Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations

BACKGROUND: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association. OBJECTIVES: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS. METHODS: Individual patient-level data from five large phase III randomized controlled trials (RCTs) was utilized to investigate the association of both age and disease duration with annualized relapse rate (ARR), contrast-enhancing lesions (CELs), and new T2 lesions on magnetic resonance imaging (MRI) at baseline and follow-up. RESULTS: The data set included 5626 participants. Higher age was associated with lower ARRs, lower CEL number on MRI at baseline and follow-up, and lower new T2 lesion numbers at follow-up. This effect was present in all disease duration groups. For example, we found a lower number of new T2 lesions on MRI during follow-up in higher age groups compared to lower age groups, independent of disease duration. CONCLUSION: Aging in RRMS is associated with a lower risk of inflammatory disease activity, across different disease durations. Age should be taken into account when designing clinical trials and future research should investigate how age should be integrated into personalized predictions of treatment response and risk profiling

Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial

Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy. // Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS. // Design, Setting, and Participants: This multicenter, rater-blinded, noninferiority randomized clinical trial was conducted between July 1, 2020, and March 20, 2023, at 14 Dutch centers. Data analysis was performed between July 2023 and January 2024. Key inclusion criteria were relapse-onset MS, aged 18 years or older, without relapses, and without substantial magnetic resonance imaging (MRI) activity in the previous 5 years under first-line DMT. Participants were randomized 1:1 to discontinue or continue first-line DMT. // Intervention: Discontinuation of first-line DMT. // Main Outcome and Measure: The primary outcome was significant inflammatory disease activity, defined as relapse and/or 3 or more new T2 lesions or 2 or more contrast-enhancing lesions on brain MRI. // Results: Of 163 potentially eligible participants, 89 participants were included in the trial at the moment of early termination. Forty-four participants (49.4%) were assigned to the continue group and 45 participants (50.6%) were assigned to the discontinue group. Median (IQR) age was 54.0 (49.0-59.0) years, and 60 participants (67.4%) were female. Two participants in the continue group were lost to follow-up. After a median (IQR) follow-up time of 15.3 (11.4-23.9) months, the trial was prematurely terminated because of inflammatory disease activity recurrence above the predefined limit. In total, 8 of 45 participants in the discontinue group (17.8%) vs 0 of 44 participants in the continue group reached the primary end point and had recurrent, mostly radiological inflammation. Two of these 8 participants had a clinical relapse. Median (IQR) time to disease activity was 12.0 (6.0-12.0) months. // Conclusions and Relevance: In this randomized clinical trial, even in patients with long-term MS stable for over 5 years, first-line DMT discontinuation can lead to recurrence of inflammatory disease activity. Although this study cohort was relatively small, the recurrence of inflammation in the discontinue group was significantly higher than in the continue group and also higher than in the previously published DISCOMS trial, which only included individuals aged 55 years or older. This study provides additional data, especially in a younger population and including longitudinal biomarker measurements, for informed decision-making in cases when treatment discontinuation is considered. // Trial Registration: ClinicalTrials.gov Identifier: NCT0426071

Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association. Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS. Methods: Individual patient-level data from five large phase III randomized controlled trials (RCTs) was utilized to investigate the association of both age and disease duration with annualized relapse rate (ARR), contrast-enhancing lesions (CELs), and new T2 lesions on magnetic resonance imaging (MRI) at baseline and follow-up. Results: The data set included 5626 participants. Higher age was associated with lower ARRs, lower CEL number on MRI at baseline and follow-up, and lower new T2 lesion numbers at follow-up. This effect was present in all disease duration groups. For example, we found a lower number of new T2 lesions on MRI during follow-up in higher age groups compared to lower age groups, independent of disease duration. Conclusion: Aging in RRMS is associated with a lower risk of inflammatory disease activity, across different disease durations. Age should be taken into account when designing clinical trials and future research should investigate how age should be integrated into personalized predictions of treatment response and risk profiling

Detection of Thermal Emission at Millimeter Wavelengths from Low-Earth Orbit Satellites

The detection of artificial satellite thermal emission at millimeter wavelengths is presented using data from the 3rd-Generation receiver on the South Pole Telescope (SPT-3G). This represents the first reported detection of thermal emission from artificial satellites at millimeter wavelengths. Satellite thermal emission is shown to be detectable at high signal-to-noise ratios on timescales as short as a few tens of milliseconds. An algorithm for downloading orbital information and tracking known satellites given observer constraints and time-ordered observatory pointing is described. Consequences for cosmological surveys and short-duration transient searches are discussed, revealing that the integrated thermal emission from all large satellites does not contribute significantly to the SPT-3G survey intensity map. Measured satellite positions are found to be discrepant from their two-line element (TLE) derived ephemerides up to several arcminutes which may present a difficulty in cross-checking or masking satellites from short-duration transient searches

Cosmology from CMB lensing and delensed EE power spectra using 2019-2020 SPT-3G polarization data

From CMB polarization data alone, we reconstruct the CMB lensing power spectrum, comparable in overall constraining power to previous temperature-based reconstructions, and an unlensed E-mode power spectrum, with clear detections of the third through the tenth acoustic peaks. The observations, taken in 2019 and 2020 with the South Pole Telescope (SPT) and the SPT-3G camera, cover 1500 deg2 at 95, 150, and 220 GHz with arcminute resolution and roughly 4.9 μK-arcmin coadded noise in polarization. The power spectrum estimates, together with systematic parameter estimates and a joint covariance matrix, follow from a Bayesian analysis using the marginal unbiased score expansion (MUSE) method. The E-mode spectrum at ℓ>2000 and lensing spectrum at L>350 are the most precise to date. Assuming the ΛCDM model, and using only these SPT data and priors on τ and absolute calibration from Planck, we find H0=66.81±0.81 km/s/Mpc, comparable in precision to the Planck determination and in 5.4σ tension with the most precise H0 inference derived via the distance ladder. We also find S8σ8(ωm/0.3)0.5=0.850±0.017, providing further independent evidence of a slight tension with low-redshift structure probes. The ΛCDM model provides a good simultaneous fit to the combined Planck, ACT, and SPT data, and thus passes a powerful test. Combining these CMB datasets with BAO observations, we explore extensions to the ΛCDM model. We find that the effective number of neutrino species, spatial curvature, and primordial helium fraction are consistent with standard model values, and that the 95% confidence upper limit on the neutrino mass sum is 0.075 eV, close to the minimum sum expected from observations of solar and atmospheric neutrino oscillations. The SPT data are consistent with the somewhat weak (<3σ) preference for excess lensing power seen in Planck and ACT data relative to predictions of the ΛCDM model given the combined Planck, ACT, and BAO datasets. We also detect at greater than 3σ the influence of nonlinear evolution in the CMB lensing power spectrum and discuss it in the context of the S8 tension. Forthcoming SPT-3G analyses will feature deeper and wider observations in temperature and polarization, providing even tighter constraints and more powerful tests of the ΛCDM model

Pointing Accuracy Improvements for the South Pole Telescope with Machine Learning

In this paper, we present improvements to the pointing accuracy of the South Pole Telescope (SPT) using machine learning. The ability of the SPT to point accurately at the sky is limited by its structural imperfections, which are impacted by the extreme weather at the South Pole. Pointing accuracy is particularly important during SPT participation in observing campaigns with the Event Horizon Telescope (EHT), which requires stricter accuracy than typical observations with the SPT. We compile a training dataset of historical observations of astronomical sources made with the SPT-3G and EHT receivers on the SPT. We train two XGBoost models to learn a mapping from current weather conditions to two telescope drive control arguments - one which corrects for errors in azimuth and the other for errors in elevation. Our trained models achieve root mean squared errors on withheld test data of 2.″14 in cross-elevation and 3.″57 in elevation, well below our goal of 5 ″ along each axis. We deploy our models on the telescope control system and perform further in situ test observations during the EHT observing campaign in April 2024. Our models result in significantly improved pointing accuracy: for sources within the range of input variables where the models are best trained, average combined pointing error improved 33%, from 15.″9 to 10.″6. These improvements, while significant, fall shy of our ultimate goal, but they serve as a proof of concept for the development of future models. Planned upgrades to the EHT receiver on the SPT will necessitate even stricter pointing accuracy which will be achievable with our methods

Mass calibration of DES Year-3 clusters via SPT-3G CMB cluster lensing

We measure the stacked lensing signal in the direction of galaxy clusters in the Dark Energy Survey Year 3 (DES Y3) redMaPPer sample, using cosmic microwave background (CMB) temperature data from SPT-3G, the third-generation CMB camera on the South Pole Telescope (SPT). Here, we estimate the lensing signal using temperature maps constructed from the initial 2 years of data from the SPT-3G 'Main' survey, covering 1500 deg2 of the Southern sky. We then use this lensing signal as a proxy for the mean cluster mass of the DES sample. The thermal Sunyaev-Zel'dovich (tSZ) signal, which can contaminate the lensing signal if not addressed, is isolated and removed from the data before obtaining the mass measurement. In this work, we employ three versions of the redMaPPer catalogue: a Flux-Limited sample containing 8865 clusters, a Volume-Limited sample with 5391 clusters, and a Volume&Redshift-Limited sample with 4450 clusters. For the three samples, we detect the CMB lensing signal at a significance of 12.4σ, 10.5σ and 10.2σ and find the mean cluster masses to be M 200m = 1.66±0.13 [stat.]± 0.03 [sys.], 1.97±0.18 [stat.]± 0.05 [sys.], and 2.11±0.20 [stat.]± 0.05 [sys.]×1014 M⊙, respectively. This is a factor of ∼ 2 improvement relative to the precision of measurements with previous generations of SPT surveys and the most constraining cluster mass measurements using CMB cluster lensing to date. Overall, we find no significant tensions between our results and masses given by redMaPPer mass-richness scaling relations of previous works, which were calibrated using CMB cluster lensing, optical weak lensing, and velocity dispersion measurements from various combinations of DES, SDSS and Planck data. We then divide our sample into 3 redshift and 3 richness bins, finding no significant discrepancies with optical weak-lensing calibrated masses in these bins. We forecast a 5.7% constraint on the mean cluster mass of the DES Y3 sample with the complete SPT-3G surveys when using both temperature and polarization data and including an additional ∼ 1400 deg2 of observations from the 'Extended' SPT-3G survey