Educational Gender Gaps.

Cross-country studies reveal two consistent gender gaps in education-underachievement in school by boys and low rates of participation in STEM studies by girls. Recent economics research has shown the importance of social influences on women's STEM avoidance, but male low achievement has been less-studied and tends to be attributed to behavior problems and deficient non-cognitive skills. I revisit the determinants of the gender gap in U.S. educational attainment with a relatively-advantaged sample of young men and women and find that school behavior and measured skills are not very important drivers of gender differences, particularly in the transition to college. Educational aspirations, on the other hand, are strongly predictive of educational gaps and the gender difference in aspirations cannot be explained, even with rich adolescent data that includes parental expectations and school achievement indicators. These results suggest that gender identity concerns may influence (and damage) the educational prospects of boys as well as girls through norms of masculinity that discourage academic achievement.

Retrospective evaluation of bone marrow cell morphology in a cohort of patients with isolated idic(20q-) karyotypic abnormalities.

Isochromosome 20q- (i(20q-)), as a rare reproducible chromosomal anomaly formed on the basis of 20q-, has not been commonly reported. Due to the rarity of this karyotypic anomaly, the bone marrow morphological characteristics of the patients with i(20q-) have not been clarified until now. In this study, the bone marrow cell morphology from MDS patients with isolated i(20q-), isolated 20q-, and normal karyotype was retrospectively compared and statistically analyzed. The results indicated that the isolated i(20q-) was mostly detected in MDS-MLD patients. The frequency and proportion dysplasia of cytoplasmic vacuolization in erythoid cells and small or unusually large size in myeloid cells of isolated i(20q-) MDS patients were significantly higher than those of normal karyotype MDS patients respectively (P < 0.05); the frequency and proportion dysplasia of decreased granules/agranularity in myeloid cells of isolated i(20q-) MDS patients were higher than those of isolated 20q- MDS patients (P < 0.05). The incidence of some specific morphological manifestations, such as deeply lobulated and hyperlobulated megakaryocytes and hypogranular and vacuolized eosinophils, may be an important morphological implication for the anomaly of isolated i(20q-). These morphological features of dysplasia may be helpful in distinguishing MDS with isolated i(20q-) from those with isolated 20q- and normal karyotype.

Boosting School Readiness: Should Preschool Teachers Target Skills or the Whole Child?

We use experimental data to estimate impacts on school readiness of different kinds of preschool curricula - a largely neglected preschool input and measure of preschool quality. We find that the widely-used "whole-child" curricula found in most Head Start and pre-K classrooms produced higher classroom process quality than did locally-developed curricula, but failed to improve children's school readiness. A curriculum focused on building mathematics skills increased both classroom math activities and children's math achievement relative to the whole-child curricula. Similarly, curricula focused on literacy skills increased literacy achievement relative to whole-child curricula, despite failing to boost measured classroom process quality.

The Effects of Changes in Kindergarten Entry Age Policies on Educational Achievement.

This study explores the effects of state kindergarten-entry-age policies on students' outcomes by exploiting variation in the kindergarten entry cutoff dates enacted by states in the United States over the last 40 years. Using the state average and standard deviation in NAEP test scores in 4th, 8th and 12th grades, we estimate the impacts of state entry-age policies on educational achievement and test score dispersion in the state. The estimation results from the baseline state and time fixed effects model show that a one month earlier cutoff increases average state reading and math scores of 4th graders by 21.7 and 13.6 percent of a standard deviation, respectively. Eighth graders' average score increases in math and science are 12.4 and 24.3 percent of a standard deviation, respectively, while the effect on reading score significantly decreases. We find no effect of kindergarten entry date on educational outcomes in 12th grade. We also find that an earlier kindergarten entry date generally reduces the standard deviation of state test scores. Robustness checks support these findings and suggest no evidence of endogeneity of the policy changes. Our findings provide novel evidence that early school start cutoffs have improved state-level achievement measures over the past 40 years.

New C(4)- and C(1)-derivatives of furo[3,4-c]pyridine-3-ones and related compounds: evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform.

A set of 18 new C(4) and C(1) derivatives of nor-cerpegin (1,1-dimethyl furo[3,4-c]pyridine-3-one), 6 model compounds (γ- and δ-lactones) and 20 furo- or thieno[2,3-d]-pyrimidine-4-one related compounds were designed and synthesized. Each compound was assayed for inhibition of CT-L, T-L and PA proteolytic activities of 20S constitutive proteasome (c20S). Most performant compounds were also assayed on 20S immunoproteasome (i20S). Compound 10 with a benzylamino group at C(4) and dimethylated at C(1) of the furopyridine ring was the most efficient PA site-specific inhibitor of the c20S (IC50(cPA) of 600nM) without noticeable inhibition of the i20S PA site (iPA). In silico docking assays for 10 at the iPA catalytic site revealed the absence of poses normally observed for this compound and related ones at the constitutive PA site (cPA). The thieno[2,3-d]pyrimidine-4-one 40 was T-L site-specific with a mild inhibition of both c20S and i20S in vitro (IC50(cT-L) of 9.9µM and IC50(iT-L) of 6.7µM). In silico docking assays of 40 at T-L sites of c20S and i20S revealed almost identical first rank poses in the two types of sites with no possibility left for nucleophilic attack by Thr1 as observed for the fused furopyridine-3-one 10.

Targeting Microglial Immunoproteasome: A Novel Approach in Neuroinflammatory-Related Disorders.

It is widely acknowledged that the aging process is linked to the accumulation of damaged and misfolded proteins. This phenomenon is accompanied by a decrease in proteasome (c20S) activity, concomitant with an increase in immunoproteasome (i20S) activity. These changes can be attributed, in part, to the chronic neuroinflammation that occurs in brain tissues. Neuroinflammation is a complex process characterized by the activation of immune cells in the central nervous system (CNS) in response to injury, infection, and other pathological stimuli. In certain cases, this immune response becomes chronic, contributing to the pathogenesis of various neurological disorders, including chronic pain, Alzheimer's disease, Parkinson's disease, brain traumatic injury, and others. Microglia, the resident immune cells in the brain, play a crucial role in the neuroinflammatory response. Recent research has highlighted the involvement of i20S in promoting neuroinflammation, increased activity of which may lead to the presentation of self-antigens, triggering an autoimmune response against the CNS, exacerbating inflammation, and contributing to neurodegeneration. Furthermore, since i20S plays a role in breaking down accumulated proteins during inflammation within the cell body, any disruption in its activity could lead to a prolonged state of inflammation and subsequent cell death. Given the pivotal role of i20S in neuroinflammation, targeting this proteasome subtype has emerged as a potential therapeutic approach for managing neuroinflammatory diseases. This review delves into the mechanisms of neuroinflammation and microglia activation, exploring the potential of i20S inhibitors as a promising therapeutic strategy for managing neuroinflammatory disorders.

A novel H­tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy.

BACKGROUND: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. OBJECTIVES: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. METHODS: Human primary sebocytes were transfected with the human tert gene (h­tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. RESULTS: The h­tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. CONCLUSIONS: We have developed an h­tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.

DISTRIBUTIONAL EFFECTS OF EDUCATION ON HEALTH.

This paper studies distributional effects of education on health. In 1972, England, Scotland, and Wales raised their minimum school-leaving age from 15 to 16 for students born after 9/1/1957. Using a regression discontinuity design and objective health measures for 129,000 individuals, we find that education reduced body size and increased blood pressure in middle age. The reduction in body size was concentrated at the upper tail of the distribution with an 8 percentage point reduction in obesity. The increase in blood pressure was concentrated at the lower tail of the distribution with no effect on stage 2 hypertension.

The Long-Run Effects of Recessions on Education and Income.

This paper examines the long-run effects of the 1980-1982 recession on education and income. Using confidential Census data, I estimate difference-in-differences regressions that exploit variation across counties in recession severity and across cohorts in age at the time of the recession. For individuals age 0-10 in 1979, a 10 percent decrease in earnings per capita in their county of birth reduces four-year college degree attainment by 15 percent and earnings in adulthood by 5 percent. Simple calculations suggest that, in aggregate, the 1980-1982 recession led to 1.3-2.8 million fewer college graduates and $66-$139 billion less earned income per year.

Effectiveness of Concrete Reinforcement with Recycled Tyre Steel Fibres.

The role of searching for industrial waste management solutions in construction is key for environmental protection. Research in recent years has focused on solutions aimed at reducing the carbon footprint. This paper presents the results of tests conducted on concrete reinforced with treated recycled tyre steel fibres (RTSFs) compared to the same amount of manufactured steel fibres (MSFs). The effectiveness of concrete reinforcement with RTSFs was analysed using the fracture mechanics parameters of cementitious composites. Rheological tests, residual flexural tensile strength tests, work of fracture measurements, toughness indices, examinations of the fibre distribution in the concrete, and SEM observations of the concrete fractures with fibres were performed. Determining the work of fracture and toughness indices was an innovative aspect of this paper. As the amount of RTSFs increased, a decrease in the consistency was observed, although the distribution of fibres in the concrete was uniform, as proven by the results of computer tomography tests. Concrete reinforced with RTSFs that is purified and refined during the recycling process might have better properties than concrete reinforced with the same amount of MSFs. The application of RTSFs in construction has environmental and economic benefits in addition to the strengthening of cementitious composites.

Utilization of an emotional intelligence workshop to enhance student pharmacists' self-awareness.

BACKGROUND AND PURPOSE: This study evaluated the impact of an emotional intelligence (EI) workshop as a tool to improve student pharmacists' self-awareness. The primary objectives were to assess the change in student pharmacists' self-awareness as measured by the Self-Awareness Outcomes Questionnaire (SAOQ) and identify trends in their self-reflection. EDUCATIONAL ACTIVITY AND SETTING: A four-hour EI workshop was delivered in a first-year required student pharmacist leadership course. The components of the workshop included: an EI assessment via the Emotional Quotient Inventory (EQ-i 2.0) administered to student pharmacists outside of class, active learning class time that applied the principles of EI to leadership and group dynamics, and peer-to-peer discussions. Personal results of the EQ-i 2.0 were reviewed individually and in small groups. Student pharmacists completed a self-reflection and EI action plan outside of class. The SAOQ was completed before and after the workshop and the aggregated Likert scales were analyzed by paired t-tests. FINDINGS: After two consecutive course offerings of the workshop (N = 100), there was a significant increase in the total SAOQ score as well as a significant increase for the three positive subscales: reflective self-development, acceptance, and proactivity. There was no change in the negative subscale: emotional costs. Student pharmacists positively perceived the workshop and reported that the activities motivated students to improve their interpersonal skills and increase extracurricular involvement. DISCUSSION: Implementing an EI workshop is an effective curricular method to improve the affective domain of student development, specifically self-awareness.

Nogo-A-Δ20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling.

Nogo-A protein consists of two main extracellular domains: Nogo-66 (rat amino acid [aa] 1019-1083) and Nogo-A-Δ20 (extracellular, active 180 amino acid Nogo-A region), which serve as strong inhibitors of axon regeneration in the adult CNS (Central Nervous System). Although receptors S1PR2 and HSPGs have been identified as Nogo-A-Δ20 binding proteins, it remains at present elusive whether other receptors directly interacting with Nogo-A-Δ20 exist, and decrease cell death. On the other hand, the key roles of EphA4 in the regulation of glioblastoma, axon regeneration and NSCs (Neural Stem Cells) proliferation or differentiation are well understood, but little is known the relationship between EphA4 and Nogo-A-Δ20 in NSCs apoptosis. Thus, we aim to determine whether Nogo-A-Δ20 can bind to EphA4 and affect survival of NSCs. Here, we discover that EphA4, belonging to a member of erythropoietin-producing hepatocellular (Eph) receptors family, could be acting as a high affinity ligand for Nogo-A-Δ20. Trans-membrane protein of EphA4 is needed for Nogo-A-Δ20-triggered inhibition of NSCs apoptosis, which are mediated by balancing p38 inactivation and JNK MAPK pathway activation. Finally, we predict at the atomic level that essential residues Lys-205, Ile-190, Pro-194 in Nogo-A-Δ20 and EphA4 residues Gln-390, Asn-425, Pro-426 might play critical roles in Nogo-A-Δ20/EphA4 binding via molecular docking.

The Consequences of the 1959-1961 Chinese Famine for Educational Attainment.

This paper finds that the Great Chinese Famine of 1959-1961 reduced lifetime educational attainment by up to 3.8 years for people who lived in areas most severely hit by the famine. Using geographical variation in famine intensity, information about place of residence during the famine, and educational attainment recorded in the China Health and Retirement Longitudinal Study, the paper demonstrates that the decline in educational attainment was particularly sharp for women. This decline interrupted substantial gains in schooling achieved in China during the middle part of the twentieth century.

Use of real-world evidence in meta-analyses and cost-effectiveness models.

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial data with valuable information on patient behaviors and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges. The objectives of this communication were to (1) summarize all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses. No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results. RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines.

Budget impact analysis of niraparib and olaparib for maintenance treatment of platinum-sensitive, recurrent ovarian cancer in the US.

AIMS: This study aimed to evaluate the budget impact of niraparib and olaparib in patients with platinum-sensitive, recurrent ovarian cancer from a US third party payer perspective. MATERIALS AND METHODS: A budget impact model was constructed to assess the additional per member per month (PMPM) costs associated with the introduction of niraparib and olaparib, two poly ADP-ribose polymerase ribose polymerase (PARP) inhibitors recently approved to be used in platinum-sensitive, recurrent ovarian cancer patients with and without a gBRCA mutation. The model assessed both pharmacy costs and medical costs. Pharmacy costs included adjusted drug costs, coinsurance, and dispensing fees. Medical costs included costs associated with disease monitoring and management of adverse events from the treatment. Epidemiological data from the literature were used to estimate the target population size. The analysis used 1-year time frame, and patients were assumed on treatment until disease progression or death. All costs were computed in 2017 USD. One-way sensitivity analyses were conducted to evaluate the model robustness. RESULTS: In a hypothetical plan of 1,000,000 members, 206 patients were estimated to be potential candidates for niraparib or olaparib maintenance treatment after applying all epidemiological parameters. At listed 30-day supply WAC prices of $14,750 for niraparib and $13,482 for olaparib, budget impacts of these two drugs were $0.169 PMPM and $0.156 PMPM, respectively, most of which were contributed by pharmacy costs. Sensitivity analyses suggested that assumptions around market share, platinum-sensitive rate after first treatment, and WAC prices affected results the most. LIMITATIONS: In this model, it was assumed that adopting niraparib and olaparib would not affect utilization of existing medications. Also, the estimated clinical parameters from clinical trials could differ from real-world data.

Healthcare costs and utilization associated with muscle weakness diagnosis codes in patients with chronic obstructive pulmonary disease: a United States claims analysis.

AIMS: Muscle weakness (MW)-attributable healthcare resource utilization (HCRU) and costs in patients with chronic obstructive pulmonary disease (COPD) have not been well-characterized in US insurance claims databases. The primary objective of this study was to estimate HCRU in patients with evidence of COPD with and without MW diagnosis codes. MATERIALS AND METHODS: This retrospective analysis used the MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Between January 2007 and March 2016, we identified patients aged ≥40 years with diagnosis codes for COPD (≥1 emergency department or inpatient claim or ≥2 outpatient claims within 1 year). The cohort was divided into patients with and without ≥1 MW diagnosis code. Propensity score matching was used to generate pairs of patients with and without MW (1:1). Multivariable regression analyses were used to estimate adjusted incremental costs and utilization attributable to the presence of MW diagnosis codes among patients with COPD. RESULTS: Of 427,131 patients who met the study inclusion criteria, 14% had evidence of MW. After matching, 107,420 unique patients remained equally distributed across MW status. Patients with MW diagnosis codes had greater predicted annual HCRU, $2,465 greater total predicted annual COPD-related costs, and $15,179 greater total all-cause costs than those without MW diagnosis codes. Overall, <1% of patients received COPD-related pulmonary rehabilitation services. LIMITATIONS: Study limitations include the potential for undercoding of MW and lack of information on severity of MW in claims data. CONCLUSION: The presence of MW diagnosis codes yielded higher HCRU in this COPD population and suggests that the burden of MW affects both all-cause and COPD-related care. However, utilization of pulmonary rehabilitation, a known effective treatment for MW, remains low. Future research should expand on our results by assessing data sources that allow for clinical confirmation of MW among patients with COPD.

First-line systemic treatment adherence, healthcare resource utilization, and costs in patients with gastrointestinal neuroendocrine tumors (GI NETs) in the USA.

AIMS: To assess treatment adherence, healthcare resource utilization, and costs in gastrointestinal neuroendocrine tumor (GI NET) patients initiating pharmacologic treatments in the US. METHODS: In two US commercial claims databases, patients ≥18 years with ≥1 inpatient or ≥2 outpatient GI NET claims within 12 months were identified. The first claim for pharmacologic treatments (e.g. somatostatin analogs [SSAs], cytotoxic chemotherapy [CC], targeted therapy [TT]) following diagnosis, between July 1, 2009 - December 31, 2014, was defined as the index date. A 6-month pre-index NET treatment-free period, and ≥1-year post-index enrollment were required. Proportion of days covered (PDC) was calculated during the follow-up period. Outcomes were reported separately for patients with 1- and 2-years post-index enrollment. Descriptive statistics, including means, standard deviations, and frequencies and percentages for continuous and categorical data, respectively, were reported. RESULTS: Of 1,322 patients with 1-year follow-up, 847 initiated SSA, 397 CC, 35 TT, two interferon, and 41 various combinations. Mean (SD) PDC was 0.669 (0.331) for SSA, 0.466 (0.236) for CC, and 0.505 (0.328) for TT. Mean (SD) office visits and hospitalizations, respectively, were 20.5 (13.5) and 0.59 (1.03) for SSA, 30.5 (19.8) and 0.89 (1.45) for CC, and 17.7 (12.5) and 1.23 (1.93) for TT. Total annual cost for patients during year 1 was $99,691 (82,423) for SSA, $134,912 (116,078) for CC, and $158,397 (82,878) for TT. Among 685 patients with 2-years follow-up, annual mean costs in year 2 were $8,071, $58,944, and $36,248 lower than year 1 for SSA, CC, and TT, respectively. LIMITATIONS: Findings may not be generalizable to the US population. Claims are designed for reimbursement, not research. The study may under-estimate costs not covered by insurance. CONCLUSION: This study reports utilization and costs associated with different treatment therapies. Costs were higher in year 1 than year 2. This two-database study offers new information on the magnitude and trends in the cost of pharmacologically-treated GI NETs.

Worms at Work: Long-run Impacts of a Child Health Investment.

This study estimates long-run impacts of a child health investment, exploiting community-wide experimental variation in school-based deworming. The program increased labor supply among men and education among women, with accompanying shifts in labor market specialization. Ten years after deworming treatment, men who were eligible as boys stay enrolled for more years of primary school, work 17% more hours each week, spend more time in nonagricultural self-employment, are more likely to hold manufacturing jobs, and miss one fewer meal per week. Women who were in treatment schools as girls are approximately one quarter more likely to have attended secondary school, halving the gender gap. They reallocate time from traditional agriculture into cash crops and nonagricultural self-employment. We estimate a conservative annualized financial internal rate of return to deworming of 32%, and show that mass deworming may generate more in future government revenue than it costs in subsidies.

Health, SES, and the Timing of Education Among Military Retirees.

The timing of education across the life cycle is differentially associated with older-age health outcomes and socioeconomic status among military retirees, a subpopulation with common levels of adolescent health but variation in educational timing. A year of education obtained before military service lowers the probability of poor health in retirement by 2.5 percentage points, while a year obtained after service reduces poor health by only 0.6 percentage point. By contrast, education raises income and wealth uniformly through vintage. This suggests that education improves health through fostering the lifelong accumulation of healthy behaviors and habits rather than raising income or wealth.

The effect of school district nutrition policies on dietary intake and overweight: a synthetic control approach.

School nutrition policies aim to eliminate ubiquitous unhealthy foods and beverages from schools to improve adolescent dietary behavior and reduce childhood obesity. This paper evaluates the impact of an early nutrition policy, Los Angeles Unified School District's food-and-beverage standards of 2004, using two large datasets on food intake and physical measures. I implement cohort and cross-section estimators using "synthetic" control groups, combinations of unaffected districts that are reweighted to closely resemble the treatment unit in the pre-intervention period. The results indicate that the policy was mostly ineffective at reducing the prevalence of overweight or obesity 8-15 months after the intervention but significantly decreased consumption of two key targets, soda and fried foods. The policy's impact on physical outcomes appears to be mitigated by substitution toward foods that are still (or newly) available in the schools.