11237 research outputs found
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Development of inhalable formulations of disulfiram metabolites for localised treatment of non-small cell lung cancer
No full textPulmonary drug delivery has gained a wide attention for targeted delivery in lung cancer treatment. Zinc Diethyldithiocarbamate (Zn(DDC)2) has a great potential for cancer treatment however, its low water solubility hinders its clinical application. Therefore, the aim of this study is enhancing the solubility of Zn(DDC)2 using cyclodextrins to form inclusion complexes, and to investigate the potential of pulmonary delivery of the developed complexes for pulmonary delivery in lung cancer treatment to help increasing drug accumulation at tumour site with lower doses and less systemic side effects which will benefit in reducing the cost of treatment and give more convenience therapeutic option to the patients.Complexation of Zn(DDC)2 with cyclodextrin was investigated using hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-CD (SBE-β-CD). Using the direct method of saturated solution has increased the solubility of Zn(DDC)2 up to up to 3.92 ± 0.07 mg/ml and 4.46 ± 0.17 mg/ml for 20% w/w SBE-β-CD and HP-β-CD, respectively. Cyclodextrin complexes prevented the drug precipitation and provided better penetration to the cells that resulted in enhancing the cytotoxicity of Zn(DDC)2 by 10-folds compared to free drug. The IC50 of Zn(DDC)2 has decreased from 54.6 ± 1.59 μM for the free drug to 6.8 ± 0.57 μM and 4.9 ± 0.34 μM, for HP-Zn(DDC)2 and SBE-Zn(DDC) respectively. The nebulisation of the complexes was investigated using next generation impactor (NGI) and two stage twin impinger (TSI) using air-jet nebuliser only, the drug output reached up to 73.88 ± 9.27% with fine particle fraction (FPF) around 48.17 ± 3.74% and respiratory fraction of 80.57 ± 1.60 % indicating a good potential for pulmonary deposition of the complexes.Dry powder formulations for Zn(DDC)2-CD complexes were produced using freeze-drying and spray-drying techniques for pulmonary delivery using dry powder inhaler. Spray-drying resulted in powders with desirable aerosolisation properties for inhalation compared to powders produced using freeze-drying. Therefore, spray-dried powders were investigated for further improvement using leucine, the incorporation of 10% leucine further improved the FPF percentage up to 76.77 ± 1.18% compared to 24.69 ± 1.84% for leucine free powders. The delivery of spray-dried powders of Zn(DDC)2-CD complexes with leucine using DPI exhibited better aerosolisation properties than their delivery via nebulisation using air-jet nebuliser. Hence, they have higher tendency to be deposited in the lungs and produce localised effect. Overall, cyclodextrin-based formulations for Zn(DDC)2 using dry powder inhalation showed a great potential for pulmonary delivery in the treatment of non-small cell lung cancer (NSCLC).</p
<i>tidypopgen</i>: Tidy Population Genetics in R
No full textAs genome-wide data has become increasingly available, software libraries for their analysis have proliferated. While new tools for downstream analyses are constantly emerging, existing workflows are hindered by inefficiencies. Switching between coding languages and object types in the early stages of pipelines wastes researchers’ time, impedes reproducibility, and creates opportunity for error. To confront these obstacles, we introducetidypopgen, a comprehensive R package for population genetic analysis of biallelic SNP data. Genotype data can be read, filtered, and analysed within a single environment, without the need for prior data cleaning or setup with other software.tidypopgen’sgen_tibbleobject structure makes analysis efficient and intuitive, while standardised tidy grammar makes data manipulation clear.Functionality withintidypopgensupports cleaning and merging datasets, basic descriptive statistics, multivariate analysis, clustering algorithms, and F-statistics, as well as integrating with existing tools for population genetic analyses in R. We use the Human Genome Diversity Project SNP dataset (Li et al., 2008) to show that a basic population genetic workflow can be executed in under 25 lines of code in a single environment using one file set, without the need to write superfluous outputs or change directories. By supporting data assembly through to data analysis,tidypopgensignificantly streamlines workflows without compromising speed or functionality.</p
Higher Education Learning Experiences pre-, peri- and post-COVID-19: What will evolve, and what will survive?
No full textThis article reports the results of a mixed-methods research project at one UK university to explore student experiences before, during, and after the COVID-19 lockdowns. The research questions were ‘Which HE learning experiences will be retained?’ and ‘Which HE learning experiences will evolve?’. All final-year undergraduates in the 2021/22 academic year (n = ~3,000) were asked, via a survey and focus groups, to rate various formats of learning and teaching for their effectiveness for learning, building positive learning communities, and overall satisfaction. Students were also asked to list any features of their learning from before the pandemic that the University should reinstate, and any from during the pandemic that should be retained. Quantitative data were analysed using SPSS, and qualitative data were analysed using NVivo. Analysis suggests that prior to the lockdowns, students felt they had the full ‘university experience’ as they had anticipated. During lockdowns, students faced disorientation, isolation, and a lack of motivation, but appreciated not having to commute, and an improved work/life balance. After lockdown ended, students wanted to return to on-campus teaching, particularly for the social aspects, and to experience higher-quality teaching. Although large-group lectures on campus scored highly for both effectiveness and satisfaction, students wanted to retain recordings of live lectures for revision and unanticipated absences. Analysis by demographics indicated variations by gender, study mode (i.e. Part-Time/Full-time), learning difficulties, and caring responsibilities, emphasising the imperative to meet the differing learning needs of diverse student populations.</p
Assessing fidelity of motivational interviewing-based ‘treatment support’ delivered by rheumatology practitioners within the TITRATE trial
No full textIntroduction: To investigate treatment fidelity of selected motivational interviewing (MI) techniques applied by trained rheumatology practitioners (who were mostly nurses) in the TITRATE randomised controlled trial (N=335), and to understand their potential contribution to reductions in rheumatoid arthritis pain and fatigue observed in the trial. Methods: Analysis of fidelity data collected across 39 NHS rheumatology outpatient clinics participating in the experimental ‘intensive management’ arm of TITRATE trial. A 10% sample of audio-recorded intensive management participant consultations (N=126) was assessed by four investigators. The dataset represented 19 NHS rheumatology outpatient clinics. Evaluation was conducted using a bespoke, piloted, intervention fidelity assessment tool, and focused on the application of taught MI techniques. Results: Over half (56%) the consultations achieved moderate or high fidelity ratings across the taught MI techniques. Practitioners demonstrated skilled rapport building during 60% of consultations, and 42% included agreement on appointment agenda and the skilled use of affirmations. Practitioners demonstrated higher skill levels at providing emotionally-supportive care and lower skill levels at supporting behaviourally-focused discussion. Practitioners demonstrating MI skills in the earlier consultations maintained these. Those initially demonstrating fewer techniques did not improve over time. Discussion: Findings evidence rheumatology practitioners learnt, and implemented, most of the MI techniques. Future research needs to examine if focusing on a person’s emotions and behaviours during a consultation facilitate behavioural changes, for example pacing and medication concordance, which may result in reduced pain and fatigue.</p
Editorial on Climate Change and Institutional Review Boards (IRBs)
No full textClimate change has a significant impact on human health. Research in this area is crucial for developing effective methods to reduce its effects. Institutional Review Boards (IRBs) play a crucial role in detecting potential gaps, mapping out patterns of consequences on vulnerable populations, health systems, and emphasising gaps in climate and health/biomedical research in specific geographic areas. In addition, IRBs are responsible for making decisions on the study’s adherence to the (bio)ethical principles of data privacy and confidentiality, equality and diversity, inclusivity, and respect for research participants' dignity.</p
The potential of independent children's magazines for the illustrator: a practice-based investigation
No full textThis practice-based research study aims to identify contemporary independent children’s magazines and their traits, understand practices and roles involved in making them, and explore the potential they offer the illustrator. It was driven by an awareness of an emergence of new independent children’s magazine titles with shared traits, particularly the prominence of illustration within, in European countries, and practitioner interest in engaging with one and its miscellaneous content. This research contributes to the under-researched field of independent children’s periodicals, providing a contemporary perspective from a practitioner’s standpoint.A multi-method approach was used, with reflective creative practice at its core. Literature and primary literature review and analysis offered theoretical and descriptive understanding of the form and particular real-world examples. Interviews provided insight into individual contemporary editorial and illustrator practices. Creative practice enabled open-ended experimentation and exploration of the limits of the children’s magazine form, allowing insight into the illustrator’s process and choices.In the development of two Prototypes for children’s magazines, identified procedural and formal aspects were replicated and subverted toward finding alternative solutions and innovative approaches in making. In so doing, the illustrator’s role shifted between editorial and authorial, and the resulting magazine issues further incorporated aspects from other artforms, defying perceived conventions.This study resulted in new knowledge on the independent children’s magazine as a form, identifying specific commonalities with related artforms and disciplines, and proposing a definition. It provides new insight into contemporary real-world cases, identifying two different editorial approaches, one of which is the illustrator collective. Creative practice demonstrates how a children’s magazine’s format, use of theme and structure may be resolved alternatively. It further shows that the illustrator has the ability to take on every aspect of production, and achieve a holistic development of the magazine and its content.</p
The New Formenlehre meets jazz: the piano sonatas of Nikolai Kapustin
No full textNikolai Kapustin (1937-2020) lived the majority of his life under the Soviet Union as a classical composer and as a touring Jazz Big Band pianist. His experiences in both the classical and jazz worlds are synthesized in his works. While the composition titles resemble the classical tradition (Sonatas, Bagatelles, Prelude and Fugues, Etudes, etc.), they nonetheless evoke the sonorities of jazz. The synthesis of jazz and classical form has been remarked upon by many concert critics and performance-studies scholars within the last decade. Prominently featured among Kapustin’s hybrid compositions are the sonatas, hallmarks of the classical era. If Kapustin’s sonatas are to be taken at face value, and they fulfil some of the expecations of a classical sonata, it stands to reason that these works can be understood by the analytical methods of today. The most recent theories of sonata form build on Caplin’s Classical Form (1998) and Hepokoski and Darcy’s Elements of Sonata Theory (2006), pioneers of an analytical school known as the “New Formenlehre”. While the New Formenlehre represents a modern approach to sonata form, the literature is still strongly rooted in 18th-century repertoire. Only within the last decade has the current discourse veered from the high classical style towards romanticism. As one would expect, Kapustin, as a composer from the 20th-century working with jazz idioms, is left out of this discourse. As such, there is a considerable gap of knowledge not only in regards to Kapustin’s compositions but also to jazz idioms more broadly. The premise of this thesis is to bridge the gap by engaging the Kapustin piano sonatas with the New Formenlehre literature in analytical dialogue. This will extend current sonata theory into newer territories such as jazz with its idiosyncratic harmonies and key relationships. This thesis develops a new jazz sonata theory, a framework built out of jazz-inclusive modifications to Caplin’s theory of Formal Functions, “microform”, and Hepokoski and Darcy’s framework, “macroform”.</p
Elite professional golfers’ physical preparation practices and perceptions
No full textPhysical preparation for improving golf performance is a topic of rising interest. However, little is known of how advancements in empirical evidence have integrated with the practices and perceptions of elite professional golfers. To address this shortfall in knowledge, forty-nine (n = 32 European Tour, n = 17 Challenge Tour) professional golfers were surveyed on their physical preparation practices and perceptions. Additionally, golfers’ in-tournament training practices were observed at the 148th Open Championship gym facility. The majority of surveyed golfers had experience of following a “structured resistance training plan” (89.8%). However, players face challenges to incorporate physical preparation throughout a tournament year. In turn, the development of physical attributes including muscular strength, power and muscle mass known to underpin clubhead speed/driver distance, and the training methods typically required to stimulate such adaptations were often not prioritised during the in-season period. Limited engagement with heavy load and high-velocity resistance training methods were observed at the Open Championship. However, in order to maximise their potential, players can enhance key physical qualities on a year-round basis (i.e., during the in-season). Consequently, further education and research on how to effectively organise and optimise resistance training within tournament constraints would be of value.</p
Microstructural Brain Changes Associated with Frailty in Older Adults: Insights from Diffusion Tensor Imaging
No full textObjectivesThis study investigates the relationship between frailty status and white matter integrity (WMI) in older adults, focusing on associations with frailty status.DesignA cross-sectional study.Setting and Participants125 older adults aged ≥65 years without dementia were included.MethodsA comprehensive geriatric assessment was conducted. Frailty status was evaluated by Fried Frailty criteria: unintentional weight loss, exhaustion, low levels of activity, weakness, and slowness: 0 for nonfrail, 1 to 2 for prefrail, and 3 to 5 for frail. Brain magnetic resonance imaging with diffusion tensor imaging (DTI) was performed, and mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity values were calculated in white matter integrity using a region of interest–based method. Multinomial logistic regression analyzed the multivariate effects of clinical variables on the frailty-WMI association, whereas canonical correlation analysis examined multivariate relationships between diffusion tensor imaging measurements and geriatric assessment parameters.ResultsThe mean age was 81.76 ± 7.07 years, and 64% were female. Of the participants, 55.2% were frail, 33.6% prefrail, and 11.2% nonfrail. After adjusting for age and sex, WMI impairment varied in the cingulum, inferior longitudinal fasciculus, and forceps major in the left hemisphere among frailty statuses. Regression analysis showed demyelination of the left cingulum [odds ratio (OR) 0.97, 95% CI 0.95-0.99] and left forceps major (OR 0.99, 95% CI 0.98-0.99) was linked to increased frailty risk. For the frail group, DTI variables and malnutrition were significant. An increase in malnutrition status or risk raised the risk of frailty by 18.86 times. Canonical correlation analysis identified the Lawton-Brody IADL and Epworth Sleepiness Scale scores as the strongest predictors, whereas the cingulum showed the highest association among white matter tracts.Conclusions and ImplicationsFrailty and prefrailty were associated with deteriorated WMI, particularly in the left cingulum and left forceps major. The strong link between frailty and WMI may reflect shared underlying mechanisms, including sleep, functionality, and nutrition. Therefore, a multidimensional approach to frailty is important.</p
They survived – Now what? The case for integrated recovery pathways for cardiac arrest survivors
No full textDespite gains in survival after out-of-hospital cardiac arrest (OHCA), the transition from “surviving” to “thriving” remains precarious for survivors and their families. At the recent 10 Years Together Sudden Cardiac Arrest UK (SCA UK) conference, our health-care professional (HCP) track brought together clinicians, researchers, survivors and relatives. Their message was unequivocal: aftercare is everyone’s responsibility and yet, no single service takes ownership.</p
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