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Baseline characteristics of the TOPaZ study: randomised trial of teriparatide and zoledronic acid compared with standard care in adults with osteogenesis imperfecta
Get PDFIntroduction
Osteogenesis imperfecta (OI) is a rare disorder causing multiple fractures throughout life. No treatment has been shown to reduce the risk of fractures in OI. Here, we present the baseline characteristics of participants in the Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid (TOPaZ) trial. The aim of the trial is to determine whether teriparatide and zoledronic acid are superior to standard care in reducing the risk of clinical fractures.
Methods
We summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.
Results
We recruited 350 adults with a clinical diagnosis of OI in 27 European referral centres between June 2017 and October 2022. Overall, 266 (76.2%) had type I OI, 55 (15.8%) had type IV, and 19 (5.4%) had type III. The type was unknown in 9 (2.6%). Blue sclera were noted in 80.8%, and 35.8% had dentinogenesis imperfecta. Bisphosphonates had been administered to 28.1% in the 2 years prior to enrolment. Pathogenic variants in COL1A1 or COL1A2 were found in 87.6%. Fractures occurring in the 2 years prior to enrolment were not associated with bone density.
Conclusions
The TOPaZ population represents a unique cohort with which to study the genetic epidemiology and outcome of OI in relation to bone density and biochemical markers of bone turnover. When the trial reports, it will also provide new insights into the effect of an anabolic therapy, followed by antiresorptive treatment in the management of OI
Patterns of traumatic brachial plexus injuries: A nationwide study of geographic, demographic, and socioeconomic factors in england and wales
No full textIntroduction
Traumatic brachial plexus injuries (TBPIs) are severe, life-altering injuries associated with significant functional impairment. While previous studies have highlighted mechanisms of injury, there is limited research on the geographical and socioeconomic factors influencing TBPI incidence. This study examines TBPI patterns across England and Wales, identifying demographic risk factors and geographic "hotspots".
Methods
A retrospective cohort study was conducted using data from the Trauma Audit and Research Network (TARN) and the STATS-19 road traffic accident database from January 2010 to March 2022. Patients with confirmed TBPIs meeting TARN inclusion criteria were analysed. Cases were categorised into vehicular collisions (VCs) and non-vehicular injuries (NVIs). Key variables included age, sex, injury mechanism, Index of Multiple Deprivation (IMD) scores, and urban-rural classification. Geographic distribution was assessed to identify high-incidence regions.
Results
A total of 1003 TBPI cases were identified: 601 (60 %) vehicular and 402 (40 %) non-vehicular related injuries. VC TBPIs were more frequent in young males (median age: 35 years), whereas NVIs occurred more in older females (median age: 63 years), mainly due to falls <2 m. Higher IMD scores were associated with penetrating injuries. Urban “hotspots” for penetrating injuries included cities in Greater London, Greater Manchester, and West Yorkshire.
Discussion
This study describes geographic and socioeconomic patterns of TBPIs across England and Wales. Although less frequent than other trauma entities, TBPIs carry a high per-patient burden due to upper-limb paralysis and neuropathic pain, with substantial indirect costs. The identification of demographic profiles and regional clustering provides an epidemiological baseline to inform clinicians and major trauma services
Inequalities and indoor air pollution: a prospective observational study of particulate matter (PM2.5) levels in 309 UK homes from the Born in Bradford cohort study
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Particulate matter (PM2.5) is associated with substantial morbidity and mortality. Evidence suggests socioeconomic and ethnic minority groups are disproportionately exposed to higher outdoor air pollution, exacerbating existing health inequalities. However, most research focuses on outdoor air pollution, despite people spending most of their time indoors. We compare how indoor PM2.5 concentrations vary between households of different socioeconomic status and ethnicity, and test for associations with asthma-related symptoms.
Methods
We recruited 321 households from the multi-ethnic Born in Bradford cohort. Low-cost commercial sensors sampled PM2.5 in three rooms over a two-week period. Information on socio-economic status, home and building characteristics, and asthma related symptoms were collected for 309 mothers and 293 children. We calculated metrics for indoor PM2.5 concentration (µg/m3) to compare with current guideline thresholds and to capture peak events that might be important for health symptoms. We investigated whether PM2.5 concentrations varied by key sociodemographic and home characteristics. Logistic regressions examined whether PM2.5 metrics predicted asthma-related symptom occurrence for mothers and children, controlling for covariates.
Results
Homes had a mean daily average indoor PM2.5 concentration of 20.2 µg/m3, exceeded the WHO 24-hour threshold an average of 41% monitored days, and exceeded 100 µg/m3 an average of 4% monitored hours. South Asian homes had higher PM2.5 concentration than White British or Other ethnicity homes (23.5 µg/m3, 17.1 µg/m3, and 16.5 µg/m3 respectively). Higher PM2.5 was observed with higher deprivation levels (most deprived, 24.0 µg/m3, least deprived, 12.7 µg/m3). Higher PM2.5 levels were seen in rented versus owned homes, smoking versus non-smoking households, terraced and semi-detached versus detached homes, and gas versus electric cooking appliances. We did not find clear associations between asthma-related symptoms and PM2.5 metrics.
Conclusions
The high indoor PM2.5 levels recorded in homes indicate an urgent need to tackle indoor air pollution as a health risk factor, particularly in deprived and minority ethnic households. Policy action should focus on launching national public awareness campaigns, supporting transition to cleaner cooking and air cleaning technologies, and addressing socioeconomic disparities related to high indoor air pollution
Make your own…Home in your pocket
Get PDFHave you every thought what “home” might mean to different people? Around the world, people move to new places, sometimes by choice and sometimes because they have to. When they do, their ideas of home can change and mix with new ones.
For some people, this can feel a bit confusing or lonely at first. It can take time to get used to new sights, sounds, and traditions. But meeting new people and sharing different ways of living can also bring new friendships.
The research behind this activity shows that home isn’t only a building or an address. It can be a person, a song, a favourite food, or something small that helps you feel safe and happy. By making your own pocket home, you can think about what makes you feel you belong and how everyone’s idea of home is special in its own way
Wise versus vertical mastopexy pattern skin-reducing mastectomy with immediate breast reconstruction: systematic review and meta-analysis
Get PDFBackground:
This study compares postoperative outcomes of Wise and vertical mastopexy pattern skin-reducing/skin-sparing masctomy, hypothesizing that incision choice affects cosmetic outcomes and complication rates.
Methods:
A systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, MEDLINE, Embase, Web of Science, and StarPlus Library. Included studies documented skin-sparing mastectomy using Wise or vertical mastopexy patterns with immediate reconstruction. The primary outcome is total mastectomy flap necrosis. The secondary outcomes are major/minor necrosis, infection, hematoma, seroma, and wound complications. Bayesian and frequentist generalized linear mixed models were used for the meta-analysis, including studies with 0 events.
Results:
Sixty-six studies were identified, with 39 included in the meta-analysis, comprising 1954 patients and 2311 breast reconstruction cases. The Wise group had a higher rate of mastectomy flap necrosis (14.2%; 95% confidence interval: 10%–20%; I² = 83%) compared with the vertical group (7.8%; 95% confidence interval: 5%–12%; I² = 0%) (P < 0.05). No significant differences were found in other domains. Subgroup analysis favored vertical mastopexy for wound-related complications (P = 0.04).
Conclusions:
The Wise pattern shows significantly higher mastectomy flap necrosis than the vertical pattern. However, there were no significant differences in major necrosis, minor necrosis, infection, hematoma, or seroma. Future studies should focus on larger, high-quality randomized controlled trials to better understand the impact of incision techniques on postoperative outcomes
Adolescent and young adult (AYA) patient involvement and engagement in European health care and research projects: expanding the scope of patient advocacy
Get PDFPatient involvement and engagement (PI&E) in health care and research has gained prominence, shifting towards person-centred approaches and shared decision making. Patients actively participating in health care design and research lead to better quality and efficiency of care. However, implementing meaningful PI&E is challenging and requires adequate resources and evaluation frameworks so that it does not result in tokenism. This is particularly important when considering niche areas like adolescents and young adults (AYAs) with cancer. As AYAs’ unique needs continue to gain recognition, it is becoming increasingly important to incorporate their expertise and diverse perspectives in navigating care. Large-scale European consortia that focus specifically on AYAs offer opportunities to establish successful partnerships with AYAs in the design and creation of the next generation of equitable, diverse, and inclusive cancer care. Concrete actions for meaningful AYA PI&E are discussed
ModelGen: Automating semiconductor parameter extraction with large language model agents
No full textDevice models require large numbers of parameters to characterize complex physical effects. Although the latest advancements in machine learning and automated tools have drastically improved efficiency over the classic methods, they still demand a considerable amount of human intervention in the loop to gain accuracy. This drastically limits further automation. Inspired by the success of Multimodal Large Language Models (MLLMs) in addressing tasks across diverse fields, we propose ModelGen, the first in-depth study to leverage MLLMs with RAG (Retrieval-Augmented Generation) to significantly reduce human effort in parameter extraction for compact model. Our contributions include (1) Automated Agentic Workflow Construction that learns to build and refine extraction workflows through iterative optimization, (2) MLLM Judge, a visual scoring mechanism that evaluates fitting quality using actual device characteristic plots rather than simple numerical metrics, and (3) Model-specific RAG for providing relevant domain knowledge during the extraction process. Experimental results demonstrate that ModelGen achieves a 26.8%–33.1% improvement in pass@1,3,5 compared to base LLM methods. The system completes complex model extractions for BSIMs and ASM-HEMT in hours (up to 168× faster) rather than days or weeks, making parameter extraction more accessible to non-experts while maintaining professional engineer-level accuracy
Ancient DNA and dating evidence for the dispersal of hippos into central Europe during the last glacial
Get PDFLate Pleistocene hippo fossils (Hippopotamus amphibius) from Europe have generally been associated with the last interglacial period (Eemian, 129-115 thousand years ago [kya]).1,2,3,4 As a widely accepted indicator species for temperate climate conditions, it was assumed they went extinct with the onset of the last glacial (Weichselian) around 115 kya.2,5 Their origin and relationships to extant African common hippos and the exact age of their extinction in central Europe, however, remain unclear. Here, we address these questions using an integrated approach applied to hippos from the Upper Rhine Graben in central Europe. By sequencing the paleogenome of a European hippo, we reveal its close genetic links to modern hippos from Africa. Six additional partial mitochondrial genomes confirm that European representatives were part of the same, once widespread species that is today restricted to sub-Saharan Africa. Surprisingly, radiocarbon dating shows that hippos were present in central Europe during the middle Weichselian (a period spanning from earlier than 47 kya until ∼31 kya), i.e., well into the last glacial. Similar radiocarbon dates for woolly mammoth and woolly rhino fossils from the same sites imply the presence of both faunas during this period. Despite the paleogenome's low coverage, we are able to confidently estimate its genome-wide diversity by recalibrating the sequencing quality scores and assessing post-mortem damage. The low genome-wide diversity recovered suggests that it belonged to a small, isolated population. Overall, our combined data imply that hippos inhabited the Upper Rhine Graben refugium during temperate phases of the middle Weichselian
Development of a core outcome set for paediatric upper limb spasticity; a structured review protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey
Get PDFBackground
Upper limb spasticity is a common condition in paediatric patients, often resulting from neurological disorders such as cerebral palsy, traumatic brain injury, or stroke. There are currently no standardised outcome measures to assess progress after interventions for upper limb spasticity in children. Wide variation in currently reported outcomes makes comparison of treatments difficult. This study aims to identify outcome measures that have previously been reported in studies evaluating the management of upper limb spasticity in children and to facilitate the development of a consensus core outcome set (COS) suitable for use in all future studies of upper limb spasticity in children.
Methods/design
This study will include a systematic review of the academic literature to identify a list of outcome measures that have previously been reported. The list of outcome measures will be used in a consensus setting exercise with focus groups of key stakeholders to identify key outcomes. A Delphi process to include two rounds will then be used to define the most important outcomes to all stakeholders forming the COS.
Discussion
Core outcomes represent the minimum expected data reported for a specific condition and will improve the quality of future studies, reducing bias, allowing easier comparison and enhancing opportunities for larger meta-analysis and more meaningful future research
Short and Long-term Grounding Zone Dynamics of Amery Ice Shelf, East Antarctica
Get PDFThe detection of grounding line (GL) positions in Antarctica is crucial for investigating the stability and health of ice sheets and glaciers. In reality the GL position is not fixed and will migrate upstream or downstream in response to varying tidal states on an hourly to daily timescale, or in response to longer-term ice dynamic change. However, the magnitude of short and long-term GL migration is not well characterised in many parts of Antarctica. In this study, we employ the Differential Range Offset Tracking method to measure the tidal GL migration on the Amery Ice Shelf in East Antarctica. We delineate 32 GL positions for the year 2021, covering 1172 km of coastline. The results show that GL migration in this region is not solely dictated by tidal height or tidal difference but is also significantly influenced by ice velocity and subglacial bed topography, providing new insights into the GL dynamics of the region. We also observe significant long-term GL retreat in the eastern part of the Amery Ice Shelf relative to the MEaSUREs Antarctic GL Version2 derived from 2000 SAR imagery (Rignot et al., 2016), with the maximum retreat reaching up to 10 km. Our findings underscore the need for continuous, high-resolution GL monitoring around the whole Antarctic coastline, to improve predictive models of ice sheet responses to climate changes and their subsequent impact on global sea-level rise
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