Several global strategies for protected area (PA) expansion have been proposed to achieve the Convention on Biological Diversity's Aichi target 11 as a means to stem biodiversity loss, as required by ...the Aichi target 12. However, habitat loss outside PAs will continue to affect habitats and species, and PAs may displace human activities into areas that might be even more important for species persistence. Here we measure the expected contribution of PA expansion strategies to Aichi target 12 by estimating the extent of suitable habitat available for all terrestrial mammals, with and without additional protection (the latter giving the counterfactual outcome), under different socio-economic scenarios and consequent land-use change to 2020. We found that expanding PAs to achieve representation targets for ecoregions under a Business-as-usual socio-economic scenario will result in a worse prognosis than doing nothing for more than 50% of the world's terrestrial mammals. By contrast, targeting protection towards threatened species can increase the suitable habitat available to over 60% of terrestrial mammals. Even in the absence of additional protection, an alternative socio-economic scenario, adopting progressive changes in human consumption, leads to positive outcomes for mammals globally and to the largest improvements for wide-ranging species.
Governments have committed to conserving ≥17% of terrestrial and ≥10% of marine environments globally, especially “areas of particular importance for biodiversity” through “ecologically ...representative” Protected Area (PA) systems or other “area‐based conservation measures”, while individual countries have committed to conserve 3–50% of their land area. We estimate that PAs currently cover 14.6% of terrestrial and 2.8% of marine extent, but 59–68% of ecoregions, 77–78% of important sites for biodiversity, and 57% of 25,380 species have inadequate coverage. The existing 19.7 million km² terrestrial PA network needs only 3.3 million km² to be added to achieve 17% terrestrial coverage. However, it would require nearly doubling to achieve, cost‐efficiently, coverage targets for all countries, ecoregions, important sites, and species. Poorer countries have the largest relative shortfalls. Such extensive and rapid expansion of formal PAs is unlikely to be achievable. Greater focus is therefore needed on alternative approaches, including community‐ and privately managed sites and other effective area‐based conservation measures.
Conservation area networks in most countries are fragmented and inadequate. To tackle this in England, government policies are encouraging stakeholders to create local‐level nature recovery networks. ...Here, we describe work led by a wildlife organization that used the systematic conservation planning approach to identify a nature recovery network for three English counties and select focal areas within it where they will focus their work. The network was based on identifying core zones to maintain current biodiversity and recovery zones for habitat restoration, meeting area‐based targets for 50 priority habitat, landscape, landcover, and ecosystem service types. It included the existing designated sites for conservation, which cover 6.05% of the study site, and identified an additional 11.6% of land as core zones and 18% as recovery zones, reflecting the organization's call for 30% of England to be conserved and connected by 2030. We found that systematic conservation planning worked well in this context, identifying a connected, adequate, representative, and efficient network and producing transparent and repeatable results. The analysis also highlighted the pressing need for government agencies to provide national‐level guidance and datasets for setting targets and including species data in spatial planning, creating a national framework to inform local action.
Here, we describe work led by a wildlife organization that used the systematic conservation planning approach to identify a nature recovery network for three English counties and select focal areas within it where they will focus their work. The proposed network contains core zones for maintaining biodiversity and recovery zones for habitat restoration, meeting targets for 50 priority habitat, landscape, landcover, and ecosystem service types. The analysis also highlighted the need for national‐level guidance and datasets for setting targets and including species data in spatial planning, creating a national framework to inform local action.
Several global strategies for protected area (PA) expansion have been proposed to achieve the Convention on Biological Diversity's Aichi target 11 as a means to stem biodiversity loss, as required by ...the Aichi target 12. However, habitat loss outside PAs will continue to affect habitats and species, and PAs may displace human activities into areas that might be even more important for species persistence. Here we measure the expected contribution of PA expansion strategies to Aichi target 12 by estimating the extent of suitable habitat available for all terrestrial mammals, with and without additional protection (the latter giving the counterfactual outcome), under different socio-economic scenarios and consequent land-use change to 2020. We found that expanding PAs to achieve representation targets for ecoregions under a Business-as-usual socio-economic scenario will result in a worse prognosis than doing nothing for more than 50% of the world's terrestrial mammals. By contrast, targeting protection towards threatened species can increase the suitable habitat available to over 60% of terrestrial mammals. Even in the absence of additional protection, an alternative socio-economic scenario, adopting progressive changes in human consumption, leads to positive outcomes for mammals globally and to the largest improvements for wide-ranging species.
Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between ...morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cytonemes, how quickly a cytoneme-delivered, receptor-dependent signal is initiated, and whether these processes are conserved across phyla are not known. Herein, we reveal that the actin motor Myosin 10 promotes vesicular transport of Sonic Hedgehog (SHH) morphogen in mouse cell cytonemes, and that SHH morphogen gradient organization is altered in neural tubes of
mice. We demonstrate that cytoneme-mediated deposition of SHH onto receiving cells induces a rapid, receptor-dependent signal response that occurs within seconds of ligand delivery. This activity is dependent upon a novel Dispatched (DISP)-BOC/CDON co-receptor complex that functions in ligand-producing cells to promote cytoneme occurrence and facilitate ligand delivery for signal activation.
We developed a rapid method to remove the native mouse thymus from NSG mice, which allowed us to compare the behavior of human immune cells in the presence or absence of human T cells in human immune ...system mice. Removing the native mouse thymus is critical for studies of human thymopiesis in grafted thymic tissue in humanized mice.
Tumor hypoxia is a negative prognostic factor in multiple cancers, due in part to its role in causing resistance to radiotherapy. Hypoxia arises in tumor regions distal to blood vessels as oxygen is ...consumed by more proximal tumor cells. Reducing the rate of oxygen consumption is therefore a potential strategy to reduce tumor hypoxia. We hypothesized that the anti-diabetic drug metformin, which reduces oxygen consumption through inhibition of mitochondrial complex I, would improve radiation response by increasing tumor oxygenation.
Tumor hypoxia was measured in xenografts before and after metformin treatment using 2-nitroimidazole hypoxia markers quantified by immunohistochemistry (IHC), flow cytometry, and positron emission tomography (PET) imaging. Radiation response was determined by tumor growth delay and clonogenic survival in xenografts with and without administration of metformin. The impact of metformin use on outcome was assessed in 504 patients with localized prostate cancer treated with curative-intent, image-guided radiotherapy (IGRT) from 1996 to 2012. Three-year biochemical relapse-free rates were assessed using the Kaplan-Meier method.
Metformin treatment significantly improved tumor oxygenation in two xenograft models as measured by IHC, flow cytometry, and PET imaging. Metformin also led to improved radiotherapy responses when mice were administered metformin immediately before irradiation. Clinically, metformin use was associated with an independent and significant decrease in early biochemical relapse rates (P = 0.0106).
Our data demonstrate that metformin can improve tumor oxygenation and response to radiotherapy. Our study suggests that metformin may represent an effective and inexpensive means to improve radiotherapy outcome with an optimal therapeutic ratio.
Platelet autoantibody (PA) testing has previously shown poor sensitivity for immune thrombocytopenia (ITP) diagnosis, but no previous study used both 2011 American Society of Hematology (ASH) ...guidelines for ITP diagnosis and 2012 International Society on Thrombosis and Haemostasis (ISTH) PA testing recommendations. We therefore performed a comprehensive retrospective study of PA testing in adult patients with ITP strictly applying these criteria. Of 986 PA assays performed, 485 assays in 368 patients met criteria and were included. Sensitivity and specificity of a positive test result for diagnosis of active ITP (n = 228 patients) were 90% and 78%, respectively. Sensitivity and specificity of a negative test result for clinical remission (n = 61 assays) were 87% and 91%. Antibodies against both glycoprotein IIb (GPIIb)/IIIa and GPIb/IX were required for the presence of antibodies against GPIa/IIa in patients with ITP. Logistic regression analysis revealed that more positive autoantibodies predicted more severe disease (relative to nonsevere ITP, relative risk ratio for severe ITP and refractory ITP was 2.27 P < .001 and 3.09 P < .001, respectively, per additional autoantibody); however, serologic testing did not meaningfully predict treatment response to glucocorticoids, intravenous immunoglobulin, or thrombopoietin receptor agonists. Sixty-four patients with ITP had multiple PA assays performed longitudinally: all 10 patients achieving remission converted from positive to negative serologic results, and evidence for epitope spreading was observed in 35% of patients with ongoing active disease. In conclusion, glycoprotein-specific direct PA testing performed using ISTH recommendations in patients meeting ASH diagnostic criteria is sensitive and specific for ITP diagnosis and reliably confirms clinical remission. More glycoproteins targeted by autoantibodies predicts for more severe disease.
•When performed in accordance with modern ASH and ISTH guidelines, PA testing is sensitive and specific for ITP diagnosis.•More glycoproteins targeted by autoantibodies predicts for more severe disease, and autoantibodies resolve with clinical remission.
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The Art of Oncology: COVID‐19 Era Reynolds, Kerry L.; Klempner, Samuel J.; Parikh, Aparna ...
The oncologist (Dayton, Ohio),
November 2020, Letnik:
25, Številka:
11
Journal Article
Purpose
: To investigate whether analysis of MRI enhancement data using a pharmacokinetic model improved a previously found correlation between contrast enhancement and tumor oxygenation measured ...using Po
2 histograph. To evaluate the prognostic value of gadolinium enhancement data for radiotherapy outcome, and to study the efficacy of combined enhancement and MRI volume data.
Methods and materials
: Fifty patients underwent dynamic gadolinium-enhanced MRI as part of their initial staging investigations before treatment. Gadolinium enhancement was analyzed using the Brix pharmacokinetic model to obtain the parameters amplitude and rate of contrast enhancement. Pretreatment tumor oxygen measurements (Eppendorf Po
2 histograph) were available for 35 patients.
Results
: Both standard and pharmacokinetic-derived enhancement data correlated with tumor oxygenation measurements, and poorly enhancing tumors had low tumor oxygen levels. However, only the pharmacokinetic-analyzed data correlated with patient outcome and patients with poorly (amplitude less than median) vs. well-enhancing tumors had significantly worse disease-specific survival (
p = 0.024). For the 50 patients studied, no relationship was found between enhancement and volume data. Combining MRI volume and enhancement information highlighted large differences in outcome (
p = 0.0054). At the time of analysis, only 55% of patients with large, poorly enhanced tumors were alive compared with 92% of patients with small, well-enhanced tumors.
Conclusion
: These preliminary results suggest that pharmacokinetic modeling of dynamic contrast-enhanced MRI provides data that reflect tumor oxygenation and yields useful prognostic information in patients with locally advanced carcinoma of the cervix. Combining MRI-derived enhancement and volume data delineates large differences in radiotherapy outcome.
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