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Sketch and Peel Focused Ion Beam Patterning of Black Phosphorus for Mid-Infrared Photonics
No full textAbstract
Black phosphorus (BP) is an important mid‐infrared semiconductor, having a direct bandgap from monolayer (≈1.7 eV) to bulk (≈0.31 eV) thicknesses. The ability to nanopattern BP could enable new optoelectronic devices. However, existing nanopatterning techniques are either limited to thin flakes or produce BP with poor optical properties. Here, focused neon ion beam lithography is used to produce functional BP nanostructures. We demonstrate a “sketch and peel” method. The “sketch” step removes BP in a narrow line that outlines the desired structure. In the “peel” step, a hardened polymer droplet is used as a handle to pull off the surrounding flake. The “sketch and peel” method minimizes the damage to BP. We show that thermal treatment allows the small amount of damage that still occurs to be mitigated, as confirmed by Raman spectroscopy and mid‐infrared photoluminescence. For the first time, this work demonstrates a method to nanopattern BP with very high resolution and to repair damage by producing high quality BP nanostructures. It thus could be an important enabling technology for future BP nanophotonic devices
Approach to prolactin monitoring and hyperprolactinaemia in transgender and gender-diverse individuals undergoing gender affirming hormone therapy
No full textEvaluation of the implementation and scalability of the Suicide Observatory in Cork and Kerry: Final report.
No full textThe aim of this project was to conduct an independent evaluation of the implementation of the Suicide Observatory in Cork and Kerry against the aims and objectives of the Suicide Observatory, with a focus on process, outcomes and outputs. We also reviewed the impacts of the Suicide Observatory in relation to its goals including suicide surveillance, intervention and prevention activities.
The study involved an audit of the data and data flow, interviews and a survey with stakeholders, and an assessment of the scalability. The ultimate goal of the evaluation is to inform the wider implementation of the Suicide Observatory at national level
Understanding the substrate recognition and catalytic mechanism of 2-O-methyl fucosidases from glycoside hydrolase family 139
No full textRhamnogalacturonan II is one of the most complex plant cell wall carbohydrates and is composed of 13 different sugars and 21 different glycosidic linkages. It is abundant in fruit and indulgence foods, such as chocolate and wine, making it common in the human diet. The human colonic commensal Bacteroides thetaiotaomicron expresses a consortium of 22 enzymes to metabolize rhamnogalacturonan II, some of which exclusively target sugars unique to rhamnogalacturonan II. Several of these enzyme families remain poorly described, and, consequently, our knowledge of rhamnogalacturonan II metabolism is limited. Chief among the poorly understood activities is glycoside hydrolase (GH) family 139, which targets α1,2-2O-methyl L-fucoside linkages, a sugar residue not found in any other plant cell wall complex glycans. Although the founding enzyme BT0984 was placed in the RG-II degradative pathway, no GH139 structure or catalytic blueprint had been available. We report the crystal structures of BT0984 and a second homolog revealing that the family operates with inverting stereochemistry. Using these data, we undertook a mutagenic strategy, backed by molecular dynamics, to identify the important substrate binding and catalytic residues, mapping these residues throughout the GH139 family revealing the importance of the O2 methyl interaction of the substrate. We propose a catalytic mechanism that uses a non-canonical Asn as a catalytic base and shares similarity with L-fucosidases/L-galactosidases of family GH95
Surveillance of left ventricular function among cancer survivors
No full textBACKGROUND: Cancer survivors have an increased risk of heart failure, but this is balanced by the risk of death from other causes. The results of this balance impact on the optimal time for guideline-recommended surveillance for cardiac dysfunction. This study aimed to investigate the association between cancer history and cardiac function at various times during follow-up. METHODS: This cross-sectional study included participants with documented cancer history from cancer registries and matched with non-cancer controls using propensity scoring based on age, sex, diabetes and blood pressure. Cardiac function, primarily left ventricular ejection fraction (LVEF), was assessed using cardiac magnetic resonance (CMR). Multivariable binomial regression analyses were conducted to analyse the association between cancer and cardiac function. RESULTS: Of 23 854 cancer survivors (aged 61.0±6.8 years, 60.9% female) and an equal number of matched controls, 1051 survivors and 1538 controls underwent CMR. Survivors from breast or haematological malignancies demonstrated minor differences in LVEF (59.5±6.4 vs 60.1±6.4, p<0.001) and global circumferential strain (-22.4±3.5 vs -22.6±3.5, p<0.001) compared with controls. Analysis stratified by time since cancer diagnosis revealed that both LVEF (p=0.014) and global circumferential strain (p=0.045) were less likely to be impaired with increasing time from diagnosis. Cancer survivors (prevalence ratio (PR)=1.19 (95% CI 1.05 to 1.35), p=0.006), particularly breast cancer (PR=1.39 (95% CI 1.18 to 1.64), p<0.001), were associated with low LVEF (≤55%) after adjusting for age, sex, years since cancer diagnoses and blood pressure medication. CONCLUSIONS: Compared with people without cancer, cancer survivors have a higher risk of subclinical cardiac dysfunction. However, dysfunction is less common with increasing time since cancer diagnosis. These findings suggest prioritising cardiac monitoring early in survivorship, especially in breast cancer survivors
“Lost in the crowd”: ethical concerns in crowdsourced evaluations of LLMs
No full textAbstract
With the acceleration of Large Language Model (LLM) use by the public, there is an urgent need to make sure the downstream effects have beneficial impacts on humans and society. Therefore, there is an increasing push for ethical evaluation of LLMs to look for potential bias, toxic behaviour, and misinformation. Thus, crowdsourcing has become a popular practice, such as OpenAI’s 2023 Evals initiative. Firstly, by reviewing the literature from software development and ethics, we wish to highlight several cautions on applying the crowdsourcing model to LLMs: including participant self-selection and non-representativeness; the diffusion of responsibility effect including ethics washing and burden shifting; and requisition of ‘incentives’ vis-a-vis issues faced by gig workers. Using the Evals GitHub repository as a case study, we study the effectiveness of an expert-driven, voluntary, crowdsourced scheme on GitHub to address socioethical issues in LLMs. This is achieved by evaluating the statistics of crowdsourced contributions on ethical and bias considerations, which pales in comparison to other technical contributions. This commentary hopes to highlight the issues of ethics, equity, and justice in LLM crowdsourcing, drawing upon interdisciplinary literature, and presents open considerations on how we can improve the state of play
Content Validity of the EQ-HWB in Caregivers of Children with Health Conditions
No full textINTRODUCTION: The EQ Health and Wellbeing instrument (EQ-HWB) is a new generic instrument designed for evaluation across health, social care, community, and caregiver populations. It has 25-item (EQ-HWB) and 9-item (EQ-HWB-S) versions. Validation across target populations is needed. As the instrument remains in an 'experimental' phase, modifications are being considered, including to item wording, item order, and positive versus negative framing of three items. We aimed to investigate the content validity of the EQ-HWB for caregivers of children with chronic health conditions and explore the potential modifications. METHODS: In total, 21 caregivers from an Australian children's hospital sample completed semi-structured interviews, answering the 25 EQ-HWB items while 'thinking aloud', followed by interviewer probing. Interviews and coding focused on the COSMIN components of relevance, comprehension (understanding), and comprehensiveness. RESULTS: Most EQ-HWB items were relevant and well understood by participants, especially the psychosocial items (e.g., loneliness, anxiety). Some participants were confused by the wording in the seeing and hearing items, which were also less relevant in this population. The item 'feeling unsafe' was only relevant for a few participants, but most considered it important. Responses to potential modifications to items were mixed. Many participants were keen to keep the three positively worded items. Some participants suggested that finishing with positive items may mitigate negative feelings on completion. CONCLUSIONS: EQ-HWB items have high relevance and are generally well understood by caregivers of children with health conditions. We recommend endorsing the modifications we tested for the EQ-HWB-S
Sustainability of healthcare system improvements, programmes and interventions in acute care settings: protocol for a mixed methods systematic review
No full textINTRODUCTION: Sustaining evidence-based care is challenging in all clinical settings. Acute care settings have a unique set of contextual factors that may impact sustainability (eg, fast-paced, regular staff turnover). Much of the previous research explores sustainability across undifferentiated healthcare settings making it difficult to determine factors that influence sustainability in acute care settings. The aim of this review is to identify facilitators and barriers that influence the delivery of sustained healthcare interventions (eg, integration of clinical guidelines) within adult and paediatric hospital-based acute care settings. METHODS AND ANALYSIS: A mixed methods systematic review updating Cowie et al's (which included studies from 2008 to 2017) previously published systematic review will be conducted. The following databases will be searched: Medline, Embase, Cochrane Database of Systematic Reviews, CINAHL and Allied and Complementary Medicine (AMED), from November 2017 to the present for studies published in English. Relevant reference lists of included studies will be manually searched. Empirical quantitative and qualitative studies that report the sustainability of an intervention or programme in acute care settings using a theoretical framework(s), model(s) or theory(ies) to explore facilitators and barriers, will be included. Studies will be exported into Covidence (Melbourne) and pairs of reviewers will independently screen abstracts and full-text studies. The discussion will be used to resolve any disagreements and a third coauthor enlisted should a consensus not be reached. Two independent coauthors will extract key study characteristics and assess each study's quality. Data will be extracted using Covidence (Melbourne). Evidence tables will be used to present descriptive data. Facilitators and barriers will be mapped to the Consolidated Framework for Sustainability Constructs in Healthcare and a narrative approach will be used to present key findings. ETHICS AND DISSEMINATION: No primary data will be collected so formal ethical approval is not required. Findings will be disseminated through peer-reviewed publications, presented at international conferences and on social media. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42024547535
Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
No full textExtracellular calcium export by the breast ductal epithelium is crucial during lactation and plays a significant role in breast cancer progression. Intraductal calcium deposition is a hallmark of aggressive premalignant lesions. This study tested the hypothesis that microbiome-derived extracellular vesicles (EVs) influence calcium modulation in premalignant breast cancer lesions. Based on the analysis of plasma, serum, saliva, and tissue collected from breast cancer patients and controls (N = 150), Lactobacillus rhamnosus (Lr) was chosen as the model microbiota. In a BT-474 human breast cancer cell line monolayer culture under acute calcium stress, Lr EVs enhanced intracellular calcium intake. In a BT474 3D spheroid model under chronic calcium stress, Lr EVs increased extracellular calcium deposition and mRNA expression of calcium export channel plasma membrane calcium-transporting ATPase 2 (PMCA2) and stromal interaction molecule 1 (STIM1) in a dose-dependent manner. We propose that Lr EVs influence calcium regulation and mineral deposition, thereby affecting premalignant breast cancer progression
Earth's early differentiation recorded by halogen abundance ratios in Hawaiian lavas
No full textHalogens (F, Cl, Br, I) and radiogenic isotopes were investigated in a suite of submarine basalt glasses from across the Hawaiian archipelago in order to better understand the origin of xenon isotope anomalies related to extinct 129I and the nature of metasomatic agents involved in peripheral Arch magmatism. We found that Lō’ihi tholeiites with high 3He/4He of up to 26 Ra (where Ra denotes the atmospheric 3He/4He) are characterised by unusually low I/Cl of (27 ± 3) × 10−6, whereas peripheral alkaline lavas from the South Arch that have 3He/4He of up to 18 Ra are characterised by unusually high I/Cl of (120 ± 20) × 10−6. In comparison, rejuvenated lavas with 3He/4He of ∼ 8 Ra have I/Cl in the range of (60 ± 30) × 10−6 that is typical of mid-ocean ridge and ocean island basalt lavas elsewhere. The variations in I/Cl, 3He/4He and radiogenic isotopes are consistent with mixing between three mantle end-members. The most primitive end-member with high 3He/4He and low 129XeI/136XePu has low I/Cl but normal Br/Cl, H2O/Cl and F/Cl ratios. Compared to the primitive mantle it is strongly depleted in I and weakly depleted in the other volatiles F, Cl, Br and H2O. The depletion of I (and 129Xe derived from extinct 129I) probably results from a combination of Earth’s heterogenous accretion and preferential partitioning of I into the Earth’s core. The high I/Cl of the South Arch lavas can be explained by input of low degree carbonatitic melts derived from carbonated eclogite in the plume source. This is implied because carbonated ocean crust is uniquely enriched in I. The involvement of carbonatitic melts is consistent with previously reported H2O, Ba and light rare earth element enrichments of South Arch lavas. Taken together the halogen abundance ratios in lavas sourced from around Hawaii record Earth’s early accretion and differentiation, the subsequent subduction of carbonated ocean crust into the mantle and its mobilisation in minor carbonatitic components enriching the periphery of the plume