Preschool participation and students’ learning outcomes in primary school: Evidence from national reform of pre-primary education in Ethiopia

This study examines whether a large expansion of pre-primary education in Ethiopia affected subsequent students’ learning outcomes during the national reform of pre-primary education. The study utilizes two comparable, representative early grade reading assessment data that straddle the reform period from 2010 to 2016, during which enrolment rates in pre-primary education soared by nearly ten times nationwide. We find that associations between preschool participation and literacy outcomes were positive and significant after the expansion, yet no such relationships were observed before the reform. However, there was little heterogeneity in the gains of the preschool participation by gender, urbanity, and parental literacy. We discuss implications for ongoing reform, including strategic and inclusive policy designed to close the learning gap between children from advantaged and disadvantaged backgrounds

The Implications of COVID-19 for Early Childhood Education in Ethiopia: Perspectives from Parents and Caregivers

Funder: World Bank Group (US)Funder: Foreign and Commonwealth Office; doi: http://dx.doi.org/10.13039/501100000617Abstract: Recent research on the effects of COVID-19 on school closures has mainly focused on primary and secondary education, with extremely limited attention to early childhood education (ECE). To address this gap, we identify the extent to which parents and caregivers with pre-primary school-aged children were engaged in their children’s learning during school closures in Ethiopia. Our focus on Ethiopia is of particular relevance given that ECE provision has expanded dramatically in recent years, aimed at ensuring children are prepared for primary school. Using data collected through a phone survey with 480 parents and caregivers, the results revealed that learning disruption due to COVID-19 school closures is likely to be substantial and will probably widen existing inequalities further. Many poorer households and those where parents or caregivers are not literate, are less likely to have child-oriented learning resources, and home learning activities between parents and children in these households are limited. The study highlights that greater attention needs to be paid to mitigate the threats of COVID-19 on Ethiopia’s recent gains in ECE, to prevent the pandemic from further reinforcing inequalities between children from advantaged and disadvantaged households

Hostility Modifies the Association between TV Viewing and Cardiometabolic Risk

Background. It was hypothesized that television viewing is predictive of cardiometabolic risk. Moreover, people with hostile personality type may be more susceptible to TV-induced negative emotions and harmful health habits which increase occurrence of cardiometabolic risk. Purpose. The prospective association of TV viewing on cardiometabolic risk was examined along with whether hostile personality trait was a modifier. Methods. A total of 3,269 Black and White participants in the coronary artery risk development in young adults (CARDIA) study were assessed from age 23 to age 35. A cross-lagged panel model at exam years 5, 10, 15, and 20, covering 15 years, was used to test whether hours of daily TV viewing predicted cardiometabolic risk, controlling confounding variables. Multiple group analysis of additional cross-lagged panel models stratified by high and low levels of hostility was used to evaluate whether the association was modified by the hostile personality trait. Results. The cross-lagged association of TV viewing at years 5 and 15 on clustered cardiometabolic risk score at years 10 and 20 was significant (B=0.058 and 0.051), but not at 10 to 15 years. This association was significant for those with high hostility (B=0.068 for exam years 5 to 10 and 0.057 for exam years 15 to 20) but not low hostility. Conclusion. These findings indicate that TV viewing is positively associated with cardiometabolic risk. Further, they indicate that hostility might be a modifier for the association between TV viewing and cardiometabolic risk

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT

BACKGROUND: Cryopreservation of PBMC and/or overnight shipping of samples are required for many clinical trials, despite their potentially adverse effects upon immune monitoring assays such as MHC-peptide tetramer staining, cytokine flow cytometry (CFC), and ELISPOT. In this study, we compared the performance of these assays on leukapheresed PBMC shipped overnight in medium versus cryopreserved PBMC from matched donors. RESULTS: Using CMV pp65 peptide pool stimulation or pp65 HLA-A2 tetramer staining, there was significant correlation between shipped and cryopreserved samples for each assay (p ≤ 0.001). The differences in response magnitude between cryopreserved and shipped PBMC specimens were not significant for most antigens and assays. There was significant correlation between CFC and ELISPOT assay using pp65 peptide pool stimulation, in both shipped and cryopreserved samples (p ≤ 0.001). Strong correlation was observed between CFC (using HLA-A2-restricted pp65 peptide stimulation) and tetramer staining (p < 0.001). Roughly similar sensitivity and specificity were observed between the three assays and between shipped and cryopreserved samples for each assay. CONCLUSION: We conclude that all three assays show concordant results on shipped versus cryopreserved specimens, when using a peptide-based readout. The assays are also concordant with each other in pair wise comparisons using equivalent antigen systems

Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine

Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices

BackgroundEmissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.MethodsSize-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8mm diameter lung slices from CD-1 mice were exposed (11μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.ResultsOn an equi-mass basis, coarse ENCF-1PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB.ConclusionsThe findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB