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Preventing drug-related deaths in Scotland:Perceptions and experiences of engagement in a ‘shared care’ model of service delivery
No full textPurposeScotland faces a crisis of drug-related deaths, disproportionately affecting people living in the most deprived areas. This paper explores patient and service provider perceptions of engagement within shared care treatment systems, acknowledged as a critical factor in preventing drug-related harms and deaths. Design/methodology/approachA qualitative case study approach was adopted, focusing on two primary care practices in highly deprived urban areas. Thematic analysis was used to investigate the interplay of individual, organizational, and structural factors acting as facilitators and barriers to service engagement. Data were collected through 34 semi-structured interviews with 6 people who use drugs (PWUD), 4 family members, 20 healthcare practitioners, and 4 policymakers. FindingsEngagement challenges were multifaceted, encompassing relational aspects (e.g. trust and stigma), and systemic issues, including poor collaboration across professional groups, fragmented services, inadequate communication, and resource constraints. Participants emphasized the cumulative impact of socioeconomic deprivation and structural inequalities, which shaped the environments in which drug use occurred and constrained effective care delivery. Practitioners employed various strategies, including harm reduction approaches and personalized support, to enhance engagement.OriginalityThe paper provides new insights into the challenges faced by practitioners, PWUD and families in navigating the shared care system. The findings highlight the need for policy action to strengthen service provision as well as reinforcing the importance of tackling cumulative health and social inequalities, seen as a key factor in drug-related deaths. <br/
Diversity of organic-walled microfossils in the phosphates of the ca. 1 Ga Diabaig Formation, Torridon Group, NW Scotland
No full textPrecambrian organic-walled microfossils preserved in fine-grained sedimentary rocks constitute the earliest fossil record of eukaryotic life. The Mesoproterozoic–Neoproterozoic transition coincided with major innovations in the evolution of early eukaryotes, including the radiation of crown-group lineages, represented in these rocks by candidate red algae, green algae, and fungi. However, the diversity of these early eukaryotes is yet to be fully explored. Here, we present a systematic description of the microfossil assemblage preserved in exceptional detail within sedimentary phosphatic nodules and bands in the Diabaig Formation of the ca. 1-Ga Torridon Group of northwest Scotland. Recent work has highlighted the lacustrine or estuarine nature of its depositional environment and confirmed that these fossils may include the oldest known non-marine eukaryotes. We identified 11 morphotaxa from newly collected material, including the new genus and species Minimarmilla multicatenaria, two undoubted eukaryotes, and two probable eukaryotes. The latter include Pterospermopsimorpha sp., and a new network-forming unnamed taxon. These microfossils present an important window on eukaryotic diversification in non-marine aquatic environments during the Mesoproterozoic–Neoproterozoic.</p
Functionally-graded SSiC/AA6082/HDPE composite shields for MMOD hypervelocity impact mitigation
No full textProtecting low Earth orbit infrastructure from micrometeoroid and orbital debris impacts remains a critical challenge in modern space engineering. Traditional shielding systems often face challenges in balancing weight and impact resistance. This study explores an impedance-graded shielding approach, incorporating sintered silicon carbide (SSiC), aluminium alloy 6082 (AA6082) and high-density polyethylene (HDPE) to enhance hypervelocity impact mitigation. The combination of graded mechanical impedance and multiple material failure mechanisms within the system offers significant potential for minimising damage to space structures by enhancing projectile fragmentation and maximising energy dissipation. The smoothed particle hydrodynamics method was implemented to model a 4 mm diameter spherical AISI 304 projectile impacting multiple arrangements of AA6082, SSiC and HDPE at 5 km/s. The resulting debris cloud data was analysed to visually assess the performance of different configurations. The findings demonstrate that the graded structure significantly improves stress wave dispersion and reduces the kinetic energy of the impactor, providing insights for the design of next-generation spacecraft shielding systems
Discovery and characterization of uracil derivatives targeting the Set-and-Ring domain of UHRF1
No full textThe Set-and-Ring domain of the UHRF1 oncogene is responsible for its interaction with hemimethylated DNA and faithful propagation of epigenetic signaling over cellular replication. Inhibiting this recognition can have serious implications in UHRF1 functionality and may possibly enable therapeutic interventions. Based on a previous finding indicating a promising in vitro DNA demethylating potential of a pyrimidine derivative, a sub-scaffold search was performed in the NCI/DTP compound repository to discover similar molecules and evaluate their affinity for the SRA domain of UHRF1. Toward this direction, several compounds were evaluated using a thermal melt screen and the most promising hits were subsequently studied by calorimetry in terms of their capacity to bind the 5-methylcytosine recognition site of UHRF1. A markedly different thermodynamic profile between the two confirmed hits with an intense enthalpy-entropy compensation signature was determined. The systems were further studied by biased and unbiased molecular simulations, computational hydration mapping and calorimetry-based heat capacity measurements to devise a hypothesis on the structural requisites for efficient SRA binding. The most potent compound was evaluated for its DNA methylation effects against the UHRF1-dependent colorectal cancer HCT116 cells, where promising global demethylating activity reaching an approximate 75% reduction compared to control was achieved after treatment with 25 μM of NSC232005. Based on the presented results, rationally substituted analogues of the uracil scaffold appear as highly promising UHRF1 modulators for exploring its diverse functionalities and validating the protein as a drug target. <br/
SLAMseq reveals potential transfer of RNA from liver to kidney in the mouse
No full textExtracellular RNA (exRNA) mediates intercellular communication in lower animals; whether it serves a signalling function in mammals is uncertain. Reductionist experiments, in which a single RNA is over-expressed or tagged, have shown RNA transfer between tissues but may not be relevant to normal physiology. Here, we seek to determine the scale of RNA transfer between liver and kidney using metabolic RNA labelling in mice. We use 4-thiouracil to label RNA in hepatocytes and then detect labelled RNA in the kidney using SLAMseq: SH-Linked Alkylation for Metabolic RNA sequencing. We show that in the kidney, 5% of mRNA transcripts are labelled in health, increasing to 34% after acute hepatocellular injury. In the kidney, we do not detect labelled small RNA, but do find higher levels of the liver-enriched miRNA, miR-122 after liver injury. Our results show potential transfer of RNA from liver to kidney: a phenomenon that is augmented by liver injury. There were important limitations: we could not confidently identify transferred RNA transcripts at the single-gene level and we did not assess the physiological consequences of any RNA transfer
Anti-aliasing of neural distortion effects via model fine tuning
No full textNeural networks have become ubiquitous with guitar distortion effects modelling in recent years. Despite their ability to yield perceptually convincing models, they are susceptible to frequency aliasing when driven by high frequency and high gain inputs. Nonlinear activation functions create both the desired harmonic distortion and unwanted aliasing distortion as the bandwidth of the signal is expanded beyond the Nyquist frequency. Here, we present a method for reducing aliasing in neural models via a teacher-student fine tuning approach, where the teacher is a pretrained model with its weights frozen, and the student is a copy of this with learnable parameters. The student is fine-tuned against an aliasing-free dataset generated by passing sinusoids through the original model and removing non-harmonic components from the output spectra. Our results show that this method significantly suppresses aliasing for both long-short-term-memory networks (LSTM) and temporal convolutional networks (TCN). In the majority of our case studies, the reduction in aliasing was greater than that achieved by two times oversampling. One side-effect of the proposed method is that harmonic distortion components are also affected. This adverse effect was found to be model dependent, with the LSTM models giving the best balance between anti-aliasing and preserving the perceived similarity to an analog reference device
Zero-phase sound via giant FFT
No full textGiven the speedy computation of the FFT in current computer hardware, there are new possibilities for examining transformations for very long sounds. A zero-phase version of any audio signal can be obtained by zeroing the phase angle of its complex spectrum and taking the inverse FFT. This paper recommends additional processing steps, including zero-padding, transient suppression at the signal’s start and end, and gain compensation, to enhance the resulting sound quality. As a result, a sound with the same spectral characteristics as the original one, but with different temporal events, is obtained. Repeating rhythm patterns are retained, however. Zero-phase sounds are palindromic in the sense that they are symmetric in time. A comparison of the zero-phase conversion to the autocorrelation function helps to understand its properties, such as why the rhythm of the original sound is emphasized. It is also argued that the zero-phase signal has the same autocorrelation function as the original sound. One exciting variation of the method is to apply the method separately to the real and imaginary parts of the spectrum to produce a stereo effect. A frame-based technique enables the use of the zero-phase conversion in real-time audio processing. The zero-phase conversion is another member of the giant FFT toolset, allowing the modification of sampled sounds, such as drum loops or entire songs
The emerging role of alternatively activated macrophages to treat acute liver injury
No full textAcute liver injury (ALI) has a clear requirement for novel therapies. One emerging option is the use of alternatively activated macrophages (AAMs); a distinct subtype of macrophage with a role in liver injury control and repair. In this comprehensive review, we provide an overview of the current limited options for ALI, and the potential advantages offered by AAMs. We describe the evidence supporting their use from in vitro studies, pre-clinical animal studies, and human clinical trials. We suggest why the first evidence for the clinical use of AAMs is likely to be found in acetaminophen toxicity, and discuss the specific evidence for AAM use in this population, as well as potential applications for AAMs in other patient populations. The key domains by which the performance of AAMs for the treatment of ALI will be assessed are identified, and remaining challenges to the successful delivery of AAMs to clinic are explored
Estimating heritability in small populations in the genomics era: a case study on Istrian sheep
No full textAccurate and reliable estimation of variance components is crucial in animal breeding programmes, as it guides selection and conservation strategies. Estimation can be particularly complicated in small-scale programmes at the start of or transition from traditional to genomic selection. In this study, we evaluate heritability estimates for milk, fat and protein yield in a local Croatian sheep breed using four approaches: pedigree- and genomic-based residual maximum likelihood (REML), single-step REML (ssREML), and REML using imputed data. We also explore how data availability and genetic relationships impact variance estimation for flocks of varying sizes and pedigree depth. Our dataset consisted of ~9500 lactation records (milk, fat and protein yield) for ~4500 Istrian sheep across ~40 flocks (ranging from 5 (6) to 430 (1129) animals (records)), ~63K in pedigree, ~1300 geno- typed with 50K SNP array and 15 key animals sequenced with 30X coverage. The results demonstrate that whilepedigree-based estimation is reliable for well-recorded flocks with many individuals, it becomes unreliable for smaller and more fragmented flocks. In such cases, genomic-based estimation, which captures additional geneticrelationships, provides more reliable heritability estimates. Our study highlights the importance of reliable heritability estimation in small-scale breeding programmes and contributes to optimising cost-effective phenotyping and genotyping strategies where large-scale actions may not be feasible due to economic constraints
From research proposal to project management. A guide from the Transkribus community on planning and executing workflows for researchers and GLAM-professionals
Get PDFTransitioning from research proposal to project management in Automatic Text Recognition (ATR) for cultural heritage text collections demands meticulous planning, realistic budgeting, and efficient team coordination. Insights from the Transkribus User Conference 2024 offer a roadmap for success, emphasising clear objectives, ethical considerations, and practical outcomes. Effective budgeting should include digitization, software, staffing, and long-term storage, while a comprehensive Data Management Plan (DMP) ensures efficient data handling. Key project management tasks include team formation, workflow documentation, and document layout optimization. High-quality training and validation data in ATR require clear guidelines, iterative testing, and agreed licensing. Crowdsourcing can enhance ATR projects, and sharing models and datasets through platforms like Transkribus Sites promotes collaboration and visibility
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