Kirchhoff's Loop Law and the maximum entropy production principle

In contrast to the standard derivation of Kirchhoff's loop law, which invokes electric potential, we show, for the linear planar electric network in a stationary state at the fixed temperature,that loop law can be derived from the maximum entropy production principle. This means that the currents in network branches are distributed in such a way as to achieve the state of maximum entropy production.Comment: revtex4, 5 pages, 2 figure

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Reconstruction of events recorded with the surface detector of the Pierre Auger Observatory

Cosmic rays arriving at Earth collide with the upper parts of the atmosphere, thereby inducing extensive air showers. When secondary particles from the cascade arrive at the ground, they are measured by surface detector arrays. We describe the methods applied to the measurements of the surface detector of the Pierre Auger Observatory to reconstruct events with zenith angles less than 60o using the timing and signal information recorded using the water-Cherenkov detector stations. In addition, we assess the accuracy of these methods in reconstructing the arrival directions of the primary cosmic ray particles and the sizes of the induced showers

An Indication of Anisotropy in Arrival Directions of Ultra-high-energy Cosmic Rays through Comparison to the Flux Pattern of Extragalactic Gamma-Ray Sources

A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above 20 EeV with zenith angles up to 80 degrees. recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi-LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi-LAT. Flux-limited samples, which include all types of galaxies from the Swift-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0 sigma, the highest value of the test statistic being for energies above 39 EeV. The three alternative models are favored against isotropy with 2.7 sigma-3.2 sigma significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed

Inferences on mass composition and tests of hadronic interactions from 0.3 to 100 EeV using the water-Cherenkov detectors of the Pierre Auger Observatory

We present a new method for probing the hadronic interaction models at ultrahigh energy and extracting details about mass composition. This is done using the time profiles of the signals recorded with the water-Cherenkov detectors of the Pierre Auger Observatory. The profiles arise from a mix of the muon and electromagnetic components of air showers. Using the risetimes of the recorded signals, we define a new parameter, which we use to compare our observations with predictions from simulations. We find, first, inconsistencies between our data and predictions over a greater energy range and with substantially more events than in previous studies. Second, by calibrating the new parameter with fluorescence measurements from observations made at the Auger Observatory, we can infer the depth of shower maximum Xmax for a sample of over 81,000 events extending from 0.3 to over 100 EeV. Above 30 EeV, the sample is nearly 14 times larger than what is currently available from fluorescence measurements and extending the covered energy range by half a decade. The energy dependence of ?Xmaxcopyright is compared to simulations and interpreted in terms of the mean of the logarithmic mass. We find good agreement with previous work and extend the measurement of the mean depth of shower maximum to greater energies than before, reducing significantly the statistical uncertainty associated with the inferences about mass composition

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI(21)) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia–reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI(21) is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI(21) at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at −70°C for later determination of plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar–arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI(21) 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI(21) ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome

Extraperitoneal approach reduces neutrophil activation, systemic inflammatory response and organ dysfunctionin aortic aneurysm surgery.

AbstractObjectives: to compare the effects of transperitoneal and extraperitoneal approaches on systemic inflammatory response, neutrophil activation and organ dysfunction in elective abdominal aortic aneurysm (AAA) repair.Patients and methods: twenty patients admitted for elective infrarenal AAA repair were prospectively randomised into transperitoneal (n =10) or extraperitoneal ( n =10) groups. Neutrophil activation was assessed by measuring the plasma levels of neutrophil elastase/α1-anti-trypsin complexes before surgery, intraoperatively and at 6 h, 12 h, 24 h and then daily after surgery. Venous blood samples for estimation of liver function tests, full blood counts, urea and electrolytes and arterial samples for blood gas analysis were taken daily from preoperatively to day 5 after surgery. Multiple organ dysfunction (MOD) and systemic inflammatory response (SIR) scores were calculated daily.Results: the concentrations of neutrophil elastase/α1-anti-trypsin complexes were significantly higher in the transperitoneal group at 6 h after surgery compared to the extraperitoneal group (799(455–921) ng/ml (median(i.q.r.)) vs 307(171–395) ng/ml, p<0.005), and at 12 h (397(364–936) ng/ml vs 319(134–352) ng/ml, p <0.05). The MOD scores were significantly higher in the transperitoneal group in comparison to the extraperitoneal group at day 1 (2.5(2–3.3) vs 1(0–1), p<0.001) and day 2 (2.5(2–3.3) vs 1(0–1), p <0.001). The SIR scores were also significantly higher at day 1 (1(0–2) vs 0, p<0.01), day 2 (1.5(0–2.3) vs 0, p <0.01), and day 3 (1(0–1) vs 0, p <0.05). Conclusions: neutrophil activation, systemic inflammatory response and organ dysfunction are increased in elective AAA repair when a transperitoneal approach is used. This may be related to intestinal manipulation and mesenteric traction which are reduced in the extraperitoneal approach