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Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.
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Magnetoencefalografía , Memoria a Corto Plazo , Testosterona , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Femenino , Adolescente , Niño , Encéfalo/fisiología , Saliva/química , Saliva/metabolismo , Mapeo Encefálico , Caracteres SexualesRESUMEN
In the early phases of growth, resurgent epidemic waves of SARS-CoV-2 incidence have been characterised by localised outbreaks. Therefore, understanding the geographic dispersion of emerging variants at the start of an outbreak is key for situational public health awareness. Using telecoms data, we derived mobility networks describing the movement patterns between local authorities in England, which we have used to inform the spatial structure of a Bayesian BYM2 model. Surge testing interventions can result in spatio-temporal sampling bias, and we account for this by extending the BYM2 model to include a random effect for each timepoint in a given area. Simulated-scenario modelling and real-world analyses of each variant that became dominant in England were conducted using our BYM2 model at local authority level in England. Simulated datasets were created using a stochastic metapopulation model, with the transmission rates between different areas parameterised using telecoms mobility data. Different scenarios were constructed to reproduce real-world spatial dispersion patterns that could prove challenging to inference, and we used these scenarios to understand the performance characteristics of the BYM2 model. The model performed better than unadjusted test positivity in all the simulation-scenarios, and in particular when sample sizes were small, or data was missing for geographical areas. Through the analyses of emerging variant transmission across England, we found a reduction in the early growth phase geographic clustering of later dominant variants as England became more interconnected from early 2022 and public health interventions were reduced. We have also shown the recent increased geographic spread and dominance of variants with similar mutations in the receptor binding domain, which may be indicative of convergent evolution of SARS-CoV-2 variants.
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COVID-19 , SARS-CoV-2 , Humanos , Teorema de Bayes , SARS-CoV-2/genética , COVID-19/epidemiología , Inglaterra/epidemiologíaRESUMEN
In May 2022, a cluster of mpox cases were detected in the UK that could not be traced to recent travel history from an endemic region. Over the coming months, the outbreak grew, with over 3000 total cases reported in the UK, and similar outbreaks occurring worldwide. These outbreaks appeared linked to sexual contact networks between gay, bisexual and other men who have sex with men. Following the COVID-19 pandemic, local health systems were strained, and therefore effective surveillance for mpox was essential for managing public health policy. However, the mpox outbreak in the UK was characterised by substantial delays in the reporting of the symptom onset date and specimen collection date for confirmed positive cases. These delays led to substantial backfilling in the epidemic curve, making it challenging to interpret the epidemic trajectory in real-time. Many nowcasting models exist to tackle this challenge in epidemiological data, but these lacked sufficient flexibility. We have developed a nowcasting model using generalised additive models that makes novel use of individual-level patient data to correct the mpox epidemic curve in England. The aim of this model is to correct for backfilling in the epidemic curve and provide real-time characteristics of the state of the epidemic, including the real-time growth rate. This model benefited from close collaboration with individuals involved in collecting and processing the data, enabling temporal changes in the reporting structure to be built into the model, which improved the robustness of the nowcasts generated. The resulting model accurately captured the true shape of the epidemic curve in real time.
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COVID-19 , Mpox , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Pandemias , COVID-19/epidemiología , Brotes de Enfermedades , Inglaterra/epidemiologíaRESUMEN
The bottom-up assembly of biological and chemical components opens exciting opportunities to engineer artificial vesicular systems for applications with previously unmet requirements. The modular combination of scaffolds and functional building blocks enables the engineering of complex systems with biomimetic or new-to-nature functionalities. Inspired by the compartmentalized organization of cells and organelles, lipid or polymer vesicles are widely used as model membrane systems to investigate the translocation of solutes and the transduction of signals by membrane proteins. The bottom-up assembly and functionalization of such artificial compartments enables full control over their composition and can thus provide specifically optimized environments for synthetic biological processes. This review aims to inspire future endeavors by providing a diverse toolbox of molecular modules, engineering methodologies, and different approaches to assemble artificial vesicular systems. Important technical and practical aspects are addressed and selected applications are presented, highlighting particular achievements and limitations of the bottom-up approach. Complementing the cutting-edge technological achievements, fundamental aspects are also discussed to cater to the inherently diverse background of the target audience, which results from the interdisciplinary nature of synthetic biology. The engineering of proteins as functional modules and the use of lipids and block copolymers as scaffold modules for the assembly of functionalized vesicular systems are explored in detail. Particular emphasis is placed on ensuring the controlled assembly of these components into increasingly complex vesicular systems. Finally, all descriptions are presented in the greater context of engineering valuable synthetic biological systems for applications in biocatalysis, biosensing, bioremediation, or targeted drug delivery.
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Polímeros , Biología Sintética , Membranas , ProteínasRESUMEN
Per- and polyfluoroalkyl substances (PFASs) have been detected in an array of environmental media due to their ubiquitous use in industrial and consumer products as well as potential release from fluorochemical manufacturing facilities. During their manufacture, many fluorotelomer (FT) facilities rely on neutral intermediates in polymer production including the FT-alcohols (FTOHs). These PFAS are known to transform to the terminal acids (perfluoro carboxylic acids; PFCAs) at rates that vary with environmental conditions. In the current study on soils from a FT facility, we employed gas chromatography coupled with conventional- and high-resolution mass spectrometry (GC-MS and GC-HRMS) to investigate the profile of these precursor compounds, the intermediary secondary alcohols (sFTOHs), FT-acrylates (FTAcr), and FT-acetates (FTAce) in soils around the former FT-production facility. Of these precursors, the general trend in detection intensity was [FTOHs] > [sFTOHs] > [FTAcrs], while for the FTOHs, homologue intensities generally were [12:2 FTOH] > [14:2 FTOH] > [16:2 FTOH] > [10:2 FTOH] > [18:2 FTOH] > [20:2 FTOH] > [8:2 FTOH] â¼ [6:2 FTOH]. The corresponding terminal acids were also detected in all soil samples and positively correlated with the precursor concentrations. GC-HRMS confirmed the presence of industrial manufacturing byproducts such as FT-ethers and FT-esters and aided in the tentative identification of previously unreported dimers and other compounds. The application of GC-HRMS to the measurement and identification of precursor PFAS is in its infancy, but the methodologies described here will help refine its use in tentatively identifying these compounds in the environment.
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Fluorocarburos , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Suelo/química , Fluorocarburos/análisis , Cromatografía de Gases y Espectrometría de Masas , Monitoreo del Ambiente , Instalaciones Industriales y de FabricaciónRESUMEN
BACKGROUND: Hyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting. METHODS: A lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF. RESULTS: Patiromer was associated with an incremental discounted cost of 4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of 24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions. CONCLUSION: Patiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.
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Heterozygous NRXN1 deletions constitute the most prevalent currently known single-gene mutation associated with schizophrenia, and additionally predispose to multiple other neurodevelopmental disorders. Engineered heterozygous NRXN1 deletions impaired neurotransmitter release in human neurons, suggesting a synaptic pathophysiological mechanism. Utilizing this observation for drug discovery, however, requires confidence in its robustness and validity. Here, we describe a multicenter effort to test the generality of this pivotal observation, using independent analyses at two laboratories of patient-derived and newly engineered human neurons with heterozygous NRXN1 deletions. Using neurons transdifferentiated from induced pluripotent stem cells that were derived from schizophrenia patients carrying heterozygous NRXN1 deletions, we observed the same synaptic impairment as in engineered NRXN1-deficient neurons. This impairment manifested as a large decrease in spontaneous synaptic events, in evoked synaptic responses, and in synaptic paired-pulse depression. Nrxn1-deficient mouse neurons generated from embryonic stem cells by the same method as human neurons did not exhibit impaired neurotransmitter release, suggesting a human-specific phenotype. Human NRXN1 deletions produced a reproducible increase in the levels of CASK, an intracellular NRXN1-binding protein, and were associated with characteristic gene-expression changes. Thus, heterozygous NRXN1 deletions robustly impair synaptic function in human neurons regardless of genetic background, enabling future drug discovery efforts.
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Proteínas de Unión al Calcio/genética , Mutación , Moléculas de Adhesión de Célula Nerviosa/genética , Neuronas/metabolismo , Neurotransmisores/metabolismo , Esquizofrenia/metabolismo , Estudios de Casos y Controles , Transdiferenciación Celular , Células Cultivadas , Estudios de Cohortes , Células Madre Embrionarias/citología , Expresión Génica , Guanilato-Quinasas/metabolismo , Heterocigoto , Humanos , Células Madre Pluripotentes Inducidas/citologíaRESUMEN
This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges. Our findings indicate that FAP patients exhibited higher Social Responsiveness Scale (SRS) scores, suggesting a greater prevalence of autistic traits when compared to unaffected siblings (mean 53.8 vs. 47.4, Wilcoxon p = 0.018). The distribution of SRS scores in cases suggested a bimodal pattern, potentially linked to the location of the APC variant, with scores increasing from the 5' to 3' end of the gene (Pearson's r = 0.33, p = 0.022). While we observed a trend toward lower educational attainment in cases, this difference was not statistically significant. This study is the first to explore the connection between APC variant location and neurodevelopmental traits in FAP, expanding our understanding of the genotype-phenotype correlation. Our results emphasize the importance of clinical assessment for autistic traits in FAP patients, shedding light on the potential role of APC gene variants in these behavioral and cognitive challenges.
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The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a s-hole interaction that is essentially absent in biocatalysis. For this purpose, stibine catalysts were equipped with a biotin derivative and combined with streptavidin mutants to identify an efficient transfer hydrogenation catalyst for the reduction of a fluorogenic quinoline substrate. Increased catalytic activity from wild-type streptavidin to the best mutants coincides with the depth of the s hole on the Sb(V) center, and the emergence of saturation kinetic behavior. Michaelis-Menten analysis reveals transition-state recognition in the low micromolar range, more than three orders of magnitude stronger than the millimolar substrate recognition. Carboxylates preferred by the best mutants contribute to transition-state recognition by hydrogen-bonded ion pairing and anion-π interactions with the emerging pyridinium product. The emergence of challenging stereoselectivity in aqueous systems further emphasizes compatibility of pnictogen bonding with higher order systems catalysis.
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Thiamine diphosphate (ThDP)-dependent enzymes possess the unique ability to generate a carbene within their active site. In this study, we sought to harness this carbene to produce a Au(I) N-heterocyclic complex directly in the active site of ThDP enzymes, thereby establishing a novel platform for artificial metalloenzymes. Because direct metalation of ThDP proved challenging, we synthesized a ThDP mimic that acts as a competitive inhibitor with a high affinity (Ki = 1.5 µM). Upon metalation with Au(I), we observed that the complex became a more potent inhibitor (Ki = 0.7 µM). However, detailed analysis of the inhibition mode, native mass spectrometry, and size exclusion experiments revealed that the complex does not bind specifically to the active site of ThDP enzymes. Instead, it exhibits unspecific binding and exceeds the 1:1 stoichiometry. Similar binding patterns were observed for other Au(I) species. These findings prompt an important question regarding the inherent propensity of ThDP enzymes to bind strongly to Au. If this phenomenon holds true, it could pave the way for the development of Au-based drugs targeting these enzymes.
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Metano , Tiamina Pirofosfato , Tiamina Pirofosfato/metabolismo , Dominio Catalítico , Unión Proteica , TiaminaRESUMEN
Iron-sulfur clusters have been reported to catalyze various redox transformations, including the multielectron reduction of CO2 to hydrocarbons. Herein, we report the design and assembly of an artificial [Fe4S4]-containing Fischer-Tropschase relying on the biotin-streptavidin technology. For this purpose, we synthesized a bis-biotinylated [Fe4S4] cofactor with marked aqueous stability and incorporated it in streptavidin. The effect of the second coordination sphere provided by the protein environment was scrutinized by cyclic voltammetry, highlighting the accessibility of the doubly reduced [Fe4S4] cluster. The Fischer-Tropschase activity was improved by chemo-genetic means for the reduction of CO2 to hydrocarbons with up to 14 turnovers.
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Proteínas Hierro-Azufre , Metaloproteínas , Estreptavidina/metabolismo , Dióxido de Carbono/metabolismo , Metaloproteínas/metabolismo , Hierro/metabolismo , Oxidación-Reducción , Hidrocarburos , Proteínas Hierro-Azufre/metabolismoRESUMEN
Enantioselective C-H amidation offers attractive means to assemble C-N bonds to synthesize high-added value, nitrogen-containing molecules. In recent decades, complementary enzymatic and homogeneous-catalytic strategies for C-H amidation have been reported. Herein, we report on an artificial metalloenzyme (ArM) resulting from anchoring a biotinylated Ir-complex within streptavidin (Sav). The resulting ArM catalyzes the enantioselective amidation of unactivated C(sp3)-H bonds. Chemogenetic optimization of the Ir cofactor and Sav led to significant improvement in both the activity and enantioselectivity. Up to >700 TON and 92% ee for the amidation of unactivated C(sp3)-H bonds was achieved. The single crystal X-ray analysis of the artificial nitrene insertase (ANIase) combined with quantum mechanics-molecular mechanics (QM-MM) calculations sheds light on critical second coordination sphere contacts leading to improved catalytic performance.
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We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.
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Neoplasias , Prioridad del Paciente , Adulto , Humanos , Femenino , Persona de Mediana Edad , Motivación , Enfermedades Raras , Genómica , Neoplasias/genéticaRESUMEN
Pulmonary rehabilitation programmes including aerobic training improve cardiorespiratory fitness in patients with COPD, but the optimal programme design is unclear. We used random effects additive component network meta-analysis to investigate the relative effectiveness of different programme components on fitness measured by VÌO2peak in COPD. The included 59 studies involving 2191 participants demonstrated that VÌO2peak increased after aerobic training of at least moderate intensity with the greatest improvement seen following high intensity training. Lower limb aerobic training (SMD 0.56 95% CI 0.32;0.81, intervention arms=86) and the addition of non-invasive ventilation (SMD 0.55 95% CI 0.04;1.06, intervention arms=4) appeared to offer additional benefit but there was limited evidence for effectiveness of other exercise and non-exercise components.
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Capacidad Cardiovascular , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metaanálisis en Red , Ejercicio Físico , Terapia por Ejercicio , Enfermedad Pulmonar Obstructiva Crónica/rehabilitaciónRESUMEN
Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high-density magnetoencephalography (MEG). The MEG data was transformed into the time-frequency domain and beta responses (16-24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole-brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group-by-time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher-order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge.
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Cannabis , Corteza Motora , Humanos , Encéfalo/diagnóstico por imagen , Magnetoencefalografía/métodos , Mapeo Encefálico , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiologíaRESUMEN
Cyclometalated iridium(III) complexes are frequently employed in organic light emitting diodes, and they are popular photocatalysts for solar energy conversion and synthetic organic chemistry. They luminesce from redox-active excited states that can have high triplet energies and long lifetimes, making them well suited for energy transfer and photoredox catalysis. Homoleptic tris(cyclometalated) iridium(III) complexes are typically very hydrophobic and do not dissolve well in polar solvents, somewhat limiting their application scope. We developed a family of water-soluble sulfonate-decorated variants with tailored redox potentials and excited-state energies to address several key challenges in aqueous photochemistry.First, we aimed at combining enzyme with photoredox catalysis to synthesize enantioenriched products in a cyclic reaction network. Since the employed biocatalyst operates best in aqueous solution, a water-soluble photocatalyst was needed. A new tris(cyclometalated) iridium(III) complex provided enough reducing power for the photochemical reduction of imines to racemic mixtures of amines and furthermore was compatible with monoamine oxidase (MAO-N-9), which deracemized this mixture through a kinetic resolution of the racemic amine via oxidation to the corresponding imine. This process led to the accumulation of the unreactive amine enantiomer over time. In subsequent studies, we discovered that the same iridium(III) complex photoionizes under intense irradiation to give hydrated electrons as a result of consecutive two-photon excitation. With visible light as energy input, hydrated electrons become available in a catalytic fashion, thereby allowing the comparatively mild reduction of substrates that would typically only be reactive under harsher conditions. Finally, we became interested in photochemical upconversion in aqueous solution, for which it was desirable to obtain water-soluble iridium(III) compounds with very high triplet excited-state energies. This goal was achieved through improved ligand design and ultimately enabled sensitized triplet-triplet annihilation upconversion unusually far into the ultraviolet spectral range.Studies of photoredox catalysis, energy transfer catalysis, and photochemical upconversion typically rely on the use of organic solvents. Water could potentially be an attractive alternative in many cases, but photocatalyst development lags somewhat behind for aqueous solution compared to organic solvent. The purpose of this Account is to provide an overview of the breadth of new research perspectives that emerged from the development of water-soluble fac-[Ir(ppy)]3 complexes (ppy = 2-phenylpyridine) with sulfonated ligands. We hope to inspire the use of some of these or related coordination compounds in aqueous photochemistry and to stimulate further conceptual developments at the interfaces of coordination chemistry, photophysics, biocatalysis, and sustainable chemistry.
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Iridio , Compuestos Organometálicos , Aminas , Electrones , Transferencia de Energía , Iridio/química , Ligandos , Compuestos Organometálicos/química , Fotoquímica , Solventes , AguaRESUMEN
By anchoring a metal cofactor within a host protein, so-called artificial metalloenzymes can be generated. Such hybrid catalysts combine the versatility of transition metals in catalyzing new-to-nature reactions with the power of genetic-engineering to evolve proteins. With the aim of gaining better control over second coordination-sphere interactions between a streptavidin host-protein (Sav) and a biotinylated cofactor, we engineered a hydrophobic dimerization domain, borrowed from superoxide dismutase C (SOD), on Sav's biotin-binding vestibule. The influence of the SOD dimerization domain (DD) on the performance of an asymmetric transfer hydrogenase (ATHase) resulting from anchoring a biotinylated Cp*Ir-cofactor - [Cp*Ir(biot-p-L)Cl] (1-Cl) - within Sav-SOD is reported herein. We show that, depending on the nature of the residue at position Sav S112, the introduction of the SOD DD on the biotin-binding vestibule leads to an inversion of configuration of the reduction product, as well as a fivefold increase in catalytic efficiency. The findings are rationalized by QM/MM calculations, combined with X-ray crystallography.
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Biotina , Superóxidos , Estreptavidina/química , Estreptavidina/metabolismo , Biotina/química , Biotina/metabolismo , Dominio Catalítico , Hidrogenación , Superóxido Dismutasa/metabolismoRESUMEN
Quality improvement (QI) initiatives have benefited patients as well as the broader practice of medicine. Large-scale QI has been facilitated by multi-institutional data registries, many of which were formed out of national or international medical society initiatives. With broad participation, QI registries have provided benefits that include but are not limited to establishing treatment guidelines, facilitating research related to uncommon procedures and conditions, and demonstrating the fiscal and clinical value of procedures for both medical providers and health systems. Because of the benefits offered by these databases, Society of Interventional Radiology (SIR) and SIR Foundation have committed to the development of an interventional radiology (IR) clinical data registry known as VIRTEX. A large IR database with participation from a multitude of practice environments has the potential to have a significant positive impact on the specialty through data-driven advances in patient safety and outcomes, clinical research, and reimbursement. This article reviews the current landscape of societal QI programs, presents a vision for a large-scale IR clinical data registry supported by SIR, and discusses the anticipated results that such a framework can produce.
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Mejoramiento de la Calidad , Radiología Intervencionista , Humanos , Sistema de Registros , Sociedades Médicas , Bases de Datos FactualesRESUMEN
Following the end of universal testing in the UK, hospital admissions are a key measure of COVID-19 pandemic pressure. Understanding leading indicators of admissions at the National Health Service (NHS) Trust, regional and national geographies help health services plan for ongoing pressures. We explored the spatio-temporal relationships of leading indicators of hospitalisations across SARS-CoV-2 waves in England. This analysis includes an evaluation of internet search volumes from Google Trends, NHS triage calls and online queries, the NHS COVID-19 app, lateral flow devices (LFDs), and the ZOE app. Data sources were analysed for their feasibility as leading indicators using Granger causality, cross-correlation, and dynamic time warping at fine spatial scales. Google Trends and NHS triages consistently temporally led admissions in most locations, with lead times ranging from 5 to 20 days, whereas an inconsistent relationship was found for the ZOE app, NHS COVID-19 app, and LFD testing, which diminished with spatial resolution, showing cross-correlation of leads between -7 and 7 days. The results indicate that novel surveillance sources can be used effectively to understand the expected healthcare burden within hospital administrative areas though the temporal and spatial heterogeneity of these relationships is a key determinant of their operational public health utility.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Medicina Estatal , Pandemias , Hospitalización , Inglaterra/epidemiología , HospitalesRESUMEN
BACKGROUND: Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. METHODS: Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. RESULTS: The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. CONCLUSION: This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow.