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The three decades from 1940 through 1970 mark a turning point in the spatial scale of Black–White residential segregation in the United States compared with earlier years. We decompose metropolitan segregation into three components: segregation within the city, within the suburbs, and between the city and its suburbs. We then show that extreme levels of segregation were well established in most cities by 1940, and they changed only modestly by 1970. In this period, changes in segregation were greater at the metropolitan scale, driven by racially selective population growth in the suburbs. We also examine major sources of rising segregation, including region, metropolitan total, and Black population sizes, and indicators of redlining in the central cities based on risk maps prepared by the Home Owners Loan Corporation (HOLC) in the late 1930s. In addition to overall regional differences, segregation between the city and suburbs and within suburbia increased more in metropolitan areas with larger Black populations, but this relationship was found only in the North. In contrast to some recent theorizing, there is no association between preparation of an HOLC risk map or the share of city neighborhoods that were redlined and subsequent change in any component of segregation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo-HCT, the independent impact of donor-recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo-HCT between 2008-2018. Our objectives were to analyze the outcomes of allo-HCT based on the donor-recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo-HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05-1.29; p=0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77-0.90; p0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12-2.30, p=0.01). Relapse, acute graft versus host disease (GVHD) grades III-IV, and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non-relapse mortality. Our study demonstrates that donor-recipient ABO status is independently associated with survival and other post-transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia. This article is protected by copyright. All rights reserved.

Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation.We report the outcomes of BMT CTN 1502, a single-arm, phase 2 clinical trial done at academic bone marrow transplantation centres in the USA. Included patients were children and adults (75 years or younger) with severe aplastic anaemia that was refractory (fulfilment of severe aplastic anaemia disease criteria at least 3 months after initial immunosuppressive therapy) or relapsed (initial improvement of cytopenias after first-line immunosuppressive therapy but then a later return to fulfilment of severe aplastic anaemia disease criteria), adequate performance status (Eastern Cooperative Oncology Group score 0 or 1, Karnofsky or Lansky score ≥60%), and the presence of an eligible related haploidentical donor. The regimen used reduced-intensity conditioning (rabbit anti-thymocyte globulin 4·5 mg/kg in total, cyclophosphamide 14·5 mg/kg daily for 2 days, fludarabine 30 mg/mBetween May 1, 2017, and Aug 30, 2020, 32 patients with relapsed or refractory severe aplastic anaemia were enrolled from 14 centres, and 31 underwent bone marrow transplantation. The median age was 24·9 years (IQR 10·4-51·3), and median follow-up was 24·3 months (IQR 12·1-29·2). Of the 31 patients who received a transplant, 19 (61%) were male and 12 (39%) female. 13 (42%) patients were site-reported as non-White, and 19 (61%) were from under-represented racial and ethnic groups; there were four (13%) patients who were Asian, seven (23%) Black, one (3%) Hawaiian/Pacific Islander, and one (3%) more than one race, with seven (23%) patients reporting Hispanic ethnicity. 24 (77%) of 31 patients were alive with engraftment at 1 year, and one (3%) patient alive with autologous recovery. The 1-year overall survival was 81% (95% CI 62-91). The most common grade 3-5 adverse events (seen in seven or more patients) included seven (23%) patients with abnormal liver tests, 15 (48%) patients with cardiovascular changes (including sinus tachycardia, heart failure, pericarditis), ten (32%) patients with gastrointestinal issues, seven (23%) patients with nutritional disorders, and eight (26%) patients with respiratory disorders. Six (19%) deaths, due to disease and unsuccessful bone marrow transplantation, were reported after transplantation.Haploidentical bone marrow transplantation using this approach results in excellent overall survival with minimal GVHD in patients who have not responded to immunosuppressive therapy, and can expand access to bone marrow transplantation across all populations. In clinical practice, this could now be considered a standard approach for salvage treatment of severe aplastic anaemia. Attention to obtaining high cell doses (2·5 × 10US National Heart, Lung, and Blood Institute and US National Cancer Institute.

At the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors due to numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within one year following hematopoietic cell transplantation (HCT). We analyzed 1,543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6-months of the pandemic and compared them to 2,499 recipients of fresh allografts during the same 6-month period in 2019. On multivariable regression analysis, we observed no difference in OS (HR, 1.12; 95% CI: 0.98-1.28; P=0.09), non-relapse mortality (HR, 1.01; 95% CI: 0.84-1.22; P=0.89), graft-versus-host disease (GVHD), or GVHD-free, relapse-free survival (HR 1.03; 95% CI 0.93-1.14; P=0.58) in recipients of cryopreserved versus fresh allografts. Disease-free survival (DFS) was lower in the cryopreserved group (HR, 1.18; 95% CI: 1.05-1.33; P=0.006) due to a higher risk of relapse (HR, 1.21; 95% CI: 1.04-1.41; P=0.01). Primary graft failure was higher with cryopreservation (OR 1.48; 95% CI: 1.10-2.00; P=0.01) and the risk of chronic GVHD was lower (HR, 0.65; 95% CI: 0.50-0.84; P=0.001). In conclusion, while there was no negative impact of cryopreservation on OS, relapse was higher and DFS was lower. Fresh grafts are recommended as the pandemic related logistical hurdles resolve. Cryopreservation should be considered an option for patients when fresh grafts are not feasible.

Preschool-age children identified as at risk for later reading difficulties can benefit from supplemental, small-group emergent literacy intervention. As such interventions become commercially available and marketed to preschool programs, it is important to understand their impacts when implemented by intended end users under routine conditions. In this study, we examined the effects of the Nemours BrightStart! (NBS!) intervention on children’s emergent literacy skills when implemented by teachers and community aides in authentic preschool classrooms. We randomly assigned 98 classrooms to one of three conditions (NBS! teacher-implemented, NBS! community aide-implemented, or control). Children enrolled in these classrooms who met eligibility criteria and were identified as at risk via an early literacy screener ( n = 281) completed pretest and posttest emergent literacy assessments; those assigned to NBS! conditions received intervention from their classroom teacher or a community aide affiliated with a local kindergarten-readiness initiative. Intent-to-treat analyses showed no significant impacts of NBS! on any outcome, and an instrumental variable, as-treated approach showed one significant intervention effect on letter writing. Consequently, we did not replicate results of prior highly controlled efficacy trials. Findings have implications for revising the NBS! theory of change, conducting dosage and as-treated analyses, and moving research-based interventions toward scale-up.

PURPOSE Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

A common challenge in developmental research is the amount of incomplete and missing data that occurs from respondents failing to complete tasks or questionnaires, as well as from disengaging from the study (i.e., attrition). This missingness can lead to biases in parameter estimates and, hence, in the interpretation of findings. These biases can be addressed through statistical techniques that adjust for missing data, such as multiple imputation. Although this technique is highly effective, it has not been widely adopted by developmental scientists given barriers such as lack of training or misconceptions about imputation methods and instead utilizing default methods within software like listwise deletion. This manuscript is intended to provide practical guidelines for developmental researchers to follow when examining their data for missingness, making decisions about how to handle that missingness, and reporting the extent of missing data biases and specific multiple imputation procedures in publications.

We study the residential patterns of blacks and mulattoes in 10 Southern cities in 1880 and 1920. Researchers have documented the salience of social differences among African Americans in this period, partly related to mulattoes’ higher occupational status. Did these differences result in clustering of these two groups in different neighborhoods, and were mulattoes less separated from whites? If so, did the differences diminish in these decades after Reconstruction due a Jim Crow system that did not distinguish between blacks and mulattoes? We use geocoded census microdata for 1880 and 1920 to address these questions. Segregation between whites and both blacks and mulattoes was already high in 1880, especially at a fine spatial scale, and it increased sharply by 1920. In this respect, whites did not distinguish between these two groups. However, blacks and mulattoes were quite segregated from one another in 1880, and even more so by 1920. This pattern did not result from mulattoes’ moderately higher-class position. Hence, as the color line between whites and all non-whites was becoming harder, blacks and mulattoes were separating further from each other. Understanding what led to this pattern remains a key question about racial identities and racialization in the early twentieth century.

The extant literature on implementation fidelity has found mixed evidence for empirically establishing the dimensionality of implementation fidelity. The current study aims to add to this growing body of literature by examining implementation fidelity in a book-reading intervention for young children’s caregivers. Caregivers ( n = 291) implemented Sit Together and Read 2 (STAR 2) with their preschool-age children. These data indicated that implementation fidelity was determined to be a four-dimensional construct including adherence/dose, quality of delivery, participant responsiveness, and program differentiation. The main findings of this work are twofold: (a) implementation fidelity is a more complex construct than some previous descriptions, and (b) early childhood education research should aim to report on all aspects of implementation fidelity.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined. METHODS We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration. RESULTS The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm ( P = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; P = .003). The survival benefit was seen across all subgroups examined. CONCLUSION We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

Purpose Narrative skill represents a higher-level linguistic skill that shows incremental development in the preschool years. During these years, there are considerable individual differences in this skill, with some children being highly skilled narrators (i.e., precocious) relative to peers of their age. In this study, we explored the contribution of three lower-level language skills to a range of narrative abilities, from children performing below expected levels for their age to those performing much higher than the expected levels for their age. We speculated that individual differences in lower-level skills would contribute meaningfully to variability in narrative skills. Method Using a sample of 336 children between 3 and 6 years of age ( M = 4.27 years, SD = 0.65), both multiple regression and quantile regression approaches were used to explore how vocabulary, grammar, and phonological awareness account for variance in children's “narrative ability index” (NAI), an index of how children scored on the Narrative Assessment Protocol–Second Edition relative to the expected performance for their age. Results Multiple regression results indicated that lower-level language skills explained a significant amount of variance (approximately 13%) in children's NAI scores. Quantile regression results indicated that phonological awareness and vocabulary accounted for significant variance in children's NAI scores at lower quantiles. At the median quantile, vocabulary and grammar accounted for significant variance in children's NAI scores. For precocious narrators, only vocabulary accounted for a significant amount of variance in children's NAI scores. Conclusion Results indicate that lower-level language skills work in conjunction to support narrative skills at different ability levels, improving understanding of how lower-level language skills contribute across a spectrum of higher-level linguistic abilities.

For myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (alloHCT) is the only available curative therapy. The Blood and Marrow Transplant Clinical Trials Network study 1102 (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial based on matched donor availability in adults aged 50-75 with higher risk de novo MDS who were candidates for reduced-intensity conditioning (RIC) alloHCT. The primary analysis showed that those who received alloHCT had a survival benefit, but whether this is at the cost of worse quality of life (QOL) has not been described in detail. English- and Spanish-speaking trial participants completed the Functional Assessment of Cancer Therapy-General (FACT-G), the SF-36, and the EQ-5D, at enrollment, every 6 months until 24 months, and 36 months. We compared patient-reported outcome (PRO) scores between study arms using an inverse probability weighted-independent estimating equation (IPW-IEE) model. Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) enrolled at 34 centers. PRO completion rates were generally high at 65%-78%. The PRO trajectories for both arms were similar, with most decreasing or stable from baseline to 6 months and improving thereafter. Baseline PRO scores were the most consistent independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. For older adults with MDS, the survival advantage associated with donor availability and alloHCT did not come at the cost of worse QOL. These results should reassure older patients and clinicians who prefer a curative approach to treating MDS.

With the recent development of transplant-specific composite endpoints for evaluation of allogeneic hematopoietic cell transplantation (alloHCT) outcomes, the use of these novel endpoints is growing rapidly. Combining multiple endpoints into a single endpoint, these composite endpoints appear simple and can be used as a summary measure for overall effectiveness of an intervention. However, all component endpoints may not have equal clinical significance, and an intervention may not work proportionally in the same direction for all components of a composite endpoint. This may complicate the interpretation of results, particularly if there are opposing effects of differing component endpoints. We assess the benefits and limitations of various composite endpoints used in alloHCT studies recently and propose guidelines for their use and interpretation. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

This paper extends the understanding of the relation between ADHD and reading comprehension, through examining how this relation differs depending on the quantile an individual falls in for each. Samples from three twin projects around the United States were used (Florida Twin Project, Colorado component of International Longitudinal Twin Study of Early Reading Development, & Western Reserve Reading and Math Projects). Phenotypic analysis using quantile regression showed relations between ADHD related behaviors and reading comprehension to be stronger in the lower quantiles of reading comprehension in two of three samples. A new method was developed extending this analysis into the bivariate genetic space. Results of this quantile genetic analysis revealed that overlapping common environmental influences accounted for a larger proportion of variance in the lower quantiles of these variables in two of three samples. Finally, in all three samples the phenotypic relation was strongest when shared environmental influences accounted for a larger proportion of the overall variance.

With complex models becoming increasingly popular in the social sciences, many researchers have begun using latent variable modeling in multiple-steps, saving, estimating, or otherwise extracting factor scores from one confirmatory factor analysis (CFA) for use in a second inferential analysis. With two or more factors identified in a CFA, there exist few practical guidelines as to how researchers should proceed. In Study 1, we examine two common practices when CFAs have two or more factors: Fitting separate CFAs or allowing them to correlate in the model used for extraction. We provide a simulation study to demonstrate the bias introduced in each of the two approaches. In Study 2, we demonstrate that the between-factor correlation bias can be mitigated through the use of a different estimator; using ten Berge estimation shows near zero bias on the critical correlations between factors. Finally, we demonstrate this with an example dataset.

COVID-19 has significantly impacted the practice of hematopoietic cell transplantation (HCT) and likely affected outcomes of HCT recipients. Early reports document substantially higher case fatality rates for HCT recipients than seen in faced by the general population. Currently we do not have a clear picture of how much of this threat is present within the first year after HCT and how infection rates and outcomes vary with time after HCT. There are important because center-specific survival estimates for reporting purposes focus on 1-year post-HCT mortality. Transplantation centers have dramatically changed their practices in response to the pandemic. At many centers, quality assurance processes and procedures were disrupted, changes that likely affected team performance. Centers have been affected unevenly by the pandemic through time, location, and COVID-19 burdens. Assessment of center-specific survival depends on the ability to adjust for risk factors, such as COVID-19, that are outside center control using consistent methods so that team performance based on controllable risk factors can be ascertained. The Center for International Blood and Marrow Transplantation Research (CIBMTR) convened a working group for the 2020 Center Outcomes Forum to assess the impact of COVID-19 on both patient-specific risks and center-specific performance. This committee reviewed the factors at play and developed recommendations for a process to determine whether adjustments in the methodology to assess center-specific performance are needed.

The COVID-19 pandemic has resulted in the increased use of cryopreserved grafts for allogeneic hematopoietic cell transplantation (HCT). However, information about the effect of cryopreservation on outcomes for patients receiving allogeneic donor grafts is limited. We evaluated outcomes of HCT recipients who received either fresh or cryopreserved allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) grafts reported to the Center for International Blood and Marrow Transplant Research. A total of 7397 patients were included in the analysis. Recipients of cryopreserved graft were divided into 3 cohorts based on graft source: HLA-matched related PBSC donors (n = 1051), matched unrelated PBSC donors (n = 678), and matched related or unrelated BM donors (n = 154). These patients were propensity score matched with 5514 patients who received fresh allografts. The primary endpoint was engraftment. Multivariate analyses showed no significant increased risk of delayed engraftment, relapse, nonrelapse mortality (NRM), or survival with cryopreservation of BM grafts. In contrast, cryopreservation of related donor PBSC grafts was associated with decreased platelet recovery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68 to 0.78; P < .001) and an increased risk of grade II-IV (HR, 1.27; 95% CI, 1.09 to 1.48; P = .002) and grade III-IV (HR, 1.48; 95% CI, 1.19 to 1.84; P < .001) acute graft-versus-host disease. Cryopreservation of unrelated PBSC grafts was associated with delayed engraftment of neutrophils (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001) and platelets (HR, 0.61; 95% CI, 0.56 to 0.66; P < .001) as well as an increased risk of NRM (HR, 1.4; 95% CI, 1.18 to 1.66; P < .001) and relapse (HR, 1.32; 95% CI, 1.11 to 1.58; P = .002) and decreased progression-free survival (HR, 1.36; 95% CI, 1.20 to 1.55; P < .001) and overall survival (OS) (HR, 1.38; 95% CI, 1.22 to 1.58; P < .001). Reasons for cryopreservation were not routinely collected; however, in a subset of unrelated donor HCT recipients, the reason was typically a change in patient condition. Products cryopreserved for patient reasons were significantly associated with inferior OS in multivariate analysis (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). We conclude that cryopreservation is associated with slower engraftment of PBSC grafts, which may be associated with inferior transplantation outcomes in some patient populations. However, the small numbers in the cryopreserved BM cohort and the lack of information on the reason for cryopreservation in all patients suggests that these data should be interpreted with caution, particularly in the context of the risks associated with unexpected loss of a graft during the pandemic. Future analyses addressing outcomes when cryopreservation is universally applied are urgently required.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded ( Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681.