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2.
FEMS Microbiol Ecol ; 100(6)2024 May 14.
Article in English | MEDLINE | ID: mdl-38653723

ABSTRACT

Cyanobacterial mats are commonly reported as hotspots of microbial diversity across polar environments. These thick, multilayered microbial communities provide a refuge from extreme environmental conditions, with many species able to grow and coexist despite the low allochthonous nutrient inputs. The visibly dominant phototrophic biomass is dependent on internal nutrient recycling by heterotrophic organisms within the mats; however, the specific contribution of heterotrophic protists remains little explored. In this study, mat community diversity was examined along a latitudinal gradient (55-83°N), spanning subarctic taiga, tundra, polar desert, and the High Arctic ice shelves. The prokaryotic and eukaryotic communities were targeted, respectively, by V4 16S ribosomal RNA (rRNA) and V9 18S rRNA gene amplicon high-throughput sequencing. Prokaryotic and eukaryotic richness decreased, in tandem with decreasing temperatures and shorter seasons of light availability, from the subarctic to the High Arctic. Taxonomy-based annotation of the protist community revealed diverse phototrophic, mixotrophic, and heterotrophic genera in all mat communities, with fewer parasitic taxa in High Arctic communities. Co-occurrence network analysis identified greater heterogeneity in eukaryotic than prokaryotic community structure among cyanobacterial mats across the Canadian Arctic. Our findings highlight the sensitivity of microbial eukaryotes to environmental gradients across northern high latitudes.


Subject(s)
Biodiversity , Cyanobacteria , RNA, Ribosomal, 16S , Arctic Regions , Cyanobacteria/genetics , Cyanobacteria/classification , Canada , RNA, Ribosomal, 16S/genetics , Microbiota , RNA, Ribosomal, 18S/genetics , Tundra
3.
Obes Surg ; 34(5): 1442-1448, 2024 May.
Article in English | MEDLINE | ID: mdl-38472705

ABSTRACT

INTRODUCTION: Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. METHODS: We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. RESULTS: Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). CONCLUSION: This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.


Subject(s)
Gastric Bypass , Gastritis , Laparoscopy , Obesity, Morbid , Pathology, Surgical , Precancerous Conditions , Stomach Neoplasms , Humans , Endoscopy, Gastrointestinal , Gastrectomy/methods , Gastritis/surgery , Laparoscopy/methods , Obesity, Morbid/surgery , Precancerous Conditions/diagnosis , Retrospective Studies , Stomach Neoplasms/pathology
5.
Water Res ; 252: 121178, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38309063

ABSTRACT

As COVID-19 becomes endemic, public health departments benefit from improved passive indicators, which are independent of voluntary testing data, to estimate the prevalence of COVID-19 in local communities. Quantification of SARS-CoV-2 RNA from wastewater has the potential to be a powerful passive indicator. However, connecting measured SARS-CoV-2 RNA to community prevalence is challenging due to the high noise typical of environmental samples. We have developed a generalized pipeline using in- and out-of-sample model selection to test the ability of different correction models to reduce the variance in wastewater measurements and applied it to data collected from treatment plants in the Chicago area. We built and compared a set of multi-linear regression models, which incorporate pepper mild mottle virus (PMMoV) as a population biomarker, Bovine coronavirus (BCoV) as a recovery control, and wastewater system flow rate into a corrected estimate for SARS-CoV-2 RNA concentration. For our data, models with BCoV performed better than those with PMMoV, but the pipeline should be used to reevaluate any new data set as the sources of variance may change across locations, lab methods, and disease states. Using our best-fit model, we investigated the utility of RNA measurements in wastewater as a leading indicator of COVID-19 trends. We did this in a rolling manner for corrected wastewater data and for other prevalence indicators and statistically compared the temporal relationship between new increases in the wastewater data and those in other prevalence indicators. We found that wastewater trends often lead other COVID-19 indicators in predicting new surges.


Subject(s)
COVID-19 , Public Health , SARS-CoV-2 , Tobamovirus , Animals , Cattle , COVID-19/epidemiology , RNA, Viral , Wastewater , Wastewater-Based Epidemiological Monitoring
6.
Neuroimage ; 285: 120494, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38086495

ABSTRACT

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the established relationship between WMH burden and age. We found that TrUE-Net was highly reliable at identifying WMH regions with low false positive rates, when compared to semi-manual segmentation as the reference standard. TrUE-Net performed similarly or favorably when compared to the other automated techniques. Moreover, TrUE-Net was able to detect relationships between WMH and age to a similar degree as the reference standard semi-manual segmentation at both the global and regional level. These results support the use of TrUE-Net for identifying WMH at the global or regional level, including in large, combined datasets.


Subject(s)
Leukoaraiosis , White Matter , Humans , White Matter/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Algorithms , Aging
7.
Br J Surg ; 111(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-37981863

ABSTRACT

BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.


Subject(s)
Bariatric Surgery , Gastric Bypass , Laparoscopy , Obesity, Morbid , Robotic Surgical Procedures , Humans , Female , Aged , Adult , Male , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Benchmarking , Retrospective Studies , Bariatric Surgery/adverse effects , Laparoscopy/adverse effects , Gastrectomy/adverse effects , Treatment Outcome
8.
BMJ Open ; 13(11): e075558, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37968006

ABSTRACT

INTRODUCTION: The English National Health Service (NHS) Diabetic Eye Screening Programme (DESP) performs around 2.3 million eye screening appointments annually, generating approximately 13 million retinal images that are graded by humans for the presence or severity of diabetic retinopathy. Previous research has shown that automated retinal image analysis systems, including artificial intelligence (AI), can identify images with no disease from those with diabetic retinopathy as safely and effectively as human graders, and could significantly reduce the workload for human graders. Some algorithms can also determine the level of severity of the retinopathy with similar performance to humans. There is a need to examine perceptions and concerns surrounding AI-assisted eye-screening among people living with diabetes and NHS staff, if AI was to be introduced into the DESP, to identify factors that may influence acceptance of this technology. METHODS AND ANALYSIS: People living with diabetes and staff from the North East London (NEL) NHS DESP were invited to participate in two respective focus groups to codesign two online surveys exploring their perceptions and concerns around the potential introduction of AI-assisted screening.Focus group participants were representative of the local population in terms of ages and ethnicity. Participants' feedback was taken into consideration to update surveys which were circulated for further feedback. Surveys will be piloted at the NEL DESP and followed by semistructured interviews to assess accessibility, usability and to validate the surveys.Validated surveys will be distributed by other NHS DESP sites, and also via patient groups on social media, relevant charities and the British Association of Retinal Screeners. Post-survey evaluative interviews will be undertaken among those who consent to participate in further research. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the NHS Research Ethics Committee (IRAS ID: 316631). Survey results will be shared and discussed with focus groups to facilitate preparation of findings for publication and to inform codesign of outreach activities to address concerns and perceptions identified.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , State Medicine , Artificial Intelligence , Secondary Care , Mass Screening/methods , Diabetes Mellitus/diagnosis
9.
Article in English | MEDLINE | ID: mdl-37949472

ABSTRACT

INTRODUCTION: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population. RESEARCH DESIGN AND METHODS: North East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR. RESULTS: There were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8-8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p<0.001) and both eyes (HR 7.88, 95% CI 7.59 to 8.18, p<0.001). Black and South Asian individuals had higher STDR hazards than white individuals (HR 1.57, 95% CI 1.50 to 1.64 and HR 1.36, 95% CI 1.31 to 1.42, respectively). Additionally, every 5-year increase in age at inclusion was associated with an 8% reduction in STDR hazards (p<0.001). CONCLUSIONS: Ethnic disparities exist in a health system limited by capacity rather than patient economic circumstances. Diabetic retinopathy at first screen is a strong determinant of STDR development. By using basic demographic characteristics, screening programmes or clinical practices can stratify risk for sight-threatening diabetic retinopathy development.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Retrospective Studies , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Mass Screening , Incidence , London/epidemiology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology
10.
Br J Ophthalmol ; 107(12): 1839-1845, 2023 11 22.
Article in English | MEDLINE | ID: mdl-37875374

ABSTRACT

BACKGROUND/AIMS: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual screening. Less frequent screening has been advocated among PLD without diabetic retinopathy (DR), but evidence for each ethnic group is limited. We examined the potential effect of biennial versus annual screening on the detection of sight-threatening diabetic retinopathy (STDR) and proliferative diabetic retinopathy (PDR) among PLD without DR from a large urban multi-ethnic English DESP. METHODS: PLD in North-East London DESP (January 2012 to December 2021) with no DR on two prior consecutive screening visits with up to 8 years of follow-up were examined. Annual STDR and PDR incidence rates, overall and by ethnicity, were quantified. Delays in identification of STDR and PDR events had 2-year screening intervals been used were determined. FINDINGS: Among 82 782 PLD (37% white, 36% South Asian, and 16% black people), there were 1788 incident STDR cases over mean (SD) 4.3 (2.4) years (STDR rate 0.51, 95% CI 0.47 to 0.55 per 100-person-years). STDR incidence rates per 100-person-years by ethnicity were 0.55 (95% CI 0.48 to 0.62) for South Asian, 0.34 (95% CI 0.29 to 0.40) for white, and 0.77 (95% CI 0.65 to 0.90) for black people. Biennial screening would have delayed diagnosis by 1 year for 56.3% (1007/1788) with STDR and 43.6% (45/103) with PDR. Standardised cumulative rates of delayed STDR per 100 000 persons for each ethnic group were 1904 (95% CI 1683 to 2154) for black people, 1276 (95% CI 1153 to 1412) for South Asian people, and 844 (95% CI 745 to 955) for white people. INTERPRETATION: Biennial screening would have delayed detection of some STDR and PDR by 1 year, especially among those of black ethnic origin, leading to healthcare inequalities.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Humans , Asian People , Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/etiology , Ethnicity , Mass Screening , Retrospective Studies , White People , Black People
11.
J Med Chem ; 66(19): 13384-13399, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37774359

ABSTRACT

Protein tyrosine phosphatase SHP2 mediates RAS-driven MAPK signaling and has emerged in recent years as a target of interest in oncology, both for treating with a single agent and in combination with a KRAS inhibitor. We were drawn to the pharmacological potential of SHP2 inhibition, especially following the initial observation that drug-like compounds could bind an allosteric site and enforce a closed, inactive state of the enzyme. Here, we describe the identification and characterization of GDC-1971 (formerly RLY-1971), a SHP2 inhibitor currently in clinical trials in combination with KRAS G12C inhibitor divarasib (GDC-6036) for the treatment of solid tumors driven by a KRAS G12C mutation.

12.
PLoS One ; 18(8): e0290278, 2023.
Article in English | MEDLINE | ID: mdl-37616264

ABSTRACT

PURPOSE: To evaluate the test performance of the QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) software in detecting retinal features from retinal images captured by health care professionals in a Danish high street optician chain, compared with test performance from other large population studies (i.e., UK Biobank) where retinal images were captured by non-experts. METHOD: The dataset FOREVERP (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability, Pilot) contains retinal images obtained from a Danish high street optician chain. The QUARTZ algorithm utilizes both image processing and machine learning methods to determine retinal image quality, vessel segmentation, vessel width, vessel classification (arterioles or venules), and optic disc localization. Outcomes were evaluated by metrics including sensitivity, specificity, and accuracy and compared to human expert ground truths. RESULTS: QUARTZ's performance was evaluated on a subset of 3,682 images from the FOREVERP database. 80.55% of the FOREVERP images were labelled as being of adequate quality compared to 71.53% of UK Biobank images, with a vessel segmentation sensitivity of 74.64% and specificity of 98.41% (FOREVERP) compared with a sensitivity of 69.12% and specificity of 98.88% (UK Biobank). The mean (± standard deviation) vessel width of the ground truth was 16.21 (4.73) pixels compared to that predicted by QUARTZ of 17.01 (4.49) pixels, resulting in a difference of -0.8 (1.96) pixels. The differences were stable across a range of vessels. The detection rate for optic disc localisation was similar for the two datasets. CONCLUSION: QUARTZ showed high performance when evaluated on the FOREVERP dataset, and demonstrated robustness across datasets, providing validity to direct comparisons and pooling of retinal feature measures across data sources.


Subject(s)
Optic Disk , Quartz , Humans , Reproducibility of Results , Allied Health Personnel , Denmark
13.
Mol Biol Evol ; 40(8)2023 08 03.
Article in English | MEDLINE | ID: mdl-37552897

ABSTRACT

The clade Pancrustacea, comprising crustaceans and hexapods, is the most diverse group of animals on earth, containing over 80% of animal species and half of animal biomass. It has been the subject of several recent phylogenomic analyses, yet relationships within Pancrustacea show a notable lack of stability. Here, the phylogeny is estimated with expanded taxon sampling, particularly of malacostracans. We show small changes in taxon sampling have large impacts on phylogenetic estimation. By analyzing identical orthologs between two slightly different taxon sets, we show that the differences in the resulting topologies are due primarily to the effects of taxon sampling on the phylogenetic reconstruction method. We compare trees resulting from our phylogenomic analyses with those from the literature to explore the large tree space of pancrustacean phylogenetic hypotheses and find that statistical topology tests reject the previously published trees in favor of the maximum likelihood trees produced here. Our results reject several clades including Caridoida, Eucarida, Multicrustacea, Vericrustacea, and Syncarida. Notably, we find Copepoda nested within Allotriocarida with high support and recover a novel relationship between decapods, euphausiids, and syncarids that we refer to as the Syneucarida. With denser taxon sampling, we find Stomatopoda sister to this latter clade, which we collectively name Stomatocarida, dividing Malacostraca into three clades: Leptostraca, Peracarida, and Stomatocarida. A new Bayesian divergence time estimation is conducted using 13 vetted fossils. We review our results in the context of other pancrustacean phylogenetic hypotheses and highlight 15 key taxa to sample in future studies.


Subject(s)
Arthropods , Copepoda , Animals , Phylogeny , Bayes Theorem , Insecta
14.
J Am Heart Assoc ; 12(14): e029346, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37449585

ABSTRACT

Background Prehospital activation of the cardiac catheter laboratory is associated with significant improvements in ST-segment-elevation myocardial infarction (STEMI) performance measures. However, there are equivocal data, particularly within Australia, regarding its influence on mortality. We assessed the association of prehospital activation on performance measures and mortality in patients with STEMI treated with primary percutaneous coronary intervention from the Queensland Cardiac Outcomes Registry (QCOR). Methods and Results Consecutive ambulance-transported patients with STEMI treated with primary percutaneous coronary intervention were analyzed from January 1, 2017 to December 31, 2020 from the QCOR. The total and direct effects of prehospital activation on the primary outcomes (30-day and 1-year cardiovascular mortality) were estimated using logistic regression analyses. Secondary outcomes were STEMI performance measures. Among 2498 patients (mean age: 62.2±12.4 years; 79.2% male), 73% underwent prehospital activation. Median door-to-balloon time (34 minutes [26-46] versus 86 minutes [68-113]; P<0.001), first-electrocardiograph-to-balloon time (83.5 minutes [72-98] versus 109 minutes [81-139]; P<0.001), and proportion of patients meeting STEMI targets (door-to-balloon <60 minutes 90% versus 16%; P<0.001), electrocardiograph-to-balloon time <90 minutes (62% versus 33%; P<0.001) were significantly improved with prehospital activation. Prehospital activation was associated with significantly lower 30-day (1.6% versus 6.6%; P<0.001) and 1-year cardiovascular mortality (2.9% versus 9.5%; P<0.001). After adjustment, no prehospital activation was strongly associated with increased 30-day (odds ratio [OR], 3.6 [95% CI, 2.2-6.0], P<0.001) and 1-year cardiovascular mortality (OR, 3.0 [95% CI, 2.0-4.6]; P<0.001). Conclusions Prehospital activation of cardiac catheterization laboratory for primary percutaneous coronary intervention was associated with significantly shorter time to reperfusion, achievement of STEMI performance measures, and lower 30-day and 1-year cardiovascular mortality.


Subject(s)
Angioplasty, Balloon, Coronary , Emergency Medical Services , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Middle Aged , Aged , Female , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/surgery , Percutaneous Coronary Intervention/adverse effects , Electrocardiography , Cardiac Catheterization
15.
BMJ Open ; 13(6): e069258, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37355273

ABSTRACT

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.


Subject(s)
Dementia , Eye Diseases , Humans , Prospective Studies , Biological Specimen Banks , Retina/diagnostic imaging , Dementia/diagnostic imaging , United Kingdom/epidemiology
17.
PLoS Genet ; 19(2): e1010583, 2023 02.
Article in English | MEDLINE | ID: mdl-36757925

ABSTRACT

The eye is the window through which light is transmitted and visual sensory signalling originates. It is also a window through which elements of the cardiovascular and nervous systems can be directly inspected, using ophthalmoscopy or retinal imaging. Measurements of ocular parameters may therefore offer important information on the physiology and homeostasis of these two important systems. Here we report the results of a genetic characterisation of retinal vasculature. Four genome-wide association studies performed on different aspects of retinal vasculometry phenotypes, such as arteriolar and venular tortuosity and width, found significant similarities between retinal vascular characteristics and cardiometabolic health. Our analyses identified 119 different regions of association with traits of retinal vasculature, including 89 loci associated arteriolar tortuosity, the strongest of which was rs35131825 (p = 2.00×10-108), 2 loci with arteriolar width (rs12969347, p = 3.30×10-09 and rs5442, p = 1.9E-15), 17 other loci associated with venular tortuosity and 11 novel associations with venular width. Our causal inference analyses also found that factors linked to arteriolar tortuosity cause elevated diastolic blood pressure and not vice versa.


Subject(s)
Genome-Wide Association Study , Retinal Vessels , Risk Factors , Retina , Phenotype
18.
Biomech Model Mechanobiol ; 22(2): 729-738, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36602717

ABSTRACT

It remains unknown that the degree of bias in computational fluid dynamics results without considering coronary cyclic bending. This study aims to investigate the influence of different rates of coronary cyclic bending on coronary hemodynamics. To model coronary bending, a multi-ring-controlled fluid-structural interaction model was designed. A coronary artery was simulated with various cyclic bending rates (0.5, 0.75 and 1 s, corresponding to heart rates of 120, 80 and 60 bpm) and compared against a stable model. The simulated results show that the hemodynamic parameters of vortex Q-criterion, temporal wall shear stress (WSS), time-averaged WSS (TaWSS) and oscillatory shear index (OSI) were sensitive to the changes in cyclic rate. A higher heart rate resulted in higher magnitude and larger variance in the hemodynamic parameters. Whereas, the values and distributions of flow velocity and relative residence time (RRT) did not show significant differences between different bending periods. This study suggests that a stable coronary model is not sufficient to represent the hemodynamics in a bending coronary artery. Different heart rate conditions were found to have significant impact on the hemodynamic parameters. Thus, cyclic bending should be considered to mimic the realistic hemodynamics in future patient-specific coronary hemodynamics studies.


Subject(s)
Heart , Hemodynamics , Humans , Heart/physiology , Coronary Vessels , Models, Cardiovascular , Stress, Mechanical
19.
Br J Ophthalmol ; 107(12): 1846-1851, 2023 11 22.
Article in English | MEDLINE | ID: mdl-36241373

ABSTRACT

AIMS: To analyse the prevalence of visual impairment (VI), compare it to certification of visual impairment (CVI) and analyse VI associations in patients with diabetic retinopathy (DR). METHODS: Retrospective cohort study, which included 8007 patients with DR referred from the English diabetic eye screening programme to a tertiary referral eye hospital. Main outcome measure was VI, defined as vision in the best eye of <6/24. We conducted a multivariable logistic regression for VI as primary outcome of interest, controlling for age, sex, type of diabetes, baseline DR grade, ethnicity and index of multiple deprivation (IMD). RESULTS: Mean age was 64.5 (SD 13.6) years; 61% of patients were men; and 31% of South Asian ethnicity. There were 68 patients with CVI during the study period, and 84% (272/325) of patients with VI did not have CVI after a mean follow-up of 1.87 (SD ±0.86) years. Older age showed a positive association with VI (OR per decade rise 1.88, 95% CI 1.70 to 2.08; p=1.8×10-34). Men had a lower risk of VI (OR 0.62, 95% CI 0.50 to 0.79, p=6.0×10-5), and less deprivation had a graded inverse association with VI (OR per IMD category increase 0.83, 95% CI 0.74 to 0.93, p value for linear trend 0.002). CONCLUSION: The majority of people with vision impairment are not registered at the point of care, which could translate to underestimation of diabetes-related VI and all-cause VI at a national level if replicated at other centres. Further work is needed to explore rates of VI and uptake of registration.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Vision, Low , Male , Humans , Middle Aged , Female , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Retrospective Studies , Tertiary Healthcare , Visual Acuity , Vision, Low/etiology , Hospitals , United Kingdom/epidemiology
20.
Crit Care Res Pract ; 2022: 8343785, 2022.
Article in English | MEDLINE | ID: mdl-36405398

ABSTRACT

Background: When compared to left ventricular ejection fraction (LVEF), previous studies have suggested the superiority of wall motion score index (WMSI) in predicting cardiac events in patients who have suffered acute myocardial infarction. However, there are limited studies assessing WMSI and mortality in ST-segment elevation myocardial infarction (STEMI). We aimed to compare the prognostic value of WMSI in a cohort of STEMI patients treated with primary percutaneous coronary intervention (PCI). Methods: A comparison of WMSI, LVEF, and all-cause mortality in STEMI patients treated with primary PCI between January 2008 and December 2020 was performed. The prognostic value of WMSI, LVEF, and traditional risk scores (TIMI, GRACE) were compared using multivariable logistic regression modelling. Results: Among 1181 patients, 27 died within 30-days (2.3%) and 49 died within 12 months (4.2%). WMSI ≥1.8 was associated with poorer survival at 12-months (9.2% vs 1.5%; p < 0.001). When used as the only classifier for predicting 12-month mortality, the discriminatory ability of WMSI (area under the curve (AUC): 0.77; 95% CI: 0.68-0.84) was significantly better than LVEF (AUC: 0.71; 95% CI: 0.61-0.79; p=0.034). After multivariable modelling, the AUC was comparable between models with either WMSI (AUC: 0.89; 95% CI: 0.85-0.94) or LVEF (AUC: 0.87; 95% CI: 0.83-0.92; p < 0.08) yet performed significantly better than TIMI (AUC: 0.71; 95% CI: 0.62-0.79; p < 0.001), or GRACE (AUC: 0.63; 95% CI: 0.54-0.71; p < 0.001) risk scores. Conclusions: When examined individually, WMSI is a superior predictor of 12-month mortality over LVEF in STEMI patients treated with primary PCI. When examined in multivariable predictive models, WMSI and LVEF perform very well at predicting 12-month mortality, especially when compared to existing STEMI risk scores.

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