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Building realistic ground truth datasets of personal identification information for entity matching
No full textEntity matching (EM) is essential for connecting data across sources, particularly in sensitive domains like human trafficking investigations. However, research faces a critical gap: the lack of realistic gold standard datasets containing personal identifying information. This paper introduces a methodology for creating gold standard datasets, demonstrated through the development of a representative dataset for personal identification information (PII). Our approach combines multiple EM techniques to identify candidate matches, followed by a systematic annotation and validation process. Notably, our findings demonstrate that different techniques identify largely non-overlapping sets of matches, validating the need for our multi-technique methodology. Our approach provides a reproducible template for creating gold standard datasets in domains where realistic evaluation resources are scarce.This publication has emanated from research supported in part by the European Digital Innovation Hub Data2Sustain, co-funded by Ireland’s National Recovery and Resilience Plan (the EU’s Recovery and Resilience Facility), the Digital Europe Programme, and the Government of Ireland.peer-reviewe
Collagen scaffolds with controlled topography and stiffness and mechanical stimulation direct tissue-specific cell phenotype for tendon regeneration
No full textTendon and ligament injuries represent a major global cause of disability, frequently requiring surgical intervention to restore function. While tissue grafts remain the clinical gold standard for tendon augmentation, their use is constrained by risks of disease transmission and suboptimal tissue integration. Emerging tissue engineering strategies aim to overcome these limitations through the ex vivo development of tendon substitutes using biomaterial scaffolds and targeted microenvironmental cues; however, further refinement is required to achieve functional regeneration. Collagen type I, the principal structural component of tendons, holds great potential as a scaffold biomaterial, yet its adoption is hindered by sourcing and processing concerns. On the one hand, traditional sources such as bovine and porcine tissues raise concerns related to zoonosis risks and ethical acceptability. On the other hand, collagen manipulation complexity has traditionally limited the architectural and mechanical properties of collagen scaffolds. In this study, we hypothesised that an appropriate collagen type I scaffold with defined architectural and mechanical properties can maintain the phenotype of human tendon cells and induce the deposition of organised tendon-specific ECM in vitro.
In the first phase of this study, collagen type I was extracted from caprine skin, digital flexor and digital extensor tendons and compared to that extracted from bovine and porcine Achilles tendons. Biochemical analysis confirmed that caprine collagen type I purity was on pair with that of traditional sources. Subsequently, collagen was either non-crosslinked or crosslinked with 4-arm succinimidyl glutarate and processed into films. Caprine scaffolds displayed macroscopic and microscopic features, including fibril diameter ranges, similar to their bovine and porcine counterparts regardless of the tissue source. Mechanical characterisation revealed that caprine scaffolds were intrinsically stiffer and less susceptible to modulus increases upon crosslinking, suggesting underlying species-specific biochemical differences. With respect to cytocompatibility, caprine tendon-derived scaffolds supported the attachment, proliferation and metabolic activity of fibroblast and macrophages at levels consistent with those observed on bovine and porcine scaffolds. Notably, caprine skin-derived collagen enhanced both fibroblast and macrophage attachment relative to tendon-derived collagen from all species, pointing to tissue-specific functional differences. Immunogenicity analysis revealed all caprine scaffolds induced lower pro-inflammatory responses than Escherichia coli lipopolysaccharides on tissue culture plastic and elicited responses comparable to traditional collagen scaffolds. Minor increases in tumour necrosis factor alpha expression were observed in crosslinked groups, likely reflecting the influence of increased surface stiffness on macrophage behaviour rather than a direct effect of the crosslinker agent, as this was not observed in the indirect cultures. Collectively, these results underscore the potential of caprine tissues as an alternative source of collagen type I for the fabrication of medical devices.
In the second phase of this study, collagen scaffolds featuring either planar or grooved (2 x 2 x 2 μm) surface topographies and tuneable mechanical properties were fabricated using soft lithography and chemical crosslinking with different concentrations of succinimidyl glutarate (0.5 mM, 1.0 mM and 1.5 mM). Surface characterisation confirmed the presence of well-defined surface grooves, particularly in crosslinked scaffolds. The crosslinking agent reduced scaffold free amine content and increased Young’s modulus, indicating the formation of covalent bonds. In addition, micro-indentation measurements revealed a concentration-dependent increase in surface stiffness. In vitro experiments using human tendon cells demonstrate that grooved topographies promoted anisotropic cell and extracellular matrix alignment, especially in crosslinked scaffolds, highlighting the importance of collagen crosslinking for pattern stability. Crosslinking also exerted a dose-dependent effect on cell phenotype, with the highest concentration reducing cell proliferation, the lowest concentration inducing the broadest tendon-marker upregulation and all tested concentrations inducing higher tenascin C deposition than the non-crosslinked counterparts, a phenomenon we attributed to crosslinker-mediated surface smoothening and scaffold stiffening, respectively. Scaffolds crosslinked with the lowest crosslinker concentration and subjected to different tensional regimes (no tension, static tension and cyclic tension) showed that, within the parameters utilised in this study (frequency, strain and rest interval), static tension resulted in higher cell proliferation, enhanced cell and extracellular alignment and increased tendon marker upregulation compared to cyclic stimulation in planar, grooved, and both planar and grooved scaffolds, respectively. Collectively, this study advocates the use of combined biophysical cues to maintain physiological cell function.
In conclusion, our findings underscore the viability of caprine tissue as a source of collagen type I for the manufacturing of collagen devices and demonstrate that precise modulation of collagen scaffold architecture and mechanical properties directly influences the maintenance of a tendon cell phenotype in vitro. Together, these insights offer a foundation for the design of collagen-based functional tendon substitutes
The power of critique in the time of emergency: on normative fiction and critical fiction
No full textThis article begins by reflecting on crisis and democracy, arguing that the claim that democracy is in a state of crisis is a normative fiction that sustains rather than transforms extant self-other-world relations. An alternative is to frame the present as ‘the time of emergency’, which implies scope for ‘emergent’ possibilities. With a view to teasing out such possibilities, the article makes a case for critical fiction as a way of radicalising our relationship to the present, looking initially to Foucault’s writings on critique before turning (via a genealogical encounter with normative fiction) to the work of Denise Ferreira da Silva, who reads the present through the lens of a past that is not past, thereby troubling a future that need not come to pass.peer-reviewe
Novel heterocyclic peptides as potential inhibitors of proteases
No full textIn the 1970s, Clarke and Lowe modified papain with phenacylbromides to convert reactive cysteine 25 to serine 25 as a way to study papain binding. When the phenacylsulfide derivative of papain is exposed to UV light, it can undergo a Norrish Type II cleavage. Expanding on the work of Clarke and Lowe, the Myers group demonstrated cysteines in short peptides can be modified using this method to generate several species including heterocycles. One product of the Norrish Type II reaction is a thioaldehyde that subsequently tautomerizes and deprotonates to the enethiolate, which can be oxidized to the isothiazolone. Isothiazolones are of interest because they are already used as biocides and fungicides in agriculture and may have potential uses as inhibitors of cysteine proteases implicated in a wide variety of diseases. If the isothiazolone moiety can be introduced to a peptide or peptide mimic, it may be recognised by a cysteine protease and cause inhibition.
Currently, one of the most popular methods for producing short peptides (>20 residues) is solid phase peptide synthesis (SPPS). SPPS can include additional steps to modify the peptides when they are still attached to the resin, which makes removal of waste and purification easier. The main goal of this project is to introduce the isothiazolone moiety with the peptide still attached to the SPPS resin. SPPS was used in this project to synthesize the tripeptide AlaCysAla as a model tripeptide which was modified on-resin. The most common protecting group for cysteine, the trityl group, was replaced with the mono-methoxytrityl (Mmt) group to allow for cysteine deprotection and modification without peptide cleavage.
Initially, AlaCysAla was modified on-resin using methods from in solution cysteine modification and subsequently new methods of modification more optimal for on-resin cysteine modification were explored with the goal of producing isothiazolones in high yield and efficiency (Figure 1). During these optimisation experiments isothiazolone and another heterocycle, thiazole, were introduced to the peptide on-resin but isothiazolone was not produced in high yield.
The successful introduction of these heterocycles to the tripeptide on-resin is a promising start and with more optimisation and understanding of the reactions involved, it should be possible to make isothiazolone containing peptides on-resin with high efficiency
The Routledge Handbook of Child and Family Social Work Research
No full textAlthough early intervention is now established as a strategic orientation and operational component of many Child Protection and Welfare (CPW) systems the underpinning research field is as yet diffuse and underdeveloped. In spite of the intuitive value of these approaches, policy makers and managers remain resistant to a fundamental value shift or significant investment towards early intervention. Based on a reflective account of an evaluation of an early intervention practice model in the context of Ireland’s statutory CPW system, this chapter identifies learning on undertaking rigorous evaluation research in this areas and explores the challenge of generating evidence about early intervention to serve as the basis of policy and practice change. The chapter firstly frames early intervention conceptually, inclusive of its value as an organising principle for services, its parameters, and boundaries, as well as the challenges in establishing its evidence base. We also consider its application in CPW systems responses to the needs of children and young people, and the risks they face. Because of its significance for practice, we include attention to the literature on risk and risk assessment here, with an emphasis on the challenges of evidencing risk management practices based on early intervention and prevention of harm. The second part of the chapter offers a case study based on longitudinal mixed method evaluation of ‘Meitheal’, an innovative, early intervention model, operated by Tusla, Ireland’s Child and Family Agency. Here we describe and contextualise the Meitheal, presenting a real-world examination of early intervention in practice drawing on selected findings from the research. In the third part of the chapter, we reflect on the technical issues involved in implementing the evaluation study, before continuing with consideration of the challenges in establishing an evidence base for early intervention, its place in the CPW system and challenges in sustainability.peer-reviewe
Investigating changes in plant diversity and species composition in a selection of Irish semi-natural grasslands over the past decade
No full textSemi-natural grasslands are managed through low-intensity management practices, such as extensive grazing and/or annual mowing. As a result, they are species-rich ecosystems. Europe has lost between 50–90% of the area of semi-natural grasslands, accompanied by losses in diversity and changed species composition in the extant semi-natural grasslands. This is largely due to agricultural intensification and abandonment. In Ireland, 1,192 semi-natural grassland sites were surveyed through the 2007–2012 Irish Semi-natural Grassland Survey (ISGS). Using the ISGS as a baseline, the current study aimed to determine if the species diversity and composition has changed since the ISGS. This study is part of the larger Department of Agriculture, Fisheries and the Marine funded project called ‘StableGrass’. The overall aim of this large project is to assess the impact of plant diversity on carbon storage and yield stability in semi-natural grasslands. This study forms one component of this StableGrass project. This study re-surveyed 12 sites from three habitats (4 sites each); GS1 (Dry calcareous and neutral grassland), GS3 (Dry-humid acid grassland) and GS4 (Wet grassland). Fifty-four relevés were collected that included data on the species composition and cover. Vegetation diversity indices (Species Richness, Simpson’s Diversity, and Simpson’s Evenness) were calculated for these relevés.
GS1 had the highest Species Richness and Simpson’s Diversity followed by the GS4 habitat, while GS3 had the lowest values. There was no significant difference in the diversity measures between the ISGS and StableGrass surveys. Ordination analysis suggested evidence for homogenisation in the StableGrass relevés in comparison to the ISGS relevés. This was also observed at the species level with the loss of specialist and rare species and decreased frequencies of herbaceous species across the grasslands. Subtle changes in management, namely an increase in intensity since the ISGS survey was the likely cause for the observed homogenisation. However, management may also be maintaining the diversity at these sites considering the lack of a significant difference since the ISGS. This suggests that these trends could be reversed, provided improved management practices and future monitoring are in place to ensure this
Ecofeminist drought and slow ecological grief in Fabienne Bayet-Charlton’s Watershed
No full textThis article analyses temporalities of drought and grief in an understudied millennial Australian novel: Fabienne Bayet-Charlton’s Watershed. Watershed depicts a young white farming couple in rural Victoria battling a fierce drought while coping with prolonged grief over the death of their ten-year-old son. I contend that the layering of drought and grief in the text – both figured as slow forms of crisis – proffer slow temporalities that deal with both the small and large scales of space and time which constitute anthropogenic climate change. Using hydrocritical, postcolonial, and ecofeminist approaches, I show how the text articulates a politicised multiscalar yet embodied perspective which demonstrates the insights that a specifically freshwater approach to the blue humanities can bring to theorisations of environmental time and narrative strategy during planetary crisis
Analysis of cancer-associated mutations in the human POLH gene encoding DNA polymerase η
No full textUnrepaired DNA damage contributes to genome instability and to cancer, due to mutations in tumour suppressor genes and oncogenes. DNA damage tolerance (DDT) pathways, including translesion synthesis (TLS) carried out by the Y-family DNA polymerases Pol η, play a critical role by allowing DNA replication in the presence of template lesions, reducing replication arrest that can lead to genome instability. Inherited mutations in the POLH gene that inactivate Pol η cause xeroderma pigmentosum variant (XPV), characterised by UV-sensitivity, loss of accurate Pol η-mediated TLS, and elevated risk of skin cancer. Here, the effect of cancer-associated somatic POLH mutations on Pol η function was investigated using in silico, cell biological and biochemical approaches. 195 different somatic missense POLH mutations from the COSMIC and cBioportal databases were analysed in silico using five variant effect prediction (VEP) and four protein stability prediction programs. All mutations predicted to be deleterious by five VEP programmes were located in the N-terminal catalytic domain, except for H654N, located in the C-terminus. Seven somatic missense mutations (M14T, S51R, C72R, L89F, W174L, A223T and R361G) were deleterious in all VEP and protein stability prediction programs and may represent a subset of somatic POLH missense mutations that could affect tumour responses to DNA damaging agents. To investigate the effect of specific Pol η amino acid substitutions on the cellular response to DNA damage, a POLH-knockout MCF7 breast cancer cell line, C2, with a phenotype consistent with Polη-deficiency, was generated by CRISPR-Cas9 targeting. Transient transfection of POLH-knockout C2 cells with plasmids expressing Pol η having the somatic missense mutations, G153D, G263A, or M595V, linked to breast cancer, prostate cancer, and melanoma, respectively, showed that the mutated forms of Pol η were recruited to UV-induced nuclear foci. Using UV-induced RPA2 S4/S8 phosphorylation as marker for replication arrest-induced strand break formation, it was shown that wild-type Pol η could suppress this response, while Pol η with mutations at G263 to A, V, E, R or W did not, identifying 263 as an important somatic mutation site. Analysis of the effect of the G263A mutation on lesion bypass activity by isolated recombinant His-tagged protein Pol η showed that the G263A mutated form had 8-oxo-dG lesion bypass activity in vitro, with initial evidence of increased incorporation of dATP across from the 8-oxo-dG lesion by the G263A form. This research has identified cancer-associated somatic missense mutations in POLH that affect Pol η function in response to DNA damage. Although not tested directly here, this information on POLH mutations could be important in predicting the sensitivity of tumours to chemotherapy drugs such as cisplatin that generate damage bypassed by Pol η.Ministry of Education, Saudi Arabia and Beckman Fund Scholarship, Irelan
A longitudinal assessment of indoor air quality and thermal environment in naturally-ventilated energy-efficient dwellings
No full textBackground: As buildings become more energy-efficient, increasing levels of airtightness challenge the effectiveness of natural ventilation in maintaining acceptable indoor environmental quality, specifically regarding indoor air quality and thermal environment. While natural ventilation offers passive cooling benefits and supports energy-saving goals, its performance can be compromised in airtight homes, particularly in colder months when airflow is reduced. These changes may contribute to inadequate air change rates, elevated pollutant concentrations, and increased risk of summertime overheating. The interplay between airtightness, natural ventilation, and thermal comfort is underexplored, and long-term monitoring studies in occupied dwellings are particularly sparse. This research aims to address the knowledge gaps relating to natural ventilation, airtightness, thermal comfort and occupant behaviour, and the interplay between these aspects, from the perspective of energy-efficient naturally ventilated dwellings. The research focuses on: (i) assessing long-term air exchange rate performance and its impact on indoor environmental quality; (ii) characterising seasonal variations in indoor pollutant concentrations and thermal conditions; and (iii) examining the risk of overheating and the overall implications for occupant comfort and indoor environmental quality.
Methodology: A longitudinal field study was conducted in nine energy-efficient Irish dwellings over a full year. Indoor environmental conditions were monitored across the main spaces in each dwelling: bedrooms, living rooms, and kitchens, during both summer and winter and for a full calendar year, to collect data for a range of indoor air pollutants and thermal parameters. The measurements were complemented with qualitative data, collected through a survey of dwelling occupants.
For investigating the ventilation performance, a longitudinal approach involving the deployment of a remotely-operated consumer grade CO2 sensors was employed over one full calendar year. The air exchange rate was calculated based on occupant-generated CO₂ decay in the main bedroom of each dwelling and annual and seasonal trends in air exchange rates were examined. For evaluating indoor air quality, research-grade equipment was deployed in the bedroom (main), living room and kitchen of each house and monitoring of key indoor air pollutants and thermal parameters took place over a week-long period during both summer and winter. Indoor air pollutants included PM₂.₅, CO₂, TVOCs, NO₂, and CO, as well as environmental parameters such as temperature and relative humidity. Air exchange rates in bedrooms were estimated using the metabolic CO₂ method. Additionally, surveys and questionnaires were deployed to gather contextual information and occupant behavioural patterns.
Finally, the study evaluated the indoor thermal environment by deploying remotely-operated consumer-cost sensors to collect long-term temperature and relative humidity data in the dwellings. Analysis was performed using standardised categorisation of temperature and relative humidity data. Overheating risk was assessed following the CIBSE TM59 criteria in the bedrooms, living rooms, and kitchens.
Results: The ventilation and CO2 study findings showed significant seasonal variations in indoor CO₂ concentrations, with notably higher levels during winter, primarily due to reduced ventilation. Seasonal median air exchange rates ranged from 0.15 h⁻¹ in winter to 0.27 h⁻¹ in summer, reflecting this seasonal disparity. Over half of the recorded air exchange rates values (51%) fell within the 0.1–0.3 h⁻¹ range, while 15% were below 0.1 h⁻¹, highlighting periods of insufficient ventilation. In contrast, only 0.4% of the data exceeded 1.0 h⁻¹. The overall mean air exchange rate across all dwellings was 0.28 h⁻¹, which is approximately 42–70% lower than typical values reported for naturally ventilated conventional buildings. Instances of purge ventilation (short periods of elevated airflow often associated with window opening) were infrequent and highly variable, with observed rates ranging from 0.4 to 2.7 h⁻¹.
The indoor air quality study revealed that significantly higher concentrations of gaseous pollutants (p < 0.01) were recorded in bedrooms compared to living rooms, and during winter compared to summer. PM₂.₅ levels in kitchens exceeded the WHO 24-hour average threshold of 15 µg/m³ during the week-long monitoring periods in 92% of winter cases and 51% of summer cases. CO₂ concentrations in bedrooms remained above 1000 ppm for 94% of the sleeping hours in winter and 39% in summer, indicating prolonged exposure to suboptimal air quality. The weekly average TVOC concentrations across bedrooms were 463 ppb in winter and 293 ppb in summer. Indoor temperature and relative humidity generally remained within acceptable comfort and health ranges. Median air change rates in bedrooms were in the range 0.08–0.35 h⁻¹ in summer and 0.09–0.26 h⁻¹ in winter, reflecting limited ventilation across seasons.
For the longitudinal thermal environment study, results showed that during the heating season, the mean temperature in bedrooms was 20.84 ±0.86 °C (Living rooms: 20.48 ±0.96 °C, Kitchens: 20.70 ±0.88 °C). In the non-heating season, it was 23.22 ±1.02 °C (Living rooms: 22.54 ±0.99 °C, Kitchens: 22.77 ±0.99 °C). Bedroom temperatures above 24 °C (The heat-related health risks guidelines by the World Health Organisation) in the non-heating season ranged from 8.5-36.6% (Living rooms: 6.6-40.8%, Kitchens: 6.9-34.2%). Regarding overheating prevalence, fourteen of twenty-seven rooms failed CIBSE TM59 Criterion A for overheating, with four of nine bedrooms failing both Criteria A and B. Overall thermal comfort was higher in winter and lower in summer, according to the survey.
Conclusion: This research highlights a clear performance gap between the intended design and actual operational outcomes of natural ventilation in airtight energy-efficient dwellings, particularly under current operational patterns. Significant seasonal fluctuations were observed in both ventilation rates and indoor air pollutants concentrations, with winter conditions associated with reduced ventilation and elevated indoor air pollutants levels, and summer marked by challenges in managing overheating. While natural ventilation can, under certain conditions, provide adequate airflow delivery, its effectiveness is highly dependent on occupant behaviour and external climatic conditions. In winter, insufficient ventilation compromises indoor air quality, while in summer, passive cooling potential remains underutilised due to limited airflow and persistent overheating. These findings underscore the need for adaptive and seasonally- responsive ventilation strategies. Improvements such as hybrid ventilation systems, enhanced user guidance, and targeted mitigation measures are essential to optimise ventilation performance, safeguard indoor environmental quality, and ensure thermal comfort across the year
Scope to improve consumption of oral nutritional supplements to manage malnutrition in cancer patients using novel sensory nutrition techniques
No full textDietary counselling combined with oral nutritional supplements (ONS) has demonstrated clinical effectiveness in enhancing nutritional status and addressing undernutrition in cancer patients. Despite these benefits, negative sensory experiences often associated with ONS have been linked to poor adherence. This thesis investigated the sensory perception and acceptance of ONS among cancer patient cohorts, aiming to identify strategies to improve compliance. By utilizing various sensory evaluation methodologies, the research also sought to assess their suitability for cancer patients, thereby contributing to advancements in sensory science tailored to this population