Geochemical fingerprints of seawater in the Late Mesoproterozoic Midcontinent Rift, North America : life at the marine-land divide

The 1.1 Ga Midcontinent Rift (MCR) is a thick volcanic-sedimentary succession that forms a curvilinear belt through central North America and crops out along its northern apex around Lake Superior. Sedimentary units of the MCR have been long interpreted as fluvial-lacustrine and invited a number of studies on the early evolution of life in non-marine habitats. One of the key units is the siliciclastic Nonesuch Formation, thought to record deposition in a large lake. However, recent sedimentological observations indicate the presence of marine incursions. To further test this interpretation, we analysed trace element abundances in a broad suite of samples from multiple drill cores through the Nonesuch Formation. We aimed to differentiate geochemical influences of sediment provenance from post-depositional hydrothermal overprint and thereby identify authigenic enrichments in fluid-mobile elements that are indicators of primary environmental conditions. Our results reveal discrete enrichments in Mo and U in organic- and sulphide-rich horizons, which are most parsimoniously interpreted as marine signatures. This conclusion is supported by Sr/Ba ratios, which suggest mixing between freshwater and saltwater, and by rare cm-thick gypsum in the upper Copper Harbor Formation immediately below the Nonesuch rocks. The gypsum displays δ34S values of +25.9 ± 0.6‰, consistent with input of marine sulphate at least during parts of the basin's history. Collectively, our geochemical data support the sedimentological interpretation that this portion of the MCR archives a marine-influenced estuarine system. Although this conclusion rules out that microbial life documented from the MCR was living in exclusively freshwater habitats, the Nonesuch Fm and associated rocks still hold important clues about organisms that were capable of withstanding salinity gradients and bridging the gap between the marine and non-marine environments of the mid-Proterozoic.PostprintPeer reviewe

Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/

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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Promoting Healthy Marriages in the Jewish and Catholic Traditions

In this program, Rabbi Morris J. Allen and Fr. Timothy Cloutier will share resources from their religious traditions that inform their understanding of what promotes healthy marriages and they will discuss what local congregations might do to promote such marriages. Rabbi Morris J. Allen is the spiritual leader of Beth Jacob Congregation in Mendota Heights. The Jewish Daily Forward identified him as one of the most influential leaders in the American Jewish Community in 2008 for his work in the area of ethical certification of kosher food. He has served as a member of the Rabbinical Assembly’s Commission on Human Sexuality. Fr. Timothy Cloutier has been a priest of the Archdiocese of St. Paul and Minneapolis since 1999 and is currently the juridical vicar of the Metropolitan Tribunal. He has served as the pastor of St. Mary in Waverly, St. Raphael in Crystal, and Immaculate Heart of Mary in Minnetonka. Prior to 1999, he spent sixteen years with a religious community in Europe. This program was initiated by UST student Elliot Polsky as a result of his summer research on the topic of healthy marriages. It is sponsored by the Jay Phillips Center for Interfaith Learning in collaboration with Marriage Club, Philosophy Club, Theology Club , and Students for Human Life. To make an accessibility request, call Disability Resources at (651) 962-631

Prioritization Planning for Culvert Replacement

Culvert failure has been an increasing concern in Massachusetts municipalities due to increased rainfall and aging structures. The goal of our project was to develop a prioritization plan to help Massachusetts municipalities prioritize culvert repair and replacement. Using the town of Sutton, MA as a case study, we conducted background research, interviews, and field assessments and developed a prioritization plan, GIS map, and outreach material. The prioritization plan includes criteria to assist towns to prioritize culverts for repair or replacement

Supplementary Figure S5

Supplementary Figure S5 Summary measures of aligned sequence data for each marker type (CNEEs, introns, UCEs), showing the total aligned sequence length per locus (a-c), variable alignment columns as a percent of the total alignment length (d-f), and the percent of parsimony informative alignment columns per locus (g-i)

Supplementary Figure S3

Supplementary Figure S3 Heatmap of the number of replicates from phylogenomic subsampling that support each alternative hypothesis for the sister group to emu + cassowary at a minimum bootstrap support of 70% (a-i) and 90% (j-r), with results from each analysis method displayed in separate panels (e.g. MP-EST a-c & j-l, ASTRAL d-f & m-o, ExaML g-I & p-r). Rows labelled H1-H4 within each panel correspond to the four alternative hypotheses outlined in the legend. Columns within each panel labelled 50-3000 indicate the number of loci subsampled at random with replacement from all loci for each marker type. Coloring of cells indicates the number of replicates (of 10 in total for each data set size category) that support each hypothesis at the given bootstrap cut off, corresponding to the colouring scheme outlined in the legend