The criminal legal system in the USA drives an incarceration rate that is the highest on the planet, with disparities by class and race among its signature features
. During the first year of the ...coronavirus disease 2019 (COVID-19) pandemic, the number of incarcerated people in the USA decreased by at least 17%-the largest, fastest reduction in prison population in American history
. Here we ask how this reduction influenced the racial composition of US prisons and consider possible mechanisms for these dynamics. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from the decrease in the US prison population and that the fraction of incarcerated Black and Latino people sharply increased. This pattern of increased racial disparity exists across prison systems in nearly every state and reverses a decade-long trend before 2020 and the onset of COVID-19, when the proportion of incarcerated white people was increasing amid declining numbers of incarcerated Black people
. Although a variety of factors underlie these trends, we find that racial inequities in average sentence length are a major contributor. Ultimately, this study reveals how disruptions caused by COVID-19 exacerbated racial inequalities in the criminal legal system, and highlights key forces that sustain mass incarceration. To advance opportunities for data-driven social science, we publicly released the data associated with this study at Zenodo
.
Background: Current guidelines advocate for antiretroviral therapy (ART) simplification in patients on complicated regimens. Simplifying ART improves patient adherence and quality of life, but ...changes in drug interactions (DIs) are uncertain. Objective: This study assessed changes in DIs following ART simplification in patients with HIV. Methods: This was an observational, retrospective cohort study of patients attending an urban HIV clinic. Patients were included if they had ART simplification (a decreased number of daily tablets) and ≥1 concomitant medication (CM). Total DI scores were generated for each patient pre–ART simplification and post–ART simplification using an online DI database. Each ART-CM pair labeled as “do not co-administer” was given a score of 2, “potential interaction” a score of 1, or “no interaction” a score of 0. Differences in total DI scores following simplification were analyzed with a Wilcoxon Signed-Rank test. Predictors of DI score reductions were examined with linear regression. Results: A total of 99 patients were included. Their median age was 54 years, and 79% were male. The median durations of HIV infection and ART were 16 and 10 years, respectively. Patients were receiving an average of 4.5 CMs. Median interaction scores presimplification and postsimplification were 3 (interquartile range IQR, 1-6) and 1 (IQR, 0-2) respectively (P < 0.001). Predictors of score reductions were the patient’s number of CMs, discontinuing a protease inhibitor, and switching to a dolutegravir-based regimen. Conclusion and Relevance: ART simplification decreased the incidence of DIs in this analysis of patients with advanced age who had ART experience and polypharmacy.
Leptospirosis affects numerous animal species, including domestic dogs, but documented transmission to humans is rare. Here, we describe epidemiologically linked cases in a 12-year-old Minnesota boy ...and his pet dog. While human leptospirosis is often thought of as a disease of tropical locations, this case report describes a rare documented example of local transmission in the northern United States, a region historically not perceived to be at high risk of Leptospira species transmission to humans. This case highlights an unusual presentation, with facial nerve palsy, underappreciated epidemiological risks, and diagnostic challenges of this reemerging infection.
AbstractThe objective of this paper is to provide details of the design and response of a full-scale cold-formed steel (CFS)-framed building that was tested under a series of dynamic excitations ...during different phases of construction. The seismic response of complete buildings framed from CFS is essentially unexplored, although significant work on the behavior of CFS members and subsystems, particularly shear walls has been conducted. The experiments described herein are the first tests of a CFS-framed building designed to North American seismic standards. Seismic testing was conducted using the twin shake tables at the University at Buffalo through the U.S. National Science Foundation Network for Earthquake Engineering Simulation program. The project was conducted in two phases. In the first phase, the building specimen was constructed and tested with only the structural components in place: CFS shear walls sheathed with oriented strand board (OSB), CFS gravity walls (unsheathed), and CFS-framed floor and roof diaphragms sheathed with OSB. Nondestructive testing and design basis earthquake-level testing were performed in this phase. In the second phase, a second building specimen was constructed, to identical specifications as in the first phase. However, the second building specimen was finished with nonstructural components including exterior sheathing of the perimeter gravity walls, gypsum-board sheathing of the interior of the perimeter gravity and shear walls, interior partition walls, ceilings, staircases, and exterior weatherproofing. Nondestructive testing was conducted at construction milestones, and the finished second-phase specimen was destructively tested at the maximum considered earthquake level. This paper presents the fundamental system-level response of these building specimens: period, percent damping, drift, and accelerations. The companion paper details component-level response. Overall, the work demonstrates the excellent performance of these structures under seismic excitation, while highlighting that this performance is related to the full system-level response and not just the designated elements in the lateral-force-resisting system.
BACKGROUND:A modified version of the International Knee Documentation Committee (IKDC), the Pedi-IKDC, is a validated patient-reported outcome measure in pediatric patients with knee pain. However, ...this questionnaire is lengthy and can fatigue patients, leading to inconsistent outcome collection. Thus, we sought to compare more easily attainable Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing patient reported outcomes to the gold standard Pedi-IKDC.
METHODS:We prospectively collected PROMIS scores and Pedi-IKDC scores in 100 new, consecutive patients presenting with knee pain to a pediatric sports medicine practice. Patients were excluded if they provided an incomplete Pedi-IKDC, had prior ipsilateral lower extremity surgery, or significant associated medical comorbidities. PROMIS domains including Mobility, Pain Interference, and Upper Extremity (control) were compared with the Pedi-IKDC with Pearson correlations. The number of questions in each metric was analyzed. Floor and ceiling effects of each test were also assessed.
RESULTS:The average age of the study cohort was 14 years (range, 7 to 18 y) with 53% female and 47% male. 70% of patients completed the Pedi-IKDC questionnaire, compared with 100% with PROMIS tests. The average Pedi-IKDC score was 48.8±22.3 (range, 5.4 to 100). Mean scores for Mobility, Pain Interference, and Upper Extremity domains were 38.4±10.1, 53.5±10.3, and 49.7±8.7, respectively. All tests demonstrated similar and acceptable floor and ceiling effects (<15%). The length of the Pedi-IKDC (22 questions) was roughly double that of combined PROMIS Pain Interference and Mobility tests (11.9±2.3 questions). Pedi-IKDC scores correlated with tested PROMIS measures (Mobility/Pain Interference, r=0.42/−0.49). When 7 highly functional patients with significant pain symptoms were removed for a secondary analysis, Mobility and Pain correlations improved to 0.69 and −0.67, respectively.
CONCLUSIONS:PROMIS Mobility and Pain scores demonstrate moderate correlations with the Pedi-IKDC, highlighting these tests are not capturing the same patient experiences. These correlations are weakened by a small group of painful yet highly functioning patients. The Pedi-IKDC was significantly longer and had a much lower completion rate than PROMIS tests, highlighting a need for a validated computer adaptive testing in evaluating pediatric patients with knee pain.
LEVELS OF EVIDENCE:Level II.
Gene expression at the level of polypeptide synthesis has been investigated in a somatic cell hybrid (20 BW-4) isolated after fusion of spontaneously transformed, tumorigenic Chinese hamster lung ...fibroblasts with mouse embryo fibroblasts. This hybrid exhibited suppression of tumorigenicity and retained--in addition to the parental Chinese hamster genome--copies of all mouse chromosomes as demonstrated by direct karyotype analysis and confirmed for 18 different mouse chromosomes by analysis of 18 different mouse isozymes. Two-dimensional gel electrophoresis of 35Smethionine-labeled polypeptides from hybrid 20 BW-4 showed that the overall polypeptide pattern corresponded to that of the hamster parent. All polypeptides detected in the hamster parental cells were also expressed in the hybrid although some of them were expressed in altered amounts. Of ≈ 1200 labeled polypeptides revealed in the parental cells, 115 mouse polypeptides could be clearly distinguished from the hamster polypeptides due to their different electrophoretic mobilities. Forty-two of these (i.e., 37%) were not expressed in the hybrid 20 BW-4. These observations were confirmed by analysis of another independently isolated hybrid (2W 23) of the same parental cells that also exhibited suppression of malignancy and that retained copies of all mouse chromosomes except no. 5. The results suggest that the genome of the tumorigenic cell after hybridization can suppress expression of more than one-third of the normal parental genome. The suppressed mouse genetic information is probably located on many, if not all, different mouse chromosomes. Even if the level of genetic suppression is high the mouse genome is able to reduce the tumorigenicity of the hamster parental cell.
Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have ...been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy-resistant niche and identified WDR5 as indispensable for this population. WDR5 is a component of the WRAD complex, which promotes SET1 family-mediated Lys4 methylation of histone H3 (H3K4me), associated with positive regulation of transcription. In GBM CSCs, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, including the POU5F1(OCT4)::SOX2 motif. Use of a SOX2/OCT4 reporter demonstrated that WDR5 inhibitor treatment diminished cells with high reporter activity. Furthermore, WDR5 inhibitor treatment and WDR5 knockdown altered the stem cell state, disrupting CSC in vitro growth and self-renewal, as well as in vivo tumor growth. These findings highlight the role of WDR5 and the WRAD complex in maintaining the CSC state and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers.
This paper reports on experiments addressing the buckling and collapse behavior of back-to-back lipped channel built-up cold-formed steel (CFS) columns assembled using 16 different CFS lipped channel ...sizes. The lipped channel sections are connected at the web using a pair of self-drilling screw fasteners at a specified spacing along the column length of 1.83 m (6 ft). These experiments aim to quantify the effect of two web fastener layouts on composite action for each section size, study member end fixity, observe buckling and collapse behavior, and provide benchmarks for design that includes specific considerations for thin-walled member buckling. A total of 32 monotonic, displacement-controlled, concentric compression tests are completed with up to 17 position transducers monitoring displacements at key locations. All tests are conducted with the built-up member seated in CFS tracks, as would be found in practice. Local–global interaction is shown to be a prevalent failure mode, and the stud-to-track end condition is determined to be semi-rigid, but generally closer to a fixed condition. End rigidities are estimated using a Southwell approach. Rational design approaches extending the application of the Direct Strength Method (DSM) and employing current state-of-the-art numerical modeling techniques are proposed and validated with test data. In addition, the development of definitive design recommendations that help reduce the complexity of fastener designs and incorporates the DSM framework when predicting built-up member strength is underway.
•The global buckling and collapse behavior of back-to-back cold-formed steel (CFS) columns is investigated.•Current AISI S100 and AS/NZS 4600 design rules are limited for built-up CFS columns.•Testing was completed on 32 columns installed in track with varying lipped channel sizes and web screw fastener arrangement.•Local-global interaction is prevalent, yet composite action develops when global (flexural) buckling controls.•Rational design approaches employing an extension of DSM are developed.
Lenalidomide (Revlimid®) is approved for the treatment of transfusion-dependent patients with anemia due to low- or intermediate-1-risk Myelodysplastic Syndromes (MDS) associated with a del 5q ...cytogenetic abnormality with or without additional cytogenetic abnormalities, and in combination with dexamethasone for the treatment of multiple myeloma patients who have received at least one prior therapy. Previous reports suggest that lenalidomide is anti-angiogenic and this property appears to be related to efficacy in patients with MDS. We have investigated the effect of lenalidomide on the formation of microvessels in a novel
in vitro angiogenesis assay utilizing human umbilical arterial rings and in a capillary-like cord formation assay using cultured primary endothelial cells. We found that lenalidomide consistently inhibits both sprout formation by arterial rings and cord formation by endothelial cells in a dose-dependent manner. We also found an inhibitory effect of lenalidomide on the associations between cadherin 5, β-catenin and CD31, adherens junction proteins whose interaction is critical for endothelial cell cord formation. Furthermore, lenalidomide inhibited VEGF-induced PI3K–Akt pathway signaling, which is known to regulate adherens junction formation. We also found a strong inhibitory effect of lenalidomide on hypoxia-induced endothelial cell formation of cords and HIF-1α expression, the main mediator of hypoxia-mediated effects and a key driver of angiogenesis and metastasis. Anti-metastatic activity of lenalidomide
in vivo was confirmed in the B16-F10 mouse melanoma model by a >
40% reduction in melanoma lung colony counts versus untreated mice. Our results suggest that inhibitory effects on microvessel formation, in particular adherens junction formation and inhibition of hypoxia-induced processes support a potential anti-angiogenic and anti-metastatic mechanism for this clinically active drug.
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