Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.

INTRODUCTION: Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study. METHODS: This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week 24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA). RESULTS: A total of 296 patients with baseline data and 192 with completed week 24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week 24 (95% CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week 24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24 weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks 12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week 24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified. CONCLUSION: The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04758117.

Upadacitinib is an antirheumatic medical therapy approved for treating psoriatic arthritis with insufficient response to previous conventional or biological therapies (DMARD-IR). Psoriatic arthritis is a chronic inflammatory disease affecting the joints, spine, tendons/entheses, skin, nails and other parts of the musculoskeletal system. Early diagnosis and treatment initiation are essential for patients with psoriatic arthritis given the potentially irreversible damage to joints, spine, and entheses and the considerable impact on quality of life. The results presented in this manuscript help clinicians evaluate whether the efficacy and the safety profile of upadacitinib found in previous clinical trials can be reproduced in patients seen in daily clinical practice. This analysis presents descriptive data on the real-world efficacy and safety of upadacitinib, measured by clinical and patient-reported outcomes assessed in four visits over 24 weeks. In summary, our findings confirm the results of previous clinical trials showing that upadacitinib effectively reduces symptom severity of PsA and substantially increases the proportion of patients achieving treatment goals relevant to clinical practice, such as remission or very low disease activity. In addition, safety data were consistent with previous studies of upadacitinib in rheumatoid arthritis or psoriatic arthritis; no new risks to the patients' safety were identified.

[Can rheuma be scanned? : Review of the current study situation on fluorescence optical imaging]. / Ist Rheuma scanbar? : Ein Überblick über die aktuelle Studienlage zur fluoreszenzoptischen Bildgebung.

BACKGROUND: The novel technique of indocyanine green (ICG)-based fluorescence optical imaging (FOI) using the Xiralite® system (Rheumascan) has been the subject of many different studies worldwide since approval for clinical use in the European Union (2009), USA (2014) and Asia. The FOI depicts the disturbed microcirculation in the joints of both hands caused by inflammation. OBJECTIVE: The aim of this article is to provide an overview of the current state of studies on ICG-based FOI in different rheumatologic indications. METHODS: A narrative literature review of publications on ICG-based FOI in the diagnosis of various inflammatory rheumatic joint diseases since 2010 is presented, its use in treatment monitoring is explained, and its value in systemic sclerosis is outlined. RESULTS: In summary, studies have extensively demonstrated the accuracy of FOI in inflammation detection. Therefore, it can be concluded that FOI is a good supplement to existing imaging modalities. Due to characteristic patterns of both skin and nails, FOI is an indicated procedure especially in psoriatic arthritis and can be very helpful in the diagnostic process in early undifferentiated arthritis. The FOI has shown its usefulness in children (juvenile idiopathic arthritis), for monitoring the course of treatment, and for demonstrating disturbed microcirculation in patients with systemic sclerosis. CONCLUSION: The presented data imply that FOI should be considered as a valuable complementary imaging tool in the diagnostic algorithm of daily rheumatologic practice, both for diagnosis and for follow-up monitoring. In particular, the automated analyses should be able in the future to objectify measurements of inflammatory activity as well as monitoring the response to treatment.

Planetary Terrestrial Analogues Library Project: 3. Characterization of Samples With MicrOmega.

The Planetary Terrestrial Analogues Library (PTAL) project aims at building and exploiting a database involving several analytical techniques, to help characterize the mineralogical evolution of terrestrial bodies, starting with Mars. Around 100 natural Earth rock samples have been collected from selected locations to gather a variety of analogs for martian geology, from volcanic to sedimentary origin with different levels of alteration. All samples are to be characterized within the PTAL project with different mineralogical and elemental analysis techniques, including techniques brought on actual and future instruments at the surface of Mars (near infrared [NIR] spectroscopy, Raman spectroscopy, and laser-induced breakdown spectroscopy). This article presents the NIR measurements and interpretations acquired with the ExoMars MicrOmega spare instrument. MicrOmega is an NIR hyperspectral microscope, mounted in the analytical laboratory of the ExoMars rover Rosalind Franklin. All PTAL samples have been observed at least once with MicrOmega using a dedicated setup. For all PTAL samples, data description and interpretation are presented. For some chosen examples, color composite images and spectra are presented as well. A comparison with characterizations by NIR and Raman spectrometry is discussed for some of the samples. In particular, the spectral imaging capacity of MicrOmega allows detections of mineral components and potential organic molecules that were not possible with other one-spot techniques. In addition, it enables estimation of heterogeneities in the spatial distribution of various mineral species. The MicrOmega/PTAL data shall support the future observations and analyses performed by MicrOmega/Rosalind Franklin instrument.

Fluorescence-optical imaging as a promising easy-to-use imaging biomarker to increase early psoriatic arthritis detection in patients with psoriasis: a cross-sectional cohort study with follow-up.

OBJECTIVES: To evaluate the ability of fluorescence-optical imaging (FOI) to detect preclinical musculoskeletal inflammatory signs in patients with skin psoriasis at risk of developing psoriatic arthritis (PsA). METHODS: This investigator-initiated prospective exploratory study evaluated adult patients with psoriasis with musculoskeletal complaints and/or nail psoriasis within the last 6 months. Patients underwent a comprehensive rheumatological clinical examination (CE) along with musculoskeletal ultrasound (MSUS) and FOI of both hands at a single visit. Patients with CE-/MSUS-/FOI+ findings had MRI performed on the symptomatic or dominant hand within 7 days. If MRI was negative, the patients were followed over 2 years for the onset of clinically manifest PsA. RESULTS: A total of 389 patients were referred from dermatology centres and evaluated at 14 rheumatology sites in Germany. Seventy-seven (20%) patients with CE-/US-/FOI- were considered to have psoriasis only. PsA was diagnosed in 140/389 patients (36%) based on CE alone and in another 55 patients (14%) by additional MSUS; overall, 50% of the patient cohort was diagnosed with PsA. One hundred sixteen patients (30%) were FOI+ (CE-) of which 40 (37%) were FOI+/MRI+. In the 2-year follow-up of the FOI+/CE- patients, clinical PsA was confirmed in another 12%. CONCLUSION: FOI is a promising method for the detection of signs of musculoskeletal inflammation in hands that may serve as an early imaging biomarker for transitions from psoriasis to PsA. This imaging technique has the potential to detect PsA in at-risk patients with psoriasis, reduce time to PsA diagnosis and improve patient outcomes.

Mineralogical and Spectral (Near-Infrared) Characterization of Fe-Rich Vermiculite-Bearing Terrestrial Deposits and Constraints for Mineralogy of Oxia Planum, ExoMars 2022 Landing Site.

Oxia Planum is a Noachian plain on Mars. It was chosen as the final landing site for in situ studies by ExoMars 2022 rover. The main scientific objectives of the mission are to understand the mineralogy and aqueous evolution of ancient Mars with relevance to habitability. Oxia is covered by vast deposits of Fe,Mg-phyllosilicates, but the exact nature of these deposits is not yet fully understood. We performed a survey of potential terrestrial analog rocks, and here we show combined mineralogical characterization of these rocks with their near-infrared spectral analysis. Samples from two terrestrial sites were studied: (1) vermiculitized chlorite-schists from Otago, New Zealand, which underwent an alteration process without significant oxidation; and (2) basaltic tuffs from Granby, Massachusetts, USA, with Fe-rich clays filling amygdales of supposedly hydrothermal origin. Both analogues are incorporated into the newly built Planetary Terrestrial Analogue Library (PTAL) collection. Oxia bedrock clay-rich deposits are spectrally matched best by a well-crystallized trioctahedral vermiculite/saponite mixture from the basaltic tuff, although the contribution of saponite must be minor. Otago vermiculite is a good analogue to Oxia vermiculite in terms of overall mineralogy and Fe content. However, spectral inconsistencies related to the Al content in the Otago clays indicate that illitization of vermiculite, which results from postalteration oxidation, did not occur at Oxia. This implies limited water/rock interactions and reducing conditions during deposition of sediments now constituting the bedrock at Oxia. Whereas the spectral match does not conclusively imply the mineralogy, trioctahedral vermiculite should be considered a likely mineral component of the bedrock unit at Oxia Planum. Vermiculite has great potential to store organic matter, and the postdeposition geological context of Oxia Planum derived from understanding of environmental conditions in analog sites is promising for organic matter preservation.

ExoMars Raman Laser Spectrometer: A Tool to Semiquantify the Serpentinization Degree of Olivine-Rich Rocks on Mars.

We evaluated the effectiveness of the ExoMars Raman laser spectrometer (RLS) to determine the degree of serpentinization of olivine-rich units on Mars. We selected terrestrial analogs of martian ultramafic rocks from the Leka Ophiolite Complex (LOC) and analyzed them with both laboratory and flight-like analytical instruments. We first studied the mineralogical composition of the samples (mostly olivine and serpentine) with state-of-the-art diffractometric (X-ray diffractometry [XRD]) and spectroscopic (Raman, near-infrared spectroscopy [NIR]) laboratory systems. We compared these results with those obtained using our RLS ExoMars Simulator. Our work shows that the RLS ExoMars Simulator successfully identified all major phases. Moreover, when emulating the automatic operating mode of the flight instrument, the RLS ExoMars Simulator also detected several minor compounds (pyroxene and brucite), some of which were not observed by NIR and XRD (e.g., calcite). Thereafter, we produced RLS-dedicated calibration curves (R2 between 0.9993 and 0.9995 with an uncertainty between ±3.0% and ±5.2% with a confidence interval of 95%) to estimate the relative content of olivine and serpentine in the samples. Our results show that RLS can be very effective in identifying serpentine, a scientific target of primary importance for the potential detection of biosignatures on Mars-the main objective of the ExoMars rover mission.

Effects of Arbuscular Mycorrhization on Fruit Quality in Industrialized Tomato Production.

Industrialized tomato production faces a decrease in flavors and nutritional value due to conventional breeding. Moreover, tomato production heavily relies on nitrogen and phosphate fertilization. Phosphate uptake and improvement of fruit quality by arbuscular mycorrhizal (AM) fungi are well-studied. We addressed the question of whether commercially used tomato cultivars grown in a hydroponic system can be mycorrhizal, leading to improved fruit quality. Tomato plants inoculated with Rhizophagus irregularis were grown under different phosphate concentrations and in substrates used in industrial tomato production. Changes in fruit gene expression and metabolite levels were checked by RNAseq and metabolite determination, respectively. The tests revealed that reduction of phosphate to 80% and use of mixed substrate allow AM establishment without affecting yield. By comparing green fruits from non-mycorrhizal and mycorrhizal plants, differentially expressed genes (DEGs) were found to possibly be involved in processes regulating fruit maturation and nutrition. Red fruits from mycorrhizal plants showed a trend of higher BRIX values and increased levels of carotenoids in comparison to those from non-mycorrhizal plants. Free amino acids exhibited up to four times higher levels in red fruits due to AM, showing the potential of mycorrhization to increase the nutritional value of tomatoes in industrialized production.

Visual chunking as a strategy for spatial thinking in STEM.

Working memory capacity is known to predict the performance of novices and experts on a variety of tasks found in STEM (Science, Technology, Engineering, and Mathematics). A common feature of STEM tasks is that they require the problem solver to encode and transform complex spatial information depicted in disciplinary representations that seemingly exceed the known capacity limits of visuospatial working memory. Understanding these limits and how visuospatial information is encoded and transformed differently by STEM learners presents new avenues for addressing the challenges students face while navigating STEM classes and degree programs. Here, we describe two studies that explore student accuracy at detecting color changes in visual stimuli from the discipline of chemistry. We demonstrate that both naive and novice chemistry students' encoding of visuospatial information is affected by how information is visually structured in "chunks" prevalent across chemistry representations. In both studies we show that students are more accurate at detecting color changes within chemistry-relevant chunks compared to changes that occur outside of them, but performance was not affected by the dimensionality of the structure (2D vs 3D) or the presence of redundancies in the visual representation. These studies support the hypothesis that strategies for chunking the spatial structure of information may be critical tools for transcending otherwise severely limited visuospatial capacity in the absence of expertise.

ExoMars Raman Laser Spectrometer: A Tool for the Potential Recognition of Wet-Target Craters on Mars.

In the present work, near-infrared, laser-induced breakdown spectroscopy, Raman, and X-ray diffractometer techniques have been complementarily used to carry out a comprehensive characterization of a terrestrial analogue selected from the Chesapeake Bay impact structure (CBIS). The obtained data clearly highlight the key role of Raman spectroscopy in the detection of minor and trace compounds, through which inferences about geological processes occurred in the CBIS can be extrapolated. Beside the use of commercial systems, further Raman analyses were performed by the Raman laser spectrometer (RLS) ExoMars Simulator. This instrument represents the most reliable tool to effectively predict the scientific capabilities of the ExoMars/Raman system that will be deployed on Mars in 2021. By emulating the analytical procedures and operational restrictions established by the ExoMars mission rover design, it was proved that the RLS ExoMars Simulator can detect the amorphization of quartz, which constitutes an analytical clue of the impact origin of craters. Beside amorphized minerals, the detection of barite and siderite, compounds crystallizing under hydrothermal conditions, helps indirectly to confirm the presence of water in impact targets. Furthermore, the RLS ExoMars Simulator capability of performing smart molecular mappings was successfully evaluated.

Fluorescence optical imaging for the detection of potential psoriatic arthritis in comparison to musculoskeletal ultrasound.

OBJECTIVE: Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA). METHODS: Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3. RESULTS: FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI. CONCLUSIONS: The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.

Spectroscopic study of olivine-bearing rocks and its relevance to the ExoMars rover mission.

We present the compositional analysis of three terrestrial analogues of Martian olivine-bearing rocks derived from both laboratory and flight-derived analytical instruments. In the first step, state-of-the-art spectroscopic (XRF, NIR and Raman) and diffractometric (XRD) laboratory systems were complementary used. Besides providing a detailed mineralogical and geochemical characterization of the samples, results comparison shed light on the advantages ensured by the combined use of Raman and NIR techniques, being these the spectroscopic instruments that will soon deploy (2021) on Mars as part of the ExoMars/ESA rover payload. In order to extrapolate valuable indicators of the mineralogical data that could derive from the ExoMars/Raman Laser Spectrometer (RLS), laboratory results were then compared with the molecular data gathered through the RLS ExoMars Simulator. Beside correctly identifying all major phases (feldspar, pyroxene and olivine), the RLS ExoMars Simulator confirmed the presence of additional minor compounds (i.e. hematite and apatite) that were not detected by complementary techniques. Furthermore, concerning the in-depth study of olivine grains, the RLS ExoMars simulator was able to effectively detect the shifting of the characteristic double peak around 820 and 850 cm-1, from which the FeMg content of the analyzed crystals can be extrapolated. Considering that olivine is one of the main mineral phases of the ExoMars landing site (Oxia Planum), this study suggests that the ExoMars/RLS system has the potential to provide detailed information about the elemental composition of olivine on Mars.

The "green nail" phenomenon in ICG-enhanced fluorescence optical imaging - a potential tool for the differential diagnosis of psoriatic arthritis.

BACKGROUND AND OBJECTIVES: Early diagnosis of psoriatic arthritis poses a particular challenge. A novel fluorescence optical imaging technique, the Xiralite® system is very useful in this regard as it allows for visualization of microvasculature and perfusion. The present study is the first to systematically examine fluorescence optical signals in a large psoriatic arthritis cohort. PATIENTS AND METHODS: In the primary study, we reviewed and analyzed extra-articular fluorescence optical signal patterns in 241 imaging sequences obtained from 187 psoriatic arthritis patients; 36 fluorescence optical sequences from 31 patients with rheumatoid arthritis served as controls. In a follow-up study, 203 consecutive fluorescence optical sequences from 54 psoriatic arthritis patients and 149 control subjects with various inflammatory rheumatic disorders were retrospectively evaluated in order to validate the primary study results in terms of the patterns previously identified. RESULTS: Psoriatic arthritis patients exhibited three different fluorescence optical signal patterns in projection of the nails that have not been previously described. One of these patterns was the "green nail" sign, which was highly specific (97 %) for psoriatic arthritis. In the follow-up study, the specificity of this phenomenon in psoriatic arthritis was 87 % in comparison to the control cohort. CONCLUSIONS: In the present study, fluorescence optical signals in the nail region proved to be highly specific for psoriatic arthritis. The "green nail" phenomenon seems to be of particular diagnostic interest as a potential sign of impaired microcirculation of the nail bed.

Kinematic assessment of an elastic-core cervical disc prosthesis in one and two-level constructs.

INTRODUCTION: Anterior cervical discectomy and fusion has been associated with the development of adjacent segment degeneration (ASD), with clinical incidence of approximately 3% per year. Cervical total disc arthroplasty (TDA) has been proposed as an alternative to prevent ASD. HYPOTHESES: TDA in optimal placement using an elastic-core cervical disc (RHINE, K2M Inc., Leesburg, Virginia) will replicate natural kinematics and will improve with optimal vs anterior placement. METHODS: Seven C3-T1 cervical cadaver spines were tested intact first, then after one-level TDA at C5-C6 anterior placement, after TDA at C5-C6 optimal placement, after two-level TDA at C5-C6 and C6-C7 optimal placement, and finally after two-level TDA at C5-C6 lateral placement and C6-C7 optimal placement. The specimens were subjected to: Flexion-Extension moments (+1.5 Nm) with compressive preloads of 0 N and 150 N, lateral bending (LB) and axial rotation (AR) (+1.5 Nm) without preload. RESULTS: C5-C6 TDA in optimal placement resulted in a non-significant increase in flexion-extension ROM compared to intact under 0 N and 150 N preload (P > 0.05). Both LB and AR ROM decreased with arthroplasty (P < 0.01). Optimal placement of C6-C7 TDA resulted in an increase in flexion-extension ROM with preload compared to intact (P < 0.05) while LB and AR ROM decreased with arthroplasty (P < 0.01). CONCLUSION: This six degree of freedom elastic-core disc arthroplasty effectively restored flexion-extension motion to intact levels. In LB the TDA maintained 42% ROM at C5-C6 and 60% at C6-C7. In AR 57% of the ROM was maintained at C5-C6 and 70% at C6-C7. These findings are supported by literature which shows cervical TDA results in restoration of approximately 50% ROM in LB and AR, which is a multifactorial phenomenon encompassing TDA design parameters and anatomical constraints. Anterior placement of this viscoelastic TDA device shows motion restoration similar to optimal placement suggesting its design may be less sensitive to suboptimal placement.

Fluorescence optical imaging in pediatric patients with inflammatory and non-inflammatory joint diseases: a comparative study with ultrasonography.

BACKGROUND: Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases. METHODS: FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0-3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1-P3) were analyzed with CE and GSUS/PDUS as reference. RESULTS: For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS. CONCLUSIONS: Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00012572 . Registered 31 July 2017.

Fluorescence optical imaging and musculoskeletal ultrasonography in juvenile idiopathic polyarticular disease before and during antirheumatic treatment - a multicenter non-interventional diagnostic evaluation.

BACKGROUND: Valid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring. METHODS: A 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24. RESULTS: Of 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase. Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US. Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84-95%), and sensitivity was only moderate. CONCLUSION: FOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00011579 . Registered 10 January 2017.

Disturbed microcirculation in the hands of patients with systemic sclerosis detected by fluorescence optical imaging: a pilot study.

BACKGROUND: Utilising fluorescence optical imaging (FOI), the distribution of an intravenously applied colouring agent indocyanine green (ICG) can be analysed with the potential to identify malperfusion by little to no tissue enhancement. Systemic sclerosis (SSc) is characterised by the presence of digital ulcers reflecting progressive vasculopathy. The objective was to investigate the potential of FOI in the detection of disturbed microcirculation in the hands and fingers of patients with SSc and to link FOI findings to clinical signs of ischemia such as digital ulcers and pitting scars. METHODS: In this cross-sectional study, 63 patients with SSc and 26 healthy subjects were examined. FOI was performed in all 89 individuals and compared to clinical data and capillaroscopic findings assembled for the SSc cohort. RESULTS: Healthy subjects showed initial ICG signals in their fingertips in 93.6%, SSc patients in 78.5% (limited SSc) and 43.2% (diffuse SSc). Moreover, in SSc patients, FOI findings were significantly associated with a late capillaroscopic pattern, disseminated SSc features, a diffuse SSc subtype, and the presence of digital ulcers or pitting scars. Intra- and inter-reader reliability for FOI amounted to κ = 0.786 and κ = 0.834, respectively. CONCLUSIONS: FOI is able to detect areas of reduced microcirculation in patients with SSc with high association to capillaroscopic findings. The results pave the way for future FOI investigations into its role in the prediction of complications due to an impaired acral perfusion.

Habitability on Early Mars and the Search for Biosignatures with the ExoMars Rover.

The second ExoMars mission will be launched in 2020 to target an ancient location interpreted to have strong potential for past habitability and for preserving physical and chemical biosignatures (as well as abiotic/prebiotic organics). The mission will deliver a lander with instruments for atmospheric and geophysical investigations and a rover tasked with searching for signs of extinct life. The ExoMars rover will be equipped with a drill to collect material from outcrops and at depth down to 2 m. This subsurface sampling capability will provide the best chance yet to gain access to chemical biosignatures. Using the powerful Pasteur payload instruments, the ExoMars science team will conduct a holistic search for traces of life and seek corroborating geological context information. Key Words: Biosignatures-ExoMars-Landing sites-Mars rover-Search for life. Astrobiology 17, 471-510.

Separation of Stabilized MOPS Gold Nanostars by Density Gradient Centrifugation.

This article describes the stabilization and postsynthetic separation of gold nanostars (AuNS) synthesized with a morpholine-based Good's buffer, 3-(N-morpholino)propanesulfonic acid. Resuspension of AuNS in ultrapure water improved the shape stability of the particles over 30 days. We demonstrated the sorting of nanostars via rate-zonal centrifugation through a linear sucrose gradient based on branch length and number. We determined that one round of centrifugation was sufficient for separation. Also, we improved the structural homogeneity and stability of the nanoparticles through the optimization of the storage conditions and established a robust method to sort AuNS based on size and shape.