Reading Performance is Predicted by More Than Phonological Processing

We compared three phonological processing components (phonological awareness, rapid automatized naming and phonological memory), verbal working memory, and attention control in terms of how well they predict the various aspects of reading: word recognition, pseudoword decoding, fluency and comprehension, in a mixed sample of 182 children ages 8–12 years. Participants displayed a wide range of reading ability and attention control. Multiple regression was used to determine how well the phonological processing components, verbal working memory, and attention control predict reading performance. All equations were highly significant. Phonological memory predicted word identification and decoding. In addition, phonological awareness and rapid automatized naming predicted every aspect of reading assessed, supporting the notion that phonological processing is a core contributor to reading ability. Nonetheless, phonological processing was not the only predictor of reading performance. Verbal working memory predicted fluency, decoding and comprehension, and attention control predicted fluency. Based upon our results, when using Baddeley’s model of working memory it appears that the phonological loop contributes to basic reading ability, whereas the central executive contributes to fluency and comprehension, along with decoding. Attention control was of interest as some children with ADHD have poor reading ability even if it is not sufficiently impaired to warrant diagnosis. Our finding that attention control predicts reading fluency is consistent with prior research which showed sustained attention plays a role in fluency. Taken together, our results suggest that reading is a highly complex skill that entails more than phonological processing to perform well

The Quantitative-MFG Test: A linear mixed effect model to detect maternal-offspring gene interactions

Maternal-offspring gene interactions, aka maternal-fetal genotype (MFG) incompatibilities, are neglected in complex diseases and quantitative trait studies. They are implicated in birth to adult onset diseases but there are limited ways to investigate their influence on quantitative traits. We present the Quantitative-MFG (QMFG) test, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects. The QMFG handles families of any size, common or general scenarios of MFG incompatibility, and additional covariates. We develop likelihood ratio tests (LRTs) and rapid score tests and show they provide correct inference. In addition, the LRT’s alternative model provides unbiased parameter estimates. We show that testing the association of SNPs by fitting a standard model, which only considers the offspring genotypes, has very low power or can lead to incorrect conclusions. We also show that offspring genetic effects are missed if the MFG modeling assumptions are too restrictive. With GWAS data from the San Antonio Family Heart Study, we demonstrate that the QMFG score test is an effective and rapid screening tool. The QMFG test therefore has important potential to identify pathways of complex diseases for which the genetic etiology remains to be discovered

Visual Processing in Reading Disorders and Attention-Deficit/Hyperactivity Disorder and Its Contribution to Basic Reading Ability

Whether visual processing deficits are common in reading disorders (RD), and related to reading ability in general, has been debated for decades. The type of visual processing affected also is debated, although visual discrimination and short-term memory (STM) may be more commonly related to reading ability. Reading disorders are frequently comorbid with ADHD, and children with ADHD often have subclinical reading problems. Hence, children with ADHD were used as a comparison group in this study. ADHD and RD may be dissociated in terms of visual processing. Whereas RD may be associated with deficits in visual discrimination and short-term memory for order, ADHD is associated with deficits in visual-spatial processing. Thus, we hypothesized that children with RD would perform worse than controls and children with ADHD only on a measure of visual discrimination and a measure of visual STM that requires memory for order. We expected all groups would perform comparably on the measure of visual STM that does not require sequential processing. We found children with RD or ADHD were commensurate to controls on measures of visual discrimination and visual STM that do not require sequential processing. In contrast, both RD groups (RD, RD/ADHD) performed worse than controls on the measure of visual STM that requires memory for order, and children with comorbid RD/ADHD performed worse than those with ADHD. In addition, of the three visual measures, only sequential visual STM predicted reading ability. Hence, our findings suggest there is a deficit in visual sequential STM that is specific to RD and is related to basic reading ability. The source of this deficit is worthy of further research, but it may include both reduced memory for order and poorer verbal mediation

Transformative spaces in the making: key lessons from nine cases in the Global South

Creating a just and sustainable planet will require not only small changes, but also systemic transformations in how humans relate to the planet and to each other, i.e., social–ecological transformations. We suggest there is a need for collaborative environments where experimentation with new configurations of social–ecological systems can occur, and we refer to these as transformative spaces. In this paper, we seek a better understanding of how to design and enable the creation of transformative spaces in a development context. We analyse nine case studies from a previous special issue on Designing Transformative Spaces that aimed to collect examples of cutting-edge action-oriented research on transformations from the Global South. The analysis showed five design phases as being essential: Problem Definition Phase; Operationalisation Phase; Tactical Phase; Outcome Phase; and Reflection Phase. From this synthesis, we distilled five key messages that should be considered when designing research, including: (a) there are ethical dilemmas associated with creating a transformative space in a system; (b) it is important to assess the readiness of the system for change before engaging in it; (c) there is a need to balance between ‘safe’ and ‘safe-enough’ spaces for transformation; (d) convening a transformative space requires an assemblage of diverse methodological frameworks and tools; and (e) transformative spaces can act as a starting point for institutionalising transformative change. Many researchers are now engaging in transdisciplinary transformations research, and are finding themselves at the knowledge–action interface contributing to transformative space-making. We hope that by analysing experiences from across different geographies we can contribute towards better understanding of how to navigate the processes needed for the urgent global transformations that are being called for to create a more equitable and sustainable planet Earth

A Comparative Exploration of Community Pharmacists' Views on the Nature and Management of Over-the-Counter (OTC) and Prescription Codeine Misuse in Three Regulatory Regimes: Ireland, South Africa and the United Kingdom

Misuse of codeine containing preparations is a public health concern given the potential for associated harms and dependence. This study explores the perspectives of community pharmacists in three regulatory regimes on issues of customer misuse of over-the-counter (OTC) and prescribed codeine. A qualitative design comprising six focus groups (n = 45) was conducted in Ireland, United Kingdom, South Africa. Transcripts were analysed using the constant comparative method of content analysis. Pharmacists described popular codeine-containing products and the need for improved medicine information and warning labels. Issues around legitimate availability of codeine and regulatory status; presence of therapeutic need; difficulties in customer–pharmacist communication; business environments and retail focus were raised. Participants also discussed how they identified customers potentially misusing codeine and difficulties in relationships between pharmacists and prescribers. A number of recommendations were put forward as ways to manage the issues. The study highlights the difficulties encountered by community pharmacists operating under various regulatory regimes when supplying codeine containing preparations in negotiating patient awareness and compliance and potential ways to deal with misuse and dependence

Controlling the Response: Predictive Modeling of a Highly Central, Pathogen-Targeted Core Response Module in Macrophage Activation

We have investigated macrophage activation using computational analyses of a compendium of transcriptomic data covering responses to agonists of the TLR pathway, Salmonella infection, and manufactured amorphous silica nanoparticle exposure. We inferred regulatory relationship networks using this compendium and discovered that genes with high betweenness centrality, so-called bottlenecks, code for proteins targeted by pathogens. Furthermore, combining a novel set of bioinformatics tools, topological analysis with analysis of differentially expressed genes under the different stimuli, we identified a conserved core response module that is differentially expressed in response to all studied conditions. This module occupies a highly central position in the inferred network and is also enriched in genes preferentially targeted by pathogens. The module includes cytokines, interferon induced genes such as Ifit1 and 2, effectors of inflammation, Cox1 and Oas1 and Oasl2, and transcription factors including AP1, Egr1 and 2 and Mafb. Predictive modeling using a reverse-engineering approach reveals dynamic differences between the responses to each stimulus and predicts the regulatory influences directing this module. We speculate that this module may be an early checkpoint for progression to apoptosis and/or inflammation during macrophage activation

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness