Now showing items 1-20 of 2599

    • Chain-Extendable Crosslinked Hydrogels Using Branching RAFT Modification

      Rimmer, Stephen; Spencer, P.; Nocita, D.; Sweeney, John; Harrison, M.; Swift, Thomas (2023-03-17)
      Functional crosslinked hydrogels were prepared from 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA). The acid monomer was incorporated both via copolymerization and chain extension of a branching, reversible addition–fragmentation chain-transfer agent incorporated into the crosslinked polymer gel. The hydrogels were intolerant to high levels of acidic copolymerization as the acrylic acid weakened the ethylene glycol dimethacrylate (EGDMA) crosslinked network. Hydrogels made from HEMA, EGDMA and a branching RAFT agent provide the network with loose-chain end functionality that can be retained for subsequent chain extension. Traditional methods of surface functionalization have the downside of potentially creating a high volume of homopolymerization in the solution. Branching RAFT comonomers act as versatile anchor sites by which additional polymerization chain extension reactions can be carried out. Acrylic acid grafted onto HEMA–EGDMA hydrogels showed higher mechanical strength than the equivalent statistical copolymer networks and was shown to have functionality as an electrostatic binder of cationic flocculants.
    • In jars: The integration of historical anatomical and pathological potted specimens in undergraduate education

      Sutton-Butler, Aoife; Croucher, Karina; Garner, Pip; Bielby-Clarke, Keren; Farrow, Matthew (2023-04)
      Across the UK, many anatomy departments possess historical potted wet cadaveric specimen collections, such as organs preserved in fluid-filled jars. Although considered obsolete by some for anatomical education, there is immense potential for their utilisation in teaching, particularly in institutes that have limited access to cadavers or have had body donation rates impacted by the Covid-19 pandemic. Another benefit of historical potted cadaveric specimens is that severe pathology, often not seen today, can be observed by the student. The aim of this study was to understand students' opinions and attitudes towards the use of historical anatomical and pathological potted wet specimen collections in undergraduate science teaching. Following their integration into the anatomy program of a Clinical Sciences degree, seventy-seven undergraduate students completed a five-point Likert questionnaire on their perspective for the integration of the historical potted specimens in anatomical education. This study was approved by the Research Ethics committee at the University of Bradford RESULTS: The study demonstrated that 90 % of students found the collection useful in teaching, 92 % would like to see the collection used more in teaching, and 76 % of students found that the collection encouraged them to consider medical ethics and the donor. In conclusion, the survey findings suggest that further utilisation of historical potted wet specimen collections would be useful in the teaching of anatomy and that these collections could potentially encourage conversations on post-mortem bodily integrity, ethics, and organ donation.
    • Stromal vascular fraction cells from individuals who have previously undergone radiotherapy retain their pro-wound healing properties

      Trevor, L.V.; Riches-Suman, Kirsten; Mahajan, A.L.; Thornton, M. Julie (2023-03)
      Beneficial effects have been observed following the transplant of lipoaspirates containing adipose-derived stem cells into chronic wounds caused by oncologic radiotherapy. It is not yet certain whether adipose-derived stem cells are resistant to radiation exposure. Therefore, the aims of this study were to isolate stromal vascular fraction from human breast tissue exposed to radiotherapy and determine the presence of adipose-derived stem cells. Stromal vascular fraction from irradiated donor tissue was compared to commercially sourced pre-adipocytes. Immunocytochemistry was used to determine the presence of adipose-derived stem cell markers. Conditioned media from stromal vascular fraction isolated from irradiated donors was used as a treatment in a scratch wound assay of dermal fibroblasts also isolated from irradiated donors and compared to pre-adipocyte conditioned media and serum free control. This is the first report of human stromal vascular fraction being cultured from previously irradiated breast tissue. Stromal vascular fraction conditioned media from irradiated donors had a similar effect in increasing the migration of dermal fibroblasts from irradiated skin to pre-adipocyte conditioned media from healthy donors. Therefore, the ability of adipose-derived stem cells in the stromal vascular fraction to stimulate dermal fibroblasts in wound healing appears to be preserved following radiotherapy. This study demonstrates that stromal vascular fraction from irradiated patients is viable, functional and may have potential for regenerative medicine techniques following radiotherapy.
    • Exploration of meaning, motivation, and preparedness to care amongst the one-child policy generation in China

      Bifarin, Oladayo O.; Quinn, Catherine; Breen, Liz; Yu, L.; Oyebode, Jan R. (2023-02)
      In China there is a cultural expectation (Xiao, -filial piety) that offspring should provide care for their parents. However, the sustainability of this is threatened by the impact of the One-Child Policy (OCP) (1979-2015), which has resulted in a diminution in numbers of children available to care, rapid urbanisation and increase in the number of women in employment. In this context, the objective was to explore the motivations, meaning, and preparedness for future caregiving of offspring affected by the OCP. We adopted a constructivist position using a hermeneutic phenomenology approach and interviewed eight current and prospective caregivers aged 20-35 years about future caregiving responsibilities. Data were obtained through in-depth interviews, analysed using reflective Thematic Analysis. Three prominent themes: (i) Caregiving beliefs, (ii) Caregiving conditions and (iii) Contextual factors were identified under an overarching theme "Competing pressures-meanings, motivation and preparedness". Despite the inherent stress, participants envisaged providing or organising care in the future to fulfil Xiao, and most viewed long-term care settings as unviable. Ultimately, the findings suggested that the actual performance of caregiving would not always measure up to ideal expectations, resulting in 'filial discrepancy' that is, a gap between societal expectations for caregiving to older relatives and actual caregiving performance. This could adversely impact the caregivers and quality of care provided. The findings highlighted the urgent need to develop culturally attuned services, including education and training for family caregivers, health and social care professionals.
    • Stabilisation of acrylic latexes containing silica nanoparticles for dirt repellent coating applications

      Swift, Thomas (Elsevier, 2023-04)
      This study examines the feasibility of using colloidal silica nanoparticles as active agents in high concentration waterborne polymer latex formulations. We showed that distributing the silica throughout the waterborne emulsion formed a composite coating material with a hydrophilic surface that consequently reduced exterior dirt pickup. Two grades of silica nanoparticles were studied, one using sodium stabilisation and another using epoxysilane modification to introduce glycidox-ypropyltrimethoxysilane surface functionality. Rheological study of the waterborne latex on mixing showed that there was an immediate pH responsive interaction between the silica sols and the polymer latex. Once loading of sodium charge stabilised silica NPs exceeded the volume required for heteroflocculation to occur the mixture demonstrated the potential to gel on standing – a process which took weeks, or months, to occur depending on the pH and relative concentrations used. At least fifty percent silane modification to the NP surface was found to be necessary to maintain a stable colloidal dispersion for long term storage of the waterborne latex. Despite this both grades of silica were found to imbue reductions in dirt pickup when applied to exterior masonry concrete studies over a 3-month weathering test
    • DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation

      Chen, G-D.; Fatima, I.; Xu, Q,; Rozhkova, E.; Fessing, Michael Y.; Mardaryev, Andrei N.; Sharov, A.A.; Xu, G-L.; Botchkarev, Vladimir A. (2023-01)
      Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14–Cre–driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation–independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.
    • Investigation into the development of novel lanthanide-based luminescent colorants for application to textiles and paper materials

      Lewis, D.M.; Broadbent, P.J.; Rigout, M.L.A.; Carr, C.M.; Seaton, Colin C.; Swift, Thomas (2023)
      This article describes the synthesis and application of lanthanide-based luminophores for visualisation under short wavelength ultraviolet (UV) activation (typically 254 nm). Luminophores are chemical compounds which re-emit light of longer wavelength than typical fluorescence and phosphorescence, following photoexcitation, because of efficient energy transfer from the ligands to the lanthanide ion emission levels. The luminophores described in this article are all derived from europium and terbium metal complexes and cover the complete colour gamut. Selection of appropriate ligands allows for water solubility or water insolubility (if required pigment or disperse “dye” applications). Similar to dyeing or printing processes, the anionic complexes can be applied to polyamide fibres or to cellulosic fibres, whereas dispersions of the non-ionic complexes are suitable for polyester or cellulose acetate fibre application. The water-soluble derivatives are also suitable for ink-jet printing and the water-insoluble derivatives are suitable for lithographic or intaglio paper printing. The novel complexes are excited by radiation below 300 nm and thus cannot be activated by sunlight (the earth's atmosphere prevents light below about 300 nm reaching the surface). Accordingly, the photo-stability of the dyed materials and prints obtained is excellent. These materials could be used in security marking applications, for example bank-notes and passports, where they could replace the current fluorophores that are rendered visible under near UV light (typically 365 nm) illumination but exhibit relatively poor photo-stability. The development of an RGB (red, green and blue) colour palette for inkjet printing based on these innovative luminophores will significantly support the design of digitally printed security features.
    • Metal-organic frameworks as potential agents for extraction and delivery of pesticides and agrochemicals

      Mahmoud, L.A.M.; dos Reis, R.A.; Chen, X.; Ting, V.P.; Nayak, Sanjit (2022-12)
      Pesticide contamination is a global issue, affecting nearly 44% of the global farming population, and disproportionately affecting farmers and agricultural workers in developing countries. Despite this, global pesticide usage is on the rise, with the growing demand of global food production with increasing population. Different types of porous materials, such as carbon and zeolites, have been explored for the remediation of pesticides from the environment. However, there are some limitations with these materials, especially due to lack of functional groups and relatively modest surface areas. In this regard, metal-organic frameworks (MOFs) provide us with a better alternative to conventionally used porous materials due to their versatile and highly porous structure. Recently, a number of MOFs have been studied for the extraction of pesticides from the environment as well as for targeted and controlled release of agrochemicals. Different types of pesticides and conditions have been investigated, and MOFs have proved their potential in agricultural applications. In this review, the latest studies on delivery and extraction of pesticides using MOFs are systematically reviewed, along with some recent studies on greener ways of pest control through the slow release of chemical compounds from MOF composites. Finally, we present our insights into the key issues concerning the development and translational applications of using MOFs for targeted delivery and pesticide control.
    • Metal-organic frameworks and their biodegradable composites for controlled delivery of antimicrobial drugs

      Livesey, T.C.; Mahmoud, L.A.M.; Katsikogianni, Maria G.; Nayak, Sanjit (2023-01)
      Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal-organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer-MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research.
    • RNA-sequencing muscle plasticity to resistance exercise training and disuse in youth and older age

      Fernandez-Gonzalo, R.; Willis, Craig R.G.; Etheridge, T.; Deane, C.S. (2022-12)
      Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.
    • Carbon and nitrogen isotope analysis for dietary reconstruction and carbon and nitrogen incremental dentine analysis

      Delaney, s.; Murphy, E.; Beaumont, Julia; Cassidy, L.; Drain, D.; Gillig, N.; Gormley, S.; Halstead, L.; Jackson, I.; Jones, M.; et al. (Transport Infrastructure Ireland, 2022-12)
      In 2015, a previously unknown enclosed settlement and burial ground was found near the summit of a low hill in Ranelagh townland, just north of Roscommon town. The site—officially designated Ranelagh 1, and hereafter referred to variously as ‘the Ranelagh site’, ‘the site at Ranelagh’ or simply ‘Ranelagh’—was excavated over a 54-week period by Excavation Director Shane Delaney for Irish Archaeological Consultancy (IAC) Ltd between October 2015 and October 20161 . Excavations revealed that the site was established during the fourth century AD; for over 1,000 years, until the final phase of burial activity proper concluded there shortly after AD 1400, the site would have been a prominent feature in both the geographical and psychological landscape of the time. Cillín (children’s) burials continued at the site until about AD 1650, further asserting this prominence.
    • Editorial: Women in integrative physiology: 2021

      Helfer, Gisela; Kadmiel, M.; Jethwa, P.H. (2022-09)
    • Co-designing an intervention to improve the process of deprescribing for older people living with frailty in the United Kingdom

      Silcock, Jonathan; Marques, Iuri; Olaniyan, Janice; Raynor, D.K.; Baxter, H.; Gray, N.; Zaidi, S.T.R.; Peat, George W.; Fylan, Beth; Breen, Liz; et al. (Elsevier, 2023-02)
      Background: In older people living with frailty, polypharmacy can lead to preventable harm like adverse drug reactions and hospitalisation. Deprescribing is a strategy to reduce problematic polypharmacy. All stakeholders should be actively involved in developing a person-centred deprescribing process that involves shared decision-making. Objective: To co-design an intervention, supported by a logic model, to increase the engagement of older people living with frailty in the process of deprescribing. Design: Experience-based co-design is an approach to service improvement, which uses service users and providers to identify problems and design solutions. This was used to create a person-centred intervention with the potential to improve the quality and outcomes of the deprescribing process. A ‘trigger film’ showing older people talking about their healthcare experiences was created and facilitated discussions about current problems in the deprescribing process. Problems were then prioritised and appropriate solutions were developed. Review located the solutions in the context of current processes and procedures. An ideal care pathway and a complex intervention to deliver better care were developed. Setting and participants: Older people living with frailty, their informal carers and professionals living and/or working in West Yorkshire, England, UK. Deprescribing was considered in the context of primary care. Results: The current deprescribing process differed from an ideal pathway. A complex intervention containing seven elements was required to move towards the ideal pathway. Three of these elements were prototyped and four still need development. The complex intervention responded to priorities about (a) clarity for older people about what was happening at all stages in the deprescribing process and (b) the quality of one-to-one consultations. Conclusions: Priorities for improving the current deprescribing process were successfully identified. Solutions were developed and structured as a complex intervention. Further work is underway to (a) complete the prototyping of the intervention and (b) conduct feasibility testing.
    • Psychology for the Common Good: The Interdependence of Citizenship, Justice, and Well-being across the Globe

      Prilleltensky, I.; Di Martino, Salvatore; Ness, O. (Frontiers in Psychology, 2022-11)
    • Design of a graphene oxide-BODIPY conjugate for glutathione depletion and photodynamic therapy

      Reina, G.; Ruiz Estrada, Amalia; Richichi, B.; Biagiotti, G.; Giacomazzo, G.E.; Jacquemin, L.; Nishina, Y.; Ménard-Moyon, C.; Al-Jamal, W.T.; Bianco, A. (2022-01)
      Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol derivatisation with the phenyl boronic acid moiety at the meso position of the BODIPY core, allowed to preserve the intrinsic properties of GO. We demonstrated that both chlorine atoms were substituted by GSH in the presence of glutathione transferase (GST), inducing a relevant bathochromic shift in the absorption/emission features and thus generating the active PS. Ex vitro assessment using cell lysates containing cytoplasmatic GST revealed the intracellular catalytic mechanism for the nucleophilic substitution of the GO-BODIPY adduct with GSH. Confocal microscopy studies showed important differences in the cellular uptake of free BODIPY and GO-BODIPY and revealed the coexistence of GO-BODIPY, GO-BODIPY-GS, and GO-BODIPY-GS2 species inside vesicles and in the cytoplasm of the cells after 24 h of incubation. In vitro biocompatibility and safety of GO and GO-BODIPY were evaluated in 2D and 3D models of prostate adenocarcinoma cells (PC-3), where no toxicity was observed up to 100 µg ml−1 of GO/GO-BODIPY in all treated groups 24 h post-treatment (cell viability > 90%). Only a slight decrease to 80% at 100 µg ml−1 was observed after 48 h of incubation. We demonstrated the efficacy of a GO adduct containing an α-chlorine-substituted BODIPY for the simultaneous depletion of intracellular GSH and the photogeneration of reactive oxygen species using a halogen white light source (5.4 mW cm−2) with a maximum in the range of 500–800 nm, which significantly reduced cell viability (<50%) after irradiation. Our study provides a new vision on how to apply BODIPY derivates and potentiate the toxicity of PDT in prostate and other types of cancer.
    • When stuff gets old: material surface characteristics and the visual perception of material change over time

      De Korte, Ellen E.M.; Logan, A.J.; Bloj, Marina (2022-11)
      Materials’ surfaces change over time due to chemical and physical processes. These processes can significantly alter a material’s visual appearance, yet we can recognise the material as the same. The present study examined the extent of changes the human visual system can detect in specific materials over time. Participants (N = 5) were shown images of different materials (Banana, Copper, Leaf) from an existing calibrated set of photographs. Participants indicated which image pair (of the 2 pairs shown) displayed the largest difference. Estimated perceptual scales showed that observers were able to rank the images of aged materials systematically. Next, we examined the role that global and local changes in material surface colour play in the perception of material change. We altered the information about colour and geometrical distribution in the images used in the first experiment, and participants repeated the task with the altered images. Our results showed significant differences between individual observers. Most importantly, participants’ ability to rank the images varied with material type. The leaf images were particularly affected by our alteration of the geometrical distribution. Together, our findings show the factors contributing to the perception of material change over time.
    • Using routine healthcare data to evaluate the impact of the Medicines at Transitions Intervention (MaTI) on clinical outcomes of patients hospitalised with heart failure: protocol for the Improving the Safety and Continuity Of Medicines management at Transitions of care (ISCOMAT) cluster randomised controlled trial with embedded process evaluation, health economics evaluation and internal pilot

      Moreau, L.A.; Holloway, I.; Fylan, Beth; Hartley, S.; Cundill, B.; Fergusson, A.; Alderson, S.; Alldred, David P.; Bojke, C.; Breen, Liz; et al. (2022-04)
      Introduction Heart failure affects 26 million people globally, approximately 900 thousand people in the UK, and is increasing in incidence. Appropriate management of medicines for heart failure at the time of hospital discharge reduces readmissions, improves quality of life and increases survival. The Improving the Safety and Continuity Of Medicines management at Transitions (ISCOMAT) trial tests the effectiveness of the Medicines at Transition Intervention (MaTI), which aims to enhance self-care and increase community pharmacy involvement in the medicines management of heart failure patients. Methods and analysis ISCOMAT is a parallel-group cluster randomised controlled trial, randomising 42 National Health Service trusts with cardiology wards in England on a 1:1 basis to implement the MaTI or treatment as usual. Around 2100 patients over the age of 18 admitted to hospital with heart failure with at least moderate left ventricular systolic dysfunction within the last 5 years, and planned discharge to the geographical area of the cluster will be recruited. The MaTI consists of training for staff, a toolkit for participants, transfer of discharge information to community pharmacies and a medicines reconciliation/review. Treatment as usual is determined by local policy and practices. The primary outcome is a composite of all-cause mortality and heart failure-related hospitalisation at 12 months postregistration obtained from national electronic health records. The key secondary outcome is continued prescription of guideline-indicated therapies at 12 months measured via patient-reported data and Hospital Episode Statistics. The trial contains a parallel mixed-methods process evaluation and an embedded health economics study.
    • The Bioarchaeology of Disability: A population-scale approach to investigating disability, physical impairment, and care in archaeological communities

      Bohling, Solange N.; Croucher, Karina T.; Buckberry, Jo (2022-09)
      Objective: This research introduces ‘The Bioarchaeology of Disability’ (BoD), a population-scale approach which allows for a comprehensive understanding of disability in past communities through a combination of palaeopathological, funerary, and documentary analyses. Methods: The BoD consists of three phases: 1) Contextualisation includes period-specific literature review; 2) Data collection consists of palaeopathological re-analysis of individuals with physical impairment and collation of mortuary treatment data; and 3) Analysis incorporates qualitative and quantitative comparison of the funerary treatment of individuals with and without physical impairment to explore contemporary perceptions of disability. Materials: The BoD is demonstrated through a case study investigation of disability in later Anglo-Saxon England (c.8th-11th centuries AD) which included four burial populations (Ntotal=1,543; Nimpaired=28). Results: Individuals with disability could be buried with normative or non-normative treatment (e.g., stone/clay inclusions, non-normative body positioning), and in marginal, non-marginal, and central locations. Conclusions: The overall funerary variation for individuals with disability was relatively slight, which may suggest that political and religious factors were influencing normative funerary treatment of disabled individuals. The funerary variability that was observed in disabled individuals was probably influenced by individual and community-specific beliefs. Significance: This research describes a population-scale approach to archaeological disability studies that can be replicated in other archaeological contexts. Limitations: Individuals with non-skeletal physical impairment (e.g., soft tissue, mental) cannot be analysed osteologically and are not considered by the BoD. Suggestions for further research: The BoD should be applied to different archaeological communities around the world to better understand disability in the past.
    • The osteological evidence for execution in Anglo-Saxon England

      Mattison, A.; Williams-Ward, Michelle L.; Buckberry, Jo; Hadley, D.M.; Holgate, R. (BAR Publishing, 2022)
      This paper reviews the osteological evidence for execution in Anglo-Saxon England, which, in the cases of modern analysis, can reveal considerable detail about the methods of decapitation, in particular, and it also provides a critical appraisal of the considerably less reliable antiquarian reports. We suggest that secure evidence for execution, principally decapitation, can be identified through modern osteological analysis but it is limited, and we also argue that assertions made in antiquarian excavation reports about apparent examples of execution need to be treated with caution.