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Aims. We determine the perpendicular and parallel proton heating rate in the solar wind, which is one of the primary goals of the Parker Solar Probe mission. Methods. To estimate the perpendicular and parallel proton heating rates from direct particle measurements by the SPAN electrostatic analyzers, the strong correlation between the proton temperature and the solar wind speed must be removed. This speed dependence is removed by normalization factors that convert the instantaneous temperature to the value it would have if the solar wind speed were 400 km s−1. One-hour and five-hour averages of the normalized perpendicular and parallel temperatures, measured on orbits 6–9, between 20 and 160 solar radii, are compared to the radial dependence they would have if there were no heating. Results. For the first time, perpendicular proton heating has been measured between 20 and 160 solar radii while there is neither heating nor cooling of the parallel protons below 70 solar radii. The extrapolated proton perpendicular temperature at one AU in a 400 km s−1 solar wind is 25 eV, which compares well with several earlier measurements. This result attests to the quality of the temperature measurements made by the particle detectors on the Parker Solar Probe. The heating rates, in ergs cm−3 s−1, that produced the observed perpendicular temperature are 6e−12 at 20 solar radii, 1e−13 at 50 solar radii, and 5e−14 at 160 solar radii.

We summarize a series of numerical experiments of collisional dynamics in dense stellar systems such as globular clusters (GCs) and in weakly collisional plasmas using a novel simulation technique, the so-called Multi-particle collision (MPC) method, alternative to Fokker-Planck and Monte Carlo approaches. MPC is related to particle-mesh approaches for the computation of self consistent long-range fields, ensuring that simulation time scales with $N\log N$ in the number of particles, as opposed to $N^2$ for direct $N$-body. The collisional relaxation effects are modelled by computing particle interactions based on a collision operator approach that ensures rigorous conservation of energy and momenta and depends only on particles velocities and cell-based integrated quantities., Comment: 7 pages, 2 figures. To appear in the proceedings of the 362 IAU symposium "Predictive Power of Computational Astrophysics as a Discovery Tool". Chamonix, France 8-12 Nov. 2021

Context. Rapid polarity reversals of the radial heliospheric magnetic field were discovered by Ulysses and they are now frequently observed as a common near-Sun phenomenon by NASA’s Parker Solar Probe (PSP). Other solar wind missions, including ESA-NASA Solar Orbiter (SolO), also observe similar phenomena. The nature of these fluctuations is unclear, and the relation between the “switchbacks” observed near the Sun and similar events observed at 1 AU is unknown. Aims. We make a detailed case study of the SolO plasma and magnetic field data obtained in a region that is magnetically connected to a coronal hole. We aim to check whether such fluctuations might have the same origin as the “switchbacks” observed by PSP. Methods. We used PSP magnetic field and plasma data to support our analysis of SolO data. We used the magnetic field data, electron pitch angle distributions, proton velocity distribution functions, and α-particle parameters measured by SolO to perform a detailed analysis of the observed solar wind perturbations. Results. On 27 September 2020, PSP and SolO were located around the same Carrington longitude and their latitudinal separation was very small. Solar wind plasma and magnetic field data during this time interval confirms that (at least at certain times) the solar wind observed by both spacecraft does originate from the same coronal hole region and that during these time intervals, SolO experiences several short variations similar to the “switchbacks” regularly observed by PSP. Conclusions. The suprathermal electron pitch angle distributions and α-particle speed variations indicate that the magnetic field line was bent by 180° by solar wind velocity shear. Variations in electron and proton velocity distribution functions suggest that bent field lines reconnect with each other, producing flux ropes. The observed flux ropes might be the surviving and modified remains of the switchbacks created near Sun and observed by PSP.

The correlation between the plasma density measured in space and the surface potential of an electrically conducting satellite body with biased electric field detectors has been recognized and used to provide density proxies. However, for Parker Solar Probe, this correlation has not produced quantitative density estimates over extended periods of time because it depends on the energy dependent exponential variation of the photoemission spectrum, the electron temperature, the ratio of the biased surface area to the conducting spacecraft surface area, the spacecraft secondary or thermal emission, the spacecraft distance from the Sun, etc. In this paper the density as a function of time and frequency to frequencies as high as the electron gyrofrequency is determined through least squares fits of a function of the spacecraft potential to the plasma density measured on the Parker Solar Probe. This function allows correction for the many effects on the spacecraft potential other than that due to the plasma density. Some examples of plasma density obtained from this procedure are presented., 12 pages, 5 figures

We use a forward modeling program to derive one-dimensional isotropic plasma characteristics in Saturn's inner, equatorial magnetosphere using a novel correction for the spacecraft potential and penetrating background radiation. The advantage of this fitting routine is the simultaneous modeling of plasma data and systematic errors when operating on large data sets, which greatly reduces the computation time and accurately quantifies instrument noise. The data set consists of particle measurements from the electron spectrometer (ELS) and the ion mass spectrometer (IMS), which are part of the Cassini Plasma Spectrometer (CAPS) instrument suite on board the data are limited to peak ion flux measurements within ±10°magnetic latitude and 3–15 geocentric equatorial radial distance (RS). Systematic errors such as spacecraft charging and penetrating background radiation are parameterized individually in the modeling and are automatically addressed during the fitting procedure. The resulting values are in turn used as cross calibration between IMS and ELS, where we show a significant improvement in magnetospheric electron densities and minor changes in the ion characteristics due to the error adjustments. adjustments. Preliminary results show ion and electron densities in close agreement, consistent with charge neutrality throughout Saturn's inner magnetosphere and confirming the spacecraft potential to be a common influence on IMS and ELS. Comparison of derived plasma parameters with results from previous studies using CAPS data and the Radio and Plasma Wave Science investigation yields good agreement.

Amyloidosis comprises a group of diseases characterized by the extracellular deposition of insoluble fibrillar proteins. This mechanism generates different clinical syndromes depending on the site and extent of organ involvement. Amyloidosis is classified into categories of systemic and localized disease. Systemic amyloidosis is further subdivided into a hereditary familial form (for example, ATTR amyloidosis), a reactive form (AA amyloidosis), dialysis-related (Abeta(2)M) amyloidosis and immunoglobulin light chain (AL) amyloidosis. Treatment can be symptomatic, directed at the affected organ, or can be directed at reducing the production of the abnormal proteins with different strategies. Despite advances in treatment, the prognosis is still poor and depends on the underlying disease as well as the type and degree of dysfunction in involved organs. Early diagnosis is essential because patients with advanced disease are generally unable to undergo intensive therapy. Patients with systemic amyloidosis often present to a rheumatologist not only because the disease can include musculoskeletal and articular symptoms but also because it can be associated with chronic rheumatic diseases. This Review discusses the clinical features of amyloidosis and its rheumatic manifestations. The various types of amyloidosis, as well their prognosis and treatment, are also presented.

Pulmonary arterial hypertension (PAH) is an important cause of death in systemic sclerosis (SSc), despite the improvement of therapies. An early diagnosis and the use of drugs interfering with the main pathogenic pathways of PAH is pivotal for the improvement of prognosis in primary PAH and PAH secondary to autoimmune rheumatic diseases, mainly SSc. Lately, new specific therapies have been developed targeting prostacyclin, endothelin, and nitric oxide pathways, the major pathogenic pathways leading to endothelial dysfunction in PAH. Epoprostenol improved life expectancy of patients with primary and secondary PAH, but its continuous intravenous administration requires experienced centers. More stable analogues of prostacyclin, administrated by intravenous (iloprost, treprostinil), subcutaneous, inhalatory (treprostinil, iloprost), and oral route (Beraprost) have shown efficacy in PAH. Bosentan, the first oral endothelin receptor antagonist (with affinity for endothelin A and B receptors) improves exercise function and survival in PAH, both primary and secondary to autoimmune rheumatic diseases. This is confirmed also for Sitaxsentan and Ambrisentan, selective A receptor antagonists. Because of its short half-life and systemic side effects, short-term NO inhalation is used only in short-term management of PAH in critically ill adults. Inhibitors of NO degradation, such as sildenafil, a phosphodiesterase (PDE) type 5 inhibitor, improved functional and hemodynamic parameters without significant side effects. Vardenafil and taladafil, longer-acting PDE inhibitors, also have vascular pulmonary selectivity. All these drugs may be used in combination, to maximize their clinical benefit not only in patients unresponsive to single drugs, but also potentially as initial therapy of PAH.

In systemic sclerosis (SSc), the involvement of the interstitium or vascular system of the lung may lead to pulmonary arterial hypertension (PAH). PAH is often asymptomatic or oligosymptomatic in early SSc and, when it becomes symptomatic, pulmonary vascular system is already damaged. Exercise echocardiography (ex-echo), measuring pulmonary artery pressure (PAP) during exercise and allowing to differentiate physiologic from altered PAP responses, may identify subclinical PAH. Our aims were (a) to evaluate by ex-echo the change of PAP in patients with SSc without lung involvement; and (b) to correlate PAP during exercise (ex-PAP) values to clinical and biohumoral parameters of PAH. Twenty-seven patients with limited SSc (ISSc) without interstitial lung involvement were studied. Patients underwent rest and exercise two-dimensional and Doppler echocardiography by supine cycloergometer. Systolic PAP was calculated using the maximum systolic velocity of the tricuspid regurgitant jet at rest and during exercise values of systolic PAP exceeding 40 mmHg at ex-echo were considered as abnormal, and biohumoral markers potentially related to PAH were assessed. Eighteen of 27 SSc patients presented an ex-PAP > 40 mmHg, while in 9 of 27 patients ex-PAP values remained < 40 mmHg (48.8 +/- 4.5 mmHg versus 36.2 +/- 3.1 mmHg; P < 0.001). Other echocardiographic and ergometric parameters, clinical tests, and biohumoral markers were not different in the two groups. Ex-PAP significantly correlated with D-dimer (P = 0.0125; r2 = 0.2029). Ex-echo identifies a cluster of SSc patients with subclinical PAH that may develop PAH. This group should be followed up and may be considered for specific therapies to prevent disease evolution.

Chronic sarcoidosis (CS) is often unresponsive to usual treatments. Melatonin, an immunoregulatory drug, was employed in CS patients in whom usual treatments were ineffective or induced severe side effects. Melatonin was given for 2 yr (20 mg/day in the first year, 10 mg/day in the second year) to 18 CS patients. Pulmonary function tests, chest X rays, pulmonary computed tomography, Ga(67) scintigraphy and angiotensin-converting enzyme (ACE) were assayed at baseline and in the follow-up. Normalization of ACE, improvement of pulmonary parameters and resolution of skin involvement were found in the patients given melatonin. After 24 months of melatonin therapy, hylar adenopathy completely resolved in eight patients and parenchymal lesions were markedly improved in all patients; in the five patients with reduced diffusion capacity of the lung for carbon monoxide, the values normalized after 6 months of therapy and remained stable until month 24. After 24 months, Ga(67) pulmonary and extra-pulmonary uptake was totally normalized in seven patients and, at month 12 months, ACE was normalized in six patients in which the values were high at the baseline. Skin lesions, present in three patients, completely disappeared at month 24 months. No side effects were experienced and no disease relapse was observed during melatonin treatment. Melatonin may be an effective and safe therapy for CS when other treatments fail or cause side effects.

The oscillometric ambulatory blood pressure recorder Daypress 500 was validated according to the British Hypertension Society protocol. Both sequential and simultaneous measurements were used. Multiple regression analysis demonstrated a significant influence of subject pulse pressure and arm circumference on device-observer systolic pressure differences. Differences between observer consecutive readings were inversely related to heart rate. Device and observer blood pressure readings were closer at simultaneous than at sequential measurements. However, both kinds of measurement led to the same final evaluation (A for diastolic and B for systolic blood pressure), provided that the appropriate grading criteria were applied for each method.

Introduction Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department. Materials and methods Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12 weeks. Results One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p = 0.014, p = 0.009 and p = 0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p = 0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients. Conclusions We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.

To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage.Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP).At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4 ± 9.5 vs 2.6 ± 3.8, p0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥ 2 ml/min/year, with a final CCr of ≤ 70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up.Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.