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Editorial: Special issue on the 10th heat powered cycles conference 2023
No full textThis editorial article accompanies a Special Issue of Applied Thermal Engineering dedicated to the 10th Heat Powered Cycles (HPC) Conference. The conference was hosted by the University of Edinburgh, in Scotland (UK), between the 3rd and 6th of September 2023. The Special Issue includes 8 articles, covering a diverse range of topics from thermal energy storage, to adsorption and thermodynamic cycles for power generation, heating and/or cooling provision, as well as hybrid systems for multigeneration
Low risk of thyroid eye disease (TED) following radioiodine (RAI) therapy in a multidisciplinary setting: a retrospective cohort study
No full textBackground
Radioiodine (RAI) is recommended by the National Institute of Clinical Excellence (NICE) as a first-line definitive treatment of Grave’s hyperthyroidism (GH). RAI is cited as a major risk factor in the development and exacerbation of thyroid eye disease (TED). We aim to identify the current risk of TED in a population treated post 2015.
Methods
This is a retrospective cohort study including all adult patients diagnosed with GH undergoing RAI over a seven-year period. Data collected included age; gender; thyroid diagnosis and pre- and post-treatment thyroid status; length of GH; TSHR-Ab titres; smoking status; RAI dose and number of treatments; ophthalmology assessment and use of steroid prophylaxis. Investigation results, clinical scoring and management details were collected from patients who developed TED following RAI.
Results
Four of 231 patients (1.7%) treated with RAI over 8 years had new onset (two patients) or progression (two patients) of TED following their RAI. One required immunosuppression and one rehabilitative TED surgery. No patient developed sight-threatening TED.
Conclusions
In our study, judicious screening for high-risk patients and the use of prophylactic steroids results in lower rates of RAI associated TED relative to those reported previously in the literature
The needs and unmet needs for people living with dementia, caregivers and care workers in dementia health care systems: a systematic review
No full textIntroduction: The prevalence and costs of dementias are rising due to demographic changes. Dementia care depends largely on informal caregivers and fragmented healthcare systems that often fail to meet the needs of people with dementia.
Objectives: This systematic review aims to identify unmet needs and barriers in European dementia care, providing a framework to improve health strategies.
Methods: Following PRISMA guidelines, articles from 2013 to 2023 were screened from Embase, PsycINFO, HTA Database, and Web of Science. The Mixed Methods Appraisal Tool was used for evaluation.
Results: From 3,738 articles, 47 met the inclusion criteria. Through a narrative synthesis, the review identified unmet needs and barriers among People Living with Dementia, caregivers, and healthcare workers. Psychosocial and emotional support are essential for managing stress and ensuring quality of life. Caregivers demand education about dementia care, progression, and self-care, while healthcare workers need training, and interdisciplinary teams. Cultural sensitivity is critical for addressing stigma and facilitating inclusive care for ethnic minorities. Healthcare access remains fragmented, thereby decreasing continuity of care for families. High costs, bureaucratic complexity, and geographical inequalities, particularly in rural areas can be barrier to care for People Living with Dementia and their families. The COVID-19 pandemic disrupted social support services, increasing distress and uncertainty. About limitation, publication bias and geographical bias from focus on Europe were possible, potentially overlooking insights from other regions.
Conclusion: There is need for public policies to enhance education, community support, and dementia awareness, with a focus on culturally sensitive care
Casualty behaviour and mass decontamination: a narrative literature review
No full textChemical, biological, radiological, and nuclear (CBRN) incidents pose significant challenges requiring swift, coordinated responses to safeguard public health. This is especially the case in densely populated urban areas, where the public is not only at risk but can also be of assistance. Public cooperation is critical to the success of mass decontamination efforts, yet prior research has primarily focused on technical and procedural aspects, neglecting the psychological and social factors driving casualty behaviour. This paper addresses this gap through a narrative literature review, chosen for its flexibility in synthesising fragmented and interdisciplinary research across psychology, sociology, and emergency management. The review identified two primary pathways influencing casualty decision making: rational and affective. Rational pathways rely on deliberate decisions supported by clear communication and trust in responders’ competence, while affective pathways are shaped by emotional responses like fear and anxiety, exacerbated by uncertainty. Trust emerged as a critical factor, with effective —i.e., transparent, empathetic, and culturally sensitive— communication being proven to enhance public cooperation. Cultural and societal norms further shape individual and group responses during emergencies. This paper demonstrates the value of narrative reviews in addressing a complex, multifaceted topic such as casualty behaviour, enabling the integration of diverse insights. By emphasising behavioural, psychological, and social dimensions, the results of this paper offer actionable strategies for emergency responders to enhance public cooperation and improve outcomes during CBRN incidents
Biomarker evidence of neurodegeneration in mid-life former rugby players
No full textRepetitive head impacts and traumatic brain injuries in contact sports, such as rugby union, are associated with increased risk of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. Advances in fluid and imaging biomarkers are transforming dementia diagnosis but have not been systematically applied to individuals previously exposed to head impacts during rugby participation.
We used biomarkers, including those with sensitivity and specificity for early Alzheimer's pathology to explore neurodegenerative risk in mid-life elite retired rugby players with significant repetitive head impact exposure. Plasma neurofilament light, glial fibrillary acid protein, amyloid-β (Aβ)42, Aβ40 and phospho-tau217 were quantified using ultrasensitive single molecule array digital enzyme-linked immunosorbent assay (SiMoA) in former elite rugby players as well as age/sex-matched unexposed controls. 3 T MRI and neuropsychology assessments were performed, with National Institute for Neurological Disorders and Stroke criteria used to ascertain the presence of traumatic encephalopathy syndrome. Regression models were used to relate plasma/imaging biomarkers to clinical phenotype. Individual-levels analyses were performed for fluid and imaging metrics, based on control biomarker distributions. Biomarker data from two aligned un-exposed Alzheimer's cohorts were included to contextualize our findings.
Two hundred ex-rugby players (median age 44 years, 90% males) and 33 unexposed controls were assessed. Twenty-four (12%) ex-players fulfilled criteria for traumatic encephalopathy syndrome but none had dementia. Plasma phospho-tau217 concentrations were 17.6% higher in ex-rugby players than controls (95% confidence interval 3.7–33.3, P = 0.047). A total of 46 (23.1%) ex-players had elevated phospho-tau217 at the individual level; as did 18 (9.0%) players in relation to raised plasma neurofilament light. Ex-players’ concentrations were lower than in unexposed adults with late onset Alzheimer's disease (n = 69). Ex-players also showed significantly reduced volumes in the frontal/cingulate cortex on voxel-based morphometry at the group level; with reduced white matter and lower hippocampal volume associated with longer career durations within ex-players. Trauma-associated white matter changes measured with diffusion tensor imaging were uncommon in ex-players (4.6%). Traumatic encephalopathy syndrome was significantly more common in ex-players with elevated phospho-tau217, while those with raised plasma neurofilament light had significantly more anxiety and depressive symptoms. Frontal brain volumes correlated negatively with neurofilament light (r = −0.21, P = 0.010), and hippocampal volumes correlated negatively with phospho-tau217 (r = −0.19, P = 0.024).
Elite rugby participation is associated with abnormal fluid and neuroimaging neurodegeneration biomarkers in mid-life. These include elevated phospho-tau217, which may indicate amyloid-dependent tau pathology. The results provide support for using state-of-the-art neurodegenerative biomarkers in the evaluation of long-term effects of sports head impact exposure
Prevalence and risk factors of cerebral microhemorrhages andsuperficial siderosis in cognitively unimpaired older adults:analysis from the CHARIOT-PRO SubStudy
No full textINTRODUCTION
Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.
METHODS
This cross-sectional study included 1414 cognitively unimpaired, treatment-naïve individuals aged 60 to 85 years from the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. Relationships between CMHs/SS and cardiovascular risk factors, amyloid beta (Aβ) load, apolipoprotein E (APOE) ε4 status, educational attainment, and white matter hyperintensities were investigated using regression analyses and structural equation modeling.
RESULTS
CMHs were observed in 8.3% of participants and SS in 1.3%. Significant risk factors for CMHs included age and hypertension. Higher education attainment appeared to have a protective effect. Elevated amyloid is a risk factor, particularly when adjusting for APOE ε4 status in individuals aged 70 or younger.
DISCUSSION
Increasing age and hypertension are significant risk factors of CMHs. Higher educational attainment may offer a protective effect.
Highlights
Of the 1414 participants from the CHARIOT-PRO SubStudy (CPSS), CMHs were present in 118 (8.3%), and SS was present in 18 (1.3%).
Age and hypertension were identified as significant risk factors for CMHs, and the latter had a stronger association with the presence of CMHs among female participants. Having a bachelor's degree or higher was found to be protective.
Elevated brain amyloid burden, particularly when adjusted for APOE ε4 carrier status, was identified as a risk factor in individuals aged 70 years and below
Polymyxin B lethality requires energy-dependent outer membrane disruption
No full textPolymyxin antibiotics target lipopolysaccharide (LPS) in both membranes of the bacterial cell envelope, leading to bacterial killing through a mechanism that remains poorly understood. Here, we demonstrate that metabolic activity is essential for polymyxin lethality and leverage this insight to determine its mode of action. Polymyxin B (PmB) efficiently killed exponential phase E. coli but was unable to eliminate stationary phase cells unless a carbon source was available. Antibiotic lethality correlated with surface protrusions, LPS loss from the outer membrane (OM), and a corresponding reduction in barrier function, processes that required LPS synthesis and transport, but were blocked by the MCR-1 polymyxin resistance determinant. While the energy-dependent OM disruption was not directly lethal, it facilitated PmB access to the inner membrane (IM), which the antibiotic permeabilised in an energy-independent manner, leading to cell death. This work reveals how metabolic inactivity confers tolerance of a clinically important, membrane-targeting antibiotic, leading to new insight into mechanism of action
Associations of leucocyte subtypes and platelet parameters with kidney cancer risk in the UK Biobank cohort
No full textBackground
Kidney cancer is related to obesity and inflammation and platelets are involved in thrombo-inflammation, but the prospective associations of individual leucocyte subtypes and platelet parameters with kidney cancer risk are unclear.
Methods
Using data from the UK Biobank cohort and multivariable Cox proportional hazards models, we obtained hazard ratios (HR per one standard deviation increase) with 95% confidence intervals (95%CI) for the mutually adjusted associations of inflammatory markers and platelet parameters (log-transformed), and allometric obesity indices (body mass index (BMI), a body shape index (ABSI), hip index) with kidney cancer risk (overall, by sex, and by follow-up time with a cut-off at 6 years).
Results
During a mean follow-up of 10.4 years, 1086 kidney cancers were ascertained in 396,482 participants. Conditional on each other and covariates, neutrophil count (HR = 1.12; 95%CI = 1.04 − 1.20), C-reactive protein (HR = 1.11; 95%CI = 1.04 − 1.19), platelet count (HR = 1.18; 95%CI = 1.10 − 1.27), platelet distribution width (HR = 1.16; 95%CI = 1.09 − 1.24), and BMI (HR = 1.22; 95%CI = 1.14 − 1.30) were positively associated, while lymphocyte count (HR = 0.90; 95%CI = 0.84 − 0.96) and hip index (HR = 0.88; 95%CI = 0.83 − 0.93) were inversely associated with kidney cancer risk in participants overall, but there was little evidence for an association with ABSI (HR = 1.05; 95%CI = 0.99 − 1.12). There were no major sex differences, but the positive association with C-reactive protein was observed only for shorter follow-up time (HR = 1.26; 95%CI = 1.14 − 1.38; p-follow-up = 0.0006).
Conclusions
Our findings support two separate longer-acting pathways in kidney cancer development– a pathway related to general rather than abdominal obesity and an immune-cell-related pathway involving neutrophils assisted by activated platelets, as well as a cancer-induced thrombo-inflammation closer to kidney cancer diagnosis
Thinking differently about thinking theoretically: developing a design-centered approach to organizational theorizing
No full textWe propose a novel, multi-faceted approach to organization theory building that is more likely to engender theories that are relevant to the work that managers and organizations do – one predicated on principles associated with design. Invoking and synthesizing a set of core design principles and applying them to the process of theory building generates an approach that not only provides organizational scholars a way of thinking differently about thinking theoretically, but also helps answer the call for increasing the relevance of our theories as a way of making contributions that are more practical, more prescient and greater in scope. The resulting model of “design theorizing”
has several significant implications for addressing how organizational scholars approach current and future issues likely to affect the theory and practice of managing
Time capsule medicine: a mixed-methods pilot study on immersive simulation for chronic disease education in medical students
No full textBackground: Chronic diseases require long-term and multidimensional care, but traditional medical education has emphasised acute care and episodic interventions. This gap limits the understanding of future clinicians about the complexity of managing chronic conditions over decades. This mix-methods quantitative-qualitative pilot study describes "Time Capsule Medicine", an innovative educational framework in which medical students acted out the progressive challenges that patients with chronic illnesses might face over a continuous period of 20 years. This paper aims to report the outcomes of this innovative educational technique. Methods: Thirty final-year medical students were engaged in the three-phase programme which included preparation, immersive simulation, and reflection and evaluation. The preparation consisted of online workshops in chronic disease progression, age-related changes, and continuity of care, while the immersive simulation featured appropriate role-play exercises in small groups that simulated the chronic disease process across four five-year increments. The reflection and evaluation consisted of debriefing sessions and reflective journals, while pre- and post-simulation questionnaires tested learning outcomes. The physical constraints included weighted garments with visual impairments simulating the age-related limitations. Results: A gender- and ethnically diverse cohort of thirty final-year medical students from three medical schools in North London participated in the programme. The simulation significantly enhanced students' confidence in managing long-term disease trajectories (pre-simulation score: 2.8 ± 0.9; post-simulation score: 4.3 ± 0.6; p < 0.01) and understanding of age-related challenges (from 3.1 ± 1.0 to 4.5 ± 0.5; p < 0.01). Empathy scores increased from 3.0 ± 0.9 to 4.7 ± 0.5 p < 0.01. The qualitative analysis showed an increased appreciation of the continuity of care, recognition of systemic barriers, and insights into the emotional burdens of chronic conditions. For many students, the simulation was transformative, changing the way they approached holistic, patient-centred care. Conclusions: This experiential learning approach has succeeded in effectively addressing one of the most important gaps known in traditional medical education in developing empathy, understanding, and confidence in the long-term management of chronic diseases. The integration of similar simulations into medical curricula may adequately arm future clinicians with the complexities of continuity of care and patient management. Further studies need to be performed exploring scalability and its impact on long-term clinical practice