Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression?

OBJECTIVES: Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. METHODS: Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. RESULTS: Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P < 0.001] and novel peripheral vascular involvement (OR = 0.79, P = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P = 0.029); and a 'severe' (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P = 0.002) and skin progression (OR = 1.70, P = 0.049). CONCLUSIONS: Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression.

The Prostacyclin Analogue Iloprost Modulates CXCL10 in Systemic Sclerosis.

The prostacyclin analogue iloprost is used to treat vascular alterations and digital ulcers, the early derangements manifesting in systemic sclerosis (SSc), an autoimmune disease leading to skin and organ fibrosis. Bioindicator(s) of SSc onset and progress are still lacking and the therapeutic approach remains a challenge. The T helper 1 (Th1) chemokine interferon (IFN)γ-induced protein 10 (IP-10/CXCL10) associates with disease progression and worse prognosis. Endothelial cells and fibroblasts, under Th1-dominance, release CXCL10, further enhancing SSc's detrimental status. We analyzed the effect of iloprost on CXCL10 in endothelial cells, dermal fibroblasts, and in the serum of SSc patients. Human endothelial cells and dermal fibroblasts activated with IFNγ/Tumor Necrosis Factor (TNF)α, with/without iloprost, were investigated for CXCL10 secretion/expression and for intracellular signaling cascade underlying chemokine release (Signal Transducer and Activator of Transcription 1, STAT1; Nuclear Factor kappa-light-chain-enhancer of activated B cells, NF-kB; c-Jun NH2-terminal kinase, JNK: Phosphatidyl-Inositol 3-kinase (PI3K)/protein kinase B, AKT; Extracellular signal-Regulated Kinase 1/2, ERK1/2). CXCL10 was quantified in sera from 25 patients taking iloprost, satisfying the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria for SSc, and in sera from 20 SSc sex/age-matched subjects without therapy, previously collected. In human endothelial cells and fibroblasts, iloprost targeted CXCL10, almost preventing IFNγ/TNFα-dependent cascade activation in endothelial cells. In SSc subjects taking iloprost, serum CXCL10 was lower. These in vitro and in vivo data suggest a potential role of iloprost to limit CXCL10 at local vascular/dermal and systemic levels in SSc and warrant further translational research aimed to ameliorate SSc understanding/management.

Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement.

OBJECTIVES: The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. METHODS: Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA. RESULTS: Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc- compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4+ but not CD8+ T cells. Controls showed no correlation between CD4+ T cells and resistin, whereas SSc showed significantly more CD4+ T cells in resistin-negative tissues. CONCLUSION: Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF.

From VEDOSS to established systemic sclerosis diagnosis according to ACR/EULAR 2013 classification criteria: a French-Italian capillaroscopic survey.

OBJECTIVES: Nailfold capillaroscopy (NC) shows microcirculatory abnormalities in systemic sclerosis (SSc). The inclusion of NC specific abnormalities increases the sensitivity of both 2013 ACR/EULAR and VEDOSS (Very Early Diagnosis of Systemic Sclerosis) classification criteria. We aimed to detect NC features able to predict progression toward established SSc in VEDOSS patients. METHODS: Sixty-six VEDOSS patients were enrolled. They had a clinical follow-up and underwent NC once a year, considering morphological parameters, appropriate pattern and semi- quantitative rating scale. RESULTS: In a mean follow-up time of 31 months, 21 patients progressed into SSc (P = Progressors), while 45 were "Non Progressor" (NP). Comparing NC basal features of both groups, significantly larger loop diameter and apex width, higher haemorrhage and NC scores were found in P respect to NP patients. When comparing NC features of P patients who progressed within one year (FP = Fast progressor), loop diameter and apex width were significantly higher compared to all VEDOSS subjects. Each unit increase of apex width was associated with an increasing risk of 1% for developing SSc and the cut-off value of 103 µm showed a positive predictive value of 56% and a negative predictive value of 71%. CONCLUSIONS: We describe NC findings in VEDOSS patients, identifying those suggesting a progression into established disease. These findings must be regarded as possible predictive risk factor to develop SSc and can also be of relevance in the detection of those cases with a faster development. Thus NC seems to have a diagnostic and prognostic role in VEDOSS cases.

Vitamin D in autoimmune rheumatic diseases: A view inside gender differences.

A large body of evidence highlights the role for vitamin D deficiency/insufficiency in rheumatic diseases, a group of different pathologies mostly of autoimmune origin. Vitamin D and vitamin D receptor agonists exquisitely modulate the immune system against over-reactivity towards tolerance; on this basis, vitamin D could be a good therapeutic candidate to control autoimmune processes in rheumatic diseases. Similarly, to other autoimmune pathologies, rheumatic diseases show a significant female bias. This sexual dimorphism seems, in part, to rely on the different sex hormone-induced regulation on male and female immune systems. Females, in fact, retain greater immune reactivity and competence likely due to estrogens, which, at variance with androgens, are associated with a greater resilience to infections but also to a higher risk for autoimmunity. In this scenario, there is growing interest on vitamin D supplementation for prevention or therapy in rheumatic diseases in relation to gender and sexual hormones. The purpose of the review is to overview vitamin D status in rheumatic diseases, related to gender and sex hormones. In particular, the main vitamin D immunoregulatory properties are summarized with some sex hormone-driven immune activities, in females and males immune systems. Topics onto vitamin D receptor agonists as potential therapeutic agents in rheumatic disease are addressed, especially in view of the role of vitamin D inadequacy in the pathogenesis of rheumatic diseases. So far, further clinical and basic studies should be encouraged to confirm the high potential power of vitamin D receptor agonists as novel pharmacological tools in rheumatic diseases particularly in light of personalized gender-related therapeutic strategies.

Occupational therapy integrated with a self-administered stretching program on systemic sclerosis patients with hand involvement.

OBJECTIVES: To evaluate the effect of occupational therapy (OT) intervention, integrated with a self-administered stretching program on the hands of patients with SSc, after one and three months of treatment. METHODS: We enrolled 31 patients with SSc, randomly allocated to the occupational group (15 patients) or to the control group (16 patients). Each patient received specific outcome measures: Canadian Occupational Performance Measure (COPM), HAQ, Short-Form Health Survey (SF-36), Duruoz Hand Index (DHI), reassessed after 1 (T1) and three months (T2). RESULTS: At T1 and T2 we found a statistically significant improvement from baseline values of COPM Performance and COPM Satisfaction in the OT group compared to baseline. At T2 HAQ values and Mental SF36 were also significantly improved. In the control group we found a statistically significant improvement of HAQ values and Mental SF36 at T1, confirmed at T2. COPM Performance was also significantly improved. The comparison between the two groups showed a greater improvement in the OT group concerning COPM Performance at T1 and T2. Mental SF-36 score greater improved in the control group at T1. CONCLUSIONS: Our results indicate that a rehabilitation program including OT and self-administered stretching exercises may be effective to improve and maintain hand function in patients with SSc.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

OBJECTIVES: This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). METHODS: Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. RESULTS: Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. CONCLUSIONS: This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

A novel multiobjective evolutionary algorithm based on regression analysis.

As is known, the Pareto set of a continuous multiobjective optimization problem with m objective functions is a piecewise continuous (m - 1)-dimensional manifold in the decision space under some mild conditions. However, how to utilize the regularity to design multiobjective optimization algorithms has become the research focus. In this paper, based on this regularity, a model-based multiobjective evolutionary algorithm with regression analysis (MMEA-RA) is put forward to solve continuous multiobjective optimization problems with variable linkages. In the algorithm, the optimization problem is modelled as a promising area in the decision space by a probability distribution, and the centroid of the probability distribution is (m - 1)-dimensional piecewise continuous manifold. The least squares method is used to construct such a model. A selection strategy based on the nondominated sorting is used to choose the individuals to the next generation. The new algorithm is tested and compared with NSGA-II and RM-MEDA. The result shows that MMEA-RA outperforms RM-MEDA and NSGA-II on the test instances with variable linkages. At the same time, MMEA-RA has higher efficiency than the other two algorithms. A few shortcomings of MMEA-RA have also been identified and discussed in this paper.

Space object identification and classification from hyperspectral material analysis.

This paper presents a data processing pipeline designed to extract information from the hyperspectral signature of unknown space objects. The methodology proposed in this paper determines the material composition of space objects from single pixel images. Two techniques are used for material identification and classification: one based on machine learning and the other based on a least square match with a library of known spectra. From this information, a supervised machine learning algorithm is used to classify the object into one of several categories based on the detection of materials on the object. The behaviour of the material classification methods is investigated under non-ideal circumstances, to determine the effect of weathered materials, and the behaviour when the training library is missing a material that is present in the object being observed. Finally the paper will present some preliminary results on the identification and classification of space objects.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. METHODS: Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. RESULTS: An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). CONCLUSION: Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

Power Doppler ultrasound of the hand and wrist joints in systemic sclerosis.

OBJECTIVES: This paper aims to investigate the prevalence and severity of hand and wrist joints power Doppler (PD) ultrasound (US) detected abnormalities in systemic sclerosis (SSc). METHODS: Hand and wrist joints of 46 consecutive SSc patients and 15 healthy controls were studied by using PDUS. Each joint was evaluated for the presence of effusion, synovial hypertrophy, hyperaemia, bone erosions and cortical irregularities; in addition, local tendons for tenosynovitis and hyperaemia, and median nerve for entrapment neuropathy were examined. RESULTS: Synovial hypertrophy was detected in 3% hand joints and in 46% wrists of SSc patients, with significant differences respect to controls (p=0.000004 and 0.000001, respectively). The prevalence of PD positivity was significantly higher in patients' hand joints (1.7%, p=0.001527) and wrists (43%, p=0.000001) than in healthy individuals. Seven percent of hand and 54% of wrist joints resulted to be positive for joint effusion with significant differences from controls (p=0.000001 and p=0.000013, respectively). The prevalence of cortical irregularities was significantly higher (p=0.006) than healthy subjects only at hand joints level. No significant difference was found for bone erosions. Tenosynovitis was found in 6% out of the 1.196 synovial tendon sites examined of SSc patients with significant differences compared to healthy subjects (p=0.000001); PD resulted to be positive in 29% of them, with significantly differences compared to controls (p=0.0038). CONCLUSIONS: This study, focused on hand and wrist joints PDUS assessment of inflammatory and structural abnormalities in SSc, demonstrated a varied and complex involvement both at joint and periarticular tissues level, showing that wrists were more frequently the site of inflammatory findings.

Rheumatic diseases and obesity: adipocytokines as potential comorbidity biomarkers for cardiovascular diseases.

Inflammation has been recognized as a common trait in the pathogenesis of multifactorial diseases including obesity, where a low-grade inflammation has been established and may be responsible for the cardiovascular risk related to the disease. Obesity has also been associated with the increased incidence and a worse outcome of rheumatoid arthritis (RA) and osteoarthritis (OA). RA is characterized by systemic inflammation, which is thought to play a key role in accelerated atherosclerosis and in the increased incidence of cardiovascular disease, an important comorbidity in patients with RA. The inflammatory process underlying the cardiovascular risk both in obesity and RA may be mediated by adipocytokines, a heterogeneous group of soluble proteins mainly secreted by the adipocytes. Many adipocytokines are mainly produced by white adipose tissue. Adipocytokines may also be involved in the pathogenesis of OA since a positive association with obesity has been found for weight-bearing and nonweight-bearing joints, suggesting that, in addition to local overload, systemic factors may contribute to joint damage. In this review we summarize the current knowledge on experimental models and clinical studies in which adipocytokines were examined in obesity, RA, and OA and discuss the potential of adipocytokines as comorbidity biomarkers for cardiovascular risk.

Implementing life cycle sustainability assessment for improved space mission design.

Within the space sector, the application of Environmental Life Cycle Assessment (E-LCA) is beginning to emerge as a credible and compelling method for scientifically quantifying environmental impacts of space missions. However, E-LCA does not fully align with the concept of triple-bottom-line sustainability, while the combination of all three sustainability dimensions (environment, society, and economy) within a single life cycle study has thus far never been attempted within the space industry. Moving toward a Life Cycle Sustainability Assessment (LCSA) is, therefore, a logical next step for the space sector to allow these three sustainability dimensions to be addressed. Consequently, this article presents the underlying principles of a new LCSA framework for space missions and demonstrates its applicability for improving system-level design concepts based on the interaction between sustainability dimensions. The framework was formed based on a systematic literature review to analyze the background, issues, and knowledge gaps related to life cycle methodologies, as well as context-specific sustainability aspects. The framework has been implemented within a life cycle database called the Strathclyde Space Systems Database (SSSD). Using the SSSD, the framework was tested on a mission concept called Moon Ice Observation Satellite to demonstrate how changes in the design for a circular economy and other sustainability-based principles will affect the functionality of the mission at the system level. It is envisaged that this framework will enable engineers to create sustainable space systems, technologies, and products that are not only cost-efficient, eco-efficient, and socially responsible, but also ones that can easily justify and evidence their sustainability. Integr Environ Assess Manag 2023;19:1002-1022. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Classification of regular and chaotic motions in Hamiltonian systems with deep learning.

This paper demonstrates the capabilities of convolutional neural networks (CNNs) at classifying types of motion starting from time series, without any prior knowledge of the underlying dynamics. The paper applies different forms of deep learning to problems of increasing complexity with the goal of testing the ability of different deep learning architectures at predicting the character of the dynamics by simply observing a time-ordered set of data. We will demonstrate that a properly trained CNN can correctly classify the types of motion on a given data set. We also demonstrate effective generalisation capabilities by using a CNN trained on one dynamic model to predict the character of the motion governed by another dynamic model. The ability to predict types of motion from observations is then verified on a model problem known as the forced pendulum and on a relevant problem in Celestial Mechanics where observational data can be used to predict the long-term evolution of the system.

Ecospheric life cycle impacts of annual global space activities.

This paper presents a first-order approximation of ecospheric life cycle impacts from annual global space activities across two scenarios using a streamlined Life Cycle Sustainability Assessment (LCSA). The first scenario considers all space missions launched throughout the 2018 calendar year whilst the second is a futuristic scenario where affordable access to space significantly increases the prevalence of space operations. A new space-specific life cycle database and sustainable design tool called the Strathclyde Space Systems Database (SSSD) has been used to compile the inventory of each scenario and generate results across numerous impact categories. The results for each scenario are then compared against normalised values to portray their contribution towards annual worldwide impacts and their severity in terms of planetary boundaries. This allows the relative life cycle sustainability impacts of space activities to be benchmarked for the first time, forming a basis for evaluation and discussion. Overall, the study highlights that despite the relatively small footprint of the space industry at present, this will likely become much more meaningful in the future based on predicted trends. This places an added importance on addressing potential adverse life cycle impacts within the design process of future space technologies and products.

Abnormal plasma levels of different angiogenic molecules are associated with different clinical manifestations in patients with systemic sclerosis.

OBJECTIVES: Systemic Sclerosis (SSc) is characterized by a microvascular damage due to an impairment of different angiogenic and angiostatic factors. Aim of this study was to measure plasma levels of nine molecules involved in these vascular processes in a group of SSc patients, respect to healthy controls (NC). METHODS: Sixty-five patients (M/F = 2/63; mean age = 57.29 yrs; mean disease duration = 9,63 yrs) with established SSc according to ARA criteria, and sixteen age- and sex-matched NC were enrolled. Plasma levels of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), platelet derived growth factor- bb (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1), leptin, hepathocyte growth factor (HGF), follistatin, granulocyte-colony stimulating factor (G-CSF) and interleukin 8 (IL-8) were measured using commercially available immunoassay kits (Human Angiogenesis 9-Plex Panel, Bio-Rad Laboratories). RESULTS: We detected a significant increase of Ang-2 (median value 1315.4 pg/ml vs 538.73 pg/ml; p=0.0292), HGF (median value 2886.16 pg/ml vs 1296.16 pg/ml; p=0.0001), IL-8 (median value 32.22 pg/ml vs 16.86 pg/ml; p=0.02), leptin (median value 32589,1 pg/mg vs 10679.61 pg/ml; p=0.0065), PDGF-BB (median value 7258.6 pg/ml vs 2913.44 pg/ml; p=0.0005), PECAM-1(median value 21681.81 pg/ml vs 10354.53 pg/ml; p=0.0003) and VEGF (median value 236.72 pg/ml vs 122.905 pg/ml; p=0.0073) in patients with SSc respect to NC. Higher levels of PDGF-BB (p=0.03) and PECAM-1 (p=0.05) were found in patients with digital ulcers while lower levels of PECAM-1 were found in patients with pulmonary hypertension (PH). Besides levels of IL-8 were higher in patients with PH (p=0.04) and lower in those with pulmonary fibrosis (p=0.5), while levels of Ang-2 were higher in those with a 'late' nailfold video-capillaroscopy (NVC) pattern respect to those with an 'early/active' one (p=0.05). Moreover, plasma levels of VEGF (p=0.02) and PDGF-BB (p= 0.04) were significantly higher in those patients positive for anti-topoisomerase 1 antibodies. CONCLUSIONS: Our findings show significantly higher circulating levels of seven angiogenic parameters in SSc patients, thus reflecting the disregulation of endothelium in this disease. Abnormal levels of these molecules may be considered an attempt for compensatory although ineffective mechanisms of vascular function, leading to the development of the main clinical manifestations of SSc.

Subclinical atherosclerosis in systemic sclerosis: Different risk profiles among patients according to clinical manifestations.

INTRODUCTION: Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways. AIM: To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients. METHODS: Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods: carotid ultrasound and flow mediated dilation (FMD) of the brachial artery. RESULTS: Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P = .006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8 mm vs 0.55 mm; P < .0001) while FMD was significantly lower (median value 9% vs 14%; P = .0086) in patients compared to healthy controls. Among the SSc patients, thickening of CCA-IMT was significantly associated with the presence of diastolic dysfunction of left ventricle (absence of diastolic dysfunction: odds ratio [OR] 0.2, 95% CI 0.04-0.92, P = .038) and with a higher Framingham score (OR 1.3, 95% CI 1.03-1.6], P = .024). The diffuse cutaneous form was slightly protective against pathological FMD (OR 0.12, 95% CI 0.022-0.71, P = .019). CONCLUSIONS: This study confirms the involvement of macrocirculation in SSc patients, detecting the presence of subclinical ATS markers more frequently in patients compared to healthy controls. Framingham score, diastolic dysfunction of left ventricle and limited cutaneous form of the disease appeared to be associated with a higher risk of developing ATS.

Synthetic database of space objects encounter events subject to epistemic uncertainty.

The databases included on this article refers to variables and parameters belonging to the Space Traffic Management (STM), Evidence Theory and Machine Learning (ML) fields. They have been used for implementing ML for autonomously predict risk associated to a close encounter between two space (Sanchez and Vasile, On the Use of Machine Learning and Evidence Theory to Improve Collision Risk Management, Acta Astronautica, Special Issue for ICSSA2020, In Press [1]). The position of the objected is assumed to be affected by epistemic uncertainty, which has been modeled according to Dempster-Shafer Evidence theory (DSt) [2]. Six datasets are presented. Two (DB1 and DB2, respectively) include samples of space object close encounters subject to epistemic uncertainty on the relative position. Other two databases (DB3 and DB4, respectively) include the values of the Cumulative Plausibility and Belief Curves (CPC and CBC, respectively) of each sample included in DB1. The remaining databases (DB5 and DB6), contain the value of the CPC and CBC of each sample included in DB2. All of them are synthetic databases created using computer simulation to obtain the results presented in [1]. DB1 database is constituted by 9,000 samples and 45 columns and a header, while DB2 is formed by 28,800 samples and 45 columns and a header. These databases come from a set of, respectively, 5 and 14 different families of encounter geometries defined by the range of values that can be assigned to the bounds of the intervals for the uncertain variables, assumed to be affected by epistemic uncertainty, considered to have been provided by two sources of information. The uncertain variables are: the miss distance, [µx, µy], on the impact plane (B plane), the standard deviation of the relative position projected on the B plane, [σx, σy], and the Hard Body Radius of the combined objects, HBR. The dataset is completed with STM related parameters: miss distance and covariance matrix of the uncertain ellipse projected on the B plane enclosing all samples defined by the uncertainty intervals, the Probability of Collision (PC ) of this ellipse or the elapsed time to the Time of Closest Approach (TCA); with DSt related parameters: Belief and Plausibility of certain values of Pc; and the class of the event according to the classification detailed in [1]. DB3 and DB4 are constituted by 34 columns and 9000 rows containing the Plausibility and Belief for Pc values and the corresponding Probabilities of Collision necessary to build the CPC and CBC of the events in DB1, while DB5 and DB6 are constituted by 34 columns and 28,800 rows containing the Plausibility and Belief for Pc values and the corresponding Probabilities of Collision values necessary to build the CPC and CBC of the events in DB2. These databases have a potential usage by the ML community interested in STM as well as for the space community, especially, space operators interested in introduce epistemic uncertainty on collision risk assessment. These databases contribute to build a scarce field such as the databases of encounter events [3].

Robust mission design through evidence theory and multiagent collaborative search.

In this paper, the preliminary design of a space mission is approached by introducing uncertainties on the design parameters and formulating the resulting reliable design problem as a multiobjective optimization problem. Uncertainties are modelled through evidence theory and the belief, or credibility, that the successful achievement of mission goals is maximized along with the reliability of constraint satisfaction. The multiobjective optimization problem is solved through a novel algorithm based on the collaboration of a population of agents in search for the set of highly reliable solutions. Two typical problems in mission analysis are used to illustrate the proposed methodology.