A combined clinical and biomarker approach to predict diuretic response in acute heart failure

Background: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF). Methods and results: We investigated explanatory and predictive models for diuretic response—weight loss at day 4 per 40 mg of furosemide—in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r2 = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (β = 0.467, P < 0.001; r2 = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r2 = 0.586, P < 0.001). Conclusions: Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h

Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens

Serum potassium levels and outcome in acute heart failure (data from the PROTECT and COACH trials)

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (<3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (>5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 – 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 – 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p [ 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p [ 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment

Reliability of Striatal [11C]Raclopride Binding in Smokers Wearing Transdermal Nicotine Patches

PURPOSE: In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches. METHODS: Eleven male smokers were scanned twice with RAC on separate days while wearing TNP. RESULTS: Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 (p < 0.0001). CONCLUSION: Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine

Entangled Rings

Consider a ring of N qubits in a translationally invariant quantum state. We ask to what extent each pair of nearest neighbors can be entangled. Under certain assumptions about the form of the state, we find a formula for the maximum possible nearest-neighbor entanglement. We then compare this maximum with the entanglement achieved by the ground state of an antiferromagnetic ring consisting of an even number of spin-1/2 particles. We find that, though the antiferromagnetic ground state does not maximize the nearest-neighbor entanglement relative to all other states, it does so relative to other states having zero z-component of spin.Comment: 19 pages, no figures; v2 includes new results; v3 corrects a numerical error for the case N=

Improving object segmentation by using EEG signals and rapid serial visual presentation

This paper extends our previous work on the potential of EEG-based brain computer interfaces to segment salient objects in images. The proposed system analyzes the Event Related Potentials (ERP) generated by the rapid serial visual presentation of windows on the image. The detection of the P300 signal allows estimating a saliency map of the image, which is used to seed a semi-supervised object segmentation algorithm. Thanks to the new contributions presented in this work, the average Jaccard index was improved from $0.47$ to $0.66$ when processed in our publicly available dataset of images, object masks and captured EEG signals. This work also studies alternative architectures to the original one, the impact of object occupation in each image window, and a more robust evaluation based on statistical analysis and a weighted F-score

Does modifying competition affect the frequency of technical skills in junior rugby league?

The technical demands of games can be affected by changing the number of players, pitch size and rules. This controlled trial compared the frequency of technical skills between a 'traditional' and newly introduced systematically 'modified' game of primary rugby league. A total of 475 primary rugby league players (Under 7s - 9s) were filmed playing traditional (n=49) and modified (n= 249) formats. Notational analysis examined the frequency of technical skills (e.g., number of passes) within 'traditional' and 'modified' games. At each age category, multivariate analysis of variance indicated the clear superiority of the 'modified' game for the frequency of technical skills (e.g., Under 7s total skill opportunities - 'traditional' = 342.9±47.0; 'modified' = 449.4±93.3, d=1.44, p<0.001). Systematically modifying the competitive game is an effective way to increase skill opportunities for children within rugby league. Future research should examine the outcomes of modifying games in optimizing skill development in youth sport

A Pleistocene legacy structures variation in modern seagrass ecosystems

Distribution of Earth's biomes is structured by the match between climate and plant traits, which in turn shape associated communities and ecosystem processes and services. However, that climate-trait match can be disrupted by historical events, with lasting ecosystem impacts. As Earth's environment changes faster than at any time in human history, critical questions are whether and how organismal traits and ecosystems can adjust to altered conditions. We quantified the relative importance of current environmental forcing versus evolutionary history in shaping the growth form (stature and biomass) and associated community of eelgrass (Zostera marina), a widespread foundation plant of marine ecosystems along Northern Hemisphere coastlines, which experienced major shifts in distribution and genetic composition during the Pleistocene. We found that eelgrass stature and biomass retain a legacy of the Pleistocene colonization of the Atlantic from the ancestral Pacific range and of more recent within-basin bottlenecks and genetic differentiation. This evolutionary legacy in turn influences the biomass of associated algae and invertebrates that fuel coastal food webs, with effects comparable to or stronger than effects of current environmental forcing. Such historical lags in phenotypic acclimatization may constrain ecosystem adjustments to rapid anthropogenic climate change, thus altering predictions about the future functioning of ecosystems.This work was supported by the US NSF (OCE-1031061, OCE-1336206, OCE0-1336741, OCE-1336905) and the Smithsonian Institution. F.T. was supported by José Castillejo Award CAS14/00177. A.H.E. was supported by the FCT (Foundation for Science and Technology) through Project UIDB/04326/2020 and Contract CEECINST/00114/2018. This is Contribution 106 from the Smithsonian’s MarineGEO and Tennenbaum Marine Observatories Network and Contribution 4105 of the Virginia Institute of Marine Science, College of William & Mary