Mechanism selection for spontaneous grain refinement in undercooled metallic melts

In a previous paper (Castle et al., 2014) [17], we employed a melt fluxing technique to study the velocity-undercooling relationship and microstructural development of a Cu-8.9 wt.% Ni alloy in order to investigate the fundamental mechanism behind the rapid solidification phenomenon of "spontaneous grain refinement". A number of growth transitions were identified with increasing undercooling, including an extended dendrite orientation transition through: fully 〈1 0 0〉-oriented → multiply twinned, mixed 〈1 0 0〉/〈1 1 1〉-oriented → fully 〈1 1 1〉-oriented. Here, we present the results of an identical study of a Cu-Ni alloy of lower Ni content and observe a similar set of growth transitions, with some notable differences. In particular, three distinct grain refinement mechanisms have been observed between the two alloys, including: recrystallization, dendrite fragmentation and dendritic seaweed fragmentation. It appears that the mechanism selected depends strongly upon the original growth structure present, which we suggest is dictated by the balance between the capillary and kinetic anisotropies; with the addition of Ni to Cu either increasing the strength of the kinetic anisotropy, decreasing the strength of the capillary anisotropy, or a combination of both. The unambiguous identification of three different spontaneous grain refinement mechanisms in two closely related alloys is significant as it may help to resolve some of the debate surrounding the "true" grain refinement mechanism

The origins of spontaneous grain refinement in deeply undercooled metallic melts

Spontaneous grain refinement in undercooled metallic melts has been a topic of enduring interest within the solidification community since its discovery more than 50 years ago. Here we present a comparative study of the solidification microstructures and velocity-undercooling behaviour in two dilute Cu-Ni alloys (3.98 & 8.90 wt.% Ni), which have been undercooled by a melt encasement (fluxing) method. Cu-3.98 wt.% Ni shows grain refinement at both low and high undercooling, with a dendritic growth regime separating the two grain refined regions. Within the grain refined region dendritic fragments are clearly evident in the centres of the refined grains and on the surface of the undercooled droplet, suggesting a dendritic fragmentation mechanism. Cu-8.90 wt.% Ni displays also grain refinement at both high and low undercoolings. In the low undercooling grain refined region the samples display curved grain boundaries with a dendritic substructure that extends across grains, indicative of a recovery and recrystallisation mechanism. Conversely, prior to the onset of the high undercooling grain refinement transition extensive regions of dendritic seaweed are observed, suggesting that it is remelting of a dendritic seaweed that gives rise to this structure. Consequently, in two closely related Cu-based systems we have strong microstructural evidence for the operation of all three mechanisms currently considered to give rise to grain refinement. This may help to resolve the grain refinement controversy, although it remains to be determined what factors determine which mechanism operates in any given system

The REgulate your SItting Time (RESIT) intervention for reducing sitting time in individuals with Type 2 diabetes: findings from a randomised-controlled feasibility trial

Trial registration: The trial was registered with ISRCTN (number ISRCTN14832389).Electronic supplementary material is available online at: https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-024-01336-6#Sec29 .Background: Reducing and breaking up sitting is recommended for optimal management of Type 2 diabetes mellitus (T2DM). Yet, there is limited evidence of interventions targeting these outcomes in individuals with this condition. The primary aim of this study was to assess the feasibility and acceptability of delivering and evaluating a tailored online intervention to reduce and break up sitting in adults with T2DM. Methods: A mixed-methods two-arm randomised controlled feasibility trial was conducted in ambulatory adults with T2DM who were randomised 1:1 to the REgulate your SItting Time (RESIT) intervention or usual care control group. The intervention included online education, self-monitoring and prompt tools (wearable devices, smartphone apps, computer apps) and health coaching. Feasibility outcomes were recruitment, attrition, data completion rates and intervention acceptability. Measurements of device-assessed sitting (intended primary outcome for definitive trial), standing and stepping, and physical function, psychosocial health and wellbeing were taken at baseline, 3 months and 6 months. Individual semi-structured interviews were conducted at six-months (post intervention) to explore acceptability, feasibility and experiences of the trial and intervention using the Framework Method. Results: Seventy participants aged 55 ± 11 years were recruited. Recruitment rate (proportion of eligible participants enrolled into the study) was 67% and participant retention rate at 6 months was 93% (n = 5 withdrawals). Data completion rates for daily sitting were 100% at baseline and ranged from 83 to 91% at 3 months and 6 months. Descriptive analysis demonstrated potential for the intervention to reduce device-measured sitting, which was 30.9 ± 87.2 and 22.2 ± 82.5 min/day lower in the intervention group at 3 and 6 months, respectively, compared with baseline. In the control group, sitting was 4.4 ± 99.5 and 23.7 ± 85.2 min/day lower at 3 and 6 months, respectively. Qualitative analysis identified three themes: reasons for participating in the trial, acceptability of study procedures, and the delivery and experience of taking part in the RESIT intervention. Overall, the measurement visits and intervention were acceptable to participants. Conclusions: This study demonstrated the feasibility and acceptability of the RESIT intervention and evaluation methods, supporting a future definitive trial. If RESIT is found to be clinically effective, this could lead to changes in diabetes healthcare with a focus on reducing sitting.Diabetes UK grant number [19/0005972]

XPS characterization of (copper-based) coloured stains formed on limestone surfaces of outdoor Roman monuments

Limestone basements holding bronzes or other copper alloys artefacts such as sculptures, decorations and dedicatory inscriptions are frequently met both in modern and ancient monuments. In outdoor conditions, such a combination implies the corrosion products of the copper based alloy, directly exposed to rainwater, will be drained off and migrate through the porous surfaces, forming stains of different colours and intensities, finally causing the limestone structures to deteriorate

Patient safety culture in care homes for older people: a scoping review

Background: In recent years, there has been an increasing focus on the role of safety culture in preventing incidents such as medication errors and falls. However, research and developments in safety culture has predominantly taken place in hospital settings, with relatively less attention given to establishing a safety culture in care homes. Despite safety culture being accepted as an important quality indicator across all health and social care settings, the understanding of culture within social care settings remains far less developed than within hospitals. It is therefore important that the existing evidence base is gathered and reviewed in order to understand safety culture in care homes. Methods: A scoping review was undertaken to describe the availability of evidence related to care homes’ patient safety culture, what these studies focused on, and identify any knowledge gaps within the existing literature. Included papers were each reviewed by two authors for eligibility and to draw out information relevant to the scoping review. Results: Twenty-four empirical papers and one literature review were included within the scoping review. The collective evidence demonstrated that safety culture research is largely based in the USA, within Nursing Homes rather than Residential Home settings. Moreover, the scoping review revealed that empirical evidence has predominantly used quantitative measures, and therefore the deeper levels of culture have not been captured in the evidence base. Conclusions: Safety culture in care homes is a topic that has not been extensively researched. The review highlights a number of key gaps in the evidence base, which future research into safety culture in care home should attempt to address

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

ReadDepth: A Parallel R Package for Detecting Copy Number Alterations from Short Sequencing Reads

Copy number alterations are important contributors to many genetic diseases, including cancer. We present the readDepth package for R, which can detect these aberrations by measuring the depth of coverage obtained by massively parallel sequencing of the genome. In addition to achieving higher accuracy than existing packages, our tool runs much faster by utilizing multi-core architectures to parallelize the processing of these large data sets. In contrast to other published methods, readDepth does not require the sequencing of a reference sample, and uses a robust statistical model that accounts for overdispersed data. It includes a method for effectively increasing the resolution obtained from low-coverage experiments by utilizing breakpoint information from paired end sequencing to do positional refinement. We also demonstrate a method for inferring copy number using reads generated by whole-genome bisulfite sequencing, thus enabling integrative study of epigenomic and copy number alterations. Finally, we apply this tool to two genomes, showing that it performs well on genomes sequenced to both low and high coverage. The readDepth package runs on Linux and MacOSX, is released under the Apache 2.0 license, and is available at http://code.google.com/p/readdepth/

Prevalence of type-specific HPV infection by age and grade of cervical cytology: data from the ARTISTIC trial

Human papillomavirus (HPV) infection causes cervical cancer and premalignant dysplasia. Type-specific HPV prevalence data provide a basis for assessing the impact of HPV vaccination programmes on cervical cytology. We report high-risk HPV (HR-HPV) type-specific prevalence data in relation to cervical cytology for 24 510 women (age range: 20–64; mean age 40.2 years) recruited into the ARTISTIC trial, which is being conducted within the routine NHS Cervical Screening Programme in Greater Manchester. The most common HR-HPV types were HPV16, 18, 31, 51 and 52, which accounted for 60% of all HR-HPV types detected. There was a marked decline in the prevalence of HR-HPV infection with age, but the proportion due to each HPV type did not vary greatly with age. Multiple infections were common below the age of 30 years but less so between age 30 and 64 years. Catch-up vaccination of this sexually active cohort would be expected to reduce the number of women with moderate or worse cytology by 45%, but the number with borderline or mild cytology would fall by only 7%, giving an overall reduction of 12% in the number of women with abnormal cytology and 27% in the number with any HR-HPV infection. In the absence of broader cross-protection, the large majority of low-grade and many high-grade abnormalities may still occur in sexually active vaccinated women

Digital Genome-Wide ncRNA Expression, Including SnoRNAs, across 11 Human Tissues Using PolyA-Neutral Amplification

Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available

The contribution of HPV18 to cervical cancer is underestimated using high-grade CIN as a measure of screening efficiency

In one geographical area, 14 high-risk human papillomavirus types in cervical intraepithelial neoplasia (CIN2/3; n=139) and cervical squamous cell carcinoma (SCC; n=84) were analysed. HPV18 was more prevalent in SCC than CIN2/3 (OR 9.8; 95% confidence interval: 2.5–39). Other high-risk types prevalences corresponded in CIN2/3 and SCC. Evaluations using CIN2/3 as a measure of efficiency underestimate the contribution of HPV18 to SCC