Transit as an Alternative Mode of Transportation: A Case Study of Its Usage, Availability, Patterns and Value for Non-Commuter Trips

The mode of transportation a user picks impacts the environment, the social environment, and the user himself/herself. While research on alternative modes of transportation is prevalent in both the engineering and sociology fields, little attention has been given to the choices people make concerning how they run errands and other social trips, focusing instead on commuter trips. This case study examines three different shopping malls and the surrounding bus stops in order to determine the role distance plays in bus usage and the value that shopping centers place on access to local bus routes. Determination of the value and potential limitations of the current bus route design enables recommendations to be made in bus route and shopping center designs to maximize transit usage to shopping centers Recommendations aim to maximize flexibility and time on the part of the consumer, and ultimately increase visitors and sales in the shopping areas, which will ultimately boost the local economy

Teacher Strikes as Education: The West Virginia Teacher Strikes Framed by a Theory of Counter-Conduct, Performativity, and Aesthetics

The success of teacher strikes is often analyzed according to tangible outcomes, such as salary gains or the prevention of privatization bills. The point of this dissertation, however, is to argue that there are significant intangible outcomes as well. Using the West Virginia teacher strikes of 2018 and 2019 as a case study, I argue that the intangible outcomes of teacher strikes comprise a political-aesthetic education that expands the possibilities for how teachers can live within a neoliberal and patriarchal context. To do this, I develop a theoretical framework using three disparate yet nested concepts: counter-conduct, as used by Michel Foucault; performativity, as used by Judith Butler; and aesthetics, including everyday aesthetics, as used by Yuriko Saito, and somaesthetics, as used by Richard Shusterman. With this theoretical framework, I analyze the West Virginia teacher strikes as both political manifestations and aesthetic experiences. I collected data on the strikes through teachers’ written and spoken first-personal narratives, media interviews, academic books and articles, podcasts, videos, and images. Ultimately, I find that in their strikes, the West Virginia teachers performed counter-conduct against particular characteristics expected of them under neoliberalism and patriarchy. Even though not articulated or asserted, this counter-conduct could be aesthetically experienced through the sensuous and felt dimensions of the strikes. Teachers could feel, see, and hear the performance of alternative ways of being. This experience led to an expansion of possibilities for how teachers live as educators and as persons, even without dismantling the governmentalities of neoliberalism and patriarchy

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Postpartum Hepatic Infarction in Antiphospholipid Syndrome Patients

CASE: Our patient is a 31-year-old woman with a complicated past medical history of Systemic Lupus Erythematosus (SLE) and Antiphospholipid Ayndrome (APS). She originally presented several years ago when she was found to have Libman-Sacks endocarditis. She was diagnosed with SLE and APS at the time and was subsequently anticoagulated with warfarin. When she became pregnant, warfarin was discontinued and she was managed with a low molecular weight heparin (LMWH). She was continued on LMWH post-partum, but was noncompliant. For a few weeks following delivery, she presented to the hospital on several occasions with acute right upper quadrant pain. CT imaging confirmed several hepatic infarcts and she was treated with steroids, fondaparinux, and plaquenil. CONCLUSIONS: APS poses several risks during and after pregnancy due to susceptibility to venous and arterial thrombosis1. There is an increased risk of thrombosis up to 12 weeks postpartum. Continuation of anticoagulation following delivery is essential in APS women who have a high baseline risk of thrombosis2. Non-compliance with medications may have contributed to this presentation. This case is unique in that hepatic infarcts rarely occur due to the dual blood supply of the liver. Moreover, the diagnosis of hepatic infarction can be difficult as it may present similarly to HELLP, possibly contributing to her multiple admissions with RUQ pain3,4. CLINICAL SIGNIFICANCE: This case is significant because it demonstrates the rare, but life-threatening risk of postpartum hepatic infarction in APS patients. Proper postpartum management and compliance with anticoagulation medications are essential to mitigating risk. Furthermore, providers may face challenges in diagnosing hepatic infarction as it could mimic other diseases

153. AYA Subspecialty Patient and Parent Views on COVID-19 Vaccination

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Purpose: Adolescents/young adults (AYA) with hematologic and oncologic (heme-onc) conditions are important targets for vaccine outreach because they are at increased risk for complications from COVID-19. AYA patients may also need additional support, as they are transitioning from parent to independent vaccine decision-making. AYA with sickle cell disease (SCD) are of particular concern because a high proportion are African American and experience structural racism in addition to their illness. Our objective was to examine AYA and parent attitudes regarding the COVID-19 vaccine among heme-onc populations. Methods: As part of a larger IRB-approved study, we recruited vaccine decision-makers in pediatric SCD and oncology survivor clinics, including parents of adolescents under 18 years (n=35), AYA patients 18-21 years old (n=21), and parents of AYA patients 18-21 years old (n=14). After informed consent, participants completed a demographic survey and a semi-structured interview regarding their vaccine decision-making process. Example questions included “What do you see as the benefits of the COVID-19 vaccine?” and “What are your concerns about the COVID-19 vaccine?”. Saturation was reached. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. Codes were developed from the literature and early interviews. Examples included “attitudes against vaccine,” “medical mistrust,” “hesitancy,” “vaccine side effects,” and “vaccine interactions with disease process.” Fisher exact statistical tests were performed to analyze quantitative data. Results: In SCD clinic, we recruited 31 index patients (mean age: 15.1±3.5 years; 30 African American and 1 Other or Mixed), yielding 11 AYA and 26 parent interviews. In survivor clinic, we recruited 26 index patients (mean age: 16.0±3.4 years; 20 White, 2 Hispanic or Latinx; 2 Other or Mixed, 1 African American, and 1 Asian), yielding 10 AYA and 23 parent interviews. Out of the total index patients, 8 had already received the vaccine, 13 were planning to receive it, 27 were considering it, and 9 had declined it. There was no clear relationship between patients’ diagnosis (SCD or cancer) and their vaccine decisions nor between the index patient’s age (under or over 18) and their vaccine decisions. A high proportion of participants saw benefits to vaccination, such as lowering personal risk, community benefits of preventing the spread of COVID-19, and a possible return to “normal.” However, many AYA and parent participants also had concerns toward the vaccine, including concerns about short-term side effects and the potential for unknown, long-term effects. Concerns were also voiced about how rapidly the vaccine was developed and misconceptions about the vaccine were common, namely the vaccine causing infertility or increasing one’s susceptibility to contracting COVID-19. Medical mistrust toward either the vaccine or providers was explicitly stated by several participants, the majority of whom were from minoritized groups. Conclusions: COVID-19 vaccines have the potential to protect medically and socially vulnerable AYA, however patient and parent concerns, misconceptions, and mistrust are still prevalent. These data provide insights into the design and implementation of vaccine counseling interviews for AYA subspecialty patients and families

A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue.

Group-2 innate lymphoid cells (ILC2), type-2 cytokines, and eosinophils have all been implicated in sustaining adipose tissue homeostasis. However, the interplay between the stroma and adipose-resident immune cells is less well understood. We identify that white adipose tissue-resident multipotent stromal cells (WAT-MSCs) can act as a reservoir for IL-33, especially after cell stress, but also provide additional signals for sustaining ILC2. Indeed, we demonstrate that WAT-MSCs also support ICAM-1-mediated proliferation and activation of LFA-1-expressing ILC2s. Consequently, ILC2-derived IL-4 and IL-13 feed back to induce eotaxin secretion from WAT-MSCs, supporting eosinophil recruitment. Thus, MSCs provide a niche for multifaceted dialogue with ILC2 to sustain a type-2 immune environment in WAT

Searching for serial refreshing in working memory:Using response times to track the content of the focus of attention over time

One popular idea is that, to support maintenance of a set of elements over brief periods of time, the focus of attention rotates among the different elements thereby serially refreshing the content of Working Memory (WM). In the research reported here, probe letters were presented between to-be-remembered letters. Response times to these probes were used to infer the status of the different items in WM. If the focus of attention cycles from one item to the next, its content should be different at different points in time and this should be reflected in a change in the response time patterns over time. Across a set of four experiments, we demonstrate a striking pattern of invariance in the response time patterns over time, suggesting that either the content of the focus of attention did not change over time or that response times cannot be used to infer the content of the focus of attention. We discuss how this pattern constrains models of WM, attention, and human information processing

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19