SAT-022 Adrenal Androgen Production Is Maintained While Ovarian Estrogens Fall Following the Final Menstrual Period in the Study of Women’s Health Across the Nation (SWAN)

The aim of this study was to clarify changes in sex steroids at the final menstrual period (FMP). We have shown previously that estradiol (E2) declines substantially in the 4-year period around the FMP, but hypothesize that testosterone (T) declines modestly and adrenal Δ5 androgens dehydroepiandrosterone (DHEA) and androstenediol (Adiol) remain unchanged. Methods: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and immunoassay was used in approximately annual samples collected before and following FMP in 1490 women. We estimated time-related changes in each log-transformed androgen using piecewise linear mixed modeling, with knots (slope changes) at FMP-2 yrs and FMP+2 yrs as seen for E2. These models then were re-estimated for subgroups with different time courses identified using group-based trajectory modeling. Results: In the full sample, T was generally stable, although time course varied by subgroup, with a significant decrease of 5%/year in T in [FMP-2yrs, FMP+2yrs] only in the lowest T women. For DHEA and Adiol, declines were similar across all 3 time segments and across subgroups. Mean circulating androgen concentration declined modestly (P> 0.05) from five years before to five years following FMP. However, when stratified only the lowest 7% of circulating T declined significantly (p< 0.05) in the four years surrounding FMP when mean circulating E2 declined. This trajectory divergence of the lower circulating T suggests a different, non-adrenal source that is decreased at FMP which may be useful in clarifying ovarian versus adrenal testosterone production during the post-menopause. Paired results from samples collected before and following FMP in the same subjects indicate mean circulating E2 is less than 5% of mean circulating T suggesting that a relatively large portion of circulating E2 may be largely a result of peripheral conversion of adrenal androgens. Longitudinal LC-MS/MS analyses of circulating E2 and T indicate that the principal change in sex steroid influence at menopause is largely a decrease and dampening of ovarian and not adrenal steroid production.

Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA

Objective To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. Methods Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. Results A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into ‘modest’ (7986 patients; 55.3%) or ‘substantial’ (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted ‘maximal’ and ‘minimal’ response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving ‘maximal’ response between 2001–2008 and 2010–2013. Conclusion This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

Neural trajectories in the supplementary motor area and primary motor cortex exhibit distinct geometries, compatible with different classes of computation

The supplementary motor area (SMA) is believed to contribute to higher-order aspects of motor control. To examine this contribution, we employed a novel cycling task and leveraged an emerging strategy: testing whether population trajectories possess properties necessary for a hypothesized class of computations. We found that, at the single-neuron level, SMA exhibited multiple response features absent in M1. We hypothesized that these diverse features might contribute, at the population level, to avoidance of ‘population trajectory divergence’ – ensuring that two trajectories never followed the same path before separating. Trajectory divergence was indeed avoided in SMA but not in M1. Network simulations confirmed that low trajectory divergence is necessary when guidance of future action depends upon internally tracking contextual factors. Furthermore, the empirical trajectory geometry – helical in SMA versus elliptical in M1 – was naturally reproduced by networks that did, versus did not, internally track context.

A Comparative Study to Quantify Sensitive Dependence in Numerical Models for a Developing Low in the Southern Plains

Studies have shown that numerical models display the characteristics of chaotic systems, and that the solutions can be sensitive to the initial conditions, the model used, or the parameterizations used. Using the Kain-Fritsch, Grell, and modified Kuo convective parameterizations in the MASS and the WRF model, the results from a case study show that 48-h forecasts were not identical. Lyapunov exponents were calculated by plotting forecast trajectories in a phase diagram and estimating the rate of trajectory divergence for two time periods outside the study of the main cyclone. These calculations did show divergence at a rate which was consistent with differences in model height in 48-h forecasts from other studies. Additionally, the integrated enstrophy can be used to estimate the Lyapunov value. Finally, a qualitative analysis comparing various model runs (pseudo-ensemble) was performed to determine if there were regions or areas where consistent differences in the runs existed between the indexes used for forecasting convective precipitation. Results demonstrated that the region of the southeast United States associated with the developing cyclone showed the most significant differences in these indexes and for heights and temperatures. The differences in the model forecasts between convective parameterizations (intramodel forecasts) in this case were not as great as the model-to-model forecast differences (intermodel forecasts).