Deterring discrimination with data

Discrimination on grounds of race, sex, and handicap persists in many local school districts in spite of nearly twenty years of sustained attention from federal policymakers. Because litigation proceeds slowly and expensively, and because administrative attacks on discrimination have been stymied by political controversy, additional policy strategies merit careful consideration. We studied the operation of one such strategy in nine local districts: the mandatory collection of data concerning civil rights matters in schools. Data collection and reporting shaped local compliance with civil rights laws in four ways: by threatening local officials with future penalties, by providing political ammunition to constituencies that care about civil rights, by allowing local districts to learn about their own performance, and by framing school practices in ways that heighten awareness about equity. In this policy setting, data collection has advantages and disadvantages that complement those of other enforcement strategies. In this and other policy settings, data collection has power to elicit compliance even in the absence of conventional enforcement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45444/1/11077_2004_Article_BF00229728.pd

Consistency and Challenges in the Ocean Carbon Sink Estimate for the Global Carbon Budget

Based on the 2019 assessment of the Global Carbon Project, the ocean took up on average, 2.5 ± 0.6 PgC yr−1 or 23 ± 5% of the total anthropogenic CO2 emissions over the decade 2009–2018. This sink estimate is based on simulation results from global ocean biogeochemical models (GOBMs) and is compared to data-products based on observations of surface ocean pCO2 (partial pressure of CO2) accounting for the outgassing of river-derived CO2. Here we evaluate the GOBM simulations by comparing the simulated surface ocean pCO2 to observations. Based on this comparison, the simulations are well-suited for quantifying the global ocean carbon sink on the time-scale of the annual mean and its multi-decadal trend (RMSE <20 μatm), as well as on the time-scale of multi-year variability (RMSE <10 μatm), despite the large model-data mismatch on the seasonal time-scale (RMSE of 20–80 μatm). Biases in GOBMs have a small effect on the global mean ocean sink (0.05 PgC yr−1), but need to be addressed to improve the regional budgets and model-data comparison. Accounting for non-mapped areas in the data-products reduces their spread as measured by the standard deviation by a third. There is growing evidence and consistency among methods with regard to the patterns of the multi-year variability of the ocean carbon sink, with a global stagnation in the 1990s and an extra-tropical strengthening in the 2000s. GOBMs and data-products point consistently to a shift from a tropical CO2 source to a CO2 sink in recent years. On average, the GOBMs reveal less variations in the sink than the data-based products. Despite the reasonable simulation of surface ocean pCO2 by the GOBMs, there are discrepancies between the resulting sink estimate from GOBMs and data-products. These discrepancies are within the uncertainty of the river flux adjustment, increase over time, and largely stem from the Southern Ocean. Progress in our understanding of the global ocean carbon sink necessitates significant advancement in modeling and observing the Southern Ocean carbon sink including (i) a game-changing increase in high-quality pCO2 observations, and (ii) a critical re-evaluation of the regional river flux adjustment

Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naïve Mice

Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli—two VAP-associated pathogens—in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections

Exorcising Grice’s ghost : an empirical approach to studying intentional communication in animals

Language’s intentional nature has been highlighted as a crucial feature distinguishing it from other communication systems. Specifically, language is often thought to depend on highly structured intentional action and mutual mindreading by a communicator and recipient. Whilst similar abilities in animals can shed light on the evolution of intentionality, they remain challenging to detect unambiguously. We revisit animal intentional communication and suggest that progress in identifying analogous capacities has been complicated by (i) the assumption that intentional (that is, voluntary) production of communicative acts requires mental-state attribution, and (ii) variation in approaches investigating communication across sensory modalities. To move forward, we argue that a framework fusing research across modalities and species is required. We structure intentional communication into a series of requirements, each of which can be operationalised, investigated empirically, and must be met for purposive, intentionally communicative acts to be demonstrated. Our unified approach helps elucidate the distribution of animal intentional communication and subsequently serves to clarify what is meant by attributions of intentional communication in animals and humans

Providing the Missing Link: the Exposure Science Ontology ExO

Environmental health information resources lack exposure data required to translate molecular insights, elucidate environmental contributions to diseases, and assess human health and ecological risks. We report development of an Exposure Ontology, ExO, designed to address this information gap by facilitating centralization and integration of exposure data. Major concepts were defined and the ontology drafted and evaluated by a working group of exposure scientists and other ontology and database experts. The resulting major concepts forming the basis for the ontology are exposure stressor , exposure receptor , exposure event , and exposure outcome . Although design of the first version of ExO focused on human exposure to chemicals, we anticipate expansion by the scientific community to address exposures of human and ecological receptors to the full suite of environmental stressors. Like other widely used ontologies, ExO is intended to link exposure science and diverse environmental health disciplines including toxicology, epidemiology, disease surveillance, and epigenetics

The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters

Combinations of direct-acting antivirals are needed to minimize drug resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and testing of a number of drug regimens has led to conflicting results. Here, we show that cobicistat, which is an FDA-approved drug booster that blocks the activity of the drug-metabolizing proteins cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Two independent cell-to-cell membrane fusion assays showed that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low-micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. This was consistent with the effects of cobicistat on two of its known targets, CYP3A4 and P-gp, the silencing of which boosted the in vitro antiviral activity of remdesivir in a cobicistat-like manner. When administered in vivo to Syrian hamsters at a high dose, cobicistat decreased viral load and mitigated clinical progression. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management