The Effect of Ventricular Assist Devices on Post-Transplant Mortality An Analysis of the United Network for Organ Sharing Thoracic Registry

ObjectivesThis study sought to determine the relationship between pre-transplant ventricular assist device (VAD) support and mortality after heart transplantation.BackgroundIncreasingly, VADs are being used to bridge patients to heart transplantation. The effect of these devices on post-transplant mortality is unclear.MethodsPatients 18 years or older who underwent first-time, single-organ heart transplantation in the U.S. between 1995 and 2004 were included in the analyses. This study compared 1,433 patients bridged with intracorporeal and 448 patients bridged with extracorporeal VADs with 9,455 United Network for Organ Sharing status 1 patients not bridged with a VAD with respect to post-transplant mortality. Because the proportional hazards assumption was not met, hazard ratios (HRs) for different time periods were estimated.ResultsIntracorporeal VADs were associated with an HR of 1.20 (95% confidence interval [CI]: 1.02 to 1.43; p = 0.03) for mortality in the first 6 months after transplant and an HR of 1.99 (95% CI: 1.44 to 2.75; p < 0.0001) beyond 5 years. Between 6 months and 5 years, the HRs were not significantly different from 1. Extracorporeal VADs were associated with an HR of 1.91 (95% CI: 1.53 to 2.37; p < 0.0001) for mortality in the first 6 months and an HR of 2.93 (95% CI: 1.19 to 7.25; p = 0.02) beyond 5 years. The HRs were not significantly different from 1 between 6 months and 5 years, except for an HR of 0.23 (95% CI: 0.06 to 0.91; p = 0.04) between 24 and 36 months.ConclusionsExtracorporeal VADs are associated with higher mortality within 6 months and again beyond 5 years after transplantation. Intracorporeal VADs are associated with a small increase in mortality in the first 6 months and a clinically significant increase in mortality beyond 5 years. These data do not provide evidence supporting VAD implantation in stable United Network for Organ Sharing status I patients awaiting heart transplantation

Graphical programming: A systems approach for telerobotic servicing of space assets

Satellite servicing is in many ways analogous to subsea robotic servicing in the late 1970's. A cost effective, reliable, telerobotic capability had to be demonstrated before the oil companies invested money in deep water robot serviceable production facilities. In the same sense, aeronautic engineers will not design satellites for telerobotic servicing until such a quantifiable capability has been demonstrated. New space servicing systems will be markedly different than existing space robot systems. Past space manipulator systems, including the Space Shuttle's robot arm, have used master/slave technologies with poor fidelity, slow operating speeds and most importantly, in-orbit human operators. In contrast, new systems will be capable of precision operations, conducted at higher rates of speed, and be commanded via ground-control communication links. Challenge presented by this environment include achieving a mandated level of robustness and dependability, radiation hardening, minimum weight and power consumption, and a system which accommodates the inherent communication delay between the ground station and the satellite. There is also a need for a user interface which is easy to use, ensures collision free motions, and is capable of adjusting to an unknown workcell (for repair operations the condition of the satellite may not be known in advance). This paper describes the novel technologies required to deliver such a capability

Patterns of Recovery from Severe Mental Illness: A Pilot Study of Outcomes

We performed a pilot study examining the patterns of recovery from severe mental illness in a model integrated service delivery system using measures from the Milestones of Recovery Scale (MORS), a valid and reliable measure of recovery outcomes which ranges from 1 to 8 (8 levels). For purposes of presentation, we constructed an aggregate MORS (6 levels) where the levels are described as follows: (1) extreme risk; (2) unengaged, poorly self-coordinating; (3) engaged, poorly self-coordinating; (4) coping and rehabilitating; (5) early recovery, and (6) self reliant. We analyzed MORS data on individuals followed over time from The Village in Long Beach, California (658 observations). Using Markov Chains, we estimated origin-destination transition probabilities, simulating recovery outcomes for 100 months. Our models suggest that after 12 months only 8% of “extreme risk” clients remain such. Over 40% have moved to “engaged, poorly self-coordinating.” After 2 years, almost half of the initial “extreme Risk” clients are “coping/rehabilitating”, “early recovery” or “Self reliant.” Most gains occur within 2 years

Amyotrophic lateral sclerosis-motor neuron disease, monoclonal gammopathy, hyperparathyroidism, and B12 deficiency: case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Amyotrophic lateral sclerosis (the most common form of motor neuron disease) is a progressive and devastating disease involving both lower and upper motor neurons, typically following a relentless path towards death. Given the gravity of this diagnosis, all efforts must be made by the clinician to exclude alternative and more treatable entities. Frequent serology testing involves searching for treatable disorders, including vitamin B12 deficiency, parathyroid anomalies, and monoclonal gammopathies.</p> <p>Case presentation</p> <p>We present the case of a 78-year-old Caucasian man with all three of the aforementioned commonly searched for disorders during an investigation for amyotrophic lateral sclerosis.</p> <p>Conclusions</p> <p>The clinical utility of these common tests and what they ultimately mean in patients with amyotrophic lateral sclerosis is discussed, along with a review of the literature.</p

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series

Abstract Background Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of anthracyclines, but in the USA and some European countries, its use had been restricted to adults with advanced breast cancer receiving a cumulative doxorubicin (an anthracycline) dose > 300 mg/m2. We evaluated the off-label use of dexrazoxane as a cardioprotectant in adult patients with preexisting cardiomyopathy, undergoing anthracycline chemotherapy. Methods Between July 2015 and June 2017, five consecutive patients, with preexisting, asymptomatic, systolic left ventricular (LV) dysfunction who required anthracycline-based chemotherapy, were concomitantly treated with off-label dexrazoxane, administered 30 min before each anthracycline dose, regardless of cancer type or stage. Demographic, cardiovascular, and cancer-related outcomes were compared to those of three consecutive patients with asymptomatic cardiomyopathy treated earlier at the same hospital without dexrazoxane. Results Mean age of the five dexrazoxane-treated patients and three patients treated without dexrazoxane was 70.6 and 72.6 years, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300 mg/m2). With dexrazoxane therapy, changes in LV systolic function were minimal with mean left ventricular ejection fraction (LVEF) decreasing from 39% at baseline to 34% after chemotherapy. None of the dexrazoxane-treated patients experienced symptomatic heart failure or elevated biomarkers (cardiac troponin I or brain natriuretic peptide). Of the three patients treated without dexrazoxane, two received doxorubicin (mean dose, 210 mg/m2), and one received daunorubicin (540 mg/m2). Anthracycline therapy resulted in a marked reduction in LVEF from 42.5% at baseline to 18%. All three developed symptomatic heart failure requiring hospitalization and intravenous diuretic therapy. Two of them died from cardiogenic shock and multi-organ failure. Conclusion The concomitant administration of dexrazoxane in patients with preexisting cardiomyopathy permitted successful delivery of anthracycline-based chemotherapy without cardiac decompensation. Larger prospective trials are warranted to examine the use of dexrazoxane as a cardioprotectant in patients with preexisting cardiomyopathy who require anthracyclines.https://deepblue.lib.umich.edu/bitstream/2027.42/147463/1/40959_2019_Article_36.pd

Evidence for a fast evolution of the UV luminosity function beyond redshift 6 from a deep HAWK-I survey of the GOODS-S field

We perform a deep search for galaxies in the redshift range 6.5<z<7.5, to measure the evolution of the number density of luminous galaxies in this redshift range and derive useful constraints on the evolution of their Luminosity Function. We present here the first results of an ESO Large Program, that exploits the unique combination of area and sensitivity provided in the near-IR by the camera Hawk-I at the VLT. We have obtained two Hawk-I pointings on the GOODS South field for a total of 32 observing hours, covering ~90 arcmin2. The images reach Y=26.7 mags for the two fields. We have used public ACS images in the z band to select z-dropout galaxies with the colour criteria Z-Y>1, Y-J<1.5 and Y-K<2. The other public data in the UBVRIJHK bands are used to reject possible low redshift interlopers. The output has been compared with extensive Monte Carlo simulations to quantify the observational effects of our selection criteria as well as the effects of photometric errors. We detect 7 high quality candidates in the magnitude range Y=25.5-26.7. This interval samples the critical range for M* at z>6 (M_1500 ~- 19.5 to -21.5). After accounting for the expected incompleteness, we rule out at a 99% confidence level a Luminosity Function constant from z=6 to z=7, even including the effects of cosmic variance. For galaxies brighter than M_1500=-19.0 we derive a luminosity density rho_UV=1.5^{+2.0}_{-0.9} 10^25 erg/s/Hz/Mpc3, implying a decrease by a factor 3.5 from z=6 to z~6.8. On the basis of our findings, we make predictions for the surface densities expected in future surveys surveys, based on ULTRA-VISTA, HST-WFC3 or JWST-NIRCam, evaluating the best observational strategy to maximise their impact.Comment: Accepted for publication in Astronomy & Astrophysic

Language, Religion, and Ethnic Civil War

Are certain ethnic cleavages more conflict-prone than others? While only few scholars focus on the contents of ethnicity, most of those who do argue that political violence is more likely to occur along religious divisions than linguistic ones. We challenge this claim by analyzing the path from linguistic differences to ethnic civil war along three theoretical steps: (1) the perception of grievances by group members, (2) rebel mobilization, and (3) government accommodation of rebel demands. Our argument is tested with a new data set of ethnic cleavages that records multiple linguistic and religious segments for ethnic groups from 1946 to 2009. Adopting a relational perspective, we assess ethnic differences between potential challengers and the politically dominant group in each country. Our findings indicate that intrastate conflict is more likely within linguistic dyads than among religious ones. Moreover, we find no support for the thesis that Muslim groups are particularly conflict-prone

Hypoxia-inducible Factor-1 Activation in Nonhypoxic Conditions: The Essential Role of Mitochondrial-derived Reactive Oxygen Species

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Here we report that the generation of mitochondrial reactive oxygen species are essential for regulating HIF-1 in normal oxygen conditions in the vasculature

Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis

Depression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging. Methods The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS. Results Patients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio. Conclusions Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally