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Ibrutinib enhances the bias of T cell responses towards staphylococcal superantigens sustaining inflammation in chronic lymphocytic leukaemia
Get PDFChronic lymphocytic leukaemia (CLL) is an uncurable haematological malignancy and is associated with significant infection morbidity. Bruton’s tyrosine-kinase inhibitors (e.g., ibrutinib) have improved disease outcomes, but severe infections and poor immunization responses afflict patients. Recently, carriage of the endemic Staphylococcus aureus (SA) was associated with lymphocytosis and decreased survival in CLL patients. We then hypothesized that exposure to staphylococcal superantigens (SAgs), known to promote hyper-inflammatory responses, impairs immunity and increases severe infection risk in CLL patients. Herein, we evaluate the reactivity of T cells and CLL cells to SA SAgs, in cultures derived from ibrutinib-treated and untreated CLL patients. We found that ibrutinib-treated patients had less naive CD8+ T cells (p=0.0348), more checkpoint receptor (TIM-3) expression in memory T cells (p<0.0001), and lower IFNγ/cytokine responses in patient T cells (p≤0.0298). Exposure to SA SAg further increased the accumulation of memory T cells with an exhaustion-phenotype, preferentially in cultures derived from ibrutinib-treated patients (p≤0.0350). Nevertheless, staphylococcal SAgs could not induce regulatory T cells from CLL patients inasmuch as healthy donors (p≤0.0461) and this was associated with accumulation of inflammatory T cells. Significantly, SAg-exposure enhanced inflammatory activation of CLL tumour cells, which acquired CD38, CD40, CD86, while downregulating CD27 (p≤0.005), even in cultures from ibrutinib-treated CLL patients. Thus, we suggest that environmental SAg-exposure promotes the accumulation of pseudo-exhausted T cells, which induce/sustain tumour cell activation, not counteracted by ibrutinib. Our study critically helps understand the chronic inflammatory milieu in CLL patients, with implications for infection morbidity, disease aetiology and future interventions
What are student nurse’s experiences and perceptions of social media activity within their peer groups and its effect on their wellbeing?
Get PDFThis study explores student nurse’s experiences and perceptions of social media activity within their peer groups and its effect on their wellbeing, focusing on Social Networking Sites (SNS). Student nurses are known to experience higher levels of stress than many other undergraduate students because in addition to the usual stressors around university and studying student nurses also must deal with the extra stressors associated with working within healthcare during clinical placements. Also, previous research has shown SNS activity is known to affect student nurse wellbeing, so it was important to establish the role SNS activity within student nurse peer groups played in relieving or exacerbating wellbeing for this student group.The study took a two-staged approach to data collection; the first stage was a scoping exercise with one hundred and twenty-two participants over four sessions, which used Nominal Group Techniques (NGT) to collect as many viewpoints as possible to prompt the story telling in stage two of the data collection. Stage two of the data collection consisted of narrative interviews with a sample of fourteen student nurses and utilised virtual techniques to conduct the interviews due to COVID 19 restrictions. Thematic analysis of the interview transcripts uncovered four main themes: information sharing; amplifiers; personas and group formation.The research found that there are positive effects of SNS activity within student nurse peer groups, including information sharing and support. However, the research also highlighted several areas where SNS activity in student nurse peer groups negatively affected student nurse wellbeing, particularly areas such as the sharing of inaccurate information, negative social comparison, imposter syndrome, social media fatigue, fear of missing out, adoption of maladaptive coping strategies and feeling left out of SNS groups. These findings are helpful in both establishing the role SNS activity plays in affecting student nurse’s ability to cope effectively with the demands of the programme and in offering some practical solutions to guide universities in how best to support student nurses in this area. This university support should include building meaningful education around effective use of SNS into the curriculum, working with student nurses employing techniques to build a sense of community and belonging and ensuring effective support mechanisms such as restorative supervision are in place to build resilience in this student group
How People with COPD Perceive and Communicate Exacerbations: A Multicountry Survey Study
Get PDFBackground and Objective: Exacerbations negatively impact quality of life of people living with chronic obstructive pulmonary disease (COPD) and can accelerate disease progression. Studies suggest that patients find it difficult to recognize exacerbations and, therefore, under-report exacerbations. We aimed to understand how people living with COPD perceive and communicate their experiences of exacerbations. Methods: A cross-sectional survey including one open-ended question was developed using a targeted literature review, with input from patients and clinicians. People diagnosed with COPD were recruited from online consumer research panels in Brazil, China, France, Spain, UK, and USA and completed the survey. Responses were described overall and in specific subgroups; thematic analysis was used for the open-ended question. Results: Of 857 respondents (median age 58 years; 50.5% male), 623 (72.7%) reported daily shortness of breath; 417 (48.7%) that daily symptoms changed “a little”. In the open-ended question, exacerbations were described through a narrative lens detailing subjective experiences of symptoms, their management, potential causes, and emotions felt during exacerbations, with no single preferred term. In the 671 (78.3%) respondents who reported ever having an exacerbation, these were identified as symptoms being “worse than usual” (52.8%) or because respondents had “more trouble than usual with daily activities” (50.1%). Conclusion: While people living with COPD report confidence in their ability to identify exacerbations, there is a disconnect between their experience of exacerbations and the language and definitions used in clinical practice. A discussion guide emphasizing the use of plain language could improve communication between healthcare providers and patients
Innovative use of cetyltrimethyl ammonium bromide (CTAB) encapsulated mesoporous silicon oxide (SiO2) nanoparticles as corrosion inhibitor in coolant for corrosion protection of aluminium alloy
Get PDFThe present study has explored to implement mesoporous silicon oxide (SiO2) nanoparticles encapsulated with Cetyltrimethyl Ammonium Bromide (CTAB) into the simulated coolant to inhibit corrosion to aluminium alloy. The synthesis of MSN-CTAB was achieved by a one-step process, where CTAB acted as micelles. The synthesis was carried out in a counter swirling impinging jet flow reactor, which enables precise control over reaction conditions. Notably, the local turbulence generated within this reactor has been considered to have a significant impact on forming highly uniform and better morphological nanoparticles. The structural evolutions and morphological characteristics of MSN-CTAB have been performed using various approaches such as FTIR, SEM and TGA analysis, by which the loading percentage of CTAB in the mesoporous silica was found to be ∼36 %. The inhibition performance was evaluated by weight loss test, electrochemical test and numerical simulation. All of the results confirmed the synergistic inhibition effect of MSN and CTAB against the corrosion of 5052 Aluminium substrate in acid solution. Besides, the potentiodynamic polarisation results revealed MSN-CTAB to be a mixed-type inhibitor, and the EIS results suggested the formation of a protective film. Comparisons between the blank and MSN-CTAB samples showed that the inhibition efficiency peaked at 0.2 wt% MSN-CTAB, particularly at high temperatures. The test solution comprised a mixture of ethylene glycol and water acted as a simulated automotive coolant. Therefore, the findings of this research can contribute to corrosion prevention in automotive coolant systems
The Potential Role of Periodised Resistance Training During Cancer Treatment
Get PDFCancer and its treatments are associated with numerous debilitating side effects, including increased fatigue and reductions in lean mass, muscular strength, physical function, and overall quality of life (QoL). Resistance training has been shown to be a safe and effective strategy for mitigating such side effects in patients undergoing cancer treatment. However, current resistance training guidelines in oncology settings are generic and do not account for the diverse nature of cancer and its treatments, thereby limiting its therapeutic potential. This highlights the need for more precise planning and manipulation of training variables, such as frequency, intensity, and volume (i.e. periodisation). Periodised resistance training has the potential to target numerous physical parameters while managing treatment-related side effects, thus reducing the risk of excessive fatigue, injury and illness. Overall, the aim of this thesis was to provide a rationale for the future investigation and implementation of home-based, virtually supervised, periodised resistance training in patients undergoing cancer treatment. Due to numerous setbacks and the COVID-19 pandemic, this rationale was presented through elderly and obese populations who share similar risk factors and characteristics including reduced physical function, elevated levels of fatigue and reduced QoL.Chapter 3 systematically reviewed and meta-analysed the efficacy of resistance training on quality of life, fatigue, physical function, muscular strength and power in cancer patients undergoing chemotherapy. Seven randomised control trials (RCTs) including 561 participants demonstrated that resistance training statistically significantly improved lower-body strength (Standardised mean difference (SMD) = 0.33) compared to controls, but had no effect on QoL, fatigue, physical function, or upper-body strength. None of the studies included in this review assessed muscular power as an outcome highlighting limited research in this area.Chapter 4 assessed the validity of a mobile application (App) (Sit-to-Stand) and Inertial measurement unit (IMU) (PUSHTM) to measure sit-to-stand (STS) velocity and power in older adults. This study demonstrated that the STS mobile App was a valid tool for measuring STS velocity (r = 0.89; ES = -0.19) and power (r = 0.74; ES = -0.11) in older adults. These findings suggest that a mobile App can be used to assess muscular power and function, especially in settings where time, money, and space are limited.Chapter 5 evaluated the effects of an 8-week home-based, virtually supervised, weekly undulating periodised (WUP) resistance training programme on anthropometry, functional performance, and health-related quality of life (HRQoL) in obese adults. Pre to post within group changes demonstrated statistically significant improvements in waist circumference (gz = -2.09) and hip circumference (gz = -1.39). Functional performance significantly improved with reductions in 40 m fast pace walk (40m FPWT) test (gz = -2.41) and timed up and go (TUG) (gz = -2.20) and increases in seated basketball throw (SBT) (gz = 1.22) and six-minute walk test (6MWT) (gz = 2.12). Health related quality of life (HRQoL), assessed via 36 item short form (SF-36) demonstrated statistically significant improvements in physical functioning (gz = 2.15), role limit emotional (gz = 1.05), social functioning (gz = 2.14), pain (gz = 2.13), energy/fatigue (gz = 1.25), general health (gz = 2.77), and health change (gz = 2.35). The Weight Related Symptom Measure (WRSM) showed a significant decrease (gz = -1.45), as did the Multidimentail Assessment of Fatigue (MAF) (gz = -1.89). These findings demonstrate that an 8-week, home-based, virtually supervised WUP resistance training programme improves anthropometry, physical function, fatigue and HRQoL in obese adults.Chapter 6 presents a study protocol to assess the feasibility and acceptability of a home-based, virtually delivered, WUP resistance training intervention during colorectal cancer (CRC) treatment. This mixed-methods study aims to address uncertainties relating to the feasibility and acceptability of delivering home-based, virtually supervised exercise sessions to patients with CRC. The findings of this study will inform whether the intervention is safe to perform and if any modifications are necessary to improve the delivery of the intervention and patient engagement. The assessment of outcome measures will provide information on the likely size and variability of intervention effects, as well as the feasibility of data collection and the appropriateness of the selected assessments. Collectively, the data generated will inform the design of a subsequent, adequately powered, randomised controlled trial to evaluate the efficacy of home-based, virtually delivered, WUP resistance training intervention in patients with CRC undergoing treatment.Overall, this thesis aimed to provide a rationale for the future investigation into the feasibility and acceptability of a home-based, virtually delivered, periodised resistance training programme in patients with cancer undergoing treatment. Evidence from obese populations demonstrates that such an intervention has the potential to improve anthropometry, functional performance, fatigue and HRQoL. Given that obese populations share similar risk factors and characteristics including reduced physical function, elevated levels fatigue and reduced HRQoL, the delivery of such an intervention could prove beneficial for patients with cancer undergoing treatment
Performance Evaluation of an Energy-Efficient Oscillating Air-Conditioning Dehumidification System through Experimental Testing and Numerical Modelling
Get PDFThis study examines the performance of a new oscillating air-conditioning dehumidification system, designed to overcome the limitations of traditional methods, such as energy-intensive defrost cycles and inconsistent dehumidification in high-humidity conditions. Experimental tests demonstrate that the system achieves a dew point as low as −9.38°C with specific humidity reaching to 1.67 g/kg and coefficient of performance (COP) ranging from 3.3 to 4.7. Apart from testing, numerical modelling of the system has been built in TRNSYS and validated using experimental data. A validated TRNSYS model was used to extend the analysis across various climate zones, revealing that the system performs optimally in high-humidity regions like Hong Kong and Chongqing, with an annual average COP of 3.89 in Hong Kong. In contrast, colder and drier regions like Urumqi maintained lower but stable energy efficiency, with an annual average COP of 2.30. These findings suggest that the oscillating air-conditioning dehumidification system offers versatile, climate-adaptable operation with potential applications in diverse building types.Practical ApplicationThis study’s findings offer built environment professionals an air-conditioning dehumidification solution suited to diverse climate conditions. The oscillating air-conditioning system, with its continuous dehumidification capability and optimised energy efficiency with COP of 3.89 in high-humidity regions, provides an approach for deep dehumidification in demanding environments. By reducing reliance on energy-intensive defrost cycles, this system is ideal for applications in commercial and industrial settings, such as healthcare facilities and battery manufacturing centres, where precise humidity control is critical
Embracing compassion and self-care: educator wellbeing amidst the chaos
Get PDFThis chapter is a call for self-understanding and hope, beginning with the individual. It explores how Higher Education professionals can apply self-compassion—through self-kindness, recognition of shared humanity, and mindfulness—to support their own wellbeing amid the growing pressures of teaching, administration, and research. As lecturers, tutors, and teachers face increasing burnout, overwork, and underpayment, self-compassion offers a practical framework for academic self-care, helping educators to hold themselves with gentleness rather than harsh self-judgment. The chapter also argues that the principles of self-compassion must extend to colleagues, fostering a more supportive and humane academic culture
URED Observer-Based Feedback Linearized Neuro Adaptive SMC for a Twin Rotor MIMO System: Design and Experimental Study
Get PDFUnmanned Aerial Vehicles (UAVs) are highly nonlinear and sophisticated systems that demand precise trajectory tracking in environments with uncertainties and disturbances. This research presents advanced nonlinear, adaptive, and artificial intelligence-based control strategies for UAVs. Beyond simulation, the strategies are experimentally evaluated on a coupled Two Degree of Freedom (2-DOF) Twin-rotor MIMO System (TRMS). The proposed strategies include Sliding Mode Control (SMC), Super Twisting (ST), BackStepping (BS), and Neuro-Adaptive SMC (NNSMC), all designed using a feedback linearized mathematical model of the system. System performance is enhanced by decoupling the TRMS into horizontal and vertical subsystems through Lie derivatives and diffeomorphism principles. A Uniform Robust Exact Differentiator (URED) estimates rotor speeds and recovers missing derivatives, while a nonlinear state feedback observer improves system observability and mitigates uncertainties and external wind gusts. Furthermore, ST and NNSMC-based laws reduce high-frequency oscillations in the control input of the first-order SMC law, resulting in improved transient response. The experimental results reveal that NNSMC significantly outperforms ST and BS in terms of trajectory tracking accuracy, transient performance, and integral performance indices for both pitch and yaw angles. These findings underscore the superior convergence performance and robustness of NNSMC, establishing it as a promising solution for precise TRMS control in real real-world environment
The CSI effect in academia: influencing forensic science enrolment and perception in higher education
Get PDFackgroundTelevision portrayals of forensic science, often referred to as the CSI effect, have been widely discussed in relation to their influence on public perceptions and jury expectations. Less explored, however, is how these portrayals shape prospective students’ motivations for enrolling in forensic science degrees and their perceptions of the subject’s academic content. This study investigates the extent to which popular forensic television programmes influence undergraduate student expectations of forensic science education and explores the discrepancies between those expectations and the realities of the curriculum. The research aims to inform curriculum design, expectation management, and student engagement strategies in higher education forensic programmes.ResultsData were collected via a mixed-methods questionnaire from undergraduate students (n = 123) enrolled in BSc Forensic Science and BA Criminology with Forensic Science programmes at a UK university. Descriptive statistics and thematic analysis were used to analyse closed- and open-ended responses. Findings indicate that a significant proportion (71.5%) of students reported popular forensic television as a factor influencing their decision to study the subject. However, many expressed surprise at the scientific depth of the curriculum, particularly regarding modules in chemistry, biology, and analytical science. Key thematic mismatches included unrealistic portrayals of evidence handling, timeframes, and investigative methods. A breakdown of findings by year of study showed that more senior students identified a greater number of technical inaccuracies in media portrayals. Although 87.8% recognised inaccuracies in television portrayals, the media remained a key influence on their understanding of the field.ConclusionsThe study reinforces previous research suggesting that media portrayals significantly shape student expectations of forensic science. These findings highlight a significant disconnect between media-shaped expectations and academic realities These expectation mismatches may impact student satisfaction, retention, and preparedness for careers in the field. Integrating media literacy into early curricula, alongside transparent course marketing and orientation strategies, may help align expectations with academic content and improve student engagement. The study adds to ongoing discussions about the CSI effect’s influence on forensic education and student engagement