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DNA double-strand breaks (DSBs) must be properly repaired within diverse chromatin domains to maintain genome stability. Whereas euchromatin has an open structure and is associated with transcription, facultative heterochromatin is essential to silence developmental genes and forms compact nuclear condensates, called polycomb bodies. Whether the specific chromatin properties of facultative heterochromatin require distinct DSB repair mechanisms remains unknown. Here, we integrate single DSB systems in euchromatin and facultative heterochromatin in Drosophila melanogaster and find that heterochromatic DSBs rapidly move outside polycomb bodies. These DSB movements coincide with a break-proximal reduction in the canonical heterochromatin mark histone H3 Lysine 27 trimethylation (H3K27me3). We demonstrate that DSB movement and loss of H3K27me3 at heterochromatic DSBs depend on the histone demethylase dUtx. Moreover, loss of dUtx specifically disrupts completion of homologous recombination at heterochromatic DSBs. We conclude that DSBs in facultative heterochromatin require dUtx-mediated loss of H3K27me3 to promote DSB movement and repair. Here the authors show that DNA double-strand breaks move outside facultative heterochromatin for repair, which coincides with demethylation of H3K27me3. This movement, demethylation and subsequent correct repair depend on the histone demethylase dUtx. [ABSTRACT FROM AUTHOR]

Hempseed (Cannabis sativa L.) is a valuable source of oil and a quality vegetable protein source, but little is known about its fiber composition. This study provides the most extensive characterization of hempseed cell wall polysaccharides to date. Quantification of total dietary fiber (TDF) and acetyl bromide soluble lignin (ABSL), monosaccharide composition through two complimentary hydrolysis methods (Saeman hydrolysis and methanolysis), and linkage analysis via derivatization of monosaccharides to partially methylated alditol acetates (PMAAs) were done. More detailed profiling of hempseed xyloglucans and pectic arabinans and galactans was performed via targeted enzymatic generation and quantification of characteristic oligosaccharides. Hempseed's cell wall polysaccharide profile is consistent with the primary cell walls of dicots, but it is particularly abundant in linear xylans, presumably from secondary cell walls. The hempseed water-insoluble cell wall material was mostly composed of cellulose and xylans, but pectins (including arabinans with a low degree of branching and galactans), xyloglucans with L- and F-motifs and a relatively low substitution rate, and mannans were also present. These data show that hempseed is a good source of complex dietary fiber for human diets and a potential fiber additive for herbivorous livestock diets. Potential consequences of these carbohydrate structural details on hempseed's microbial fermentability are discussed. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts. To overcome challenges posted by vast number of GPCR genes and redundancy, the authors disrupted nearly all GPCR-encoding genes in C. elegans, enabling effective examination of GPCR signaling and offering a valuable resource for the research community. [ABSTRACT FROM AUTHOR]

Vibrio natriegens is a halophilic bacterium with the fastest generation time of non-pathogenic bacteria reported so far. It therefore has high potential as a production strain for biotechnological production processes or other applications in biotechnology. Culture media for V. natriegens typically contain high sodium chloride concentrations. The corresponding high chloride concentrations can lead to corrosion processes on metal surfaces in bioreactors. Here we report the development of a low-chloride chemically defined medium for V. natriegens. Sodium chloride was completely replaced by the sodium salts disodium hydrogen phosphate, disodium sulfate, and sodium citrate, while keeping the total concentration of sodium ions constant. The use of citrate prevents the occurrence of precipitates, especially of ammonium magnesium phosphate. With this defined medium, high-cell-density fed-batch cultivations in laboratory-scale bioreactors using exponential feeding yielded biomass concentrations of more than 60 g L−1. Key points: A defined medium for V. natriegens that only contains traces of chloride was developed Corrosion processes on metal surfaces in industrial bioreactors can thus be prevented High yields of biomass can be achieved in fed-batch cultivation with this medium [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Evaluating the environmental impact of debit card payments" published in the International Journal of Life Cycle Assessment. The authors made an error in their analysis, using an incorrect number of debit card payments in their calculations. As a result, the environmental impact and global warming potential of debit card payments in the Netherlands in 2015 are much lower than originally reported. The corrected results show that one Dutch debit card transaction in 2015 had an environmental impact of 89 µPt and a global warming potential of 0.85 g CO2 equivalents. The document also includes revised figures and tables reflecting the new calculations. [Extracted from the article]

Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons. Voltage-gated sodium channels function as multiprotein signaling complexes. Here, authors show that the dispanin TMEM233 is essential for activity of stinging nettle toxins and that co-expression of TMEM233 modulates the gating properties of NaV1.7. [ABSTRACT FROM AUTHOR]

DNA double-strand breaks are a major threat to cellular survival and genetic integrity. In addition to high fidelity repair, three intrinsically mutagenic DNA break repair routes have been described, i.e. single-strand annealing (SSA), polymerase theta-mediated end-joining (TMEJ) and residual ill-defined microhomology-mediated end-joining (MMEJ) activity. Here, we identify C. elegans Helicase Q (HELQ-1) as being essential for MMEJ as well as for SSA. We also find HELQ-1 to be crucial for the synthesis-dependent strand annealing (SDSA) mode of homologous recombination (HR). Loss of HELQ-1 leads to increased genome instability: patchwork insertions arise at deletion junctions due to abortive rounds of polymerase theta activity, and tandem duplications spontaneously accumulate in genomes of helq-1 mutant animals as a result of TMEJ of abrogated HR intermediates. Our work thus implicates HELQ activity for all DSB repair modes guided by complementary base pairs and provides mechanistic insight into mutational signatures common in HR-defective cancers. Microhomology-mediated end-joining (MMEJ) is a poorly defined mutagenic DNA break repair pathway. Here the authors show that the helicase HELQ is essential for polymerase theta-independent MMEJ, single-strand annealing and homologous recombination through synthesis dependent strand annealing in C. elegans. [ABSTRACT FROM AUTHOR]

Objectives: Mindfulness-Based Stress Reduction (MBSR) involves training in mindful meditation and has been shown to improve functioning across a range of different disorders. However, little research has focused on the use of MBSR in stroke patients, and previous MBSR studies typically have not included an active control condition to account for non-specific factors that could contribute to the observed benefits. Methods: We conducted a pilot study of MBSR in chronic stroke patients, comparing MBSR to an active control condition. Half of participants were randomly assigned to a standard 8-week MBSR class, and the other half of participants were assigned to an 8-week Brain Health class matched for schedule, instructor, and format. Participants were assessed pre- and post-intervention by blinded examiners on a neuropsychological battery that included primary outcome measures of psychological and cognitive functioning. Participants were also given an anonymous questionnaire following the post-intervention testing session to measure class satisfaction. Results: Both the MBSR and Brain Health classes were rated favorably by participants. Recruitment and retention rates were high, and methods for participant randomization and examiner blinding were successful. Class implementation in terms of execution was also successful, as rated by outside experts. Conclusions: This study established the feasibility of conducting MBSR and Brain Health classes in a chronic stroke population. Trial Registration: https://ClinicalTrials.gov, NCT #: 02600637 [ABSTRACT FROM AUTHOR]

This study aimed to investigate factors associated with a delayed autism spectrum (ASD) diagnosis when compared to children with either no or early ASD diagnosis. Among 893 children assessed for ASD before age 8, 39% had no ASD at baseline, of which 21% received a later ASD diagnosis. Autism symptoms, diagnostic history of other developmental disorders, cognitive ability, and socioeconomic factors were associated with delayed ASD. Autism Diagnostic Observation Schedule (ADOS) scores in delayed ASD fell between early and no ASD. Other developmental disorders, time and clinical trends like ADOS use and low parental education distinguished delayed and early ASD, whereas higher frequency of IQ < 70 at baseline and a diagnosis of emotional disorders during follow-up distinguished delayed and no ASD. [ABSTRACT FROM AUTHOR]

Small tandem duplications of DNA occur frequently in the human genome and are implicated in the aetiology of certain human cancers. Recent studies have suggested that DNA double-strand breaks are causal to this mutational class, but the underlying mechanism remains elusive. Here, we identify a crucial role for DNA polymerase α (Pol α)-primase in tandem duplication formation at breaks having complementary 3′ ssDNA protrusions. By including so-called primase deserts in CRISPR/Cas9-induced DNA break configurations, we reveal that fill-in synthesis preferentially starts at the 3′ tip, and find this activity to be dependent on 53BP1, and the CTC1-STN1-TEN1 (CST) and Shieldin complexes. This axis generates near-blunt ends specifically at DNA breaks with 3′ overhangs, which are subsequently repaired by non-homologous end-joining. Our study provides a mechanistic explanation for a mutational signature abundantly observed in the genomes of species and cancer cells. Error-prone repair of DNA double-strand breaks have been implied to cause cancer-associated genome alterations, but the mechanism of their formation remains unclear. Here the authors find that DNA polymerase α primase plays part in tandem duplication formation at CRISPR/Cas9-induced complementary 3′ ssDNA protrusions. [ABSTRACT FROM AUTHOR]

The present study aimed to explore clinical trends in the period 2000–2010, along with discriminating clinical factors for autism spectrum disorder (ASD), in young children suspected of ASD. The following trends were observed: (1) a rise in referrals including an increase in referrals among language-abled children, (2) an increase in children assigned an ASD diagnosis after assessment, and (3) a decrease in Autism Diagnostic Observation Schedule total score. The distribution of ASD subtypes and IQ level did not change. Results suggest that a higher proportion of children with less severe autism symptoms were referred and diagnosed. Further, restricted and repetitive behaviors seemed to be a key discriminating factor when distinguishing between ASD and no-ASD children with a discordant symptom profile. [ABSTRACT FROM AUTHOR]

Any catalyst should be efficient and stable to be implemented in practice. This requirement is particularly valid for manganese hydrogenation catalysts. While representing a more sustainable alternative to conventional noble metal-based systems, manganese hydrogenation catalysts are prone to degrade under catalytic conditions once operation temperatures are high. Herein, we report a highly efficient Mn(I)-CNP pre-catalyst which gives rise to the excellent productivity (TOF° up to 41 000 h−1) and stability (TON up to 200 000) in hydrogenation catalysis. This system enables near-quantitative hydrogenation of ketones, imines, aldehydes and formate esters at the catalyst loadings as low as 5–200 p.p.m. Our analysis points to the crucial role of the catalyst activation step for the catalytic performance and stability of the system. While conventional activation employing alkoxide bases can ultimately provide catalytically competent species under hydrogen atmosphere, activation of Mn(I) pre-catalyst with hydride donor promoters, e.g. KHBEt3, dramatically improves catalytic performance of the system and eliminates induction times associated with slow catalyst activation. Manganese-based hydrogenation catalysts are sensitive to high temperatures and may degrade under industrially relevant conditions. Here, the authors report a highly efficient manganese pincer pre-catalyst displaying high TOF values (up to 41 000 h−1) and stability (TON up to 200 000) at loadings as low as 5-200 ppm. [ABSTRACT FROM AUTHOR]

Early services for ASD need to canvas the opinions of both parents and professionals. These opinions are seldom compared in the same research study. This study aims to ascertain the views of families and professionals on early detection, diagnosis and intervention services for young children with ASD. An online survey compiled and analysed data from 2032 respondents across 14 European countries (60.9% were parents; 39.1% professionals). Using an ordinal scale from 1 to 7, parents' opinions were more negative (mean = 4.6; SD 2.2) compared to those of professionals (mean = 4.9; SD 1.5) when reporting satisfaction with services. The results suggest services should take into account child's age, delays in accessing services, and active stakeholders' participation when looking to improve services. [ABSTRACT FROM AUTHOR]

Background: We sought to determine the prevalence of common anatomic landmarks around the gallbladder that may be useful in orienting surgeons during laparoscopic cholecystectomy.Methods: The subhepatic anatomy of 128 patients undergoing elective cholecystectomy was recorded. We searched and recorded the presence of five anatomic landmarks: the bile duct (B), the Sulcus of Rouviere (S), the left hepatic artery (A), the umbilical fissure (F), and the duodenum (E). These are the previously described B-SAFE landmarks.Results: We found that the duodenum and umbilical fissure were present reliably in almost all patients. The position of the left hepatic artery could be reliably determined by its pulsation in 84% of patients. A portion of the bile duct could be seen in 77% and the Sulcus of Rouviere was present in 80%. Furthermore, the hepatobiliary triangle was always found superior or at the same level as the Sulcus of Rouviere.Conclusions: We found that these five anatomic landmarks were reliably present. This suggest that using the B-SAFE landmarks may allow a surgeon to more easily orient before and during laparoscopic cholecystectomy and prevent bile duct injuries. [ABSTRACT FROM AUTHOR]

Failure to preserve the integrity of the genome is a hallmark of cancer. Recent studies have revealed that loss of the capacity to repair DNA breaks via homologous recombination (HR) results in a mutational profile termed BRCAness. The enzymatic activity that repairs HR substrates in BRCA-deficient conditions to produce this profile is currently unknown. We here show that the mutational landscape of BRCA1 deficiency in C. elegans closely resembles that of BRCA1-deficient tumours. We identify polymerase theta-mediated end-joining (TMEJ) to be responsible: knocking out polq-1 suppresses the accumulation of deletions and tandem duplications in brc-1 and brd-1 animals. We find no additional back-up repair in HR and TMEJ compromised animals; non-homologous end-joining does not affect BRCAness. The notion that TMEJ acts as an alternative to HR, promoting the genome alteration of HR-deficient cells, supports the idea that polymerase theta is a promising therapeutic target for HR-deficient tumours. Cancer mutational signatures have been associated with defects in genome maintenance pathways. Here the authors, by using a worm germline mutagenesis model defective of human orthologue BRCA-1, identify polymerase theta-mediated end-joining (TMEJ) as causing the BRCAness mutational signature. [ABSTRACT FROM AUTHOR]

Advances in microbiome research suggest involvement in chronic inflammatory diseases such as rheumatoid arthritis (RA). Searching for initial trigger(s) in RA, we compared transcriptome profiles of highly inflamed RA synovial tissue (RA-ST) and osteoarthritis (OA)-ST with 182 selected reference transcriptomes of defined cell types and their activation by exogenous (microbial) and endogenous inflammatory stimuli. Screening for dominant changes in RA-ST demonstrated activation of monocytes/macrophages with gene-patterns induced by bacterial and fungal triggers. Gene-patterns of activated B- or T-cells in RA-ST reflected a response to activated monocytes/macrophages rather than inducing their activation. In contrast, OA-ST was dominated by gene-patterns of non-activated macrophages and fibroblasts. The difference between RA and OA was more prominent in transcripts of secreted proteins and was confirmed by protein quantification in synovial fluid (SF) and serum. In total, 24 proteins of activated cells were confirmed in RA-SF compared to OA-SF and some like CXCL13, CCL18, S100A8/A9, sCD14, LBP reflected this increase even in RA serum. Consequently, pathogen-like response patterns in RA suggest that direct microbial influences exist. This challenges the current concept of autoimmunity and immunosuppressive treatment and advocates new diagnostic and therapeutic strategies that consider microbial persistence as important trigger(s) in the etiopathogenesis of RA. [ABSTRACT FROM AUTHOR]

We estimated autism spectrum disorder (ASD) prevalence in 7–9 year-old children in 2015 using data from three nationwide health registry systems (Denmark, Finland, Iceland) and two French population-based regional registries. Prevalence ranged from 0.48% in South-East France to 3.13% in Iceland (South-West France: 0.73%, Finland: 0.77%, Denmark: 1.26%). Male/female ratios ranged from 3.3 in Finland to 5.4 in South-West France. Between 12% (Denmark) and 39% (South-West France) of cases were diagnosed with intellectual disability. The variations in population-based ASD prevalence across four European countries with universal health care practices likely reflect variation in detection, referral and diagnosis practices and autism awareness across these areas. Using established population-based data systems is an efficient approach to monitor ASD prevalence trends over time. [ABSTRACT FROM AUTHOR]

Season of birth has been hypothesized to be a risk factor for autism spectrum disorder (ASD). However, the evidence has been mixed and limited due to methodological challenges. We examine ASD birth trends for 5,464,628 births across 5 countries. ASD birth prevalence data were obtained from the International Collaboration for Autism Registry Epidemiology database, including children born in Denmark, Finland, Norway, Sweden, and Western Australia. Empirical mode decomposition and cosinor modeling were used to assess seasonality. We show seasonal variation in ASD births for the countries of Finland and Sweden. There was a modest increase in risk for children born in the fall and a modest decrease in risk for children born in the spring. Solar radiation levels around conception and the postnatal period were inversely correlated with seasonal trends in ASD risk. In the first multinational study of birth seasonality of ASD, there was evidence supporting the presence of seasonal trends in Finland and Sweden. The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD. [ABSTRACT FROM AUTHOR]

Low Apgar score has been associated with higher risk for several neurological and psychiatric disorders, including cerebral palsy and intellectual disability. Studies of the association between Apgar score and autism spectrum disorder (ASD) have been inconsistent. We aimed to investigate (1) the association between low Apgar score at 5 min and risk for ASD, and (2) the modifying effects of gestational age and sex on this association in the largest multinational database of ASD. We included prospective data from 5.5 million individuals and over 33,000 cases of ASD from Norway, Sweden, Denmark and Western Australia who were born between 1984 and 2007. We calculated crude and adjusted risk ratios (RR) with 95% confidence intervals (95% CIs) for the associations between low Apgar score and ASD. All analyses for ASD were repeated for autistic disorder (AD). We used interaction terms and stratified analysis to investigate the effects of sex, gestational age, and birth weight on the association. In fully adjusted models, low Apgar scores (1-3) (RR, 1.42; 95% CI, 1.16-1.74), and intermediate Apgar scores (4-6) (RR, 1.50; 95% CI, 1.36-1.65) were associated with a higher RR of ASD than optimal Apgar score (7-10). The point estimates for low (RR, 1.88; 95% CI, 1.41-2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32-1.81) were larger for AD than for ASD. This study suggests that low Apgar score is associated with higher risk of ASD, and in particular AD. We did not observe any major modifying effects of gestational age and sex, although there seems to be substantial confounding by gestational age and birth weight on the observed association. [ABSTRACT FROM AUTHOR]

Purpose: Consumers in the Netherlands made more than 3.2 billion debit card transactions at points-of-sale in 2015, corresponding to over half of all point-of-sale payments in that year. This study provides insights into the environmental impact of debit card transactions based on a life cycle assessment (LCA). In addition, it identifies several areas within the debit card payment chain where the environmental impact can be reduced.Methods: The debit card payment system can be divided into three subsystems: debit cards, payment terminals, and data centers used for transaction processing. Input data for all elements within each subsystem (manufacturing, transport, energy use, and disposal) were retrieved from interviews and literature study. Seven key companies and authorities within the debit card system such as the Dutch Payments Association, two banks, two data centers, one payment terminal producer and a recycling company contributed data. The analysis is conducted using SimaPro, the Ecoinvent 3.0 database and the ReCiPe endpoint (H) impact assessment method.Results and discussion: One Dutch debit card transaction in 2015 is estimated to have an absolute environmental impact of 470 μPt. Within the process chain of a debit card transaction, the relative environmental impact of payment terminals is dominant, contributing 75% of the total impact. Terminal materials (37%) and terminal energy use (27%) are the largest contributors to this share, while the remaining impact comprises data center (11%) and debit card (15%) subsystems. For data centers, this impact mainly stems from their energy use. Finally, scenario analyses show that a significant decrease (44%) in the environmental impact of the entire debit card payment system could be achieved by stimulating the use of renewable energy in payment terminals and data centers, reducing the standby time of payment terminals and increasing the lifetimes of debit cards.Conclusions: For the first time, the environmental consequences of electronic card payment systems are evaluated. The total environmental impact of debit card transactions in the Netherlands is relatively modest compared to the impact of cash payments, which are the closest substitute of debit card payments at the point-of-sale. Scenario analysis indicates that the environmental impact can be reduced by 44%. [ABSTRACT FROM AUTHOR]

Copyright of Tijdschrift voor Bedrijfs- En Verzekeringsgeneeskunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one job during pregnancy. Asthmagen exposure was estimated from a published job-exposure matrix. The adjusted odds ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96-2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in this study, but this result does not exclude some involvement of maternal exposure to asthma-causing agents in ASD. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including challenges of equity and quality in low- and middle-income countries in terms of expanding higher education systems; expansion of enrolments; and importance of higher education.

In recent years, there have been numerous attempts to improve the quality of higher education in Africa, but there is limited knowledge about the impact of these initiatives on student learning. The results of a study published in 2015 offered some initial data in this regard by identifying a lack of improvement in the critical thinking ability of students enrolled at three of Rwanda's public universities, despite extensive pedagogical reforms across the sector. However, subsequent analysis of the study data suggests that this lack of improvement is not a general phenomenon, as students graduating from the KIST Faculty of Architecture and Environmental Design appear to exhibit deeper approaches to learning and stronger critical thinking skills than graduates with similar backgrounds from other Faculties involved in the study. This paper examines the factors that appear to have contributed to this outlying Faculty's success and argues that departmental culture has played a crucial role, by fostering the conditions necessary for pedagogical innovation. [ABSTRACT FROM AUTHOR]

Copyright of Natur und Recht is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study examined the phenotypic profiles of children aged 30-68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive, behavioral, and social functioning and the presence of parent-reported conditions. Children with ASD and DD with ASD symptoms had mild to severe ASD risk on several measures compared to children with other DD and POP who had little ASD risk across measures. We conclude that children in SEED have varying degrees of ASD impairment and associated deficits. SEED thus provides a valuable sample to explore ASD phenotypes and inform risk factor analyses. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all children born in Denmark from 1994, through 2010, and surviving the first year of life. Children with ASD as a whole have significantly elevated rates of a range of neurologic, respiratory, inflammatory, and metabolic problems in the neonatal period compared to the general population, but there are few if any indicators of a distinctive neonatal morbidity profile in ASD compared to other neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Identifying T-cell receptors (TCRs) that bind tumor-associated antigens (TAAs) with optimal affinity is a key bottleneck in the development of adoptive T-cell therapy of cancer. TAAs are unmutated self proteins, and T cells bearing high-affinity TCRs specific for such antigens are commonly deleted in the thymus. To identify optimal-affinity TCRs, we generated antigen-negative humanized mice with a diverse human TCR repertoire restricted to the human leukocyte antigen (HLA) A*02:01 (ref. 3). These mice were immunized with human TAAs, for which they are not tolerant, allowing induction of CD8+ T cells with optimal-affinity TCRs. We isolate TCRs specific for the cancer/testis (CT) antigen MAGE-A1 (ref. 4) and show that two of them have an anti-tumor effect in vivo. By comparison, human-derived TCRs have lower affinity and do not mediate substantial therapeutic effects. We also identify optimal-affinity TCRs specific for the CT antigen NY-ESO. Our humanized mouse model provides a useful tool for the generation of optimal-affinity TCRs for T-cell therapy. [ABSTRACT FROM AUTHOR]

The objective of this study is to compare the time trend of reported diagnoses of autism spectrum disorder (ASD), hyperkinetic disorder, Tourette's syndrome, and obsessive-compulsive disorder across four countries after standardizing the study period, diagnostic codes used to define the conditions and statistical analyses across countries. We use a population-based cohort, including all live-born children in Denmark, Finland, Sweden and Western Australia, from January 1, 1990, through December 31, 2007 and followed through December 31, 2011. The main outcome measure is age-specific prevalence of diagnoses reported to population-based registry systems in each country. We observe an increase in age-specific prevalence for reported diagnoses of all four disorders across birth-year cohorts in Denmark, Finland, Sweden, and (for ASD) Western Australia. Our results highlight the increase in the last 20 years in the number of children and families in contact with health care systems for diagnosis and services for an array of childhood neuropsychiatric disorders, a phenomenon not limited to ASD. Also, the age of diagnosis of the studied disorders was often much higher than what is known of the typical age of onset of symptoms, and we observe limited leveling off in the incidence rate with increasing age. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance. [ABSTRACT FROM AUTHOR]