Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission’s
Perseverance
rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband ...red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 μrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 μrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory
Curiosity
rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover’s Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover’s traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover’s sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.
The Mars Exploration Rovers have accumulated airborne dust on different types of permanent magnets. Images of these magnets document the dynamics of dust capture and removal over time. The strongly ...magnetic subset of airborne dust appears dark brown to black in Panoramic Camera (Pancam) images, while the weakly magnetic one is bright red. Images returned by the Microscopic Imager reveal the formation of magnetic chains diagnostic of magnetite‐rich grains with substantial magnetization (>8 Am2 kg−1). On the basis of Mössbauer spectra the dust contains magnetite, olivine, pyroxene, and nanophase oxides in varying proportions, depending on wind regime and landing site. The dust contains a larger amount of ferric iron (Fe3+/Fetot ∼ 0.6) than rocks in the Gusev plains (∼0.1–0.2) or average Gusev soil (∼0.3). Alpha Particle X‐Ray Spectrometer data of the dust show that some of the iron in magnetite is substituted by titanium and chromium. The good correlation of the amount of calcium and sulfur in the dust may be caused by the presence of a calcium sulfate related phase. The overall mineralogical composition points to a basaltic origin of the airborne dust, although some alteration has taken place as indicated by the large degree of oxidation.
A proton beam delivery system on a gantry with continuous uniform scanning and dose layer stacking at the Midwest Proton Radiotherapy Institute has been commissioned and accepted for clinical use. ...This paper was motivated by a lack of guidance on the testing and characterization for clinical uniform scanning systems. As such, it describes how these tasks were performed with a uniform scanning beam delivery system. This paper reports the methods used and important dosimetric characteristics of radiation fields produced by the system. The commissioning data include the transverse and longitudinal dose distributions, penumbra, and absolute dose values. Using a
208
MeV
cyclotron’s proton beam, the system provides field sizes up to 20 and
30
cm
in diameter for proton ranges in water up to 27 and
20
cm
, respectively. The dose layer stacking method allows for the flexible construction of spread-out Bragg peaks with uniform modulation of up to
15
cm
in water, at typical dose rates of
1
–
3
Gy
∕
min
. For measuring relative dose distributions, multielement ion chamber arrays, small-volume ion chambers, and radiographic films were employed. Measurements during the clinical commissioning of the system have shown that the lateral and longitudinal dose uniformity of 2.5% or better can be achieved for all clinically important field sizes and ranges. The measured transverse penumbra widths offer a slight improvement in comparison to those achieved with a double scattering beam spreading technique at the facility. Absolute dose measurements were done using calibrated ion chambers, thermoluminescent and alanine detectors. Dose intercomparisons conducted using various types of detectors traceable to a national standards laboratory indicate that the measured dosimetry data agree with each other within 5%.
In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an ...anti-interleukin-17A monoclonal antibody, in such patients.
In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains.
ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval CI, 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group.
Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).
Summary Background Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a ...human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01752634. Findings Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 54% patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 51% patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 29% patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 15% patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four 4%, eight 8%, ten 10%, and seven 7% with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six 6%, four 4%, six 6%, and eight 8%, respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. Funding Novartis.
Substantial epidemiological and genetic evidence suggests that ankylosing spondylitis (AS) is likely due to an interplay of genetic and environmental factors. Recently, CARD15, located in chromosome ...16q12, has been established as a disease susceptibility gene for Crohn's disease, Blau syndrome, and possibly psoriatic arthritis. Association studies in admixed populations from Northern European ancestry noted no such association between CARD15 mutations and AS. However, a homogenous population has yet to be studied. We investigated the prevalence of the 3 common CARD15 variants in a homogenous Korean population with AS.
All subjects were native Koreans with AS satisfying the modified New York criteria. Korean controls were examined and confirmed to be unaffected by AS. Subjects with AS were genotyped for the R702W, G908R, and Leu1007fsinsC variants of CARD15 using mass array MALDI-TOF mass spectrometry.
A total of 205 AS subjects and 200 controls were genotyped. No subject with AS had any variants at the 702 and 1007 sites of CARD15. Only one subject was heterozygous for the 908 variant. The overall genotype frequency in AS for any CARD15 variant was 0.5%. No control had any of the 3 CARD15 variants.
Our findings indicate that the CARD15 gene is not a major contributor to AS susceptibility in the Korean population.
The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov ...NCT01989468).
Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ).
Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported.
Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously.
ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013-004002-25 . Registered 17 December 2013.
The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and ...safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis.
This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting).
From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 64% of 245 95% CI 57–70) and every 8 weeks group (159 64% of 248 58–70) than in the placebo group (81 33% of 246 27–39) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% 95% CI 22–39 for the every 4 weeks group and 31% 23–40 for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred.
Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit–risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis.
Janssen Research and Development.
Purpose
Chemical shift‐encoded MRI (CSE‐MRI) is well‐established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias ...PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature‐controlled experiments, and a multi‐center, multi‐vendor phantom study.
Theory and Methods
A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude‐, complex‐, and hybrid‐based CSE‐MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine‐site multi‐vendor phantom study and compared to temperature‐corrected PDFF estimation using an a priori guess for ambient room temperature.
Results
Simulations and temperature‐controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude‐based CSE‐MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction.
Conclusion
Correction for temperature reduces temperature‐related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude‐based CSE‐MRI, even without a priori information about the temperature.
Summary Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic ...interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov , number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 53% patients; effect size vs placebo 33·8% 95% CI 22·4–45·2; p<0·0001) and ixekizumab every 2 weeks (59 48% patients; 28.5% 17·1–39.8; p<0·0001) than did patients with placebo (23 20% patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.
PDF
