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Atmospheric chemistry and transport of mercury play a key role in the global mercury cycle. However, there are still considerable knowledge gaps concerning the fate of mercury in the atmosphere. This is the second part of a model intercomparison study investigating the impact of atmospheric chemistry and emissions on mercury in the atmosphere. While the first study focused on ground-based observations of mercury concentration and deposition, here we investigate the vertical and interhemispheric distribution and speciation of mercury from the planetary boundary layer to the lower stratosphere. So far, there have been few model studies investigating the vertical distribution of mercury, mostly focusing on single aircraft campaigns. Here, we present a first comprehensive analysis based on various aircraft observations in Europe, North America, and on intercontinental flights. The investigated models proved to be able to reproduce the distribution of total and elemental mercury concentrations in the troposphere including interhemispheric trends. One key aspect of the study is the investigation of mercury oxidation in the troposphere. We found that different chemistry schemes were better at reproducing observed oxidized mercury patterns depending on altitude. High concentrations of oxidized mercury in the upper troposphere could be reproduced with oxidation by bromine while elevated concentrations in the lower troposphere were better reproduced by OH and ozone chemistry. However, the results were not always conclusive as the physical and chemical parameterizations in the chemistry transport models also proved to have a substantial impact on model results.

Biological, biomimetic, and engineering systems make extensive use of hydraulic asymmetries to control flow inside tubular structures. Examples span physiological valves, the guided transport observed in shark intestines, and passive devices such as Tesla valves. Here we investigate the mechanisms that generate these asymmetries using the notion of diodicity, defined as the ratio between pressure drops required to drive the same flow in opposite directions. We first focus on 2D geometries, which allow us to identify and study the main contributions to hydraulic asymmetry: channel geometry and internal obstacles embedded within a channel with rigid walls. By considering both rigid and deformable obstacles, we model channels that always remain open in both directions and channels that can be completely blocked by valve-like structures. We then extend the analysis to 3D geometries, again considering rigid and elastic cases. As a general trend, we find that geometry alone establishes a baseline diodicity, while higher dimensionality and structural reconfiguration consistently amplify the effect.

Background After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. Objectives To provide guidance for clinicians in daily practice for areas in which there is limited guidance. Methods A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. Results Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. Conclusions In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients’ risk factors and carry out proper monitoring during the course of treatment.

Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel’s triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells’ electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an “Autonomic Coumel Triangle” that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel’s triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes’ action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an “Autonomic Coumel’s Triangle” instead of simply “Coumel’s Triangle”.

Abstract Context Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes. Objective The objective of this study was to analyze characteristics of adults with type 1 diabetes for associations with COVID-19 hospitalization. Design An observational multisite cross-sectional study was performed. Diabetes care providers answered a 33-item questionnaire regarding demographics, symptoms, and diabetes- and COVID-19-related care and outcomes. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between glycated hemoglobin (HbA1c), age, and comorbidities and hospitalization. Setting Cases were submitted from 52 US sites between March and August 2020. Patients or Other Participants Adults over the age of 19 with type 1 diabetes and confirmed COVID-19 infection were included. Interventions None. Main Outcome Measures Hospitalization for COVID-19 infection. Results A total of 113 cases were analyzed. Fifty-eight patients were hospitalized, and 5 patients died. Patients who were hospitalized were more likely to be older, to identify as non-Hispanic Black, to use public insurance, or to have hypertension, and less likely to use continuous glucose monitoring or insulin pumps. Median HbA1c was 8.6% (70 mmol/mol) and was positively associated with hospitalization (odds ratio 1.42, 95% confidence interval 1.18-1.76), which persisted after adjustment for age, sex, race, and obesity. Conclusions Baseline glycemic control and access to care are important modifiable risk factors which need to be addressed to optimize care of people with type 1 diabetes during the worldwide COVID-19 pandemic.

Cam-Clay nonassociative plasticity exhibits both hardening and softening behaviour, depending on the loading. For many initial data the classical formulation of the quasistatic evolution problem has no smooth solution. We propose here a notion of generalized solution, based on a viscoplastic approximation. To study the limit of the viscoplastic evolutions we rescale time, in such a way that the plastic strain is uniformly Lipschitz with respect to the rescaled time. The limit of these rescaled solutions, as the viscosity parameter tends to zero, is characterized through an energy-dissipation balance, that can be written in a natural way using the rescaled time. As shown in Dal Maso and DeSimone (Math Models Methods Appl Sci 19:1–69, 2009) and Dal Maso and Solombrino (Netw Heterog Media 5:97–132, 2010), the proposed solution may be discontinuous with respect to the original time. Our formulation allows us to compute the amount of viscous dissipation occurring instantaneously at each discontinuity time.

Background As literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead. Methods Data of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate. Results Forty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units ( P  < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar ( P  = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation ( P  < 0.0001) and scored higher Comprehensive Complication Index ( P  < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index  ≥ 42) was similar ( P  = 0.52). ICU stay ( P  = 0.97), total hospital stay ( P  = 0.57), in hospital ( P  = 1.00) and 6 months ( P  = 1.00) death were similar. Conclusion Selected octogenarian and cardiac-dead donors can be used safely for liver transplantation.

Cam-Clay plasticity is a well-established model for the description of the mechanics of fine grained soils. As solutions can develop discontinuities in time, a weak notion of solution, in terms of a rescaled time s , has been proposed in Dal Maso, DeSimone and Solombrino (Calc Var Partial Equ 40:125–181, 2011 ) to give a meaning to this discontinuous evolution. In this paper we first prove that this rescaled evolution satisfies the flow-rule for the rate of plastic strain, in a suitable measure-theoretical sense. In the second part of the paper we consider the behavior of the evolution in terms of the original time variable t . We prove that the unrescaled solution satisfies an energy-dissipation balance and an evolution law for the internal variable, which can be expressed in terms of integrals depending only on the original time. Both these integral identities contain terms concentrated on the jump times, whose size can only be determined by looking at the rescaled formulation.

The interpretation of serial electrocardiographic (ECG) changes in hypertensive subjects is uncertain. We tested the hypothesis that serial changes in repolarization and voltage are independent determinants of outcome. The Hypertrophy at ECG And its Regression during Treatment (HEART) Survey was a prospective observational study performed at 61 centers. We studied 711 subjects with hypertension and ECG left-ventricular hypertrophy (LVH) at entry. Tracings from 496 subjects at entry and one or more visits during follow-up were available for central reading. The prevalence of ECG LVH progressively decreased by 49.6% at 3 years. The crude rate of a prespecified primary composite end point of cardiovascular events was 4.17 per 100 subjects per year (95% confidence interval [CI], 3.27 to 5.33). We used Cox regression models of ECG LVH indexes as time-varying covariates at baseline and at follow-up. Time-varying LVH, defined as an absence of ST-T alterations (“strain”), was associated with a lower event rate hazard ratio (HR), 0.47; 95% CI, 0.28 to 0.78; P = .0035), whereas the LVH changes defined in terms of ECG voltages did not achieve significance (HR, 0.91; 95% CI, 0.74 to 1.13; P = .39). The crude event rate in subjects with versus without in-treatment ST-T alterations on the last available ECG before the event or before censoring was 8.38 versus 3.17 per 100 subjects per year ( P < .0001). In this study of subjects with hypertension and ECG LVH at entry, serial changes in repolarization significantly predicted the prognosis, independent of voltage change (which was not significantly predictive in this study). The persistence or new development of ST-T alterations identifies subjects at very high risk of cardiovascular events.