Morbid and Mortal Inequities among Indigenous People in Canada and the United States during the COVID-19 Pandemic Critical Review of Relative Risks and Protections

The COVID-19 pandemic focused the world’s attention on gross racialized health inequities and injustices. For political and scientific reasons much less is known about the plight of Indigenous peoples than about other ethnic groups. In fact, some of the early pandemic evidence suggested that Indigenous peoples, while clearly experiencing prevalent structural violence probably also experience certain cultural protections. Aiming to begin to clarify their relative risks and protections, we conducted a rapid critical research review and sample-weighted synthesis or meta-analysis of the publishedand gray literature on four COVID-19-relevant outcomes in Canada and the United States between January 1, 2020 and August 1, 2021: vaccination, infection, severe infection, and death rates. Twenty-nine Indigenous-non-Indigenous comparative surveys or cohorts that observed 33, typically age-standardized, incidence or mortality rates or their proxies were included. Consistent with structural violence theory, we found that Indigenous peoples were significantly more likely to be infected, to experience severe COVID-19 illness, or to die as a result of their illness, Indigenous mortal risks (RR = 2.45) being significantly greater than Indigenous morbid risks (RR = 1.40). Consistent with cultural strengths theory, vaccinations seemed equitably distributed (RR = 1.02) with a suggestion of greater vaccine willingness among Indigenous peoples in some places. Clearly, much work remains to be done to decolonize Indigenous research and ultimately practices and policies in North America. Indigenous knowledge user-researcher teams and their allies have much to teach about cultural and ultimately, policy protections

Motor vehicle collision‑related injuries and deaths among Indigenous Peoples in Canada: Meta‑analysis of geo‑structural factors

Introduction: Indigenous Peoples are much more likely than non‑Indigenous Peoples to be seriously injured or die in motor vehicle collisions (MVCs). This study updates and extends a previous systematic review, suggesting that future re‑ search ought to incorporate social–environmental factors. Methods: We conducted a systematic review and meta‑analysis of the published and grey literature on MVCs involving Indigenous Peoples in Canada between 2010 and 2020. We focussed on personal (e.g. driving an old vehicle) and community social– environmental–economic factors (e.g. prevalent low socioeconomic status). Results: Eleven comparative cohorts that resulted in 23 at minimum, age‑standardised, mortality or morbidity rate outcomes were included in our meta‑analysis. Indigenous Peoples were twice as likely as non‑Indigenous Peoples to be seriously injured (rate ratio [RRpooled] = 2.18) and more than 3 times as likely to die (RRpooled = 3.40) in MVCs. Such great risks to Indigenous Peoples do not seem to have diminished over the past generation. Furthermore, such risks were greater on-reserves and in smaller, rural and remote, places. Conclusion: Such places may lack community resources, including fewer transportation and healthcare infrastructural investments, resulting in poorer road conditions in Indigenous communities and longer delays to trauma care. This seems to add further evidence of geo‑structural violence (geographical and institutional violence) perpetrated against Indigenous Peoples in yet more struc‑ tures (i.e. institutions) of Canadian society. Canada’s system of highways and road‑ ways and its remote health‑care system represent legitimate policy targets in aiming to solve this public health problem

Submillimeter Array Observation of the Proto-Planetary Nebula CRL 618 in the CO J=6-5 Line

We report on the results of a Submillimeter Array interferometric observation of the proto-planetary nebula CRL 618 in the 12CO J=6-5 line. With the new capability of SMA enabling us to use two receivers at a time, we also observed simultaneously in the 12CO J=2-1 and 13CO J=2-1 lines. The 12CO J=6-5 and 13CO J=2-1 lines were first interferometrically observed toward CRL 618. The flux of the high velocity component of the 12CO J=6-5 line is almost fully recovered, while roughly 80% of the flux of the low velocity component is resolved out. The low recovery rate suggests that the emission region of the low velocity component of the 12CO J=6-5 line is largely extended. Continuum emission is detected both at 230 and 690 GHz. The flux of the 690 GHz continuum emission seems to be partially resolved out, suggesting dust emission partly contaminates the 690 GHz continuum flux. The cavity structure, which has been confirmed in a previous observation in the 12CO J=2-1 line, is not clearly detected in the 12CO J=6-5 line, and only the south wall of the cavity is detected. This result suggests that the physical condition of the molecular envelope of CRL 618 is not exactly axial symmetric.Comment: 24 pages, 9 figures, 1 table, accepted for publication in AJ. Full resolution version available at http://www.asiaa.sinica.edu.tw/~junichi/paper

Really Trying or Merely Trying

We enjoy first-person authority with respect to a certain class of actions: for these actions, we know what we are doing just because we are doing it. This paper first formulates an epistemological principle that captures this authority in terms of trying to act in a way that one has the capacity to act. It then considers a case of effortful action – running a middle distance race – that threatens this principle. And proposes the solution of changing the metaphysics of action: one can keep hold of the idea that we have first-person authority over what we are doing by adopting a disjunctive account of action

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFb1 reduces production of proinflammatory cytokines, including TNFa, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. PAPERCLIP

A Review of the Tools Used for Marine Monitoring in the UK: Combining Historic and Contemporary Methods with Modeling and Socioeconomics to Fulfill Legislative Needs and Scientific Ambitions

Marine environmental monitoring is undertaken to provide evidence that environmental management targets are being met. Moreover, monitoring also provides context to marine science and over the last century has allowed development of a critical scientific understanding of the marine environment and the impacts that humans are having on it. The seas around the UK are currently monitored by targeted, impact-driven, programmes (e.g., fishery or pollution based monitoring) often using traditional techniques, many of which have not changed significantly since the early 1900s. The advent of a new wave of automated technology, in combination with changing political and economic circumstances, means that there is currently a strong drive to move toward a more refined, efficient, and effective way of monitoring. We describe the policy and scientific rationale for monitoring our seas, alongside a comprehensive description of the types of equipment and methodology currently used and the technologies that are likely to be used in the future. We contextualize the way new technologies and methodologies may impact monitoring and discuss how whole ecosystems models can give an integrated, comprehensive approach to impact assessment. Furthermore, we discuss how an understanding of the value of each data point is crucial to assess the true costs and benefits to society of a marine monitoring programme

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra®, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m²) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m²IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.</p> <p>Results</p> <p>54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed.</p> <p>Conclusion</p> <p>Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov: NCT00035867</p