Localized soft elasticity in liquid crystal elastomers.

This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms10781Synthetic approaches to prepare designer materials that localize deformation, by combining rigidity and compliance in a single material, have been widely sought. Bottom-up approaches, such as the self-organization of liquid crystals, offer potential advantages over top-down patterning methods such as photolithographic control of crosslink density, relating to the ease of preparation and fidelity of resolution. Here, we report on the directed self-assembly of materials with spatial and hierarchical variation in mechanical anisotropy. The highly nonlinear mechanical properties of the liquid crystalline elastomers examined here enables strain to be locally reduced >15-fold without introducing compositional variation or other heterogeneities. Each domain (⩾0.01 mm(2)) exhibits anisotropic nonlinear response to load based on the alignment of the molecular orientation with the loading axis. Accordingly, we design monoliths that localize deformation in uniaxial and biaxial tension, shear, bending and crack propagation, and subsequently demonstrate substrates for globally deformable yet locally stiff electronics.T.H.W., A.F.S. and T.J.W. would like to acknowledge financial support from the Materials and Manufacturing Directorate and the Office of Scientific Research of the Air Force Research Laboratory

Encoding Gaussian curvature in glassy and elastomeric liquid crystal solids.

We describe shape transitions of thin, solid nematic sheets with smooth, preprogrammed, in-plane director fields patterned across the surface causing spatially inhomogeneous local deformations. A metric description of the local deformations is used to study the intrinsic geometry of the resulting surfaces upon exposure to stimuli such as light and heat. We highlight specific patterns that encode constant Gaussian curvature of prescribed sign and magnitude. We present the first experimental results for such programmed solids, and they qualitatively support theory for both positive and negative Gaussian curvature morphing from flat sheets on stimulation by light or heat. We review logarithmic spiral patterns that generate cone/anti-cone surfaces, and introduce spiral director fields that encode non-localized positive and negative Gaussian curvature on punctured discs, including spherical caps and spherical spindles. Conditions are derived where these cap-like, photomechanically responsive regions can be anchored in inert substrates by designing solutions that ensure compatibility with the geometric constraints imposed by the surrounding media. This integration of such materials is a precondition for their exploitation in new devices. Finally, we consider the radial extension of such director fields to larger sheets using nematic textures defined on annular domains.C. Mostajeran is supported by the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom. T. J. White and T. H. Ware acknowledge financial support from the Materials and Manufacturing Directorate of the Air Force Research Laboratory and the Air Force Office of Scientific Research.This is the final version of the article. It first appeared from Royal Society Publishing via https://doi.org/10.1098/rspa.2016.011

Encoding Gaussian curvature in glassy and elastomeric liquid crystal solids

We describe shape transitions of thin, solid nematic sheets with smooth, preprogrammed, in-plane director fields patterned across the surface causing spatially inhomogeneous local deformations. A metric description of the local deformations is used to study the intrinsic geometry of the resulting surfaces upon exposure to stimuli such as light and heat. We highlight specific patterns which encode constant Gaussian curvature of prescribed sign and magnitude. We present the first experimental results for such programmed solids, and they qualitatively support theory for both positive and negative Gaussian curvature morphing from flat sheets on stimulation by light or heat. We review logarithmic spiral patterns which generate cone/anti-cone surfaces, and introduce spiral director fields that encode nonlocalised positive and negative Gaussian curvature on punctured discs, including spherical caps and spherical spindles. Conditions are derived where these cap-like, photomechanically-responsive regions can be anchored in inert substrates by designing solutions that ensure compatibility with the geometric constraints imposed by the surrounding media. This integration of such materials is a precondition for their exploitation in new devices. Finally, we consider the radial extension of such director fields to larger sheets using nematic textures defined on annular domains.C. Mostajeran is supported by the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom. T. J. White and T. H. Ware acknowledge financial support from the Materials and Manufacturing Directorate of the Air Force Research Laboratory and the Air Force Office of Scientific Research.This is the final version of the article. It first appeared from Royal Society Publishing via https://doi.org/10.1098/rspa.2016.011

Investigating causality in the association between 25(OH)D and schizophrenia

Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia.</p

Evaluating cutpoints for the MHI-5 and MCS using the GHQ-12: a comparison of five different methods

Background The Mental Health Inventory (MHI-5) and the Mental Health Component Summary score (MCS) derived from the Short Form 36 (SF-36) instrument are well validated and reliable scales. A drawback of their construction is that neither has a clinically validated cutpoint to define a case of common mental disorder (CMD). This paper aims to produce cutpoints for the MHI-5 and MCS by comparison with the General Health Questionnaire (GHQ-12). Methods Data were analysed from wave 9 of the British Household Panel Survey (2000), providing a sample size of 14,669 individuals. Receiver Operating Characteristic (ROC) curves were used to compare the scales and define cutpoints for the MHI-5 and MCS, using the following optimisation criteria: the Youden Index, the point closest to (0,1) on the ROC curve, minimising the misclassification rate, the minimax method, and prevalence matching. Results For the MHI-5, the Youden Index and the (0,1) methods both gave a cutpoint of 76, minimising the misclassification rate gave a cutpoint of 60 and the minimax method and prevalence matching gave a cutpoint of 68. For the MCS, the Youden Index and the (0,1) methods gave cutpoints of 51.7 and 52.1 respectively, minimising the error rate gave a cutpoint of 44.8 and both the minimax method and prevalence matching gave a cutpoint of 48.9. The correlation between the MHI-5 and the MCS was 0.88. Conclusion The Youden Index and (0,1) methods are most suitable for determining a cutpoint for the MHI-5, since they are least dependent on population prevalence. The choice of method is dependent on the intended application. The MHI-5 performs remarkably well against the longer MCS

Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background&lt;p&gt;&lt;/p&gt; Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.&lt;p&gt;&lt;/p&gt; Results&lt;p&gt;&lt;/p&gt; Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Limits on Gravitational-Wave Emission from Selected Pulsars Using LIGO Data

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10^(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10^(-5) for the four closest pulsars