Generalisation of Social Communication Skills by Autistic Children During Play-Based Assessments Across Home, School and an Unfamiliar Research Setting

\ua9 The Author(s) 2024.We investigated autistic children’s generalisation of social communication over time across three settings during a play-based assessment with different adults and explore the potential moderating effects on generalisation of age, nonverbal IQ and level of restricted and repetitive behaviours. The social communication abilities of 248 autistic children (2–11 years, 21% female, 22% single parent, 60% white) from three UK sites were assessed from 1984 video interactions in three contexts with three different interaction partners (parent/home, teaching assistant/school, researcher/clinic) at baseline, midpoint (+ 7m) and endpoint (+ 12m) within the Paediatric Autism Communication Trial-Generalised (PACT-G), a parent-mediated social communication intervention. Children’s midpoint social communication at home generalised to school at midpoint and to clinic at endpoint. Generalisation was stronger from home to school and clinic than school to home and clinic. Generalisation was not moderated by age, nonverbal IQ or restricted and repetitive behaviour. Broader child development did not explain the pattern of results. The current study is the largest study to date to explore generalisation with autistic children and provides novel insight into their generalisation of social communication skills. Further research is needed to gain a more comprehensive understanding of facilitators of generalisation across settings and interaction partners in order to develop targeted strategies for interventions to enhance outcomes for young autistic children

Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin.

The rates at which lesions are removed by DNA repair can vary widely throughout the genome, with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that, in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organized within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells and cells defective in the global genome-NER (GG-NER) subpathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation, revealing that GG-NER is organized and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone acetyl-transferase Gcn5 is controlled by the GG-NER complex, which regulates histone H3 acetylation and chromatin structure, thereby promoting efficient DNA repair of UV-induced lesions. Chromatin remodeling during the GG-NER process is therefore organized into these genomic domains. Importantly, loss of Gcn5 significantly alters the genomic distribution of NER rates; this has implications for the effects of chromatin modifiers on the distribution of mutations that arise throughout the genome.Medical Research Council (Career Establishment Grant), Cancer Research UK (project grant A12340), Cancer Research UK (programme grant C6/A11224), European Research Council, European Community Seventh Framework Programme (grant agreement no. HEALTH-F2- 2010-259893; DDResponse), Cancer Research UK (C6946/A14492), Wellcome Trust (WT092096)This is the author accepted manuscript. The final version is available from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gr.209106.11

Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community.</p> <p>Methods</p> <p>Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology), a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17.</p> <p>Results</p> <p>Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9), social phobia (OR = 5.8), overanxious disorder (OR = 6.1), panic disorder (OR = 12.1), and oppositional defiant disorder (OR = 3.7).</p> <p>Conclusions</p> <p>These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.</p

Sustainability, epistemology, ecocentric business and marketing strategy:ideology, reality and vision

This conceptual article examines the relationship between marketing and sustainability through the dual lenses of anthropocentric and ecocentric epistemology. Using the current anthropocentric epistemology and its associated dominant social paradigm, corporate ecological sustainability in commercial practice and business school research and teaching is difficult to achieve. However, adopting an ecocentric epistemology enables the development of an alternative business and marketing approach that places equal importance on nature, the planet, and ecological sustainability as the source of human and other species' well-being, as well as the source of all products and services. This article examines ecocentric, transformational business, and marketing strategies epistemologically, conceptually and practically and thereby proposes six ecocentric, transformational, strategic marketing universal premises as part of a vision of and solution to current global un-sustainability. Finally, this article outlines several opportunities for management practice and further research

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Cryptanalysis of MQV with partially known nonces

In this paper we present the first lattice attack on an authenticated key agreement protocol, which does not use a digital signature algorithm to produce the authentication. We present a two stage attack on MQV in which one party may recover the other party&apos;s static private key from partial knowledge of the nonces from several runs of the protocol. The first stage reduces the attack to a hidden number problem which is partially solved by considering a closest vector problem and using Babai&apos;s algorithm. This stage is closely related to the attack of Nguyen and Shparlinski on DSA but is complicated by a non-uniform distribution of multipliers. The second stage recovers the rest of the key using the baby-step/giant-step algorithm or Pollard&apos;s Lambda algorithm and runs in time O(q ). The attack has been proven to work with high probability and validated experimentally. We have thus reduced the security from O(q ) down to O(q ) when partial knowledge of the nonces is given