Time Delay Between Dst Index and Magnetic Storm Related Structure in the Solar Wind

Benson et al. (2015, this volume) selected 10 large magnetic storms, with associated Dst minimum values less than or equal to -100 nT, for which high-latitude topside ionospheric electron density profiles are available from topside-sounder satellites. For these 10 storms, we performed a superposition of Dst and interplanetary parameters B, v, N(sub p) and T(sub p). We have found that two interplanetary parameters, namely B and v, are sufficient to reproduce Dst with correlation coefficient cc approximately 0.96 provided that the interplanetary parameter times are taken 0.15 days earlier than the associated Dst times. Thus we have found which part of the solar wind is responsible for each phase of the magnetic storm. This result is also verified for individual storms as well. The total duration of SRS (storm related structure in the solar wind) is 4 - 5 days which is the same as the associated Dst interval of the magnetic storm

Changes in the High-Latitude Topside Ionospheric Vertical Electron-Density Profiles in Response to Solar-Wind Perturbations During Large Magnetic Storms

The latest results from an investigation to establish links between solar-wind and topside-ionospheric parameters will be presented including a case where high-latitude topside electron-density Ne(h) profiles indicated dramatic rapid changes in the scale height during the main phase of a large magnetic storm (Dst < -200 nT). These scale-height changes suggest a large heat input to the topside ionosphere at this time. The topside profiles were derived from ISIS-1 digital ionograms obtained from the NASA Space Physics Data Facility (SPDF) Coordinated Data Analysis Web (CDA Web). Solar-wind data obtained from the NASA OMNIWeb database indicated that the magnetic storm was due to a magnetic cloud. This event is one of several large magnetic storms being investigated during the interval from 1965 to 1984 when both solar-wind and digital topside ionograms, from either Alouette-2, ISIS-1, or ISIS-2, are potentially available

High-Latitude Topside Ionospheric Vertical Electron-Density-Profile Changes in Response to Large Magnetic Storms

Large magnetic-storm induced changes have been detected in high-latitude topside vertical electron-density profiles Ne(h). The investigation was based on the large database of topside Ne(h) profiles and digital topside ionograms from the International Satellites for Ionospheric Studies (ISIS) program available from the NASA Space Physics Data Facility (SPDF) at http://spdf.gsfc.nasa.gov/isis/isis-status.html. This large database enabled Ne(h) profiles to be obtained when an ISIS satellite passed through nearly the same region of space before, during, and after a major magnetic storm. A major goal was to relate the magnetic-storm induced high-latitude Ne(h) profile changes to solar-wind parameters. Thus an additional data constraint was to consider only storms where solar-wind data were available from the NASA/SPDF OMNIWeb database. Ten large magnetic storms (with Dst less than -100 nT) were identified that satisfied both the Ne(h) profile and the solar-wind data constraints. During five of these storms topside ionospheric Ne(h) profiles were available in the high-latitude northern hemisphere and during the other five storms similar ionospheric data were available in the southern hemisphere. Large Ne(h) changes were observed during each one of these storms. Our concentration in this paper is on the northern hemisphere. The data coverage was best for the northern-hemisphere winter. Here Ne(h) profile enhancements were always observed when the magnetic local time (MLT) was between 00 and 03 and Ne(h) profile depletions were always observed between 08 and 10 MLT. The observed Ne(h) deviations were compared with solar-wind parameters, with appropriate time shifts, for four storms

Investigating Changes in the High-Latitude Topside Ionosphere During Large Magnetic Storms

A search was conducted to locate periods of nearly simultaneous solar-wind and high latitude topside-ionospheric data during magnetic storms. The focus was on the 20-yr interval from 1965 to 1985 when both solar-wind and Alouette/ISIS topside-sounder data are potentially available. The search yielded 125 large magnetic storms (minimum Dst less than 100) and 280 moderate magnetic storms (minimum Dst between -60 and -100). Solar wind data were available for most, but not all, of these storms. A search of the available high-latitude topside electron-density Ne(h) profiles available from the National Space Science Data Center (NSSDC), both from manual inspection of 35-mm film ionograms in the 1960s and more recent auto-processing of ISIS-2 topside digital ionograms using the TOPIST software, during 9-day intervals associated with the 125 large magnetic storm minimum Dst times yielded the following results: 31 intervals had 10 or more manual-scaled profiles (21 intervals had more than 100 profiles and 5 of these had more than 1,000 profiles), and 34 intervals had 10 or more TOPIST profiles (2 intervals had more than 100 profiles). In addition, a search of the available Alouette-2, ISIS-1 and ISIS-2 digital ionograms during the above periods has yielded encouraging initial results in that many ISIS-1 ionograms were found for the early time intervals. Future work will include the search for 35-mm film ionograms during selected intervals. This presentation will illustrate the results of this investigation to date

Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series

Purpose To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC). Materials and methods We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test. Results We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001). Conclusions We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease

Medical Treatment Can Unintentionally Alter the Regulatory T-Cell Compartment in Patients with Widespread Pathophysiologic Conditions

Regulatory T cells (Tregs) are non-redundant mediators of immune tolerance that are critical to prevent autoimmune disease and promote an anti-inflammatory tissue environment. Many individuals experience chronic diseases and physiologic changes associated with aging requiring long-term medication. Unfortunately, adverse effects accompany every pharmacologic intervention and may affect overall outcomes. We focus on medications typically prescribed during the treatment of prevalent chronic diseases and disorders, including cardiovascular disease, autoimmune disease, and menopausal symptoms, that affect >200 million individuals in the United States. Increasing studies continue to report that treatment of patients with estrogen, metformin, statins, vitamin D, and tumor necrosis factor blockers are unintentionally modulating the Treg compartment. Effects of these medications likely comprise direct and/or indirect interaction with Tregs via other immune and parenchymal populations. Differing and sometimes opposing effects on the Treg compartment have been observed using the same medication. The length of treatment, dosing regimen and stage of disease, patient age, ethnicity, and sex may account for such findings and determine the specific signaling pathways affected by the medication. Enhancing the Treg compartment can skew the patient's immune system toward an anti-inflammatory phenotype and therefore could provide unanticipated benefit. Currently, multiple medicines prescribed to large numbers of patients influence the Treg compartment; however, how such effects affect their disease outcome and long-term health remains unclear

T cell metabolism in metabolic disease-associated autoimmunity

This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity.Biopharmaceutic

Mycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysis

Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223