Grain refinement of stainless steel in ultrasound-assisted additive manufacturing

Metals and alloys fabricated by fusion-based additive manufacturing (AM), or 3D printing, undergo complex dynamics of melting and solidification, presenting challenges to the effective control of grain structure. Herein, we report on the use of high-intensity ultrasound that controls the process of solidification during AM of 316L stainless steel. We find that the use of ultrasound favours the columnar-to-equiaxed transition, promoting the formation of fine equiaxed grains with random crystallographic texture. Moreover, the use of ultrasound increases the number density of grains from 305 mm−2 to 2748 mm−2 despite an associated decrease in cooling rate and temperature gradient in the melt pool during AM. Our assessment of the relationship between grain size and cooling rate indicates that the formation of crystallites during AM is enhanced by ultrasound. Furthermore, the use of ultrasound increases the amount of constitutional supercooling during solidification by lowering the temperature gradient in the bulk of the melt pool, thus creating an environment that favours nucleation, growth, and survival of grains. This new understanding provides opportunities to better exploit ultrasound to control grain structure in AM-fabricated metal products

Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study

\ua9 2024 The Author(s). Background: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. Methods: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. Results: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres’ catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. Conclusions: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Intimate partner violence against women in an economically vulnerable urban area, Central-West Brazil

OBJETIVO: Estimar a prevalência de tipos de violência e de comportamentos de controle praticados por parceiros íntimos contra mulheres residentes em área economicamente vulnerável. MÉTODOS: Conduziu-se estudo transversal com 278 mulheres de 15 a 49 anos que tiveram parceiros íntimos alguma vez na vida, residentes em uma área metropolitana de Brasília, DF, em 2007. Utilizou-se processo de amostragem aleatória sistemática. O instrumento de pesquisa constou de um questionário com 58 perguntas desenvolvido pela Organização Mundial de Saúde. Foram analisadas as prevalências de violência física, psicológica e sexual. As variáveis independentes consideradas foram características sociodemográficas da mulher, de contexto familiar e comunitário bem como as sociodemográfi cas do parceiro, de comportamento (freqüência do uso de bebidas ou drogas ilícitas e relacionamento extraconjugal). RESULTADOS: A prevalência de violência psicológica foi a mais alta: 80,2% (n=223) das mulheres entrevistadas relataram pelo menos um ato no decorrer da vida e 50% (n=139) nos últimos 12 meses. A prevalência de violência física ao longo da vida foi (58,6%) e nos últimos 12 meses (32%), enquanto a prevalência de mulheres que sofreram violência sexual foi de 28,8% e 15,5%, respectivamente. CONCLUSÕES: As altas prevalências das violências mostram a magnitude da vulnerabilidade e das agressões praticadas contra mulheres nas relações com parceiros íntimos.OBJECTIVE: To estimate the prevalence of gender-based controlling behavior and types of violence committed by intimate partners against women living in an economically vulnerable area. METHODS: A cross-sectional study was performed with 278 women aged between 15 and 49 years, who had had at least one male intimate partner in their lives and lived in a metropolitan area of the city of Brasília, Central-West Brazil, in 2007. Systematic random sampling process was used. The research instrument consisted of a questionnaire with 58 questions, developed by the World Health Organization. Prevalences of physical, psychological and sexual violence were analyzed. Independent variables considered were women’s sociodemographic, family and community context characteristics, in addition to their partners’ sociodemographic and behavior characteristics (frequency of alcohol or illicit drug use and extra-marital relationship). RESULTS: The highest prevalence was that of psychological violence: 80.2% (n=223) of the women interviewed reported at least one act throughout their lives and 50% (n=139) in the last 12 months. Prevalence of physical violence was 58.6% throughout life and 32% in the last 12 months, whereas those of sexual violence were 28.8% and 15.5%, respectively. CONCLUSIONS: High prevalences of violence show the magnitude of vulnerability and aggressions committed against women in relationships with intimate partners

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing

The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank