Suchergebnisse

The specialty of fetal surgery or fetal intervention is one of the most exciting emerging fields of modern medicine. It is made possible by decades of major developments in antenatal imaging, obstetric anaesthesia, fetal medicine, paediatric surgery, and of course by the bold and novel practitioners willing to take new steps to advance the field. Beginning in the 1970s, it has now reached a stage of maturity where there are several established in utero procedures and countless clinical trials and studies to develop more. But what is the legal situation that fetal surgeons find themselves in? What are the rights and legal protections for the fetus and the mother, both of which are arguably the patient? This article will address this question, discussing and summarising the current legal frameworks governing fetal surgery in the jurisdictions of the United Kingdom, European Court of Human Rights, and the United States of America as well as discuss what the future may hold and how researchers and physicians in the specialty can best navigate the legal environment.

BACKGROUND: In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. METHODS: In this prospective cohort study, data from UK school-aged children (age 5-17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5-11 years) and older (age 12-17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. FINDINGS: 258 790 children aged 5-17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3-11) versus 3 days (2-7) in children testing negative, and was positively associated with age (Spearman's rank-order rs 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3-12) than younger children (5 days, 2-9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1-4) compared with the first week of illness (median 6 symptoms, 4-8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7-11·0 vs 8, 6-9) and after day 28 (5 symptoms, IQR 1·5-6·5 vs 2, 1-4) than did children who tested positive for SARS-CoV-2. INTERPRETATION: Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. FUNDING: Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.

Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots. Findings: From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023–17 885) daily cases, a prevalence of 0·53% (0·45–0·60), and R(t) of 1·17 (1·15–1·19) in England. On a geographically granular level, on Sept 28, 2020, we detected 15 (75%) of the 20 regions with highest incidence according to government test data. Interpretation: Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance. Funding: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer's Society, Chronic Disease Research Foundation.

BACKGROUND: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. METHODS: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots. FINDINGS: From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023–17 885) daily cases, a prevalence of 0·53% (0·45–0·60), and R(t) of 1·17 (1·15–1·19) in England. On a geographically granular level, on Sept ...

BACKGROUND: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. METHODS: We performed modelling on longitudinal, self-reported data from users of the COVID Symptom Study app in England between 24 March and 29 September, 2020. Combining a symptom-based predictive model for COVID-19 positivity and RT-PCR tests provided by the Department of Health we were able to estimate disease incidence, prevalence and effective reproduction number. Geographically granular estimates were used to highlight regions with rapidly increasing case numbers, or hotspots. FINDINGS: More than 2.6 million app users in England provided 115 million daily reports of their symptoms, and recorded the results of 170,000 PCR tests. On a national level our estimates of incidence and prevalence showed similar sensitivity to changes as two national community surveys: the ONS and REACT studies. On a geographically granular level, our estimates were able to highlight regions before they were subject to local government lockdowns. Between 12 May and 29 September we were able to flag between 35–80% of regions appearing in the Government's hotspot list. INTERPRETATION: Self-reported data from mobile applications can provide a cost-effective and agile resource to inform a fast-moving pandemic, serving as an independent and complementary resource to more traditional instruments for disease surveillance. FUNDING: Zoe Global Limited, Department of Health, Wellcome Trust, EPSRC, NIHR, MRC, Alzheimer's Society.

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy. ; This work was supported by an Alzheimer's Research UK Senior Research Fellowship and ESRC/NIHR (ES/L001810/1) and EPSRC (EP/M006093/1) grants to S.J.C. K.Y. is funded by the Alzheimer's Society. The Dementia Research Centre is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation. This work was also supported by the NIHR Queen Square Dementia Biomedical Research Unit, and the NIHR UCL/H Biomedical Research Centre. N.F. is funded by EPSRC (EP/M006093/1). R.V.M. was supported by the EPSRC Centre For Doctoral Training in Medical Imaging with grant EP/L016478/1. R.W.P. is an NIHR Academic Clinical lecturer. J.M.S. acknowledges the support of the Wolfson Foundation, EPSRC (EP/J020990/1), MRC (MR/L023784/1), ARUK (ARUK-Network 2012–6-ICE; ARUK-PG2017–1946), Brain Research Trust (UCC14191) and European Union's Horizon 2020 research and innovation programme (Grant 666992). T.J.S. was supported by an Alzheimer's Research UK Research Fellowship. J.W. was supported by funding from the Alzheimer's Society and the NIHR UCLH Biomedical Research Centre. Some authors (N.P.O., S.O., D.C.A., and J.M.S.) acknowledge funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 666992. The work was also supported by funding from National Institutes of Health R01-AG045611 (to G.D.R.), P50-AG23501 (to B.L.M. and G.D.R.)

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.