A Data-Driven, Non-Linear, Parameterized Reduced Order Model of Metal 3D Printing

Directed energy deposition (DED) is a promising metal additive manufacturing technology capable of 3D printing metal parts with complex geometries at lower cost compared to traditional manufacturing. The technology is most effective when process parameters like laser scan speed and power are optimized for a particular geometry and alloy. To accelerate optimization, we apply a data-driven, parameterized, non-linear reduced-order model (ROM) called Gaussian Process Latent Space Dynamics Identification (GPLaSDI) to physics-based DED simulation data. With an appropriate choice of hyperparameters, GPLaSDI is an effective ROM for this application, with a worst-case error of about 8% and a speed-up of about 1,000,000x with respect to the corresponding physics-based data

Orientation gradients in rapidly solidified pure aluminum thin films: comparison of experiments and phase-field crystal simulations

Rapid solidification experiments on thin film aluminum samples reveal the presence of lattice orientation gradients within crystallizing grains. To study this phenomenon, a single-component phase-field crystal (PFC) model that captures the properties of solid, liquid, and vapor phases is proposed to model pure aluminium quantitatively. A coarse-grained amplitude representation of this model is used to simulate solidification in samples approaching micrometer scales. The simulations reproduce the experimentally observed orientation gradients within crystallizing grains when grown at experimentally relevant rapid quenches. We propose a causal connection between formation of defects and orientation gradients

Additively manufactured hierarchical stainless steels with high strength and ductility

Many traditional approaches for strengthening steels typically come at the expense of useful ductility, a dilemma known as strength–ductility trade-off. New metallurgical processing might offer the possibility of overcoming this. Here we report that austenitic 316L stainless steels additively manufactured via a laser powder-bed-fusion technique exhibit a combination of yield strength and tensile ductility that surpasses that of conventional 316L steels. High strength is attributed to solidification-enabled cellular structures, low-angle grain boundaries, and dislocations formed during manufacturing, while high uniform elongation correlates to a steady and progressive work-hardening mechanism regulated by a hierarchically heterogeneous microstructure, with length scales spanning nearly six orders of magnitude. In addition, solute segregation along cellular walls and low-angle grain boundaries can enhance dislocation pinning and promote twinning. This work demonstrates the potential of additive manufacturing to create alloys with unique microstructures and high performance for structural applications

Dynamic Observation of Dendritic Quasicrystal Growth upon Laser-Induced Solid-State Transformation

We report the laser-induced solid-state transformation between a periodic “approximant” and quasicrystal in the Al-Cr system during rapid quenching. Dynamic transmission electron microscopy allows us to capture in situ the dendritic growth of the metastable quasicrystals. The formation of dendrites during solid-state transformation is a rare phenomenon, which we attribute to the structural similarity between the two intermetallics. Through ab initio molecular dynamics simulations, we identify the dominant structural motif to be a 13-atom icosahedral cluster transcending the phases of matter

Observation of Fundamental Mechanisms in Compression-Induced Phase Transformations Using Ultrafast X-ray Diffraction

As theoretically hypothesized for several decades in group IV transition metals, we have discovered a dynamically stabilized body-centered cubic (bcc) intermediate state in Zr under uniaxial loading at sub-nanosecond timescales. Under ultrafast shock wave compression, rather than the transformation from alpha-Zr to the more disordered hex-3 equilibrium omega-Zr phase, in its place we find the formation of a previously unobserved nonequilibrium bcc metastable intermediate. We probe the compression-induced phase transition pathway in zirconium using time-resolved sub-picosecond x-ray diffraction analysis at the Linac Coherent Light Source. We also present molecular dynamics simulations using a potential derived from first-principles methods which independently predict this intermediate phase under ultrafast shock conditions. In contrast with experiments on longer timescale (> 10 ns) where the phase diagram alone is an adequate predictor of the crystalline structure of a material, our recent study highlights the importance of metastability and time dependence in the kinetics of phase transformations

Developing decision support tools incorporating personalised predictions of likely visual benefit versus harm for cataract surgery:research programme

Background Surgery for established cataract is highly cost-effective and uncontroversial, yet uncertainty remains for individuals about when to proceed and when to delay surgery during the earlier stages of cataract. Objective We aimed to improve decision-making for cataract surgery through the development of evidence-based clinical tools that provide general information and personalised risk/benefit information. Design We used a mixed methodology consisting of four work packages. Work package 1 involved the development and psychometric validation of a brief, patient self-reported measure of visual difficulty from cataract and its relief from surgery, named Cataract Patient-Reported Outcome Measure, five items (Cat-PROM5). Work package 2 involved the review and refinement of risk models for adverse surgical events (posterior capsule rupture and visual acuity loss related to cataract surgery). Work package 3 involved the development of prediction models for the Cat-PROM5-based self-reported outcomes from a cohort study of 1500 patients; assessment of the validity of preference-based health economic indices for cataract surgery and the calibration of these to Cat-PROM5; assessment of patients’ and health-care professionals’ views on risk–benefit presentation formats, the perceived usefulness of Cat-PROM5, the value of personalised risk–benefit information, high-value information items and shared decision-making; development of cataract decision aid frequently asked questions, incorporation of personalised estimates of risks and benefits; and development of a cataract decision quality measure to assess the quality of decision-making. Work package 4 involved a mixed-methods feasibility study for a fully powered randomised controlled trial of the use of the cataract decision aid and a qualitative study of discordant or mismatching perceptions of outcome between patients and health-care professionals. Setting Four English NHS recruitment centres were involved: Bristol (lead centre), Brighton, Gloucestershire and Torbay. Multicentre NHS cataract surgery data were obtained from the National Ophthalmology Database. Participants Work package 1 – participants (n = 822) were from all four centres. Work package 2 – electronic medical record data were taken from the National Ophthalmology Database (final set > 1M operations). Work package 3 – cohort study participants were from Bristol (n = 1200) and Gloucestershire (n = 300); qualitative and development work was undertaken with patients and health-care professionals from all four centres. Work package 4 – Bristol, Brighton and Torbay participated in the recruitment of patients (n = 42) for the feasibility trial and recruitment of health-care professionals for the qualitative elements. Interventions For the feasibility trial, the intervention was the use of the cataract decision aid, incorporating frequently asked questions and personalised estimations of both adverse outcomes and self-reported benefit. Main outcome measures There was a range of quantitative and qualitative outcome measures: questionnaire psychometric performance metrics, risk indicators of adverse surgical events and visual outcome, predictors of self-reported outcome following cataract surgery, patient and health-care practitioner views, health economic calibration measures and randomised controlled trial feasibility measures. Data sources The data sources were patient self-reported questionnaire responses, study clinical data collection forms, recorded interviews with patients and health-care professionals, and anonymised National Ophthalmology Database data. Results Work package 1 – Cat-PROM5 was developed and validated with excellent to good psychometric properties (Rasch reliability 0.9, intraclass correlation repeatability 0.9, unidimensionality with residual eigenvalues ≤ 1.5) and excellent responsiveness to surgical intervention (Cohen delta –1.45). Work package 2 – earlier risk models for posterior capsule rupture and visual acuity loss were broadly affirmed (C-statistic for posterior capsule rupture 0.64; visual acuity loss 0.71). Work package 3 – the Cat-PROM5-based self-reported outcome regression models were derived based on 1181 participants with complete data (R2 ≈ 30% for each). Of the four preference-based health economic indices assessed, two demonstrated reasonable performance. Cat-PROM5 was successfully calibrated to health economic indices; adjusted limited dependent variable mixture models offered good to excellent fit (root-mean-square error 0.10–0.16). The personalised quantitative risk information was generally perceived as beneficial. A cataract decision aid and cataract decision quality measure were successfully developed based on the views of patients and health-care professionals. Work package 4 – data completeness was good for the feasibility study primary and secondary variables both before and after intervention/surgery (data completeness range 100–88%). Considering ability to recruit, the sample size required, instrumentation and availability of necessary health economic data, a fully powered randomised controlled trial (patients, n = 800, effect size 0.2 standard deviations, power 80%; p = 0.05) of the cataract decision aid would be feasible following psychometric refinement of the primary outcome (the cataract decision quality measure). The cataract decision aid was generally well-received by patients and health-care professionals, with cautions raised regarding perceived time and workload barriers. Discordant outcomes mostly related to patient dissatisfaction, with no clinical problem found. Limitations The National Ophthalmology Database data are expected to include some errors (mitigated by large multicentre data aggregations). The feasibility randomised controlled trial primary outcome (the cataract decision quality measure) displayed psychometric imperfections requiring refinement. The clinical occurrence of discordant outcomes is uncommon and the study team experienced difficulty identifying patients in this situation. Future work Future work could include regular review of the risk models for adverse outcomes to ensure currency, and the technical precision of complex-numbers analysis of refractive outcome to invite opportunities to improve post-operative spectacle-free vision. In addition, a fully powered randomised controlled trial of the cataract decision aid would be feasible, following psychometric refinement of the primary outcome (the cataract decision quality measure); this would clarify its potential role in routine service delivery. Conclusions In this research programme, evidence-based clinical tools have been successfully developed to improve pre-operative decision-making in cataract surgery. These include a psychometrically robust, patient-reported outcome measure (Cat-PROM5); prediction models for patient self-reported outcomes using Cat-PROM5; prediction models for clinically adverse surgical events and adverse visual acuity outcomes; and a cataract decision aid with relevant general information and personalised risk/benefit predictions. In addition, the successful mapping of Cat-PROM5 to existing health economic indices was achieved and the performances of indices were assessed in patients undergoing cataract surgery. A future full-powered randomised controlled trial of the cataract decision aid would be feasible (patients, n = 800, effect size 0.2 standard deviations, power 80%; p = 0.05). Trial registration This trial is registered as ISRCTN11309852. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 9. See the NIHR Journals Library website for further project information

A qualitative analysis exploring preferred methods of peer support to encourage adherence to a Mediterranean diet in a Northern European population at high risk of cardiovascular disease.

BACKGROUND: Epidemiological and randomised controlled trial evidence demonstrates that adherence to a Mediterranean diet (MD) can reduce cardiovascular disease (CVD) risk. However, methods used to support dietary change have been intensive and expensive. Peer support has been suggested as a possible cost-effective method to encourage adherence to a MD in at risk populations, although development of such a programme has not been explored. The purpose of this study was to use mixed-methods to determine the preferred peer support approach to encourage adherence to a MD. METHODS: Qualitative (focus groups) and quantitative methods (questionnaire and preference scoring sheet) were used to determine preferred methods of peer support. Sixty-seven high CVD risk participants took part in 12 focus groups (60% female, mean age 64 years) and completed a questionnaire and preference scoring sheet. Focus group data were transcribed and thematically analysed. RESULTS: The mean preference score (1 being most preferred and 5 being least preferred) for group support was 1.5, compared to 3.4 for peer mentorship, 4.0 for telephone peer support and 4.0 for internet peer support. Three key themes were identified from the transcripts: 1. Components of an effective peer support group: discussions around group peer support were predominantly positive. It was suggested that an effective group develops from people who consider themselves similar to each other meeting face-to-face, leading to the development of a group identity that embraces trust and honesty. 2. Catalysing Motivation: participants discussed that a group peer support model could facilitate interpersonal motivations including encouragement, competitiveness and accountability. 3. Stepping Stones of Change: participants conceptualised change as a process, and discussed that, throughout the process, different models of peer support might be more or less useful. CONCLUSION: A group-based approach was the preferred method of peer support to encourage a population at high risk of CVD to adhere to a MD. This finding should be recognised in the development of interventions to encourage adoption of a MD in a Northern European population

Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing

<p>Abstract</p> <p>Background</p> <p>Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene.</p> <p>The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues.</p> <p>Results</p> <p>Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of <it>transformer </it>that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors.</p> <p>Conclusions</p> <p>We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific transcripts. No transcription unit structural feature was robustly enriched in the sex-differentially expressed transcript isoforms. Additionally, we found that many genes with male-biased expression were enriched on the × chromosome and reside adjacent to dosage compensation entry sites, suggesting that differences in sex chromosome composition contributes to dimorphism in gene expression. Taken together, this study provides new insight into the molecular underpinnings of sexual differentiation.</p