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center dot PURPOSE: To optimize artificial intelligence (AI) algo-rithms to integrate Scheimpflug-based corneal tomogra-phy and biomechanics to enhance ectasia detection.center dot DESIGN: Multicenter cross-sectional case-control ret-rospective study.center dot METHODS: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Op-tikgerate GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy.center dot RESULTS: The area under the receiver operating char-acteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sen-sitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), devel-oped with 18 features in 156 trees using 10-fold cross -validation, had a significantly higher AUC (0.945; De -Long, P < .0001) for detecting VAE-NT (84.4% sen-sitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001).center dot CONCLUSIONS: AI optimization to integrate Scheimpflug-based corneal tomography and biome-chanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning consider-ing additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will con-tinuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society. (Am J Ophthalmol 2023;251: 126-142. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))

Background/Introduction The bactericidal/permeability-increasing fold-containing family-B-member-4 (BPIFB4) serves as a biomarker of healthy aging [1,2] and displays prognostic relevance in vascular pathology [3–5]. We recently described a drop in plasma BPIFB4 level in patients with severe COVID-19 compared to low-grade disease patients [6]. Purpose As COVID-19 is associated with autoimmune features, we developed the methods for determination of Anti-BPIFB4 IgG (autoAbs) and then characterized their neutralizing activity in COVID-19 patients. Methods A sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs against BPIFB4 in 60 hospitalized COVID-19 patients and in 30 healthy volunteers. Compared to the healthy controls, the optical density (OD) level of autoAbs in COVID-19 showed considerable variability distributing over a range between 0.13 and 0.85. We thus divided the patients into two groups, one with OD >0,29 and the other one with a OD >0,29, where 0,29 represents the OD mean value of autoAbs against BPIFB4 in physiological conditions. Results Since patients with higher OD are mainly those who spend in average a higher number of days in hospital, we stratified the patients according to the Length of Stay (LoS) in hospital (Figure 1), and found a trend towards a positive correlation between AutoAbs OD level and length of hospitalization within COVID-19 patients. When present, autoAbs exclusively target the WT-BPIFB4 autoantigens and neglect the recognition of the Longevity-associated-variant-(LAV) of the BPIFB4 gene known for its therapeutic efficacy in cardiomyopathy, atherosclerosis (4), diabetes (6) and platelets' reactivity. As expected, the pre-treatment of human PrP with the recombinant rhLAV-BPIFB4 reduces platelets' aggregation in response to ADP and collagen in COVID-19 patients in vitro. On the other hand, at functional level, the well established LAV-BPIFB4-regulated M2 macrophage polarization (4,7), is neutralized in presence of anti-BPIFB4 autoAbs-enriched plasma. Conclusion We conclude that a significant proportion of hospitalized COVID-19 patients displays BPIFB4-AutoAbs which are positively correlated with the Length of Stay (LoS) in hospital. In future, it will be of utmost importance to clarify if the 4 missense SNPs which distinguish LAV-BPIFB4 gene from its WT-counterpart, are instrumental to prevent the self-tolerance brake-down and the potential development of specific antibodies against endogenous cardiovascular protectors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Cariplo Foundation (n.2016-0874) to AAP and CV; Ministry of Health (RF-2016-02364864) to AAP and CV

Peripheral nerve injuries affect millions of people per year and cause loss of sensation and muscle control alongside chronic pain. The most severe injuries are treated through a nerve autograft; however, donor site morbidity and poor outcomes mean alternatives are required. One option is to engineer nerve replacement tissues to provide a supportive microenvironment to encourage nerve regeneration as an alternative to nerve grafts. Currently, progress is hampered due to a lack of consensus on how to arrange materials and cells in space to maximize rate of regeneration. This is compounded by a reliance on experimental testing, which precludes extensive investigations of multiple parameters due to time and cost limitations. Here, a computational framework is proposed to simulate the growth of repairing neurites, captured using a random walk approach and parameterized against literature data. The framework is applied to a specific scenario where the engineered tissue comprises a collagen hydrogel with embedded biomaterial fibres. The size and number of fibres are optimized to maximize neurite regrowth, and the robustness of model predictions is tested through sensitivity analyses. The approach provides an in silico tool to inform the design of engineered replacement tissues, with the opportunity for further development to multi-cue environments.

The aim of the present study is to compare the effectiveness of a computerised system (QuickSleeper) compared to traditional syringe in injection of local anaesthetic focusing on the perception of anxiety and pain in paediatric patients.Study design: 100 children aged between 3 and 15 years in need of two dental treatments that required local anaesthesia were selected and treated randomly but alternately with computerised and traditional local anaesthesia. After each anaesthetic injection, patient's anxiety was measured using the Venham test.Electronic anaesthesia showed statistically significant better results than traditional anaesthesia according to the Venham pain scale, in both mandibular and maxillary sites. Statistics: Data were analysed using the paired Wilcoxon test.The computer-assisted anaesthesia system resulted in a significantly lower pain perception score and yielded to helpful, cooperative behaviour. For this reason, it is an advantageous alternative to traditional injection anaesthesia and can avoid invasive treatments and trauma for young patients.

Loggerhead turtles (Caretta caretta) spend most of their life in large marine areas occupying a variety of habitats where they are exposed to different types of threats. Among these, marine litter is known to pose a risk of entanglement or ingestion. Areas of risk exposure can be identified where the species overlap with litter accumulations, but gathering data on this highly mobile species and marine litter, especially in high sea areas, is challenging. Here we analysed five years of sea turtle and marine litter data collected by a network of research bodies along fixed trans-border transects in the Mediterranean Sea. Ferries were used as observation platforms to gather systematic data on a seasonal basis using standard protocols. The Sightings Per Unit of Effort was used as an index to compare loggerhead turtle sightings over time and space, and risk exposure areas were assessed based on seasonal overlap of species hot spots and high-density plastic areas revealed by Kernel analysis. In almost 180,000 km surveyed, 1258 sea turtles were recorded, concentrated mostly during all seasons in the central Adriatic Sea and Sardinia-Sicilian channels, and during spring in central Tyrrhenian. Plastic was the highest fraction of litter items detected. Several areas of higher risk exposure, both permanent and seasonal, were identified, mainly in the Adriatic Sea and during the spring-summer seasons. Records of both species and floating litter were highly variable, underlying the need for continuous long-term monitoring to develop sound conservation and management measures, especially in the identified areas of risk exposure.

BackgroundPatients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments.ObjectivesOur long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves.MethodsA large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1).ResultsA significantly increased prevalence of COVID-19 (8.37% vs 6.49%; pInterestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000).ConclusionThe cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series.Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population.Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy.Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.References[1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113.[2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744.[3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248Disclosure of InterestsNone declared

BackgroundElectrocardiographic (EKG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) patients and they are associated with other systemic manifestations1 as well as with a worse prognosis.2 There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic approaches to patients with EKG abnormalities.3In the last decade, many studies focused on the components of the interleukin (IL)-33/ST2 axis. Under physiological conditions, IL-33 is released by apoptotic cardiac cells, promoting a protective mechanism of cell survival, thanks to the binding with its transmembrane receptor ST2.4 During pathological cardiovascular events, an abnormal secretion of the IL-33 soluble receptor (sST2) by Th2 cells occurs. It binds IL-33 not allowing the physiological mechanism driven by the IL-33/ST2 binding previously described.4 For these reasons, sST2 has been proposed as a biomarker of cardiac injury in a variety of diseases.5ObjectivesAim of this study was to analyse clinical and demographical parameters in a group of SSc patients, trying to define any possible feature associated with EKG abnormalities. Furthermore, the role of IL-33/ST2 axis components as biomarkers of cardiac injury in patients with SSc-related EKG abnormalities was evaluated, also assessing the possible correlation with serum concentration of NT-pro-BNP, a well-known cardiac injury biomarker in SSc.MethodsData from 277 SSc patients, fulfilling the 2013 ACR/EULAR classification criteria,6 attending our Scleroderma Clinic were retrospectively analysed. We selected patients with EKG trace and a blood sample available, collected after the SSc diagnosis. The sera levels of sST2 (ELISA Kit, Abcam), IL-33 (ELISA kit, RayBiotech) and NT-pro-BNP (ELISA Kit, Abcam) were measured. Patients with a history of heart diseases occurring before the diagnosis of SSc or features of secondary cardiac involvement (pulmonary arterial hypertension, severe interstitial lung disease or renal disease) were excluded.ResultsForty-six SSc patients showed significant EKG abnormalities (rhythm and conduction disorders). Thirty-one SSc patients without pathologic finding at EKG traces were recruited as the control group.From the analysis of the clinical characteristic of the disease at the moment of serum collection, patients with EKG anomalies have more frequently both a diffuse form of disease (n°-%: 23-50 vs 7-23; p 0.01), with a mean value of mRSS higher than controls (11±9 vs 6±6; p 0.01), and a scleroderma “late” pattern at the nailfold capillaroscopy (n°-% 23-50 vs 6-19; p 0.027).Significantly higher median values of serum levels of sST2 in SSc patients with EKG disorders compared to the control group (4289pg/mL, IQR 2383 vs 2560 pg/mL, IQR 1455; p 0.0002) were detected, while opposite results were found analyzing serum levels of IL-33 (2.89 pg/mL IQR 101 vs 9 pg/mL IQR 277; p 0.032) (Graph 1). Serum NT-pro-BNP median values were significantly higher in the group of patients with EKG abnormalities than in the control group (149 pg/mL, IQR 354 vs 26 pg/mL, IQR 62; p 0.0007). These values correlated with sST2 serum levels (rho Spearman correlation 0.37; p 0.0006).ConclusionSSc patients with EKG abnormalities showed an increased skin and vascular involvement with respect to the control group. These associations could help clinicians in clinically stratifying SSc patients at risk of EKG abnormalities. To our knowledge, this is the first report evaluating the serum concentration of sST2 in SSc patients. Based on these results, we can speculate on the role of this molecule as potential biomarkers of early cardiac injury during SSc, although further studies involving a larger cohort of patients are needed.References[1]Vacca et al. Rheumatol 2014[2]Tyndall et al. Ann Rheum Dis 2010[3]Muresan et al. Clin Rheumatol 2018[4]Vianello et al. Int J Biochem Cell Biol 2019[5]Dudek et al. Adv Clin Exp Med 2020[6]van den Hoogen et al. Arthritis Rheum 2013Figure 1:Graph 1. Serum sST2 (a) and IL-33 (b) concentrations in patients with EKG abnormalities (EKG+) vs control group (EKG)Disclosure of InterestsNone declared.

BackgroundRheumatoid arthritis (RA) is the most common systemic autoimmune disease that primarily affects joints but is also often characterized by extra-articular involvement1. Cardiovascular diseases are the most important causes of sudden death in these patients, which present a risk of developing cardiovascular events increased by 48%2. The causes of increased cardiovascular risk are several and not completely understood, but recent evidence supports the key role of endothelial dysfunction in pathogenesis. In this complex scenario, it is known that IL-6 receptors are present at the endothelial level and can be activated leading to endothelial dysfunction. SARS-Cov-2 is a coronavirus responsible for the disease called ‘coronavirus disease 2019’ (CoViD-19) characterized by clinical manifestations ranging from a flu-like syndrome up to severe lung damage associated with systemic hyper cytokine syndrome that can lead to multiple organ failure and death. Therefore, both RA and Covid-19 are associated with an increased pro-thrombotic and cardiovascular risk and IL-6 might be crucial in the pathophysiological mechanisms of both diseases.ObjectivesThe main hypothesis of this study was to evaluate the possible role of IL-6 as a promoter of endothelial dysfunction in RA and CoViD-19.MethodsIn vitro experiments were conducted on the endothelial cell line EA. hy926. Cells were treated for 24 h with fetal bovine serum (FBS), a pool of RA patients’ sera or a pool of CoViD-19 patients’ sera. The expression levels of adhesion molecules (V-CAM1/CD-106, I-CAM/CD-54, p-selectine/CD-62, tissue factor/CD-142) and apoptosis were analyzed using cytofluorimetric technique. In addition, the autophagy level, using the autophagy markers p62 and LC3II, were evaluated through a western-blot analysis. The same experiments were conducted co-treating cells with the same pool of sera in addition to tocilizumab (TCZ), an anti-IL-6 drug, to verify the reversibility of the process and test the role of the aforementioned cytokine. Data are reported as interquartile median values. The Kruskal Wallis test was used for unpaired samples and the Mann-Whitney test for paired samples. PResultsEA. hy926 cells, when treated with both RA and CoViD-19 patients’ sera, showed increased levels of activation molecules and apoptosis compared to FBS treated cells. In addition, we observed increased levels of both p62 and LC3 proteins after both rheumatoid arthritis and CoViD-19 patients’ sera treatment. All these findings were reversible in the presence of TCZ. The results are presented in Figure 1.Figure 1.Figures show the adhesion molecules levels (A), apoptosis levels (B), p62 and LC3II levels (C), in all experimental conditions. FBS 10% (cells treated with FBS at 10% concentration), S AR (cells treated with a pool of RA patients’ sera); S Covid (cells treated with a pool of COVID-19 patients’ sera); FBS 10%+toci (cells co-treated with FBS at 10% concentration and TCZ); S AR+toci (cells co-treated with a pool of RA patients’ sera and TCZ); S Covid+toci (cells co-treated with a pool of CoViD-19 patients’ sera and TCZ).ConclusionOur data showed that treatment with RA and CoViD-19 patients’ sera increase the activation and death of endothelial cells in vitro. The increased level of cells death is possibly due to a block of autophagy. The reversibility of the process after blocking IL-6 with TCZ co-treatment confirms the hypothesis that IL-6 can play a key role in the pathogenesis of endothelial damage in patients with RA and CoViD-19.References[1]Bordy R et al. Microvascular endothelial dysfunction in rheumatoid arthritis. Nat Rev Rheumatol. 2018 Jul;14(7):404-420.[2]Avina-Zubieta et al. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann. Rheum. Dis. 2012; 71:1524–1529.Disclosure of InterestsNone declared.

BackgroundIn psoriatic arthritis (PsA) and rheumatoid arthritis (RA) systemic inflammation is known to cause endothelial dysfunction(1). Nailfold videocapillaroscopy (NVC) analyzes in vivo blood vessels, looking for alterations due to microvascular damage, and its application in these pathologies often highlights interesting abnormalities. PsA is characterized by lower mean capillary length and density and abnormal morphology, such as tight terminal convolutions. In RA typically elongated and dilated capillaries and prominent subpapillary plexus are described(2, 3). Differences between RA and PsA NCV patterns are known but not well defined yet(3).ObjectivesAim of our study was to evaluate the microvascular features circulation by NVC in patients affected by PsA and RA, looking for possible differences that may characterize the two diseases.MethodsWe recruited outpatients affected by PsA or RA classified according to standard criteria(4, 5) referring to the Rheumatology Unit at Sapienza University of Rome. Healthy controls (HCs) without known risk factors for nailfold capillary alterations(6) were also recruited. Patients and HCs underwent NVC with a 200x magnification lens. The following morphological parameters were considered: number of capillaries per square millimeter, alterations in length, dimension, morphology and distribution of the capillary; presence of ectatic loops, hemorrhages, flux abnormalities(7, 8). A semi-quantitative rating scale was adopted to score these changes, according to previous studies(9). The mean score for each subject was obtained by analyzing all fingers, except the thumbs.For the statistical analysis, Chi-square and Mann-Whitney tests were used. All tests were two-sided with a significance level set at pResultsWe recruited 34 patients (20 with PsA and 14 with RA) and 30 HCs. For patients, the mean age was 61,7 years (SD 15,4), median disease duration was 184 months (SD 204) and males were 18 (53%). Active or past smokers were 11 (18%), 9 (15%) suffered from arterial hypertension and 2 (0.03%) from type 2 diabetes mellitus. Raynaud’s phenomenon was present in 4 patients with PsA (20%) and 6 with RA (43%).The most frequent morphological changes were tortuous capillaries (90% in PsA and 100% in RA), single-crossing shape (90% and 86%) and bizarre capillaries (30% in both groups) while multiple crossing and ramified capillaries were present in 50% and 21 % RA patients only.With respect to HCs, we found significantly more frequent changes concerning morphology, ectatic loops, presence of hemorrhages and capillary plexus visibility in both PsA and RA patients. Moreover, patients with RA showed significantly more frequent abnormalities of the blood flow with respect to HCs. These results are shown in Table 1.Table 1.Comparison of the main NVC changes in patients and HCs.NVC ChangesHCPsARAN (%)N (%)P value vs HCsN (%)P value vs HCsMorphology3 (10%)14 (70%)p12 (86%)pEctatic loops0 (0%)11 (55%)p8 (57%)pHemorrhages2 (0.07%)1 (5%)p6 (43%)pPlexus19 (63%)10 (50%)p7 (50%)pFlux abnormalities3 (10%)6 (30%)p>0.055 (36%)pThe presence of hemorrhages was significantly higher in RA rather than in PsA patients (pConclusionOur study confirms and completes the frame of NCV alterations in PsA and RA. We described for the first time alterations in the capillary morphology and the presence of hemorrhages in both groups of patients with respect to HCs. It remains to evaluate how these findings can reflect the microvascular environment of chronic arthritis.References[1]Fromm, S et al. Arthritis Res Ther 2019[2]Lambova SN, Müller-Ladner U. Microvasc Res 2012[3]Graceffa D, et al. Arthritis 2013[4]Taylor W, et al. Arthritis Rheum 2006[5]Aletaha D, et al. Ann Rheum Dis 2010[6]Ciaffi J, et al. Microvasc Res 2020[7]Maricq HR. Arthritis Rheum 1981[8]Smith V, et al. Autoimmun Rev. 2020[9]Cutolo M, et al. J Rheumatol 2000Disclosure of InterestsNone declared

BackgroundLung ultrasound (LUS) is a technique that showed a high diagnostic accuracy for interstitial lung disease (ILD) detection in systemic sclerosis (SSc) patients and currently in progress of standardization. Traditionally, B-lines represented the finding of ILD, with the ≥10 total cut-off reported by Tardella et al. resulting to be closely related to moderate ILD detected on high resolution chest computed tomography (HRCT). Recently, Fairchild et al. proposed novel LUS criteria for the evaluation of pleural line, disclosing high accuracy and reproducibility.ObjectivesTo compare B lines cut-off with novel pleural line criteria and the respectively associated variables.MethodsWe enrolled 55 consecutive patients affected by SSc according to ACR/EULAR 2013 criteria who underwent respiratory functional tests (RFTs) during 2021, excluding smokers and those with arterial pulmonary hypertension. Twenty-four of them carried out a HRCT during a ± 6-months’ time. In the same day of RFTs, two certified blinded operators performed LUS for each patient applying the 14-areas technique proposed by Gutierrez et al., looking for the presence of total ≥10 cumulative B lines and the fulfilling of Fairchild’s criteria for pleural line. A 3-13 MHz operating linear probe was used. Clinical-demographic data and ongoing therapies were collected.ResultsAmong 55 total SSc patients, the agreement between the two operators for Fairchild’s criteria was almost perfect (Cohen’s kappa (k) =0.81) and substantial for ≥10 cumulative B-lines count (k=0.74). Fairchild’s criteria showed a higher diagnostic accuracy compared with ILD detected on HRCT, with an overall specificity (SP) and a positive predicted value (PPV) of 100% (Table 1). A negative correlation emerged between total lung capacity values (TLC%) and both B lines cut-off [first operator (IO): p 0.04, r -0.27; second operator (IIO): p 0.042, r-0.28] and pleural line criteria (IO: p 0.009, r -0.35; IIO: p 0.08, r – 0.36), but only the latter negatively correlated also with forced vital capacity values (FVC%) (IO: p 0.04, r – 0.27; IIO p 0.03, r -0.28). The ≥10 total B lines amount correlated positively with concurrent mycophenolate therapy (IO: p 0.09, r 0.28; IIO: p 0.005, r 0.37) and negatively with anti-centromere antibodies (IO: p 0.002, r -0.3; IIO p 0.009, r -0.34). The presence of digital ulcers showed a positive correlation with pleural line criteria (IO: p 0.03, r 0.29; IIO: p 0.005, r 0.37), with a significant association on multivariate analysis (IO: p 0.03, IIO: p 0.01).Table 1.Overall sensitivity, specificity, positive predictive value, negative predictive value of LUS compared to ILD detected on HRCT. C.I. 95% confidence interval.SE (C.I.)SP (C.I.)PPV (C.I.)NPV (C.I.)Fairchild’s criteria fulfilling0.91 (0.76 - 0,97)1 (0.78 – 1.000)1 (0.88 -1.00)0.82 (0,59 – 0.94)≥10 cumulative B-lines count0.73 (0.56 – 0.85)0.8 (0.55 – 0.93)0.89 (0.72 – 0.96)0.57 (0.36 – 0.75)ConclusionWe confirmed the feasibility and reliability of Fairchild’s recently proposed pleural line LUS criteria, that showed a higher diagnostic accuracy versus ≥10 cumulative B-lines count for ILD detected on HRCT, presenting SP and PPV values of 100% in SSc. Furthermore, these LUS features seem to differently associate with other aspects of the disease such as autoantibody specificity and vascular lesions, thus deserving future deeper evaluations. For the first time, we found that Fairchild’s criteria were associated with a clinical variable such as digital ulcers. Our results highlight the relevance of pleural line evaluation for ILD detection in SSc on LUS and its possible role towards a standardization of this diagnostic technique.References[1]Gutierrez M et al., Radiol Med, 2019.[2]Xie, H.Q et al. Arthritis Res Ther, 2019.[3]Tardella M et al., Medicine (Baltimore), 2018.[4]Fairchild R et al. Arthritis Care Res, 2021.Disclosure of InterestsNone declared

The Sardinian and Sicilian Channels are considered hotspots of biodiversity and key ecological passages between Mediterranean sub-basins, but with significant knowledge gaps about marine mammal presence and potential threats they face. Using data collected between 2013 and 2019 along fixed transects, inter and intra-annual cetacean index of abundance was assessed. Habitat suitability, seasonal hot spots, and risk exposure for plastic were performed using the Kernel analysis and the Biomod2 R-package. 661 sightings of 8 cetacean species were recorded, with bottlenose and striped dolphins as the most sighted species. The north-eastern pelagic sector, the coastal waters and areas near ridges resulted the most suitable habitats for these species. The risk analysis identified the Tunis, Palermo, and Castellammare gulfs and the Egadi Island as areas of particular risk of plastic exposure. The study represents a great improvement for cetacean knowledge in this region and contributes to the development of effective conservation strategies.

Background The Mediterranean subpopulation of fin whale Balaenoptera physalus (Linnaeus, 1758) has recently been listed as Vulnerable by the IUCN Red List of threatened species. The species is also listed as species in need of strict protection under the Habitat Directive and is one of the indicators for the assessment of Good Environmental Status under the MSFD. Reference values on population abundance and trends are needed in order to set the threshold values and to assess the conservation status of the population. Methods Yearly summer monitoring using ferries as platform of opportunity was performed since 2008 within the framework of the FLT Med Network. Data were collected along several fixed transects crossing the Western Mediterranean basin and the Adriatic and Ionian region. Species presence, expressed by density recorded along the sampled transects, was inspected for assessing interannual variability together with group size. Generalized Additive Models were used to describe density trends over a 11 years’ period (2008–2018). A spatial multi-scale approach was used to highlight intra-basin differences in species presence and distribution during the years. Results Summer presence of fin whales in the western Mediterranean area showed a strong interannual variability, characterized by the alternance of rich and poor years. Small and large groups of fin whales were sighted only during rich years, confirming the favorable feeding condition influencing species presence. Trends highlighted by the GAM can be summarized as positive from 2008 to 2013, and slightly negative from 2014 to 2018. The sub-areas analysis showed a similar pattern, but with a more stable trend during the second period in the Pelagos Sanctuary sub-area, and a negative one in the other two sub-areas. Our findings further confirm the need for an integrated approach foreseeing both, large scale surveys and yearly monitoring at different spatial scales to correct and interpret the basin wide abundance estimates, and to correlate spatial and temporal trends with the ecological and anthropogenic drivers.

Recent advances in human motion sensing technologies and machine learning have enhanced the potential of AI to simulate artificial agents exhibiting human-like movements. Human movements are typically explored via experimental recordings with the aim of establishing relationships between neural and mechanical activities. A recent trend in AI research shows that AI algorithms work remarkably well when combined with sufficient computing resources and data. One common criticism is that all of these methods are gradient-based, which involves a gradient approximation, thus suffering of the well-known vanishing gradient problem. In this paper, the goal is to build an ANN-based controller that enables an agent to walk in a human-like way. In particular, the proposed methodology is based on a new approach to Neuroevolution based on NeuroEvolution of Augmenting Topologies (NEAT). The original algorithm has been endowed with a different type of selection-reproduction mechanism and a modified management of the population, with the aim to improve the performance and to reduce the computational effort. Experiments have evidenced the effectiveness of the proposed approach and have highlighted the interdependence among three key aspects: the reward framework, the Evolutionary Algorithm chosen and the hyper-parameters' configuration. As a consequence, none of the above aspects can be ignored and their balancing is crucial for achieving suitable results and good performance.

The upper Triassic Streppenosa and Noto Formations are considered the main source rocks of the Hyblean Plateau in south-eastern Sicily, that represents the present-day deformed foreland of the Sicilian fold-and-thrust belt. This work focusses on the Upper Triassic Streppenosa and Noto Formations, penetrated by the Eureka 1 onshore well (south-eastern Sicily, Italy) in order to constrain the burial-thermal history of this basin of the western Tethys. According to previous paleogeographic reconstructions, starting from Norian, the palaeogeographic scenario consisted, moving from north to south, of a wide carbonate platform (Sciacca Fm.), adjacent to two different domains: the euxinic lagoon/basin of the Noto Formation, and, to the south, the basin of the Streppenosa Formation. Eureka 1 well is located in the inner portion of the platform-basin system and its Triassic succession consists of alternation of black shales and micritic, microbial dolomitic laminated limestones. A detailed description of the sedimentological facies from cores samples has been performed together with detailed organic petrography/Raman spectroscopy and clay mineralogy on fine grained sediments to assess thermal maturity of the Streppenosa and Noto Fms. The main facies consist of light-grey limestones (wackestone-mudstone) with scattered sub-angular intraclast, light grey finely laminated limestones, dark grey-black laminated mudstones, brownish undulated algal laminae saturated with bitumen. The cores are often bitumen saturated and interrupted by different sets of open microfractures, veins filled with calcite, and stylolites (parallel and vertical with respect to lamination) that may enhance and/or inhibit at places the fluid flow. Concerning thermal maturity, the studied interval falls in the lower-mid portion of the oil window, with robust agreement among the geothermometers derived from the three adopted techniques.

Objective. Systemic sclerosis (SSc) is a severe multiple-organ disease charac- terised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society of Rheumatology pro- moted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods. The SPRING is a multi- centre rheumatological cohort study encompassing the wide scleroder- ma spectrum, namely the primary Raynaud’s phenomenon (pRP), sus- pected secondary RP, Very Early Diag- nosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteris- tics of 2,028 Italian patients’ popula- tion at the initial phase of enrollment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results. Definite SSc showed signifi- cantly higher prevalence of digital ul- cers, capillaroscopic ‘late’ pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cu- taneous subset, and anti-Scl70 sero- positivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased preva- lence of unfavorable clinico-serologi- cal features. Conclusion. Nationwide registries with suitable patients’ subsetting and follow-up studies since the prodromal phase of the disease may give us valu- able insights on the SSc natural history and main prognostic factors.

Background:Conflicting results have been published regarding the risk of infection with SARS-CoV-2 and development of severe COVID-19 among patients affected by rheumatic musculoskeletal diseases (RMDs). [1-4] Taking into account the lack of effective drugs to treat the COVID-19 and despite the burdensome and costly lockdown measures adopted to counteract the spread of SARS-CoV-2, effective and safe vaccines appear reasonably to be the best strategy for fighting the virus. [6] Before vaccines availability, several reports showed that a non-negligible proportion of subjects, among the general population or within specific categories, would have refused vaccination against COVID-19 once possible;[6, 7] data on vaccination hesitation among patients with RMD are not available yet.Objectives:This study aimed to evaluate the attitude of patients with RMDs to vaccination against SARS-CoV-2 and explore the factors which may influence it.Methods:During the first weeks of Europe vaccination campaign, we proposed an online survey to Italian adult patients with RMDs followed up in the Rheumatology Unit. All patients fulfilled the most recent classification criteria for each disease. HCs were recruited using a “best friend” system. The informed consent was collected for all participants. The questionnaires included the following items: demographic features, presence of comorbidities, educational level, and ongoing therapy. The individual’s perception of the COVID-19 vaccination, as well as the willingness to receive a COVID-19 vaccination with targeted questions was properly assessed.For the statistical analyses, Mann-Whitney and Chi-square tests were used. To account for baseline clinical differences among RMD-patients and controls, multivariable logistic regression analysis was used; covariates were selected according to a clinical criterion. The hypothesis that willingness for COVID-19 vaccine varied in specific subgroups of patients was tested using interaction terms at logistic regression analysis. All statistical tests were performed using the RStudio graphical interface and all tests were two-sided with a significance level set at pResults:We provided an online survey to 830 adult RMD-patients and 370 healthy controls (HCs). Overall, 626 RMD-patients and 345 HCs completed the survey. Patients with RMDs were less willing to receive a COVID-19 vaccination compared to HCs (Odds Ratio (OR) 0.24, 95% CI 0.17 – 0.34, pConclusion:The results of our study indicate for the first time that patients with RMDs are less willing to receive COVID-19 vaccination compared to the general population, despite perceiving themselves as at higher risk of getting infected with SARS-CoV-2 and develop severe COVID-19. However, our data underscored a meaningful aspect: patients with RMDs may change their attitude to COVID-19 vaccination if properly informed about risks and benefits by their trusted specialist.The results of this study encourage the entire rheumatologist community to become more committed to patient education, increasing their willingness to COVID-19 vaccine, which is the most promising strategy to protect them from the virus.References:1]Favalli EG et al. Arthritis Rheumatol, 2020[2]Fredi M, et al. Lancet Rheumatol, 2020.[3]Giardina F et al. Rheumatol Int 2021.[4]Pellegrino G et al. Clin Rheumatol 2020.[5]Frederiksen LSF, et al. Front Immunol, 2020.[6]La Vecchia C et al. Med Lav 2020.[7]Qiao S, et al. medRxiv 2020.Disclosure of Interests:None declared

The present paper has two aims: first, to re-evaluate the rotation of the Hyblean Plateau with respect to Africa in the light of updated African paleopoles; second, to obtain information about the block rotation pattern, possibly associated with the Scicli-Ragusa strike-slip fault zone. Our results complement pre-existing data and firmly indicate that: 1) the Hyblean Plateau did not rotate with respect to Africa, even during the Pliocene-Pleistocene rifting of the Strait of Sicily; 2) the Scicli-Ragusa fault system did not induce significant block rotations around vertical axis and therefore, the horizontal displacement of this tectonic lineament has to be considered less than 3 km.

Lava fountains have a major impact on the local population since they cause ash plumes that spread several kilometers above and hundreds of kilometers away from the crater. Ash fallout is responsible for disrupting airports and traffic on the motorways well beyond the area of the volcano itself, as well as affecting the stability of buildings and causing public health issues. It is thus a primary scientific target to forecast the impact of this activity on local communities on the basis of parameters recorded by the monitoring network. Between 2011 and 2015, 49 paroxysmal explosive episodes occurred at two of Mt Etna's five summit craters: the New South-East Crater (NSEC) and the Voragine (VOR). In this paper, we examine the features of the 40 episodes occurring at the NSEC during 2011–2013, and of the 4 events at VOR in December 2015. We study these paroxysms using geophysical monitoring data, characterize the episodes, and analyse all available data statistically. Our main results are two empirical relationships allowing us to forecast the maximum elevation of the ash plume from the average height of the lava fountain, useful for hazard assessment and risk mitigation. For Etna, and using the examples described in this paper, we can infer that wind speed 10 m s−1 is normally associated with weak plumes, bent-over along the wind direction and reaching lower elevations.

Kodamaea ohmeri, also known as Pichia ohmeri, is a yeast belonging to the Saccharomycetes family. In 2012, our hospital has recorded the first case of fungemia caused by K. ohmeri in an 80-year-old male, admitted to intensive care following an acute anterior-lateral myocardial infarction. K. ohmeri grew in blood cultures. Biochemical identification was confirmed using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry and molecular sequencing. Antifungal susceptibility has been performed by broth dilution technique. This case confirms that K. ohmeri is an emergent pathogen even though rarely isolated in human disease. Permanent catheterization is a risk factor and may cause the persistence of a K. ohmeri infection, as well as support treatments (mechanical ventilation, tracheotomy, dialysis). Our therapeutic strategy has been empirical and based exclusively on tested antifungals MIC because EUCAST recommendations does not indicate breakpoints.

While cetacean distribution and habitat is well investigated in some areas in the Mediterranean, only a few studies have been conducted so far in the central part of the Mediterranean basin. In order to fill this gap, a dedicated research program has been developed using ferries operating between Tunis and Genoa as platforms of opportunity to collect data on cetacean presence and distribution. The area was subdivided in three sub-regions: the Sardo-Tunisian channel, the eastern Sardinian margin and the international sanctuary for marine mammals Pelagos. During fall 2013, marine mammal observers surveyed 1900 nautical miles and recorded 39 encounters of 5 identified species including balaenopteridae, delphinidae, ziphiidae and physeteridae families. Bottlenose dolphin (Tursiops truncatus) and striped dolphin (Stenella coeruleoalba) were the most common species followed in decreasing occurrence by fin whale (Balaenoptera physalus), Cuvier’s beaked whale (Ziphius cavirostris) and sperm whale (Physeter macrocephalus). The distribution of bottlenose dolphin was restricted to the shallow waters of the Tunisian plateau over the continental shelf. Striped dolphins were sighted in the open sea waters and the eastern Sardinia margin. Large cetaceans as sperm whale and fin whale were mainly recorded over the canyon of Bizerte in the Sardo-Tunisian channel. Highest diversity index was reported in the Pelagos sanctuary even during autumn, confirming the area as a preferred habitat for several cetacean species. Our results also highlight the importance of the Sardo-Tunisian channel, where a relatively important diversity index has been computed, especially over the canyon of Bizerte. This study is the first to investigate cetacean diversity in pelagic central Mediterranean waters and highlights the insistent need to develop regular monitoring in this area.

Infrared focal plane arrays (IRFPA) based on HgCdTe semiconductor alloys have been shown to be ideal for tactical and strategic applications. High density (>1 M pixel), high operability HgCdTe detectors on large area, low-cost composite substrates, such as CdTe-buffered Si or GaAs, are envisioned for next-generation IRFPAs. Thermal expansion mismatch is among various material parameters that govern the structural properties of the final detector layer. It has previously been shown that thermal expansion mismatch plays the dominant role in the residual stress characteristics of these heteroepitaxial structures (Jacobs et al. in J Electron Mater 37:1480, 2008). The wafer curvature (bowing) resulting from residual stress, is a likely source of problems that may occur during subsequent processing. This includes cracking of the film and substrate during post-growth annealing processes or even certain characterization techniques. In this work, we examine dynamic curvature and stress during molecular beam epitaxy (MBE), of CdTe on Si and GaAs substrates. The effect of temperature changes on wafer curvature throughout the growth sequence is documented using a multi-beam optical sensor developed by K-Space Associates. This monitoring technique makes possible the study of growth sequences which employ annealing schemes and/or interlayers to influence the final residual stress state of the heteroepitaxial structures.

Minimization of operating bias and generation–recombination dark current in long wavelength infrared (LWIR) strained layer superlattice (SLS) detectors, consisting of a lightly doped p-type absorber layer and a wide band gap hole barrier, are investigated with respect to the band alignment between the wide band gap barrier and absorber layers. Dark current vs. bias, photoresponse, quantum efficiency, lifetime, and modeling are used to correlate device performance with the wide gap barrier composition. Decreases in dark current density and operating bias were observed as the conduction band of the wide gap barrier was lowered with respect to the absorber layer. The device achieved 95% of its maximum quantum efficiency at 0 V bias, and 100% by 0.05 V. This study demonstrates key device design parameters responsible for optimal performance of heterojunction based SLS LWIR detectors.

The Hamamatsu R12199-02 3-inch photomultiplier tube is the photodetector chosen for the first phase of the KM3NeT neutrino telescope. About 7000 photomultipliers have been characterised for dark count rate, timing spread and spurious pulses. The quantum efficiency, the gain and the peak-to-valley ratio have also been measured for a sub-sample in order to determine parameter values needed as input to numerical simulations of the detector. © 2018 The Author(s).

Marine litter is a major source of pollution in the Mediterranean basin, but despite legislative requirements, scant information is available for the ongoing assessment of this threat. Using higher size classes as proxy for litter distribution, this study gave a synoptic estimation of the amount, composition, and distribution of floating macro-litter in the Mediterranean. The average amount of macro-litter was in a range of 2-5 items/km2, with the highest in the Adriatic basin. Seasonal patterns were present in almost all study areas and were significant in the Ligurian Sea, Sardinian-Balearic basin, and Central Tyrrhenian Sea. Plastic accounted for > 80% of litter in all areas and seasons, with the highest proportion in the Adriatic Sea, Ligurian Sea, and Sicilian-Sardinian Channels; in the Bonifacio Strait, Tyrrhenian Sea, and Sardinian-Balearic basin, litter composition was instead more diverse. Spatial analysis suggested an almost homogeneous distribution of litter without evident regular aggregation zones.

Molecular beam epitaxy n-type long-wavelength infrared (LWIR) Hg1−xCdxTe (MCT) has been investigated using variable-field Hall measurement in the temperature range from 50 K to 293 K. A quantitative mobility spectrum analysis technique has been used to determine the role of multicarrier transport properties with respect to epilayer growth on lattice-matched cadmium zinc telluride, as well as lattice-mismatched silicon (Si) and gallium arsenide (GaAs) buffered substrates. Overall, after postgrowth annealing, all layers were found to possess three distinct electron species, which were postulated to originate from the bulk, transitional (or higher-x-value) regions, and an interfacial/surface layer carrier. Further, the mobility and concentration with respect to temperature were analyzed for all carriers, showing the expected mobility temperature dependence and intrinsic behavior of the bulk electron. Electrons from transitional regions were seen to match expected values based on the carrier concentration of the resolved peak. At high temperature, the lowest-mobility carrier was consistent with the properties of a surface carrier, while below 125 K it was postulated that interfacial-region electrons may influence peak values. After corrections for x-value and doping density at 77 K, bulk electron mobility in excess of 105 cm2 V−1 s−1 was observed in all epilayers, in line with expected values for lightly doped n-type LWIR material. Results indicate that fundamental conduction properties of electrons in MCT layers are unchanged by choice of substrate.

The surface kinetics of CdTe (211)B grown by molecular beam epitaxy (MBE) is investigated using spectroscopic ellipsometry (SE) during in situ cyclic annealing. A method of measuring sublimation rates from high-index surfaces without use of reflection high-energy electron diffraction is presented. The effect of Te2 overpressure on the activation energy of sublimation for the CdTe (211)B surface is reported. The sensitivity of SE to surface temperature and film thickness was leveraged to monitor sublimation rates of CdTe stabilized by a Te2 overpressure. The sublimation activation energy was found to increase from 0.45 eV to 2.94 eV under the Te2 beam pressure regime investigated.

Design parameters for the heterojunction-based strained layer superlattice (SLS) long-wave infrared (LWIR) detector are investigated so that it operates at a lower bias voltage with lower dark current and higher photo response. At typical operating temperatures ( T ∼ 77 K), the dark current of GaSb/InAs SLS LWIR detectors is dominated by the Shockley–Read–Hall (SRH) generation–recombination (g–r) process in the space-charge (depletion) region. In order to suppress this dark current, a wide bandgap region next to the absorber layer has been included in recent SLS designs. A series of heterojunction-based LWIR SLS detectors with various doping and barrier profiles have been designed and characterized. The significance of the doping profile and thickness of the wide-bandgap layer in optimization of the heterojunction-based SLS detector performance are exhibited from the modeling and experimental results of these devices.

The development of the nanotechnologies has brought concrete benefits on our daily life, finding application in several fields. In particular, a recent strategy in the water treatment consists in the development of photocatalytic hybrid nanocomposites (HyNC), in which the inorganic photoactive material is immobilized into a polymeric matrix to prevent their dispersion in the aqueous medium . The synthesis of HyNC, in which an inorganic layer grows on a polymeric surface via covalent bonds, persists to be a challenging goal for many applications such as catalysis, sensing, and optoelectronics. Herein, we report the growth of ZnO nanostructures by Atomic Layer Deposition (ALD) technique on modified polyetherimide (PEI-ULTEM® 1000) substrates. The high quality of the ALD materials originate from the peculiar growth mechanism based on selective and self-limiting reactions between the ALD gaseous precursors and the reactive groups exposed at surface of the substrate. The growth of the material on the substrate is controlled at the atomic scale, uniformly and conformably on large areas. A photo-oxidative process of the polymer surface has been properly performed to promote the production of reactive surface-sites suitable for ALD mechanism. The chemical anchoring of the metal species from the gas-phase is demonstrated by spectroscopy, MALDI-TOF mass spectrometry as well as AFM. In the operative ALD conditions used, the chemical grafting exclusively occurred on the pre-oxidized films, whilst the ZnO does not covalently reacted on the untreated ULTEM® 1000 films. Notably, we demonstrate that two different regimes of growth take place in the oxidized polymer as a function of the photo-exposure time. In particular, the formation of a nanostructured coating of ZnO on the polyetherimide surface is found in the case of short-time photo-exposed polyetherimide (ALD-like regime), whilst an intermixed organic/polymer layer is found on the long-time oxidized films (Vapor Phase Infiltration, VPI-like regime). The photocatalytic activity of the synthesized materials has been tested through the degradation of methylene blue dye in aqueous solution under UV light irradiation, so to give a proof of concept of a possible application of the nano-composites.

Studying atmospheric neutrino oscillations in the few-GeV range with a multimegaton detector promises to determine the neutrino mass hierarchy. This is the main science goal pursued by the future KM3NeT/ORCA water Cherenkov detector in the Mediterranean Sea. In this paper, the processes that limit the obtainable resolution in both energy and direction in charged-current neutrino events in the ORCA detector are investigated. These processes include the composition of the hadronic fragmentation products, the subsequent particle propagation and the photon-sampling fraction of the detector. GEANT simulations of neutrino interactions in seawater produced by GENIE are used to study the effects in the 1-20 GeV range. It is found that fluctuations in the hadronic cascade in conjunction with the variation of the inelasticity y are most detrimental to the resolutions. The effect of limited photon sampling in the detector is of significantly less importance. These results will therefore also be applicable to similar detectors/media, such as those in ice.

Spacecraft designers are driving observatories to the distant Sun-Earth Lagrange Point 2 (SEL2) to meet ever-increasing science requirements. The mass fraction dedicated to propellant for these observatories to reach and operate at SEL2 will be allocated with the upmost care, as it comes at the expense of optics and instrument masses. As such, these observatories could benefit from on-orbit refueling, allowing greater dry-to-wet mass ratio at launch and/or longer mission life. NASA is developing technologies, capabilities and integrated mission designs for multiple servicing applications in low Earth orbit (LEO), geosynchronous Earth orbit (GEO) and cisluner locations. Restore-L, a mission officially in formulation, will launch a free-flying robotic servicer to refuel a government-owned satellite in LEO by mid 2020. This paper will detail the results of a point design mission study to extend Restore-L servicing technologies from LEO to SEL2. This SEL2 mission would launch an autonomous, robotic servicer spacecraft equipped to extend the life of two space assets through refueling. Two space platforms were chosen to 1) drive the requirements for achieving SEL2 orbit and rendezvous with a spacecraft, and 2) to drive the requirements to translate within SEL2 to conduct a follow-on servicing mission. Two fuels, xenon and hydrazine, were selected to assess a multiple delivery system. This paper will address key mission drivers, such as servicer autonomy (necessitated due to communications latency at L2). Also discussed will be the value of adding cooperative servicing elements to the client observatories to reduce mission risk.

Pathophysiological mechanisms of primary headache remain obscure, despite of numerous hypotheses that have been postulated for either migraine and cluster headache. Human experimental models are not available, however, observation of clinical features of migraine or cluster headache attacks support animal studies documenting the development of neurogenic inflammation in tissues receiving trigeminal innervation. The latter studies provided also the background for better understanding the mechanism of action of aborting drugs such as sumatriptan and dihydroergotamine. The debate is whether the primary cause of migraine and other neurovascular headaches is central or peripheral in origin. Trigger factors (stressful events) and personality traits in migraine patients suggest that activation of neurovascular systems is secondary to more complex events taking place in the central nervous system.

We present the results of a detailed study of the changes that occur on CdTe buffer layer surfaces grown on ZnTe/Si(211) and GaAs(211)B during the routine thermal cyclic annealing (TCA) process. Observations indicate that CdTe buffer layer surfaces are Te saturated when the TCA is performed under Te overpressure. In the absence of Te flux during the TCA step, the CdTe surface loses CdTe congruently and the typical CdTe nanowires show the presence of nodules on their surfaces. The observed changes in reflection high-energy electron diffraction patterns during TCA are explained in terms of surface chemistry and topography observations. Overall, the Te overpressure is necessary to maintain a smoother and pristine surface to continue the molecular beam epitaxy (MBE) growth.