Mortality Outcomes in People with Lung Cancer with and without Type2 Diabetes: A Cohort Study in England.

IntroductionThe impact of type 2 diabetes (T2DM) on mortality following lung cancer diagnosis remains unclear, with conflicting evidence across studies. We aimed to assess differences in all-cause and cause-specific mortality between people with lung cancer with and without T2DM within a primary care population in England.MethodsThe study population was 69,674 people with incident lung cancer within the Clinical Practice Research Datalink (CPRD) Aurum primary care database (2010-2022). The study exposure was T2DM at cancer diagnosis, and the outcomes were all-cause and cause-specific mortality (cancer, cardio-vascular, respiratory). Cox models were fitted for each outcome adjusting for age, gender, smoking status, body mass index, calendar year and socioeconomic status (Index of Multiple Deprivation).ResultsAfter adjusting for age and gender, there was no evidence for a difference in all-cause mortality in people with T2DM compared with people without T2DM (IRR 0.98 95% CI 0.96, 1.01). After fully-adjusting for measured confounders, there was a small positive effect (IRR 1.07 95% CI 1.04, 1.09). After adjusting for age and gender, people with T2DM had lower rates of cancer-specific mortality compared to people without T2DM (IRR 0.96 95% CI 0.94, 0.98). However, after adjustment for all measured confounders there was a small positive association (IRR 1.05 95% CI 1.02, 1.07). In both age and gender adjusted and fully adjusted models people with T2DM had higher cardiovascular (fully adjusted HR 1.30 95% CI 1.15, 1.47) and respiratory disease mortality (fully adjusted HR 1.30 95% CI 1.15, 1.47).ConclusionThere was robust evidence that people with T2DM had higher cardiovascular and respiratory disease mortality following lung cancer diagnosis. The relationships between T2DM and all-cause and cancer-specific mortality were highly sensitive to adjustment for confounding. Differences in studies on approaches to confounding and levels of missing data may contribute to the mixed findings on this association in the literature

Trade unionism for England’s classroom teachers: the individual-collective division of responses to New Public Management’s decollectivisation of industrial relations

This dissertation explores teacher unions’ responses to decollectivisation and disaggregation generated through New Public Management in England’s schools. The research took place in a densely unionised public sector context with competitive multiunionism and fractured traditional collective bargaining. Decollectivisation and disaggregation are conceptualised as interwoven processes undermining trade unions’ capacity to develop or deploy countervailing collective power resources to neoliberal marketisation of education. Structural changes within the sector include academisation and the individualisation of rights at work. An overarching state project of reverse juridification multiplies individualised employment rights to deliver labour market flexibilities, and minimises, limits, or revokes collective employment rights to deliver labour market equity. Applying labour process theory in relation to the degradation via managerialism and performativity of teachers’ work, and actor-centred institutional theory to the broader political economy, the research applies lenses from the critical industrial relations perspective and radical legal research, adding the construct of trade union collective memory as a potential collective power resource. Through twenty-two semi-structured interviews with NASUWT and NEU respondents analysed thematically, their perceptions on how individual-collective division of issues occurs as they arise were interrogated. The study found the unions faced considerable decollectivising challenges. Foremost was misalignment of trade union and employer structures leading to a form of “workplace blindness” allied to a default individualisation of issue-handling. Contra that specific recollectivising tactics and evidence of novel legal mobilisation framed in terms of the right to justice for all teachers were found. The thesis contributes to knowledge of the challenges for and responses of workers and their unions in an under-researched sector at a time of conflict with the state and of change within the two unions involved

Investigating a structured diagnostic approach for chronic breathlessness in primary care: a mixed-methods feasibility cluster randomised controlled trial

Background: There is a need to reduce delays to diagnosis for chronic breathlessness to improve patient outcomes. Objective: To conduct a mixed-methods feasibility study of a larger cluster randomised controlled trial (cRCT) investigating a structured symptom-based diagnostic approach versus usual care for chronic breathlessness in primary care. Methods: 10 general practitioner practices were cluster randomised to a structured diagnostic approach for chronic breathlessness including early parallel investigations (intervention) or usual care. Adults over 40 years old at participating practices were eligible if presenting with chronic breathlessness without an existing explanatory diagnosis. The primary feasibility outcomes were participant recruitment and retention rate at 1 year. Secondary outcomes included number of investigations at 3 months, and investigations, diagnoses and patient-reported outcome measures (PROMs) at 1 year. Semistructured interviews were completed with patients and clinicians, and analysed using thematic analysis. Results: Recruitment rate was 32% (48/150): 65% female, mean (SD) age 66 (11) years, body mass index 31.2 kg/m2 (6.5), median (IQR) Medical Research Council dyspnoea 2 (2–3). Retention rate was 85% (41/48). At 3 months, the intervention group had a median (IQR) of 8 (7–9) investigations compared with 5 (3–6) investigations with usual care. 11/25 (44%) patients in the intervention group had coded diagnosis for breathlessness at 12 months compared with 6/23 (26%) with usual care. Potential improvements in symptom burden and quality of life were observed in the intervention group above usual care. Conclusions: A cRCT investigating a symptom-based diagnostic approach for chronic breathlessness is feasible in primary care showing potential for timely investigations and diagnoses, with PROMs potentially indicating patient-level benefit. A further refined fully powered cRCT with health economic analysis is needed

Physiotherapy for the Management of Polymyalgia Rheumatica: Results From a UK Cross‐Sectional Survey

Introduction: Polymyalgia rheumatica (PMR) international management guidelines advocate patient education and individualised exercises but lack evidence and physiotherapy practice for PMR is unknown. PMR is typically treated with glucocorticoids, but side effects are frequent and concerning to patients. This study investigated UK physiotherapy practice in PMR. Method: Physiotherapists recruited from UK rheumatology and physiotherapy professional networks and university alumni were invited to complete a postal or online questionnaire. Topics included experiences of managing PMR, perceived role and value of physiotherapy in PMR, assessment and management priorities and physiotherapists' education about PMR. Results were summarised using descriptive statistics. Results: 4288 invitations to participate were sent, and 1072 (25%) responses were received. Physiotherapy referrals for PMR were infrequent; 5.8% of respondents had treated ≥ 10 patients in the previous year. 80% of respondents advocated a physiotherapy role for PMR. 38% reported receiving some pre‐registration education about PMR within their qualifying physiotherapy programme. Establishing patients' knowledge and understanding of PMR, pain levels, and ability to undertake activities of daily living were physiotherapists' assessment priorities. 90% of respondents promoted self‐management approaches, including pacing and activity modification. Prioritising upper limbs, 89% prescribed individualised graded exercises to improve movement, muscle strength and activities of daily living function. Conclusion: A positive role for physiotherapy was reported for some people with PMR. Exercise, education and advice to improve daily functioning may be useful adjuncts to glucocorticoids. The limited PMR education for UK physiotherapists warrants attention. Further research is needed to evaluate the effectiveness of physiotherapy approaches for PMR

Metallosupramolecular polymer generated from a N,N,O-tridentate (1,2,3-triazol-4-yl)-picolinamide (tzpa) ligand possessing terminal pyridyl units

The synthesis and characterisation of a new (1,2,3-triazol-4-yl)-picolinamide (tzpa) ligand HL1 is described, achieved in three steps from commercially available starting materials. This ligand, possessing two terminal pyridyl units, was used in the generation of a copper-based coordination polymer formed in CH3OH using [Cu(CH3CN)4](CF3SO3). The polymer, poly-[Cu3(L1)2(CF3SO3)(OCH3)(H2O)](CF3SO3)2, is the first example of the use of an unsymmetric triply-bridging tzpa in coordination chemistry, giving a coordination polymer through in situ oxidation of Cu(I) to Cu(II) coupled with deprotonation of the tzpa ligand to the anionic L1−

Low-temperature growth of metal chalcogenide semiconductors

Metal chalcogenides exhibit a variety of intriguing properties and promising applications. However, a significant challenge in utilising these materials for electronic devices lies in producing high quality thin films. Chemical vapour deposition (CVD) is a scalable technique that can produce extraordinarily high-quality thin films which are nanometres in thickness, over large areas. High growth temperatures are often required in order to synthesise the best quality materials which hinder the use of CVD techniques for commercial thin film manufacture. This work centres on the development, optimisation and use of low-temperature CVD growth systems to grow metal chalcogenides films and two-dimensional materials utilising both aerosol-assisted chemical vapour deposition (AACVD) and salt-assisted chemical vapour deposition (SA-CVD), respectively. This enables film deposition to occur at lower temperatures when compared to existing reported traditional CVD methods, using single source dithiocarbamate precursors and halide salts. To synthesise metal sulfide, oxide and selenide semiconductors, that are suitable for a wide range of uses, such as optoelectronic, thermoelectric and catalytic applications. Thus, this could offer exciting opportunities for scalable renewable energy research by determining if low-temperature CVD methods can produce high quality films, that are comparable to their existing high temperature counterparts. In this project, materials morphology, crystal quality, lattice strain and structural composition were explored through various characterisation techniques, including Raman spectroscopy, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray (EDX) analysis. The research has proven that low-temperature chemical vapour deposition methods can be utilized to produce high quality molybdenum, zinc and tin chalcogenide semiconductors, which are suitable for optoelectronic and thermoelectric devices and also show great promise for catalysing hydrogen evolution reactions. This mean we are one step closer to a highly efficient, low-cost clean energy future

Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders

Fear, whether innate or learned, is an essential emotion required for survival. The learning, and subsequent memory, of fearful events enhances our ability to recognise and respond to threats, aiding adaptation to new, ever-changing environments. Considerable research has leveraged associative learning protocols such as contextual or auditory forms of fear conditioning in rodents, to understand fear learning, memory consolidation and extinction phases of memory. Such assays have led to detailed characterisation of the underlying neurocircuitry and neurobiology supporting fear learning processes. Given fear processing is conserved across rodents and humans, fear conditioning experiments provide translational insights into fundamental memory processes and fear-related pathologies. This review examines associative learning protocols used to measure fear learning, memory and extinction, before providing an overview on the underlying complex neurocircuitry including the amygdala, hippocampus and medial prefrontal cortex. This is followed by an in-depth commentary on the neurobiology, particularly synaptic plasticity mechanisms, which regulate fear learning, memory and extinction. Next, we consider how fear conditioning assays in rodents can inform our understanding of disrupted fear memory in human disorders such as post-traumatic stress disorder (PTSD), anxiety and psychiatric disorders including schizophrenia. Lastly, we critically evaluate fear conditioning protocols, highlighting some of the experimental and theoretical limitations and the considerations required when conducting such assays, alongside recent methodological advancements in the field. Overall, rodent-based fear conditioning assays remain central to making progress in uncovering fundamental memory phenomena and understanding the aetiological mechanisms that underpin fear associated disorders, alongside the development of effective therapeutic strategies

Aberrant expression of nuclear prothymosin α contributes to epithelial‐mesenchymal transition in lung cancer

Elevated expression of prothymosin α (ProT) is frequently observed in cancers, but the underlying molecular mechanism remains poorly understood. Here, we report the clinical relevance of ProT expression and its correlation with lung cancer progression. We have shown that ProT was highly expressed in early‐stage lung cancer, exhibiting nuclear localization; on the contrary, a loss of nuclear ProT expression was detected in late‐stage tumor specimens. Furthermore, the expression of nuclear ProT impaired lung cancer cell migration, suppressed TGF‐β‐induced epithelial‐to‐mesenchymal transition (EMT)‐associated transcription factor expression, and inhibited in vivo tumor metastasis. The suppressive effect of ProT was further found to trigger Smad7 acetylation‐dependent deregulation of TGF‐β signaling. ProT enhanced Smad7 stability by promoting its lysine acetylation, thereby competing with the binding of Smad2 to the SNAI1, TWIST1, and ZEB1 promoters. Eventually, the binding of Smad7 in the presence of ProT resulted in reduced expression of the EMT transcription factors, leading to the inhibition of TGF‐β‐induced EMT and tumor metastasis. Collectively, this study unravels the role of ProT in lung cancer progression and highlights the potential of nuclear ProT as an indicator for monitoring tumor development

Benchmark stars for mean stellar density and surface gravity estimates of solar-type stars

Adding an independent estimate of the mean stellar density, , as a constraint in the analysis of stars that host transiting exoplanets can significantly improve the precision of the planet radius estimate in cases where the light curve is too noisy to yield an accurate value of the transit impact parameter, e.g. the light curves of Earth-size planets orbiting in the habitable zone of Sun-like stars that will be obtained by the PLAnetary Transits and Oscillations of stars (PLATO) mission. I have compiled a sample of 36 solar-type stars for which analysis of high-quality light curves together with constraints on the orbital eccentricity yield mean stellar density measurements with a median error of 2.3 per cent. Of these, 8 are in transiting exoplanet systems and 28 in eclipsing binary systems with very low mass companions that contribute <0.1 per cent of the total flux in the V band. A recalibrated empirical relation for stellar mass as a function of T, , and [Fe/H] has been used to find mass estimates with a typical precision of 5.2 per cent for the stars in this sample. Examples are given of how this sample can be used to test the accuracy and precision of and estimates from catalogues of stellar parameters for solar-type stars