Clinical characteristics and mortality of patients with heart failure in Southern Sweden from 2013 to 2019: a population-based cohort study.

OBJECTIVES: To describe clinical characteristics and prognosis related to heart failure (HF) phenotypes in a community-based population by applying a novel algorithm to obtain ejection fractions (EF) from electronic medical records. DESIGN: Retrospective population-based cohort study. SETTING: Data were collected for all patients with HF in Southwest Sweden. The region consists of three acute care hospitals, 40 inpatient wards, 2 emergency departments, 30 outpatient specialty clinics and 48 primary healthcare. PARTICIPANTS: 8902 patients had an HF diagnosis based on the International Classification of Diseases, Tenth Revision during the study period. Patients <18 years as well as patients declining to participate were excluded resulting in a study population of 8775 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was distribution of HF phenotypes by echocardiography. The secondary outcome measures were 1 year all-cause mortality and HR for all-cause mortality using Cox regression models. RESULTS: Out of 8775 patients with HF, 5023 (57%) had a conclusive echocardiography distributed into HF with reduced EF (35%), HF with mildly reduced EF (27%) and HF with preserved EF (38%). A total of 43% of the cohort did not have a conclusive echocardiography, and therefore no defined phenotype (HF-NDP). One-year all-cause mortality was 42% within the HF-NDP group and 30% among those with a conclusive EF. The HR of all-cause mortality in the HF-NDP group was 1.27 (95% CI 1.17 to 1.37) when compared with the confirmed EF group. There was no significant difference in survival within the HF phenotypes. CONCLUSIONS: This population-based study showed a distribution of HF phenotypes that varies from those in selected HF registries, with fewer patients with HF with reduced EF and more patients with HF with preserved EF. Furthermore, 1-year all-cause mortality was significantly higher among patients with HF who had not undergone a conclusive echocardiography at diagnosis, highlighting the importance of correct diagnostic procedure to improve treatment strategies and outcomes.

Inducing fear using acoustic stimuli-A behavioral experiment on moose (Alces alces) in Sweden.

Prey species may display anti-predatory behavior, i.e., flight, increased vigilance, and decreased feeding, in response to the true presence of a predator or to the implied presence of a predator through, e.g., acoustic cues. In this study, we investigated the anti-predatory reactions of moose (Alces alces) to acoustic stimuli related to hunting, at saltlick stones, a known attractant. In before-during-after-control-impact experiments, we compared the behavioral responses of individuals to: (i) two hunting-related acoustic stimuli-hunting dog barking and human speaking; (ii) nonpredatory acoustic stimuli-bird sounds and; and (iii) no acoustic stimulus (control). We asked: (1) How does the probability of moose leaving the site differ depending on the stimulus they are exposed to?; (2) What affect do the acoustic stimuli have on the amount of time moose spend vigilant, feeding, or away from the site?; and (3) What affect do the stimuli have on the time between events at a site? We found that when exposed to the human stimulus, moose left the sites in 75% of the events, which was significantly more often compared to the dog (39%), bird (24%), or silent (11%) events. If moose did not leave the site, they spent more time vigilant, and less time feeding, particularly when exposed to a dog or human stimulus. Furthermore, moose spent the most time away from the site and took the longest to visit the site again after a human stimulus. Moose were also more likely to leave the site when exposed to the bird stimulus than during silent controls. Those that remained spent more time vigilant, but their behaviors returned to baseline after the bird stimulus ended. These findings suggest that acoustic stimuli can be used to modify the behavior of moose; however, reactions towards presumably threatening and nonthreatening stimuli were not as distinct as we had expected.

Ungulates and trains - Factors influencing flight responses and detectability.

Wildlife-train collisions can have deleterious effects on local wildlife populations and come with high socio-economic costs, such as damages, delays, and psychological distress. In this study, we explored two major components of wildlife-train collisions: the response of wildlife to oncoming trains and the detection of wildlife by drivers. Using dashboard cameras, we explored the flight response of roe deer (Capreolus capreolus) and moose (Alces alces) to oncoming trains and explored which factors, such as lighting and physical obstructions, affect their detection by drivers. In a majority of cases, roe deer and moose fled from an oncoming train, at an average flight initiation distance (FID) of 78 m and 79 m respectively. Warning horns had unexpected influences on flight behaviour. While roe deer initiated flight, on average, 44 m further away from the train when warned, they usually fled towards the tracks, in the direction of danger. FID of moose, however, was unaffected by the use of a warning horn. As train speed increased, moose had a lower FID, but roe deer FID did not change. Finally, detection of wildlife was obstructed by the presence of vegetation and uneven terrain in the rail-side verge, which could increase the risk of collisions. Our results indicate the need for early detection and warning of wildlife to reduce the risk of collisions. We propose that detection systems should include thermal cameras to allow detection behind vegetation and in the dark, and warning systems should use cues early to warn of oncoming trains and allow wildlife to escape the railway corridor safely.

Ungulate use of non-wildlife underpasses.

Wildlife crossing structures can provide safe passage for wildlife across transportation corridors, and can help mitigate the effects of highways and exclusion fencing on wildlife. Due to their costs, wildlife crossing structures are usually installed sparsely and at strategic locations along transportation networks. Alternatively, non-wildlife underpasses (i.e. conventional underpasses for human and domestic animal use) are usually abundant along major infrastructure corridors and could potentially provide safe crossing opportunities for wildlife. To investigate this, we monitored the use of 40 non-wildlife underpasses by roe deer (Capreolus capreolus), and moose (Alces alces) in south-central Sweden. We found that roe deer and moose use non-wildlife underpasses, and prefer underpasses that are at least 11.5 m wide and 5 m tall. Furthermore, roe deer used structures that had little human co-use and were in locations where the forest cover differed on both sides of the highway. In most cases, roe deer and moose were detected within 50 m of the underpass more than they were detected crossing under them. This suggests that animals often approach underpasses without crossing under them, however modifications to underpass design may improve non-wildlife underpass use. We recommend non-wildlife underpasses at gravel and minor roads, particularly those with little human co-use and with variable forest cover on both sides of the highway, be built wider than 11.5 m and taller than 5 m.

Direct measurement of fast transients by using boot-strapped waveform averaging.

An approximation to coherent sampling, also known as boot-strapped waveform averaging, is presented. The method uses digital cavities to determine the condition for coherent sampling. It can be used to increase the effective sampling rate of a repetitive signal and the signal to noise ratio simultaneously. The method is demonstrated by using it to directly measure the fluorescence lifetime from Rhodamine 6G by digitizing the signal from a fast avalanche photodiode. The obtained lifetime of 4.0 ns is in agreement with the known values.

Red blood cells with elevated cytoplasmic Ca(2+) are primarily taken up by splenic marginal zone macrophages and CD207+ dendritic cells.

BACKGROUND: The normal red blood cell (RBC) life span may be significantly reduced when RBCs are stored under blood bank conditions, resulting in a reduced 24-hour survival after transfusion. The damage of stored RBCs is probably multifactorial as stored RBCs share features of both senescence and suicidal RBC death (eryptosis). Since an increased intracellular Ca(2+) concentration ([Ca(2+) ]i ) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca(2+) ]i and the mechanisms behind uptake of such RBCs in a murine model. STUDY DESIGN AND METHODS: The intracellular Ca(2+) content of RBCs was determined using the Ca(2+) probe Fluo-3 and flow cytometry. In vivo uptake of Ca(2+) ionophore-treated murine RBCs (Ca(2+) -RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis. RESULTS: A small fraction of human RBCs accumulated [Ca(2+) ]i during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca(2+) -RBCs were transfused, Ca(2+) -RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ CD207+ dendritic cells (DCs) within 1 hour after transfusion. In marked contrast, freshly transfused RBCs aging normally in circulation were cleared much slower and preferentially by F4/80+ red pulp macrophages. CD47 on the Ca(2+) -RBCs did not affect their clearance by splenic phagocytic cells. CONCLUSIONS: A small fraction of RBCs accumulate [Ca(2+) ]i during storage, and in a murine model such RBCs are recognized by splenic macrophages and DCs in ways similar to what has been reported for nucleated apoptotic cells.

Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease.

OBJECTIVE: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). METHODS: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). ß-Amyloid (Aß) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. RESULTS: The best CSF measures for identifying MCI-AD were Aß42/total tau (t-tau) and Aß42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aß42/t-tau and Aß42/p-tau performed better than CSF Aß42 and Aß42/40 (AUC difference 0.03-0.12, p<0.05). Using nonoptimized cutoffs, CSF Aß42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. CONCLUSIONS: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aß deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcgamma receptor-mediated but not scavenger receptor-mediated recognition by macrophages.

CD47 functions as a marker of self on red blood cells (RBCs) by binding to signal regulatory protein alpha on macrophages, preventing phagocytosis of autologous RBCs by splenic red pulp macrophages, and Fcgamma receptor (FcgammaR)- or complement receptor-mediated phagocytosis by macrophages in general. RBC senescence involves a series of biochemical changes to plasma membrane proteins or lipids, which may regulate phagocytosis by macrophages. Here, we investigated whether CD47 on experimentally senescent murine RBCs affects their phagocytosis by macrophages in vitro. Clustering of CD47 with antibodies was more pronounced in the plasma membrane of untreated RBCs, compared with that in in vitro oxidized RBCs (Ox-RBCs). Phagocytosis of Ox-RBCs was mediated by scavenger receptors (SRs) distinct from SR-A or CD36 and required serum factors. We found that wild-type (WT) and CD47(-/-) Ox-RBCs were phagocytosed equally well by macrophages in the presence of serum, suggesting that phagocytosis via SRs is not inhibited by CD47. Despite this, FcgammaR-mediated phagocytosis of IgG-opsonized Ox-RBCs was strongly inhibited by CD47. These data suggest that based on the specific prophagocytic receptors mediating uptake of senescent RBCs, the phagocytosis-inhibitory role of CD47 may be more or less involved.

Dose-dependent inhibitory effect of CD47 in macrophage uptake of IgG-opsonized murine erythrocytes.

The cell surface glycoprotein CD47 on target cells can bind to the inhibitory receptor SIRPalpha on macrophages to inhibit phagocytosis of antibody sensitized blood cells. The aim of this study was to determine if CD47 dose-dependently can regulate macrophage uptake of IgG-opsonized RBCs. CD47(+/-) RBCs express about 50% of the CD47 level found on CD47(+/+) RBCs. When injected into CD47(+/+) mice, CD47(+/-) RBCs showed a significantly faster antibody-mediated clearance as compared with CD47(+/+) RBCs injected into the same recipient. In vitro phagocytosis experiments confirmed that CD47(+/-) RBCs were taken up significantly more than CD47(+/+) RBCs, but significantly less than CD47(-/-) RBCs. A reduction in RBC CD47 expression just below 50% of that in normal RBCs can significantly accelerate RBC clearance by macrophages in the presence of RBC autoantibodies. This may have relevance for transfusion of stored RBCs, where loss of CD47 is seen over time, and in clearance of these cells by antibody-dependent phagocytosis.

Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia.

Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein alpha (SIRPalpha) counteracts macrophage phagocytosis of CD47-expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRPalpha signaling regulates normal platelet turnover and clearance of platelets in immune thrombocytopenic purpura (ITP). CD47(-/-) mice had a mild spontaneous thrombocytopenia, which was not due to a decreased platelet half-life as a result of increased expression of P-selectin, CD61, or phosphatidylserine. In contrast, CD47(-/-) platelets were rapidly cleared when transfused into CD47(+/+) recipients, whereas CD47(+/-) platelets had a nearly normal half-life in CD47(+/+) mice under nonautoimmune conditions. CD47(-/-) mice were more sensitive to ITP, as compared with CD47(+/+) mice. In vitro, macrophage phagocytosis of immunoglobulin G (IgG)-opsonized CD47(-/-) platelets was significantly higher than that for equally opsonized CD47(+/+) platelets. However, when SIRPalpha was blocked, phagocytosis of CD47(+/+) platelets increased to the level of CD47(-/-) platelets. Phagocytosis of opsonized CD47(+/-) platelets was higher than that for CD47(+/+) platelets, but lower than that for CD47(-/-) platelets, suggesting a gene-dose effect of CD47 in this system. In conclusion, we suggest that inhibitory CD47/SIRPalpha signaling is involved in regulating platelet phagocytosis in ITP, and that targeting SIRPalpha may be a new means of reducing platelet clearance in ITP.

Multivariate data analysis of dynamic amperometric biosensor responses from binary analyte mixtures-application of sensitivity correction algorithms.

In this paper, it is demonstrated that a single-receptor biosensor can be used to quantitatively determine each analyte in binary mixtures using multivariate data analysis tools based on the dynamic responses received from flow injection peaks. Mixtures with different concentrations of two phenolic compounds, catechol and 4-chlorophenol, were measured with a graphite electrode modified with tyrosinase enzyme at an applied potential of -50mV versus Ag/AgCl. A correction algorithm based on measurements of references in-between samples was applied to compensate for biosensor ageing as well as differences caused by deviations between biosensor preparations. After correction, the relative prediction errors with partial least squares regression (PLS-R) for catechol and 4-chlorophenol were 7.4 and 5.5%, respectively, using an analysis sequence measured on one biosensor. Additional validation mixtures of the two phenols were measured with a new biosensor, prepared with the same procedure but with a different batch of tyrosinase enzyme. Using the mixture responses for the first sensor as a calibration set in PLS-R, the relative prediction errors of the validation mixtures, after applying correction procedures, were 7.0% for catechol and 16.0% for 4-chlorophenol. These preliminary results indicate that by applying correction algorithms it could be possible to use less stable biosensors in continuous on-line measurements together with multivariate data analysis without time-consuming calibration procedures.

Sorption of Pu(VI) onto TiO2.

The sorption of Pu(VI) onto TiO(2) was studied as a function of pH (2-10) and Pu concentration (10(-8)-10(-4) M) under an N(2) atmosphere, in 0.016 and 0.1 M NaClO(4). A batch-wise method was used, in which pH was measured in separate experimental containers after removal of a sample to determine the amount of Pu that had been sorbed. As Pu is radioactive, it was used as a tracer and measured by liquid scintillation counting. No ionic strength dependence was discerned, which was taken as an indication of inner sphere complex formation. In the interval of pH 2-7 the system could be described by the formation of two positively charged surface complexes using a 1-pK Stern model. Sorption of the plutonyl ion (PuO(2)(2+)) and the first hydrolysis species (PuO(2)(OH)(+)) was estimated using FITEQL to logK(1)=6.9 and logK(2)=1.4, respectively.