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Troubling Trigger Warnings: Toward an Informed Praxis of Care within Intercollegiate Forensics
Get PDFIn light of widespread (mis)use of trigger warnings, content warnings, and content notes in intercollegiate competitive speech, in this essay we interrogate the implementation of these devices and propose an intervention to ensure the activity moves toward a better-informed praxis to accomplish its goal of community care. By identifying the activity’s current propensity for misused warnings, missed messages, a misrepresentation of safety, and misguided performances, our intervention aspires to ensure these important warnings are more thoughtfully employed so as to limit potential harm to our messages, our community members, our activity, and our collective educational aim toward advocacy
PROPELLING WHOLE-CELL BIOSENSOR CREATION BY LEVERAGING GENE FUSION TO ASSEMBLE SYNTHETIC FUNCTIONAL TRANSCRIPTION FACTORS FOR THE DETECTION OF BIOMARKERS
No full textBiosensors are analytical devices that leverage biological modules for the detection of molecules of interest. As customizable tools designed to aid in a wide array of diagnostics, these instruments are rapidly advancing the field of synthetic biology. While varied in their construction and purpose, biosensors are ultimately concerned with converting a physicochemical stimulus into a detectable signal. Among the many existing variants, whole-cell biosensors (WCBs) stand out due to their versatility and engineering potential. WCBs are a type of biosensor in which a physiologically active cell sustains an array of biomolecular elements - receptors, transporters, regulators, etc. - capable of signal recognition, integration and actuation of an observable output. We focus here on the design of WCBs based on synthetic transcription factors, as they are adaptable sensing tools for the detection of small, soluble molecules of interest. This anthology describes the pipeline for the construction of a prokaryotic strain bearing a genetic circuit that integrates a custom-made transcription factor. To this end, we have utilized a live Escherichia coli cell in the construction of a library of synthetic transcription factors engineered to detect N-acetylneuraminic acid (Neu5Ac) - a salivary sialic acid and biomarker of oral cancer. Prominent among this library is a novel chimeric transcription factor known as Sphnx - MG1655 (pCKT-Sphnx, pHC_DYO-LacI-R) - which has been constructed and validated to detect exogenous Neu5Ac. This WCB and its cognates serve as proof-of-concept of a platform that can eventually be applied to clinical screening panels for a multitude of oral and systemic medical conditions whose biomarkers are present in saliva
RECOGNIZING SPECULATIVE LITERATURE: CONCEIVING IDENTITY IN THE ARCHIVES OF ENSLAVEMENT
No full textOne of the key problems of the archive of enslavement, borne out of the violent erasure of enslaved identities, is the struggle to reconstruct and honor those lost identities. Recognizing Speculative Literature: Conceiving Identity in the Archives of Enslavement investigates postcolonial archival processes and the resulting documents to identify a spectrum of speculative literary genres that can be used to supplement traumatic archival erasures, often of female voices and identities, to further understand the power dynamics. To clarify, I use the term ‘speculative literature’ here to refer to a mode of literature that relies on the few fragments that may exist within archival texts, photos, documents, etc. and entangles them to create a restoration of hypothesized identity, history, or perspective where there was only previously a mere fragment or mention, if that. Because it is founded on fragmented source information, it can only amount to a speculative notion of what could be missing from this supposedly representative archive as ‘prologue’ within history. My intention is to challenge the established conception of the genre to focus on texts that deal specifically with speculation as a methodology to supplement erasures. I also aim to destabilize rigid genre conceptions of fiction, novels and poetry, and nonfiction, memoirs and autobiography. Challenging these genre conceptions allows a more nuanced understanding of speculative literature to develop which can be identified, and writers can then continue to write into these speculative modes. While there are some common authorial tactics in the dissertation’s chapters, allowing for a new and broader understanding of speculative literature makes room for creation of new supporting documents out of the flawed and fragmented archives of enslavement. We are simultaneously narrowing the existing conception of the speculative literature genre, to then broaden those boundaries across forms, allowing for more opportunity to supplement archival absences
Shifting the Discourse: How Asset-Based Literacy Practices Unlock Multilingual Learners\u27 Potential
Get PDFAs multilingual learners (MLs) grow in number, educators must shift from deficit-based literacy instruction to asset-based approaches that leverage students\u27 home languages, cultures, and identities. This article explores three research-backed strategies, culturally responsive texts, digital storytelling, and community-integrated literacy projects, that empower MLs and enhance engagement, motivation, and literacy development. Grounded in real-world classroom applications and empirical research, the discussion provides practical solutions for integrating these strategies, addressing common challenges, and fostering an inclusive learning environment. The author, an experienced teacher educator, shares anecdotes on how his students implement these strategies in their diverse classroom settings to maximize ML success. The article concludes with a call to action, urging educators to implement small but meaningful shifts that amplify student voices, strengthen literacy skills, and create lasting educational equity for MLs
COST-EFFECTIVENESS OF PSILOCYBIN-ASSISTED THERAPY VERSUS STANDARD OF CARE FOR PATIENTS WITH TREATMENT-RESISTANT DEPRESSION
Get PDFObjectives: Patients with treatment-resistant depression (TRD) experience high relapse rates and a relentless cycle of ineffective treatments, significantly impairing their quality of life and burdening healthcare resources. Psilocybin has emerged as a promising alternative, offering rapid and sustained symptom relief. However, its cost-effectiveness remains unexplored. This study conducted a pioneering cost-effectiveness analysis of psilocybin-assisted therapy (PAT) versus standard care (SoC) for individuals with TRD using a Markov model from a U.S. healthcare perspective. Methods: The model, parameterized by randomized trial efficacy data and a micro-costing approach, simulated patient transitions every six-week cycle, consistent with American Psychiatric Association guidelines. Outcomes focused on response/remission rates and incremental cost-effectiveness ratios (ICERs), expressed in 2023 U.S. dollars per quality-adjusted life years (QALYs). Extensive deterministic and probabilistic sensitivity analyses (PSA) explored uncertainties. Dosing and price point variations were also examined in scenario analysis to identify optimal strategies. Results: Psilocybin consistently dominated SoC, providing cost savings (ΔCosts = -50,000/QALY threshold, with 65.89% of iterations showing greater effectiveness at lower costs. Notably, the Incremental Net Monetary Benefit (INMB) analysis indicated a value of 50,000 to 500 to $10,000). Scenario analysis revealed that administering two doses three weeks apart was the most cost-effective regimen. Conclusions: Psilocybin offers a groundbreaking, cost-effective alternative to SoC for TRD. These findings support its integration into treatment protocols, warrant further research into its long-term benefits, and position PAT as a promising strategy for future clinical guideline
FORMULATION STRATEGIES TO IMPROVE BIOAVAILABILITY AND ORAL ABSORPTION OF SOTORASIB (AMG 510)
No full textBiovariability poses a significant challenge in the oral administration of sotorasib, an FDA-approved KRAS G12C inhibitor for non-small cell lung cancer (NSCLC). Sotorasib, weakly basic nature, limited aqueous and pH-dependent solubility, necessitates a high daily dose (960 mg; 8 tablets), impacting patient compliance and therapeutic outcomes. Co-administration with acid-reducing medications (PPIs), commonly used by cancer patients, significantly reduces maximum concentration (Cmax) and area under the curve (AUClast), hindering absorption. To address these limitations, we developed a pH-independent nanocrystalline formulation through wet media milling, aiming to achieve a stable formulation with enhanced bioavailability, improved redispersibility, and minimized fasted/fed variability. The nanosuspension, achieved a high drug load (45% w/w) with uniformly distributed nanocrystals (173 ± 21.54 nm) and a stable negative zeta potential (-36.0 ± 0.57 mV). Cryoprotectants hydroxypropyl-β-cyclodextrin (HPβ-CD) and trehalose were effective in preventing aggregation, ensuring excellent redispersibility across pH conditions in both simulated gastric (pH 4.0) and intestinal (pH 6.8) environments. In vitro dissolution studies demonstrated \u3e 95% drug release within 5 minutes at both pH levels, indicating rapid dissolution and robust stability. Solid State Characterization studies, including X-ray diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and cryo-TEM, confirmed the preserved crystallinity, reduced particle size, and improved homogeneity. Additionally, BET surface area analysis indicated an increased surface area for the lyophilized nanosuspension, supporting enhanced dissolution. Evaluated in a novel continuous dissolution-permeation assembly mimicking in vivo conditions, the nanosuspension demonstrated a significantly improved dissolution and permeability profile, capturing the shift from dissolution rate-limited to permeation rate-limited absorption. In vivo pharmacokinetic studies in animal models revealed superior systemic exposure, with a significant increase in Cmax (3529 ± 564.57 ng/mL) compared to the physical mixture. These findings suggest that the sotorasib nanosuspension, designed to address biovariability and reduce dosing frequency, holds potential to substantially improve therapeutic outcomes for NSCLC patients
IN DEFENSE OF BINARY SYMPTOM COUNT SCORING: PSYCHOMETRIC BENEFITS AND CLINICAL UTILITY
Get PDFBackground: Assessment of mental health symptomology is essential for clinical research and patient care. Traditional measures of mental health symptoms typically use a Likert-type rating scale with scores and interpretations based on the sum of numeric Likert item responses. However, in addition to the psychometric difficulties posed by summing ordinal items, Likert sums are not directly linked to the proposed underlying construct of clinical distress and may not be clinically appropriate for patients in treatment due to a few specific symptoms rather than global distress across all symptoms. Aim & Method: The current study proposes an alternative binary scoring approach to reflect if a symptom is an issue for a patient. Symptoms are considered at two levels of occurrence: “present” (occurring at least sometimes), or “persistent” (occurring frequently or always). The study aims to empirically and conceptually compare item-level binary scoring with traditional Likert sum scoring using data from the OQ-45.2 (N = 433 adults) and the ARES—short form (N = 1019 children). The impact of binary scoring on the factor structure of each measure is examined. IRT models and SDT analyses are employed to differentiate symptoms based on how they relate to the underlying latent trait of distress. This information is used to create a binary scoring model based on optimal cut-points for each item. Results: Results indicate that binary symptom count scoring provides a psychometrically sound and clinically useful alternative to Likert scoring that is simple, easy to interpret, and can directly guide diagnostic decision making
EVALUATING SCHOOL PSYCHOLOGISTS’ UNDERSTANDING OF PSW APPROACHES IN SLD IDENTIFICATION
Get PDFSpecific Learning Disability (SLD) is the most common classification for special education children in the United States (National Center for Education Statistics, 2018). With the high prevalence of this disorder, an increase in the use of the pattern of strengths and weaknesses (PSW) method, and the responsibility of the school psychologist to engage in competent practice, this study aimed to investigate the level of understanding school psychologists have in three of the most common PSW methods: Naglieri’s (1999) discrepancy/consistency method (DCM), Flanagan and colleagues’ (2002, 2013) dual-discrepancy consistency method (DD/C), and Hale and Fiorello’s (2004) concordance-discordance method (C-DM; Maki & Adams, 2018; National Association of School Psychologists [NASP], 2020). Seventy-three participants completed a survey that included questions about the three approaches\u27 core elements. Results indicated that on average, participants did not demonstrate sufficient knowledge of the PSW method (e.g., C-DM, DCM, or DD/C) they reported moderate to extreme familiarity with. However, the results nonetheless demonstrated that, in general, as participants’ self-reported familiarity levels of DCM and DD/C increased, their knowledge scores improved as well. Lastly, participants indicated the highest preference for and familiarity with the DD/C method. The need for additional training in PSW methods and implications for the field of school psychology are discussed
EXTRACURRICULAR ACTIVITY INVOLVEMENT AS A PROTECTIVE FACTOR FOR ADOLESCENT DELINQUENCY FOR YOUTH EXPOSED TO PARENTAL ALCOHOL AND/OR DRUG DEPENDENCY
Get PDFThe present study investigated whether extracurricular involvement in adolescence serves as a protective factor against adolescent delinquency for youth exposed to parental alcohol and/or drug dependency in early childhood. While previous research has established parental substance use as a risk factor for adolescent delinquency, less is known about whether extracurricular activities moderate this association. The present study included a subsample of 3,251 youth (n = 1,662 boys, 1,589 girls) from the Future of Families and Child Wellbeing Study (FFCWS), a probability sample of births in large US cities (\u3e 200,000) between 1998 and 2000. Parental alcohol and/or drug dependency was assessed at age 3 using the Composite International Diagnostic Interview Short-Form. Adolescent delinquency was measured at age 15 by self-report and included behaviors such as selling marijuana or other drugs, taking something from a store without paying for it, and using or threatening to use a weapon to get something. Extracurricular activity involvement was measured at age 15 and reflects participation in athletic or sports teams, group performance activities, scouts or hobby clubs, school activities, religious services, and volunteer service activities. Hierarchical linear regression was performed to examine whether extracurricular activity involvement at age 15 moderated the association between parental alcohol and/or drug dependency at age 3 and adolescent delinquency at age 15, while controlling for child’s sex, birth mother’s marital status at the time of child’s birth, and adolescent delinquency at age 9. Results indicated that parental alcohol and/or drug dependency at age 3 predicted higher levels of adolescent delinquency at age 15. Adolescents with greater levels of extracurricular activity involvement at age 15 reported lower levels of delinquency at age 15. However, extracurricular activity involvement did not moderate the association between parent alcohol and/or drug dependency exposure during childhood and adolescent delinquency. Findings from the present study show that although extracurricular activity involvement is protective for youth, regardless of exposure to parental alcohol and/or drug dependence. This study offers valuable insights on the protective role of extracurricular activities during adolescence