Showing papers by "University of London published in 2019"

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients

Abstract: Background Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) an...

Performance of neural network basecalling tools for Oxford Nanopore sequencing.

Abstract: Basecalling, the computational process of translating raw electrical signal to nucleotide sequence, is of critical importance to the sequencing platforms produced by Oxford Nanopore Technologies (ONT). Here, we examine the performance of different basecalling tools, looking at accuracy at the level of bases within individual reads and at majority-rule consensus basecalls in an assembly. We also investigate some additional aspects of basecalling: training using a taxon-specific dataset, using a larger neural network model and improving consensus basecalls in an assembly by additional signal-level analysis with Nanopolish. Training basecallers on taxon-specific data results in a significant boost in consensus accuracy, mostly due to the reduction of errors in methylation motifs. A larger neural network is able to improve both read and consensus accuracy, but at a cost to speed. Improving consensus sequences (‘polishing’) with Nanopolish somewhat negates the accuracy differences in basecallers, but pre-polish accuracy does have an effect on post-polish accuracy. Basecalling accuracy has seen significant improvements over the last 2 years. The current version of ONT’s Guppy basecaller performs well overall, with good accuracy and fast performance. If higher accuracy is required, users should consider producing a custom model using a larger neural network and/or training data from the same species.

Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.

Abstract: Objective To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15–49 years, in 2016.

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus.

Abstract: The global population at risk from mosquito-borne diseases-including dengue, yellow fever, chikungunya and Zika-is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.

The current and future global distribution and population at risk of dengue

Abstract: Dengue is a mosquito-borne viral infection that has spread throughout the tropical world over the past 60 years and now affects over half the world's population. The geographical range of dengue is expected to further expand due to ongoing global phenomena including climate change and urbanization. We applied statistical mapping techniques to the most extensive database of case locations to date to predict global environmental suitability for the virus as of 2015. We then made use of climate, population and socioeconomic projections for the years 2020, 2050 and 2080 to project future changes in virus suitability and human population at risk. This study is the first to consider the spread of Aedes mosquito vectors to project dengue suitability. Our projections provide a key missing piece of evidence for the changing global threat of vector-borne disease and will help decision-makers worldwide to better prepare for and respond to future changes in dengue risk.

The Imperative for Climate Action to Protect Health.

Abstract: The Imperative for Climate Action to Protect Health The WHO predicts that 250,000 deaths yearly from 2030 to 2050 will be attributable to climate change. Reductions in greenhouse-gas emissions woul...

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease

Abstract: Background Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients wit...

Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

Abstract: The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.

Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans

Abstract: Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention : A Consensus Document From the Academic Research Consortium for High Bleeding Risk

Abstract: Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limi ...

Human placenta has no microbiome but can contain potential pathogens.

Abstract: We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae, a major cause of neonatal sepsis.

Effects of fossil fuel and total anthropogenic emission removal on public health and climate.

Abstract: Anthropogenic greenhouse gases and aerosols are associated with climate change and human health risks. We used a global model to estimate the climate and public health outcomes attributable to fossil fuel use, indicating the potential benefits of a phaseout. We show that it can avoid an excess mortality rate of 3.61 (2.96-4.21) million per year from outdoor air pollution worldwide. This could be up to 5.55 (4.52-6.52) million per year by additionally controlling nonfossil anthropogenic sources. Globally, fossil-fuel-related emissions account for about 65% of the excess mortality, and 70% of the climate cooling by anthropogenic aerosols. The chemical influence of air pollution on aeolian dust contributes to the aerosol cooling. Because aerosols affect the hydrologic cycle, removing the anthropogenic emissions in the model increases rainfall by 10-70% over densely populated regions in India and 10-30% over northern China, and by 10-40% over Central America, West Africa, and the drought-prone Sahel, thus contributing to water and food security. Since aerosols mask the anthropogenic rise in global temperature, removing fossil-fuel-generated particles liberates 0.51(±0.03) °C and all pollution particles 0.73(±0.03) °C warming, reaching around 2 °C over North America and Northeast Asia. The steep temperature increase from removing aerosols can be moderated to about 0.36(±0.06) °C globally by the simultaneous reduction of tropospheric ozone and methane. We conclude that a rapid phaseout of fossil-fuel-related emissions and major reductions of other anthropogenic sources are needed to save millions of lives, restore aerosol-perturbed rainfall patterns, and limit global warming to 2 °C.

A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy.

Abstract: Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain-affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent and longer-term research is sorely needed to inform and guide evidence-based response and management of monkeypox outbreaks.

REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes

Abstract: Copyright: 2018. Due to copyright restrictions, the attached PDF file only contains the abstract version of the full-text item. For access to the full-text item, please consult the publisher's website. The definitive version of the work is published in Nature Microbiology, vol 4, pp. 46-54

Stigma in health facilities: why it matters and how we can change it

Abstract: Stigma in health facilities undermines diagnosis, treatment, and successful health outcomes. Addressing stigma is fundamental to delivering quality healthcare and achieving optimal health. This correspondence article seeks to assess how developments over the past 5 years have contributed to the state of programmatic knowledge—both approaches and methods—regarding interventions to reduce stigma in health facilities, and explores the potential to concurrently address multiple health condition stigmas. It is supported by findings from a systematic review of published articles indexed in PubMed, Psychinfo and Web of Science, and in the United States Agency for International Development’s Development Experience Clearinghouse, which was conducted in February 2018 and restricted to the past 5 years. Forty-two studies met inclusion criteria and provided insight on interventions to reduce HIV, mental illness, or substance abuse stigma. Multiple common approaches to address stigma in health facilities emerged, which were implemented in a variety of ways. The literature search identified key gaps including a dearth of stigma reduction interventions in health facilities that focus on tuberculosis, diabetes, leprosy, or cancer; target multiple cadres of staff or multiple ecological levels; leverage interactive technology; or address stigma experienced by health workers. Preliminary results from ongoing innovative responses to these gaps are also described. The current evidence base of stigma reduction in health facilities provides a solid foundation to develop and implement interventions. However, gaps exist and merit further work. Future investment in health facility stigma reduction should prioritize the involvement of clients living with the stigmatized condition or behavior and health workers living with stigmatized conditions and should address both individual and structural level stigma.

The dark side of coproduction: do the costs outweigh the benefits for health research?

Abstract: Coproduction, a collaborative model of research that includes stakeholders in the research process, has been widely advocated as a means of facilitating research use and impact. We summarise the arguments in favour of coproduction, the different approaches to establishing coproductive work and their costs, and offer some advice as to when and how to consider coproduction. Despite the multiplicity of reasons and incentives to coproduce, there is little consensus about what coproduction is, why we do it, what effects we are trying to achieve, or the best coproduction techniques to achieve policy, practice or population health change. Furthermore, coproduction is not free risk or cost. Tensions can arise throughout coproduced research processes between the different interests involved. We identify five types of costs associated with coproduced research affecting the research itself, the research process, professional risks for researchers and stakeholders, personal risks for researchers and stakeholders, and risks to the wider cause of scholarship. Yet, these costs are rarely referred to in the literature, which generally calls for greater inclusion of stakeholders in research processes, focusing exclusively on potential positives. There are few tools to help researchers avoid or alleviate risks to themselves and their stakeholders. First, we recommend identifying specific motivations for coproduction and clarifying exactly which outcomes are required for whom for any particular piece of research. Second, we suggest selecting strategies specifically designed to enable these outcomes to be achieved, and properly evaluated. Finally, in the absence of strong evidence about the impact and process of coproduction, we advise a cautious approach to coproduction. This would involve conscious and reflective research practice, evaluation of how coproduced research practices change outcomes, and exploration of the costs and benefits of coproduction. We propose some preliminary advice to help decide when coproduction is likely to be more or less useful.

Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

Abstract: In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Blood Flow Restriction Exercise: Considerations of Methodology, Application, and Safety

Abstract: The current manuscript sets out a position stand for blood flow restriction (BFR) exercise, focusing on the methodology, application and safety of this mode of training. With the emergence of this technique and the wide variety of applications within the literature, the aim of this position stand is to set out a current research informed guide to BFR training to practitioners. This covers the use of BFR to enhance muscular strength and hypertrophy via training with resistance and aerobic exercise and preventing muscle atrophy using the technique passively. The authorship team for this article was selected from the researchers focused in BFR training research with expertise in exercise science, strength and conditioning and sports medicine.

Mapping HIV prevalence in sub-Saharan Africa between 2000 and 2017

Abstract: HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15–49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa. Fine-scale estimates of the prevalence of HIV in adults across sub-Saharan Africa reveal substantial within-country variation and local differences in both the direction and rate of change in the prevalence of HIV between 2000 and 2017.

Deep Affect Prediction in-the-Wild: Aff-Wild Database and Challenge, Deep Architectures, and Beyond

Abstract: Automatic understanding of human affect using visual signals is of great importance in everyday human–machine interactions. Appraising human emotional states, behaviors and reactions displayed in real-world settings, can be accomplished using latent continuous dimensions (e.g., the circumplex model of affect). Valence (i.e., how positive or negative is an emotion) and arousal (i.e., power of the activation of the emotion) constitute popular and effective representations for affect. Nevertheless, the majority of collected datasets this far, although containing naturalistic emotional states, have been captured in highly controlled recording conditions. In this paper, we introduce the Aff-Wild benchmark for training and evaluating affect recognition algorithms. We also report on the results of the First Affect-in-the-wild Challenge (Aff-Wild Challenge) that was recently organized in conjunction with CVPR 2017 on the Aff-Wild database, and was the first ever challenge on the estimation of valence and arousal in-the-wild. Furthermore, we design and extensively train an end-to-end deep neural architecture which performs prediction of continuous emotion dimensions based on visual cues. The proposed deep learning architecture, AffWildNet, includes convolutional and recurrent neural network layers, exploiting the invariant properties of convolutional features, while also modeling temporal dynamics that arise in human behavior via the recurrent layers. The AffWildNet produced state-of-the-art results on the Aff-Wild Challenge. We then exploit the AffWild database for learning features, which can be used as priors for achieving best performances both for dimensional, as well as categorical emotion recognition, using the RECOLA, AFEW-VA and EmotiW 2017 datasets, compared to all other methods designed for the same goal. The database and emotion recognition models are available at http://ibug.doc.ic.ac.uk/resources/first-affect-wild-challenge .