AI is a viable alternative to high throughput screening : a 318-target study

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Affirmative Action Dents the National Labor Policy

In this author\u27s earlier review of Executive Order 11,246, published in February, 1971, it was predicted that 1971 would be the year in which affirmative action would achieve the awe and the respect of the legal profession. Among the reasons then given for the profession\u27s expanding awareness were the following: (1) the far greater circulation of equal opportunity certification forms among government contractors and subcontractors; (2) the growing tendency of federal, state and local civil rights enforcement agencies to use affirmative action criteria in adjudicating issues of discrimination; (3) the federal government\u27s readiness to use stop orders in the construction industry; (4) and perhaps most significant, the serious challenges of affirmative action to the Congressionally mandated national labor policy. Since February, 1971, construction industry affirmative action plans have survived concentrated attacks in two landmark cases: Contractors Association of Eastern Pennysylvania [sic] v. Sec. of Labor and Southern Illinois Builders Association v. Ogilvie

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals' adaptive skills naturally improve or remain stable, while others' decrease. To pave the way for 'precision-medicine' approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful "Increasers", "No-changers", and "Decreasers" in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup's neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences' potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes

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RoadMap for the Development of Education in Kazakhstan: Higher Education Roadmap Recommendations

This document presents a set of recommendations for the Roadmap Project of the Republic of Kazakhstan developed by the Higher Education Project Team (Mary Canning, Joni Finney, Dennis Jones and Aims McGuinness). It is based on the July 2013 report Development of Strategic Directions for Education Reforms in Kazakhstan for 2015-2020.and on the reports of the Steering Committee

AI is a viable alternative to high throughput screening: a 318-target study

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Involvement in midwifery education: experiences from a service user and carer partnership.

This article provides a critical reflection on the experiences of the Bournemouth University Public Involvement in Education and Research (PIER) partnership in developing approaches to involving service users and user groups within midwifery programmes of education; an NMC requirement since 2009. Specific models and activities are explored, including using social media to consult with expectant and new parents; organising direct conversations between women, their families, academics and students to explore experiences such as grief and loss and the use of support networks during pregnancy; and developing digital resources to create real, in depth and meaningful case studies. Three key benefits to having meaningful and well supported involvement are identified: emotional impact and the opportunity to develop insight and resilience; knowledge impact and the opportunity to better understand the application of theory; and practical impact, which can lead to tangible changes to students’ subsequent practice

Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, padj = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation