Research Foundation for the State University of New York

Approximately 20% of patients with rheumatoid arthritis (RA) cycle through multiple therapies without achieving treatment goals and are classified as having "difficult-to-treat" RA (D2T-RA); however, no risk prediction tools exist to identify which patients are at highest risk. Our aim was to develop and validate a predictive model for progression to D2T-RA among patients with RA. We used data from two large independent observational cohorts of patients with RA to develop and externally validate a multivariable prediction model to identify participants at risk of D2T-RA, defined using EULAR 2021 criteria. We developed a multivariable predictive model for D2T-RA using random survival forests in participants treated with their first biologic and/or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) (derivation cohort). We validated the model in a cohort of participants initiating or switching b/tsDMARD therapies. A total of 700 participants were in the derivation cohort (84% female, mean age 55 years, median follow-up 40 months, 113 [16%] with D2T-RA), and 2,070 participants were included in the validation cohort (79% female, mean age 56 years, median follow-up 8 months, 571 [28%] with D2T-RA). We observed C-index values of 0.643 (95% confidence interval [CI] 0.585-0.698; derivation cohort) and 0.620 (95% CI 0.596-0.643; validation cohort). Calibration measures suggested overall moderate predictive ability. Worsened functional status, pain, fatigue, and global disease activity were consistently top predictors across both cohorts. Our model demonstrated moderate discrimination and calibration, highlighting the challenge in accurately predicting D2T-RA outcomes. These findings underscore the need for further research to improve predictive performance, potentially through the incorporation of additional biomarkers.

Alstrom syndrome is an autosomal recessive disease. It affects multiple systems, including cardiovascular, renal, endocrine, and eyes. Our patient is a 25-year-old female who presented with elevated creatinine. Her past medical history was significant forhypothyroidism, polycystic ovarian syndrome, blindness, cataracts, hearing loss, and heart problems. She had genetic testing done that revealed that she was homozygous for the ALMS1 gene and was diagnosed with Alstrom syndrome. She was followed by nephrology in the clinic and had chronic kidney disease (CKD) stage V. The patient traveled to Italy and was lost to follow-up.

A vertical-junction, carrier-depletion, micro-ring modulator is demonstrated with an extinction ratio around 30 dB, a modulation efficiency ~40 pm, and works with drive voltages as low as 0.5 V.

AIM Photonics has developed a high precision laser attach process using an ultra-precise ASM Amicra NANO 300 mm die-to-wafer flip-chip bonder and integrated solder stamping system. Laser die are placed with high accuracy (<1 µm) and soldered to form a AuSn eutectic bond. This photonic platform has low optical losses, with SiN waveguides measuring on the order of 0.4 dB/cm and a calculated laser-to-waveguide coupling loss of 1.86 dB.

Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real-world experiences comparing these strategies have not been well studied. We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics-naive or biologics-exposed status of study participants. Patients eligible for analysis in this study included biologics-naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics-exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93-98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63-2.88] in the biologics-naive group; adjusted HR of 1.51 [95% confidence interval 1.06-2.15] in the biologics-exposed group). At 6 months, the proportion of biologics-naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (-9.3 units versus -5.5 [95% confidence interval -1.5, -6.1]). Corresponding results in the biologics-exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.

This paper reports the high frequency (HF) noise characterized performance and modeling on 22nm FD-SOI technology transistor (GLOBALFOUNDRIES’ 22FDX® technology) from 2 GHz to the maximum E-band millimetre-Wave (mmWave) frequency of 90 GHz. The measurement was performed using the Focus Microwaves noise system with different customised setups and optimised for each discrete frequency bands. The data measured from each frequency bands were subsequently combined to produce the noise spectrum covering from 2 GHz to 90 GHz, with high accuracy, good continuity and excellent correlation to the compact model. The 22FDX® technology transistor demonstrated very low mmWave noise figure, which is favourable for RF and mmWave applications such as LNA.

Extant U.S. research shows that when a persuader’s initial message is rebuffed, the next requesting message will tend to be ruder and more aggressive than the initial appeal. The robustness of these results has rarely been tested cross-culturally. Using conversational constraints theory, we further explicate implicit theories by investigating the perceived importance of constraints of re-requesting styles across two cultural-linguistic groups (i.e., Korean and American English speakers). Consistent with the “rebuff phenomenon,” results revealed that people rated the task constraint (“clarity”) as significantly more important, and the three face-related constraints (“concern for the other’s feelings,” “minimizing imposition,” and “avoiding negative evaluation”) as significantly less important for the second-attempt requesting than for the initial requesting. Some of these tendencies were more pronounced among American English speakers than among Korean speakers.

The report covers pioneering research on proton and ion generation in gas jets by the world's first picosecond TW CO₂ laser developed at Brookhaven National Laboratory