Diagnosing Viral Infections Through T-Cell Receptor Sequencing of Activated CD8+ T Cells.

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3ß TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3ß sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/ß sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics.

Probing the aggregated effects of purifying selection per individual on 1,380 medical phenotypes in the UK Biobank.

Understanding the relationship between natural selection and phenotypic variation has been a long-standing challenge in human population genetics. With the emergence of biobank-scale datasets, along with new statistical metrics to approximate strength of purifying selection at the variant level, it is now possible to correlate a proxy of individual relative fitness with a range of medical phenotypes. We calculated a per-individual deleterious load score by summing the total number of derived alleles per individual after incorporating a weight that approximates strength of purifying selection. We assessed four methods for the weight, including GERP, phyloP, CADD, and fitcons. By quantitatively tracking each of these scores with the site frequency spectrum, we identified phyloP as the most appropriate weight. The phyloP-weighted load score was then calculated across 15,129,142 variants in 335,161 individuals from the UK Biobank and tested for association on 1,380 medical phenotypes. After accounting for multiple test correction, we observed a strong association of the load score amongst coding sites only on 27 traits including body mass, adiposity and metabolic rate. We further observed that the association signals were driven by common variants (derived allele frequency > 5%) with high phyloP score (phyloP > 2). Finally, through permutation analyses, we showed that the load score amongst coding sites had an excess of nominally significant associations on many medical phenotypes. These results suggest a broad impact of deleterious load on medical phenotypes and highlight the deleterious load score as a tool to disentangle the complex relationship between natural selection and medical phenotypes.

Elucidating the Mechanism of Fe Incorporation in In Situ Synthesized Co-Fe Oxygen-Evolving Nanocatalysts.

Ni- and Co-based catalysts with added Fe demonstrate promising activity in the oxygen evolution reaction (OER) during alkaline water electrolysis, with the presence of Fe in a certain quantity being crucial for their enhanced performance. The mode of incorporation, local placement, and structure of Fe ions in the host catalyst, as well as their direct/indirect contribution to enhancing the OER activity, remain under active investigation. Herein, the mechanism of Fe incorporation into a Co-based host was investigated using an in situ synthesized Co-Fe catalyst in an alkaline electrolyte containing Co2+ and Fe3+. Fe was found to be uniformly incorporated, which occurs solely after the anodic deposition of the Co host structure and results in exceptional OER activity with an overpotential of 319 mV at 10 mA cm-2 and a Tafel slope of 28.3 mV dec-1. Studies on the lattice structure, chemical oxidation states, and mass changes indicated that Fe is incorporated into the Co host structure by replacing the Co3+ sites with Fe3+ from the electrolyte. Operando Raman measurements revealed that the presence of doped Fe in the Co host structure reduces the transition potential of the in situ Co-Fe catalyst to the OER-active phase CoO2. The findings of our facile synthesis of highly active and stable Co-Fe particle catalysts provide a comprehensive understanding of the role of Fe in Co-based electrocatalysts, covering aspects that include the incorporation mode, local structure, placement, and mechanistic role in enhancing the OER activity.

Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.

The clinical success of T cell receptor (TCR) gene-transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin-2 production and the expression levels of TCR activation markers on BW cells. In TCR-expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD-1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor-infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD-1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high-functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high-functional TCRs among tumor-reacting TCRs, which will promote TCR-T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD-1 allows us to select highly responsive TCRs.

Genome-wide polygenic risk score for retinopathy of type 2 diabetes.

Diabetic retinopathy (DR) is a common consequence in type 2 diabetes (T2D) and a leading cause of blindness in working-age adults. Yet, its genetic predisposition is largely unknown. Here, we examined the polygenic architecture underlying DR by deriving and assessing a genome-wide polygenic risk score (PRS) for DR. We evaluated the PRS in 6079 individuals with T2D of European, Hispanic, African and other ancestries from a large-scale multi-ethnic biobank. Main outcomes were PRS association with DR diagnosis, symptoms and complications, and time to diagnosis, and transferability to non-European ancestries. We observed that PRS was significantly associated with DR. A standard deviation increase in PRS was accompanied by an adjusted odds ratio (OR) of 1.12 [95% confidence interval (CI) 1.04-1.20; P = 0.001] for DR diagnosis. When stratified by ancestry, PRS was associated with the highest OR in European ancestry (OR = 1.22, 95% CI 1.02-1.41; P = 0.049), followed by African (OR = 1.15, 95% CI 1.03-1.28; P = 0.028) and Hispanic ancestries (OR = 1.10, 95% CI 1.00-1.10; P = 0.050). Individuals in the top PRS decile had a 1.8-fold elevated risk for DR versus the bottom decile (P = 0.002). Among individuals without DR diagnosis, the top PRS decile had more DR symptoms than the bottom decile (P = 0.008). The PRS was associated with retinal hemorrhage (OR = 1.44, 95% CI 1.03-2.02; P = 0.03) and earlier DR presentation (10% probability of DR by 4 years in the top PRS decile versus 8 years in the bottom decile). These results establish the significant polygenic underpinnings of DR and indicate the need for more diverse ancestries in biobanks to develop multi-ancestral PRS.

Assessment of cyclic volatile methyl siloxanes (CVMSs) in indoor dust from different micro-environments in northern and central Vietnam.

Comprehensive studies on emerging contaminants like volatile methyl siloxanes in settled dust from different micro-environments are still limited. In this study, concentrations and distribution of cyclic volatile methyl siloxanes (CVMSs) including D3, D4, D5, and D6 were examined in indoor dust samples collected from various micro-environments in northern and central Vietnam. Concentrations of total CVMSs in the dust samples ranged from 86.0 to 5890 (median 755) ng/g and decreased in the order: waste processing workshops (median 1560; range 329-5890) > common houses (650; 115-1680) > university classrooms (480; 86.0-1540) > vehicle repair shops (295; 126-1950) ng/g. This observation suggests that informal waste processing activities are sources of CVMSs. Among the studied CVMSs, D5 was the most predominant compound (41 ± 14%), followed by D6 (26 ± 13%), D4 (23 ± 12%), and D3 (11 ± 11%). Moderate positive correlations between D3/D4, D4/D5, and D5/D6 were found. Median daily intake doses of D3, D4, D5, and D6 through dust ingestion were 0.016, 0.051, 0.11, and 0.054 ng/kg/d, respectively, which were comparable to water consumption and markedly lower than the air inhalation pathway.

Portable wedge prism scanner for laser surface cleaning of corroded 304L stainless steel.

A compact wedge prism scanner for laser surface cleaning is proposed, wherein the concept of system was studied based on geometric analysis. The final equations for the design express the transposition of the laser beam focal point and scanning radius. The results were verified through comparisons to both Zemax simulation and experiments. There was satisfactory agreement between the equations and Zemax simulation, but slight disagreement with the experiments. Additionally, two main factors of wedge prism scanner in commercial laser removal applications (circumferential overlap and spot overlap) was also discussed and the completely corrosion removal experiment indicated the potential use of our scanner.

Distribution and ecological risk assessment of phthalic acid esters in surface sediments of three rivers in Northern Vietnam.

Pollution status and distribution characteristics of ten typical phthalic acid esters (PAEs) were investigated in 36 sediment samples collected from three rivers in Northern Vietnam from June to October 2020. The total concentrations of PAEs in sediment samples collected from the To Lich River (n = 9), the Nhue River (n = 12), and the Day River (n = 15) were in ranges of 11,000-125,000 ng/g-dwt (mean/median: 50,000/42,200 ng/g-dwt), 2140-89,900 ng/g-dwt (mean/median: 29,300/20,700 ng/g-dwt), and 1140-43,100 ng/g-dwt (mean/median: 13,800/10,400 ng/g-dwt), respectively. Among ten PAEs studied, di-(2-ethylhexyl) phthalate (DEHP) was found at the highest levels in all samples meanwhile dimethyl phthalate (DMP), diethyl phthalate (DEP), and dipropyl phthalate (DPP) were detected at low frequency and concentration. Significant correlations have existed between the median-chain (C4-C7) PAE pairs in sediment samples. Due to the high accumulation in the sediments, the median-chain PAEs had a higher ecological risk than the short-chain (C1-C3) PAEs. These contaminants may present a longstanding influence on organisms and ecosystems.

Population-Based Penetrance of Deleterious Clinical Variants.

Importance: Population-based assessment of disease risk associated with gene variants informs clinical decisions and risk stratification approaches. Objective: To evaluate the population-based disease risk of clinical variants in known disease predisposition genes. Design, Setting, and Participants: This cohort study included 72 434 individuals with 37 780 clinical variants who were enrolled in the BioMe Biobank from 2007 onwards with follow-up until December 2020 and the UK Biobank from 2006 to 2010 with follow-up until June 2020. Participants had linked exome and electronic health record data, were older than 20 years, and were of diverse ancestral backgrounds. Exposures: Variants previously reported as pathogenic or predicted to cause a loss of protein function by bioinformatic algorithms (pathogenic/loss-of-function variants). Main Outcomes and Measures: The primary outcome was the disease risk associated with clinical variants. The risk difference (RD) between the prevalence of disease in individuals with a variant allele (penetrance) vs in individuals with a normal allele was measured. Results: Among 72 434 study participants, 43 395 were from the UK Biobank (mean [SD] age, 57 [8.0] years; 24 065 [55%] women; 2948 [7%] non-European) and 29 039 were from the BioMe Biobank (mean [SD] age, 56 [16] years; 17 355 [60%] women; 19 663 [68%] non-European). Of 5360 pathogenic/loss-of-function variants, 4795 (89%) were associated with an RD less than or equal to 0.05. Mean penetrance was 6.9% (95% CI, 6.0%-7.8%) for pathogenic variants and 0.85% (95% CI, 0.76%-0.95%) for benign variants reported in ClinVar (difference, 6.0 [95% CI, 5.6-6.4] percentage points), with a median of 0% for both groups due to large numbers of nonpenetrant variants. Penetrance of pathogenic/loss-of-function variants for late-onset diseases was modified by age: mean penetrance was 10.3% (95% CI, 9.0%-11.6%) in individuals 70 years or older and 8.5% (95% CI, 7.9%-9.1%) in individuals 20 years or older (difference, 1.8 [95% CI, 0.40-3.3] percentage points). Penetrance of pathogenic/loss-of-function variants was heterogeneous even in known disease predisposition genes, including BRCA1 (mean [range], 38% [0%-100%]), BRCA2 (mean [range], 38% [0%-100%]), and PALB2 (mean [range], 26% [0%-100%]). Conclusions and Relevance: In 2 large biobank cohorts, the estimated penetrance of pathogenic/loss-of-function variants was variable but generally low. Further research of population-based penetrance is needed to refine variant interpretation and clinical evaluation of individuals with these variant alleles.

Selection of a density separation solution to study microplastics in tropical riverine sediment.

Microplastics (MPs) are small (< 5 mm) plastic particles that are widely found in marine, freshwater, terrestrial and atmospheric environments. Due to their prevalence and persistence, MPs are considered an emerging contaminant of environmental concern. The separation and quantitation of MPs from freshwater sediments is a challenging and critical issue. It is necessary to identify the fate and sources of MPs in the environment, minimise their release and adverse effects. Compared to marine sediments, standardised methods for extracting and estimating the amount of MPs in freshwater sediments are relatively limited. The present study focuses on MP recovery efficiency of four commonly used salt solutions (NaCl, NaI, CaCl2 and ZnCl2) for isolating MPs during the density separation step from freshwater sediment. Known combinations of artificial MP particles (PS, PE, PVC, PET, PP and HDPE) were spiked into standard river sediment. Extraction using NaI, ZnCl2 and NaCl solutions resulted in higher recovery rates from 37 to 97% compared to the CaCl2 solution (28-83%) and varied between polymer types. Low-density MPs (PE, HDPE, PP and PS) were more effectively recovered (> 87%) than the denser polymers (PET and PVC: 37 to 88.8%) using NaCl, NaI and ZnCl2 solutions. However, the effective flotation of ZnCl2 and NaI solutions is relatively expensive and unsafe to the environment, especially in the context of developing countries. Therefore, considering the efficiency, cost and environmental criteria, NaCl solution was selected. The protocol was then tested by extracting MPs from nine riverine sediment samples from the Red River Delta. Sediments collected from urban rivers were highly polluted by MPs (26,000 MPs items·kg-1 DW) compared to sediments located downstream. Using a NaCl solution was found to be effective in this case study and might also be used in long-term and large-scale MP monitoring programmes in Vietnam.

Genetic pleiotropy of ERCC6 loss-of-function and deleterious missense variants links retinal dystrophy, arrhythmia, and immunodeficiency in diverse ancestries.

Biobanks with exomes linked to electronic health records (EHRs) enable the study of genetic pleiotropy between rare variants and seemingly disparate diseases. We performed robust clinical phenotyping of rare, putatively deleterious variants (loss-of-function [LoF] and deleterious missense variants) in ERCC6, a gene implicated in inherited retinal disease. We analyzed 213,084 exomes, along with a targeted set of retinal, cardiac, and immune phenotypes from two large-scale EHR-linked biobanks. In the primary analysis, a burden of deleterious variants in ERCC6 was strongly associated with (1) retinal disorders; (2) cardiac and electrocardiogram perturbations; and (3) immunodeficiency and decreased immunoglobulin levels. Meta-analysis of results from the BioMe Biobank and UK Biobank showed a significant association of deleterious ERCC6 burden with retinal dystrophy (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.5-4.6; p = 8.7 × 10-4 ), atypical atrial flutter (OR = 3.5, 95% CI: 1.9-6.5; p = 6.2 × 10-5 ), arrhythmia (OR = 1.5, 95% CI: 1.2-2.0; p = 2.7 × 10-3 ), and lymphocyte immunodeficiency (OR = 3.8, 95% CI: 2.1-6.8; p = 5.0 × 10-6 ). Carriers of ERCC6 LoF variants who lacked a diagnosis of these conditions exhibited increased symptoms, indicating underdiagnosis. These results reveal a unique genetic link among retinal, cardiac, and immune disorders and underscore the value of EHR-linked biobanks in assessing the full clinical profile of carriers of rare variants.

Non-back-reflecting polygon scanner with applications in surface cleaning.

Polygon mirror scanners are attracting considerable interest owing to their rapid speed and large scanning area. Here, we focused on the back-reflection effect of the polygon scanner. A new polygon scanner system was designed based on a geometric analysis. The final equations for the design express the position of the laser beam source having the largest scanning length without the reflected beam traveling back to the fiber. The proposed system performed a raster scan on an area. Additionally, a paint stripping experiment was conducted to demonstrate the potential use of our scanner in commercial laser cleaning applications.

Tailoring Dispersion of Room-Temperature Exciton-Polaritons with Perovskite-Based Subwavelength Metasurfaces.

Exciton-polaritons represent a promising platform for studying quantum fluids of light and realizing prospective all-optical devices. Here we report on the experimental demonstration of exciton-polaritons at room temperature in resonant metasurfaces made from a sub-wavelength two-dimensional lattice of perovskite pillars. The strong coupling regime is revealed by both angular-resolved reflectivity and photoluminescence measurements, showing anticrossing between photonic modes and the exciton resonance with a Rabi splitting in the 200 meV range. Moreover, by tailoring the photonic Bloch mode to which perovskite excitons are coupled, polaritonic dispersions are engineered exhibiting linear, parabolic, and multivalley dispersions. All of our results are perfectly reproduced by both numerical simulations based on a rigorous coupled wave analysis and an elementary model based on a quantum theory of radiation-matter interaction. Our results suggest a new approach to study exciton-polaritons and pave the way toward large-scale and low-cost integrated polaritonic devices operating at room temperature.

Oxygen Evolution Reaction in Ba0.5Sr0.5Co0.8Fe0.2O3-δ Aided by Intrinsic Co/Fe Spinel-Like Surface.

Among the perovskites used to catalyze the oxygen evolution reaction (OER), Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) exhibits excellent activity which is thought to be related to dynamic reconstruction at the flexible perovskite surface due to accommodation of large amount of oxygen vacancies. By studying the local structure and chemistry of BSCF surfaces, in detail, via a range of transmission electron microscopy (TEM) methods, we show that the surfaces of the as-synthesized BSCF particles are Co/Fe rich, and remarkably, adopt a spinel-like structure with a reduced valence of Co ions. Post-mortem and identical location TEM analyses reveal that the Co/Fe spinel-like surface retains a stable chemical environment of the Co/Fe ions, although its structure weakens after electrochemical processing. Further, it is verified that prior to the onset of OER, the Co/Fe spinel-like surface promotes the formation of the highly active Co(Fe)OOH phase, which enhances the OER electrocatalytic properties of the underlying conductive BSCF perovskite. This study provides a detailed understanding of the fundamental transformations that oxide catalysts undergo during electrochemical processes and can aid in the development of novel oxide catalysts with enhanced activity.

Mass Cytometry and Single-Cell RNA-seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles.

Understanding the interactions between nanoparticles (NPs) and human immune cells is necessary for justifying their utilization in consumer products and biomedical applications. However, conventional assays may be insufficient in describing the complexity and heterogeneity of cell-NP interactions. Herein, mass cytometry and single-cell RNA-sequencing (scRNA-seq) are complementarily used to investigate the heterogeneous interactions between silver nanoparticles (AgNPs) and primary immune cells. Mass cytometry reveals the heterogeneous biodistribution of the positively charged polyethylenimine-coated AgNPs in various cell types and finds that monocytes and B cells have higher association with the AgNPs than other populations. scRNA-seq data of these two cell types demonstrate that each type has distinct responses to AgNP treatment: NRF2-mediated oxidative stress is confined to B cells, whereas monocytes show Fcγ-mediated phagocytosis. Besides the between-population heterogeneity, analysis of single-cell dose-response relationships further reveals within-population diversity for the B cells and naïve CD4+ T cells. Distinct subsets having different levels of cellular responses with respect to their cellular AgNP doses are found. This study demonstrates that the complementary use of mass cytometry and scRNA-seq is helpful for gaining in-depth knowledge on the heterogeneous interactions between immune cells and NPs and can be incorporated into future toxicity assessments of nanomaterials.

Sandaracinobacter neustonicus sp. nov., isolated from the sea surface microlayer in the Southwestern Pacific Ocean, and emended description of the genus Sandaracinobacter.

A Gram-stain-negative, non-motile, facultatively anaerobic and rod-shaped bacterial strain, designated PAMC 28131T, was isolated from a sea surface microlayer sample in the open water of the Pacific Ocean. Phylogenetic analysis of the 16S rRNA gene sequence of strain PAMC 28131T revealed an affiliation to the genus Sandaracinobacter with the closest species Sandaracinobacter sibiricus RB16-17T (sequence similarity of 98.2 %). Strain PAMC 28131T was able to grow optimally with 0.5-1.0 % NaCl and at pH 6.5-7.0 and 30 °C. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. The major cellular fatty acids (>10 %) were C18 : 1 ω6c and/or C18 : 1 ω7c, (42.6 %), C17 : 1 ω6c (19.3 %) and C16 : 1 ω6c and/or C16 : 1 ω7c (15.8 %), and the respiratory quinone was Q-10. The genomic DNA G+C content was 65.3 mol%. The phylogenetic, phenotypic and chemotaxonomic data showed that strain PAMC 28131T could be clearly distinguished from S. sibiricus RB16-17T. Thus, strain PAMC 28131T should be classified as representing a novel species in the genus Sandaracinobacter, for which the name Sandaracinobacter neustonicus sp. nov. is proposed. The type strain is PAMC 28131T (=KCCM 43127T=JCM 30734T).

Multiple Modes of Positive Selection Shaping the Patterns of Incomplete Selective Sweeps over African Populations of Drosophila melanogaster.

It remains a challenge in evolutionary genetics to elucidate how beneficial mutations arise and propagate in a population and how selective pressures on mutant alleles are structured over space and time. By identifying "sweeping haplotypes (SHs)" that putatively carry beneficial alleles and are increasing (or have increased) rapidly in frequency, and surveying the geographic distribution of SH frequencies, we can indirectly infer how selective sweeps unfold in time and thus which modes of positive selection underlie those sweeps. Using population genomic data from African Drosophila melanogaster, we identified SHs from 37 candidate loci under selection. At more than half of loci, we identify single SHs. However, many other loci harbor multiple independent SHs, namely soft selective sweeps, either due to parallel evolution across space or a high beneficial mutation rate. At about a quarter of the loci, intermediate SH frequencies are found across multiple populations, which cannot be explained unless a certain form of frequency-dependent positive selection, such as heterozygote advantage, is invoked given the reasonable range of migration rates between African populations. At one locus, many independent SHs are observed over multiple populations but always together with ancestral haplotypes. This complex pattern is compatible with a large number of mutational targets in a gene and frequency-dependent selection on new variants. We conclude that very diverse modes of positive selection are operating at different sets of loci in D. melanogaster populations.

Health professional perceptions regarding screening tools for developmental surveillance for children in a multicultural part of Sydney, Australia.

BACKGROUND: Encouraging early child development and the early identification of developmental difficulties is a priority. The Ministry of Health in the Australian State of New South Wales (NSW), has recommended a program of developmental surveillance using validated screening questionnaires, namely, the Parents' Evaluation of Development Status (PEDS) and Ages and Stages Questionnaire (ASQs), however, the use of these tools has remained sub-optimal. A longitudinal prospective birth cohort "Watch Me grow" study was carried out in the South Western Sydney (SW) region of NSW to ascertain the uptake as well as the strategies and the resources required to maximise engagement in the surveillance program. This paper reports on a qualitative component of the study examining the attitudes, enablers and barriers to the current developmental surveillance practices, with reference to screening tools, amongst health professionals. METHODS: Qualitative data from 37 primary health care providers in a region of relative disadvantage in Sydney was analysed. RESULTS: The major themes that emerged from the data were the "difficulties/problems" and "positives/benefits" of surveillance in general, and "specificity" of the tools which were employed. Barriers of time, tool awareness, knowledge and access of referral pathways, and services were important for the physician providers, while the choice of screening tools and access to these tools in other languages were raised as important issues by Child and Family Health Nurses (CFHN). The use of these tools by health professionals was also influenced by what the professionals perceived as the parents' understanding of their child's development. While the PEDS and ASQs was utilised by CFHNs, both General Practitioners (GPs) and paediatricians commented that they lacked awareness of developmental screening tools and highlighted further training needs. CONCLUSIONS: The results highlight the practical challenges to, and limited knowledge and uptake of, the use of recommended screening tools as part of developmental surveillance. There is a need for further research regarding the most effective integrated models of care which will allow for a better collaboration between parents and service providers and improve information sharing between different professionals such as CFHNs GPs, Practices nurses and Paediatricians involved in screening and surveillance programs.

Flow Cytometry-Based Quantification of Cellular Au Nanoparticles.

There has been a great deal of research regarding the cellular association of nanoparticles (NPs), although there are only a few methods available yet for the quantitative measurements of cellular NPs. In this study, we propose a simple and quantitative method to estimate the cellular uptake of Au NPs into cervical cancer cells (HeLa) based on their side scattering (SSC) intensities measured by flow cytometry (FCM). We have compared SSC intensities of HeLa cells exposed to eight different types of Au NPs (40-100 nm size, with positive or negative surface charge) with the amount of cellular Au NPs measured by inductively coupled plasma mass spectrometry (ICPMS). On the basis of these comparisons, we have found linear correlations between the cellular Au NPs and the SSC intensities and used them to estimate the amount of Au NPs associated with HeLa cells. Once the correlations were found for specific cell lines and types of nanoparticles, this approach is useful for simple and quantitative estimation of the cellular Au NPs, without performing labor-intensive and complicated sample preparation procedures required for the ICPMS approach.