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The UK northern talking therapies practice research network: lessons from 10 years of generating practice-based evidence
Get PDFPractice research networks (PRNs) have been proposed as a mechanism to support continuous service evaluation and improvement in the field of psychological therapies. In theory, PRNs could help to generate high quality practice-based evidence that has potential to inform and improve clinical care. However, in practice, many obstacles pose challenges to the sustainability and impact of such networks. The UK Northern Talking Therapies PRN is an exemplar that has generated over 20 scientific publications over a decade of successful clinical-academic collaborations. This article distils key lessons learned over that time, to guide and promote the wider adoption of PRNs in psychological services
L-Quebrachitol attenuates RANKL-Induced osteoclastogenesis and bone resorption in ovariectomized rat model
Get PDFInositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Existing research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells, and bone resorption in an ovariectomized rat model. The results revealed that L-quebrachitol suppressed RANK-mediated signaling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both the gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. In addition, proteasome subunit alpha type-5 (PSMA5), which is involved in the degradation of the NF-κB inhibitor, was also suppressed. In particular, the animal study clearly supported the bone homeostasis property of the agent by increasing the BV/TV (bone volume/total volume) and Tb.Th (trabecular thickness) in ovariectomized rats. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of RANK-mediated signaling pathways and prevention of bone loss in an animal model. However, further exploration of the potential of L-quebrachitol as an effective approach for osteoporosis is required
Least-regret hydrogen infrastructure design under demand uncertainty
Get PDFThis study presents a routing-and-sizing framework for hydrogen pipeline networks that minimises max regret across uncertain demand. An obstacle-aware genetic algorithm generates corridors over a weighted-GIS surface; a multi-period hydraulic sizing step selects commercial diameters subject to pressure, velocity, and wall-thickness constraints. Decisions are taken in a rolling-horizon so topology and capacity adapt as information arrives. Applied to the UK Humber cluster from 2030 to 2050, built length reaches 165–200 km, with a Spine-First routing strategy averaging 185 km. Least-regret oversizing adds £40 m compared to a myopic approach but cuts 2040 worst-case incremental outlay from £260 m to < £80 m. By 2050, Spine-First achieves £2.07 m/km, LCOT 54 £/kt and regret 12 £/kt, rivalling a Perfect-Foresight strategy (44 £/kt; 3 £/kt). The results show how a short, centrally aligned trunk combined with anticipatory sizing reduces stranded-asset risk and budget shocks, providing a transferable least-regret template for hydrogen pipelines under deep uncertainty
Cross-linguistic constraints on subjecthood in causative psych verbs:An experimental investigation of Korean, Mandarin Chinese and English
No full textThis study investigates whether cross-linguistic constraints on subject selection in physical causative constructions extend to causative psychological verbs (psych verbs, e.g., frighten, surprise), with a focus on subject volitionality. According to Wolff et al.’s (2009) initiator hypothesis, languages tend to restrict subjecthood in causative events to entities that can plausibly initiate a causal chain. While this has been established for physical causatives, it remains unclear whether similar constraints apply in psychological causation. To test this, we conducted an Acceptability Judgment Task in which native speakers of Korean, Mandarin Chinese, and English rated grammatical sentences varying in subject volitionality. The results showed that only Korean speakers consistently dispreferred non-volitional subjects, suggesting that their subject selection is more constrained by volitionality. These findings indicate that the initiator hypothesis extends beyond physical causatives to psych verbs and that cross-linguistic variation in subject selection persists across domains
Are equity, diversity and inclusion considered in early-phase studies evaluating innovative and developing surgical procedures? Protocol for a scoping review
Get PDFIntroduction
Increased risks and concerns regarding patient safety in early-phase studies exist because knowledge about the new intervention is still accumulating. This means that narrow eligibility criteria are needed. However, if early-phase studies are narrow in their inclusion, for example, by not including diverse populations, there is a potential risk that new therapies have insufficient relevant efficacy and safety data. Existing research has explored equity, diversity and inclusion (EDI) factors in early-phase pharmaceutical studies, but it has not been possible to find studies that have systematically examined whether EDI factors have been considered in surgical studies reporting innovative procedures. We aim to examine how EDI factors are considered in early-phase surgical studies and surgical innovation reports to explore how this may impact on later-phase evaluation and inclusive intervention implementation.
Methods and analysis
A scoping review following the JBI (Joanna Briggs Institute) and Arksey and O’Malley’s five-step process is being conducted. We will search Scopus, PubMed and Web of Science for surgical early-phase studies. A two-step screening process for eligibility is being used. Independent double screening will take place for 20% of the papers. Eligible articles will report early evaluation of an innovative surgical/invasive procedure. Excluded will be comparative and later-phase studies and early evaluations of pharmaceutical products even in a surgical setting. Data on article details, patient eligibility and whether protected characteristics are reported and considered will be extracted. Information about EDI considerations reported in the introduction or discussion of the papers will also be extracted. Findings will be discussed with a patient advisory group. A content synthesis approach will be undertaken and descriptive summaries presented.
Ethics and dissemination
This study does not require ethical approval being a secondary analysis. The findings will be disseminated through academic journal publications and oral presentations
Protocol for a James Lind Alliance priority setting partnership to identify the most important research priorities addressing respiratory health disparities affecting the Black community in the UK
Get PDFIntroduction
Respiratory diseases affect millions of people in the UK, with a disproportionately high burden seen among many marginalised communities. They are the third leading cause of death in the UK and a major driver of morbidity, disability and healthcare service use. Many respiratory conditions cause debilitating symptoms and deterioration in patients’ health and quality of life over time, resulting in substantial increases in National Health Service (NHS) expenditure. Social inequalities, including occupational, housing and environmental disparities, have led to a disproportionate burden of respiratory disease among the Black community. For many Black people living in the UK, respiratory conditions have been under-recognised, misdiagnosed or inadequately treated, further contributing to disparities in health outcomes. Despite the need to address these urgent challenges, research in this area is fragmented and rarely informed by the views and opinions of those most affected. Research prioritisation provides a structured methodology to address this unmet need. The Equal Breath Priority Setting Partnership (PSP) aims to identify the 10 most urgent research priorities in respiratory health for people of Black heritage through meaningful collaboration with people with lived experience of respiratory disease, their caregivers and family members and the healthcare professionals caring for them.
Methods and analysis
The top 10 research priorities for the Equal Breath PSP will be established using the James Lind Alliance (JLA) method. A steering group comprising approximately 12 people from key stakeholder groups will first be assembled to guide the PSP. Once the context and scope of the PSP has been agreed, the first survey will be developed and disseminated among stakeholder communities to identify evidence uncertainties. Data analysis of the survey responses will create summary questions and critical appraisal of available evidence will verify which of these are evidence gaps. A longlist of approximately 50 summary questions derived from the first survey will be shared with stakeholders in a second shortlisting survey. The highest ranking questions from this survey will be taken into a workshop where the top 10 research priorities will be established through a consensus process.
Ethics and dissemination
This PSP employs the JLA methodology, which does not constitute research as defined by the Health Research Authority. Survey respondent data will be stored in accordance with UK General Data Protection Regulation by Asthma+Lung UK. The final 10 research priorities will be shared with funders, policymakers, professional bodies and relevant communities to inform future investment and promote equity in respiratory health
Experimental characterisation of near-field blast loading using digital image correlation on thin plates
Get PDFDirect measurement of near-field blast loading is seldom in the academic literature, and currently available techniques either produce a small number of discreet temporal measurements, or a single time- and area-integrated value. This limitation is addressed in the current work through the use of stereo high-speed video cameras and Digital Image Correlation (DIC); a technique typically used to determine temporally-resolved, full-field deformation of flexible plates subjected to blast loading. Herein, the focus is on the very first instants of plate response, from which distributions of initial velocity are measured, and– through conservation of momentum– specific impulse is inferred. In total, 29 experiments were performed at 5 different scaled distances covering the entire near-field range (0.17–1.03 m/kg1/3). Plate displacements were recorded at 100,000 fps and around 2100 points on the plate surface, effectively enabling full-field measurements of near-field loading distributions, which has previously been unattainable. The results are used to comment on the form and magnitude of blast loading, which ranges from highly centralised, high magnitude loading in the extreme near-field, to relatively uniform, low magnitude loading in the late far-field. The results also show distinct regions of increased localised variability in loading in the mid near-field range, and it is suggested that an idealised, deterministic loading model is not appropriate to capture the true complexity of loading in this region
Polymorphic self-poisoning in poly(lactic acid): a new phenomenon in polymer crystallization
Get PDFSelf-poisoning is ubiquitous in polymer crystallization but has so far manifested itself visibly only as minima in growth rate vs temperature in either monodisperse systems where, e.g., unstable folded chains obstruct crystallization of stable extended chains, or in periodically segmented chains where unstable stems with n-1 segments disturb deposition of stable stems with n segments. Here, we report a new type of self-poisoning found in poly(lactic acid), where a less stable crystal form (�′) disturbs growth of the stable form (�). While � requires strict up-down order of the polar chains, α’ does not, hence is kinetically favored. Unexpectedly, below the temperature of the growth rate minimum, the lamellar thickness increases rather than drops, as in all other reported cases of polymer crystallization with decreasing temperature. A growth rate equation model is developed, giving good match with experiments, but revealing an unexpectedly low fold surface free energy of �′ form. Delayed crystallization due to self-poisoning of � in practical fast-cooling processing not only gives the low-modulus �′ form, but also leads to an increased glassy amorphous fraction that results in embrittlement of the biofriendly poly(lactic acid) through physical aging
Intersectional Inequalities in Neighbourhood Air Pollution Concentration in England: A Quantitative Analysis of Ecological Data Using Eco-Intersectional Multilevel (EIM) Modelling
Get PDFAir pollution is detrimentally associated with many health outcomes, yet its impacts are not equally distributed. Research consistently finds inequalities by ethnicity, area deprivation and age. However, such inequalities are typically investigated separately, potentially underestimating the extent of differential exposures. We aim to investigate inequalities in NOx concentrations across multiple intersecting neighbourhood characteristics in England simultaneously. We do this using the novel Eco-Intersectional Multilevel (EIM) modelling approach, we define analytic “strata” of neighbourhoods based on sociodemographic characteristics. This enables us to quantify NOx concentration inequalities across community types, simultaneously considering area deprivation, ethnicity, education, rurality and age of residents. We find that neighbourhoods belonging to the “most deprived, high proportion minority ethnic, high education, urban and not ageing” stratum had the highest average NOx concentration. This concentration was five times higher than places with the lowest concentration in the mid deprivation, low proportion minority ethnic, high education, rural and ageing stratum. We find clear and striking inequalities by ethnicity. However, we do not find evidence of inequalities by area deprivation that operate independently of community ethnicity, likely due to the strong relationship between ethnicity and deprivation distributions. This study demonstrates the value of taking an intersectional approach to geographical inequalities
Signal processing for the cluster wideband data burst mode
Get PDFThe Wideband Data instrument is part of the Cluster spacecraft Wave Experiment Consortium. Its primary data path is a direct connection to the spacecraft data handling system providing real time downlink to the ground stations of the Deep Space Network and Panska Ves Observatory. However, it was recognized during the mission design phase that this link may not always be available, especially given that simultaneous data acquisition from the four Cluster spacecraft required the use of four ground stations. Therefore, a secondary data path at reduced bit rate was included whereby the data was transferred to the Digital Wave Processor instrument and then to the spacecraft Solid State Recorder. Given that available resources were limited, both for onboard hardware and within the spacecraft assembly, integration and testing program, the design of this backup data path was less than optimal. Although it was verified during ground testing that data could be acquired via this route, the design did not make the best use of the available telemetry bandwidth, and the timing accuracy was too limited to support some multi-spacecraft observations. This paper describes work around solutions to optimize bandwidth utilization and timing accuracy. These involve patches to the onboard software of the Digital Wave Processor instrument and ingenious signal processing on the ground
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