tested positive for HIV and 24 (6.5%) tested positive for ever having an HCV infection. CONCLUSION: Prevalence of HIV and HCV in this population was high. Given high rates of study enrolment and testing, efforts should be made to reach men who purchase sex with expanded STBBI programming

The migration of the great snipe Gallinago media: intriguing variations on a grand theme

The migration of the great snipe Gallinago media was previously poorly known. Three tracks in 2010 suggested a remarkable migratory behaviour including long and fast overland non-stop flights (Klaassen et al. 2011). Here we present the migration pattern of Swedish male great snipes, based on 19 individuals tracked by light-level geolocators in four different years. About half of the birds made stopover(s) in northern Europe in early autumn. They left the breeding area 15 days earlier than those which flew directly to sub-Sahara, suggesting two distinct autumn migration strategies. The autumn trans-Sahara flights were on average 5500 km long, lasted 64 h, and were flown at ground speeds of 25 m s-1 (90 km h-1). The arrival in the Sahel zone of West Africa coincided with the wet season there, and the birds stayed for on average three weeks. The birds arrived at their wintering grounds around the lower stretches of the Congo River in late September and stayed for seven months. In spring the great snipes made trans-Sahara flights of similar length and speed as in autumn, but the remaining migration through eastern Europe was notably slow. All birds returned to the breeding grounds within one week around mid-May. The annual cycle was characterized by relaxed temporal synchronization between individuals during the autumn-winter period, with maximum variation at the arrival in the wintering area. Synchronization increased in spring, with minimum time variation at arrival in the breeding area. This suggests that arrival date in the breeding area is under strong stabilizing selection, while there is room for more flexibility in autumn and arrival to the wintering area. The details of the fast non-stop flights remain to be elucidated, but the identification of the main stopover and wintering areas is important for future conservation work on this red-listed bird species

A novel small molecule inhibitor of MRCK prevents radiation-driven invasion in glioblastoma

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes severe neurological, cognitive, and psychological symptoms. Symptoms are caused and exacerbated by the infiltrative properties of GBM cells, which enable them to pervade the healthy brain and disrupt normal function. Recent research has indicated that, while radiotherapy (RT) remains the most effective component of multimodality therapy for GBM patients, it can provoke a more infiltrative phenotype in GBM cells that survive treatment. Here we demonstrate an essential role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related CDC42- binding kinase (MRCK) in mediating the pro-invasive effects of radiation. MRCK-mediated invasion occurred via downstream signaling to effector molecules MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of radiation, and this activation was concomitant with an increase in GBM cell motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or by inhibition with the novel small molecule inhibitor BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy

OC6 Phase II: Integration and verification of a new soil–structure interaction model for offshore wind design

This paper provides a summary of the work done within the OC6 Phase II project, which was focused on the implementation and verification of an advanced soil–structure interaction model for offshore wind system design and analysis. The soil–structure interaction model comes from the REDWIN project and uses an elastoplastic, macroelement model with kinematic hardening, which captures the stiffness and damping characteristics of offshore wind foundations more accurately than more traditional and simplified soil–structure interaction modeling approaches. Participants in the OC6 project integrated this macroelement capability to coupled aero-hydro-servo-elastic offshore wind turbine modeling tools and verified the implementation by comparing simulation results across the modeling tools for an example monopile design. The simulation results were also compared to more traditional soil–structure interaction modeling approaches like apparent fixity, coupled springs, and distributed springs models. The macroelement approach resulted in smaller overall loading in the system due to both shifts in the system frequencies and increased energy dissipation. No validation work was performed, but the macroelement approach has shown increased accuracy within the REDWIN project, resulting in decreased uncertainty in the design. For the monopile design investigated here, that implies a less conservative and thus more cost-effective offshore wind design.US Department of Energy Office of Energy Efficiency and Renewable Energy Wind Energy Technologies Office, Grant/Award Number: DE-AC36-08GO2830