Search

A molecular level understanding of the aqueous Mg corrosion mechanism will be essential in developing improved alloys for battery electrodes, automobile parts, and biomedical implants. The structure and reactivity of the hydroxylated surface is expected to be key to the overall mechanism because (i) it is predicted to be the metastable surface state (rather than the bare surface) under a range of conditions and (ii) it provides a reasonable model for the outer corrosion film/water interface. We investigate the structure, interactions, and reactivity at the hydroxylated Mg(0001)/water interface using a combination of static Density Functional Theory calculations and second-generation Car–Parrinello ab initio molecular dynamics. We carry out detailed structural analyses into, among other properties, near-surface water orientations, favored adsorption sites, and near-surface hydrogen bonding behavior. Despite the short timescale (tens of ps) of our molecular dynamics run, we observe a cathodic water splitting event; the rapid timescale for this reaction is explained in terms of near-surface water structuring lowering the reaction barrier. Furthermore, we observe oxidation of an Mg surface atom to effectively generate a univalent Mg species (Mg+). Results are discussed in the context of understanding the Mg corrosion mechanism: For example, our results provide an explanation for the catalytic nature of the Mg corrosion film toward water splitting and a feasible mechanism for the generation of the univalent Mg species often proposed as a key intermediate. [ABSTRACT FROM AUTHOR]

A molecular level understanding of metal/bulk water interface structure is key for a wide range of processes, including aqueous corrosion, which is our focus, but their buried nature makes experimental investigation difficult and we must mainly rely on simulations. We investigate the Mg(0001)/water interface using second generation Car–Parrinello molecular dynamics (MD) to gain structural information, combined with static density functional theory calculations to probe the atomic interactions and electronic structure (e.g., calculating the potential of zero charge). By performing detailed structural analyses of both metal–surface atoms and the near-surface water, we find that, among other insights: (i) water adsorption causes significant surface roughening (the planar distribution for top-layer Mg has two peaks separated by ≈ 0.6 A ̊ ), (ii) strongly adsorbed water covers only ≈ 1 4 of available surface sites, and (iii) adsorbed water avoids clustering on the surface. Static calculations are used to gain a deeper understanding of the structuring observed in MD. For example, we use an energy decomposition analysis combined with calculated atomic charges to show that adsorbate clustering is unfavorable due to Coulombic repulsion between adsorption site surface atoms. Results are discussed in the context of previous simulations carried out on other metal/water interfaces. The largest differences for the Mg(0001)/water system appear to be the high degree of surface distortion and the minimal difference between the metal work function and metal/water potential of zero charge (at least compared to other interfaces with similar metal–water interaction strengths). The structural information, in this paper, is important for understanding aqueous Mg corrosion, as the Mg(0001)/water interface is the starting point for key reactions. Furthermore, our focus on understanding the driving forces behind this structuring leads to important insights for general metal/water interfaces. [ABSTRACT FROM AUTHOR]

Background: Healthcare and support workers play a pivotal role in delivering quality services and support to people seeking sanctuary who have experienced poor physical and mental health linked to previous trauma, relocation and loss of freedoms. However, they often encounter various challenges in their daily work, ranging from communication barriers to resource constraints. This qualitative study seeks to delve into the perspectives of healthcare and support workers' experience of workarounds, employed to overcome barriers to providing care., Aim: This study aims to describe healthcare providers', practitioners' and health and third sector support workers' views on barriers and workarounds to providing care for people seeking sanctuary, to inform policy and practice., Design: A qualitative study was carried out using semi-structured telephone interviews., Setting: This study focused on primary, secondary, community and specialist National Health Service (NHS) support services for people seeking sanctuary in Wales, United Kingdom (2018)., Method: We interviewed 32 healthcare providers, practitioners and support workers employed by primary care and third sector organisations. Our approach involved obtaining verbal informed consent before digitally recording and transcribing all interviews. To analyse the data, we used the Four Levels of Change for Improving Quality model as a guiding framework for interpretation., Results: Our study findings reveal that certain respondents expressed challenges in meeting the needs of people seeking sanctuary; notably, their experience of delivering care differed by care settings. Specifically, those involved in providing specialist NHS care believed that there was room for improvement. Mainstream primary, secondary and community health practitioners faced limitations due to resource constraints and lacked tailored information to address the unique circumstances and needs of sanctuary seekers. To address these gaps, workarounds emerged at both individual and local levels (team/departmental and organisational level). These included establishing informal communication channels between providers, fostering cross service collaboration to fill gaps and adapting existing services to enhance accessibility., Conclusion: Understanding healthcare providers', practitioners' and support workers' perspectives offers invaluable insights into ways to enhance healthcare delivery to sanctuary seekers. Acknowledging challenges and harnessing innovative workarounds can foster a more effective and compassionate service for this vulnerable population., Patient or Public Contribution: The HEAR study actively involved public contributors in the design, delivery and dissemination of the research. Two public contributors (S. M. and G. R.) who had personal experience of seeking asylum served as study co-applicants. They played pivotal roles in shaping the research by participating in its development and securing funding. Alongside other co-applicants, S. M. and G. R. formed the Research Management Group, overseeing study delivery. Their contributions extended to strategic decision-making and specific feedback at critical junctures, including participant recruitment, data collection, analysis and reporting. Additionally, S. M. and G. R. were instrumental in recruiting and supporting a team of peer researchers, enhancing respondent participation among people seeking sanctuary. To facilitate effective public involvement, we provided named contacts for support (A. K. and R. F.), research training, honoraria, reimbursement of expenses and accessible information in line with best practice., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Histopathological classification in prostate cancer remains a challenge with high dependence on the expert practitioner. We develop a deep learning (DL) model to identify the most prominent Gleason pattern in a highly curated data cohort and validate it on an independent dataset. The histology images are partitioned in tiles (14,509) and are curated by an expert to identify individual glandular structures with assigned primary Gleason pattern grades. We use transfer learning and fine-tuning approaches to compare several deep neural network architectures that are trained on a corpus of camera images (ImageNet) and tuned with histology examples to be context appropriate for histopathological discrimination with small samples. In our study, the best DL network is able to discriminate cancer grade (GS3/4) from benign with an accuracy of 91%, F 1 -score of 0.91 and AUC 0.96 in a baseline test (52 patients), while the cancer grade discrimination of the GS3 from GS4 had an accuracy of 68% and AUC of 0.71 (40 patients).

Purpose: Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research., Methods: Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets., Results: Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated., Conclusions: This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.

Background: Asylum seekers and refugees (ASRs) often experience poor health in host countries. The United Nations High Commissioner for Refugees (UNHCR) requires hosts to ensure these sanctuary seekers have access to basic health care., Aim: To identify barriers and facilitators that affect access to health care by ASRs in Wales., Design & Setting: Participatory research approach using qualitative focus groups across Wales, which hosts 10 000 refugees., Method: Eight focus groups were undertaken with ASRs, support workers, and volunteers ( n = 57)., Results: Specialist NHS-funded services and grant-aided non-governmental organisations (NGOs) facilitated access to health care, including primary care. Most ASRs understood the role of general practice in providing and coordinating care, but were unaware of out-of-hours services. Reported barriers included: language difficulties, health literacy, unrecognised needs, and the cost of travel to appointments. Participants recognised the importance of mental health, but were disappointed by the state of mental health care. Some feared seeking support for mental health from their GP, and few were aware they had the right to move practice if they were unhappy. Written information about health care was not as accessible to refugees as to asylum seekers (ASs). While some participants read such material before consulting, others struggled to access information when in need. Few participants were aware of health prevention services. Even when they knew about services, such as smoking cessation, these services' difficulty in accommodating ASRs was a barrier., Conclusion: The main barriers identified were: availability of interpreters; knowledge about entitlements; and access to specialist services., (Copyright © 2021, The Authors.)

Statement of Problem: Additive manufacturing (AM) technologies can be used to fabricate definitive casts for implant-supported restorations. However, information regarding the accuracy of the implant replica position on the polymeric AM cast generated with different scan bodies and digital implant replica systems is lacking., Purpose: The purpose of this in vitro study was to compare with a conventional stone cast the linear and angular discrepancies of the implant analog positions in a polymeric AM cast obtained from 3 different scan body and digital implant replica systems., Material and Methods: A partially edentulous maxillary typodont with 3 implant replicas (Implant replica RP Branemark system; Nobel Biocare) was prepared. Two duplicating methods were evaluated: conventional (CNV group) and AM (AM group) procedures. For the CNV group, polyvinyl siloxane open-tray implant impressions (CNV) were made at room temperature (23 °C). The AM group was further divided into the subgroups Elos Medtech, Nt-Trading, and Dynamic Abutment. For the Elos Medtech subgroup, the corresponding scan bodies were placed on each implant, and the typodont was digitized by using a laboratory scanner (E3 scanner; 3Shape A/S). The same procedure was repeated with the remaining subgroups. All the AM polymer casts were fabricated at once by using the same 3D printer (Eden 500V; Stratasys). Ten specimens of each group were obtained (n=10). A coordinate-measuring machine (CMM) was used to measure the position of each implant replica, and distortion was calculated for each system at the x-, y-, and z-axes and 3D distortion measurement (3D=x 2 +y 2 +z 2 ). The Shapiro-Wilk test revealed that the data were not normally distributed. The Kruskal-Wallis and pairwise Mann-Whitney U tests (α=.05) were used for the analysis., Results: The CNV group presented significantly higher linear discrepancy than the Dynamic Abutment group on the x- and y-axes. On the z-axis, however, the CNV group showed significantly lower linear discrepancy than the Nt-Trading and Dynamic Abutment groups. The 3D linear discrepancy was 12 ±12 μm for the CNV group, 4 ±100 μm for the Elos Medtech group, 8 ±52 μm for the Nt-Trading group, and 5 ±19 μm for the Dynamic Abutment. The CNV group demonstrated a significantly higher angle than the Nt-Trading group but a significantly smaller angle than the Elos Medtech and Dynamic Abutment groups., Conclusions: The AM groups had lower 3D discrepancies than the CNV group. The Dynamic Abutment group had significantly better accuracy for the mesiodistal and buccolingual implant replica positions than the CNV group, but the conventional procedures had significantly better results for the apicocoronal implant replica position. Scan body and digital implant replica design systems only influenced the accuracy of the angular implant replica position on the AM casts., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The preparation of inorganic nanomaterials with a desired structure and specific properties requires the ability to strictly control their size, shape and composition. A series of chemical reactions with platinum compounds carried out within the 1.5 nm wide channel of single-walled carbon nanotubes (SWNTs) have demonstrated the ability of SWNTs to act as both a very effective reaction vessel and a template for the formation of nanocrystals of platinum di-iodide and platinum di-sulphide, materials that are difficult to synthesise in the form of nanoparticles by traditional synthetic methods. The stepwise synthesis inside nanotubes has enabled the formation of Pt compounds to be monitored at each step of the reaction by aberration-corrected high resolution transmission electron microscopy (AC-HRTEM), verifying the atomic structures of the products, and by an innovative combination of fluorescence-detected X-ray absorption spectroscopy (FD-XAS) and Raman spectroscopy, monitoring the oxidation states of the platinum guest-compounds within the nanotube and the vibrational properties of the host-SWNT, respectively. This coupling of complementary spectroscopies reveals that electron transfer between the guest-compound and the host-SWNT can occur in either direction depending on the composition and structure of the guest. A new approach for nanoscale synthesis in nanotubes developed in this study utilises the versatile coordination chemistry of Pt which has enabled the insertion of the required chemical elements (e.g. metal and halogens or chalcogens) into the nanoreactor in the correct proportions for the controlled formation of PtI 2 and PtS 2 with the correct stoichiometry.

Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.

Purpose: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex., Methods: Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared., Results: A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 × 10-18). This association was stronger in females (OR, 1.5; P = 5 × 10-13) than in males (OR, 1.35; P = 7 × 10-7), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10-2). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 × 10-4) but not in males (OR, 1.15; P = 2.8 × 10-1), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10-4)., Conclusions: This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.