Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data

Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress

International audience; High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics and metabolomics together with pharmacokinetics for drug testing regimes. Cultured human renal epithelial cells (RPTEC/TERT1) were exposed to the nephrotoxin Cyclosporine A (CsA) at therapeutic and supratherapeutic concentrations for 14 days. CsA was quantified in supernatants and cellular lysates by LC-MS/MS for kinetic modeling. There was a rapid cellular uptake and accumulation of CsA, with a non-linear relationship between intracellular and applied concentrations. CsA at 15 µM induced mitochondrial disturbances and activation of the Nrf2-oxidative-damage and the unfolded protein-response pathways. All three omic streams provided complementary information, especially pertaining to Nrf2 and ATF4 activation. No stress induction was detected with 5 µM CsA; however, both concentrations resulted in a maximal secretion of cyclophilin B. The study demonstrates for the first time that CsA-induced stress is not directly linked to its primary pharmacology. In addition we demonstrate the power of integrated omics for the elucidation of signaling cascades brought about by compound induced cell stress

The tyranny of the male preserve

Within this paper I draw on short vignettes and quotes taken from a two-year ethnographic study of boxing to think through the continuing academic merit of the notion of the male preserve. This is an important task due to evidence of shifts in social patterns of gender that have developed since the idea was first proposed in the 1970s. In aligning theoretical contributions from Lefebvre and Butler to discussions of the male preserve, we are able to add nuance to our understanding of how such social spaces are engrained with and produced by the lingering grasp of patriarchal narratives. In particular, by situating the male preserve within shifting social processes, whereby certain men’s power is increasingly undermined, I highlight the production of space within which narratives connecting men to violence, aggression and physical power can be consumed, performed and reified in a relatively unrestricted form. This specific case study contributes to gender theory as an illustration of a way in which we might explore and understand social enclaves where certain people are able to lay claim to space and power. As such, I argue that the notion of the male preserve is still a useful conceptual, theoretical and political device especially when considered as produced by the tyranny of gender power through the dramatic representation and reification of behaviours symbolically linked to patriarchal narrations of manhood

Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data

Indigenous Peoples and research: self-determination in research governance

Indigenous Peoples are reimagining their relationship with research and researchers through greater self-determination and involvement in research governance. The emerging discourse around Indigenous Data Sovereignty has provoked discussions about decolonizing data practices and highlighted the importance of Indigenous Data Governance to support Indigenous decision-making and control of data. Given that much data are generated from research, Indigenous research governance and Indigenous Data Governance overlap. In this paper, we broaden the concept of Indigenous Data Sovereignty by using the CARE Principles for Indigenous Data Governance to discuss how research legislation and policy adopted by Indigenous Peoples in the US set expectations around recognizing sovereign relationships, acknowledging rights and interests in data, and enabling Indigenous Peoples' participation in research governance

Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. RESULTS: Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F-mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F-mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. CONCLUSION: Dynamic eIF4F-mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The NANOGrav 15-Year Data Set: Detector Characterization and Noise Budget

Pulsar timing arrays (PTAs) are galactic-scale gravitational wave detectors. Each individual arm, composed of a millisecond pulsar, a radio telescope, and a kiloparsecs-long path, differs in its properties but, in aggregate, can be used to extract low-frequency gravitational wave (GW) signals. We present a noise and sensitivity analysis to accompany the NANOGrav 15-year data release and associated papers, along with an in-depth introduction to PTA noise models. As a first step in our analysis, we characterize each individual pulsar data set with three types of white noise parameters and two red noise parameters. These parameters, along with the timing model and, particularly, a piecewise-constant model for the time-variable dispersion measure, determine the sensitivity curve over the low-frequency GW band we are searching. We tabulate information for all of the pulsars in this data release and present some representative sensitivity curves. We then combine the individual pulsar sensitivities using a signal-to-noise-ratio statistic to calculate the global sensitivity of the PTA to a stochastic background of GWs, obtaining a minimum noise characteristic strain of $7\times 10^{-15}$ at 5 nHz. A power law-integrated analysis shows rough agreement with the amplitudes recovered in NANOGrav's 15-year GW background analysis. While our phenomenological noise model does not model all known physical effects explicitly, it provides an accurate characterization of the noise in the data while preserving sensitivity to multiple classes of GW signals.Comment: 67 pages, 73 figures, 3 tables; published in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]

The NANOGrav 15-year Data Set: Evidence for a Gravitational-Wave Background

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15-year pulsar-timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings-Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law-spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of $10^{14}$, and this same model is favored over an uncorrelated common power-law-spectrum model with Bayes factors of 200-1000, depending on spectral modeling choices. We have built a statistical background distribution for these latter Bayes factors using a method that removes inter-pulsar correlations from our data set, finding $p = 10^{-3}$ (approx. $3\sigma$) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of inter-pulsar correlations yields $p = 5 \times 10^{-5} - 1.9 \times 10^{-4}$ (approx. $3.5 - 4\sigma$). Assuming a fiducial $f^{-2/3}$ characteristic-strain spectrum, as appropriate for an ensemble of binary supermassive black-hole inspirals, the strain amplitude is $2.4^{+0.7}_{-0.6} \times 10^{-15}$ (median + 90% credible interval) at a reference frequency of 1/(1 yr). The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black-hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings-Downs correlations points to the gravitational-wave origin of this signal.Comment: 30 pages, 18 figures. Published in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication