Towards continual learning in medical imaging

This work investigates continual learning of two segmentation tasks in brain MRI with neural networks. To explore in this context the capabilities of current methods for countering catastrophic forgetting of the first task when a new one is learned, we investigate elastic weight consolidation, a recently proposed method based on Fisher information, originally evaluated on reinforcement learning of Atari games. We use it to sequentially learn segmentation of normal brain structures and then segmentation of white matter lesions. Our findings show this recent method reduces catastrophic forgetting, while large room for improvement exists in these challenging settings for continual learning

Competition between In-Plane vs Above-Plane Configurations of Water with Aromatic Molecules: Non-Covalent Interactions in 1,4-Naphthoquinone-(H2O)1-3Complexes

Non-covalent interactions between aromatic molecules and water are fundamental in many chemical and biological processes, and their accurate description is essential to understand molecular relative configurations. Here we present the rotational spectroscopy study of the water complexes of the polycyclic aromatic hydrocarbon 1,4-naphthoquinone (1,4-NQ). In 1,4-NQ-(H2O)1,2, water molecules bind through O-H···O and C-H···O hydrogen bonds and are located on the plane of 1,4-NQ. For 1,4-NQ-(H2O)3, in-plane and above-plane water configurations are observed exhibiting O-H···O, C-H···O, and lone pair···π-hole interactions. The observation of different water arrangements for 1,4-NQ-(H2O)3 allows benchmarking theoretical methods and shows that they have great difficulty in predicting energy orderings due to the strong competition of C-H···O binding with πand π-hole interactions. This study provides important insight into water interactions with aromatic systems and the challenges in their modeling

Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis

BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived Extracellular Vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune-cell derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n=15; B n=16; C n=43 and Child-C with sepsis (n=38)], and healthy controls (HC, n=11). In-vitro and in-vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (p0.3, p<0.001), which further increased in Child C sepsis than without sepsis(p<0.001); monocyte EV showing the highest association with disease stage [p=0.013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC=0.76, p<0.01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (p=0.004), reduced basal oxygen consumption rate (p<0.001) and induced pro-inflammatory genes (p<0.05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis like condition within 24h with leukocytopenia (p=0.005), intrahepatic inflammation with increased CD11b+ cells (p=0.03) and bone marrow hyperplasia (p<0.01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients

Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design

HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at ∼2.5–3.0 Å resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Å resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Å resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (&lt;135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration &gt;10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was &gt;3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A Multiscale and Efficient Recognition of Land Cover by Using Both Decomposition and Deep Visual Feature Analysis

As we know that when we use the colour bands that are pure in nature it will help some of the public authorities to update the land information. It will be a sensing platform so it will take less time and the cost we will be spending will not be much heavy, in that manner aircraft system will be used that should be unmanned. Here we will be using a method for optical aerial imagery that will come under land use classification with decision tree. In the beginning the ownership parcel map will come under play for taking the land cover information through maximum likelihood classifier. Then, to make the relation between land usage and land coverage we will generate the decision tree. A well structured parcel map will be produced by the merits of geographical characteristics of parcels.Hence the aftereffects of the spatial resolution under the classification approach will be discussed completely by sampling them again from the 20 then 50 then 100cm. This land use can be widely used in landscape and urban planning because of the flexible classification method. Using aerial images the object oriented approach for image based analysis is used for urban land cover mapping.&nbsp

Bioreactor cleans up Canada: Performance results point to a better way

NRC publication: Ye