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Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and ineligible individuals
No full textBackground: randomised controlled trials (RCTs) evaluating attention-deficit/hyperactivity disorder (ADHD) medications often use strict eligibility criteria, potentially limiting generalisability to patients in real-world clinscal settings. We aimed to 1) determine the proportion of individuals with ADHD who would be ineligible for medication RCTs and 2) evaluate differences in treatment patterns and clinical/functional outcomes between RCT-eligible and ineligible individuals.Methods: we used Swedish national registries to identify individuals with ADHD, aged 4-68, initiating pharmacological treatment between January 1, 2007, and December 31, 2019, with follow-up through December 31, 2020. Hypothetical RCT ineligibility was determined using exclusion criteria from the international MED-ADHD dataset, including 164 RCTs of ADHD medications. Cox models evaluated differences in medication switching and discontinuation within 1 year between eligible and ineligible individuals. Poisson models compared eligible and ineligible individuals on rates of psychiatric hospitalizations, injuries/accidents, and substance misuse within 1 year of initiating ADHD medications. People with lived experience were not involved in the research and writing process. Ethnicity data were not available.Outcomes: out of 189,699 individuals (112,153 males [59%] and 77,546 [41%] females; mean age=21[range 4-68] years) initiating ADHD medication, 53% (74% of adults, 35% of adolescents, and 21% of children) would have been ineligible for RCT participation. Ineligible individuals had a higher likelihood of treatment switching (HR=1·15, 95% CI 1·12-1·17), and a decreased likelihood of medication discontinuation (HR=0·96 [0·94-0·98]) compared to eligible individuals. RCT-ineligible individuals had significantly higher rates of psychiatric hospitalizations (IRR=3·76 [3·67-3·85]) and specialist care visits related to substance misuse (IRR=3·42 [3·30-3·54]), depression (IRR=6·00 [5·94-6·06]), and anxiety (IRR=11·63 [11·56-11·69]).Interpretation: individuals ineligible for ADHD medication trials face higher risks of adverse outcomes. This study provides the first empirical evidence for the limited generalisability of ADHD RCTs to real world clinical populations, by applying eligibility criteria extracted from a comprehensive dataset of RCTs to a large real-world cohort. Triangulating evidence from RCTs and real-world studies is crucial to inform rigorous evidence-based treatment guidelines.Funding: National Institute of Healthcare and Research (NIHR); European Union’s Horizon 2020, Swedish Research Council.<br/
A surrogate FRAX model for Mongolia
No full textSummary: a surrogate FRAX® model for Mongolia has been constructed using age- and sex-specific hip fracture rates for mainland China and age- and sex-specific mortality rates from Mongolia.Introduction: FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country.Objective: this report describes the development and characteristics of a surrogate FRAX model for Mongolia.Methods: the FRAX model used the ethnic-specific incidence of hip fracture in mainland China, combined with the death risk for Mongolia in 2015-2019. Intervention thresholds were developed based on fracture probabilities equivalent to women with a prior fragility fracture, and their impact was assessed in a referral cohort comprising men at age 50 and above and postmenopausal women. The number of hip fractures in 2015 and 2050 was estimated based on United Nations' predicted changes in population demography.Results: the surrogate model gave similar hip fracture probabilities to estimates from China. Age-dependent intervention thresholds for a major osteoporotic fracture ranged from a 10-year probability of 2.4% at the age of 40 years to 13.7% at the age of 90 years. In the cohort of those eligible for assessment, 46% of men and 36% of women were eligible for treatment because of a prior fracture. Based on intervention thresholds, a further 0.5% of men and 7.0% of women would be eligible for treatment. It was estimated that 440 hip fractures arose in 2015 in individuals aged 50 years and older in Mongolia, with a predicted 4.3-fold increase expected by 2050, when 1896 hip fractures are expected nationally.Conclusion: the surrogate FRAX model for Mongolia provides an opportunity to determine fracture probability within the Mongolian population and help guide decisions about treatment.</p
Latent space atmospheric particulate science
No full textParticulate matter air pollution is a major contributor to global illness and originates from a range of natural and anthropogenic sources. These particles can undergo agglomeration, whereby individual units cluster into larger, structurally complex assemblies. This process can span multiple spatial and temporal scales, from nanometre-sized particles interacting over seconds to minutes, to the formation of larger aggregates that form and evolve over hours or days. Understanding how particles agglomerate, and transport is essential for accurately predicting their dispersion, environmental impact, and potential health risks. However, traditional analytical models struggle to capture the multivariate, nonlinear nature of these processes. Recent advances in deep learning, in particular the use of latent space representations offer promising new tools for addressing this complexity. More specifically, latent spaces allow high-dimensional data, such as particle morphology and spatial-temporal measurements, to be projected into lower-dimensional manifolds where hidden structure and dynamics may become more interpretable. In this work, I explore how latent space methods can be applied to model particulate agglomeration and its evolution over space and time, providing an alternative framework for understanding aerosol behaviour beyond conventional techniques
Lost landscapes of Plymouth: historical land reclamation and coastal urbanisation continue to shape Britain's ocean city
No full textCoastal cities worldwide face increasing vulnerability to erosion, storm damage, flooding, and sea-level rise. Many are partially situated on reclaimed land and the transformation of coastal and estuarine habitats into hard infrastructure has led to significant losses of vital wetlands and intertidal habitats, impacting biodiversity and ecosystem service provision. Shifting Baseline Syndrome (lack of awareness of the historical existence and extent of due to changes in human perception) complicates conservation efforts. Using Plymouth, UK, as a case study, we used a combination of historical maps, satellite imagery, and published works to characterise and quantify historical transformations of the coastline. We estimated that approximately 800 hectares of land have been reclaimed in Plymouth Sound and its estuaries since the medieval period (~1200 years CE). Land reclamation occurred for various purposes, including agriculture, milling, urban expansion, infrastructure development and industrialization. A survey of Plymouth residents revealed limited understanding of local land reclamation history, with the majority unaware of the extent and impact of past transformations. Longer-term residents showed greater awareness, highlighting evidence of Shifting Baseline Syndrome. Additionally, we assessed the multifunctional potential of coastal structures along Plymouth Hoe foreshore, revealing their historical significance and ecological value. Many structures supported diverse marine life, serving as valuable habitat whilst simultaneously supporting human activities (e.g., swimming, access, fishing). Understanding the cultural and natural heritage value and historical context of coastal structures can inform conservation and management efforts in urban coastal areas. Greater public awareness of past transformations and their ecological consequences is essential for informed decision-making and sustainable coastal management globally
The fishery for Antarctic krill – conflicts between industrial production, protection of biodiversity, and legal governance
No full textThe Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) is responsible for conserving the Antarctic marine ecosystem, where conservation also includes the management of commercial fisheries. The largest fishery (by weight) in Antarctic waters is that for Antarctic krill, a species vital to biogeochemical cycles and carbon sequestration, and a critical dietary item for a broad guild of marine predators. Fishing interests grew from the 1960s onwards, but catches then declined following the breakup of the Soviet Union. Now catches are again increasing, CCAMLR has been developing a revised krill fishery management framework intended to reduce ecosystem risks to predators at critical times of year. At the CCAMLR meeting in 2024, ongoing development of the revised framework was considered, however no progress was made. Progress is urgent, since part of the existing management approach was not renewed. Consequently, by default, catches in the southwest Atlantic may now aggregate in space and time; the interim catch limit for krill (620,000 t) can now be taken from anywhere and at any time, including at times and in places critical to krill predators, possibly with unintended consequences. Allowing catches to aggregate in space and time is something CCAMLR has long sought to avoid. Existing voluntary measures implemented by the fishery will help distribute catches, but are no substitute for de jure management. In addition to risks to the ecosystem, the current situation also presents risks for fishing nations and for CCAMLR itself. Rapid progress with the revised management framework now depends upon rebuilding consensus.</p
The influence of obstacle geometric fidelity on blast wave propagation: a reduced-scale case study examining the role of the grain siloes in the 2020 Beirut explosion
No full textIn the field of blast protection engineering, it remains challenging to validate large, complex numerical models and the implications of modelling assumptions relating to how structures are represented (e.g., geometric fidelity) are not well understood. This paper presents experimental work addressing these two issues, in the context of the 2020 Beirut explosion, which remains an important case study for understanding urban blast effects. A series of reduced-scale (1:250) blast tests examined shielding effects caused by the Beirut grain siloes and investigated the influence of the siloes’ geometric fidelity on blast loading. Rigid obstacles were constructed at two geometric fidelities: “rectangular” (i.e., cuboid), and “accurate”, with closer resemblance to the siloes. Pressure gauges were mounted at multiple locations but at fixed blast scaled distances to examine blast-obstacle interaction behaviour. Additionally, Viper::Blast was used to perform computational fluid dynamics analyses of the tests. Experimental findings confirmed significant shielding (reduced pressure and specific impulse) locally behind the siloes (Z<3 m/kg1/3), although models indicated that these effects ceased further afield (Z>5 m/kg1/3). Overall, blast wave parameters did not exhibit significant differences between the rectangular and accurate representation of the siloes geometry, except for minor differences (+/-10%) in peak overpressures in localised zones. Numerical models confirmed that these discrepancies were caused by differing blast wave scattering, diffraction and superposition behaviour attributed to the siloes outer geometry. The results suggest that city-scale blast loading analyses can yield reliable results through idealising structures as simplified, cuboidal obstacles. These findings will be of direct relevance to blast protection practitioners and researchers concerned with modelling urban blast scenarios
Ten years of Tridacna sclerochemistry at up to daily resolution from a controlled aquarium environment – records of habitat change, induced seasonality and growth variability
No full textGiant clams such as Tridacna sp., with their rapid shell accretion (mm-cm/year), decade-long lifespans and aragonitic shells, are invaluable (palaeo)environmental archives, potentially providing information at (sub-)seasonal timescales. Royal Burgers' Zoo aquarium in Arnhem, The Netherlands, opened a live coral reef eco-display in 2000 and introduced T. squamosa from Vietnam in 2001. One specimen (TS2) that died in 2011 facilitated a decade-long comparison of carefully monitored aquarium conditions with Tridacna sclerochemistry and growth, whose results we present herein. Spatially resolved El/Ca ratios by LA-ICPMS (at up to daily resolution) as well as micromilled δ13C and δ18O data were transferred onto a sclerochronological framework at a daily resolution, which enabled the detailed correlation of aquarium parameters with sclerochemistry. We show that environmental stresses such as transportation, introduction to a new aquarium environment, shifts in water change regimes and artificial seasonality from 2009 onwards have severe impacts on the organism's growth and sclerochemistry, and are particularly manifest in this sample in increased Mg/Ca and Sr/Ca ratios. Growth rates were reduced from ∼20 to ∼7 μm/day during transportation into the aquarium, and from ∼10 to ∼2 μm/day during shifts in water change regimes in the aquarium. A disruption of daily El/Ca cyclicity was marked during transportation-induced stress, but within three weeks of introduction the organism acclimatised to the aquarium and returned to natural growth rates and cyclicity. Three years of induced temperature seasonality (25.0–26.5 °C) most notably affected Na/Ca, while the resulting expected δ18O variability was not resolvable due to TS2's strongly decreased growth rate coupled with our large drill-step size for sampling. Despite a transient spike in aquarium [NO-3] from ∼0.02 to 2.4 mg/L, caused by accidental over-fertilisation, no stress effect was apparent in the organism's sclerochemistry or growth rate. Changes in the water-exchange regime appear to have far more sclerochemical impact, as these are reflected in the overall δ18O, Ba/Ca and associated growth rates. The detailed decade-long Tridacna record shows that even systems with comparatively little environmental variability can produce large degrees of shell heterogeneity, and also highlights the importance of establishing a detailed (counted) chronology for sclerochemical interpretations.</p
Measuring a pollutant plume over a 3D printed city model
No full textThe modelling of urban air pollution requires an understanding of the turbulent processes involved. This projects aims to provide direct measurements of turbulent dispersion over urban terrain with a high-fidelity experimental study. An investigation into scalar dispersion over a 3D-printed model of the City of Southampton, which is a medium-size coastal city in the south of England, was carried out. This 1000:1 scale model was created to represent 1 km2 of Southampton’s city centre experiencing an onshore south-south-westerly wind. Experimentally measuring turbulent scalar fluxes is challenging as it requires both concentration and velocity measurements in the same place, and at the same time. Particle image velocimetry (PIV) and planar laser induced fluorescence (PLIF) were used to measure full fields of these turbulent scalar fluxes. Measurements were carried out in streamwise-vertical and wall-parallel planes to create a detailed map of concentration and velocity data for a case in which a plume from an offshore point source was introduced upstream of this model
First IFU observations of two GRB host galaxies at cosmic noon with JWST/NIRSpec
No full textLong gamma-ray bursts (GRBs) serve as powerful probes of distant galaxies. Their luminous afterglow pinpoints galaxiesindependent of luminosity, in contrast to most flux-limited surveys. Nevertheless, GRB-selected galaxy samples are not freefrom bias, instead tracing the conditions favoured by the progenitor stars. Characterizing the galaxy populations traced by GRBs is therefore important both to effectively use GRBs as probes as well as to place stronger constraints on the progenitor starscapable of forming long GRBs. Spatially resolved spectroscopic observations with integral field units (IFUs) provide valuableinsights into the interstellar medium and stellar populations of GRB host galaxies. In this paper, we present results of the firsttwo GRB host galaxies observed with the JWST/Near-Infrared Spectrograph IFU with a spatial resolution of ∼ 1.6 kpc; thehosts of GRB 150403A and GRB 050820A at redshifts z ∼ 2.06 and ∼ 2.61, respectively. The data reveal two complex galaxyenvironments made up of two or more star-forming galaxies that are likely interacting given their small spatial separation (< 20kpc) and line-of-sight velocity offsets (< 100 km s−1). The measured gas-phase metallicity, star formation rates (SFRs), and keydiagnostic line ratios for each of the detected galaxies are overall consistent with the properties of other star-forming galaxiesand GRB hosts at z > 2. However, differences in the SFR and metallicities of the interacting galaxies highlight the importanceof spatially resolved observations in order to accurately characterize the galaxy properties traced by GRBs
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