To examine the real-world performance of a support vector machine learning software (RetinaLyze) in order to identify the possible presence of diabetic retinopathy (DR) in patients with diabetes via ...software implementation in clinical practice.
1001 eyes from 1001 patients-one eye per patient-participating in the Danish National Screening Programme were included. Three independent ophthalmologists graded all eyes according to the International Clinical Diabetic Retinopathy Disease Severity Scale with the exact level of disease being determined by majority decision. The software detected DR and no DR and was compared to the ophthalmologists' gradings.
At a clinical chosen threshold, the software showed a sensitivity, specificity, positive predictive value and negative predictive value of 84.9% (95% CI: 81.8-87.9), 89.9% (95% CI: 86.8-92.7), 92.1% (95% CI: 89.7-94.4), and 81.0% (95% CI: 77.2-84.7), respectively, when compared to human grading. The results from the routine screening were 87.0% (95% CI: 84.2-89.7), 85.3% (95% CI: 81.8-88.6), 89.2% (95% CI: 86.3-91.7), and 82.5% (95% CI: 78.5-86.0), respectively. AUC was 93.4%. The reference graders Conger's Exact Kappa was 0.827.
The software performed similarly to routine grading with overlapping confidence intervals, indicating comparable performance between the two groups. The intergrader agreement was satisfactory. However, evaluating the updated software alongside updated clinical procedures is crucial. It is therefore recommended that further clinical testing before implementation of the software as a decision support tool is conducted.
The search to identify disease-susceptible genes requires access to biological material from numerous well-characterized subjects. Archived residual dried blood spot (DBS) samples, also known as ...Guthrie cards, from national newborn screening programs may provide a DNA source for entire populations. Combined with clinical information from medical registries, DBS samples could provide a rich source for productive research. However, the amounts of DNA which can be extracted from these precious samples are minute and may be prohibitive for numerous genotypings. Previously, we demonstrated that DBS DNA can be whole-genome amplified and used for reliable genetic analysis on different platforms, including genome-wide scanning arrays. However, it remains unclear whether this approach is workable on a large sample scale. We examined the robustness of using DBS samples for whole-genome amplification following genome-wide scanning, using arrays from Illumina and Affymetrix.
This study is based on 4,641 DBS samples from the Danish Newborn Screening Biobank, extracted for three separate genome-wide association studies. The amount of amplified DNA was significantly (P < 0.05) affected by the year of storage and storage conditions. Nine (0.2%) DBS samples failed whole-genome amplification. A total of 4,586 (98.8%) samples met our criterion of success of a genetic call-rate above 97%. The three studies used different arrays, with mean genotyping call-rates of 99.385% (Illumina Infinium Human610-Quad), 99.722% (Illumina Infinium HD HumanOmni1-Quad), and 99.206% (Affymetrix Axiom Genome-Wide CEU). We observed a concordance rate of 99.997% in the 38 methodological replications, and 99.999% in the 27 technical replications. Handling variables such as time of storage, storage conditions and type of filter paper were shown too significantly (P < 0.05) affect the genotype call-rates in some of the arrays, although the effect was minimal.
Our study indicates that archived DBS samples from the Danish Newborn Screening Biobank represent a reliable resource of DNA for whole-genome amplification and subsequent genome-wide association studies. With call-rates equivalent to high quality DNA samples, our results point to new opportunities for using the neonatal biobanks available worldwide in the hunt for genetic components of disease.
Ecosystems in the Sacramento–San Joaquin Delta are changing rapidly, as are ecosystems around the world. Extreme events are becoming more frequent and thresholds are likely to be crossed more often, ...creating greater uncertainty about future conditions. The accelerating speed of change means that ecological systems may not remain stable long enough for scientists to understand them, much less use their research findings to inform policy and management. Faced with these challenges, those involved in science, policy, and management must adapt and change and anticipate what the ecosystems may be like in the future. We highlight several ways of looking ahead-scenario analyses, horizon scanning, expert elicitation, and dynamic planning-and suggest that recent advances in distributional ecology, disturbance ecology, resilience thinking, and our increased understanding of coupled human–natural systems may provide fresh ways of thinking about more rapid change in the future. To accelerate forward-looking science, policy, and management in the Delta, we propose that the State of California create a Delta Science Visioning Process to fully and openly assess the challenges of more rapid change to science, policy, and management and propose appropriate solutions, through legislation, if needed.
Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood ...pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold.
This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery.
The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients.
The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK).
EudraCT number: 2021-002816-30.
Improvements in sensor accuracy, greater convenience and ease of use, and expanding reimbursement have led to growing adoption of continuous glucose monitoring (CGM). However, successful utilization ...of CGM technology in routine clinical practice remains relatively low. This may be due in part to the lack of clear and agreed-upon glycemic targets that both diabetes teams and people with diabetes can work toward. Although unified recommendations for use of key CGM metrics have been established in three separate peer-reviewed articles, formal adoption by diabetes professional organizations and guidance in the practical application of these metrics in clinical practice have been lacking. In February 2019, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address this issue. This article summarizes the ATTD consensus recommendations for relevant aspects of CGM data utilization and reporting among the various diabetes populations.
Measurement of glycated hemoglobin (HbA
) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute ...events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA
testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA
measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.
Objective
Exploring associations between antenatal detection of fetal growth restriction (FGR) and adverse outcome.
Design
Retrospective, observational, register‐based study.
Setting
Zealand, ...Denmark.
Population or sample
Children born from 1 September 2012 to 31 August 2015.
Methods
Diagnoses from birth until 1 January 2018 were retrieved from The National Patient Registry. Detection was defined as estimated fetal weight less than the 2.3rd centile. Cox regression was used to associate detection status with the hazard rate of adverse outcome, adjusted for fetal weight deviation, maternal age, ethnicity, body mass index and smoking.
Main outcome measures
Adverse neonatal outcome, adverse neuropsychiatric outcome, respiratory disorders, endocrine disorders, gastrointestinal/urogenital disorders.
Results
A total of 2425 FGR children were included. An association was found for gastrointestinal/urogenital disorders (hazard ratio HR 1.68, 95% CI 1.26–2.23, P < 0.001) and respiratory disorders (HR 1.22, 95% CI 1.02–1.46, P = 0.03) in detected versus undetected infants. For adverse neuropsychiatric outcome, HR was 1.32 (95% CI 1.00–1.75, P = 0.05). There was no evidence of an association between detection and adverse neonatal outcome (HR 1.00, 95% CI 0.62–1.61, P = 0.99) and endocrine disorders (HR 1.39, 95% CI 0.88–2.19, P = 0.16). Detected infants were smaller (median −28% versus −25%, P < 0.0001), more often born preterm (odds ratio OR 4.15, 3.12–5.52, P < 0.0001) and more often born after induction or caesarean section (OR 5.19, 95% CI 4.13–6.51, P < 0.0001). Stillbirth risk was increased in undetected FGR fetuses (OR 2.63, 95% CI 1.37–5.04, P = 0.004).
Conclusions
We found an association between detection of FGR and risk of adverse childhood conditions, possibly caused by prematurity. Iatrogenic prematurity may be inevitable in stillbirth prevention, but is accompanied by a risk of long‐term childhood conditions.
Tweetable
Antenatal detection of growth‐restricted fetuses is associated with adverse childhood outcomes but fewer intrauterine deaths.
Tweetable
Antenatal detection of growth‐restricted fetuses is associated with adverse childhood outcomes but fewer intrauterine deaths.
Liver X receptor (LXR)α and LXRβ play key roles in hepatic de novo lipogenesis through their regulation of lipogenic genes, including sterol regulatory element-binding protein (SREBP)-1c and ...carbohydrate responsive element-binding protein (ChREBP). LXRs activate lipogenic gene transcription in response to feeding, which is believed to be mediated by insulin. We have previously shown that LXRs are targets for glucose-hexosamine-derived O-linked β-N-acetylglucosamine (O-GlcNAc) modification enhancing their ability to regulate SREBP-1c promoter activity in vitro. To elucidate insulin-independent effects of feeding on LXR-mediated lipogenic gene expression in vivo, we subjected control and streptozotocin-treated LXRα/β+/+ and LXRα/β−/− mice to a fasting-refeeding regime. We show that under hyperglycemic and hypoinsulinemic conditions, LXRs maintain their ability to upregulate the expression of glycolytic and lipogenic enzymes, including glucokinase (GK), SREBP-1c, ChREBPα, and the newly identified shorter isoform ChREBPβ. Furthermore, glucose-dependent increases in LXR/retinoid X receptor-regulated luciferase activity driven by the ChREBPα promoter was mediated, at least in part, by O-GlcNAc transferase (OGT) signaling in Huh7 cells. Moreover, we show that LXR and OGT interact and colocalize in the nucleus and that loss of LXRs profoundly reduced nuclear O-GlcNAc signaling and ChREBPα promoter binding activity in vivo. In summary, our study provides evidence that LXRs act as nutrient and glucose metabolic sensors upstream of ChREBP by modulating GK expression, nuclear O-GlcNAc signaling, and ChREBP expression and activity.
This study sought to compare the influence of the extent of multidetector computed tomography (MDCT) area oversizing on the incidence of paravalvular aortic regurgitation (PAR) between the Sapien 3 ...and the Sapien XT transcatheter heart valve (THV) to define a new MDCT sizing guideline suitable for the Sapien 3 platform.
The inverse relationship of PAR occurrence and oversizing has been demonstrated for the Sapien XT but the incidence of PAR with comparable oversizing with the Sapien 3 is not known.
Sixty-one prospectively enrolled patients who underwent transcatheter aortic valve replacement with the Sapien 3 THV were compared with 92 patients who underwent transcatheter aortic valve replacement with the Sapien XT THV. Patients were categorized depending on the degree of MDCT area oversizing percentage: undersizing (below 0%), 0% to 5%, 5% to 10%, and above 10%. The primary endpoint was mild or greater PAR on transthoracic echocardiography.
Mild or greater PAR was present in 19.7% of patients (12 of 61) in the Sapien 3 group and in 54.3% of patients (50 of 92) in the Sapien XT group (p < 0.01). The Sapien 3 group, compared with the Sapien XT group, consistently demonstrated significantly lower rates of mild or greater PAR except for oversizing >10% (p for interaction = 0.54). Moderate or severe PAR rates were also lower in the Sapien 3 group than in the Sapien XT group (3.3% vs. 13.0%, p = 0.04). In the Sapien 3 group, a MDCT area oversizing percentage value of ≤4.17% was identified as the optimal cutoff value to discriminate patients with or without mild or greater PAR.
Our retrospective analysis suggests that the Sapien 3 THV displays significantly lower rates of PAR than does the Sapien XT THV. A lesser degree of MDCT area oversizing may be employed for this new balloon-expandable THV.
Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly ...understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.
PDF
