Consistent Point Data Assimilation in Firedrake and Icepack

We present methods and tools that significantly improve the ability to estimate quantities and fields which are difficult to directly measure, such as the fluidity of ice, using point data sources, such as satellite altimetry. These work with both sparse and dense point data with estimated quantities and fields becoming more accurate as the number of measurements are increased. Such quantities and fields are often used as inputs to mathematical models that are used to make predictions so improving their accuracy is of vital importance. We demonstrate how our methods and tools can increase the accuracy of results, ensure posterior consistency, and aid discourse between modellers and experimenters. To do this, we bring point data into the finite element method ecosystem as discontinuous fields on meshes of disconnected vertices. Point evaluation can then be formulated as a finite element interpolation operation (dual-evaluation). Our new abstractions are well-suited to automation. We demonstrate this by implementing them in Firedrake, which generates highly optimised code for solving PDEs with the finite element method. Our solution integrates with dolfin-adjoint/pyadjoint which allows PDE-constrained optimisation problems, such as data assimilation, to be solved through forward and adjoint mode automatic differentiation. We demonstrate our new functionality through examples in the fields of groundwater hydrology and glaciology

Physical activity mediates the association between personality and biomarkers of inflammation

Objectives: The current study investigated whether personality traits and facets were associated with interleukin-6, C-reactive protein, and fibrinogen, and whether physical activity mediated the relationship between personality and biomarkers of inflammation. Methods: Personality was assessed in the Midlife Development in the United States study using the Multi-Dimensional Personality Questionnaire and Midlife Development Inventory personality scale. Data were included from 960 participants (mean age = 57.86 years, standard deviation = 11.46). Personality was assessed from 2004 to 2009. Serum levels of interleukin-6, fibrinogen, and C-reactive protein were assessed in 2005–2009 as part of the Midlife Development in the United States biomarkers subproject. Results: Lower neuroticism was associated with elevated interleukin-6, and achievement was associated with lower fibrinogen. Higher physical activity was associated with lower interleukin-6 and C-reactive protein. Mediation models suggested that physical activity mediated the associations between achievement and both interleukin-6 and C-reactive protein. Discussion: Physical activity is an important factor in the Health Behavior Model of personality and explains some of the associations between personality and inflammation. These findings contribute to the fields of aging and health by linking individual difference factors to markers of inflammation, and showing that these processes may function partially through specific behaviors, in this case physical activity

A network analysis to compare biomarker profiles in patients with and without diabetes mellitus in acute heart failure

Aims: It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways. Methods and results: We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal function (NGAL, KIM-1) (adjusted P-value <0.05). Among patients with diabetes, network analysis revealed that periostin strongly clustered with C-reactive protein and interleukin-6. Furthermore, renal markers (creatinine and NGAL) closely associated with potassium and glucose. These findings were not seen among patients without diabetes. Conclusion: Patients with AHF and diabetes, compared with those without diabetes, have distinct biomarker profiles. Network analysis suggests that cardiac remodelling, inflammation, and fibrosis are closely associated with each other in patients with diabetes. Furthermore, potassium levels may be sensitive to changes in renal function as reflected by the strong renal–potassium–glucose correlation. These findings were not seen among patients without diabetes and may suggest distinct pathophysiological processes among AHF patients with diabetes

Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient’s clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.

Reduced Career Longevity but Return to Baseline Performance After Arthroscopic Shoulder Labral Repair in National Hockey League Players

PURPOSE: To investigate the impact of arthroscopic shoulder labral repair without shoulder instability on career longevity, game use, and performance in National Hockey League (NHL) athletes. METHODS: A retrospective review of all NHL players who underwent arthroscopic shoulder labral repair from 2004 to 2020 was performed. A 2:1 matched control group was used for comparison. Controls were matched by age, body mass index, position, and experience prior to the index year. Demographic characteristics, game use, and performance metrics were collected for all athletes. Statistical analysis examined game use and performance both at 1-year and 3-year follow-up compared with one season before injury. RESULTS: Twenty-nine players who underwent arthroscopic shoulder labral surgery returned to play (100%) and were matched with 55 control players. The operative cohort experienced shorter careers compared with controls (4.4 ± 3.1 vs 6.0 ± 3.6 seasons, P < .05). After one season, injured players experienced significant reductions in goals per 60 (0.6 ± 0.4 vs 0.8 ± 0.5, P = .013), points per 60 (1.5 ± 0.9 vs 2.0 ± 0.9, P = .001), and shooting percentage, (8.5 ± 5.8 vs 10.5 ± 5.2, P = .02) compared with the year prior. The reduction in goals (0.6 ± 0.4 vs 0.8 ± 0.5, P = .01) and shooting % (8.5 ± 4.7 vs 10.5 ± 5.2, P = .04) persisted at 3 years. Compared with controls, the surgical group experienced significant reductions at one season postindex in percentage of goals, assists, points per 60, and shooting percentage. Only the reduction in goals per 60 persisted at 3 seasons postindex. CONCLUSIONS: Following return to play after arthroscopic shoulder labral repair, NHL players demonstrated reduced career longevity compared with healthy controls. Players exhibited significant reductions in game use and performance at one season after injury but returned closer to baseline after 3 seasons. LEVEL OF EVIDENCE: Level III; retrospective case control

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of &lt;40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend &lt;0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction &lt;0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

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 &lt; 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 &lt; 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

The first GCT camera for the Cherenkov Telescope Array

The Gamma Cherenkov Telescope (GCT) is proposed to be part of the Small Size Telescope (SST) array of the Cherenkov Telescope Array (CTA). The GCT dual-mirror optical design allows the use of a compact camera of diameter roughly 0.4 m. The curved focal plane is equipped with 2048 pixels of ~0.2{\deg} angular size, resulting in a field of view of ~9{\deg}. The GCT camera is designed to record the flashes of Cherenkov light from electromagnetic cascades, which last only a few tens of nanoseconds. Modules based on custom ASICs provide the required fast electronics, facilitating sampling and digitisation as well as first level of triggering. The first GCT camera prototype is currently being commissioned in the UK. On-telescope tests are planned later this year. Here we give a detailed description of the camera prototype and present recent progress with testing and commissioning.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

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 (&lt;3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (&gt;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