The Frequency of Withdrawal from Acute Care Is Impacted by Severe Acute Renal Failure

Introduction: In the general intensive care setting, decisions to withdraw life support when patients deteriorate despite aggressive treatment are estimated to occur in 10% of all patients and in 40% of the patients who die. Acute renal failure (ARF) severe enough to necessitate renal replacement therapy (RRT) is associated with in-hospital mortality approximating 50%. Yet the impact of severe ARF on decisions to withdraw treatment has not been previously described. In chronic renal failure patients, voluntary withdrawal from maintenance dialysis occurs in 10%–20% of patients when increasing complications and poor quality of life ensue, and knowing these data facilitates discussions with patients and families. Having similar data for complicated ARF would facilitate decision making for families and caregivers when these difficult situations arise. Methods: All cases of ARF requiring RRT during 2000–2001 at University of Michigan Hospital (n = 383) were entered prospectively into an outcome study at the time RRT was initiated. Comprehensive data collection included demographic and clinical characteristics, outcome and complications, and severity of illness. Additional information for patients who died included cause of death, life-support withdrawal decisions, and the presence of prior advance directives. Results: Overall mortality in severe ARF (i.e., severe enough to require RRT) was 53%. Lifesupport withdrawal occurred in 72% of deaths (compared to 40%–50% reported among general intensive care cases) and was associated with intensive care stay well beyond 2 weeks. Severity of illness, as indicated by modified APACHE III scores, was higher in patients who died than in survivors, but severity of illness was not higher for withdrawal from treatment than death without withdrawal decisions. Life-support withdrawal was not associated with other demographic or clinical characteristics (hospital service, primary admitting diagnosis, ventilator or pressor dependence, sepsis, or initial type of RRT chosen). Prior advance directives were available in 29% of patients overall, but having advance directives did not predict withdrawal from acute treatment. Death occurred within 2 days of withdrawal in more than 90% of cases, emphasizing the severity of underlying illness. Conclusions: Severe ARF reflects the severity of underlying illness, impacts overall survival, and is associated with more frequent withdrawal from aggressive treatment. High severity of illness and prolonged intensive care without improvement beyond 2 weeks presage decisions to withdraw treatment and signal patients and caregivers that death is imminent and that further aggressive care should be reconsidered or limited.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63219/1/jpm.2004.7.676.pd

The K2 & TESS Synergy II: Revisiting 26 systems in the TESS Primary Mission

The legacy of NASA's K2 mission has provided hundreds of transiting exoplanets that can be revisited by new and future facilities for further characterization, with a particular focus on studying the atmospheres of these systems. However, the majority of K2-discovered exoplanets have typical uncertainties on future times of transit within the next decade of greater than four hours, making observations less practical for many upcoming facilities. Fortunately, NASA's Transiting exoplanet Survey Satellite (TESS) mission is reobserving most of the sky, providing the opportunity to update the ephemerides for $\sim$300 K2 systems. In the second paper of this series, we reanalyze 26 single-planet, K2-discovered systems that were observed in the TESS primary mission by globally fitting their K2 and TESS lightcurves (including extended mission data where available), along with any archival radial velocity measurements. As a result of the faintness of the K2 sample, 13 systems studied here do not have transits detectable by TESS. In those cases, we re-fit the K2 lightcurve and provide updated system parameters. For the 23 systems with $M_* \gtrsim 0.6 M_\odot$, we determine the host star parameters using a combination of Gaia parallaxes, Spectral Energy Distribution (SED) fits, and MESA Isochrones and Stellar Tracks (MIST) stellar evolution models. Given the expectation of future TESS extended missions, efforts like the K2 & TESS Synergy project will ensure the accessibility of transiting planets for future characterization while leading to a self-consistent catalog of stellar and planetary parameters for future population efforts.Comment: Accepted for publication in ApJ. 29 pages, 9 figures, 12 table

Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys

Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian–human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.National Institutes of Health (U.S.) (AI055332)National Institutes of Health (U.S.) (AI060354)National Institutes of Health (U.S.) (AI078526)National Institutes of Health (U.S.) (AI084794)National Institutes of Health (U.S.) (AI095985)National Institutes of Health (U.S.) (AI096040)National Institutes of Health (U.S.) (AI100148)National Institutes of Health (U.S.) (AI10063)Bill & Melinda Gates Foundation (OPP1033091)Bill & Melinda Gates Foundation (OPP1033115)Bill & Melinda Gates Foundation (OPP1040741)Bill & Melinda Gates Foundation (OPP1040753)Ragon Institute of MGH, MIT, and HarvardStavros S. Niarchos FoundationHoward Hughes Medical Institute (Investigator

275 Candidates and 149 Validated Planets Orbiting Bright Stars in K2 Campaigns 0-10

Since 2014, NASA's K2 mission has observed large portions of the ecliptic plane in search of transiting planets and has detected hundreds of planet candidates. With observations planned until at least early 2018, K2 will continue to identify more planet candidates. We present here 275 planet candidates observed during Campaigns 0-10 of the K2 mission that are orbiting stars brighter than 13 mag (in Kepler band) and for which we have obtained high-resolution spectra (R = 44,000). These candidates are analyzed using the VESPA package (Morton 2012, 2015b) in order to calculate their false-positive probabilities (FPP). We find that 149 candidates are validated with an FPP lower than 0.1%, 39 of which were previously only candidates and 56 of which were previously undetected. The processes of data reduction, candidate identification, and statistical validation are described, and the demographics of the candidates and newly validated planets are explored. We show tentative evidence of a gap in the planet radius distribution of our candidate sample. Comparing our sample to the Kepler candidate sample investigated by Fulton et al. (2017), we conclude that more planets are required to quantitatively confirm the gap with K2 candidates or validated planets. This work, in addition to increasing the population of validated K2 planets by nearly 50% and providing new targets for follow-up observations, will also serve as a framework for validating candidates from upcoming K2 campaigns and the Transiting Exoplanet Survey Satellite, expected to launch in 2018.Comment: Published in AJ, 47 pages, 18 figures, 7 tables, associated supplementary dataset available at https://zenodo.org/record/116479

Widespread retreat of coastal habitat is likely at warming levels above 1.5 °C

Several coastal ecosystems—most notably mangroves and tidal marshes—exhibit biogenic feedbacks that are facilitating adjustment to relative sea-level rise (RSLR), including the sequestration of carbon and the trapping of mineral sediment. The stability of reef-top habitats under RSLR is similarly linked to reef-derived sediment accumulation and the vertical accretion of protective coral reefs. The persistence of these ecosystems under high rates of RSLR is contested. Here we show that the probability of vertical adjustment to RSLR inferred from palaeo-stratigraphic observations aligns with contemporary in situ survey measurements. A defcit between tidal marsh and mangrove adjustment and RSLR is likely at 4 mm yr−1 and highly likely at 7 mm yr−1 of RSLR. As rates of RSLR exceed 7 mm yr−1, the probability that reef islands destabilize through increased shoreline erosion and wave over-topping increases. Increased global warming from 1.5 °C to 2.0 °C would double the area of mapped tidal marsh exposed to 4 mm yr−1 of RSLR by between 2080 and 2100. With 3 °C of warming, nearly all the world’s mangrove forests and coral reef islands and almost 40% of mapped tidal marshes are estimated to be exposed to RSLR of at least 7 mm yr−1. Meeting the Paris agreement targets would minimize disruption to coastal ecosystems

Kelt-4Ab: An inflated hot jupiter transiting the bright (V ∼ 10) component of a hierarchical triple

We report the discovery of KELT-4Ab, an inflated, transiting Hot Jupiter orbiting the brightest component of ahierarchical triple stellar system. The host star is an F star with Teff =6206 ± 75 K, log g =4.108 ± 0.014, [Fe/H]= -0.116+0.069+0.065, M∗ = 1.201-0.061+0.067 M⊙, and R∗ = 1.603-0.038+0.039 R⊙. The best-fit linear ephemeris is BJDTDB =2456193.29157±0.00021 + E(2.9895936±0.0000048). With a magnitude of V∼10, a planetary radius of 1.699-0.045+0.046 RJ, and a mass of 0.902-0.059+0.060 MJ, it is the brightest host among the population of inflated Hot Jupiters (RP \u3e 1.5RJ), making it a valuable discovery for probing the nature of inflated planets. In addition, its existence within a hierarchical triple and its proximity to Earth (210 pc) provide a unique opportunity for dynamical studies with continued monitoring with high resolution imaging and precision radial velocities. The projected separation between KELT-4A and KELT-4BC is 328±16 AU and the projected separation between KELT-4B and KELT-4C is 10.30±0.74 AU. Assuming face-on, circular orbits, their respective periods would be 3780±290 and 29.4±3.6 years and the astrometric motions relative to the epoch in this work of both the binary stars around each other and of the binary around the primary star would be detectable now and may provide meaningful constraints on the dynamics of the system

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies