BRITE-Constellation reveals evidence for pulsations in the enigmatic binary η\eta Carinae

$\eta$ Car is a massive, eccentric binary with a rich observational history. We obtained the first high-cadence, high-precision light curves with the BRITE-Constellation nanosatellites over 6 months in 2016 and 6 months in 2017. The light curve is contaminated by several sources including the Homunculus nebula and neighboring stars, including the eclipsing binary CPD$-$59$^\circ$2628. However, we found two coherent oscillations in the light curve. These may represent pulsations that are not yet understood but we postulate that they are related to tidally excited oscillations of $\eta$ Car's primary star, and would be similar to those detected in lower-mass eccentric binaries. In particular, one frequency was previously detected by van Genderen et al. and Sterken et al. through the time period of 1974 to 1995 through timing measurements of photometric maxima. Thus, this frequency seems to have been detected for nearly four decades, indicating that it has been stable in frequency over this time span. These pulsations could help provide the first direct constraints on the fundamental parameters of the primary star if confirmed and refined with future observations.Comment: 8 pages, 4 figures, accepted to MNRA

981-46 Impact of a Comprehensive Management Program on the Hospitalization Rate for Patients with Advanced Heart Failure

Patients with advanced heart failure have a course that is often characterized by frequent hospitalizations and progressive deterioration. These patients are commonly referred to specialized centers for consideration of heart transplantation (Tx). To assess the impact of the changes in therapy made in conjunction with heart transplantation evaluation on patient outcomes, we assessed the hospitalization rate and patient's functional status in the 6 months prior to referral compared to the 6 months after referral. Since 1/91, 214 patients were evaluated, accepted for Tx, and discharged having undergone adjustments in medical therapy and a comprehensive patient education program. At time of referral patients had mean LVEF 0.21, NYHA class 3.3, VO2 max 11.0ml/kg, and had undergone a total of 429 hospitalizations in the previous 6 months. During evaluation patients had their ACE inhibitor dose increased by a mean 91.5mg/day of captopril or the equivalent, were diuresed a mean 4.2 liters, were placed on a flexible regimen of loop diuretics, and were counseled on dietary management and home based progressive aerobic exercise. After 6 months of follow-up there were only 63 hospitalizations required (mean hospitalization rate per patient over the 6 months pre-evaluation 2.00±1.45 vs post-evaluation 0.29±0.53 p<0.00001). Patient's NYHA class improved to 2.4 (p<0.0001) and VO2 max increased to 15.2 (p<0.001). Excluding the 12 elective status Tx, 14 urgent status Tx, and 9 deaths within 6 months yielded similar results (344 pre vs 34 post-evaluation hospitalizations). 64 patients (30%) improved their functional status to the point that transplantation was deferred in favor of sustained medical therapy.Referral to a heart failure specialty program is associated with a dramatic occurred between day 10±1 and 3 month. 4 patients died after hospital discharge (no death directly related to thromboembolic disease). Thus no higher risk of PE can be seen in patients with free floating prox-DVT and anticoagulant therapy should be efficient to prevent recurrent PE in such patient

Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age.

The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain

Infrastructural Speculations: Tactics for Designing and Interrogating Lifeworlds

This paper introduces “infrastructural speculations,” an orientation toward speculative design that considers the complex and long-lived relationships of technologies with broader systems, beyond moments of immediate invention and design. As modes of speculation are increasingly used to interrogate questions of broad societal concern, it is pertinent to develop an orientation that foregrounds the “lifeworld” of artifacts—the social, perceptual, and political environment in which they exist. While speculative designs often imply a lifeworld, infrastructural speculations place lifeworlds at the center of design concern, calling attention to the cultural, regulatory, environmental, and repair conditions that enable and surround particular future visions. By articulating connections and affinities between speculative design and infrastructure studies research, we contribute a set of design tactics for producing infrastructural speculations. These tactics help design researchers interrogate the complex and ongoing entanglements among technologies, institutions, practices, and systems of power when gauging the stakes of alternate lifeworlds

Improving survival for patients with advanced heart failure: A study of 737 consecutive patients

Objectives.This study sought to determine whether survival and risk of sudden death have improved for patients with advanced heart failure referred for consideration for heart transplantation as advances in medical therapy were systematically implemented over an 8-year period.Background.Recent survival trials in patients with mild to moderate heart failure and patients after a myocardial infarction have shown that angiotensin-converting enzyme inhibitors are beneficial, type I antiarrhythmic drugs can be detrimental, and amiodarone may be beneficial in some groups. The impact of advances in therapy may be enhanced or blunted when applied to severe heart failure.Methods.One-year mortality and sudden death were determined in relation to time, baseline variables and therapeutics for 737 consecutive patients referred for heart transplantation and discharged home on medical therapy from 1986 to 1988, 1989 to 1990 and 1991 to 1993. Medical care was directed by a single team of physicians with policies established by consensus. From 1986 to 1990, the hydralazine/isosorbide dinitrate combination or angiotensin-converting enzyme inhibitors were the initial vasodilators, and class I antiarrhythmic drugs were allowed. After 1990, captopril was the initial vasodilator, given to 86% of patients compared with 46% of patients before 1989. After mid-1989, class I agents were routinely withdrawn, and amiodarone was used for frequent ventricular ectopic beats or atrial fibrillation (53% of patients after 1990 vs. 10% before 1989).Results.The total 1-year mortality rate decreased from 33% before 1989 to 16% after 1990 (p = 0.0001), and sudden death decreased from 20% to 8% (p = 0.0006). Adjusted for clinical and hemodynamic variables in multivariate proportional hazards models, total mortality and sudden death were lower after 1990.Conclusions.The large reduction in mortality, particularly in sudden death, from advanced heart failure since 1990 may reflect an enhanced impact of therapeutic advances shown in large randomized trials when they are incorporated into a comprehensive approach in this population. This improved survival supports the growing practice of maintaining potential heart transplant candidates on optimal medical therapy until clinical decompensation mandates transplantation

Modeling Mayfly Nymph Length Distribution and Population Dynamics Across a Gradient of Stream Temperatures and Stream Types

We analyze a process-based temperature model for the length distribution and population over time of mayfly nymphs. Model parameters are estimated using a Markov Chain Monte Carlo parameter estimation method utilizing length distribution data at five different stream sites. Two different models (a standard exponential model and a modified Weibull model) of mayfly mortality are evaluated, where in both cases mayfly length growth is a function of stream temperature. Based on model-data comparisons to the modeled length distribution and the Bayesian Information Criterion, we found that approaches that length distribution data can reliably estimate 2–3 model parameters. Future model development could include additional factors include such as upstream environmental factors, abiotic conditions, inter- specific competition, predation, or stream salinity. Outputs of this model could be applied to predict mayfly emergence across a geographic domain or to forecast mayfly population responses to climate change

Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age

Abstract: The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain

CD103 Deficiency Prevents Graft-versus-Host Disease but Spares Graft-versus-Tumor Effects Mediated by Alloreactive CD8 T Cells

Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis

Background: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as ‘walking on pebbles’, may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. Methods: In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. Results: There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38–326.97], p < 0.001). Conclusion: The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA