Can Peers Help Sustain the Positive Effects of an Early Childhood Mathematics Intervention?

Our study assessed whether the peer environment in kindergarten and first grade affected student learning following an early mathematics intervention. We leveraged longitudinal data from a cluster-RCT to examine whether math achievement in kindergarten (n = 1,218) and first grade (n = 1,126) was affected by either the share of high-achieving classmates or the proportion of classroom peers who received a preschool math curriculum intervention. Analyses indicated that exposure to treated peers in first grade, but not kindergarten, was significantly associated with small gains in end-of-year achievement. Some analyses also suggested that average peer math achievement was generally positively related to children's kindergarten and first-grade achievement across conditions, though these results were less robust. We did not find consistent evidence to suggest that the proportion of treated peers coincided with better teaching practices. Taken together, these findings suggest that classroom peer effects may play only a limited role in sustaining early intervention effects.

Investigating if high-quality kindergarten teachers sustain the pre-K boost to children's emergent literacy skill development in North Carolina.

This study tested the hypothesis that high-quality kindergarten teachers sustain and amplify the skill development of children who participated in North Carolina's NC Pre-K program during the previous year, compared to matched non-participants (N = 17,330; 42% African American, 40% Non-Hispanic White, 15% Hispanic; 51% male; Mage = 4.5 years at fall of pre-K). Kindergarten teacher quality was measured using a "value-added" approach. NC Pre-K participants outperformed non-participants in the fall of kindergarten (ß = .22) and 11% of this boost remained evident by the spring of kindergarten. Higher value-added teachers promoted the skill development of all children (ß = .30 in the spring) but did not differentially benefit the skill development of former NC Pre-K participants compared to non-participants.

A Phase-I pharmacokinetic, safety and food-effect study on flubentylosin, a novel analog of Tylosin-A having potent anti-Wolbachia and antifilarial activity.

BACKGROUND: The parasitic filariae responsible for onchocerciasis and lymphatic filariasis are host to an endosymbiotic bacterium, Wolbachia, which is essential to the fertility and development of the parasites. We performed a Phase-I pharmacokinetic, safety and food-effect study on single and multiple ascending doses of flubentylosin (ABBV-4083), a macrolide antibacterial with activity against Wolbachia, intended to sterilize and eliminate the parasites. METHODS: Seventy-eight healthy adults were exposed to flubentylosin; 36 were exposed to single ascending 40, 100, 200, 400 or 1000 mg doses; 12 received 1000 mg in the food-effect part; and 30 received multiple ascending daily doses of 100 mg for 7 days, 200 mg for 7 or 14 days, or 400 mg for 7 or 14 days. Twenty-two subjects received placebo. RESULTS: Maximum concentrations (Cmax) of flubentylosin were reached after 1-2 hours, with a half-life < 4 hours at doses ≤ 400 mg. Cmax and AUC increased in a more than dose-proportional manner, with similar exposure after multiple dose administration. The most frequently reported adverse events were nausea (8/78, 10%) and headache (6/78, 8%). Two subjects given a single dose of flubentylosin 1000 mg in the food-effect part experienced reversible asymptomatic ALT and AST elevations at Grade 2 or Grade 4, with no elevation in bilirubin, deemed related to study drug. The effect of food on exposure parameters was minimal. No treatment-related serious adverse events were reported. DISCUSSION: Flubentylosin 400 mg for 14 days was the maximum tolerated dose in this first-in-human, Phase-I study in healthy adults. Based on preclinical pharmacokinetic/pharmacodynamic modeling, flubentylosin 400 mg once daily for 7 or 14 days is expected to be an effective dose. A Phase-II, proof-of-concept study with flubentylosin using these regimens is currently ongoing in patients with onchocerciasis in Africa.

DOSE - Global data set of reported sub-national economic output.

Many phenomena of high relevance for economic development such as human capital, geography and climate vary considerably within countries as well as between them. Yet, global data sets of economic output are typically available at the national level only, thereby limiting the accuracy and precision of insights gained through empirical analyses. Recent work has used interpolation and downscaling to yield estimates of sub-national economic output at a global scale, but respective data sets based on official, reported values only are lacking. We here present DOSE - the MCC-PIK Database Of Sub-national Economic Output. DOSE contains harmonised data on reported economic output from 1,661 sub-national regions across 83 countries from 1960 to 2020. To avoid interpolation, values are assembled from numerous statistical agencies, yearbooks and the literature and harmonised for both aggregate and sectoral output. Moreover, we provide temporally- and spatially-consistent data for regional boundaries, enabling matching with geo-spatial data such as climate observations. DOSE provides the opportunity for detailed analyses of economic development at the subnational level, consistent with reported values.

Understanding Heterogeneity in the Impact of Public Preschool Programs.

We examine the North Carolina Pre-K (NC Pre-K) program to test the hypothesis that observed variation in effects resulting from exposure to the program can be attributed to interactions with other environmental factors that occur before, during, or after the pre-k year. We examine student outcomes in 5th grade and test interaction effects between NC's level of investment in public pre-k and moderating factors. Our main sample includes the population of children born in North Carolina between 1987 and 2005 who later attended a public school in that state, had valid achievement data in 5th grade, and could be matched by administrative record review (n = 1,207,576; 58% White non-Hispanic, 29% Black non-Hispanic, 7% Hispanic, 6% multiracial and Other race/ethnicity). Analyses were based on a natural experiment leveraging variation in county-level funding for NC Pre-K across NC counties during each of the years the state scaled up the program. Exposure to NC Pre-K funding was defined as the per-4-year-old-child state allocation of funds to a county in a year. Regression models included child-level and county-level covariates and county and year fixed effects. Estimates indicate that a child's exposure to higher NC Pre-K funding was positively associated with that child's academic achievement 6 years later. We found no effect on special education placement or grade retention. NC Pre-K funding effects on achievement were positive for all subgroups tested, and statistically significant for most. However, they were larger for children exposed to more disadvantaged environments either before or after the pre-k experience, consistent with a compensatory model where pre-k provides a buffer against the adverse effects of prior negative environmental experiences and protection against the effects of future adverse experiences. In addition, the effect of NC Pre-K funding on achievement remained positive across most environments, supporting an additive effects model. In contrast, few findings supported a dynamic complementarity model. Instrumental variables analyses incorporating a child's NC Pre-K enrollment status indicate that program attendance increased average 5th grade achievement by approximately 20% of a standard deviation, and impacts were largest for children who were Hispanic or whose mothers had less than a high school education. Implications for the future of pre-k scale-up and developmental theory are discussed.

Prognostic parameters on baseline and interim [ 18 F]FDG-PET/computed tomography in diffuse large B-cell lymphoma patients.

OBJECTIVE: 2-[ 18 F]fluoro-2-deoxy- d -glucose PET/computed tomography ([ 18 F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different PET biomarkers in a multicenter setting. METHODS: We investigated baseline volumetric values [metabolic tumor volume (MTV) and total lesion glycolysis (TLG), also normalized for body weight] segmented with three different methods [>SUV4 (glob4); 41% isocontour (41pc), and a gradient-based lesion growing algorithm (grad)] and interim parameters [Deauville score, maximal standardized uptake value (ΔSUVmax), modified qPET, and ratio PET (rPET)] alongside clinical parameters (stage, revised International Prognostic Index), using 24-month progression-free survival as the clinical endpoint. Receiver operating characteristics analyses were performed to define optimal cutoff points for the continuous PET parameters. RESULTS: A total of 107 diffuse large B-cell lymphoma patients were included (54 women; mean age: 53.7 years). MTV and TLG calculations showed good correlation among glob4, 41pc, and grad methods; however, optimal cutoff points were markedly different.Significantly different PFS was observed between low- and high-risk groups according to baseline MTV, body weight-adjusted (bwa) MTV, TLG, bwaTLG, as well as interim parameters Deauville score, ΔSUVmax, mqPET, and rPET. Univariate Cox regression analyses showed hazard ratios (HRs) lowest for bwaMTVglob4 (HR = 2.3) and highest for rPET (HR = 9.09). In a multivariate Cox-regression model, rPET was shown to be an independent predictor of PFS ( P = 0.041; HR = 9.15). Combined analysis showed that ΔSUVmax positive patients with high MTV formed a group with distinctly poor PFS (35.3%). CONCLUSION: Baseline MTV and TLG values and optimal cutoff points achieved with different segmentation methods varied markedly and showed a limited prognostic impact. Interim PET/CT parameters provided more accurate prognostic information with semiquantitative 'Deauville-like' parameters performing best in the present study.

Mechanistic Insight Into the Application of Alumina-Supported Pd Catalysts for the Hydrogenation of Nitrobenzene to Aniline.

Two Pd/γ-Al2O3 catalysts are examined for the vapor phase hydrogenation of nitrobenzene over the temperature range of 60-200 °C. A 1 wt % catalyst is selected as a reference material that is diluted with γ-alumina to produce a 0.3 wt % sample, which is representative of a metal loading linked to a candidate industrial specification aniline synthesis catalyst. Cyclohexanone oxime is identified as a by-product that is associated with reagent transformation. Temperature-programed infrared spectroscopy and temperature-programed desorption measurements of chemisorbed CO provide information on the morphology of the crystallites of the higher Pd loading catalyst. The lower Pd loading sample exhibits a higher aniline selectivity by virtue of minimization of product overhydrogenation. Reaction testing measurements that were undertaken employing elevated hydrogen flow rates lead to the proposition of separate reagent and product-derived by-product formation pathways, each of which occurs in a consecutive manner. A global reaction scheme is proposed that defines the by-product distribution accessible by the grades of catalyst examined. This information is helpful in defining product purification procedures that would be required in certain heat recovery scenarios connected with large-scale aniline production.

Early maternal language input and classroom instructional quality in relation to children's literacy trajectories from pre-kindergarten through fifth grade.

Both early childhood maternal language input and the quality of classroom instruction in elementary school have been shown to be important environmental supports in predicting children's literacy skill development. However, no studies have simultaneously examined these two environmental supports in relation to children's early language skills and later literacy skills across elementary school. The current study examined how multiple years of early maternal language input from 6 to 36 months and later classroom instructional quality from pre-kindergarten (pre-K) through fifth grade were related to children's early language at 36 months and later literacy trajectories in word recognition and reading comprehension across elementary school. The study included a diverse, population-representative sample of 1,292 children who were born in low-wealth rural communities and followed through fifth grade. Video recordings and subsequent transcripts of mother-child shared picture book tasks in the home at four timepoints during early childhood were used to assess maternal diversity of vocabulary, utterance complexity, and engagement (wh-questions) during book sharing. The quality of instruction in elementary school was assessed using classroom observations from pre-K through fifth grade. Maternal complexity and engagement were indirectly related to children's literacy trajectories across pre-K to fifth grade through effects on early child language at 36 months. Higher-quality classroom instruction was not reliably related to concurrent literacy skills in pre-K through fifth grade. Findings suggested the enduring importance of early maternal language input in predicting children's early language and later literacy skill development during elementary school. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Psychological distress and resilience in a multicentre sample of adolescents and young adults with cancer during the COVID-19 pandemic.

Understanding impact of the coronavirus pandemic (COVID-19) on Adolescents and Young Adults (AYA) with cancer is important to inform care. Online survey of 16-24 year olds receiving cancer treatment at eight cancer centres in the UK. We measured: self-perceived increased anxiety since COVID-19, impact of COVID-19 on treatment, life and relationships, PHQ-8, GAD and the two-item Connor-Davidson Resilience Scale (CD-RISC). 112 AYA participated. 59.8% had previous mental health difficulties. 78.6% reported COVID-19 having a significant impact on life. 79% reported experiencing increased anxiety since COVID-19.43.4% had moderate-severe PHQ-8 scores and 37.1% GADS-7 scores. Impact on life was associated with moderate-severe PHQ-8 scores (OR 5.23, 95% CI 1.65-16.56, p < 0.01), impact on relationships with moderate-severe GADS-7 and PHQ-8 score (OR 2.89, 95% CI 1.11-7.54, p = 0,03; OR 3.54, 95% CI 2.32-15.17, p < 0.01; OR 2.42, 95% CI 1.11-5.25, p =0.03). Greater resilience was associated with lower mod-severe GADS-7and PHQ-8 scores (OR 0.58, 95% CI 0.41-0.81, p < 0.01; OR 0.55 95% CI 0.4-0.72, p < 0.01; OR 0.52, 95% CI 0.38-0.69, p < 0.01). We found high levels of psychological distress. Perceived impact of COVID-19 on relationships and life was predictive of poorer mental health, with resilience a protective factor.

Effects of North Carolina's Pre-Kindergarten Program at the End of Kindergarten: Contributions of School-Wide Quality.

The positive effects of pre-kindergarten (pre-K) programming may be enhanced in later grades for children who subsequently experience high-quality educational environments in elementary school. The current study tested this hypothesis in relation to the effects of North Carolina's NC Pre-K program on child outcomes at the end of kindergarten, including language, literacy, mathematics, and working memory. Measures of elementary school quality were examined as moderators of the NC Pre-K effects, including school-wide academic proficiency and school-wide growth in academic achievement. We found no reliable effects of NC Pre-K participation for children attending elementary schools with average levels of quality. However, the positive effects of NC Pre-K participation on language and working memory skills were evident for children attending elementary schools with higher levels of academic proficiency and academic growth, respectively. No evidence of moderation was found in relation to literacy and mathematics skills.

Phosgene Synthesis Catalysis: The Influence of Small Quantities of Bromine in the Chlorine Feedstream.

The effect of relatively low concentrations of Br2(g) in the Cl2(g) feedstock for phosgene synthesis catalysis via the reaction of CO(g) and Cl2(g) over activated carbon (Donau Supersorbon K40) is explored. Under the stated reaction conditions and in the absence of a catalyst, BrCl(g) forms from the reaction of Cl2(g) and Br2(g). Phosgene synthesis over the catalyst at 323 K is investigated for Br2(g):Cl2(g) molar flow ratios in the range 0-1.52% (0-15,190 ppm) and shows enhanced rates of phosgene production. Maximum phosgene production is observed at a Br2(g):Cl2(g) molar flow ratio of 1.52% (15,190 ppm), which corresponds to an enhancement in the rate of phosgene production of ∼227% with respect to the phosgene flow rate observed in the absence of an incident bromine co-feed. A reaction model is proposed to account for the experimental observables, where BrCl(g) is highlighted as a significant intermediate. Specifically, enhanced rates of phosgene production are associated with the dissociative adsorption of BrCl(g) that indirectly increases the pool of Cl(ad) available for reaction.

Examining the Effects of Changes in Classroom Quality on Within-Child Changes in Achievement and Behavioral Outcomes.

This study examines whether changes in classroom quality predict within-child changes in achievement and behavioral problems in elementary school (ages spanning approximately 6-11 years old). Drawing on data from a longitudinal study of children in predominantly low-income, nonurban communities (n = 1,078), we relied on child fixed effects modeling, which controlled for stable factors that could bias the effects of classroom quality. In general, we found that changes in classroom quality had small and statistically nonsignificant effects on achievement and behavior. However, we found that moving into a high-quality classroom, particularly those rated as high in Classroom Organization, had positive effects on achievement and behavior for children with significant exposure to poverty in early life.

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease.

OBJECTIVE: The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. METHODS: Foslevodopa and foscarbidopa were prepared and the equilibrium solubility and chemical stability examined in aqueous media with different values of pH. Solutions of foslevodopa/foscarbidopa (ratios ranging from 4:1 to 20:1) were prepared by dissolving pH-adjusted lyophilized materials in water and infused s.c. in healthy volunteers for ≤72 hours. Frequent blood samples were collected to measure LD and CD exposure, and safety was monitored throughout the study. RESULTS: Foslevodopa/foscarbidopa (ABBV-951) demonstrates high water solubility and excellent chemical stability near physiological pH, enabling continuous s.c. infusion therapy. After s.c. infusion, a stable LD pharmacokinetic (PK) profile was maintained for ≤72 hours, and the infusion was well tolerated. INTERPRETATION: Preparation of foslevodopa and foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In phase 1 clinical trials, foslevodopa/foscarbidopa demonstrates consistent and stable LD plasma exposure, supporting further studies of this treatment as a potentially transformational option for those suffering from PD. ANN NEUROL 2021;90:52-61.

Toward High Selectivity Aniline Synthesis Catalysis at Elevated Temperatures.

In connection with an initiative to enhance heat recovery from the large-scale operation of a heterogeneously catalyzed nitrobenzene hydrogenation process to produce aniline, it is necessary to operate the process at elevated temperatures (>100 °C), a condition that can compromise aniline selectivity. Alumina-supported palladium catalysts are selected as candidate materials that can provide sustained aniline yields at elevated temperatures. Two Pd/Al2O3 catalysts are examined that possess comparable mean Pd particle sizes (∼5 nm) for different Pd loading: 5 wt % Pd/Al2O3 and 0.3 wt % Pd/Al2O3. The higher Pd loading sample represents a reference catalyst for which the Pd crystallite morphology has previously been established. The lower Pd loading technical catalyst more closely corresponds to industrial specifications. The morphology of the Pd crystallites of the 0.3 wt % Pd/Al2O3 sample is explored by means of temperature-programmed infrared spectroscopy of chemisorbed CO. Reaction testing over the range of 60-180 °C shows effectively complete nitrobenzene conversion for both catalysts but with distinction in their selectivity profiles. The low loading catalyst is favored as it maximizes aniline selectivity and avoids the formation of overhydrogenated products. A plot of aniline yield as a function of WHSV for the 0.3 wt % Pd/Al2O3 catalyst at 100 °C yields a "volcano" like curve, indicating aniline selectivity to be sensitive to residence time. These observations are brought together to provide an indication of an aniline synthesis catalyst specification suited to a unit operation equipped for enhanced heat transfer.

Latent Class Growth Trajectories of Letter Name Knowledge During Pre-Kindergarten and Kindergarten.

A major developmental task for young children in the United States involves the acquisition of knowledge about the letters in the English alphabet. In the current study, we examined the growth trajectories of children's letter name knowledge (LNK) during pre-kindergarten and kindergarten. A diverse sample of 1,015 children was drawn from the National Center for Early Development and Learning Multi-State Study of Pre-Kindergarten. Latent class growth analyses were used to identify three heterogeneous classes of children based on their LNK growth trajectories. Children's fall-of-pre-kindergarten language skills were associated with trajectory class membership, which in turn was associated with children's spring-of-kindergarten literacy skills. We also found that the association between children's fall-of-pre-kindergarten language skills and spring-of-kindergarten literacy skills was partially mediated by trajectory class membership. These findings point to the importance of LNK skill development as a marker variable to monitor and support children's emergent literacy development.

Infant and Toddler Child-Care Quality and Stability in Relation to Proximal and Distal Academic and Social Outcomes.

This study considered the quality and stability of infant and toddler nonparental child care from 6 to 36 months in relation to language, social, and academic skills measured proximally at 36 months and distally at kindergarten. Quality was measured separately as caregiver-child verbal interactions and caregiver sensitivity, and stability was measured as having fewer sequential child-care caregivers. This longitudinal examination involved a subsample (N = 1,055) from the Family Life Project, a representative sample of families living in rural counties in the United States. Structural equation modeling revealed that children who experienced more positive caregiver-child verbal interactions had higher 36-month language skills, which indirectly led to higher kindergarten academic and social skills. Children who experienced more caregiver stability had higher kindergarten social skills.

Outcomes of T-lymphoblastic lymphoma treated with pediatric ALL-like protocol.

BACKGROUND: The management of T-lymphoblastic lymphoma (T-LBL) in adults poses uncertainties, including optimal chemotherapy regimen, need for radiotherapy, and the benefit of stem cell transplant. This retrospective case series investigated the efficacy of the pediatric BFM-90 regimen in adult patients and evaluated the role of early response assessment by positron emission tomography with computed tomography (PET-CT) in predicting outcomes. METHODS: Patients aged 15 years or older with T-LBL diagnosed at Tata Memorial Hospital, Mumbai, India were given chemotherapy according to the European BFM-90 protocol (n = 38). The patients were evaluated for early response by interim PET-CT, post-induction and monitored for toxicity and long-term outcomes. RESULTS: Thirty-eight consecutive patients (median age 23.5 years) were analyzed. After a median follow-up of 33.5 (1-77) months, following induction, 35 out of 38 patients (92.1%) had achieved complete response (CR) on PET-CT. Thirty (78.9%) patients treated according to BFM-90 were alive in first remission. Three-year event-free survival for those with CR on PET-CT was 78%, against no survivors for those who remained PET-positive. CONCLUSION: This study demonstrates the feasibility and efficacy of BFM-90 approach in adults with T-LBL. We found an early PET response to be highly predictive of outcome.

Genomic insights into the early peopling of the Caribbean.

The Caribbean was one of the last regions of the Americas to be settled by humans, but where they came from and how and when they reached the islands remain unclear. We generated genome-wide data for 93 ancient Caribbean islanders dating between 3200 and 400 calibrated years before the present and found evidence of at least three separate dispersals into the region, including two early dispersals into the Western Caribbean, one of which seems connected to radiation events in North America. This was followed by a later expansion from South America. We also detected genetic differences between the early settlers and the newcomers from South America, with almost no evidence of admixture. Our results add to our understanding of the initial peopling of the Caribbean and the movements of Archaic Age peoples in the Americas.