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Background: Alcohol use disorders (AUD) are prevalent and responsible for substantial morbidity and mortality; yet efficacious treatments are underused. Previous studies have identified demographic and clinical predictors of medication fills, yet these studies typically do not include patients who were prescribed a medication but did not fill it. Objectives: To examine rates of and factors associated with prescription order and prescription fill for medications for AUD (MAUD) among individuals diagnosed with AUD in outpatient settings. Design: In a cross-sectional analysis, we used multivariate logistic regression to identify factors associated with prescription order and fill. Patients: We used data from the Optum Labs Data Warehouse that linked 2016–2021 de-identified claims and electronic health record (EHR) data, allowing us to observe prescription orders and whether they were filled. We identified 14,674 patients aged ≥ 18 who had an index outpatient encounter with an AUD diagnosis in the EHR. Key Measures: We computed the proportion for whom a MAUD prescription was ordered within 1 year of index visit, and for whom one was filled within 30 days of the order. Key Results: 5.8% of the sample had a MAUD prescription order within 1 year of their index visit. Among those with an order, 87% filled their MAUD prescription within 30 days of receipt (i.e., 5.1% of full sample). After multivariable adjustment, receipt of a MAUD prescription order was more likely for patients who were female (adjusted odds ratio (aOR) [95%CI] = 1.44 [1.24–1.67]), or had moderate or severe AUD (1.74 [1.50–2.01]). Patients receiving an order were more likely to fill it if they had a comorbid mental disorder (1.64 [1.09–2.49]). Conclusions: The low rate of prescription orders was notable. Low use of MAUD appears to result chiefly from prescription order decisions, rather than from prescription fill decisions made by patients. [ABSTRACT FROM AUTHOR]

Background: The rise in prevalence of high deductible health plans (HDHPs) in the United States may raise concerns for high-need, high-utilization populations such as those with comorbid chronic conditions. In this study, we examine changes in total and out-of-pocket (OOP) spending attributable to HDHPs for enrollees with comorbid substance use disorder (SUD) and cardiovascular disease (CVD). Methods: We used de-identified administrative claims data from 2007 to 2017. SUD and CVD were defined using algorithms of ICD 9 and 10 codes and HEDIS guidelines. The main outcome measures of interest were spending measure for all non-SUD/CVD-related services, SUD-specific services, and CVD-specific services, for all services and medications specifically. We assessed both total and OOP spending. We used an intent-to-treat two-part model approach to model spending and computed the marginal effect of HDHP offer as both the dollar change and percent change in spending attributable to HDHP offer. Results: Our sample included 33,684 enrollee-years and was predominantly white and male with a mean age of 53 years. The sample had high demonstrated substantial healthcare utilization with 94% using any non-SUD/CVD services, and 84% and 78% using SUD and CVD services, respectively. HDHP offer was associated with a 17.0% (95% CI = [0.07, 0.27] increase in OOP spending for all non-SUD/CVD services, a 21.1% (95% CI = [0.11, 0.31]) increase in OOP spending for all SUD-specific services, and a 13.1% (95% CI = [0.04, 0.23]) increase in OOP spending for all CVD-specific services. HDHP offer was also associated with a significant increase in OOP spending on non-SUD/CVD-specific medications and SUD-specific medications, but not CVD-specific medications. Conclusions: This study suggests that while HDHPs do not change overall levels of annual spending among enrollees with comorbid CVD and SUD, they may increase the financial burden of healthcare services by raising OOP costs, which could negatively impact this high-need and high-utilization population. [ABSTRACT FROM AUTHOR]

Background: Due to the progressive deterioration of motor, cognitive, and psychological function, individuals with Huntington's disease (HD) rely heavily on family caregivers, including children in the home. This "young carer" role can result in responsibilities that are inappropriate for the child's age and abilities. Also referred to as parentification, this experience can result in both positive and negative outcomes for the child, spanning multiple domains of health and well-being. Objective: To explore the manifestation of parentification among young carers of a parent with HD. Method: Directed content analysis, guided by a literature-derived framework of parentification, was utilized for this qualitative study. Participants included 28 young carers (mean age of 16.6 (± 2.6)) who self-identified as engaging in caregiving activities related to HD with the majority providing care for 1–3 years (53.6%)- averaging 25.4 h of care per week. Results: Three main themes with subthemes emerged: (1) being a young carer [perceptions of caregiving, learning to be a caregiver, caregiver burden, coping], (2) living with a new normal (school and friends, feeling unheard/alone, support system, personal growth), and (3) facing HD as a young carer (stigma and isolation, parent/child relationship, end of life, genetic risk). Conclusions: Young carers in the context of HD experience many attributes and consequences of parentification generally present among young carers of ill parents. However, HD specific findings emerged from this study that can be used to inform clinicians and direct future research aimed at guiding policy and developing tailored support services. [ABSTRACT FROM AUTHOR]

Adverse effects of obesity on reproduction are believed in part due to diet related factors leading to hyperlipidemia and hyperinsulinemia. It is unknown whether administration of a low fat eating plan, regardless of weight loss, will improve reproductive axis function in women with obesity. To develop an acceptable and feasible low fat eating plan for a diverse group of reproductive aged women with obesity. Focus groups to determine preferences and barriers to a planned dietary intervention providing very low fat (22% daily calories from fat) eucaloric food to control fat exposure, but not cause weight loss. Logistics of the intervention and monitoring over three menstrual cycles were discussed. Eighteen women enrolled into 4 different focus groups both live and video, 2 at the University of Colorado and 2 at the Morehouse School of Medicine. All participants expressed interest in implementing a low fat dietary intervention and were further interested in instruction on how to maintain healthy eating habits for future fertility. Provision of ethnically appropriate foods, social support to avoid lapses, and tasty alternatives to high fat foods were considered ideal aspects of a feasible intervention. Incentives and graduated compensation for adherence were considered desirable features. Women with obesity are interested in implementing dietary interventions that may improve their health and fertility. Given the diversity of responses based upon the demographics of our sample, it is important to assess geographical and cultural preferences prior to implementing of a dietary strategy. [ABSTRACT FROM AUTHOR]

Community violence and crime are significant public health problems with serious and lasting effects on young people, families, and communities. This violence and crime have significant ripple effects, affecting not just those who are directly physically injured, but also those who witness violent episodes, those who have friends or loved ones killed or injured, and those who must everyday navigate streets that they know have been frequent sites of serious violence and crime. The current study presents evidence of the impact that a data-driven, collective impact approach — the Communities that Care prevention system — can have on violence and crime outcomes within a large urban, high-burden community. Established as one of the national Youth Violence Prevention Centers (YVPC) funded by the Centers for Disease Control and Prevention, the Chicago Center for Youth Violence Prevention is among the first to implement the CTC approach in a large, urban community. The current study's findings show reductions in violence (i.e., aggravated assaults and robberies) in the Bronzeville community, compared to similar communities in Chicago. [ABSTRACT FROM AUTHOR]

Prevention science has increasingly turned to integrative data analysis (IDA) to combine individual participant-level data from multiple studies of the same topic, allowing us to evaluate overall effect size, test and model heterogeneity, and examine mediation. Studies included in IDA often use different measures for the same construct, leading to sparse datasets. We introduce a graph theory method for summarizing patterns of sparseness and use simulations to explore the impact of different patterns on measurement bias within three different measurement models: a single common factor, a hierarchical model, and a bifactor model. We simulated 1000 datasets with varying levels of sparseness and used Bayesian methods to estimate model parameters and evaluate bias. Results clarified that bias due to sparseness will depend on the strength of the general factor, the measurement model employed, and the level of indirect linkage among measures. We provide an example using a synthesis dataset that combined data on youth depression from 4146 youth who participated in 16 randomized field trials of prevention programs. Given that different synthesis datasets will embody different patterns of sparseness, we conclude by recommending that investigators use simulation methods to explore the potential for bias given the sparseness patterns they encounter. [ABSTRACT FROM AUTHOR]

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As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of − 5.5 (− 6.5, − 3.5) points from baseline to 3-months follow-up (Z = − 2.6, p = 0.009, r = − 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care. [ABSTRACT FROM AUTHOR]

Purpose: Describe spirituality’s role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors. Methods: This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants’ lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2–5 years ago were virtually recruited for participation. Participants completed virtual semi-structured interviews about their experiences with hope during cancer treatments and cancer survivorship and prepared narratives about their experiences. Thematic analyses were iteratively performed across the data set to identify final themes. Results: Ten Hispanic AYA cancer survivors (mean age 30.2, SD = 4.5) years participated in this pilot study. Seven participants (70%) were female, and three participants (30%) were male. Six participants (60%) experienced non-hematologic malignancies, and four participants (40%) experienced hematologic malignancies. Eight (80%) participants’ language preference was Spanish, while two (20%) participants’ language preference was English. The theme spirituality and subthemes living by faith, god as a resource, and spiritual gratitude were identified as concepts participants linked to their conceptualization of hope during cancer treatment and survivorship. Conclusions: Hope and spirituality may be conceptually linked to coping behaviors among Hispanic AYA cancer survivors. Hope through faith may be a learned spiritual value in Hispanic AYAs and might play a role in their spiritual and cognitive development. Further research is needed to explore the potentially protective value of hope and spirituality for the Hispanic AYA population. [ABSTRACT FROM AUTHOR]

Immunogenicity evaluation is a critical part of drug development. Regulatory guidelines from multiple health agencies provide recommendations for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity in clinical trials. These recommendations primarily describe an ADA method run in one bioanalytical laboratory supporting a biotherapeutic molecule; however, there are increasing instances that may necessitate the support of the ADA method being run in more than one laboratory. A program can rapidly expand into multiple clinical studies within one or multiple countries, where the most appropriate way to support the program is by having multiple laboratories perform ADA sample analysis. In addition, there may be certain country-specific challenges that may make it infeasible to transport samples outside of the country for analysis. China for example has a lengthy sample exportation process that has potential to negatively impact study timelines. If multiple laboratories analyze samples using the same ADA method, comparable method performance should be established. Here, we describe a three-way assessment of ADA assay comparability between two US-based bioanalytical laboratories and one based in China. [ABSTRACT FROM AUTHOR]

Science centers and museums are uniquely positioned to spark climate action. In this commentary, we describe opportunities to further increase the field's impact through research on the psychological states that drive action and public engagement approaches for sparking those states. We also introduce Seeding Action, an initiative led by the Association of Science and Technology Centers to address the opportunities for cross-museum research and coordination. [ABSTRACT FROM AUTHOR]

Rapid urbanization and escalating climate change impacts have heightened stormwater-related concerns (e.g., pluvial flooding) in cities. Understanding catchment dynamics and characteristics, including precise catchment mapping, is essential to accurate surface water monitoring and management. Traditionally, topography is the primary data set used to model surface water flow dynamics in undisturbed natural landscapes. However, urban systems also contain stormwater drainage infrastructure, which can alter catchment boundaries and runoff behavior. Acknowledging both natural and built environmental influences, this study introduces three GIS-based approaches to enhance urban catchment mapping: (1) Modifying DEM elevations at inlet locations; (2) Adjusting DEM elevations along pipeline paths; (3) Applying the QGRASS plug-in to systematically incorporate infrastructure data. Our evaluation using the geographical Friedman test (p > 0.05) and Dice Similarity Coefficient (DSC = 0.80) confirms the statistical and spatial consistency among the studying methods. Coupled with onsite flow direction validation, these results support the feasibility and reliability of integrating elements of nature and built infrastructure in urban catchment mapping. The refined mapping approaches explored in this study offer improved and more accurate and efficient urban drainage catchment zoning, beyond using elevation and topographic data alone. Likewise, these methods bolster predictive stormwater management at catchment scales, ultimately strengthening urban stormwater and flooding resilience. [ABSTRACT FROM AUTHOR]

Handling potatoes individually or collectively in packages can create opportunities for potatoes to develop quality defects including blackspot and shatter bruise. Three trials were conducted to examine how handling packaged potatoes can influence the risk for physical damage including shatter and blackspot bruise. An impact recording device was used to record peak acceleration (max g-force) in common fresh market packaging options (boxes or bales) at four drop heights (15 to 91 cm) on to three different surface types. When boxed potatoes were dropped onto concrete or a plastic slip, the potatoes on the bottom of the box had the highest risk of damage (greater than 100 g-force). When drop heights were lowered, or when cushioning material was added to hard surfaces (e.g., wooden pallet on top of concrete floor), the risk for impact damage was decreased throughout the box. When palletizing boxed potatoes, the risk of bruise decreased after the first layer was stacked on the pallet. Drop heights need to be below 15 cm, especially when making the first layer in a palletized stack of packaged potatoes to reduce potential bruising. The risk of high peak accelerations was not seen in the dropped or stationary bales for any of the drop heights examined. This study provided information for educating personnel on handling packaged potatoes and determining situations in which robotic stacking equipment needs to be adjusted to lower drop heights of packaged potatoes. [ABSTRACT FROM AUTHOR]

Policy implementation is a key component of scaling effective chronic disease prevention and management interventions. Policy can support scale-up by mandating or incentivizing intervention adoption, but enacting a policy is only the first step. Fully implementing a policy designed to facilitate implementation of health interventions often requires a range of accompanying implementation structures, like health IT systems, and implementation strategies, like training. Decision makers need to know what policies can support intervention adoption and how to implement those policies, but to date research on policy implementation is limited and innovative methodological approaches are needed. In December 2021, the Johns Hopkins ALACRITY Center for Health and Longevity in Mental Illness and the Johns Hopkins Center for Mental Health and Addiction Policy convened a forum of research experts to discuss approaches for studying policy implementation. In this report, we summarize the ideas that came out of the forum. First, we describe a motivating example focused on an Affordable Care Act Medicaid health home waiver policy used by some US states to support scale-up of an evidence-based integrated care model shown in clinical trials to improve cardiovascular care for people with serious mental illness. Second, we define key policy implementation components including structures, strategies, and outcomes. Third, we provide an overview of descriptive, predictive and associational, and causal approaches that can be used to study policy implementation. We conclude with discussion of priorities for methodological innovations in policy implementation research, with three key areas identified by forum experts: effect modification methods for making causal inferences about how policies' effects on outcomes vary based on implementation structures/strategies; causal mediation approaches for studying policy implementation mechanisms; and characterizing uncertainty in systems science models. We conclude with discussion of overarching methods considerations for studying policy implementation, including measurement of policy implementation, strategies for studying the role of context in policy implementation, and the importance of considering when establishing causality is the goal of policy implementation research. [ABSTRACT FROM AUTHOR]

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.A high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients with non-small cell lung cancer treated with atezolizumab plus tiragolumab, but not with atezolizumab alone. [ABSTRACT FROM AUTHOR]

Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury occurring because of an infection, most commonly with group A beta-hemolytic streptococcus in children. C3 glomerulopathy (C3G) is a distinct clinicopathological entity occurring secondary to dysregulation of alternate complement pathway encompassing both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). While most patients with PIGN attain complete remission with normalized complement levels by 6–8 weeks after presentation, patients with C3G continue to have hypocomplementemia with high rates of progressive kidney disease. Here, we report a patient diagnosed with dense deposit disease after his initial presentation with PIGN three years prior. While current literature continues to explore the overlapping and distinguishing features of PIGN and C3G, including how underlying defects in the alternate complement pathway may commonly contribute to both diseases, this case further exemplifies the importance of recognizing the clinico-pathogenic features of PIGN and C3G in pediatric patients with glomerulonephritis. [ABSTRACT FROM AUTHOR]

Background: Two major factors that determine the efficiency of programs designed to mitigate greenhouse gases by encouraging voluntary changes in U.S. agricultural land management are the effect of land use changes on producers' profitability and the net sequestration those changes create. In this work, we investigate how the interaction of these factors produces spatial heterogeneity in the cost-efficiency of voluntary programs incentivizing tillage reduction and cover-cropping practices. We map county-level predicted rates of adoption for each practice with the greenhouse gas mitigation or carbon sequestration benefits expected from their use. Then, we use these bivariate maps to describe how the cost efficiency of agricultural mitigation efforts is likely to vary spatially in the United States. Results: Our results suggest the combination of high adoption rates and large reductions in net emissions make reduced tillage programs most cost efficient in the Chesapeake Bay watershed or the Upper Mississippi and Lower Missouri sub-basins of the Mississippi River. For programs aiming to reduce net emissions by incentivizing cover-cropping, we expect cost-efficiency to be greatest in the areas near the main stem of the Mississippi River within its Middle and Lower sections. Conclusions: Many voluntary agricultural conservation programs offer the same incentives across the United States. Yet spatial variation in profitability and efficacy of conservation practices suggest that these uniform approaches are not cost-effective. Spatial targeting of voluntary agricultural conservation programs has the potential to increase the cost-efficiency of these programs due to regional heterogeneity in the profitability and greenhouse gas mitigation benefits of agricultural land management practices across the continental United States. We illustrate how predicted rates of adoption and greenhouse gas sequestration might be used to target regions where efforts to incentivize cover-cropping and reductions in tillage are most likely to be cost -effective. [ABSTRACT FROM AUTHOR]

An ethical challenge arose when the parents of an adolescent girl living with severe intellectual disability requested for a permanent surgical intervention (hysterectomy) that would cause cessation of menstruation and reduce the possibility of pregnancy following nonconsensual sex. The family background was rural with poor access to extended family/community support, financial and social welfare resources. The parental distress was real with the adolescent incompetent to give informed consent. Is a non-therapeutic hysterectomy in an adolescent living with severe intellectual disability ethical? Views of a pediatrician, adolescent specialist, nurse, and an ethicist referring to literature suggesting an approach to an ethical decision are discussed herein. [ABSTRACT FROM AUTHOR]

The tripartite ATP-independent periplasmic (TRAP) transporters use an extra cytoplasmic substrate binding protein (SBP) to transport a wide variety of substrates in bacteria and archaea. The SBP can adopt an open- or closed state depending on the presence of substrate. The two transmembrane domains of TRAP transporters form a monomeric elevator whose function is strictly dependent on the presence of a sodium ion gradient. Insights from experimental structures, structural predictions and molecular modeling have suggested a conformational coupling between the membrane elevator and the substrate binding protein. Here, we use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from Haemophilus influenzae in different conformational states. The SBP, HiSiaP, is locked in its substrate-bound form and the transmembrane elevator, HiSiaQM, is locked in either its assumed inward- or outward-facing states. We characterize the disulfide-locked constructs and use single-molecule total internal reflection fluorescence (TIRF) microscopy to study their interactions. Our experiments demonstrate that the SBP and the transmembrane elevator are indeed conformationally coupled, meaning that the open and closed state of the SBP recognize specific conformational states of the transporter and vice versa. Tripartite ATP-independent periplasmic (TRAP) transporters use an extra substrate binding protein to transport a variety of substrates in bacteria and archaea. Here the authors use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from H. influenzae in different conformational states for characterisation. [ABSTRACT FROM AUTHOR]

The historic momentum from national conversations on the roots and current impacts of racism in the USA presents an incredible window of opportunity for prevention scientists to revisit how common theories, measurement tools, methodologies, and interventions can be radically re-envisioned, retooled, and rebuilt to dismantle racism and promote equitable health for minoritized communities. Recognizing this opportunity, the NIH-funded Prevention Science and Methodology Group (PSMG) launched a series of presentations focused on the role of Prevention Science to address racism and discrimination guided by a commitment to social justice and health equity. The current manuscript aims to advance the field of Prevention Science by summarizing key issues raised during the series' presentations and proposing concrete research priorities and steps that hold promise for promoting health equity by addressing systemic racism. Being anti-racist is an active practice for all of us, whether we identify as methodologists, interventionists, practitioners, funders, community members, or an intersection of these identities. We implore prevention scientists and methodologists to take on these conversations with us to promote science and practice that offers every life the right to live in a just and equitable world. [ABSTRACT FROM AUTHOR]

Background: Inflammation suppresses cytochrome P450 (CYP) enzyme activity, and single-dose interleukin 6 receptor antagonists (anti-IL-6R) reverse this effect. Here, we assess the impact of continuous anti-IL-6R therapy in patients with rheumatoid arthritis. Methods: In a clinical pharmacokinetic trial, the Basel cocktail was administered before and after 3 and 12 weeks of anti-IL-6R therapy to assess CYP enzyme activity (registered in the ClinicalTrials.gov database (identifier NCT04842981) on April 13th, 2021). In a retrospective study, the 4β-hydroxycholesterol/cholesterol ratio was measured as a biomarker for CYP3A4 activity before and after 3 and 6 months of anti-IL-6R therapy. The control group was patients initiating a tumor necrosis factor alfa (TNF-α) inhibitor. Results: In the clinical pharmacokinetic trial (n = 3), midazolam metabolic ratio (CYP3A4) was inconclusive due to the limited sample size. Midazolam AUC and Cmax indicate a weak impact on CYP3A4 activity after 3 weeks of anti-IL-6R therapy compared to baseline (AUC geometric mean ratio (GMR): 0.80, 95% CI: 0.64–0.99 and Cmax GMR: 0.58, 95% CI: 0.37–0.91), which returns to baseline levels after 12 weeks of therapy (AUC GMR 1.02, 95% CI: 0.72–1.46 and Cmax GMR 1.03, 95% CI 0.72–1.47). No effect on the 4β-hydroxycholesterol/cholesterol ratio was observed in the retrospective study. Conclusion: Based on sparse data from three patients, continuous anti-IL-6R therapy seems to cause an acute but transient increase in CYP3A4 activity in rheumatoid arthritis patients, which may be due to a normalization of the inflammation-suppressed CYP activity. Further studies are warranted to understand the mechanism behind this putative transient effect. Trial registration Registered in the ClinicalTrials.gov database (identifier NCT04842981) on April 13th, 2021. [ABSTRACT FROM AUTHOR]

The current special issue of Prevention Science indicates that momentum in using individual participant data (IPD) and integrative data analysis (IDA) to combine and synthesize findings in prevention science has accelerated over the past decade. In this commentary, we focus on two general themes involving methods for harmonizing measures and findings of effect heterogeneity. We describe methods for harmonization as retrospective psychometrics, requiring that we attend to the assumptions necessary for accurate measurement, but adjust our methods given the constraints of working with existing datasets that often involve different measures in different studies. We point to novel approaches for increasing confidence that semantic matching and empirical modeling used in these studies will yield accurate and valid measurements that can be combined in IDA. We also review findings about effect heterogeneity, emphasizing the importance of using etiologic and action theories to identify and evaluate sources of such effects. We note that all of the papers in this issue deserve careful attention, as they illustrate how prevention scientists are approaching the complexities of IDA and exploring novel methods for overcoming its challenges. [ABSTRACT FROM AUTHOR]

Background: The young generation of surgeons sets new requirements for educational and working conditions. This is frequently interpreted as a lack of motivation to perform; however, instead there is a claim for high-quality training with the aim of acquiring competence in the operative and perioperative setting as well as for responsible working time models. Objective: Aim of this article is to present expectations of surgical residents regarding residency training under current influencing factors, such as a high workload, the new training regulations or expected changes in the hospital landscape and to identify options for optimizing training and working conditions. Material and methods: In addition to an extensive literature search, this article is based on published opinions and survey results as well as lectures and discussions at congresses held in the past year. Results and discussion: To ensure a modern high-quality education and to maintain enthusiasm for surgery, the need for adjustments and innovation must be recognized and long-requested modifictions to established structures must be implemented. Flexible working models, the structured and transparent implementation of surgical residency training and modern training units, long-term planning of training curricula and new personnel structures with an expansion of teaching and feedback culture are options for improvement. [ABSTRACT FROM AUTHOR]

Nanomaterials (NMs) are nanoscale materials of different shapes that are made of a variety of materials such as carbon, silicon, and transition metals. Wastewater treatment plants and nano-enabled consumer products have been identified as major sources of nanomaterials in the environment. Findings from many research studies revealed nanomaterials to be toxic to non-targeted species. Despite presenting an ecological risk to the environment and human health, little is known about the occurrence, formation, transport, and environmental impacts, owing to limited regulated quantitative and sensitive techniques for their assessment. More also, the realisation of nanomaterials' impact on the environment depends on emerging analytical methods. Therefore, it is paramount to continuously develop and optimise analytical methods that are promising to sensitively detect and quantify the nanomaterials in trace and ultra-trace levels in the environment. In this review, we discuss engineered metal/carbonaceous nanomaterials; production, pathways, fate, impact, toxicity, and their analytical methods of detection and quantification from the current literature. [ABSTRACT FROM AUTHOR]

Ocrelizumab (OCREVUS®) is a humanized anti-CD20 monoclonal antibody approved for the treatment of adult patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). Here, we discuss the strategic and technical considerations needed to develop a robust antibody-dependent cellular cytotoxicity (ADCC)-based neutralizing antibody (NAb) assay to detect anti-ocrelizumab NAb in patients enrolled in the ocrelizumab registered clinical trials. The NAb detection assay consisted of a two-tier assay that included a screening assay and a confirmation assay. In the screening assay, patient samples were analyzed in the presence of ocrelizumab. Samples that tested positive in the screening assay were subsequently analyzed in the confirmatory assay where another anti-CD20 mAb, obinutuzumab, was replaced by ocrelizumab, to verify NAb specificity. Both assays utilized MEC-2 cells, a chronic B cell leukemia cell line, pre-labeled with calcein AM as the target cells, and natural killer (NK) cells engineered to stably express Fc gamma receptor IIIa_ F158 as effector cells. Both cell lines were prepared to be thaw-and-use cells. The NAb assay measures fluorescence from the calcein AM released into the assay media upon the lysis of target cells by ADCC in the presence of ocrelizumab or obinutuzumab. Our validated NAb assay showed a relative sensitivity of 743 ng/mL and can detect 1500 ng/mL of a surrogate positive control antibody in the presence of 1500 ng/mL ocrelizumab. This ADCC assay is the first reported NAb assay that directly measures target cell lysis by using thaw-and-use target and effector cells simultaneously. [ABSTRACT FROM AUTHOR]

Airborne laser scanners (ALS) are used to map the sea-ice surface at sub-meter resolution. We conducted 64 flights over the Arctic sea ice between September 2019 and September 2020 during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition to measure sea-ice surface elevation. The flights ranged from repeated, local-scale 5 × 5 km2 floe grid surveys to regional-scale transects more than 100 km long. We provide data at different processing levels: geolocated elevation point clouds and gridded segments of elevation and freeboard with a spatial resolution of 0.5 m. The latter product is corrected for atmospheric backscatter, sea-ice drift, and offset in elevation due to degraded INS/GNSS solutions > 85° N. For floe grid surveys, all data are combined to merged two-dimensional elevation maps. Other provided parameters include laser reflectance and echo width. The presented data offer a unique possibility to study the temporal evolution, spatial distribution, and variability of the snow and sea-ice surface and their properties in addition to validating satellite products. [ABSTRACT FROM AUTHOR]

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization." [ABSTRACT FROM AUTHOR]

Purpose of Review: The number of older adults with cancer relying on support from caregivers continues to increase. Health disparities in older adults with cancer often extend to their caregivers. This review aims to assess the state of cancer caregiving research in historically underrepresented diverse populations and provide recommendations for future research and policy. Recent Findings: Research on caregivers of older adults with cancer from diverse backgrounds has primarily been descriptive. Health disparities for historically underrepresented caregivers (LGBTQ + , BIPOC, rural, young adults, youth) exist across several dimensions (e.g., financial, mental, and physical health, and access to caregiver support). Few published studies have closely examined the unique experiences of these caregivers nor provided culturally appropriate tailored interventions. Summary: Health equity research within caregiving populations is in its infancy. Priorities for future work should focus on identifying modifiable targets for intervention, changing systems-level processes in acknowledging and supporting caregivers, and creating policies that reduce financial inequities of caregiving. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit hyperactivity disorder is a common disorder that affects both children and adults. However, for adults, little is known about ADHD-attributable medical expenditures. Objective: To estimate the medical expenditures associated with ADHD, stratified by age, in the US adult population. Design: Using a two-part model, we analyzed data from Medical Expenditure Panel Survey for 2015 to 2019. The first part of the model predicts the probability that individuals incurred any medical costs during the calendar year using a logit model. The second part of the model estimates the medical expenditures for individuals who incurred any medical expenses in the calendar year using a generalized linear model. Covariates included age, sex, race/ethnicity, geographic region, Charlson comorbidity index, insurance, asthma, anxiety, and mood disorders. Participants: Adults (18 +) who participated in the Medical Expenditure Panel Survey from 2015 to 2019 (N = 83,776). Main Measures: Overall and service specific direct ADHD-attributable medical expenditures. Key Results: A total of 1206 participants (1.44%) were classified as having ADHD. The estimated incremental costs of ADHD in adults were $2591.06 per person, amounting to $8.29 billion nationally. Significant adjusted incremental costs were prescription medication ($1347.06; 95% CI: $990.69–$1625.93), which accounted for the largest portion of total costs, and office-based visits ($724.86; 95% CI: $177.75–$1528.62). The adjusted incremental costs for outpatient visits, inpatient visits, emergency room visits, and home health visits were not significantly different. Among older adults (31 +), the incremental cost of ADHD was $2623.48, while in young adults (18–30), the incremental cost was $1856.66. Conclusions: The average medical expenditures for adults with ADHD in the US were substantially higher than those without ADHD and the incremental costs were higher in older adults (31 +) than younger adults (18–30). Future research is needed to understand the increasing trend in ADHD attributable cost. [ABSTRACT FROM AUTHOR]

Gear hobbing is a well-established manufacturing process for cylindrical spur gears. The cutting edge of a hobbing tool is, among others, characterized by the cutting edge radius and the form-factor K. The magnitude of these parameters is ideally chosen based on the machining conditions given by the workpiece and cutting material and the cutting parameters as well as the gear and tool geometry. However, the influence of the cutting edge geometry on tool life and wear behavior is hardly known, which complicates an optimized tool design. Furthermore, the preparation process regarding the coating thickness distribution on the wear behavior is equally relevant. Therefore, the objective was to identify the influence of the cutting edge radius, the form-factor K, and the preparation process on the wear behavior of gear hobbing tools made of powder metallurgical high-speed steel (PM-HSS). Fly-cutting trials were performed as an analogy process for gear hobbing in order to study the wear behavior and identify the respective tool lives. The trials indicated that the form-factor K influences the wear behavior, while a variation of the cutting edge radius did not have a significant effect. A homogenous coating thickness could extend the tool life significantly. [ABSTRACT FROM AUTHOR]

While there is evidence for an acceleration in global mean sea level (MSL) since the 1960s, its detection at local levels has been hampered by the considerable influence of natural variability on the rate of MSL change. Here we report a MSL acceleration in tide gauge records along the U.S. Southeast and Gulf coasts that has led to rates (>10 mm yr−1 since 2010) that are unprecedented in at least 120 years. We show that this acceleration is primarily induced by an ocean dynamic signal exceeding the externally forced response from historical climate model simulations. However, when the simulated forced response is removed from observations, the residuals are neither historically unprecedented nor inconsistent with internal variability in simulations. A large fraction of the residuals is consistent with wind driven Rossby waves in the tropical North Atlantic. This indicates that this ongoing acceleration represents the compounding effects of external forcing and internal climate variability. Sea level rise along the U.S. Southeast and Gulf Coast has accelerated since 2010 due to changes in steric expansion and the ocean's circulation. The acceleration represents the compounding effects of external forcing and natural climate variability. [ABSTRACT FROM AUTHOR]

Objectives: Previous research has investigated potential synergies between classic psychedelics and meditation practice, but relatively little remains known about the relationship between classic psychedelic experiences and engagement with meditation practice. The purpose of this study was to investigate associations between classic psychedelic experiences and engagement with two popular types of meditation: mindfulness meditation and loving-kindness or compassion meditation. Method: This retrospective, population-based observational study included 2822 respondents aged 18 years or older in the United States. Using covariate-adjusted regression models, this study examined associations of classic psychedelic experiences with current practice of mindfulness meditation and loving-kindness or compassion meditation. Results: In covariate-adjusted regression models, lifetime classic psychedelic use was associated with a higher frequency of current mindfulness meditation practice but not current loving-kindness or compassion meditation practice. Both psychological insight and "ego dissolution" were associated with a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice. Notably, when psychological insight and "ego dissolution" were entered into the regression model simultaneously, only greater psychological insight was associated with having a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice. Conclusions: Although the findings in this study cannot demonstrate causality, they suggest that classic psychedelic experiences may exert a positive effect on the cultivation and maintenance of health-related behaviors such as regular meditation practice, with psychological insight appearing to be a stronger predictor than "ego dissolution." Preregistration: This study was not preregistered. [ABSTRACT FROM AUTHOR]

Using environmental DNA (eDNA) to monitor biodiversity in aquatic environments is becoming an efficient and cost-effective alternative to other methods such as visual and acoustic identification. Until recently, eDNA sampling was accomplished primarily through manual sampling methods; however, with technological advances, automated samplers are being developed to make sampling easier and more accessible. This paper describes a new eDNA sampler capable of self-cleaning and multi-sample capture and preservation, all within a single unit capable of being deployed by a single person. The first in-field test of this sampler took place in the Bedford Basin, Nova Scotia, Canada alongside parallel samples taken using the typical Niskin bottle collection and post-collection filtration method. Both methods were able to capture the same aquatic microbial community and counts of representative DNA sequences were well correlated between methods with R 2 values ranging from 0.71–0.93. The two collection methods returned the same top 10 families in near identical relative abundance, demonstrating that the sampler was able to capture the same community composition of common microbes as the Niskin. The presented eDNA sampler provides a robust alternative to manual sampling methods, is amenable to autonomous vehicle payload constraints, and will facilitate persistent monitoring of remote and inaccessible sites. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that rates of occupational injuries in the US are decreasing. As several different occupational injury surveillance systems are used in the US, more detailed investigation of this trend is merited. Furthermore, studies of this decrease remain descriptive and do not use inferential statistics. The aim of this study was to provide both descriptive and inferential statistics of temporal trends of occupational injuries treated in US emergency departments (EDs) for 2012 to 2019. Methods: Monthly non-fatal occupational injury rates from 2012 to 2019 were estimated using the national electronic injury surveillance system—occupational supplement (NEISS-Work) dataset, a nationally representative sample of ED-treated occupational injuries. Rates were generated for all injuries and by injury event type using monthly full-time worker equivalent (FTE) data from the US Current Population Survey as a denominator. Seasonality indices were used to detect seasonal variation in monthly injury rates. Trend analysis using linear regression adjusted for seasonality was conducted to quantify changes in injury rates from 2012 to 2019. Results: Occupational injuries occurred at an average rate of 176.2 (95% CI = ± 30.9) per 10,000 FTE during the study period. Rates were highest in 2012 and declined to their lowest level in 2019. All injury event types occurred at their highest rate in summer months (July or August) apart from falls, slips, and trips, which occurred at their highest rate in January. Trend analyses indicated that total injury rates decreased significantly throughout the study period (− 18.5%; 95% CI = ± 14.5%). Significant decreases were also detected for injuries associated with contact with foreign object and equipment (− 26.9%; 95% CI = ± 10.5%), transportation incidents (− 23.2%; 95% CI = ± 14.7%), and falls, slips, and trips (− 18.1%; 95% CI = ± 8.9%). Conclusions: This study supports evidence that occupational injuries treated in US EDs have decreased since 2012. Potential contributors to this decrease include increased workplace mechanization and automation, as well as changing patterns in US employment and health insurance access. [ABSTRACT FROM AUTHOR]

Background: Effective and efficient implementation of the Collaborative Care Model (CoCM) for depression and anxiety is imperative for program success. Studies examining barriers to implementation often omit patient perspectives. Objectives: To explore experiences and attitudes of eligible patients referred to CoCM who declined participation or were unable to be reached, and identify implementation barriers to inform strategies. Design: Convergent mixed-methods study with a survey and interview. Participants: Primary care patients at an academic medical center who were referred to a CoCM program for anxiety and depression by their primary care clinician (PCC) but declined participation or were unable to be reached by the behavioral health care manager to initiate care (n = 80). Interviews were conducted with 45 survey respondents. Main Measures: Survey of patients' referral experiences and behavioral health preferences as they related to failing to enroll in the program. Interview questions were developed using the Consolidated Framework for Implementation Research version 2.0 (CFIR 2.0) to identify implementation barriers to enrollment. Key Results: Survey results found that patients were uncertain about insurance coverage, did not understand the program, and felt services were not necessary. Referred patients who declined participation were concerned about how their mental health information would be used and preferred treatment without medication. Men agreed more that they did not need services. Qualitative results exhibited a variety of implementation determinants (n = 23) across the five CFIR 2.0 domains. Barriers included mental health stigma, perceiving behavioral health as outside of primary care practice guidelines, short or infrequent primary care appointments, prioritizing physical health over mental health, receiving inaccurate program information, low motivation to engage, and a less established relationship with their PCC. Conclusions: Multiple barriers to enrollment led to failing to link patients to care, which can inform implementation strategies to address the patient-reported experiences and concerns. [ABSTRACT FROM AUTHOR]

Handling potatoes can create opportunities to develop bruise resulting in quality defects that reduce the acceptability for purchase among retailers, processors, and consumers. Understanding cultivar specific bruise susceptibility can aid in developing appropriate bruise management programs. A two-year trial was conducted to examine bruise susceptibility in six commercially grown russet cultivars as affected by impact height. Russet Burbank, Ranger Russet, Clearwater Russet, Dakota Russet, Teton Russet, and Umatilla Russet were impacted using a device that dropped a 100 g steel weight from 8, 18, or 30 cm height to deliver a uniform impact on both the bud and stem end of a stationary tuber. Blackspot bruise incidence, severity and depth, and shatter bruise incidence were evaluated. Blackspot and shatter bruise were significantly influenced by impact height and tuber end in all cultivars. As impact height increased, blackspot bruise incidence, severity, depth, and shatter bruise incidence increased. There were no significant differences among cultivars or tuber ends in shatter bruise at the 8 cm impact height, but differences became evident at 18 and 30 cm impact heights. Overall, the bud end had lower blackspot bruise incidence, severity, and depth compared to the stem end for all cultivars, although the response difference between ends was dependent on cultivar. Clearwater Russet and Dakota Russet had the highest blackspot bruise incidence compared to other cultivars. Teton Russet had the lowest blackspot bruise incidence, severity rating, and depth among the six cultivars but had the highest shatter bruise incidence. This study provided insight on the importance of including more than one impact height to develop robust bruise susceptibility research protocols as well as develop cultivar-specific bruise management recommendations for the industry. [ABSTRACT FROM AUTHOR]

Purpose: A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [99mTc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. Methods: A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. Results: From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [99mTc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [11C]-methionine or [11C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56). Conclusion: [11C]-Methionine or [11C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA. [ABSTRACT FROM AUTHOR]

Introduction: Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. Methods: Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum für Krebsregisterdaten—ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. Results: A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07% were female and 36.93% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86% of cases (n = 152). A total of 49.34% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77% vs. 73.27%). Discussion: In this study, we observed an incidence of LAMN in 0.13% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up. [ABSTRACT FROM AUTHOR]

Many preventive trials randomize individuals to intervention condition which is then delivered in a group setting. Other trials randomize higher levels, say organizations, and then use learning collaboratives comprised of multiple organizations to support improved implementation or sustainment. Other trials randomize or expand existing social networks and use key opinion leaders to deliver interventions through these networks. We use the term contextually driven to refer generally to such trials (traditionally referred to as clustering, where groups are formed either pre-randomization or post-randomization — i.e., a cluster-randomized trial), as these groupings or networks provide fixed or time-varying contexts that matter both theoretically and practically in the delivery of interventions. While such contextually driven trials can provide efficient and effective ways to deliver and evaluate prevention programs, they all require analytical procedures that take appropriate account of non-independence, something not always appreciated. Published analyses of many prevention trials have failed to take this into account. We discuss different types of contextually driven designs and then show that even small amounts of non-independence can inflate actual Type I error rates. This inflation leads to rejecting the null hypotheses too often, and erroneously leading us to conclude that there are significant differences between interventions when they do not exist. We describe a procedure to account for non-independence in the important case of a two-arm trial that randomizes units of individuals or organizations in both arms and then provides the active treatment in one arm through groups formed after assignment. We provide sample code in multiple programming languages to guide the analyst, distinguish diverse contextually driven designs, and summarize implications for multiple audiences. [ABSTRACT FROM AUTHOR]

RO7297089, an anti-B-cell maturation antigen (BCMA)/CD16A bispecific tetravalent antibody, is being developed as a multiple myeloma (MM) therapeutic. This study characterized nonclinical pharmacokinetics (PK), pharmacodynamics (PD), soluble BCMA (sBCMA), and soluble CD16 (sCD16) changes following administration of RO7297089 to support clinical trials. Unbound and total RO7297089 concentrations were measured in cynomolgus monkeys. RO7297089 exhibited a bi-phasic systemic concentration-time profile, similar to a typical human immunoglobulin 1 antibody. Target engagement by RO7297089 led to a robust increase (~100-fold) in total systemic sBCMA levels and relatively mild increase (~2-fold) in total sCD16 levels. To describe the relationship of nonclinical PK/PD data, we developed a target-mediated drug disposition (TMDD) model that includes the systemic target engagement of membrane BCMA (mBCMA), sBCMA, membrane CD16 (mCD16), and sCD16. We then used this model to simulate the PK/PD relationship of RO7297089 in MM patients by translating relevant PK parameters and target levels, based on the literature and newly generated data such as baseline sCD16A levels. Our model suggested that the impact of TMDD on RO7297089 exposure may be more significant in MM patients due to significantly higher expression levels of both mBCMA and sBCMA compared to healthy cynomolgus monkeys. Based on model simulations, we propose more frequent dosing of RO7297089 compared to regular monthly frequency in the clinic at the beginning of treatment to ensure sustained target engagement. This study demonstrates a translational research strategy for collecting relevant nonclinical data, establishing a TMDD model, and using simulations from this model to inform clinical dose regimens. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown if foveal hypoplasia in full-term born children differs in structure and function from that observed in children born preterm. We compared macular structure and visual function in children with history of prematurity and full-term children diagnosed with foveal hypoplasia. Methods: We compared three groups of subjects (3–18 years old): (1) full-term hypoplasia (FH, n = 56, gestational age ≥ 36 weeks); (2) preterm hypoplasia (n = 57, gestational age ≤ 31 weeks, birth weight ≤ 1500 g); (3) control (n = 54), full-term normal. Using spectral-domain optical coherence tomography volume-scan images, macular structure within 3 mm of Early-Treatment-Diabetic-Retinopathy-Study circle was segmented. Total, inner, and outer foveal thickness of right eyes were compared. Foveal hypoplasia was graded according to the Leicester Grading System. Results: The mean total foveal thickness in micrometers was 263 ± 19 for the control, 299 ± 30 for the full-term hypoplasia, and 294 ± 28 for the preterm hypoplasia groups (F = 33, p < 0.001). Foveal inner retinal layer thickness differed among groups (p < 0.001), but not in the outer layers (p = 0.10). The full-term hypoplasia group had significantly thicker foveal inner layers (p < 0.05) and greater frequency of higher-grade hypoplasia than the preterm hypoplasia group. LogMAR visual acuity was worse in the full-term hypoplasia group (0.35 ± 0.36) than in the preterm hypoplasia group (0.19 ± 0.27, p < 0.001). Conclusion: Fovea was thicker in both hypoplasia groups. The full-term hypoplasia group is associated with more severe structure changes and poorer visual function than the preterm hypoplasia group. [ABSTRACT FROM AUTHOR]

We examine firm disclosure choice when information is received on a real-time, continuous basis. We use transaction-level credit and debit card sales for a sample of retail firms to construct a weekly measure of abnormal revenue for each firm. We validate the informativeness of this abnormal real-time revenue information, confirming its positive correlation with abnormal returns, unexpected revenue realizations, and management revenue forecast news. Using revenue forecasts, we find that firms are less likely to disclose abnormally negative news early in the quarter. As the quarter progresses, firms reduce their withholding of negative news. These results are consistent with impending earnings announcements disciplining managers to provide negative news. This pattern of initial withholding and then disclosure exists primarily in firms with high analyst coverage, high institutional ownership, or high litigation risk. Finally, we find increased insider stock sales in weeks with abnormally negative news and no firm disclosure. Overall, our study provides evidence of the informativeness of real-time information and manager discretion in its release. [ABSTRACT FROM AUTHOR]