Shared Governance Through Bylaws: Transformation Within a College of Nursing.

BACKGROUND: Enhancing faculty voice and promoting shared governance within academia has long been called for but has not been well-reported. A college of nursing in the midwestern United States identified shortcomings in its organizational structure including lack of faculty voice, communication barriers, lack of faculty participation in decision making, and academic programs operating independently. METHOD: A workgroup was formed to transform the bylaws to promote shared governance, including faculty voice, equality, and engagement. RESULTS: The bylaws were revised and presented to faculty for discussion, further revisions, and vote. The revised bylaws were approved and implemented in August 2021. CONCLUSION: Through transformation of the bylaws, the college's 12-committee structure was reconceptualized to five standing committees and 13 subcommittees. Clear communication lines and cross-committee collaboration was established to break down the former academic program silos. Faculty with primary teaching assignments are equally represented throughout the structure with voice, vote, and responsibility. [J Nurs Educ. 2024;63(5):277-281.].

Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes.

Background: Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods: Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results: Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.

Primary and Secondary Intracerebral Hemorrhage in Pregnant and Nonpregnant Young Adults by SMASH-UP Criteria.

BACKGROUND: Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity, but its pathophysiology is poorly characterized. We investigated characteristics of pregnancy-associated ICH (P-ICH), compared with ICH in similar aged nonpregnant adults of both sexes. METHODS AND RESULTS: We performed a retrospective analysis of 134 adults aged 18 to 44 years admitted to our center with nontraumatic ICH from January 1, 2012, to December 31, 2021. We compared ICH characteristics among 3 groups: those with P-ICH (pregnant or within 12 months of end of pregnancy); nonpregnant women; and men. We categorized ICH pathogenesis according to a modified scheme, SMASH-UP (structural, medications, amyloid angiopathy, systemic, hypertension, undetermined, posterior reversible encephalopathy syndrome/reversible cerebral vasoconstriction syndrome), and calculated odds ratios and 95% CIs for primary (spontaneous small-vessel) ICH versus secondary ICH (structural lesions or coagulopathy related), using nonpregnant women as the reference. We also compared specific ICH pathogenesis by SMASH-UP criteria and functional outcomes between groups. Of 134 young adults with nontraumatic ICH, 25 (19%) had P-ICH, of which 60% occurred postpartum. Those with P-ICH had higher odds of primary ICH compared with nonpregnant women (adjusted odds ratio, 4.5 [95% CI, 1.4-14.7]). The odds of primary ICH did not differ between men and nonpregnant women. SMASH-UP pathogenesis for ICH differed significantly between groups (P<0.001). While the in-hospital mortality rate was lowest in the P-ICH group (4%) compared with nonpregnant women (13%) and men (24%), 1 in 4 patients with P-ICH were bedbound and dependent at the time of discharge. CONCLUSIONS: In our cohort of young adults with ICH, 1 in 5 was pregnancy related. P-ICH differed in pathogenesis compared with non-pregnancy-related ICH in young adults, suggesting unique pathophysiology.

Improving the standardisation, timeliness and efficiency of the occupational therapy admission process in an older adult inpatient service.

Occupational therapists (OTs) are at the forefront of providing recovery-oriented care for older people through timely assessments of patient's engagement in daily living activities among many other interventions. This aids a timely, safe and successful discharge from hospital.This project built on the foundations of previous work while considering the context and requirements of two older adult wards, the rates of admission and staff retention. The specific aim agreed was for 90% of patients admitted to the older adults' inpatient units to be assessed by the occupational therapy (OTY) team within days of admission by December 2022.The OTs worked in collaboration to initiate two tests of change with a total of five PDSA cycles.Our tests of change resulted in an increase of patients engaging in OTY initial assessments within seven days of admission from 47.65% (May to November 2021) to 78% (December 2021 to December 2022).Our team embarked on a quality improvement project to improve standardisation, efficiency and timeliness of the OTY process in an older adult inpatient service by using a pragmatic measure and tests of change evidenced in a previous study. This evidenced the generalisability of the findings of this study. While we were able to improve the timeliness of OTY initial assessments, we concluded that the overall impact on outcomes such as timely discharge was also dependent on other clinical and social factors.

Access, Interest, and Barriers to Incorporation of Birth Doula Care in the United States.

Doula care improves maternal care, yet barriers exist to incorporating doula care. The purpose of this study was to evaluate interest and barriers to doula care. Overall, 508 women, 26-35 years of age (54.5%), White/Caucasian (89.8%), and married (88.6%), completed this study. Most reported ≥1 previous birth (97.6%). Respondents would "feel comfortable" (73.2%) and "more confident" (54.9%) with doula care at birth, and 57.9% reported their provider would be supportive of doula care. Only 39.0% expressed benefits to doula care during pregnancy compared to 72.6% at birth and 68.1% during postpartum. Most would hire a doula if health insurance covered some of the costs. Despite the recognized benefits and support of doula care, cost-associated barriers exist to the incorporation of doula care.

Interactions of azole-based inhibitors with human heme oxygenase.

Human heme oxygenase-1 (hHO-1) plays a crucial role in human physiology because of its ability to metabolize free heme. The heme degradation products, biliverdin and bilirubin, were shown to have protective antioxidant properties in cells. In the context of cancer, hHO-1 function grants cancer cells defense from standard chemotherapy treatments, leading to the development of azole-based inhibitors that target hHO-1 for potential anticancer therapy. This work reports experimental and theoretical characterization of interactions between three azole-based inhibitors and the active site of hHO-1. It was found that all three compounds have Kd values within the µM order. The electronic absorption and resonance Raman (rR) spectra indicated that they bind to the ferric heme and coordinate through a nitrogen atom. rR measurements revealed varying effects of inhibitors on the geometry of heme vinyl groups in the ferric form of hHO-1. Changes in peripheral group orientation are known to affect heme redox potential, and consequently can reflect the inhibitory properties of studied azoles. The subsequent docking studies showed that inhibitors with lower Kd values are located close to two vinyl groups, while the compound with higher Kd is situated near only one, consistent with the rR studies. Finally, the rR studies of the CO adducts showed that the inhibitors bind to the heme in a reversible manner. Altogether, the combination of ligand binding studies, UV-Vis and rR spectroscopies, as well as computational approach revealed an importance of the steric hindrance imposed by the inhibitor's side chain.

KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition.

Acute myeloid leukemia (AML) is a heterogeneous, aggressive malignancy with dismal prognosis and with limited availability of targeted therapies. Epigenetic deregulation contributes to AML pathogenesis. KDM6 proteins are histone-3-lysine-27-demethylases that play context-dependent roles in AML. We inform that KDM6-demethylase function critically regulates DNA-damage-repair-(DDR) gene expression in AML. Mechanistically, KDM6 expression is regulated by genotoxic stress, with deficiency of KDM6A-(UTX) and KDM6B-(JMJD3) impairing DDR transcriptional activation and compromising repair potential. Acquired KDM6A loss-of-function mutations are implicated in chemoresistance, although a significant percentage of relapsed-AML has upregulated KDM6A. Olaparib treatment reduced engraftment of KDM6A-mutant-AML-patient-derived xenografts, highlighting synthetic lethality using Poly-(ADP-ribose)-polymerase-(PARP)-inhibition. Crucially, a higher KDM6A expression is correlated with venetoclax tolerance. Loss of KDM6A increased mitochondrial activity, BCL2 expression, and sensitized AML cells to venetoclax. Additionally, BCL2A1 associates with venetoclax resistance, and KDM6A loss was accompanied with a downregulated BCL2A1. Corroborating these results, dual targeting of PARP and BCL2 was superior to PARP or BCL2 inhibitor monotherapy in inducing AML apoptosis, and primary AML cells carrying KDM6A-domain mutations were even more sensitive to the combination. Together, our study illustrates a mechanistic rationale in support of a novel combination therapy for AML based on subtype-heterogeneity, and establishes KDM6A as a molecular regulator for determining therapeutic efficacy.

Material circumstances, health care access, and self-reported health: A latent class analysis.

Latent class analysis was used to explore intersections of material circumstances and health care access among 308 adults, and associations between classes with health outcomes. Good fit was found for a four-class model: Resource Stable (Class 1, 62.43%), Unbalanced Meals with Health Care (Class 2, 16.91%), Resource Insecurity with Delayed Health Care (Class 3, 14.75%), and Resource Stability without Access to Health Care (Class 4, 5.91%). Class 1 reported greater well-being and self-rated health than Class 2 and 3. Class 1 reported lower BMI than Class 2. Findings document intersections among economic marginalization indicators with varying health outcomes among classes.

Maintaining distance and avoiding going out during the COVID-19 pandemic: a longitudinal examination of an integrated social cognition model.

Objective: To test an integrated social cognition model predicting two forms of social distancing behavior (maintaining distance and avoiding going out in public) during COVID-19.Design: Participants from the U.S. (Sample 1, n = 433) and Canada (Sample 2, n = 239) completed online measures, reflecting the theory of planned behavior (attitudes, norms, perceived control, intention), COVID-19-specific risk, anticipated regret, fear of catching COVID-19, and perceived capacity related to using technology to connect with others. Self-reported behavior was collected from the U.S. sample at 6-month follow-up.Results: Intention to maintain distance and avoid going out predicted behavior within the U.S. sample. For both samples, intention was predicted by attitudes, subjective norms and perceived behavioral control. Perceived severity of COVID-19, anticipated inaction regret, and fear of catching COVID-19 predicted intention to maintain distance and avoid going out across both samples. Finally, within the U.S. sample, significant indirect effects were present for perceived behavioral control predicting future maintaining distance and avoiding going out via intention to engage in these behaviors.Conclusion: The integrated social cognition model predicts social distancing intentions and long-term social distancing behaviors. Hazard-specific risk and affect were relevant determinants added to the models. Potential avenues for intervention research are described.Supplemental data for this article is available online at https://doi.org/10.1080/08870446.2021.2023746 .

Precise single-cell transcriptomic mapping of normal and leukemic cell states reveals unconventional lineage priming in acute myeloid leukemia.

Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states. Cell state annotations were benchmarked against purified cell populations, and in-depth characterization of gene expression programs underlying hematopoietic differentiation was undertaken. Projection of single-cell transcriptomes from 175 samples spanning acute myeloid leukemia (AML), mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) revealed 11 subtypes involving distinct stages of hematopoietic differentiation. These included AML subtypes with notable lymphoid or erythroid lineage priming, challenging traditional diagnostic boundaries between AML, MPAL, and AEL. Quantification of lineage priming in bulk patient cohorts revealed specific genetic alterations associated with this unconventional lineage priming. Integration of transcriptional and genetic information at the single-cell level revealed how genetic subclones can induce lineage restriction, differentiation blocks, or expansion of mature myeloid cells. Furthermore, we demonstrate that distinct cellular hierarchies can co-exist within individual patients, providing insight into AML evolution in response to varying selection pressures. Together, precise mapping of hematopoietic cell states can serve as a foundation for refining disease classification in acute leukemia and understanding response or resistance to emerging therapies.

A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome.

Many cancers are organized as cellular hierarchies sustained by cancer stem cells (CSC), whose eradication is crucial for achieving long-term remission. Difficulties to isolate and undertake in vitro and in vivo experimental studies of rare CSC under conditions that preserve their original properties currently constitute a bottleneck for identifying molecular mechanisms involving coding and non-coding genomic regions that govern stemness. We focussed on acute myeloid leukemia (AML) as a paradigm of the CSC model and developed a patient-derived system termed OCI-AML22 that recapitulates the cellular hierarchy driven by leukemia stem cells (LSC). Through classical flow sorting and functional analyses, we established that a single phenotypic population is highly enriched for LSC. The LSC fraction can be easily isolated and serially expanded in culture or in xenografts while faithfully recapitulating functional, transcriptional and epigenetic features of primary LSCs. A novel non-coding regulatory element was identified with a new computational approach using functionally validated primary AML LSC fractions and its role in LSC stemness validated through efficient CRISPR editing using methods optimized for OCI-AML22 LSC. Collectively, OCI-AML22 constitutes a valuable resource to uncover mechanisms governing CSC driven malignancies.

Repetitive negative thinking during pregnancy and postpartum: Associations with mental health, inflammation, and breastfeeding.

INTRODUCTION: Repetitive negative thinking (RNT) is a transdiagnostic feature that predicts increased mental health risks, inflammation, and reduced engagement in health promoting behaviors. Depression, anxiety, stress, inflammation, higher body mass index (BMI), and low engagement in health behaviors are associated with adverse outcomes during pregnancy as well as postpartum. However, there is limited literature on the associations between RNT and these contributing factors in the perinatal period, an at-risk time during which women may benefit from clinical interventions directed at RNT. METHODS: This study examined the contribution of RNT to inflammation [interleukin (IL)-6] and breastfeeding duration through mediating indicators of mental health and BMI. Behavioral and biological assessments occurred during late pregnancy as well as at 4-6 weeks, 4 months, 8 months, and 12 months postpartum. RESULTS: RNT was positively associated with depressive symptoms, anxiety, and perceived stress (ps ≤ .001) at each assessment timepoint, with the strongest associations observed at the pregnancy assessment and significant, but attenuated, associations during postpartum (ps < .01). In modeling of the association between RNT and IL-6, the indirect effect of BMI was significant at each timepoint (95%CIs 0.0013, 0.0052). Women with lower RNT exhibited longer breastfeeding duration (p = .02). These effects were not significantly mediated by mental health indicators. CONCLUSIONS: Clinically meaningful relationships, in which RNT predicts mental health, inflammation, and health behavior engagement during pregnancy and postpartum were observed. Clinical interventions to reduce RNT may have unique benefits this time. LIMITATIONS: Further research is warranted to determine if therapies to reduce RNT confer unique benefits for maternal and child health.

Addressing health in psychotherapy from a community wellness framework: Introduction to the special section.

This introductory article to the special section on addressing health in psychotherapy offers the Community Wellness Model (CWM) as a useful framework for addressing illness in the context of therapy at the sites of personal, relational, and collective well-being. We provide information on the prevalence of health concerns in the general public and clients seeking psychotherapy, and how health psychology intervention research largely focuses on outcomes without attending to therapeutic processes. In this introductory article, we then highlight the nine articles that comprise the following two parts in the special section: (a) Identifying What is (Un)Known About Health in Psychotherapy and (b) Focus on Psychotherapy for Specific Health Conditions and Populations. This introductory article concludes with suggestions to psychotherapy practitioners and researchers on how to incorporate the CWM when integrating health into psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Addressing health in psychotherapy: Future directions from a community wellness lens.

Building off insight provided by authors in this special section and in the broader literature, this closing article describes future directions in health in psychotherapy. We use the community wellness model (CWM; Prilleltensky, 2005) sites of personal, relational, and collective to highlight psychotherapy constructs that offer future directions for more fully embracing a community and social justice perspective in health in psychotherapy. Within each level, we describe implications for researchers and clinicians: the personal level focuses on individual psychotherapy, including theoretical orientation, interventions, and feedback-informed treatment; the relational level covers clinician-client dynamics and group psychotherapy; the collective level addresses the scope and innovation of our interventions as well as advocacy efforts. Our hope is that these psychotherapy constructs and processes offer researchers and clinicians future directions for more fully integrating health into psychotherapy in a way that embeds a social justice perspective. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia.

The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor and mature cell types. Leukemia hierarchy composition was associated with functional, genomic and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP and Intermediate. Critically, variation in hierarchy composition along the Primitive versus GMP or Primitive versus Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A seven-gene biomarker derived from the Primitive versus Mature axis was associated with response to 105 investigational drugs. Cellular hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.

Perceived social support predicts self-reported and objective health and health behaviors among pregnant women.

Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p = 0.001), greater sleep quality (p = 0.001), fewer health-impairing behaviors (p = 0.02), and higher RBC omega-3 fatty acids (p = 0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.

Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration.

BACKGROUND AND OBJECTIVES: Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear. METHODS: We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease-MRI-based CMBs and autopsy-based CAA-as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55-90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples. RESULTS: We included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (ß = 4.49 ± 1.13, p = 0.04) and white matter (ß = 4.72 ± 2.1, p = 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (ß = 5.17 ± 2.47, p = 0.04) than in those with ≥2 CMBs (ß = 1.97 ± 3.41, p = 0.56). In BARS, CAA was associated with increased cortical thickness (ß = 6.5 ± 2.3, p = 0.016) but not with increased brain weight (ß = 1.54 ± 1.29, p = 0.26). DISCUSSION: Superficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease.

Association of cancer caregiver stress and negative attribution style with depressive symptoms and cortisol: a cross-sectional study.

PURPOSE: We examined the effect of informal cancer caregiver stress and negative attribution style (NAS) on depressive symptoms and salivary cortisol. METHOD: The sample came from a hospital bone marrow unit and caregiver support organizations and included 60 informal cancer caregivers (51.7% partners) of individuals with cancer (provided care for a median of 27.5 h per week for 12 months) and 46 non-caregiver participants. In this cross-sectional study, participants completed questionnaires assessing NAS and depressive symptoms and provided saliva samples to measure cortisol. RESULTS: Linear regressions demonstrated that cancer caregiver stress (p = 0.001) and the cancer caregiver stress by NAS interaction (p = 0.017), but not NAS alone (p = 0.152), predicted depressive symptoms. Caregivers independent of their NAS and non-caregivers high in NAS reported high depression while non-caregivers low in NAS reported low depression. Neither cancer caregiver stress (p = 0.920) nor NAS alone (p = 0.114), but their interaction, predicted cortisol (p = 0.036). Higher NAS was associated with a higher cortisol in both groups while non-caregivers had higher cortisol than caregivers. CONCLUSIONS: If the findings can be replicated, consideration of NAS in existing interventions to support informal cancer caregivers in managing chronic stress appears warranted.

Predictors of family violence in North Carolina following initial COVID-19 stay-at-home orders.

BACKGROUND: Although there is evidence that family violence increased in the United States during the COVID-19 pandemic, few studies have characterized longitudinal trends in family violence across the course of initial stay-at-home orders. OBJECTIVE: The purpose of the present study is to investigate patterns and predictors of family violence, such as child maltreatment and harsh punishment, during the first eight weeks of the pandemic after initial stay-at-home orders in North Carolina. PARTICIPANTS AND SETTING: Participants included 120 families with children ages 4-11 (53% non-White, 49% female) and a primary caregiver (98% female) living in rural and suburban areas in North Carolina. Participants were recruited based on high risk of pre-pandemic family violence exposure. METHODS: Caregivers completed weekly surveys during the pandemic assessing family violence, caregiver employment status, and caregiver emotion reactivity. In addition, all caregivers completed pre-pandemic surveys on family violence. RESULTS: Mixed-effects models revealed that family violence was highest following initial stay-at-home orders and decreased linearly over time. Higher pre-pandemic child violence exposure and caregiver unemployment were associated with higher initial family violence. Higher caregiver emotion reactivity was associated with changes in family violence across time. CONCLUSIONS: We observed high levels of family violence following stay-at-home orders, especially in families with higher baseline violence, higher caregiver emotion reactivity, and caregiver unemployment or underemployment. These associations suggest that vulnerable families may respond to the additional stressor of stay-at-home orders with increased violence and thus need additional support in moments of crisis.

A clinical laboratory-developed LSC17 stemness score assay for rapid risk assessment of patients with acute myeloid leukemia.

Leukemia stem cells (LSCs) are linked to relapse in acute myeloid leukemia (AML). The LSC17 gene expression score robustly captures LSC stemness properties in AML and can be used to predict survival outcomes and response to therapy, enabling risk-adapted, upfront treatment approaches. The LSC17 score was developed and validated in a research setting. To enable widespread use of the LSC17 score in clinical decision making, we established a laboratory-developed test (LDT) for the LSC17 score that can be deployed broadly in clinical molecular diagnostic laboratories. We extensively validated the LSC17 LDT in a College of American Pathologists/Clinical Laboratory Improvements Act (CAP/CLIA)-certified laboratory, determining specimen requirements, a synthetic control, and performance parameters for the assay. Importantly, we correlated values from the LSC17 LDT to clinical outcome in a reference cohort of patients with AML, establishing a median assay value that can be used for clinical risk stratification of individual patients with newly diagnosed AML. The assay was established in a second independent CAP/CLIA-certified laboratory, and its technical performance was validated using an independent cohort of patient samples, demonstrating that the LSC17 LDT can be readily implemented in other settings. This study enables the clinical use of the LSC17 score for upfront risk-adapted management of patients with AML.