Future Exploration of the Outer Heliosphere and Very Local Interstellar Medium by Interstellar Probe.

A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.

Color, composition, and thermal environment of Kuiper Belt object (486958) Arrokoth.

The outer Solar System object (486958) Arrokoth (provisional designation 2014 MU69) has been largely undisturbed since its formation. We studied its surface composition using data collected by the New Horizons spacecraft. Methanol ice is present along with organic material, which may have formed through irradiation of simple molecules. Water ice was not detected. This composition indicates hydrogenation of carbon monoxide-rich ice and/or energetic processing of methane condensed on water ice grains in the cold, outer edge of the early Solar System. There are only small regional variations in color and spectra across the surface, which suggests that Arrokoth formed from a homogeneous or well-mixed reservoir of solids. Microwave thermal emission from the winter night side is consistent with a mean brightness temperature of 29 ± 5 kelvin.

The geology and geophysics of Kuiper Belt object (486958) Arrokoth.

The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, is composed of primitive objects preserving information about Solar System formation. In January 2019, the New Horizons spacecraft flew past one of these objects, the 36-kilometer-long contact binary (486958) Arrokoth (provisional designation 2014 MU69). Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters in diameter) within a radius of 8000 kilometers. Arrokoth has a lightly cratered, smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism.

Probing the energetic particle environment near the Sun.

NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

Alfvénic velocity spikes and rotational flows in the near-Sun solar wind.

The prediction of a supersonic solar wind1 was first confirmed by spacecraft near Earth2,3 and later by spacecraft at heliocentric distances as small as 62 solar radii4. These missions showed that plasma accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy5-7. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams8. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii9-11, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age12-14.

Pluto's Interaction With Energetic Heliospheric Ions.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

The "Puck" energetic charged particle detector: Design, heritage, and advancements.

Energetic charged particle detectors characterize a portion of the plasma distribution function that plays critical roles in some physical processes, from carrying the currents in planetary ring currents to weathering the surfaces of planetary objects. For several low-resource missions in the past, the need was recognized for a low-resource but highly capable, mass-species-discriminating energetic particle sensor that could also obtain angular distributions without motors or mechanical articulation. This need led to the development of a compact Energetic Particle Detector (EPD), known as the "Puck" EPD (short for hockey puck), that is capable of determining the flux, angular distribution, and composition of incident ions between an energy range of ~10 keV to several MeV. This sensor makes simultaneous angular measurements of electron fluxes from the tens of keV to about 1 MeV. The same measurements can be extended down to approximately 1 keV/nucleon, with some composition ambiguity. These sensors have a proven flight heritage record that includes missions such as MErcury Surface, Space ENvironment, GEochemistry, and Ranging and New Horizons, with multiple sensors on each of Juno, Van Allen Probes, and Magnetospheric Multiscale. In this review paper we discuss the Puck EPD design, its heritage, unexpected results from these past missions and future advancements. We also discuss high-voltage anomalies that are thought to be associated with the use of curved foils, which is a new foil manufacturing processes utilized on recent Puck EPD designs. Finally, we discuss the important role Puck EPDs can potentially play in upcoming missions.

The formation of Charon's red poles from seasonally cold-trapped volatiles.

A unique feature of Pluto's large satellite Charon is its dark red northern polar cap. Similar colours on Pluto's surface have been attributed to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon's high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.

Pluto's interaction with its space environment: Solar wind, energetic particles, and dust.

The New Horizons spacecraft carried three instruments that measured the space environment near Pluto as it flew by on 14 July 2015. The Solar Wind Around Pluto (SWAP) instrument revealed an interaction region confined sunward of Pluto to within about 6 Pluto radii. The region's surprisingly small size is consistent with a reduced atmospheric escape rate, as well as a particularly high solar wind flux. Observations from the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument suggest that ions are accelerated and/or deflected around Pluto. In the wake of the interaction region, PEPSSI observed suprathermal particle fluxes equal to about 1/10 of the flux in the interplanetary medium and increasing with distance downstream. The Venetia Burney Student Dust Counter, which measures grains with radii larger than 1.4 micrometers, detected one candidate impact in ±5 days around New Horizons' closest approach, indicating an upper limit of <4.6 kilometers(-3) for the dust density in the Pluto system.

Energetic particles in the jovian magnetotail.

When the solar wind hits Jupiter's magnetic field, it creates a long magnetotail trailing behind the planet that channels material out of the Jupiter system. The New Horizons spacecraft traversed the length of the jovian magnetotail to >2500 jovian radii (RJ; 1 RJ identical with 71,400 kilometers), observing a high-temperature, multispecies population of energetic particles. Velocity dispersions, anisotropies, and compositional variation seen in the deep-tail (greater, similar 500 RJ) with a approximately 3-day periodicity are similar to variations seen closer to Jupiter in Galileo data. The signatures suggest plasma streaming away from the planet and injection sites in the near-tail region (approximately 200 to 400 RJ) that could be related to magnetic reconnection events. The tail structure remains coherent at least until it reaches the magnetosheath at 1655 RJ.

Oxygen ions observed near Saturn's A ring.

Ions were detected in the vicinity of Saturn's A ring by the Ion and Neutral Mass Spectrometer (INMS) instrument onboard the Cassini Orbiter during the spacecraft's passage over the rings. The INMS saw signatures of molecular and atomic oxygen ions and of protons, thus demonstrating the existence of an ionosphere associated with the A ring. A likely explanation for these ions is photoionization by solar ultraviolet radiation of neutral O2 molecules associated with a tenuous ring atmosphere. INMS neutral measurements made during the ring encounter are dominated by a background signal.

Patients' values for health states associated with hepatitis C and physicians' estimates of those values.

OBJECTIVES: Hepatitis C is the leading cause of chronic hepatitis in the United States. Little information is available regarding how persons with hepatitis C view health with their disease. We studied patients' perceptions about the value of hepatitis C health states and evaluated whether physicians understand their patients' perspectives about this disease. METHODS: A total of 50 consecutive persons with hepatitis C were surveyed when they presented as new patients to a hepatology practice. Subjects provided utility assessments (preference values) for five hepatitis C health states and for treatment side effects. They also stated their threshold for accepting antiviral therapy. Five hepatologists used the same scales to estimate their patients' responses. RESULTS: On average, patients believed that hepatitis C without symptoms was associated with an 11% reduction in preference value from that of life without infection, and the most serious condition (severe symptoms, cirrhosis) was believed to carry a 73% decrement. Patients judged the side effects of antiviral therapy quite unfavorably, and their median stated threshold for accepting treatment was a cure rate of 80%. Physicians' estimates were not significantly associated with patients' preference values for hepatitis C health states, treatment side effects, or with patients' thresholds for accepting treatment. In multivariate analysis, patients' stated thresholds for taking treatment were significantly associated with their decisions regarding therapy (beta = -2.72+/-1.21, p = 0.025). CONCLUSIONS: There was little agreement between patients' preference values about hepatitis C and their physicians' estimates of those values. Utility analysis could facilitate shared decision making about hepatitis C.

Physicians' preference values for hepatitis C health states and antiviral therapy: a survey.

BACKGROUND: Physicians' perspectives regarding hepatitis C shape their approach to patient management. We used utility analysis to evaluate physicians' perceptions of hepatitis C-related health states (HS) and their threshold to recommend treatment. METHODS: A written questionnaire was administered to practicing physicians. They were asked to rate hepatitis C health states on a visual analog scale ranging from 0% (death) to 100% (health without hepatitis C). Physicians then judged quality of life associated with the side effects of antiviral therapy for hepatitis C and indicated the sustained virological response rate that they would require to recommend treatment. RESULTS: One hundred and thirteen physicians from five states were included. Median utility ratings for hepatitis C health states declined significantly with increasing severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms, Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of antiviral therapy was 47%, suggesting a 53% reduction from good health. That was similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median threshold value for recommending treatment was a sustained response rate of 60%. CONCLUSIONS: 1) Physicians' utility ratings for hepatitis C health states were inversely related to the severity of disease manifestations described. 2) Physicians viewed side effects of therapy unfavorably and indicated that on average, they would require a 60% sustained response rate before recommending treatment, which far exceeds the efficacy of current antiviral therapy for hepatitis C in the majority of patients.

Adult living donor liver transplantation: Preferences about donation outside the medical community.

An increasing number of transplant centers are performing adult living donor liver transplantation (LDLT). We evaluated peoples' perspectives on possible outcomes of living donation, thresholds for donating, and views regarding the donation process. One hundred fifty people were surveyed; half were from a medical care group serving an indigent population and half were from a private clinic. Preferences about outcomes of adult living donation were ranked and quantified on a visual analogue scale. Thresholds for donation to a loved one were quantified. Sixty percent of the respondents suggested they would prefer to donate and die and have the transplant recipient live rather than forego donation and have the potential transplant recipient die of liver failure. Participants' stated threshold for living donation was a median survival for themselves of only 79%. They would require that their loved one have a median survival of 55% with transplantation before they would agree to donate. Respondents from the medical care group reported higher survival thresholds for themselves and the transplant recipient, and race was the most statistically significant predictor of those thresholds. Sex was more predictive of threshold probabilities from the private clinic. Eighty-one percent of the respondents believed that the potential donor, not a physician, should have the final say regarding candidacy for living donation. In conclusion, the findings of this survey support the use of adult LDLT. Most respondents were willing to accept mortality rates that far exceed the estimated risk of donation and favored outcomes in which a loved one was saved.

Finding cancer in primary care outpatients with low back pain: a comparison of diagnostic strategies.

OBJECTIVE: To compare strategies for diagnosing cancer in primary care patients with low back pain. Strategies differed in their use of clinical findings, erythrocyte sedimentation rate (ESR), and plain x-rays prior to imaging and biopsy. DESIGN: Decision analysis and cost effectiveness analysis with sensitivity analyses. Strategies were compared in terms of sensitivity, specificity, and diagnostic cost effectiveness ratios. SETTING: Hypothetical MEASUREMENTS: Estimates of disease prevalence and test characteristics were taken from the literature. Costs were represented by the Medicare reimbursement for the tests and procedures employed. MAIN RESULTS: In the baseline analysis, using magnetic resonance imaging (MRI) as the imaging procedure prior to a single biopsy, strategies ranged in sensitivity from 0.40 to 0.73, with corresponding diagnostic costs of $14 to $241 per patient and average cost effectiveness ratios of $5,283 to $49,814 per case of cancer found. Incremental cost effectiveness ratios varied from $8,397 to $624,781; 5 strategies were dominant in the baseline analysis. Use of a higher ESR cutoff point (50 mm/hr) improved specificity and cost effectiveness for certain strategies. Imaging with MRI, or bone scan followed in series by MRI, resulted in a fewer unnecessary biopsies than imaging with bone scan alone. Cancer prevalence was an important determinant of cost effectiveness. CONCLUSIONS: We recommend a strategy of imaging patients who have a clinical finding (history of cancer, age > or = 50 years, weight loss, or failure to improve with conservative therapy) in combination with either an elevated ESR (> 50 mm/hr) or a positive x-ray, or using the same approach but imaging directly those patients with a history of cancer.

Emergency department admissions to inpatient cardiac telemetry beds: a prospective cohort study of risk stratification and outcomes.

PURPOSE: Little is known about physicians' use of inpatient cardiac telemetry units among emergency department patients at risk for cardiac complications. We therefore studied the outcomes of patients admitted to inpatient telemetry beds to identify a subset of patients from whom cardiac monitoring could be withheld safely. SUBJECTS AND METHODS: We conducted a prospective cohort study of 1, 033 consecutive adult patients admitted to an inpatient telemetry unit from the emergency department of a 700-bed urban public teaching hospital. Subjects with or without chest pain were risk-stratified using a prediction rule and observed for in-hospital cardiac complications, acute myocardial infarction, and transfer to an intensive care unit (ICU). RESULTS: There were no significant differences between patients with (n = 677) or patients without chest pain (n = 356) in the rates of major cardiac complications, myocardial infarctions, or transfers to an ICU. Among 318 patients with chest pain who were classified as being very low risk, none suffered major complications (negative predictive value 100%; 95% confidence interval [CI]: 98.8% to 100%). Among 214 very low risk patients without chest pain, 1 (0.5%) had a major complication (negative predictive value 99.5%; 95% CI: 97.4% to 99.9%). CONCLUSIONS: The prediction rule accurately identified patients with or without chest pain who were at very low risk of major complications, identifying a subset from whom cardiac monitoring could be withheld safely.

A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity.

Earlier we reported potent cRaf1 kinase inhibitors with a key acidic phenol pharmacophore that had, at best, adequate cellular efficacy. To improve the cellular potency, phenol isosteres and prodrugs were investigated. Many phenol isosteres were synthesized and tested, but failed to provide adequate enzyme potency. A prodrug approach resulted in a 2- to 17-fold improvement over the parent compound in cell-based efficacy.

Teaching residents evidence-based medicine skills: a controlled trial of effectiveness and assessment of durability.

OBJECTIVES: To measure the effectiveness of an educational intervention designed to teach residents four essential evidence-based medicine (EBM) skills: question formulation, literature searching, understanding quantitative outcomes, and critical appraisal. DESIGN: Firm-based, controlled trial. SETTING: Urban public hospital. PARTICIPANTS: Fifty-five first-year internal medicine residents: 18 in the experimental group and 37 in the control group. INTERVENTION: An EBM course, taught 2 hours per week for 7 consecutive weeks by senior faculty and chief residents focusing on the four essential EBM skills. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was performance on an EBM skills test that was administered four times over 11 months: at baseline and at three time points postcourse. Postcourse test 1 assessed the effectiveness of the intervention in the experimental group (primary outcome]; postcourse test 2 assessed the control group after it crossed over to receive the intervention; and postcourse test 3 assessed durability. Baseline EBM skills were similar in the two groups. After receiving the EBM course, the experimental group achieved significantly higher postcourse test scores (adjusted mean difference, 21%; 95% confidence interval, 13% to 28%; P < .001). Postcourse improvements were noted in three of the four EBM skill domains (formulating questions, searching, and quantitative understanding [P < .005 for all], but not in critical appraisal skills [P = .4]). After crossing over to receive the educational intervention, the control group achieved similar improvements. Both groups sustained these improvements over 6 to 9 months of follow-up. CONCLUSIONS: A brief structured educational intervention produced substantial and durable improvements in residents' cognitive and technical EBM skills.