Chapter 8- Making Asynchronous Online Discussions Meaningful: An Introduction to the Pioneer Method With Robust Scaffolding

The students in my graduate cohort were motivated. Most were teachers with years of experience. Some had won national awards. Several were experts on working with at-risk learners. These were people who knew how to learn. Yet we were all struggling with our online classes

Ocean Temperatures Do Not Account for a Record-Setting Winter in the U.S. West

The record-setting winter of 2022–2023 came as an answer to both figurative and literal prayers for political leaders, policy makers, and water managers reliant on snowpacks in the Upper Colorado River Basin, a vital source of water for tens of millions of people across the Western United States. But this “drought-busting” winter was not well-predicted, in part because while interannual patterns of tropical ocean temperatures have a well-known relationship to precipitation patterns across much of the American West, the Upper Colorado is part of a liminal region where these connections tend to be comparatively weak. Using historical sea surface temperature and snowpack records, and leveraging a long-term cross-basin relationship to extend the timeline for evaluation, this analysis demonstrates that the 2022–2023 winter did not present in accordance with other high-snowpack winters in this region, and that the associative pattern of surface temperatures in the tropical Pacific, and snow water equivalent in the regions that stored and supplied most of the water to the Colorado River during the 2022–2023 winter, was not substantially different from a historically incoherent arrangement of long-term correlation. These findings suggest that stochastic variability plays an outsized role in influencing water availability in this region, even in extreme years, reinforcing the importance of other trends to inform water policy and management

Chicago Recovery Partnership Evaluation of the American Recovery and Reinvestment Act

From 2009-2011, the City of Chicago and Cook County received a total of $2.35 billion in funding provided by the American Recovery and Reinvestment Act [ARRA]. The stimulus money was allocated to seven areas: education, basic needs, transportation and infrastructure, housing and energy, public safety, broadband and workforce development. The Chicago Recovery Partnership Evaluation of ARRA analyzes the impact of the stimulus spending using a costbenefit analysis framework. This report evaluated$1.09 billion of total spending in Chicago and Cook County, resulting in net benefits ranging from -$173.9 to$2,740.2 million. The wide range in net benefits is attributed largely to education, which received over half of ARRA funding

Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia

Objectives: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia. Design: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database. Settings: One-hundred twenty-two hospitals in the Veterans Affairs Health System. Patients: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated. Interventions: Time to appropriate antibiotic administration and 30-day mortality. Measurements and Main Results: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02–1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4–2.2%) for every hour that passes before antibiotics are administered. Conclusions: The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of \u3e5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.

Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex

The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7–14 Hz) and beta (15–29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant K25MH072941)National Institutes of Health (U.S.) (Grant K01AT003459)National Institutes of Health (U.S.) (Grant K24AT004095)National Institutes of Health (U.S.) (Grant RO1-NS045130-01)National Institutes of Health (U.S.) (Grant T32GM007484)National Science Foundation (U.S.) (Grant 0316933)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-1147470

Changes in Fire Weather Climatology Under 1.5 ◦C and 2.0 ◦C Warming

The 2015 Paris Agreement led to a number of studies that assessed the impact of the 1.5 ◦C and 2.0 ◦C increases in global temperature over preindustrial levels. However, those assessments have not actively investigated the impact of these levels of warming on fire weather. In view of a recent series of high-profile wildfire events worldwide, we access fire weather sensitivity based on a set of multi-model large ensemble climate simulations for these low-emission scenarios. The results indicate that the half degree difference between these two thresholds may lead to a significantly increased hazard of wildfire in certain parts of the world, particularly the Amazon, African savanna and Mediterranean. Although further experiments focused on human land use are needed to depict future fire activity, considering that rising temperatures are the most influential factor in augmenting the danger of fire weather, limiting global warming to 1.5 ◦C would alleviate some risk in these parts of the world

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p \u3c 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response

Open Problems in Extracellular RNA Data Analysis: Insights From an ERCC Online Workshop.

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19-20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop presentations and discussions are available (https://exRNA.org/exRNAdata2021-videos/). There were three target audiences: experimentalists who generate exRNA sequencing data, computational and data scientists who work with those groups to analyze their data, and experimental and data scientists new to the field. Here we summarize issues explored during the workshop, including progress on an effort to develop an exRNA data analysis challenge to engage the community in solving some of these open problems