The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Bismuth(V) mediated meta-arylation

Despite offering many options for functionalisation, unattractive synthetic routes have left 2,4-cyclohexadienones relatively unexplored. Reported methods to make these substrates are marred by poor regio- and chemoselectivity, toxic reagents, and inefficient processes. The work detailed in this thesis aims to remove barriers to implementation by presenting a synthetic method for their preparation that is selective and predictive, uses benign reagents, and offers excellent yields. To showcase their applicability in synthetic organic chemistry, they will be used as intermediates in the synthesis of meta-substituted phenols and anilines. A three-step process was developed to access the elusive meta-position of phenols and is described in Chapter 2. Here, a straightforward procedure was developed to access a 6,6-disubstituted 2,4-cyclohexadienone from a single, universal bismuth precursor and a phenol. Following the isolation and full characterisation of the 2,4-cyclohexadienone, a Lewis acid mediated 1,2-aryl migration was optimised to provide the meta-arylated phenol. An extensive substrate scope showed that this methodology is applicable to phenols and arylboronic acids bearing a range of electronic descriptors and is permitting of highly functionalised handles poised for subsequent diversification chemistry. In addition to this, the selectivity of the arylation step was assessed and found to be influenced more by electronics than sterics, occurring ipso to the most electron rich position. A comprehensive mechanistic study was undertaken on the 1,2-aryl migration step: passing through a phenonium ion intermediate. Using this chemistry to access meta-substituted phenols, analogues of mexiletine, lidocaine, and dimethachlor were synthesised in excellent yield to showcase how this chemistry can be applied to the targeted synthesis of important biologically active molecules. Chapter 3 builds on this work, developing a route to meta-arylated anilines. Using Bi(V) mediated synthesis of 2,4-cyclohexadienones developed in Chapter 2, a deoxyamination reaction step was implemented to deliver a 2,4-cyclohexadienimine. This was found to be competent in a similar 1,2-aryl migration step, yielding the meta-arylated aniline. This method not only describes a means to access these contra-electronic products, but also a formal phenol to aniline conversion – a highly sought-after transformation

Bismuth(V) mediated meta-arylation

Despite offering many options for functionalisation, unattractive synthetic routes have left 2,4-cyclohexadienones relatively unexplored. Reported methods to make these substrates are marred by poor regio- and chemoselectivity, toxic reagents, and inefficient processes. The work detailed in this thesis aims to remove barriers to implementation by presenting a synthetic method for their preparation that is selective and predictive, uses benign reagents, and offers excellent yields. To showcase their applicability in synthetic organic chemistry, they will be used as intermediates in the synthesis of meta-substituted phenols and anilines. A three-step process was developed to access the elusive meta-position of phenols and is described in Chapter 2. Here, a straightforward procedure was developed to access a 6,6-disubstituted 2,4-cyclohexadienone from a single, universal bismuth precursor and a phenol. Following the isolation and full characterisation of the 2,4-cyclohexadienone, a Lewis acid mediated 1,2-aryl migration was optimised to provide the meta-arylated phenol. An extensive substrate scope showed that this methodology is applicable to phenols and arylboronic acids bearing a range of electronic descriptors and is permitting of highly functionalised handles poised for subsequent diversification chemistry. In addition to this, the selectivity of the arylation step was assessed and found to be influenced more by electronics than sterics, occurring ipso to the most electron rich position. A comprehensive mechanistic study was undertaken on the 1,2-aryl migration step: passing through a phenonium ion intermediate. Using this chemistry to access meta-substituted phenols, analogues of mexiletine, lidocaine, and dimethachlor were synthesised in excellent yield to showcase how this chemistry can be applied to the targeted synthesis of important biologically active molecules. Chapter 3 builds on this work, developing a route to meta-arylated anilines. Using Bi(V) mediated synthesis of 2,4-cyclohexadienones developed in Chapter 2, a deoxyamination reaction step was implemented to deliver a 2,4-cyclohexadienimine. This was found to be competent in a similar 1,2-aryl migration step, yielding the meta-arylated aniline. This method not only describes a means to access these contra-electronic products, but also a formal phenol to aniline conversion – a highly sought-after transformation

International consensus statement on allergy and rhinology: Sinonasal tumors

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represents a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior ICAR documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICNST document consists of 4 major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represents a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior ICAR documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICNST document consists of 4 major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses

International consensus statement on allergy and rhinology: Sinonasal tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represents a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior ICAR documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICNST document consists of 4 major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses. This article is protected by copyright. All rights reserved

International consensus statement on allergy and rhinology: Sinonasal tumors

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represents a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. Methods: In accordance with prior ICAR documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. Results: The ICNST document consists of 4 major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses. This article is protected by copyright. All rights reserved

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding