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Recent changes in national and state mathematics standards have increased the level of algebraic thinking taught in younger grades. These changes have prompted more inclusive curriculum designs that open the opportunity to enroll in advanced mathematics courses at younger ages. Of particular interest to this study is the access to eighth-grade algebra, once traditionally reserved for select populations. This study examined long-term academic outcomes for students who did or did not enroll in eighth-grade algebra in one district that implemented an initiative to increase access. The outcomes of students with similar ability, as measured by preassessment in seventh grade, were compared. The groups performed similarly on end-of-course exams in high school math and the mathematics section of the SAT I. However, students who completed algebra in the eighth grade stayed in the mathematics pipeline longer and attended college at greater rates than those who did not. Because of the sequential nature of mathematics course work, students taking algebra at an earlier age have the opportunity to enroll in more advanced courses in the future. Results suggest the need for further exploration of how to provide access and promote enrollment in eighth-grade algebra for students who demonstrate readiness. (Contains 10 tables.)

Sediment DNA (sedDNA) analyses are rapidly emerging as powerful tools for the reconstruction of environmental and evolutionary change. While there are an increasing number of studies using molecular genetic approaches to track changes over time, few studies have compared the coherence between quantitative polymerase chain reaction (PCR) methods and metabarcoding techniques. Primer specificity, bioinformatic analyses, and PCR inhibitors in sediments could affect the quantitative data obtained from these approaches. We compared the performance of droplet digital polymerase chain reaction (ddPCR) and high-throughput sequencing (HTS) for the quantification of target genes of cyanobacteria in lake sediments and tested whether the two techniques similarly reveal expected patterns through time. Absolute concentrations of cyanobacterial 16S rRNA genes were compared between ddPCR and HTS using dated sediment cores collected from two experimental (Lake 227, fertilized since 1969 and Lake 223, acidified from 1976 to 1983) and two reference lakes (Lakes 224 and 442) in the Experimental Lakes Area (ELA), Canada. Relative abundances of Microcystis 16S rRNA (MICR) genes were also compared between the two methods. Moderate to strong positive correlations were found between the molecular approaches among all four cores but results from ddPCR were more consistent with the known history of lake manipulations. A 100-fold increase in ddPCR estimates of cyanobacterial gene abundance beginning in ~1968 occurred in Lake 227, in keeping with experimental addition of nutrients and increase in planktonic cyanobacteria. In contrast, no significant rise in cyanobacterial abundance associated with lake fertilization was observed with HTS. Relative abundances of Microcystis between the two techniques showed moderate to strong levels of coherence in top intervals of the sediment cores. Both ddPCR and HTS approaches are suitable for sedDNA analysis, but studies aiming to quantify absolute abundances from complex environments should consider using ddPCR due to its high tolerance to PCR inhibitors.

Summary: In a multi-level “deconstruction” of omental metastases, we previously identified a prognostic matrisome gene expression signature in high-grade serous ovarian cancer (HGSOC) and twelve other malignancies. Here, our aim was to understand how six of these extracellular matrix (ECM) molecules, COL11A1, cartilage oligomeric matrix protein, FN1, versican, cathepsin B, and COL1A1, are upregulated in cancer. Using biopsies, we identified significant associations between TGFβR activity, Hedgehog (Hh) signaling, and these ECM molecules and studied the associations in mono-, co-, and tri-culture. Activated omental fibroblasts (OFs) produced more matrix than malignant cells, directed by TGFβR and Hh signaling cross talk. We “reconstructed” omental metastases in tri-cultures of HGSOC cells, OFs, and adipocytes. This combination was sufficient to generate all six ECM proteins and the matrisome expression signature. TGFβR and Hh inhibitor combinations attenuated fibroblast activation and gel and ECM remodeling in these models. The tri-culture model reproduces key features of omental metastases and allows study of diseased-associated ECM.

Summary: Guided by a multi-level “deconstruction” of omental metastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human metastases and allowed malignant cell invasion into the artificial omental structure. Prompted by findings in patient biopsies, we used the model to investigate the role of platelets in malignant cell invasion and extracellular matrix, ECM, production. RNA (sequencing and quantitative polymerase-chain reaction), protein (proteomics and immunohistochemistry) and image analysis revealed that platelets stimulated malignant cell invasion and production of ECM molecules associated with poor prognosis. Moreover, we found that platelet activation of mesothelial cells was critical in stimulating malignant cell invasion. Whilst platelets likely activate both malignant cells and mesothelial cells, the tetra-culture model allowed us to dissect the role of both cell types and model the early stages of HGSOC metastases.

Objectives The CDC has warned of increased risk for severe COVID-19 illness among those with certain preexisting conditions. Protective behaviors such as social distancing and mask-wearing have been shown effective at curbing infection rates. These practices are subject to individual perceptions of risk and responsibility. This study aimed to characterize the risk perceptions and protective behaviors of residents in a rural central Michigan region. Specifically, we examined whether individual risk status predicted protective behaviors and concern about the pandemic. Methods Participants were identified via medical records at participating clinics. The high-risk group was those with conditions that put them at increased risk of severe illness from COVID-19, and was compared to healthy controls. Data were collected via phone survey. Participants were asked about their protective behaviors and level of concern about the ongoing pandemic. Results A total of 150 patients participated in the survey; 73 were high-risk acknowledgers, 29 were high-risk deniers, and 48 were healthy controls. There was no significant difference between the groups on level of concern regarding the pandemic or protective behaviors ( P > .05). Compared to other comorbidities, obese people were significantly more likely to deny their risk ( P

AimsWe evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence.MethodsThis 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome.ResultsThe 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths.ConclusionsThe vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence.

There are limited real‐world data on the effectiveness of tixagevimab‐cilgavimab as pre‐exposure prophylaxis of COVID‐19. We describe lessons learned when coordinating data collection and identifying breakthrough SARS‐CoV‐2 infections among patients across indications and institutions in a major US city. The Chicago Department of Public Health requested patient‐level tixagevimab‐cilgavimab administration data from all prescribing providers in Chicago, for treatments December 8, 2021 through June 30, 2022. Records were matched to COVID‐19 vaccinations and laboratory‐confirmed SARS‐CoV‐2 infections through December 31, 2022. Due to difficulty collecting data from all providers, targeted follow‐up was conducted to improve completeness on key variables (demographics, vaccination status, clinical indication for prophylaxis). Over half of reported tixagevimab‐cilgavimab administrations were to patients residing outside Chicago. Five hundred forty‐four Chicago residents who received at least one dose of tixagevimab‐cilgavimab were included in this analysis. Most were age 50 years or older (72%), Black non‐Latinx (33%) or White non‐Latinx (29%), and fully vaccinated (80%). Seventy‐five patients (14%) had laboratory‐confirmed COVID‐19. Patients with and without breakthrough infections were demographically similar. Clinical indication was missing for >95% of cases, improved to 64% after follow‐up; the most frequently specified was hematologic malignancy (10%). Severe outcomes were uncommon: 16% had documented COVID‐19‐related hospitalizations, one death was identified. Tixagevimab‐cilgavimab recipients in Chicago had a lower rate of severe SARS‐CoV‐2 infection than reported among other untreated high‐risk patients, including during predominance of non‐neutralizing variants. Improving stakeholder collaboration is essential for generation of real‐world effectiveness data, informing pandemic preparedness and optimizing use of medical countermeasures. [ABSTRACT FROM AUTHOR]

Integrating Polyvagal Theory and Reinforcement Sensitivity Theory (RST), we examined pre‐ejection period (PEP) reward reactivity, which was suggested to index trait impulsivity, as a moderator between respiratory sinus arrhythmia (RSA) reactivity and antisocial behavior (ASB), and substance use in an urban male, adult sample. To understand the inconsistent findings between RSA reactivity and externalizing problems, we proposed to study both negatively and positively valenced tasks for RSA reactivity and to include PEP reward reactivity as a moderator for the RSA‐behavior link. Data were collected from an urban sample of 131 male adults (active offenders, demographic controls, and college students). ICG (impedance cardiography) and ECG (electrocardiogram) were recorded, computing PEP (sympathetic nervous system activity marker) and RSA (parasympathetic nervous system activity marker), while participants completed the modified Trier Social Stress Test and a simple reward task. Reactivity was calculated by subtracting the baseline from the task activity. Consistent with prior studies, more RSA withdrawal to stress and less PEP shortening to reward predicted the most ASB and substance use. Less RSA withdrawal to reward and more PEP shortening to reward predicted the most ASB and substance use. We incorporated autonomic space, RST, and Polyvagal Theory to discuss our findings, and specifically highlight how clarifying what each reactivity captures based on the task demand (e.g., presence of social threat, need for vagal‐mediated social affiliative behavior) can illuminate our understanding of the result patterns. We found that less parasympathetic nervous system (PNS) control in response to stress corresponds to more externalizing problems when the sympathetic nervous system (SNS) has less control. More PNS control in response to reward corresponds to more externalizing problems when SNS has more control. This study highlights the significance of task valences and provides further support for the integration of Gray's Reinforcement Sensitivity Theory and Porges's Polyvagal Theory. [ABSTRACT FROM AUTHOR]

Introduction: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. Methods: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. Results: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. Conclusion: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population. [ABSTRACT FROM AUTHOR]