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Pregnancy Outcomes After Glp-1 Receptor Agonist Exposure And Ethical Considerations
Full text linkThe objective of this study is 1) to understand the effect of GLP-1 receptor agonist (GLP-1RA) use in the year prior to conception on risk of developing hypertensive disorders of pregnancy (HDP) and on gestational weight gain (GWG), and 2) to analyze important ethical considerations relevant to research in pregnancy and specifically related to GLP-1RAs.All patients delivering between 2014-2024 with evidence of GLP-1RA exposure in the year prior to conception were identified through electronic medical record (EMR) query with hand review to confirm exposure. GLP-1RA exposed patients were classified according to GLP-1RA indication for use: 1) pregestational diabetes mellitus (PGDM) or 2) weight management (WM) for increased body mass index (BMI). Control groups for each indication cohort were identified from 2021-2022 delivery EMR data. PGDM controls were patients with pregestational type 1 or type 2 diabetes mellitus managed with medication other than GLP-1RA in the year prior to conception. WM controls were a stratified random sample of patients without PGDM not on antihyperglycemic medication in the year prior to conception with BMIs between 30\u3c40 kg/m2 and ≥40 kg/m2. Demographic and clinical characteristics and obstetrical outcomes were compared. Logistic regression was employed to assess the crude (OR) and adjusted odds ratios (aOR) for HDP controlling for covariates significant in bivariate tests at \u3c0.05. Multinomial logistic regression was employed to assess the crude (OR) and adjusted odds ratios (aOR) for GWG controlling for covariates significant in bivariate tests at \u3c0.05. 243 patients had GLP-1RA exposure in the year prior to conception. Of these, 103 were exposed for PGDM and 140 for WM. For the PGDM cohort, 175 controls were identified from the two years of EMR data interrogated. For the WM cohort, random sampling yielded 200 controls, with half (n=100) having BMI between 30\u3c40 kg/m2 and the other half (n=100) BMI ≥40 kg/m2. Bivariate tests for race/ethnicity, pre-pregnancy BMI, and chronic hypertension identified significant differences between exposed and unexposed patients in the PGDM cohort. For the WM cohort, exposed and unexposed patients had significant differences in PCOS diagnosis, gestational weight gain, and HDP. Within the PGDM group, GLP-1RA exposure did not significantly affect GWG. Those exposed to a GLP-1RA in the WM cohort had significantly decreased risk of GWG below recommendations (aOR1=0.42 (0.18-0.80)). This effect was driven by post-conception GLP-1RA exposure as it significantly decreased risk of GWG below recommendations (aOR=0.32 (0.14-0.77)). For both the PGDM and WM cohort, exposed patients were half as likely to develop HDP compared to unexposed counterparts (PGDM aOR=0.52 (0.30-0.90); WM aOR=0.49 (0.30-0.81)). This effect was driven by post-conception GLP-1RA exposure as it significantly decreased risk of HDP in PGDM (aOR=0.52 (0.28-0.96)) and WM (aOR=0.47 (0.25-0.89)) cohorts. GLP-1RA use in the year prior to conception decreases risk of GWG under recommendations, which may reflect rebound weight gain during pregnancy after GLP-1RA cessation. GLP-1RA use in the year prior to conception significantly reduced the likelihood of developing HDP for patients with PGDM and undergoing WM. Both of these effects appear to be driven by post-conception exposure. There are large evidence gaps for pregnant people, and research in pregnancy should be prioritized to ensure strong evidence to guide safe clinical practice. Several considerations are more complicated in pregnancy, including risk, potential maternal and fetal benefit, and study design, but strong ethical analyses are critical to informing clinical science in pregnant humans to narrow the evidence gaps. Reproductive justice as an organizing theoretical framework offers many important insights into critically evaluating research, pregnancy, and GLP-1RAs and should be centered throughout research in pregnancy efforts
Chimerism Testing In Myeloid Malignancies: Practical Guidance And Clinical Correlates
Full text linkRelapse is the primary cause of mortality for patients with myeloid malignancies post-allogeneic stem cell transplant (aSCT). As early intervention for those deemed high risk for relapse may improve outcomes, identification of residual malignant cell burden is of critical importance. Chimerism testing, the use of DNA sequencing technology to determine the relative percentage of donor to recipient hematopoietic cells post-aSCT, offers a practical metric to monitor for residual leukemic cell burden. The precise value of donor chimerism is influenced by many procedural and contextual factors, and multiple strategies, including the analysis of specific hematopoietic cell subsets, termed lineage-specific chimerism (LSC), may offer more robust associations with prognosis and help guide the use of pre-emptive therapy. The use of donor lymphocyte infusion (DLI) is one such intervention and may mitigate relapse risk, but no widely accepted LSC threshold exists to guide its initiation. The current investigation sought to define an LSC threshold below which relapse is most likely, investigate the threshold’s association with overall survival (OS), and quantify the survival benefit of DLI use within high-risk patients based on this threshold. A retrospective chart review of all patients seen at Yale New Haven Hospital, between 2016-2023, for myeloid malignancies who were treated with aSCT and had available LSC data before the time of relapse or graft failure (N=94) was undertaken. ROC curves were employed to create a threshold based on the difference between one’s T cell (TCC) and myeloid specific (MSC) chimerism. Kaplan-Meier curves and Cox proportional hazards models were used to investigate effects on OS. Having ≥14.5% discrepancy between TCC and MSC was a significant predictor of relapse or graft failure at 1 year (AUC= .831, sensitivity= .796, specificity= .775). Patients with chimerism difference scores above this cutoff point had significantly poorer OS (HR= 2.58, 95% CI= [1.30, 5.13], p= 0.01) despite controlling for covariates. DLI use among this high-risk patient subgroup was shown to significantly improve survival (HR= 0.32, 95% CI= [0.13, 0.79], p= 0.01) with a median OS benefit of 28 months. Our 14.5% chimerism difference threshold may offer promise in triaging high-risk patients for relapse-related work up and serve as one data point on which to support the use of DLI to improve post-aSCT outcomes among high-risk patients
Analysis Of Post-Operative Recovery From Microsurgical Breast Reconstruction As Modified By Anterior Quadratus Lumborum Regional Blockade
Full text linkBreast cancer patients who undergo mastectomy for treatment have the option to proceed with cosmetic breast reconstruction, of which microsurgical flap techniques have become more and more predominant. Optimized recovery from these large-scale surgeries can impact both hospital resources and long-term patient health. The abdominal donor site is the prime suspect for the postoperative pain and delay in return of baseline functional status. Previous literature and clinical practice support the surgically placed transverses abdominal regional block as part of the multimodal analgesia regimen to aid recovery due to incisional pain control, but the technique lacks the ability to impact visceral pain. The anterior quadratus lumborum block, an emerging advanced fascial plane block is a promising alternative, because of its ability to block stimuli in the anterior abdominal region from both somatic and visceral stimuli.
This study follows a quality improvement initiative completed as part of a larger movement to implement new Early Recovery After Surgery (ERAS)-informed guidelines to improve recovery of patients who undergo the Deep Inferior Epigastric Artery Perforator (DIEP) microsurgical breast reconstruction procedure. 413 patients in total were retrospectively analyzed in this study. The control group (N=254) underwent the procedure before implementation of the pilot and received the standard clinical practice of an intraoperative surgically placed, landmark-based intraoperative transversus abdominus plane block using bupivacaine and liposomal bupivacaine. The experimental group (N=159) underwent the procedure after implementation of this new clinical pathway and received preoperative ultra-sound guided bilateral anterior quadratus lumborum block (aQLB) by a regional anesthesia team using bupivacaine plus dexamethasone sodium phosphate (DXP) and methylprednisolone acetate (MPA). Our working hypothesis was implementation of preoperative anesthesiologist-placed aQLB would improve postoperative outcomes after DIEP breast reconstruction. The primary outcome measured was average daily opioid consumption, and secondary outcomes included average daily pain scores, time to first ambulation, and hospital length of stay.
Final analysis of the data revealed a statistically significant decrease in the time to first ambulation in the experimental group by 17% or 7.7 hours (p = \u3c0.005). Other secondary outcome metrics such as average daily opioid usage and hospital length of stay trended towards improvement in the experimental group, but did not reach statistical significance. Average daily pain was statistically significantly higher for the experimental group, but as stated above, did not result in increased opioid consumption for the experimental group. Subgroup analysis showed that the patients who received a quadratus lumborum block alongside a regional chest block were the ones who saw the greatest improvement in time to first ambulation, compared to those who only received a quadratus lumborum block.
The data demonstrates that the anterior quadratus lumborum block may have utility in improving the return to functional status in the immediate postoperative period following DIEP breast reconstruction. We also see that chest regional blockade may have a synergistic effect alongside the quadratus lumborum block in amplifying the improvements seen in mobility. The quadratus lumborum block was also shown to be non-inferior in terms of opioid consumption or hospital length of stay compared to the status quo surgically placed landmark-based transversus abdominus block with liposomal bupivacaine
Reclaiming the Body: A Womanist Bioethics Approach to Christian Authoritarianism
Full text linkThis paper uses womanist bioethics as a theoretical lens to explore how authoritarian leadership practices violate Black women\u27s well-being and autonomy. Womanist bioethics uniquely centers Black women\u27s lived experiences, integrating spiritual, historical, and social dimensions of justice that mainstream bioethics often ignores. The womanist bioethics framework is applied to critique religious authoritarianism and to propose alternative leadership models rooted in shared leadership and communal accountability. The discussion unfolds in four parts: (1) how womanist bioethics critiques the bodily and moral harm authoritarian leadership inflicts on Black women, (2) testimonials of Black women who resisted high-control church systems, (3) an exploration of shared leadership as a justice-oriented ecclesial model, and (4) the role of Black liberation narrative care in ministerial training to address religious authoritarianism. By calling attention to how Black women are both upholders and casualties of oppressive church structures, this paper advocates for transformative religious frameworks that prioritize healing, accountability, and equity
Revisiting the Lasting Impacts of Incarceration
Full text linkUsing newly-linked administrative and commercial data from Virginia spanning 25 years, we study the consequences of incarceration. While previous research has examined labor market outcomes and recidivism, we focus on two of the primary channels through which low-income households build wealth: asset ownership (homes and cars) and human capital formation. To identify causal effects, we use a matched differencein-differences design. In line with much of the literature on the impact of incarceration in the U.S., we find no evidence of scarring effects on labor market outcomes or changes in recidivism beyond the incapacitation period. However, we find that incarceration leads to a persistent reduction in asset accumulation: seven years after sentencing, homeownership has declined by 1.1 percentage points (12.1%) and car ownership by 2.7 percentage points (18.1%). Incarceration also lowers human capital formation, reducing college enrollment by 1.4 percentage points (15.1%)
Tracing Transformations: (Digitized) World War II Correspondence Through the Lens of the Records Continuum Model
Full text linkThis paper traces the transformations of a historical archival collection of personal wartime correspondence. Most of the records in this collection were created in the context of the German Occupation of the Netherlands during World War II (1940–1945) and/or the War of Independence in Indonesia (1945-1950). The collection was gathered and curated by the NIOD Institute for War, Holocaust, and Genocide Studies in Amsterdam from 1945 onwards and was digitised between 2020 and 2023. We navigate the convergence of past and future transformations of the records and illuminate the intricate web of considerations and decisions of historical preservation, archiving, digitisation, research, and (re-)use. We focus on the initial creators of the records, but also on family custodians, professional record-keepers, and the digitisation project team. We address the implications and impacts of their actions, as they present important considerations in the selection, source criticism, and interpretation of such records as sources in historical scholarship.
We use a simplified version of the Records Continuum Model (RCM) as an analytical framework to enhance our understanding of this complex collection of varied historical ‘egodocuments’. By doing so, we evaluate the practical implementation of RCM as an analytical instrument in expanding current practices of source criticism in historical scholarship. We show how different dimensions of mutually interacting dynamic processes add new layers to the context and meaning of historical records, and how ‘egodocuments’ such as wartime correspondence are not only a reflection of the experiences, perceptions, and emotions of their initial writers, but are also influenced by contemporary cultural and social conventions and time- and location-specific contexts and various curatorial and record-keeping activities through time. To conclude, this paper emphasizes the value of collaboration between historical scholars and archivists and stresses the importance of accountability and transparency in record-keeping practices, both in the historical archive and the digital realm
One Move, Many Wins: Green Social Housing As A Solution For Housing Insecurity And Residential Energy Inefficiency In New Haven, Ct
Full text linkThis thesis explores the dual challenges of housing insecurity and residential energy inefficiency in New Haven, Connecticut, and advances green social housing as a transformative policy response. Through a qualitative research design that integrates semi-structured interviews, document analysis, and policy review, the study uncovers the structural conditions that drive unaffordable, unhealthy, and energy-inefficient housing for low- and moderate-income residents. The findings reveal that high utility costs, poor building infrastructure, and disempowering tenant–landlord dynamics are not isolated issues but manifestations of deeper systemic inequities in housing and energy governance. Green social housing emerges as a strategic intervention that aligns sustainable building practices with affordability, equity, and public health outcomes. By centering community control, ecological design, and long-term investment in underserved neighborhoods, this model addresses both the root causes and symptoms of energy and housing precarity. The study calls for an integrated policy framework that includes stronger tenant protections, equitable financing mechanisms, institutional accountability, and cross-sector collaboration. New Haven’s case offers critical insights for other cities seeking to advance environmental justice, climate resilience, and social equity through holistic approaches to the built environment. This research contributes to a growing body of scholarship that frames housing policy as a key site of climate action and public health innovation
Modeling Impacts Of Water Improvements On Typhoid In Urban South Asia
Full text linkIntroduction: Typhoid fever represents a significant burden of disease in urban areas across South Asia. While the recent implementation of routine typhoid conjugate vaccinations (TCVs) has demonstrated significant protective effectiveness against disease, it fails to mitigate environmental transmission through contaminated water, which individuals without access to improved water sources (IWS) may be infected by. Objectives: The primary aim of this study is to estimate the potential reductions to typhoid fever incidence that populations could experience when increasing proportions of the population that have IWS across three high-burden cities in South Asia. The relationship between this reduction and the proportion of water-borne transmission and the overall basic reproduction rate will be additionally explored. Methods: Transmission dynamic models were fitted to data from a TCV trial in Dhaka and surveillance data from Karachi and Kathmandu to estimate transmission parameters for each site for those with and without IWS. These parameters are used to simulate the reduction in incidence with increasing proportions of IWS. Results: Incidence is reduced by less than 2 percent in both Dhaka and Karachi, and more than 93 percent in Kathmandu when increasing the proportion with IWS with and without vaccination at baseline transmission parameters. Increasing the proportion of water-borne transmission and decreasing the overall R0 yielded greater reductions to incidence compared to baseline. Conclusion: Increasing the proportion of the population with access to IWS has the greatest potential to reduce typhoid incidence in urban areas of South Asia where the overall basic reproduction rate is low, or the proportion of water-borne transmission is high, with and without vaccination
Defining The Genetic Basis Of Autosomal Dominant Polycystic Liver Disease With Whole Exome Sequencing
Full text linkPolycystic liver and kidney diseases are inherited disorders marked by progressive cyst formation in hepatic and renal tissues, leading to significant morbidity through organ enlargement, impaired function, and eventual kidney failure or painful hepatic enlargement. While several genes—including PKD1, PKD2, GANAB, and PRKCSH—are implicated, a substantial proportion of cases remain genetically unexplained, limiting diagnostic precision and therapeutic development. This thesis aims to refine the genetic understanding of polycystic liver diseases through whole exome sequencing of 292 individuals with liver and/or kidney cysts. We first identify pathogenic variants in known disease genes in 133 individuals (46%), confirming the recurrent involvement of PRKCSH, SEC63, PKHD1, GANAB, and others. Subsequently, we analyzed the rest of 159 unsolved cases using rare variant burden testing against Genome Aggregation Database (gnomAD) controls. This approach uncovered MED16 as a novel candidate gene, enriched for deleterious variants and functionally supported by gene intolerance scores, conserved domain localization, and high expression in liver and kidney tissues. Mouse model data further suggest MED16 deficiency may disrupt hepatic physiology and potentially impair pathways.The identification of MED16 expands the genetic landscape of Polycystic liver and kidney diseases and underscores the clinical value of stringent exome analysis in genetically unresolved cohorts. While these initial findings are promising, further validation studies are required to confirm MED16’s pathogenic role before consideration for inclusion in clinical diagnostic panels. Broadly, this research contributes to a deeper understanding of the genetic architecture underlying polycystic liver and kidney diseases, laying groundwork for future investigations that could eventually improve patient diagnosis and clinical management
Lessons Learned: Vincenzo La Via
Full text linkVincenzo La Via joined the World Bank Group in 2005 as chief financial officer, in charge of financial reporting, accounting, strategic planning and budgeting, credit risk, corporate finance, market risk, liquidity and asset management, and product development. During his tenure, La Via took part in the bank’s response to the Global Financial Crisis (GFC) and the subsequent European Sovereign Debt Crisis. He left the bank in 2012 to become director general of the Treasury in the Italian Ministry of Economy and Finance as the Italian government took on reform of the banking sector. He left the public sector in 2019 to become managing director and CEO for Europe and the Middle East at Promontory Financial Group