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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Breen, RJ; Karlson, KB; Holm, A;

    Methods textbooks in sociology and other social sciences routinely recommend the use of the logit or probit model when an outcome variable is binary, an ordered logit or ordered probit when it is ordinal, and a multinomial logit when it has more than two categories. But these methodological guidelines take little or no account of a body of work that, over the past 30 years, has pointed to problematic aspects of these nonlinear probability models and, particularly, to difficulties in interpreting their parameters. In this review, we draw on that literature to explain the problems, show how they manifest themselves in research, discuss the strengths and weaknesses of alternatives that have been suggested, and point to lines of further analysis.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Oxford University Re...arrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Annual Review of Sociology
    Article . 2018
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Oxford University Re...arrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Annual Review of Sociology
      Article . 2018
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Almoudaris, A; Mamidanna, R; Bottle, A; Aylin, P; +3 Authors

    IMPORTANCE: Gastroesophageal cancer resections are associated with significant reintervention and perioperative mortality rates. OBJECTIVE: To compare outcomes following operative and nonoperative reinterventions between high- and low-mortality gastroesophageal cancer surgical units in England. DESIGN: All elective esophageal and gastric resections for cancer between 2000 and 2010 in English public hospitals were identified from a national administrative database. Units were divided into low- and high-mortality units (LMUs and HMUs, respectively) using a threshold of 5% or less for 30-day adjusted mortality. The groups were compared for reoperations and nonoperative reinterventions following complications. SETTING: Both LMUs and HMUs. PARTICIPANTS: Patients who underwent esophageal and gastric resections for cancer. EXPOSURE: Elective esophageal and gastric resections for cancer, with reoperations and nonoperative reinterventions following complications. MAIN OUTCOMES AND MEASURES: Failure to rescue is defined as the death of a patient following a complication; failure to rescue-surgical is defined as the death of a patient following reoperation for a surgical complication. RESULTS: There were 14 955 esophagectomies and 10 671 gastrectomies performed in 141 units. For gastroesophageal resections combined, adjusted mortality rates were 3.0% and 8.3% (P < .001) for LMUs and HMUs, respectively. Complications rates preceding reoperation were similar (5.4% for LMUs vs. 4.9% for HMUs; P = .11). The failure to rescue-surgical rates were lower in LMUs than in HMUs (15.3% vs. 24.1%; P < .001). The LMUs performed more nonoperative reinterventions than the HMUs did (6.7% vs. 4.7%; P < .001), with more patients surviving in LMUs than in HMUs (failure to rescue rate, 7.0% vs. 12.5%; P < .001). Overall, LMUs reintervened more than HMUs did (12.2% vs 9.6%; P < .001), and LMUs had lower failure to rescue rates following reintervention than HMUs did (9.0% vs. 18.3%; P = .001). All P values stated refer to 2-sided values. CONCLUSIONS AND RELEVANCE: Overall, LMUs were more likely to reintervene and rescue patients following gastroesophageal cancer resections in England. Patients were more likely to survive following both reoperations and nonsurgical interventions in LMUs.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ JAMA Surgery; Oxford...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    JAMA Surgery
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ JAMA Surgery; Oxford...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      JAMA Surgery
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Pamela J. Maxwell; Melanie McKechnie; Christopher W. Armstrong; Judith M. Manley; +10 Authors

    Abstract Inhibiting androgen signaling using androgen signaling inhibitors (ASI) remains the primary treatment for castrate-resistant prostate cancer. Acquired resistance to androgen receptor (AR)-targeted therapy represents a major impediment to durable clinical response. Understanding resistance mechanisms, including the role of AR expressed in other cell types within the tumor microenvironment, will extend the clinical benefit of AR-targeted therapy. Here, we show the ASI enzalutamide induces vascular catastrophe and promotes hypoxia and microenvironment adaptation. We characterize treatment-induced hypoxia, and subsequent induction of angiogenesis, as novel mechanisms of relapse to enzalutamide, highlighting the importance of two hypoxia-regulated cytokines in underpinning relapse. We confirmed AR expression in CD34+ vascular endothelium of biopsy tissue and human vascular endothelial cells (HVEC). Enzalutamide attenuated angiogenic tubule formation and induced cytotoxicity in HVECs in vitro, and rapidly induced sustained hypoxia in LNCaP xenografts. Subsequent reoxygenation, following prolonged enzalutamide treatment, was associated with increased tumor vessel density and accelerated tumor growth. Hypoxia increased AR expression and transcriptional activity in prostate cells in vitro. Coinhibition of IL8 and VEGF-A restored tumor response in the presence of enzalutamide, confirming the functional importance of their elevated expression in enzalutamide-resistant models. Moreover, coinhibition of IL8 and VEGF-A resulted in a durable, effective resolution of enzalutamide-sensitive prostate tumors. We conclude that concurrent inhibition of two hypoxia-induced factors, IL8 and VEGF-A, prolongs tumor sensitivity to enzalutamide in preclinical models and may delay the onset of enzalutamide resistance. Implications: Targeting hypoxia-induced signaling may extend the therapeutic benefit of enzalutamide, providing an improved treatment strategy for patients with resistant disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Queen's University R...arrow_drop_down
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Queen's University R...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Hyung-Seop Han; Sergio Loffredo; Indong Jun; James R. Edwards; +5 Authors

    Abstract During the last decade, translational research on biodegradable metallic materials has shown the feasibility of these novel materials for use in the fields of cardiology and orthopedics. Implants prepared with biodegradable metals are significantly stronger than their polymer counterparts, and there is now convincing evidence demonstrating that these materials fully biodegrade in vivo, thus reducing the need for secondary surgery. Clinical trials of such novel materials show significant potential, with the prospect of a paradigm shift in the way musculoskeletal and cardiovascular conditions are treated. This work provides an overview of the rapidly advancing technology of biodegradable metals, as well as defining some challenges in the application of these new biodegradable materials in the medical field.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Materials Today
    Article . 2019
    License: CC BY NC ND
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Materials Today
      Article . 2019
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Patrick Smallhorn-West; Patrick Smallhorn-West; Patrick Smallhorn-West; Edward Allison; +13 Authors

    Human rights matter for marine conservation because people and nature are inextricably linked. A thriving planet cannot be one that contains widespread human suffering or stifles human potential; and a thriving humanity cannot exist on a dying planet. While the field of marine conservation is increasingly considering human well-being, it retains a legacy in some places of protectionism, colonialism, and fortress conservation. Here, we i) provide an overview of human rights principles and how they relate to marine conservation, ii) document cases where tensions have occurred between marine conservation goals and human rights, iii) review the legal and ethical obligations, and practical benefits, for marine conservation to support human rights, and iv) provide practical guidance on integrating human rights principles into marine conservation. We argue that adopting a human rights-based approach to marine conservation, that is integrating equity as a rights-based condition rather than a charitable principle, will not only help meet legal and ethical obligations to respect, protect, and fulfil human rights, but will also result in greater and more enduring conservation impact.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Oxford University Research Archive
    Other literature type . 2023
    License: CC BY
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Marine Science
    Article . 2023
    License: CC BY
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    DOAJ
    Article . 2023
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Oxford University Research Archive
      Other literature type . 2023
      License: CC BY
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Marine Science
      Article . 2023
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      Article . 2023
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Kennedy, J; Quan, H; Ghali, W; Feasby, T;

    BACKGROUND: Carotid endarterectomy (CE), when performed on appropriate patients, reduces the incidence of stroke, yet there are marked variations in rates of this procedure. We sought to determine reasons for the variation in CE rates in 4 Canadian provinces. METHODS: We identified all CEs performed in 4 Canadian provinces between January 2000 and December 2001, inclusive. From chart review and expert assessment, we determined the proportion of these procedures that were appropriate, inappropriate or of uncertain appropriateness, using the RAND/UCLA Appropriateness Method. We sought to determine the variation in rates by province and whether the variation was due to differences in type of hospital, surgical specialty or surgical volume. RESULTS: Overall, 1656 (52.3%) of the 3167 CEs studied were performed for appropriate indications. The proportions of appropriate procedures were 78.2% (176/225) in Saskatchewan, 58.7% (481/819) in Alberta, 49.1% (350/713) in Manitoba and 46.0% (649/1410) in British Columbia (p < 0.001 across provinces). Rates of appropriate procedures per 100 000 population ranged from 44.3 in Manitoba to 16.2 in Saskatchewan (p < 0.001 across provinces). CEs were more likely to be appropriate when performed by a neurosurgeon compared with all other surgeons (74.4% v. 49.4% were appropriate; p < 0.001), when performed by surgeons doing fewer than 31 procedures over 2 years compared with surgeons doing more than 31 (70.1% v. 49.5% were appropriate; p < 0.001) and when performed in hospitals doing fewer than 135 procedures per year compared with hospitals doing more than 135 (63.4% v. 49.1% were appropriate; p < 0.001). Overall, 10.3% of procedures were done for inappropriate reasons. INTERPRETATION: Our findings suggest some overuse (for inappropriate or uncertain indications) but also some underuse (low population rates in some regions). High rates of CE are associated with lower rates of appropriateness for both surgeons and hospitals. That 1 in 10 CEs is done inappropriately suggests the need for preoperative assessment of appropriateness.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CMAJarrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CMAJarrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Authors: J. E. F. Green; Sarah L. Waters; Jonathan P. Whiteley; Leah Edelstein-Keshet; +2 Authors

    Liver cell aggregates may be grown in vitro by co-culturing hepatocytes with stellate cells. This method results in more rapid aggregation than hepatocyte-only culture, and appears to enhance cell viability and the expression of markers of liver-specific functions. We consider the early stages of aggregate formation, and develop a new mathematical model to investigate two alternative hypotheses (based on evidence in the experimental literature) for the role of stellate cells in promoting aggregate formation. Under Hypothesis 1, each population produces a chemical signal which affects the other, and enhanced aggregation is due to chemotaxis. Hypothesis 2 asserts that the interaction between the two cell types is by direct physical contact: the stellates extend long cellular processes which pull the hepatocytes into the aggregates. Under both hypotheses, hepatocytes are attracted to a chemical they themselves produce, and the cells can experience repulsive forces due to overcrowding. We formulate non-local (integro-partial differential) equations to describe the densities of cells, which are coupled to reaction-diffusion equations for the chemical concentrations. The behaviour of the model under each hypothesis is studied using a combination of linear stability analysis and numerical simulations. Our results show how the initial rate of aggregation depends upon the cell seeding ratio, and how the distribution of cells within aggregates depends on the relative strengths of attraction and repulsion between the cell types. Guided by our results, we suggest experiments which could be performed to distinguish between the two hypotheses. © 2010 Elsevier Ltd.

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    Journal of Theoretical Biology; Oxford University Research Archive
    Other literature type . Article . 2010 . 2016
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      Journal of Theoretical Biology; Oxford University Research Archive
      Other literature type . Article . 2010 . 2016
      License: Elsevier TDM
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    Authors: Munari, U.; Tomasella, L.; Fiorucci, M.; Bienayme, O.; +19 Authors

    We have used spectra of hot stars from the RAVE Survey in order to investigate the visibility and properties of five diffuse interstellar bands previously reported in the literature. The RAVE spectroscopic survey for Galactic structure and kinematics records CCD spectra covering the 8400-8800 Ang wavelength region at 7500 resolving power. The spectra are obtained with the UK Schmidt at the AAO, equipped with the 6dF multi-fiber positioner. The DIB at 8620.4 Ang is by far the strongest and cleanest of all DIBs occurring within the RAVE wavelength range, with no interference by underlying absorption stellar lines in hot stars. It correlates so tightly with reddening that it turns out to be a reliable tool to measure it, following the relation E(B-V) = 2.72 (+/- 0.03) x E.W.(Ang), valid throughout the general interstellar medium of our Galaxy. The presence of a DIB at 8648 Ang is confirmed. Its intensity appears unrelated to reddening, in agreement with scanty and preliminary reports available in the literature, and its measurability is strongly compromised by severe blending with underlying stellar HeI doublet at 8649 Ang. The two weak DIBS at 8531 and 8572 Ang do not appear real and should actually be blends of underlying stellar lines. The very weak DIB at 8439 Ang cannot be resolved within the profile of the much stronger underlying hydrogen Paschen 18 stellar line. Comment: Accepted in press by A&A

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    Astronomy and Astrophysics
    Article . 2008
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    https://doi.org/10.48550/arxiv...
    Article . 2008
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Astronomy and Astrophysics
      Article . 2008
      Data sources: NARCIS
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      https://doi.org/10.48550/arxiv...
      Article . 2008
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    Authors: Anthony Waldron; Daniel C. Miller; Dave Redding; Arne Ø. Mooers; +5 Authors

    Empirical two-part models describe the relationship between conservation spending, human development pressures and biodiversity loss and can inform sustainable development strategies by predicting the effects of financing decisions on future biodiversity losses. Financial investments into conservation are often held back by a lack of certainty over the benefits of spending more. Anthony Waldron and colleagues assess the impact of conservation spending on biodiversity between 1996 and 2008 in 109 countries that signed up to the Convention on Biological Diversity. They find that conservation spending over this period reduced national-level biodiversity loss by 29%, on average. They also find that the funding needed to achieve specific conservation goals rises with socioeconomic pressures. The authors develop a predictive model of biodiversity decline, which takes into account the effects of human development pressures and conservation financing. They propose that this could help to predict the funding that each country needs to achieve specific biodiversity policy goals, including those laid out in the Convention on Biological Diversity and the broader United Nations Sustainable Development Goals. Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals1,2, but success to date has been very limited3,4,5. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity6,7,8,9; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment6,7,8,9. For greater effectiveness, we need an evidence-based model10,11,12 that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008 We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures)13,14,15,16,17,18. Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

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    Nature
    Article
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nature
    Article . 2017
    License: Springer TDM
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    Nature
    Article . 2016
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      Nature
      Article . 2017
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    Authors: Kawamura, Akane; Münzel, Martin; Kojima, Tatsuya; Yapp, Clarence; +15 Authors

    The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs. JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—via in vitro selection from a vast library of cyclic peptides—that show selectivity over other KDMs.

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    Europe PubMed Central
    Article . 2017
    Data sources: PubMed Central
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      Europe PubMed Central
      Article . 2017
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Breen, RJ; Karlson, KB; Holm, A;

    Methods textbooks in sociology and other social sciences routinely recommend the use of the logit or probit model when an outcome variable is binary, an ordered logit or ordered probit when it is ordinal, and a multinomial logit when it has more than two categories. But these methodological guidelines take little or no account of a body of work that, over the past 30 years, has pointed to problematic aspects of these nonlinear probability models and, particularly, to difficulties in interpreting their parameters. In this review, we draw on that literature to explain the problems, show how they manifest themselves in research, discuss the strengths and weaknesses of alternatives that have been suggested, and point to lines of further analysis.

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    Annual Review of Sociology
    Article . 2018
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      Annual Review of Sociology
      Article . 2018
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    Authors: Almoudaris, A; Mamidanna, R; Bottle, A; Aylin, P; +3 Authors

    IMPORTANCE: Gastroesophageal cancer resections are associated with significant reintervention and perioperative mortality rates. OBJECTIVE: To compare outcomes following operative and nonoperative reinterventions between high- and low-mortality gastroesophageal cancer surgical units in England. DESIGN: All elective esophageal and gastric resections for cancer between 2000 and 2010 in English public hospitals were identified from a national administrative database. Units were divided into low- and high-mortality units (LMUs and HMUs, respectively) using a threshold of 5% or less for 30-day adjusted mortality. The groups were compared for reoperations and nonoperative reinterventions following complications. SETTING: Both LMUs and HMUs. PARTICIPANTS: Patients who underwent esophageal and gastric resections for cancer. EXPOSURE: Elective esophageal and gastric resections for cancer, with reoperations and nonoperative reinterventions following complications. MAIN OUTCOMES AND MEASURES: Failure to rescue is defined as the death of a patient following a complication; failure to rescue-surgical is defined as the death of a patient following reoperation for a surgical complication. RESULTS: There were 14 955 esophagectomies and 10 671 gastrectomies performed in 141 units. For gastroesophageal resections combined, adjusted mortality rates were 3.0% and 8.3% (P < .001) for LMUs and HMUs, respectively. Complications rates preceding reoperation were similar (5.4% for LMUs vs. 4.9% for HMUs; P = .11). The failure to rescue-surgical rates were lower in LMUs than in HMUs (15.3% vs. 24.1%; P < .001). The LMUs performed more nonoperative reinterventions than the HMUs did (6.7% vs. 4.7%; P < .001), with more patients surviving in LMUs than in HMUs (failure to rescue rate, 7.0% vs. 12.5%; P < .001). Overall, LMUs reintervened more than HMUs did (12.2% vs 9.6%; P < .001), and LMUs had lower failure to rescue rates following reintervention than HMUs did (9.0% vs. 18.3%; P = .001). All P values stated refer to 2-sided values. CONCLUSIONS AND RELEVANCE: Overall, LMUs were more likely to reintervene and rescue patients following gastroesophageal cancer resections in England. Patients were more likely to survive following both reoperations and nonsurgical interventions in LMUs.

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    JAMA Surgery
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      JAMA Surgery
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    Authors: Pamela J. Maxwell; Melanie McKechnie; Christopher W. Armstrong; Judith M. Manley; +10 Authors

    Abstract Inhibiting androgen signaling using androgen signaling inhibitors (ASI) remains the primary treatment for castrate-resistant prostate cancer. Acquired resistance to androgen receptor (AR)-targeted therapy represents a major impediment to durable clinical response. Understanding resistance mechanisms, including the role of AR expressed in other cell types within the tumor microenvironment, will extend the clinical benefit of AR-targeted therapy. Here, we show the ASI enzalutamide induces vascular catastrophe and promotes hypoxia and microenvironment adaptation. We characterize treatment-induced hypoxia, and subsequent induction of angiogenesis, as novel mechanisms of relapse to enzalutamide, highlighting the importance of two hypoxia-regulated cytokines in underpinning relapse. We confirmed AR expression in CD34+ vascular endothelium of biopsy tissue and human vascular endothelial cells (HVEC). Enzalutamide attenuated angiogenic tubule formation and induced cytotoxicity in HVECs in vitro, and rapidly induced sustained hypoxia in LNCaP xenografts. Subsequent reoxygenation, following prolonged enzalutamide treatment, was associated with increased tumor vessel density and accelerated tumor growth. Hypoxia increased AR expression and transcriptional activity in prostate cells in vitro. Coinhibition of IL8 and VEGF-A restored tumor response in the presence of enzalutamide, confirming the functional importance of their elevated expression in enzalutamide-resistant models. Moreover, coinhibition of IL8 and VEGF-A resulted in a durable, effective resolution of enzalutamide-sensitive prostate tumors. We conclude that concurrent inhibition of two hypoxia-induced factors, IL8 and VEGF-A, prolongs tumor sensitivity to enzalutamide in preclinical models and may delay the onset of enzalutamide resistance. Implications: Targeting hypoxia-induced signaling may extend the therapeutic benefit of enzalutamide, providing an improved treatment strategy for patients with resistant disease.

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    Authors: Hyung-Seop Han; Sergio Loffredo; Indong Jun; James R. Edwards; +5 Authors

    Abstract During the last decade, translational research on biodegradable metallic materials has shown the feasibility of these novel materials for use in the fields of cardiology and orthopedics. Implants prepared with biodegradable metals are significantly stronger than their polymer counterparts, and there is now convincing evidence demonstrating that these materials fully biodegrade in vivo, thus reducing the need for secondary surgery. Clinical trials of such novel materials show significant potential, with the prospect of a paradigm shift in the way musculoskeletal and cardiovascular conditions are treated. This work provides an overview of the rapidly advancing technology of biodegradable metals, as well as defining some challenges in the application of these new biodegradable materials in the medical field.

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    Materials Today
    Article . 2019
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      Materials Today
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    Authors: Patrick Smallhorn-West; Patrick Smallhorn-West; Patrick Smallhorn-West; Edward Allison; +13 Authors

    Human rights matter for marine conservation because people and nature are inextricably linked. A thriving planet cannot be one that contains widespread human suffering or stifles human potential; and a thriving humanity cannot exist on a dying planet. While the field of marine conservation is increasingly considering human well-being, it retains a legacy in some places of protectionism, colonialism, and fortress conservation. Here, we i) provide an overview of human rights principles and how they relate to marine conservation, ii) document cases where tensions have occurred between marine conservation goals and human rights, iii) review the legal and ethical obligations, and practical benefits, for marine conservation to support human rights, and iv) provide practical guidance on integrating human rights principles into marine conservation. We argue that adopting a human rights-based approach to marine conservation, that is integrating equity as a rights-based condition rather than a charitable principle, will not only help meet legal and ethical obligations to respect, protect, and fulfil human rights, but will also result in greater and more enduring conservation impact.

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    Oxford University Research Archive
    Other literature type . 2023
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    Frontiers in Marine Science
    Article . 2023
    License: CC BY
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    Article . 2023
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    Authors: Kennedy, J; Quan, H; Ghali, W; Feasby, T;

    BACKGROUND: Carotid endarterectomy (CE), when performed on appropriate patients, reduces the incidence of stroke, yet there are marked variations in rates of this procedure. We sought to determine reasons for the variation in CE rates in 4 Canadian provinces. METHODS: We identified all CEs performed in 4 Canadian provinces between January 2000 and December 2001, inclusive. From chart review and expert assessment, we determined the proportion of these procedures that were appropriate, inappropriate or of uncertain appropriateness, using the RAND/UCLA Appropriateness Method. We sought to determine the variation in rates by province and whether the variation was due to differences in type of hospital, surgical specialty or surgical volume. RESULTS: Overall, 1656 (52.3%) of the 3167 CEs studied were performed for appropriate indications. The proportions of appropriate procedures were 78.2% (176/225) in Saskatchewan, 58.7% (481/819) in Alberta, 49.1% (350/713) in Manitoba and 46.0% (649/1410) in British Columbia (p < 0.001 across provinces). Rates of appropriate procedures per 100 000 population ranged from 44.3 in Manitoba to 16.2 in Saskatchewan (p < 0.001 across provinces). CEs were more likely to be appropriate when performed by a neurosurgeon compared with all other surgeons (74.4% v. 49.4% were appropriate; p < 0.001), when performed by surgeons doing fewer than 31 procedures over 2 years compared with surgeons doing more than 31 (70.1% v. 49.5% were appropriate; p < 0.001) and when performed in hospitals doing fewer than 135 procedures per year compared with hospitals doing more than 135 (63.4% v. 49.1% were appropriate; p < 0.001). Overall, 10.3% of procedures were done for inappropriate reasons. INTERPRETATION: Our findings suggest some overuse (for inappropriate or uncertain indications) but also some underuse (low population rates in some regions). High rates of CE are associated with lower rates of appropriateness for both surgeons and hospitals. That 1 in 10 CEs is done inappropriately suggests the need for preoperative assessment of appropriateness.

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    Authors: J. E. F. Green; Sarah L. Waters; Jonathan P. Whiteley; Leah Edelstein-Keshet; +2 Authors

    Liver cell aggregates may be grown in vitro by co-culturing hepatocytes with stellate cells. This method results in more rapid aggregation than hepatocyte-only culture, and appears to enhance cell viability and the expression of markers of liver-specific functions. We consider the early stages of aggregate formation, and develop a new mathematical model to investigate two alternative hypotheses (based on evidence in the experimental literature) for the role of stellate cells in promoting aggregate formation. Under Hypothesis 1, each population produces a chemical signal which affects the other, and enhanced aggregation is due to chemotaxis. Hypothesis 2 asserts that the interaction between the two cell types is by direct physical contact: the stellates extend long cellular processes which pull the hepatocytes into the aggregates. Under both hypotheses, hepatocytes are attracted to a chemical they themselves produce, and the cells can experience repulsive forces due to overcrowding. We formulate non-local (integro-partial differential) equations to describe the densities of cells, which are coupled to reaction-diffusion equations for the chemical concentrations. The behaviour of the model under each hypothesis is studied using a combination of linear stability analysis and numerical simulations. Our results show how the initial rate of aggregation depends upon the cell seeding ratio, and how the distribution of cells within aggregates depends on the relative strengths of attraction and repulsion between the cell types. Guided by our results, we suggest experiments which could be performed to distinguish between the two hypotheses. © 2010 Elsevier Ltd.

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    Journal of Theoretical Biology; Oxford University Research Archive
    Other literature type . Article . 2010 . 2016
    License: Elsevier TDM
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      Journal of Theoretical Biology; Oxford University Research Archive
      Other literature type . Article . 2010 . 2016
      License: Elsevier TDM
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    Authors: Munari, U.; Tomasella, L.; Fiorucci, M.; Bienayme, O.; +19 Authors

    We have used spectra of hot stars from the RAVE Survey in order to investigate the visibility and properties of five diffuse interstellar bands previously reported in the literature. The RAVE spectroscopic survey for Galactic structure and kinematics records CCD spectra covering the 8400-8800 Ang wavelength region at 7500 resolving power. The spectra are obtained with the UK Schmidt at the AAO, equipped with the 6dF multi-fiber positioner. The DIB at 8620.4 Ang is by far the strongest and cleanest of all DIBs occurring within the RAVE wavelength range, with no interference by underlying absorption stellar lines in hot stars. It correlates so tightly with reddening that it turns out to be a reliable tool to measure it, following the relation E(B-V) = 2.72 (+/- 0.03) x E.W.(Ang), valid throughout the general interstellar medium of our Galaxy. The presence of a DIB at 8648 Ang is confirmed. Its intensity appears unrelated to reddening, in agreement with scanty and preliminary reports available in the literature, and its measurability is strongly compromised by severe blending with underlying stellar HeI doublet at 8649 Ang. The two weak DIBS at 8531 and 8572 Ang do not appear real and should actually be blends of underlying stellar lines. The very weak DIB at 8439 Ang cannot be resolved within the profile of the much stronger underlying hydrogen Paschen 18 stellar line. Comment: Accepted in press by A&A

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    Astronomy and Astrophysics
    Article . 2008
    Data sources: NARCIS
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    https://doi.org/10.48550/arxiv...
    Article . 2008
    License: arXiv Non-Exclusive Distribution
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      Astronomy and Astrophysics
      Article . 2008
      Data sources: NARCIS
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      https://doi.org/10.48550/arxiv...
      Article . 2008
      License: arXiv Non-Exclusive Distribution
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    Authors: Anthony Waldron; Daniel C. Miller; Dave Redding; Arne Ø. Mooers; +5 Authors

    Empirical two-part models describe the relationship between conservation spending, human development pressures and biodiversity loss and can inform sustainable development strategies by predicting the effects of financing decisions on future biodiversity losses. Financial investments into conservation are often held back by a lack of certainty over the benefits of spending more. Anthony Waldron and colleagues assess the impact of conservation spending on biodiversity between 1996 and 2008 in 109 countries that signed up to the Convention on Biological Diversity. They find that conservation spending over this period reduced national-level biodiversity loss by 29%, on average. They also find that the funding needed to achieve specific conservation goals rises with socioeconomic pressures. The authors develop a predictive model of biodiversity decline, which takes into account the effects of human development pressures and conservation financing. They propose that this could help to predict the funding that each country needs to achieve specific biodiversity policy goals, including those laid out in the Convention on Biological Diversity and the broader United Nations Sustainable Development Goals. Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals1,2, but success to date has been very limited3,4,5. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity6,7,8,9; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment6,7,8,9. For greater effectiveness, we need an evidence-based model10,11,12 that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008 We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures)13,14,15,16,17,18. Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

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    Nature
    Article
    Data sources: UnpayWall
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nature
    Article . 2017
    License: Springer TDM
    Data sources: Crossref
    Nature
    Article . 2016
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      Nature
      Article . 2017
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      Article . 2016
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    Authors: Kawamura, Akane; Münzel, Martin; Kojima, Tatsuya; Yapp, Clarence; +15 Authors

    The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs. JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—via in vitro selection from a vast library of cyclic peptides—that show selectivity over other KDMs.

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    Europe PubMed Central
    Article . 2017
    Data sources: PubMed Central
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      Europe PubMed Central
      Article . 2017
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