Ice giant system exploration in the 2020s: an introduction.

The international planetary science community met in London in January 2020, united in the goal of realizing the first dedicated robotic mission to the distant ice giants, Uranus and Neptune, as the only major class of solar system planet yet to be comprehensively explored. Ice-giant-sized worlds appear to be a common outcome of the planet formation process, and pose unique and extreme tests to our understanding of exotic water-rich planetary interiors, dynamic and frigid atmospheres, complex magnetospheric configurations, geologically-rich icy satellites (both natural and captured), and delicate planetary rings. This article introduces a special issue on ice giant system exploration at the start of the 2020s. We review the scientific potential and existing mission design concepts for an ambitious international partnership for exploring Uranus and/or Neptune in the coming decades. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.

Immune senescence: significance of the stromal microenvironment.

The immune system undergoes age-associated changes known as immunosenescence, resulting in increased susceptibility to infections, cancers and autoimmunity in the aged. The basis of our understanding of immunosenescence has been derived primarily from studies examining intrinsic defects within many of the cells of the immune system. While these studies have provided insight into the mechanisms of immunosenescence, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age-associated decline of immune function. These extrinsic defects appear to impact the functional activity of immune cells and may offer a potential target to recover immune activity. Indeed, rejuvenation studies which have targeted the stromal niche have restored immune function in aged successfully, highlighting the impact of the microenvironment towards the aetiology of immunosenescence.

Quasiperpendicular High Mach Number Shocks.

Shock waves exist throughout the Universe and are fundamental to understanding the nature of collisionless plasmas. Reformation is a process, driven by microphysics, which typically occurs at high Mach number supercritical shocks. While ongoing studies have investigated this process extensively both theoretically and via simulations, their observations remain few and far between. In this Letter we present a study of very high Mach number shocks in a parameter space that has been poorly explored and we identify reformation using in situ magnetic field observations from the Cassini spacecraft at 10 AU. This has given us an insight into quasiperpendicular shocks across 2 orders of magnitude in Alfvén Mach number (M_{A}) which could potentially bridge the gap between modest terrestrial shocks and more exotic astrophysical shocks. For the first time, we show evidence for cyclic reformation controlled by specular ion reflection occurring at the predicted time scale of ~0.3τ_{c}, where τ_{c} is the ion gyroperiod. In addition, we experimentally reveal the relationship between reformation and M_{A} and focus on the magnetic structure of such shocks to further show that for the same M_{A}, a reforming shock exhibits stronger magnetic field amplification than a shock that is not reforming.

Asymmetries observed in Saturn's magnetopause geometry.

For over 10 years, the Cassini spacecraft has patrolled Saturn's magnetosphere and observed its magnetopause boundary over a wide range of prevailing solar wind and interior plasma conditions. We now have data that enable us to resolve a significant dawn-dusk asymmetry and find that the magnetosphere extends farther from the planet on the dawnside of the planet by 7 ± 1%. In addition, an opposing dawn-dusk asymmetry in the suprathermal plasma pressure adjacent to the magnetopause has been observed. This probably acts to reduce the size asymmetry and may explain the discrepancy between the degree of asymmetry found here and a similar asymmetry found by Kivelson and Jia (2014) using MHD simulations. Finally, these observations sample a wide range of season, allowing the "intrinsic" polar flattening (14 ± 1%) caused by the magnetodisc to be separated from the seasonally induced north-south asymmetry in the magnetopause shape found theoretically (5 ± 1% when the planet's magnetic dipole is tilted away from the Sun by 10-17°).

Trans-pulmonary stent placement for pulmonary stenosis in a dog with a type R2A coronary artery anomaly.

A one-year-old male intact American bulldog was presented for evaluation of previously diagnosed pulmonary stenosis. Echocardiography identified ultra-severe stenosis with an instantaneous trans-pulmonary pressure gradient of 240 mmHg. Angiography confirmed the presence of an anomalous coronary artery with a prepulmonic course of the left coronary artery arising from a single right coronary ostium consistent with a type R2A coronary anomaly. A trans-pulmonary stent was successfully placed transvenously with diameter sizing based on coronary compression testing. No coronary compression was present on postimplantation angiography. A marked reduction in the pressure gradient was obtained on postoperative echocardiography (reduction to 68 mmHg), despite selecting a stent diameter less than the pulmonary annulus diameter. This is the first report of the use of coronary compression testing in transvenous trans-pulmonic stent implantation in a dog with a type R2A coronary artery anomaly. Selection of a stent diameter less than the pulmonary annulus diameter conveyed a clinically relevant reduction in the trans-pulmonic pressure gradient while avoiding coronary compression in this case.

Jupiter's Low-Altitude Auroral Zones: Fields, Particles, Plasma Waves, and Density Depletions.

The Juno spacecraft's polar orbits have enabled direct sampling of Jupiter's low-altitude auroral field lines. While various data sets have identified unique features over Jupiter's main aurora, they are yet to be analyzed altogether to determine how they can be reconciled and fit into the bigger picture of Jupiter's auroral generation mechanisms. Jupiter's main aurora has been classified into distinct "zones", based on repeatable signatures found in energetic electron and proton spectra. We combine fields, particles, and plasma wave data sets to analyze Zone-I and Zone-II, which are suggested to carry upward and downward field-aligned currents, respectively. We find Zone-I to have well-defined boundaries across all data sets. H+ and/or H3 + cyclotron waves are commonly observed in Zone-I in the presence of energetic upward H+ beams and downward energetic electron beams. Zone-II, on the other hand, does not have a clear poleward boundary with the polar cap, and its signatures are more sporadic. Large-amplitude solitary waves, which are reminiscent of those ubiquitous in Earth's downward current region, are a key feature of Zone-II. Alfvénic fluctuations are most prominent in the diffuse aurora and are repeatedly found to diminish in Zone-I and Zone-II, likely due to dissipation, at higher altitudes, to energize auroral electrons. Finally, we identify significant electron density depletions, by up to 2 orders of magnitude, in Zone-I, and discuss their important implications for the development of parallel potentials, Alfvénic dissipation, and radio wave generation.

In Search of Subsurface Oceans Within the Uranian Moons.

The Galileo mission to Jupiter discovered magnetic signatures associated with hidden subsurface oceans at the moons Europa and Callisto using the phenomenon of magnetic induction. These induced magnetic fields originate from electrically conductive layers within the moons and are driven by Jupiter's strong time-varying magnetic field. The ice giants and their moons are also ideal laboratories for magnetic induction studies. Both Uranus and Neptune have a strongly tilted magnetic axis with respect to their spin axis, creating a dynamic and strongly variable magnetic field environment at the orbits of their major moons. Although Voyager 2 visited the ice giants in the 1980s, it did not pass close enough to any of the moons to detect magnetic induction signatures. However, Voyager 2 revealed that some of these moons exhibit surface features that hint at recent geologically activity, possibly associated with subsurface oceans. Future missions to the ice giants may therefore be capable of discovering subsurface oceans, thereby adding to the family of known "ocean worlds" in our Solar System. Here, we assess magnetic induction as a technique for investigating subsurface oceans within the major moons of Uranus. Furthermore, we establish the ability to distinguish induction responses created by different interior characteristics that tie into the induction response: ocean thickness, conductivity and depth, and ionospheric conductance. The results reported here demonstrate the possibility of single-pass ocean detection and constrained characterization within the moons of Miranda, Ariel, and Umbriel, and provide guidance for magnetometer selection and trajectory design for future missions to Uranus.

Phase I clinical trial and pharmacokinetics of intravesical mitomycin C in dogs with localized transitional cell carcinoma of the urinary bladder.

BACKGROUND: Transitional cell carcinoma (TCC) is the most common cancer of the urinary tract in dogs. The most frequent cause of death is urinary obstruction from the primary tumor. Standard medical therapy for TCC is only partially effective. HYPOTHESIS/OBJECTIVES: Intravesical administration of mitomycin C (MMC) in dogs with invasive TCC will result in antitumor activity against the primary tumor and minimal systemic drug absorption. ANIMALS: Thirteen privately owned dogs with naturally occurring, histopathologically diagnosed TCC of the urinary bladder. METHODS: A prospective phase I trial was performed. MMC was given intravesically (600 µg/mL initial concentration) for 1 h/d for 2 consecutive days each month. The MMC concentration was escalated to a maximum of 800 µg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was determined. Serum assays for MMC were performed to determine the extent of systemic absorption of the MMC. RESULTS: The MTD of MMC based on local toxicoses was 700 µg/mL (1-h dwell time, 2 consecutive days). In addition, 2 dogs had severe myelosuppression and appeared to have systemic absorption of MMC. Five dogs had partial remission, and 7 dogs had stable disease. CONCLUSIONS: Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.

A review of the in situ probe designs from recent Ice Giant mission concept studies.

For the Ice Giants, atmospheric entry probes provide critical measurements not attainable via remote observations. Including the 2013-2022 NASA Planetary Decadal Survey, there have been at least five comprehensive atmospheric probe engineering design studies performed in recent years by NASA and ESA. International science definition teams have assessed the science requirements, and each recommended similar measurements and payloads to meet science goals with current instrument technology. The probe system concept has matured and converged on general design parameters that indicate the probe would include a 1-meter class aeroshell and have a mass around 350 to 400-kg. Probe battery sizes vary, depending on the duration of a post-release coast phase, and assumptions about heaters and instrument power needs. The various mission concepts demonstrate the need for advanced power and thermal protection system development. The many completed studies show an Ice Giant mission with an in situ probe is feasible and would be welcomed by the international science community.

Dogkeeping practices as reported by readers of an Australian dog enthusiast magazine.

OBJECTIVE: To characterise Australian domestic dogkeeping practices relevant to canine health and welfare. PROCEDURE: A quantitative questionnaire was distributed nationally through Dog's Life magazine. Data on management practices, household and dog demographics from 690 Australian dogs in 485 self-selected respondent households were analysed using ordinal and binary regression. RESULTS: Several variables, relating to dog, owner and environment were associated with management practices. The size of the dog correlated positively with being fed outdoors (P < 0.001), gameplaying (P = 0.016) and being trained (P = 0.001) and negatively with time spent indoors (P < 0.001). Neutered dogs were more likely to be walked every day (P = 0.027) and have had prior treatment for unwelcome behaviours (P < 0.001) but less likely to be fed outdoors (P < 0.013). The number of children in the household correlated with the dog being fed outdoors (P < 0.001). The number of adult female humans in the household correlated with dog being neutered (P < 0.001) whereas the reverse was linked to number of adult male humans in the household (P < 0.013). Larger numbers of adult female humans in the household were associated with a higher incidence of prior treatment for unwelcome behaviours (P = 0.020). The number of dogs in the household correlated negatively with dogs being walked every day (P < 0.004) and gameplaying (P = 0.001). Pure bred dogs were more likely to have attended puppy preschool than cross breeds (P = 0.002). CONCLUSION: Reference to previous studies of Australian dog owners suggests that the current data are representative in terms of location of households, sex and age of dogs, however, the proportion of pure bred dogs in the current survey was surprisingly high. This was perhaps because respondents were from a particular sector of the Australian dog-owning population. It must be acknowledged that Dog's Life magazine readers may be atypical of Australian dog owners, nevertheless, the study demonstrates that variables relating to the dog, owner or environment can be used to characterise management styles.

Detection of pS2 messenger RNA in gynecological cancers.

Estrogen-inducible pS2 mRNA was previously detected in human cancer cell lines the growth of which was sensitive to estrogen. In the present study, the expression of the pS2 gene was analyzed in 111 gynecological carcinomas. The pS2 message was detected in greatest abundance in 6 primary carcinomas of the ovary (6 of 29), 4 of these being mucinous cystadenocarcinomas. A secondary carcinoma of the ovary, and another of the omentum (1 of 4), also contained detectable levels of pS2 mRNA. Weak pS2 mRNA signals were occasionally observed in endometrial (2 of 55) and cervical carcinomas (2 of 33) as well. There was a poor correlation between estrogen receptor and pS2 mRNA in ovarian carcinomas.

Phase behavior of shape-changing spheroids.

We introduce a simple model for a biaxial nematic liquid crystal. This consists of hard spheroids that can switch shape between prolate (rodlike) and oblate (platelike) subject to an energy penalty Δε. The spheroids are approximated as hard Gaussian overlap particles and are treated at the level of Onsager's second-virial description. We use both bifurcation analysis and a numerical minimization of the free energy to show that, for additive particle shapes, (i) there is no stable biaxial phase even for Δε=0 (although there is a metastable biaxial phase in the same density range as the stable uniaxial phase) and (ii) the isotropic-to-nematic transition is into either one of two degenerate uniaxial phases, rod rich or plate rich. We confirm that even a small amount of shape nonadditivity may stabilize the biaxial nematic phase.

Internally driven large-scale changes in the size of Saturn's magnetosphere.

Saturn's magnetic field acts as an obstacle to solar wind flow, deflecting plasma around the planet and forming a cavity known as the magnetosphere. The magnetopause defines the boundary between the planetary and solar dominated regimes, and so is strongly influenced by the variable nature of pressure sources both outside and within. Following from Pilkington et al. (2014), crossings of the magnetopause are identified using 7 years of magnetic field and particle data from the Cassini spacecraft and providing unprecedented spatial coverage of the magnetopause boundary. These observations reveal a dynamical interaction where, in addition to the external influence of the solar wind dynamic pressure, internal drivers, and hot plasma dynamics in particular can take almost complete control of the system's dayside shape and size, essentially defying the solar wind conditions. The magnetopause can move by up to 10-15 planetary radii at constant solar wind dynamic pressure, corresponding to relatively "plasma-loaded" or "plasma-depleted" states, defined in terms of the internal suprathermal plasma pressure.

Dyspnea: the heart or the lungs? Differentiation at bedside by use of the simple Valsalva maneuver.

Thirty-seven patients with dyspnea, clinical chronic obstructive pulmonary disease and abnormal pulmonary function tests demonstrating an obstructive airways pattern underwent six-foot posteroanterior chest radiography, radionuclide ventriculography and sphygmomanometer-monitored arterial pressure response during a bedside Valsalva maneuver. Patients could be separated into three groups (square wave, absent overshoot, sinusoidal) on the basis of their Valsalva response which corresponded to left ventricular ejection fractions on radionuclide ventriculography of 0.19 +/- 0.05, 0.42 +/- 0.20, 0.64 +/- 0.13 (p less than 0.005 for differences between all group means). Pulmonary function test results and a detailed patient history could not accurately separate patients with primary pulmonary dyspnea from those with concomitant left ventricular dysfunction (ejection fraction less than 0.50). In this population of patients, however, both the sensitivity (88 percent) and predictive value (88 percent) for the presence of left ventricular dysfunction of an abnormal (square wave or absent overshoot) systolic arterial pressure response during Valsalva maneuver were high. Thus, in dyspneic subjects with clinical evidence of chronic obstructive airways disease, concomitant left ventricular dysfunction can be accurately diagnosed using the simple Valsalva maneuver without sophisticated equipment or highly trained personnel.

Yersinia enterocolitica septicaemia.

Septicaemia from Yersinia enterocolitica carries a mortality of up to 80%. We report the successful management of a case who required intensive therapy, including inotropic and ventilatory support.

Difference between lambs with chronic and mild dermatophilosis in frequency of alleles of CD3 gamma.

Southern blots prepared with DNA from 20 Merino lambs that previously had chronic dermatophilosis (chronic) and 20 lambs that previously had mild dermatophilosis lesions (resistant) were hybridised with DNA sequences of the genes for the T-cell receptor-beta (TCR beta), a TCR-associated peptide 'cluster designation 3 gamma chain' (CD3 gamma) and ovine Major Histocompatibility Complex class 1 (ov. MHC class 1). There was a significant difference in the incidence of an allele of CD3 gamma between the chronic and resistant lambs. No significant difference in the incidence of alleles of TCR beta or ov. MHC class 1 was detected.

Dermatophilus congolensis: strain differences in expression of phospholipase activities.

Interactions between Dermatophilus congolensis strains and with other bacteria of known haemolytic activities were used to elucidate the complex nature of haemolytic activities present in various D. congolensis strains. This was further analysed by measuring their specific phospholipase activities against defined substrates by thin layer chromatography. D. congolensis strains demonstrated haemolytic interactions (synergistic or antagonistic) with other D. congolensis strains and also other species of bacteria. Most isolates expressed lyso-phospholipase-D activity, while various strains also expressed sphingomyelinase-D activity, phospholipase-A versus phosphatidylcholines and/or cephalins, phospholipase-D versus phosphatidylcholines or all these activities, under the culture conditions used.

Blood T6-lymphocyte antigen levels as a poor resistance marker in ovine dermatophilosis.

Merino ewes lambs from a flock expected to have a high prevalence of dermatophilosis were examined for lesions at marking, weaning and prior to first shearing. Blood was collected at marking and prior to shearing to enable quantification of T6-lymphocyte antigen levels in peripheral blood mononuclear cells (PBM) using monoclonal antibody SBU-T6 20-27. A group of the lambs that had persistent and/or severe dermatophilosis had significantly lower (P < 0.05) mean levels of T6-lymphocyte staining in PBM than those with minimal or no dermatophilosis in blood samples collected prior to shearing. However, the wide variability of this parameter in resistant and susceptible lambs indicated that this would not be a satisfactory procedure to rank sheep for resistance to dermatophilosis.

Variation in cultural, morphological, biochemical properties and infectivity of Australian isolates of Dermatophilus congolensis.

Recent vaccination studies with Dermatophilus congolensis showed that variation of challenge strains had a considerable influence on protection afforded by the vaccines. In this study cultural, morphological and biochemical properties of 30 D. congolensis isolates from throughout Australian were investigated. The infective dose required to produce lesions of equivalent severity by these isolates for sheep, rabbits and guinea pigs was also examined and the isolates were grouped into four clusters of similar infectivity ranking. Analysis of the relationship between cultural, morphological and biochemical characteristics and infectivity rankings of clusters was undertaken to determine if certain properties were linked to infectivity. Considerable variability was found in haemolytic activity on blood agar, mucoid nature of colonies, motility, flagella density and polarity, capsule width, restriction enzyme profiles of bacterial DNA, protein electropherotype, carbohydrate content, and enzymic activity against proteins, maltose, chondroitin-4-sulphate, phospholipids and lipids. Of these properties haemolytic activity and enzyme activity against casein, chondroitin-4-sulphate and lipids showed some link with infectivity ranking for these isolates.