Vanderbilt Psychiatric Hospital

To compare survival between gynecologic cancer patients with carboplatin hypersensitivity thereafter managed with carboplatin desensitization, cisplatin replacement, and alternative non-platinum therapy. A retrospective review of patients who experienced a hypersensitivity reaction to carboplatin and were treated at the same comprehensive cancer center between 2010 and 2024 was completed. The primary analysis compared progression-free survival between carboplatin desensitization, cisplatin substitution, and alternative non-platinum therapy patients. Secondary analysis compared survival between platinum therapy and non-platinum alternative therapy patients. Descriptive analysis was further performed to delineate the clinical phenotypes of patients with carboplatin hypersensitivity. There were 47 gynecologic cancer patients with carboplatin hypersensitivity, and 38 patients with known progression-free survival. Progression-free survival was significantly longer in desensitized patients (31.1months) vs. cisplatin patients (22.0months, p=0.045). There were no significant differences in progression-free survival between desensitized (31.3months) and alternative therapy patients (36.0months), as well as platinum (31.1months) and non-platinum-based alternative therapy patients (36.0months). A majority of our cohort was observed to have recurrent disease at the time of hypersensitivity (70.2%), a carboplatin-free interval of 12months or more (57.4%), history of adverse reactions to other drugs (76.6%), advanced stage disease (78.8%), and serous histology (70.2%). Desensitized patients demonstrated increased progression-free survival as compared to cisplatin patients. This progression-free survival advantage may be due to the increased toxicity profiles noted for cisplatin and comparatively better tolerability of carboplatin desensitization. Progression-free survival was similar between carboplatin-desensitized and alternative therapy patients, as well as platinum-based and alternative therapy patients.

Alcohol use disorder (AUD) is a chronic, relapsing disease, highly comorbid with anxiety and depression. The bed nucleus of the stria terminalis (BNST), and Crh + neurons in this region are thought to play a key role in chronic ethanol-induced increases in volitional ethanol intake. This role has been hypothesized to be driven by emergent BNST-dependent negative affective behaviors. Indeed, we report here that in female mice undergoing a home cage chronic drinking forced abstinence model (CDFA), excitatory transmission undergoes time-dependent upregulation in BNST Crh + cells. Excitatory NMDA receptors (NMDARs) are a major target of ethanol, and chronic ethanol exposure has been shown to regulate NMDAR function and expression. GluN2D subunit-containing NMDARs have emerged as a target of interest due to their limited distribution and potential roles in affective behavior. We find that knockdown of dorsal BNST (dBNST) GluN2D expression significantly decreases ethanol intake in female, but not male, mice. While BNST Grin2b expression was significantly increased in protracted abstinence following CDFA, no differences in Grin2d expression were observed in dBNST or specifically in dBNST Crh + neurons. Finally, to determine the impact of GluN2D expression on negative affective behaviors, open field, elevated zero maze, and forced swim tasks were used to measure anxiety- and depressive-like behaviors in constitutive and conditional BNST GluN2D knockout mice. Surprisingly, we find that deletion of GluN2D fails to alter negative affect in ethanol-naïve female mice. Together, these data suggest a role for BNST GluN2D-containing NMDARs in ethanol drinking behaviors but not abstinence from ethanol, highlighting potential sex differences and behavioral specificity in the context of AUD behaviors. Overall, these data further suggest roles for BNST synaptic signaling in volitional ethanol intake that are partially independent of actions on affective behavior.

Increasing employment outcomes for individuals with intellectual and developmental disabilities (IDD) remains an enduring emphasis of research, policy, and practice. Parents are often primary partners in the pursuit of meaningful work for their family members with IDD. This qualitative study examined the views of 55 parents regarding the importance of this pursuit and the features of employment that matter most to them. Participants discussed a range of reasons they valued employment for their family members with IDD, including factors that extended beyond a paycheck. Likewise, they described an array of features that they considered to be important to their family member thriving in the workplace (e.g., inclusivity, match with interests, opportunities for growth). We offer recommendations for promoting integrated employment among families and conceptualizing employment outcomes within future research.

Abstract This study investigates how pedagogical, cultural and institutional factors interact with technical knowledge in educational technology integration and how they relate to equitable and effective technology use in low‐resource settings. In the context of a one‐to‐one tablet initiative in rural Kenya, we explore how these factors constrain or support access to technology, instructor capacity, student engagement and student learning, as well as their implications for reducing educational and digital divides. We employ a mixed methods, such as a quasi‐experimental (prepost, nonequivalent control group) research design that draws on data from classroom observations, teacher interviews, student surveys and focus groups, and assessments of student academic performance to generate evidence on classroom practices and student learning in schools with access to tablets, while also highlighting core challenges to successful technology integration. Our findings contribute to the identification of prerequisites and supporting factors for successful educational technology integration, as well as policy levers and school‐based strategies that are likely to increase equitable access to quality learning experiences in schools in low‐resource contexts. Practitioner Notes What is already known about this topic A lack of funding, planning and infrastructure hinder information and communication technology (ICT) integration. Procurement of educational technology and infrastructure improvement efforts has reduced digital divides, but learning divides persist in implementation. Insufficient teacher technology expertise and professional development constrain teacher's effective use of educational technology in classrooms. What this paper adds We employ mixed methods—triangulating the student assessment data with data from student surveys and focus groups, teacher interviews and classroom observations—to identify how pedagogical, cultural and institutional factors interact with technical knowledge in ICT integration in ways that support or constrain student learning in low‐resource contexts. We find that more attention is needed for cultural factors that interact with pedagogical and technical skills to ensure that the classroom instructors' attention is equitability distributed in ways that discourage in‐class “tracking” and differential access to quality learning experiences, such as some teachers' disregard of “slow learners” in the classroom. In low‐resource contexts, providing even basic levels of infrastructure (eg, a consistent power source) and access to general technical knowledge requires more creative and concerted efforts from school leadership and instructors, such as the offer of tutorials and reading clubs outside of the class to expand access and improve the use of devices. Implications for practice and/or policy We find that device sharing can have positive effects on peer‐to‐peer learning, which suggests that policymakers in Kenya should weigh the benefits of achieving one‐to‐one device access against the potential advantages of alternative investments, such as expanding professional development on the integration and use of currently available devices. Increasing opportunities for peer‐to‐peer learning and exchange (among teachers and students) and building shared capacities for ICT integration can help reduce technical issues and lost instructional time.

Aggression ratings were lower by a mean of 1.5 points (SD56.2) in children whose mothers had phosphatidylcholine supplementation compared with placebo, but there was no similar effect of phosphatidylcholine supplementation compared with placebo for children whose mothers were abusing drugs and alcohol (20.4, SD55.7). These differences are not significant, and the number of children studied limits the certainty of any conclusions. As Wakschlag et al. note in their reply to Bell and Ajula, other risk factors may also affect these children. However, it would seem that public health efforts should encourage both prenatal drug and alcohol abstinence and phosphatidylcholine supplementation, now recommend by the American Medical Association (3), along with other elements of good maternal care, at the time of conception or as early in gestation as possible.

Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter (WM) integrity in schizophrenia is unclear. Individuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory and executive functioning. Group differences in WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested. WM integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed but not in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed. Cognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.