“It’s the Procedure, Stupid!”: Amendment Procedures and Their Effects on Constitutional Stability

Constitutions must change. No human can stop time from marching forward, nor the social, economic, cultural, and technological developments associated. As a result, constitutions necessitate mechanisms that allow for their own progress. The amendment procedure of a constitution—the rules that govern what changes can occur—is therefore fundamental to any constitutional system. Importantly, scholars, politicians, and citizens alike fail to take into account the significance of these amendment processes and their effects on the constitutions they govern. While usually treated as a constitutional after-thought, amendment procedures have one of the most pronounced, substantive effects on the permanence of a constitutional order. Amendment procedures not only create the environment in which amendments are passed, but they also inform whether or not constitutional change occurs outside the formal amendment process—via things like judicial reinterpretation. As a result, amendment procedures have a relationship with the constitutional stability of a nation—the extent to which the constitution’s principles and institutions are followed. This thesis posits a procedure-based theory—that amendments are introduced and passed as a result of their amendment process, and when analyzing constitutional developments, it is first fundamental to analyze that nation’s amendment process. By placing procedure in the centre of the discussion, this thesis hopes to help politicians, scholars, and citizens alike better understand their constitutional systems. To address the threats modern democracies face, citizens must understand where these threats come from. Sometimes, the threat is not external or caused by a political actor, but it is instead the amendment procedure itself. When people fail to comprehend this reality, they blame the ills of their amendment procedure on democratic government. In turn, constitutional stability is undermined in the ways seen in America today. To ensure the permanence of democratic constitutional orders across the world, citizens must understand that sometimes, “it’s the procedure, stupid!

Accounting for Ecosystem Alteration Doubles Estimates of Conservation Risk in the Conterminous United States

Previous national and global conservation assessments have relied on habitat conversion data to quantify conservation risk. However, in addition to habitat conversion to crop production or urban uses, ecosystem alteration (e.g., from logging, conversion to plantations, biological invasion, or fire suppression) is a large source of conservation risk. We add data quantifying ecosystem alteration on unconverted lands to arrive at a more accurate depiction of conservation risk for the conterminous United States. We quantify ecosystem alteration using a recent national assessment based on remote sensing of current vegetation compared with modeled reference natural vegetation conditions. Highly altered (but not converted) ecosystems comprise 23% of the conterminous United States, such that the number of critically endangered ecoregions in the United States is 156% higher than when calculated using habitat conversion data alone. Increased attention to natural resource management will be essential to address widespread ecosystem alteration and reduce conservation risk

The views are not necessarily those of the Bank of England or the interim Financial Policy Committee.

Peter Zimmerman for comments and contributions. All speeches are available online at www.bankofengland.co.uk/publications/speeches2 1

An Updated Algorithm for the Generation of Neutral Landscapes by Spectral Synthesis

Background: Patterns that arise from an ecological process can be driven as much from the landscape over which the process is run as it is by some intrinsic properties of the process itself. The disentanglement of these effects is aided if it possible to run models of the process over artificial landscapes with controllable spatial properties. A number of different methods for the generation of so-called ‘neutral landscapes’ have been developed to provide just such a tool. Of these methods, a particular class that simulate fractional Brownian motion have shown particular promise. The existing methods of simulating fractional Brownian motion suffer from a number of problems however: they are often not easily generalisable to an arbitrary number of dimensions and produce outputs that can exhibit some undesirable artefacts. Methodology: We describe here an updated algorithm for the generation of neutral landscapes by fractional Brownian motion that do not display such undesirable properties. Using Monte Carlo simulation we assess the anisotropic properties of landscapes generated using the new algorithm described in this paper and compare it against a popular benchmark algorithm. Conclusion/Significance: The results show that the existing algorithm creates landscapes with values strongly correlated in the diagonal direction and that the new algorithm presented here corrects this artefact. A number of extensions of the algorithm described here are also highlighted: we describe how the algorithm can be employed to generate landscapes that display different properties in different dimensions and how they can be combined with an environmental gradient to produce landscapes that combine environmental variation at the local and macro scales

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Jaguar Densities across Human-Dominated Landscapes in Colombia: The Contribution of Unprotected Areas to Long Term Conservation

Large carnivores such as jaguars (Panthera onca) are species of conservation concern because they are suffering population declines and are keystone species in their ecosystems. Their large area requirements imply that unprotected and ever-increasing agricultural regions can be important habitats as they allow connectivity and dispersal among core protected areas. Yet information on jaguar densities across unprotected landscapes it is still scarce and crucially needed to assist management and range-wide conservation strategies. Our study provides the first jaguar density estimates of Colombia in agricultural regions which included cattle ranching, the main land use in the country, and oil palm cultivation, an increasing land use across the Neotropics. We used camera trapping across two agricultural landscapes located in the Magdalena River valley and in the Colombian llanos (47–53 stations respectively; >2000 trap nights at both sites) and classic and spatially explicit capture-recapture models with the sex of individuals as a covariate. Density estimates were 2.52±0.46–3.15±1.08 adults/100 km2 in the Magdalena valley, whereas 1.12±0.13–2.19±0.99 adults/100 km2 in the Colombian llanos, depending on analysis used. We suggest that jaguars are able to live across unprotected human-use areas and co-exist with agricultural landscapes including oil-palm plantations if natural areas and riparian habitats persist in the landscape and hunting of both jaguar and prey is limited. In the face of an expanding agriculture across the tropics we recommend land-use planning, adequate incentives, regulations, and good agricultural practices for range-wide jaguar connectivity and survival