External validity in healthy public policy: application of the RE-AIM tool to the field of housing improvement

<b>Background</b><p></p> Researchers and publishers have called for improved reporting of external validity items and for testing of existing tools designed to assess reporting of items relevant to external validity. Few tools are available and most of this work has been done within the field of health promotion.<p></p> <b>Methods</b><p></p> We tested a tool assessing reporting of external validity items which was developed by Green & Glasgow on 39 studies assessing the health impacts of housing improvement. The tool was adapted to the topic area and criteria were developed to define the level of reporting, e.g. “some extent”. Each study was assessed by two reviewers.<p></p> <b>Results</b><p></p> The tool was applicable to the studies but some items required considerable editing to facilitate agreement between the two reviewers. Levels of reporting of the 17 external validity items were low (mean 6). The most commonly reported items related to outcomes. Details of the intervention were poorly reported. Study characteristics were not associated with variation in reporting.<p></p> <b>Conclusions</b><p></p> The Green & Glasgow tool was useful to assess reporting of external validity items but required tailoring to the topic area. In some public health evaluations the hypothesised impact is dependent on the intervention effecting change, e.g. improving socio-economic conditions. In such studies data confirming the function of the intervention may be as important as details of the components and implementation of the intervention

Effects of Housing First approaches on health and wellbeing of adults who are homeless or at risk of homelessness: systematic review and meta-analysis of randomised controlled trials

Background: Homelessness is associated with poor health. A policy approach aiming to end homelessness across Europe and North America, the ‘Housing First’ (HF) model, provides rapid housing, not conditional on abstinence from substance use. We aimed to systematically review the evidence from randomised controlled trials for the effects of HF on health and well-being. Methods: We searched seven databases for randomised controlled trials of interventions providing rapid access to non-abstinence-contingent, permanent housing. We extracted data on the following outcomes: mental health; self-reported health and quality of life; substance use; non-routine use of healthcare services; housing stability. We assessed risk of bias and calculated standardised effect sizes. Results: We included four studies, all with ‘high’ risk of bias. The impact of HF on most short-term health outcomes was imprecisely estimated, with varying effect directions. No clear difference in substance use was seen. Intervention groups experienced fewer emergency department visits (incidence rate ratio (IRR)=0.63; 95% CI 0.48 to 0.82), fewer hospitalisations (IRR=0.76; 95% CI 0.70 to 0.83) and less time spent hospitalised (standardised mean difference (SMD)=−0.14; 95% CI −0.41 to 0.14) than control groups. In all studies intervention participants spent more days housed (SMD=1.24; 95% CI 0.86 to 1.62) and were more likely to be housed at 18–24 months (risk ratio=2.46; 95% CI 1.58 to 3.84). Conclusion: HF approaches successfully improve housing stability and may improve some aspects of health. Implementation of HF would likely reduce homelessness and non-routine health service use without an increase in problematic substance use. Impacts on long-term health outcomes require further investigation. Trial registration number: CRD42017064457

Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs

Background: Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: ‘Evidence Synthesis for Constructing Directed Acyclic Graphs’ (ESC-DAGs)’.\ud Methods: ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are ‘mapped’ into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more ‘integrated DAGs’. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence. Conclusions: ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis

Nature-based early childhood education and children's social, emotional and cognitive development : a mixed-methods systematic review

This systematic review synthesised evidence on associations between nature-based early childhood education (ECE) and children's social, emotional, and cognitive development. A search of nine databases was concluded in August 2020. Studies were eligible if: (a) children (2-7 years) attended ECE, (b) ECE integrated nature, and (c) assessed child-level outcomes. Two reviewers independently screened full-text articles and assessed study quality. Synthesis included effect direction, thematic analysis, and results-based convergent synthesis. One thousand three hundred and seventy full-text articles were screened, and 36 (26 quantitative; 9 qualitative; 1 mixed-methods) studies were eligible. Quantitative outcomes were cognitive ( = 11), social and emotional ( = 13), nature connectedness ( = 9), and play ( = 10). Studies included controlled ( = 6)/uncontrolled ( = 6) before-after, and cross-sectional ( = 15) designs. Based on very low certainty of the evidence, there were positive associations between nature-based ECE and self-regulation, social skills, social and emotional development, nature relatedness, awareness of nature, and play interaction. Inconsistent associations were found for attention, attachment, initiative, environmentally responsible behaviour, and play disruption/disconnection. Qualitative studies ( = 10) noted that nature-based ECE afforded opportunities for play, socialising, and creativity. Nature-based ECE may improve some childhood development outcomes, however, high-quality experimental designs describing the dose and quality of nature are needed to explore the hypothesised pathways connecting nature-based ECE to childhood development (Systematic Review Registration CRD42019152582)

Nature-based early childhood education and children's physical activity, sedentary behavior, motor competence, and other physical health outcomes : a mixed-methods systematic review

Background: The purpose was to synthesize evidence on the association between nature-based Early Childhood Education (ECE) and children’s physical activity (PA) and motor competence (MC). Methods: A literature search of 9 databases was concluded in August 2020. Studies were eligible if (1) children were aged 2–7 years old and attending ECE, (2) ECE settings integrated nature, and (3) assessed physical outcomes. Two reviewers independently screened full-text articles and assessed study quality. Synthesis was conducted using effect direction (quantitative), thematic analysis (qualitative), and combined using a results-based convergent synthesis. Results: 1370 full-text articles were screened and 39 (31 quantitative and 8 qualitative) studies were eligible; 20 quantitative studies assessed PA and 6 assessed MC. Findings indicated inconsistent associations between nature-based ECE and increased moderate to vigorous PA, and improved speed/agility and object control skills. There were positive associations between nature-based ECE and reduced sedentary time and improved balance. From the qualitative analysis, nature-based ECE affords higher intensity PA and risky play, which could improve some MC domains. The quality of 28/31 studies was weak. Conclusions: More controlled experimental designs that describe the dose and quality of nature are needed to better inform the effectiveness of nature-based ECE on PA and MC

Regulation of the let-7a-3 Promoter by NF-κB

Changes in microRNA expression have been linked to a wide array of pathological states. However, little is known about the regulation of microRNA expression. The let-7 microRNA is a tumor suppressor that inhibits cellular proliferation and promotes differentiation, and is frequently lost in tumors. We investigated the transcriptional regulation of two let-7 family members, let-7a-3 and let-7b, which form a microRNA cluster and are located 864 bp apart on chromosome 22q13.31. Previous reports present conflicting data on the role of the NF-κB transcription factor in regulating let-7. We cloned three fragments upstream of the let-7a-3/let-7b miRNA genomic region into a plasmid containing a luciferase reporter gene. Ectopic expression of subunits of NF-κB (p50 or p65/RelA) significantly increased luciferase activity in HeLa, 293, 293T and 3T3 cells, indicating that the let-7a-3/let-7b promoter is highly responsive to NF-κB. Mutation of a putative NF-κB binding site at bp −833 reduced basal promoter activity and decreased promoter activity in the presence of p50 or p65 overexpression. Mutation of a second putative binding site, at bp −947 also decreased promoter activity basally and in response to p65 induction, indicating that both sites contribute to NF-κB responsiveness. While the levels of the endogenous primary let-7a and let-7b transcript were induced in response to NF-κB overexpression in 293T cells, the levels of fully processed, mature let-7a and let-7b miRNAs did not increase. Instead, levels of Lin-28B, a protein that blocks let-7 maturation, were induced by NF-κB. Increased Lin-28B levels could contribute to the lack of an increase in mature let-7a and let-7b. Our results suggest that the final biological outcome of NF-κB activation on let-7 expression may vary depending upon the cellular context. We discuss our results in the context of NF-κB activity in repressing self-renewal and promoting differentiation

Large-Scale Meta-GWAS Reveals Common Genetic Factors Linked to Radiation-Induced Acute Toxicities across Cancers

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.RESULTS: Shared SNP-based heritability of STATacute among all cancer types was estimated at 10% (se = 0.02), and was higher for prostate (17%, se = 0.07), head and neck (27%, se = 0.09), and breast (16%, se = 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0x10-8&lt;P-value&lt;1.0x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size -0.17; P-value=1.7x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 x10-6, Pcorrected =0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected=0.004; sun exposed Pcorrected=0.026).CONCLUSIONS: There is shared SNP-based heritability for acute RIT across and within individual cancer sites. Future meta-GWAS among large radiotherapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.</p

Comparative Study of Hematopoietic Differentiation between Human Embryonic Stem Cell Lines

Directed differentiation of human embryonic stem cells (hESCs) into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34+ or CD34+CD45+ hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34+ precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34+ hematopoietic precursors generated in vitro versus in vivo

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164\ua0Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models