An Interview with APPLE Lecture Guest Speaker Professor Leo van Lier

On February 10, 2012, the TESOL/AL Web Journal (represented by Catherine Box, Farah Akbar, and Nancy Boblett) had the pleasure of sitting down with Professor Leo van Lier, guest speaker for the 2012 APPLE Lecture Series. He was kind to take the time to answer our questions pertaining to the tremendous breadth and depth of his work: sociocultural theory and ecological approaches to language learning, scaffolding in the classroom, action-based research, and technology-assisted language learning. Leo van Lier is professor of educational linguistics in the Graduate School of Translation, Interpretation, and Language Education at the Monterey Institute of International Studies. He is the author of several books, including Scaffolding the academic success of adolescent English language learners (2010, with Aída Walqui); The ecology and semiotics of language learning (2004); Interaction in the language curriculum (1996); Introducing language awareness (1995); and The classroom and the language learner (1988). He has published numerous book chapters and articles in journals such as TESOL Quarterly, Applied Linguistics, International Journal of the Sociology of Language, The English Language Teaching Journal, Language Awareness, Le Français dans le Monde, Signos, and Applied Language Learning. Professor van Lier is the Editor-in-Chief of The Modern Language Journal and is also on the editorial boards of a number of different journals. He is co-editor of the book series Educational Linguistics for Springer Publishers

The challenges, uncertainties and opportunities of bioaerosol dispersion modelling from open composting facilities

Bioaerosols are ubiquitous organic particles that comprise viruses, bacteria and coarser fractions of organic matter. Known to adversely affect human health, the impact of bioaerosols on a population often manifests as outbreaks of illnesses such as Legionnaires Disease and Q fever, although the concentrations and environmental conditions in which these impacts occur are not well understood. Bioaerosol concentrations vary from source to source, but specific human activities such as water treatment, intensive agriculture and composting facilitate the generation of bioaerosol concentrations many times higher than natural background levels. Bioaerosols are not considered ‘traditional’ pollutants in the same way as PM10, PM2.5, and gases such as NO2, and consequently dispersion models do not include a bespoke method for their assessment. As identified in previous studies, priority areas for improving the robustness of these dispersion models include: 1) the development of bespoke monitoring studies designed to generate accurate modelling input data; 2) the publication of a robust emissions inventory; 3) a code of practice to provide guidelines for consistent bioaerosol modelling practices; and 4) a greater understanding of background bioaerosol emissions. The aim of this research project, funded by the Natural Environmental Research Council (NERC), is to address these key areas through a better understanding of the generation, concentration and potential dispersion of bioaerosols from intensive agricultural and biowaste facilities, using case studies developed at specific locations within the UK. The objective is to further refine existing bioaerosol monitoring and modelling guidelines to provide a more robust framework for regulating authorities and site operators. This contribution outlines the gaps that hinder robust dispersion modelling, and describes the on-site bioaerosol data collection methods used in the study, explaining how they might be used to close these gaps. Examples of bioaerosol dispersion modelled using ADMS 5 are presented and discussed

Towards improved bioaerosol model validation and verification

Bioaerosols, comprised of bacteria, fungi and viruses are ubiquitous in ambient air. Known to adversely affect human health, the impact of bioaerosols on a population often manifests as outbreaks of illnesses such as Legionnaires Disease and Q fever, although the concentrations and environmental conditions in which these impacts occur are not well understood. Bioaerosol concentrations vary from source to source, but specific industrialised human activities such as water treatment, intensive agriculture and open windrow composting facilitate the generation of bioaerosol concentrations many times higher than natural background levels. Bioaerosol sampling is currently undertaken according to the requirements of the Environment Agency’s regulatory framework, in which the collection of bioaerosols and not its long-term measurement is of most importance. As a consequence, sampling devices are often moved around site according to changing wind direction and sampling intervals are invariably short-term. The dispersion modelling of bioaerosols from composting facilities typically relies on proxy pollutant parameters. In addition, the use of short term emission data gathering strategies in which monitors are moved frequently with wind direction, do not provide a robust reliable and repeatable dataset by which to validate any modelling or to verify its performance. New sampling methods such as the Spectral Intensity Bioaerosol Sensor (SIBS) provide an opportunity to address several gaps in bioaerosol model validation and verification. In the context of model validation, this paper sets out the current weaknesses in bioaerosol monitoring from the perspective of robust modelling requirements

Sources of Airborne Endotoxins in Ambient Air and Exposure of Nearby Communities—A Review

Endotoxin is a bioaerosol component that is known to cause respiratory effects in exposed populations. To date, most research focused on occupational exposure, whilst much less is known about the impact of emissions from industrial operations on downwind endotoxin concentrations. A review of the literature was undertaken, identifying studies that reported endotoxin concentrations in both ambient environments and around sources with high endotoxin emissions. Ambient endotoxin concentrations in both rural and urban areas are generally below 10 endotoxin units (EU) m−3; however, around significant sources such as compost facilities, farms, and wastewater treatment plants, endotoxin concentrations regularly exceeded 100 EU m−3. However, this is affected by a range of factors including sampling approach, equipment, and duration. Reported downwind measurements of endotoxin demonstrate that endotoxin concentrations can remain above upwind concentrations. The evaluation of reported data is complicated due to a wide range of different parameters including sampling approaches, temperature, and site activity, demonstrating the need for a standardised methodology and improved guidance. Thorough characterisation of ambient endotoxin levels and modelling of endotoxin from pollution sources is needed to help inform future policy and support a robust health-based risk assessment process

Scoping studies to establish the capability and utility of a real-time bioaerosol sensor to characterise emissions from environmental sources

A novel dual excitation wavelength based bioaerosol sensor with multiple fluorescence bands called Spectral Intensity Bioaerosol Sensor (SIBS) has been assessed across five contrasting outdoor environments. The mean concentrations of total and fluorescent particles across the sites were highly variable being the highest at the agricultural farm (2.6 cm−3 and 0.48 cm−3, respectively) and the composting site (2.32 cm−3 and 0.46 cm−3, respectively) and the lowest at the dairy farm (1.03 cm−3 and 0.24 cm−3, respectively) and the sewage treatment works (1.03 cm−3 and 0.25 cm−3, respectively). In contrast, the number-weighted fluorescent fraction was lowest at the agricultural site (0.18) in comparison to the other sites indicating high variability in nature and magnitude of emissions from environmental sources. The fluorescence emissions data demonstrated that the spectra at different sites were multimodal with intensity differences largely at wavelengths located in secondary emission peaks for λex 280 and λex 370. This finding suggests differences in the molecular composition of emissions at these sites which can help to identify distinct fluorescence signature of different environmental sources. Overall this study demonstrated that SIBS provides additional spectral information compared to existing instruments and capability to resolve spectrally integrated signals from relevant biological fluorophores could improve selectivity and thus enhance discrimination and classification strategies for real-time characterisation of bioaerosols from environmental sources. However, detailed lab-based measurements in conjunction with real-world studies and improved numerical methods are required to optimise and validate these highly resolved spectral signatures with respect to the diverse atmospherically relevant biological fluorophores

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Achieving drinking water compliance levels for metaldehyde with an acclimated sand bioreactor

Metaldehyde removal was delivered to below the 0.1 μg L−1 regulatory concentration in a laboratory scale continuous upflow fluidised sand bioreactor that had undergone acclimation through selective enrichment for metaldehyde degradation. This is the first reported case of successful continuous flow biological treatment of metaldehyde from real drinking water sources treating environmentally realistic metaldehyde concentrations. The impact of the acclimation process was impermanent, with the duration of effective treatment directly related to the elevated concentration of metaldehyde used during the enrichment process. The efficacy of the approach was demonstrated in continuous flow columns at both laboratory and pilot scale enabling degradation rates of between 0.1 and 0.2 mg L−1 h−1. Future work needs to focus on optimisation of the sand bioreactor and the acclimation process to ensure viability and feasibility of the approach at full scale