Judicial Interpretation and Nullum Crimen Sine Lege at the International Criminal Court: An Exercise in Utilizing 'Other Inhumane Acts' under Crimes Against Humanity

This PhD aims to explore how the International Criminal Court (ICC) can inject elements of judicial creativity when expansively interpreting the contents of the crimes under which it has jurisdiction without violating the principle of legality (more specifically nullum crimen sine lege). This has been of key interest to the scholarly community, especially in regard to the development of international criminal law. While prior international criminal tribunals have contributed a great deal to the expansion of the body of international criminal law, they were crafted with this specific task in mind. Their statutes and accompanying crimes were broad, encouraging them to creatively interpret their contents. This coupled with lack of reference to the principle of nullum crimen sine lege permitted them to adopt a generic definition of it which, in turn, enabled them to more easily define or include new crimes within their jurisdiction. The Rome Statute which binds the ICC, on the other hand, is a much more specific document, devised to reflect the stricter standards for interpretation that is often seen in civil law legal systems. It includes a detailed set of definitions of crimes, as well as explicit reference to the principle of nullum crimen sine lege. This indicates that the ICC will not be able to expansively interpret the Rome Statute in the same way as was done at other international criminal tribunals. The dichotomy between the ICC and other international criminal tribunals becomes clearer when considering the inclusion of 'other inhumane acts' under crimes against humanity. This residual clause was constructed with the intent to provide a means for adapting the Rome Statute for the inclusion of novel criminal acts. However, due to the fact that these acts have not been formally codified within the Rome Statute itself, the provision runs risk of violating the principle of nullum crimen sine lege (without established law an individual cannot be held criminally accountable for their acts). The objective of this research was then to identify how the ICC can creatively interpret its statute to include novel criminal acts under 'other inhumane acts' without violating the principle of nullum crimen sine lege. This PhD implements a novel method for judicial interpretation at the ICC by combining the concept of 'judicial creativity' as detailed by Shane Darcy with statutory restrictions placed within the Rome Statute and a contemporary understanding of nullum crimen sine lege. This is then applied to a number of acts which have not been codified within the Rome Statute, namely: forced marriage, 'ethnic cleansing' and terrorist acts, to identify how the principle impacts the ICC's ability to exert judicial discretion. This PhD finds that indeed, the court can actively utilize 'other inhumane acts' under crimes against humanity to include novel abhorrent acts without violating the principle of nullum crimen sine lege. The principle itself, when applied through the above methodology, acts as a sifting agent, syphoning out acts which are incompatible with the Statute and promoting judicial consistency. In doing so, it also aids in highlighting the key tenets of the acts being examined and forces the unique aspects of them to the forefront. As such, the principle serves a threefold purpose; it protects the accused from arbitrary application of the law, it aids in better representing victims through highlighting the unique aspects of the act committed and it provides others with a deeper understanding of the act being examined

Toward the Construction Knowledge Economy: The E-Cognos Project

The paper focuses upon the contribution that knowledge management portals can make to the enhancement, development and improvement of professional expertise in the Construction domain. The paper is based on the e-COGNOS project1 which aims at specifying and developing an open model-based infrastructure and a set of tools that promote consistent knowledge management within collaborative construction environments. The specified solution emerged from a comprehensive analysis of the business and information / knowledge management practices of the project end-users. The system architect uses a Construction specific ontology as a basis for specifying adaptive mechanisms that can organise documents according to their contents and interdependencies, while maintaining their overall consistency. e-COGNOS has a web-based infrastructure will include services allowing to create, capture, index, retrieve and disseminate knowledge. It also promotes the integration of third-party services, including proprietary tools. The e-COGNOS approach will be tested and evaluated through a series of field trials. This will be followed by the delivery of business recommendations regarding the deployment of e-COGNOS in the construction sector. The research is ongoing and supported by the European Commission under the IST programme – Key Action I

Past, present and future of information and knowledge sharing in the construction industry: Towards semantic service-based e-construction

The paper reviews product data technology initiatives in the construction sector and provides a synthesis of related ICT industry needs. A comparison between (a) the data centric characteristics of Product Data Technology (PDT) and (b) ontology with a focus on semantics, is given, highlighting the pros and cons of each approach. The paper advocates the migration from data-centric application integration to ontology-based business process support, and proposes inter-enterprise collaboration architectures and frameworks based on semantic services, underpinned by ontology-based knowledge structures. The paper discusses the main reasons behind the low industry take up of product data technology, and proposes a preliminary roadmap for the wide industry diffusion of the proposed approach. In this respect, the paper stresses the value of adopting alliance-based modes of operation

Finding the trigger to Iapetus' odd global albedo pattern: Dynamics of dust from Saturn's irregular satellites

The leading face of Saturn's moon Iapetus, Cassini Regio, has an albedo only one tenth that on its trailing side. The origin of this enigmatic dichotomy has been debated for over forty years, but with new data, a clearer picture is emerging. Motivated by Cassini radar and imaging observations, we investigate Soter's model of dark exogenous dust striking an originally brighter Iapetus by modeling the dynamics of the dark dust from the ring of the exterior retrograde satellite Phoebe under the relevant perturbations. In particular, we study the particles' probabilities of striking Iapetus, as well as their expected spatial distribution on the Iapetian surface. We find that, of the long-lived particles (greater than about 5 microns), most particle sizes (greater than about 10 microns) are virtually certain to strike Iapetus, and their calculated distribution on the surface matches up well with Cassini Regio's extent in its longitudinal span. The satellite's polar regions are observed to be bright, presumably because ice is deposited there. Thus, in the latitudinal direction we estimate polar dust deposition rates to help constrain models of thermal migration invoked to explain the bright poles (Spencer & Denk 2010). We also analyze dust originating from other irregular outer moons, determining that a significant fraction of that material will eventually coat Iapetus--perhaps explaining why the spectrum of Iapetus' dark material differs somewhat from that of Phoebe. Finally we track the dust particles that do not strike Iapetus, and find that most land on Titan, with a smaller fraction hitting Hyperion. As has been previously conjectured, such exogenous dust, coupled with Hyperion's chaotic rotation, could produce Hyperion's roughly isotropic, moderate-albedo surface.Comment: Accepted for publication in Icaru

Endocrine Disruptor Regulation of MicroRNA Expression in Breast Carcinoma Cells

Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe