K-12 Life Skills Education, Independence, and Employment of Autistic Individuals: Giving Voice to Autistic Adults.

Autistic adults are often challenged to engage in and complete life skill tasks independently and are underrepresented in employment. No prior study has explored the perceptions of autistic individuals regarding K-12 life skills experiences and postsecondary employment. As such, the purposes of this study were to explore the association between components of life skills instruction and employment for 12 autistic individuals, and to elicit the perspectives of and experiences in K-12 education and employment of six autistic adults. As this was a mixed methods study, surveys and semi-structured interviews were conducted. Results of Fisher's test indicated no statistically significant associations between employment and instructional components; however, the associations between employment and household chores [Cramer's V = .60]; cooking [Cramer's V = .66]; one-on-one instruction [Cramer's V = .63]; and field trips [Cramer's V = .41]) were large. The associations between employment and job site training [Cramer's V = .33] and token boards [Cramer's V = .33]) were moderate. Three themes and 10 subthemes emerged. Specifically, participants remembered Memorable Components from K-12 instruction: (a) job site training, (b) field trips, and (c) household chores. Participants perceived Beneficial Practices as: (a) job site training and (b) skills learned. Participants described shortcomings of K-12 instruction as need (a) for more skills training, (c) for social skills training, (d) to eliminate unnecessary instruction and (e) to carefully consider student placement. In conclusion, participants described experiences that helped them gain and attain post-secondary employment. More specific individualized programming in K-12 instruction would be beneficial to develop independence and post-secondary employment.

Effects of -H and -OH Termination on Adhesion of Si-Si Contacts Examined Using Molecular Dynamics and Density Functional Theory.

The contact between nanoscale single-crystal silicon asperities and substrates terminated with -H and -OH functional groups is simulated using reactive molecular dynamics (MD). Consistent with previous MD simulations for self-mated surfaces with -H terminations only, adhesion is found to be low at full adsorbate coverages, be it self-mated coverages of mixtures of -H and -OH groups, or just -OH groups. As the coverage reduces, adhesion increases markedly, by factors of ∼5 and ∼6 for -H-terminated surfaces and -OH-terminated surfaces, respectively, and is due to the formation of covalent Si-Si bonds; for -OH-terminated surfaces, some interfacial Si-O-Si bonds are also formed. Thus, covalent linkages need to be broken upon separation of the tip and substrate. In contrast, replacing -H groups with -OH groups while maintaining complete coverage leads to negligible increases in adhesion. This indicates that increases in adhesion require unsaturated sites. Furthermore, plane-wave density functional theory (DFT) calculations were performed to investigate the energetics of two Si(111) surfaces fully terminated by either -H or -OH groups. Importantly for the adhesion results, both DFT and MD calculations predict the correct trends for the relative bond strengths: Si-O > Si-H > Si-Si. This work supports the contention that prior experimental work observing strong increases in adhesion after sliding Si-Si nanoasperities over each other is due to sliding-induced removal of passivating species on the Si surfaces.

Pathway-specific polygenic scores for Alzheimer's disease are associated with changes in brain structure in younger and older adults.

Genome-wide association studies have identified multiple Alzheimer's disease risk loci with small effect sizes. Polygenic risk scores, which aggregate these variants, are associated with grey matter structural changes. However, genome-wide scores do not allow mechanistic interpretations. The present study explored associations between disease pathway-specific scores and grey matter structure in younger and older adults. Data from two separate population cohorts were used as follows: the Avon Longitudinal Study of Parents and Children, mean age 19.8, and UK Biobank, mean age 64.4 (combined n = 18 689). Alzheimer's polygenic risk scores were computed using the largest genome-wide association study of clinically assessed Alzheimer's to date. Relationships between subcortical volumes and cortical thickness, pathway-specific scores and genome-wide scores were examined. Increased pathway-specific scores were associated with reduced cortical thickness in both the younger and older cohorts. For example, the reverse cholesterol transport pathway score showed evidence of association with lower left middle temporal cortex thickness in the younger Avon participants (P = 0.034; beta = -0.013, CI -0.025, -0.001) and in the older UK Biobank participants (P = 0.019; beta = -0.003, CI -0.005, -4.56 × 10-4). Pathway scores were associated with smaller subcortical volumes, such as smaller hippocampal volume, in UK Biobank older adults. There was also evidence of positive association between subcortical volumes in Avon younger adults. For example, the tau protein-binding pathway score was negatively associated with left hippocampal volume in UK Biobank (P = 8.35 × 10-05; beta = -11.392, CI -17.066, -5.718) and positively associated with hippocampal volume in the Avon study (P = 0.040; beta = 51.952, CI 2.445, 101.460). The immune response score had a distinct pattern of association, being only associated with reduced thickness in the right posterior cingulate in older and younger adults (P = 0.011; beta = -0.003, CI -0.005, -0.001 in UK Biobank; P = 0.034; beta = -0.016, CI -0.031, -0.001 in the Avon study). The immune response score was associated with smaller subcortical volumes in the older adults, but not younger adults. The disease pathway scores showed greater evidence of association with imaging phenotypes than the genome-wide score. This suggests that pathway-specific polygenic methods may allow progress towards a mechanistic understanding of structural changes linked to polygenic risk in pre-clinical Alzheimer's disease. Pathway-specific profiling could further define pathophysiology in individuals, moving towards precision medicine in Alzheimer's disease.

The impact of genetic risk for Alzheimer's disease on the structural brain networks of young adults.

Introduction: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer's disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. Methods: Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant's genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks. Results: In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = -0.19, p = 1.4 × 10-3), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10-3), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = -0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = -0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = -0.16, p = 0.035; r = -0.15, p = 0.036). Discussion: We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer's disease in later life.

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

BACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

Interfacial Properties of Linear Alkane/Nitrogen Binary Mixtures: Molecular Dynamics Vapor-Liquid Equilibrium Simulations.

Molecular dynamics simulations were used to investigate the vapor-liquid equilibria (VLE) and interfacial properties of binary mixtures of N2 with either ethane, propane, n-decane, or n-dodecane. Alkanes and N2 were modeled by using the TraPPE-UA and Rivera force fields, respectively. The typically used Lorentz-Berthelot combining rules resulted in liquid phases that are too N2-rich compared to experiment. To improve the accuracy of VLE predictions, the hydrocarbon-nitrogen interactions were fine-tuned, and these improved parameters were used to investigate interfacial properties. Scaling the interaction strength between nitrogen and -CH3 and -CH2- groups by factors of 0.95 and 0.85, respectively, relative to the Lorentz-Berthelot value, was found to minimize error in pressure-composition phase diagrams. These scaling parameters gave excellent agreement with experimental phase diagrams for mixtures of N2 with ethane, propane, or n-dodecane over a range of state points. For ethane/N2 and n-decane/N2 mixtures, trends in surface tension as a function of temperature and pressure are correctly reproduced, although the simulated values are slightly too high compared to experimental values. To assess how the accuracy of hydrocarbon-N2 interaction strength impacts interfacial property predictions, we have compared density profiles and surface tension using several different scaling factors. Using the Lorentz-Berthelot combining rules rather than optimized parameters gave the same qualitative trends, although some quantitative results, such as liquid-phase N2 mole fraction, were found to differ by a factor of ∼1.5. Using the optimized interaction parameters, interfacial behavior was examined by calculating density and free energy profiles. Nitrogen molecules preferentially adsorb at the interfacial region between the liquid and vapor phases. This interfacial adsorption becomes less energetically favorable as either the temperature, pressure, or length of the alkane chain increases.

Comparison of Four Classroom-Based Strategies for Middle School Students With ADHD: A Pilot Randomized Controlled Trial.

Middle school students with ADHD often experience negative academic outcomes. To intervene, schools frequently provide services through special education or section 504. These services include strategies, such as breaks, prompting, and sensory proprioception to remove the impact of construct-irrelevant variance. Student plans rarely include strategies, such as selfmanagement, designed to teach students skills to increase independent functioning. The purpose of this study was to compare the effectiveness of four strategies on engagement, disruptive behavior, and time to initiate tasks. Fifteen sixth and seventh grade students were randomized daily to one of four conditions. Results indicated large statistically significant differences. Social validity data indicated that students found prompting and self-management helpful, but preferred breaks and sensory proprioception. This study builds on a growing empirical base that supports the prioritization of strategies to teach skills over strategies to remove the impact of ADHD on performance.

A novel hybrid scale for the assessment of cognitive and executive function: The Free-Cog.

BACKGROUND: Scales measuring cognitive and executive functions are integral to the assessment and management of patients with suspected cognitive impairment. Some of the most commonly used cognitive tests are now subject to copyright restrictions. Furthermore, no existing scale assesses both executive and cognitive abilities. AIMS: We aimed to develop and validate a novel hybrid scale for use in clinical practice which integrate measures of cognition and executive abilities ('Free-Cog'). METHODS: The instrument was devised through a national collaboration including health professionals, those with lived experience of dementia and researchers. Following ethics committee approval, the Free-Cog was assessed in 25 real-world clinical settings across England, Wales and Scotland. It was compared to three other cognitive tests routinely administered in clinical practice: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Addenbrooke's Cognitive Examination (ACE). RESULTS: The Free-Cog was tested in 960 patients with clinical diagnoses of dementia, Mild Cognitive Impairment (MCI), and normal controls. Similar to the MMSE, MOCA and ACE, it discriminated well between the three groups (p < 0.001). It correlated well with the other instruments. Using a receiver operating characteristic curve analysis, Free-Cog achieved an Area Under Curve of 0.94 for dementia versus controls, 0.80 for MCI versus controls and 0.77 for dementia versus MCI. A version of the tool adapted for telephone consultation, the Tele Free-Cog, also discriminated well between patient groups. CONCLUSIONS: Free-Cog is a non-proprietary, empirically derived, concise assessment. Uniquely, it combines cognitive and executive function questions in the one instrument. It could be used to inform the assessment of people presenting with cognitive impairment and is available to anyone interested in trialling it.

Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review.

Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer's Disease. This paper aims to systematically review studies that examined the effect of Alzheimer's risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer's Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer's disease.

Comparison of accommodations and interventions for youth with ADHD: A randomized controlled trial.

School psychologists have a variety of evidence-based interventions from which to choose when recommending classroom-based strategies for students with attention deficit hyperactivity disorder (ADHD); however, strategies frequently found on individualized education plans are accommodations designed to remove barriers to learning, which have limited empirical evidence. As such, the purpose of the current study was to compare the efficacy of three interventions (i.e., organization training, self-management, note-taking instruction) and three accommodations (i.e., organization support, extended time, copy of teacher notes) to address difficulties with organization and maintaining attention during a science lesson and associated independent practice. The study included 64 middle school students with ADHD randomized to either an intervention or an accommodation condition. The intervention group was further divided into two subgroups, consisting of (a) students who were willing to follow intervention procedures and (b) students who were not willing to follow the procedures (behavioral indicators of social validity). Results indicated that adolescents with ADHD in the intervention group were statistically significantly more likely to organize and maintain binder organization and to take complete and accurate notes than those in the accommodation group. In addition, exploratory analyses indicated that adolescents who demonstrated willingness to follow intervention procedures were more likely to be academically engaged during instruction and independent work and to complete independent work accurately than those who resisted the procedures.

From Polygenic Scores to Precision Medicine in Alzheimer's Disease: A Systematic Review.

BACKGROUND: Late-onset Alzheimer's disease (AD) is highly heritable. The effect of many common genetic variants, single nucleotide polymorphisms (SNPs), confer risk. Variants are clustered in areas of biology, notably immunity and inflammation, cholesterol metabolism, endocytosis, and ubiquitination. Polygenic scores (PRS), which weight the sum of an individual's risk alleles, have been used to draw inferences about the pathological processes underpinning AD. OBJECTIVE: This paper aims to systematically review how AD PRS are being used to study a range of outcomes and phenotypes related to neurodegeneration. METHODS: We searched the literature from July 2008-July 2018 following PRISMA guidelines. RESULTS: 57 studies met criteria. The AD PRS can distinguish AD cases from controls. The ability of AD PRS to predict conversion from mild cognitive impairment (MCI) to AD was less clear. There was strong evidence of association between AD PRS and cognitive impairment. AD PRS were correlated with a number of biological phenotypes associated with AD pathology, such as neuroimaging changes and amyloid and tau measures. Pathway-specific polygenic scores were also associated with AD-related biologically relevant phenotypes. CONCLUSION: PRS can predict AD effectively and are associated with cognitive impairment. There is also evidence of association between AD PRS and other phenotypes relevant to neurodegeneration. The associations between pathway specific polygenic scores and phenotypic changes may allow us to define the biology of the disease in individuals and indicate who may benefit from specific treatments. Longitudinal cohort studies are required to test the ability of PGS to delineate pathway-specific disease activity.

Covalent Bonding and Atomic-Level Plasticity Increase Adhesion in Silicon-Diamond Nanocontacts.

Nanoindentation and sliding experiments using single-crystal silicon atomic force microscope probes in contact with diamond substrates in vacuum were carried out in situ with a transmission electron microscope (TEM). After sliding, the experimentally measured works of adhesion were significantly larger than values estimated for pure van der Waals (vdW) interactions. Furthermore, the works of adhesion increased with both the normal stress and speed during the sliding, indicating that applied stress played a central role in the reactivity of the interface. Complementary molecular dynamics (MD) simulations were used to lend insight into the atomic-level processes that occur during these experiments. Simulations using crystalline silicon tips with varying degrees of roughness and diamond substrates with different amounts of hydrogen termination demonstrated two relevant phenomena. First, covalent bonds formed across the interface, where the number of bonds formed was affected by the hydrogen termination of the substrate, the tip roughness, the applied stress, and the stochastic nature of bond formation. Second, for initially rough tips, the sliding motion and the associated application of shear stress produced an increase in irreversible atomic-scale plasticity that tended to smoothen the tips' surfaces, which resulted in a concomitant increase in adhesion. In contrast, for initially smooth tips, sliding roughened some of these tips. In the limit of low applied stress, the experimentally determined works of adhesion match the intrinsic (van der Waals) work of adhesion for an atomically smooth silicon-diamond interface obtained from MD simulations. The results provide mechanistic interpretations of sliding-induced changes and interfacial adhesion and may help inform applications involving adhesive interfaces that are subject to applied shear forces and displacements.

Venous thromboembolism risk in psychiatric in-patients: a multicentre cross-sectional study.

Aims and methodWe assessed venous thromboembolism (VTE) risk, barriers to prescribing VTE prophylaxis and completion of VTE risk assessment in psychiatric in-patients. This was a cross-sectional study conducted across three centres. We used the UK Department of Health VTE risk assessment tool which had been adapted for psychiatric patients. RESULTS: Of the 470 patients assessed, 144 (30.6%) were at increased risk of VTE. Patients on old age wards were more likely to be at increased risk than those on general adult wards (odds ratio = 2.26, 95% CI 1.51-3.37). Of those at higher risk of VTE, auditors recorded concerns about prescribing prophylaxis in 70 patients (14.9%). Only 20 (4.3%) patients had a completed risk assessment.Clinical implicationsMental health in-patients are likely to be at increased risk of VTE. VTE risk assessment is not currently embedded in psychiatric in-patient care. There is a need for guidance specific to this population.Declaration of interestNone.

#BJPsych and social media - likes, followers and leading?

This article explores the growing interface between social media and academic publishing. We discuss how the British Journal of Psychiatry (BJPsych) and other scientific journals are engaging with social media to communicate in a digital world. A growing body of evidence suggests that public visibility and constructive conversation on social media networks can be beneficial for researchers and clinicians, influencing research in a number of key ways. This engagement presents new opportunities for more widely disseminating information, but also carries risks. We note future prospects and ask where BJPsych should strategically place itself in this rapidly changing environment.Declaration of interestJ.R.H., J.F.H. and D.T. are on the editorial board of the BJPsych. D.T. runs its social media arm.

Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder type I, type II, unaffected siblings and healthy controls.

BACKGROUND: Fractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research.AimsThis study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings. METHOD: Fractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II. RESULTS: The main effects were found in both the right and left uncinate fasciculus, with patients with BD-I showing significantly lower fractional anisotropy than both patients with BD-II and healthy controls. Participants with BD-II did not differ from healthy controls. Siblings showed similar effects in the left uncinate fasciculus. In a subsequent complementary analysis, we investigated the association between fractional anisotropy in the uncinate fasciculus and polygenic risk for bipolar disorder and psychosis in a large cohort (n = 570) of healthy participants. However, we found no significant association. CONCLUSIONS: Fractional anisotropy in the uncinate fasciculus differs significantly between patients with BD-I and patients with BD-II and healthy controls. This supports the hypothesis of differences in the physiological sub-tract between bipolar disorder subtypes. Similar results were found in unaffected siblings, suggesting the potential for this biomarker to represent an endophenotype for BD-I. However, fractional anisotropy in the uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or psychosis.Declaration of interestNone.

Impact of Molecular Structure on Properties of n-Hexadecane and Alkylbenzene Binary Mixtures.

Because of the complexity of petroleum-based fuels, researchers typically use simplified mixtures, known as surrogates, to study combustion behavior and to attempt to identify how physical properties are related to combustion. The process of determining the surrogate composition to yield a desired set of thermophysical properties can be a complicated and time-consuming task. As a result, the use of computer simulations to narrow the number of possible surrogate compositions is beginning to be explored. Herein, molecular dynamics (MD) simulations are used to model binary mixtures of n-hexadecane with either benzene, toluene, n-ethylbenzene, n-propylbenzene, or n-butylbenzene. Calculated densities are in quantitative agreement with experimental values. With the exception of the mixtures containing benzene, simulated excess molar volumes are also in very good agreement with measured values. Isentropic bulk moduli are in qualitative agreement with experiment, and reproduce interesting trends observed in the experimental data. Specifically, minima in the bulk moduli at intermediate compositions of several of the alkylbenzenes are correctly reproduced. In addition, the structures of the fluids are also examined. For mixtures of n-hexadecane with alkylbenzenes with longer chains, the orientation of the aromatic rings is not substantially impacted by composition. In contrast, increasing n-hexadecane content increases the ratio of parallel to perpendicular arrangements of benzene and toluene molecules. In those mixtures, this change in orientation of the aromatic rings could be responsible for the minima observed in the bulk moduli data. These results show that MD simulations can assist in development of fuel surrogates, both by predicting thermophysical properties and by providing insight into how molecular structure and composition affect those properties.

The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: A systematic review.

BACKGROUND: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. AIMS: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes. METHODS: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 - 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. RESULTS: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%). LIMITATIONS: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis. CONCLUSIONS: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine.