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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Aerosol-cloud interactions contribute significant uncertainty to modern climate model predictions. Analysis of complex observed aerosol-cloud parameter relationships is a crucial piece of reducing this uncertainty. Here, we apply two machine learning methods to explore variability in in-situ observations from the NASA ACTIVATE mission. These observations consist of flights over the Western North Atlantic Ocean, providing a large repository of data including aerosol, meteorological, and microphysical conditions in and out of clouds. We investigate this dataset using principal component analysis (PCA), a linear dimensionality reduction technique, and an autoencoder, a deep learning non-linear dimensionality reduction technique. We find that we can reduce the dimensionality of the parameter space by more than a factor of 2 and verify that the deep learning method outperforms a PCA baseline by two orders of magnitude. Analysis in the low dimensional space of both these techniques reveals two consistent physically interpretable regimes—a low pollution regime and an in-cloud regime. Through this work, we show that unsupervised machine learning techniques can learn useful information from in-situ atmospheric observations and provide interpretable results of low-dimensional variability.
Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.
Amur honeysuckle [Lonicera maackii (Rupr.) Herder] is an aggressive invader of forests throughout the eastern United States. While self-pollination has been identified as an important trait of invasive plant species, this trait is understudied, and L. maackii is anecdotally described as lacking this characteristic. To examine the ability of L. maackii to self-pollinate, we selected 171 individual shrubs distributed across nine sites. Each site was grouped into one of three invasion types: heavy, light, and sprouting (sites on which a basal cutting treatment previously occurred, but L. maackii was allowed to reestablish). We compared the number of berries, seeds per berry, and seed germination rates of self- and open-pollinated flowers by pairing branches covered with pollination bags before flower emergence with uncovered branches on the same individual shrub. Out of 171 individuals, 48 produced berries from self-pollination within pollination bags (28%), with 48% of bagged branches exhibiting some degree of necrosis or chlorosis, presumably due to increased temperature and humidity. Berries from self-pollination produced 1.5 ± 1.4 (mean ± 1 SD) seeds per berry, whereas berries resulting from open pollination produced 3.3 ± 1.5 seeds per berry. In a germination trial, 47.3% of self-pollinated seeds germinated compared with 41.7% of open-pollinated seeds. This study has shown that L. maackii can self-pollinate and set viable seed, providing the species with an important mechanism to increase population abundance during the early stages of invasion.
We perform direct numerical simulations of soluble bubbles dissolving in a Taylor–Couette (TC) flow reactor with a radius ratio of $\eta =0.5$ and Reynolds number in the range $0 \leq Re \leq 5000$, which covers the main regimes of this flow configuration, up to fully turbulent Taylor vortex flow. The numerical method is based on a geometric volume-of-fluid framework for incompressible flows coupled with a phase-change solver that ensures mass conservation of the soluble species, whilst boundary conditions on solid walls are enforced through an embedded boundary approach. The numerical framework is validated extensively against single-phase TC flows and competing mass transfer in multicomponent mixtures for an idealised infinite cylinder and for a bubble rising in a quiescent liquid. Our results show that when bubbles in a TC flow are mainly driven by buoyancy, theoretical formulae derived for spherical interfaces on a vertical trajectory still provide the right fundamental relationship between the bubble Reynolds and Sherwood numbers, which reduces to $Sh \propto \sqrt {Pe}$ for large Péclet values. For bubbles mainly transported by TC flows, the dissolution of bubbles depend on the TC Reynolds number and, for the turbulent configurations, we show that the smallest characteristic turbulent scales control mass transfer, in agreement with the small-eddy model of Lamont & Scott (AIChE J., vol. 16, 1970, pp. 513–519). Finally, the interaction between two aligned bubbles is investigated and we show that a significant increase in mass transfer can be obtained when the rotor of the apparatus is operated at larger speeds.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
Few studies have examined the genetic population structure of vector-borne microparasites in wildlife, making it unclear how much these systems can reveal about the movement of their associated hosts. This study examined the complex host–vector–microbe interactions in a system of bats, wingless ectoparasitic bat flies (Nycteribiidae), vector-borne microparasitic bacteria (Bartonella) and bacterial endosymbionts of flies (Enterobacterales) across an island chain in the Gulf of Guinea, West Africa. Limited population structure was found in bat flies and Enterobacterales symbionts compared to that of their hosts. Significant isolation by distance was observed in the dissimilarity of Bartonella communities detected in flies from sampled populations of Eidolon helvum bats. These patterns indicate that, while genetic dispersal of bats between islands is limited, some non-reproductive movements may lead to the dispersal of ectoparasites and associated microbes. This study deepens our knowledge of the phylogeography of African fruit bats, their ectoparasites and associated bacteria. The results presented could inform models of pathogen transmission in these bat populations and increase our theoretical understanding of community ecology in host–microbe systems.
Pediatric medical devices lag behind adult devices due to economic barriers, smaller patient populations, changing anatomy and physiology of patients, regulatory hurdles, and especially difficulties in executing clinical trials. We investigated the requirements, challenges, associated timeline, and costs of conducting a multi-site pivotal clinical trial for a Class II pediatric physiologic monitoring device.
Methods:
This case study focused on the negotiation of clinical trial agreements (CTAs), budgets, and Institutional Review Board (IRB) processing times for a pediatric device trial. We identified key factors contributing to delays in clinical trial execution and potential best practices to expedite the process while maintaining safety, ethics, and efficacy.
Results:
The total time from site contact to first patient enrollment averaged 14 months. CTA and budget negotiations were the most time-consuming processes, averaging nearly 10 and 9 months, respectively. Reliance and local IRB processing also contributed significantly to the timeline, overall adding an average of 6.5 months across institutions. Nearly half of all costs were devoted to regulatory oversight. The COVID-19 pandemic caused significant slowdowns and delays at multiple institutions during study enrollment. Despite these pandemic-induced delays, it is important to note that the issues and themes highlighted remain relevant and have post-pandemic applicability.
Conclusions:
Our case study results underscore the importance of establishing efficient and standardized processing of CTAs, budget negotiations, and use of reliance IRBs to expedite clinical trial execution for pediatric devices. The findings also highlight the need for a national clinical trials network to streamline the clinical trial process.
NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
The Paleozoic represents a key time interval in the origins and early diversification of chondrichthyans (cartilaginous fishes), but their diversity and macroevolution are largely obscured by heterogenous spatial and temporal sampling. The predominantly cartilaginous skeletons of chondrichthyans pose an additional limitation on their preservation potential and hence on the quality of their fossil record. Here, we use a newly compiled genus-level dataset and the application of sampling standardization methods to analyze global total-chondrichthyan diversity dynamics through time from their first appearance in the Ordovician through to the end of the Permian. Subsampled estimates of chondrichthyan genus richness were initially low in the Ordovician and Silurian but increased substantially in the Early Devonian. Richness reached its maximum in the middle Carboniferous before dropping across the Carboniferous/Permian boundary and gradually decreasing throughout the Permian. Sampling is higher in both the Devonian and Carboniferous compared with the Silurian and most of the Permian stages. Shark-like scales from the Ordovician are too limited to allow for some of the subsampling techniques. Our results detect two Paleozoic radiations in chondrichthyan diversity: the first in the earliest Devonian, led by acanthodians (stem-group chondrichthyans), which then decline rapidly by the Late Devonian, and the second in the earliest Carboniferous, led by holocephalans, which increase greatly in richness across the Devonian/Carboniferous boundary. Dispersal of chondrichthyans, specifically holocephalans, into deeper-water environments may reflect a niche expansion following the faunal displacement in the aftermath of the Hangenberg extinction event at the end of the Devonian.
Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown.
Aims
To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD.
Method
National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored.
Results
People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08–8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15–7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92–0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04–2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96–0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51–0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10–3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09–1.16, P < 0.001) were associated with worse therapy outcomes in PLWD.
Conclusions
Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.
The extremely toxic protein, ricin, is derived from castor beans and is a potential terrorist weapon. Adsorption to clays might minimize the environmental persistence and toxic effects of this toxin. Ricin adsorption to clay minerals was measured using batch adsorption isotherms. Enzyme-linked immunoassay methods were used to quantify aqueous ricin concentrations. Montmorillonite, sepiolite and palygorskite effectively adsorbed ricin from aqueous solutions and yielded mostly Langmuir-type isotherms. The monolayer adsorption capacity from a Langmuir equation fit at pH 7 was 444 g ricin/kg for montmorillonite (SWy-2), but was only 5.6 g ricin/kg for kaolinite (KGa-1b). Monolayer capacities for sepiolite (SepSp-1) and palygorskite (PFl-1) at pH 7 were 59.2 and 58.1 g ricin/kg. The high-charge montmorillonite (SAz-1) effectively adsorbed ricin at pH 7, but yielded a linear isotherm with K = 5530 L/kg. At pH 5, both montmorillonites (SWy-2 and SAz-1) yielded Langmuir-type isotherms with monolayer capacities of 694 and 641 g ricin/kg. Clay samples with higher cation exchange capacities generally adsorbed more ricin, but adsorption also followed specific surface area. X-ray diffraction of <2 μm SWy-2 treated with 470 g ricin/kg indicated expansion up to 34.6 Å at buffered pHs of 4 and 7, but not at pH 10. Furthermore, ricin adsorption was greatest at pH 4 and 7, but minimal at pH 10. Treatment with 1.41 kg of purified ricin/kg clay at pH 5 yielded a 35.3 Å peak and adsorption of ~1.2 kg ricin/kg. Similar treatment with lower-purity ricin yielded less expansion and lower adsorption. The 35.3 Å peak interpreted either as a d002 or d001 reflection indicates a 70.6 Å or a 35.3 Å ricin/SWy-2 complex. This implies that adsorption and air drying have compressed interlayer ricin molecules by 18 to 65%. Effective ricin adsorption by montmorillonite suggests that it could be used to minimize the toxic effects of dispersed ricin.
A critical need in the neuropsychology field is development and validation of efficient, scalable assessments of cognition. The Mobile Toolbox (MTB), a novel suite of mobile device-compatible, app-based cognitive assessments, was developed to address this need. The goals of this study were (1) To collect longitudinal normative data for the MTB assessments in a large, ethnoculturally and educationally diverse cohort; (2) To assess the feasibility and usability of remote assessment using MTB.
Participants and Methods:
Participants were recruited from the UCSF Brain Health Registry (BHR), an online cohort (N>100,000) that collects longitudinal cognitive, functional, behavioral, and health data using online neuropsychological tests and self- and study-partner report surveys. BHR participants who opted to learning about additional research opportunities were sent automated email invitations to enroll in the MTB study. Those who indicated study interest were provided instructions within the BHR online portal for downloading the MTB app. All participants had the opportunity to complete a single baseline administration of MTB (Word Meaning, Sequences, Spelling, Arranging Pictures, Arrow Matching, Faces and Names, Shape-Color Sorting, Number Match). Those who completed the baseline assessment within three days were invited to continue into the longitudinal study, where they complete MTB assessments at a single, short-term timepoint (day 7, 14, or 21; study arms sequentially assigned), and then at 6-month intervals. Enrollment across demographic groups was monitored, and study invitations were sent to specific demographic groups, with the goal of enrolling a sample of 800 participants in the longitudinal study: equal distribution across eight, 10-year age bands (ages 18-80+); 60% with <16 years of education; 10% non-Latinx Black, 15% Latinx, and 5% non-White other ethnocultural identity.
Results:
Between January-June 2022, 48,110 BHR participants were invited to the MTB study. Of those, 8294 (17%) expressed interest, 3401 (7%) completed the baseline assessment, 850 (1.8%) were assigned to the longitudinal study, and 782 (1.6%) completed a short-term longitudinal assessment. Study staff received 797 help tickets submitted by participants asking for email support to complete MTB. The baseline cohort had and average age of 64 years and an average of 16.6 years of education, 76.2% female, 2.1% non-Latinx Black, 7.1% Latinx, 86.8% non-Latinx White, and 4% from other ethnocultural groups. The longitudinal cohort had an average age of 62.3 years and an average of 16.1 years of education, 80% female, 2.8% non-Latinx Black, 8.5% Latinx, 83.5% non-Latinx White; and 5% other ethnocultural group. Compared to those invited to the study, those who enrolled in the longitudinal study were older, had higher educational attainment, and were more likely to be female and self-identify as non-Latinx White (p<0.05 for all).
Conclusions:
Efficient enrollment and task completion of a large cohort in a novel, app-based mobile cognitive assessment is feasible in a completely remote setting. Most participants were able to complete MTB without individual support, indicating good usability. This approach can be scaled up to efficiently assess cognition in many research and healthcare settings. A remaining challenge is achieving robust ethnocultural and educational diversity.
Sedimentary rocks exposed at Dob’s Linn, Scotland, have significantly influenced our understanding of how life evolved over the Ordovician to Early Silurian. The current interpreted chronostratigraphic boundary between the Ordovician and Silurian periods is a Global Boundary Stratotype Section and Point (GSSP), calibrated to 443.8 ± 1.5 Ma (Hirnatian–Rhuddanian age), based on biostratigraphic markers, radioisotopic dates and statistical modelling. However, challenges arise due to tectonic disturbances, complex correlation issues and the lack of systematic dating in Ordovician–Silurian stratigraphic sections. Here, hundreds of zircon grains from three metabentonite ash horizons were dated using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). A subset of the grains were re-analyzed using Chemical Abrasion Isotope Dilution Thermal Ionization Mass Spectrometry (CA-ID-TIMS). We present a high-precision CA-ID-TIMS 238U-206Pb weighted mean date of 440.44 ± 0.55/0.56/0.72 Ma (±analytical/with tracer/with U-decay constant) for the Coronagraptus cyphus biozone. However, the study reports younger, and in certain cases, older LA-ICP-MS zircon dates within the Coronagraptus cyphus, Akidograptus ascensus and Dicellograptus anceps zones, suspected as being influenced by Pb loss and LA-ICP-MS matrix mismatch. The study reports concerns about the suitability of Dob’s Linn as a GSSP section and examines various LA-ICP-MS maximum depositional age (MDA) approaches, suggesting the use of the TuffZirc date and the youngest mode weighted mean (YMWM) as suitable MDA calculations consistent with CA-ID-TIMS results.
What explains right-wing radicalization in the United States? Existing research emphasizes demographic changes, economic insecurity, and elite polarization. This paper highlights an additional factor: the impact of foreign wars on society at home. We argue communities that bear the greatest costs of foreign wars are prone to higher rates of right-wing radicalization. To support this claim, we present robust correlations between activity on Parler, a predominantly right-wing social media platform, and fatalities among residents who served in U.S. wars in Iraq and Afghanistan, at both the county and census tract level. The findings contribute to understanding right-wing radicalization in the US in two key respects. First, it examines widespread, nonviolent radical-right activity that, because it is less provocative than protest and violence, has eluded systematic measurement. Second, it highlights that U.S. foreign wars have important implications for domestic politics beyond partisanship and voting, to potentially include radicalization.
The coronavirus disease 2019 (COVID-19) pandemic highlighted the lack of agreement regarding the definition of aerosol-generating procedures and potential risk to healthcare personnel. We convened a group of Massachusetts healthcare epidemiologists to develop consensus through expert opinion in an area where broader guidance was lacking at the time.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.