Closed Fluxtubes and Dispersive Proton Conics at Jupiter's Polar Cap.

Two distinct proton populations are observed over Jupiter's southern polar cap: a ∼1 keV core population and ∼1-300 keV dispersive conic population at 6-7 RJ planetocentric distance. We find the 1 keV core protons are likely the seed population for the higher-energy dispersive conics, which are accelerated from a distance of ∼3-5 RJ. Transient wave-particle heating in a "pressure-cooker" process is likely responsible for this proton acceleration. The plasma characteristics and composition during this period show Jupiter's polar-most field lines can be topologically closed, with conjugate magnetic footpoints connected to both hemispheres. Finally, these observations demonstrate energetic protons can be accelerated into Jupiter's magnetotail via wave-particle coupling.

Water-Group Pickup Ions From Europa-Genic Neutrals Orbiting Jupiter.

Water-group gas continuously escapes from Jupiter's icy moons to form co-orbiting populations of particles or neutral toroidal clouds. These clouds provide insights into their source moons as they reveal loss processes and compositions of their parent bodies, alter local plasma composition, and act as sources and sinks for magnetospheric particles. We report the first observations of H2 + pickup ions in Jupiter's magnetosphere from 13 to 18 Jovian radii and find a density ratio of H2 +/H+ = 8 ± 4%, confirming the presence of a neutral H2 toroidal cloud. Pickup ion densities monotonically decrease radially beyond 13 R J consistent with an advecting Europa-genic toroidal cloud source. From these observations, we derive a total H2 neutral loss rate from Europa of 1.2 ± 0.7 kg s-1. This provides the most direct estimate of Europa's H2 neutral loss rate to date and underscores the importance of both ion composition and neutral toroidal clouds in understanding satellite-magnetosphere interactions.

Multi-model Meteorological and Aeolian Predictions for Mars 2020 and the Jezero Crater Region.

Nine simulations are used to predict the meteorology and aeolian activity of the Mars 2020 landing site region. Predicted seasonal variations of pressure and surface and atmospheric temperature generally agree. Minimum and maximum pressure is predicted at Ls ∼ 145 ∘ and 250 ∘ , respectively. Maximum and minimum surface and atmospheric temperature are predicted at Ls ∼ 180 ∘ and 270 ∘ , respectively; i.e., are warmest at northern fall equinox not summer solstice. Daily pressure cycles vary more between simulations, possibly due to differences in atmospheric dust distributions. Jezero crater sits inside and close to the NW rim of the huge Isidis basin, whose daytime upslope (∼east-southeasterly) and nighttime downslope (∼northwesterly) winds are predicted to dominate except around summer solstice, when the global circulation produces more southerly wind directions. Wind predictions vary hugely, with annual maximum speeds varying from 11 to 19 ms - 1 and daily mean wind speeds peaking in the first half of summer for most simulations but in the second half of the year for two. Most simulations predict net annual sand transport toward the WNW, which is generally consistent with aeolian observations, and peak sand fluxes in the first half of summer, with the weakest fluxes around winter solstice due to opposition between the global circulation and daytime upslope winds. However, one simulation predicts transport toward the NW, while another predicts fluxes peaking later and transport toward the WSW. Vortex activity is predicted to peak in summer and dip around winter solstice, and to be greater than at InSight and much greater than in Gale crater. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-020-00788-2.

A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185).

BACKGROUND: Hip fracture is a procedure with high mortality and complication rates, and there exists a group especially at risk of these outcomes identified by their Nottingham Hip Fracture Score (NHFS). Meta-analysis suggests a possible benefit to this patient group from intravascular volume optimisation. We investigated whether intraoperative fluid and blood pressure optimisation improved complications in this group. METHODS: Patients with a NHFS ≥ 5 were enrolled into this multicentre observer-blinded randomised control trial. Patients were allocated to either standard care or a combination of fluid optimisation and blood pressure control using a non-invasive system. The primary outcome was the number of patients with one or more complications in each group. Secondary outcomes included hospital length of stay (LOS), incidence of hypotension and fluid and vasopressor usage. RESULTS: Forty-six percent of patients in the intervention group suffered one or more complications compared to the 51% in the control group (OR 0.82 (95% CI 0.49-1.36)). Per-protocol analysis improved the OR to 0.73 (95% CI 0.43-1.24). Median LOS was the same between both groups; however, the mean LOS on a per-protocol analysis was longer in the control group compared to the intervention group (23.2 (18.0) days vs. 18.5 (16.5), p = 0.047). CONCLUSIONS: Haemodynamic optimisation including blood pressure management in high-risk patients undergoing repair of a hip fracture did not result in a statistically significant reduction in complications; however, a potential reduction in length of stay was seen. TRIAL REGISTRATION: A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185).

Comparing Electron Energetics and UV Brightness in Jupiter's Northern Polar Region During Juno Perijove 5.

We compare electron and UV observations mapping to the same location in Jupiter's northern polar region, poleward of the main aurora, during Juno perijove 5. Simultaneous peaks in UV brightness and electron energy flux are identified when observations map to the same location at the same time. The downward energy flux during these simultaneous observations was not sufficient to generate the observed UV brightness; the upward energy flux was. We propose that the primary acceleration region is below Juno's altitude, from which the more intense upward electrons originate. For the complete interval, the UV brightness peaked at ~240 kilorayleigh (kR); the downward and upward energy fluxes peaked at 60 and 700 mW/m2, respectively. Increased downward energy fluxes are associated with increased contributions from tens of keV electrons. These observations provide evidence that bidirectional electron beams with broad energy distributions can produce tens to hundreds of kilorayleigh polar UV emissions.

Energetic Oxygen and Sulfur Charge States in the Outer Jovian Magnetosphere: Insights From the Cassini Jupiter Flyby.

On 10 January 2001, Cassini briefly entered into the magnetosphere of Jupiter, en route to Saturn. During this excursion into the Jovian magnetosphere, the Cassini Magnetosphere Imaging Instrument/Charge-Energy-Mass Spectrometer detected oxygen and sulfur ions. While Charge-Energy-Mass Spectrometer can distinguish between oxygen and sulfur charge states directly, only 95.9 ± 2.9 keV/e ions were sampled during this interval, allowing for a long time integration of the tenuous outer magnetospheric (~200 RJ) plasma at one energy. For this brief interval for the 95.9 keV/e ions, 96% of oxygen ions were O+, with the other 4% as O2+, while 25% of the energetic sulfur ions were S+, 42% S2+, and 33% S3+. The S2+/O+ flux ratio was observed to be 0.35 (±0.06 Poisson error).

Energyscapes and prey fields shape a North Atlantic seabird wintering hotspot under climate change.

There is an urgent need for a better understanding of animal migratory ecology under the influence of climate change. Most current analyses require long-term monitoring of populations on the move, and shorter-term approaches are needed. Here, we analysed the ecological drivers of seabird migration within the framework of the energyscape concept, which we defined as the variations in the energy requirements of an organism across geographical space as a function of environmental conditions. We compared the winter location of seabirds with their modelled energy requirements and prey fields throughout the North Atlantic. Across six winters, we tracked the migration of 94 little auks (Alle alle), a key sentinel Arctic species, between their East Greenland breeding site and wintering areas off Newfoundland. Winter energyscapes were modelled with Niche Mapper™, a mechanistic tool which takes into account local climate and bird ecophysiology. Subsequently, we used a resource selection function to explain seabird distributions through modelled energyscapes and winter surface distribution of one of their main prey, Calanus finmarchicus. Finally, future energyscapes were calculated according to IPCC climate change scenarios. We found that little auks targeted areas with high prey densities and moderately elevated energyscapes. Predicted energyscapes for 2050 and 2095 showed a decrease in winter energy requirements under the high emission scenario, which may be beneficial if prey availability is maintained. Overall, our study demonstrates the great potential of the energyscape concept for the study of animal spatial ecology, in particular in the context of global change.

Pre-operative evaluation prior to soft tissue sarcoma excision - Why can't we get it right?

BACKGROUND: To define the association between an appropriate pre-operative workup (pre-operative advanced imaging studies, diagnostic biopsy) and incomplete soft tissue sarcoma (STS) excision. PATIENTS AND METHODS: This was a retrospective review of 397 consecutive patient records (2000-2008), looking at primary site advanced imaging (MRI or CT) and diagnostic biopsy procedures completed prior to the initial attempt at definitive surgical excision. Downstream effects of an inadequate pre-operative workup were also evaluated, including time to referral to a sarcoma multi-disciplinary care team and perceived alteration of surgical care in order to obtain a complete excision of the altered sarcoma bed. RESULTS: Thirty-eight percent (149/397) of soft tissue sarcomas identified underwent an incomplete excision prior to referral. A significant difference in the incidence of pre-operative primary site advanced imaging (91% vs. 42%, p < 0.001) and a pre-operative diagnostic biopsy (85% vs. 16%, p < 0.001) was found between the wide excision group and incomplete excision groups. Pre-operative biopsy (p < 0.001), tumor size >5 cm (p < 0.001), and a referral from an orthopaedic surgeon (p < 0.02) were all associated with reduced risk of incomplete excision in multivariate analysis. Seventy-four percent of patients in the incomplete excision group required an alteration in their definitive wide margin surgical resection, including rotational muscle flap coverage (37%), free flap coverage (11%), or amputation (11%). CONCLUSION: A minority of patients referred following incomplete excision of a STS had undergone an appropriate pre-operative workup prior to referral, leading to increased long-term morbidity following definitive re-excision. Education efforts to heighten awareness of suspicious soft tissue lesions remain vital.

Juno-UVS approach observations of Jupiter's auroras.

Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Prior to the bow shock crossing on 24 June 2016, the Juno approach provided a rare opportunity to correlate local solar wind conditions with Jovian auroral emissions. Some of Jupiter's auroral emissions are expected to be controlled or modified by local solar wind conditions. Here we compare synoptic Juno-UVS observations of Jupiter's auroral emissions, acquired during 3-29 June 2016, with in situ solar wind observations, and related Jupiter observations from Earth. Four large auroral brightening events are evident in the synoptic data, in which the total emitted auroral power increases by a factor of 3-4 for a few hours. Only one of these brightening events correlates well with large transient increases in solar wind ram pressure. The brightening events which are not associated with the solar wind generally have a risetime of ~2 h and a decay time of ~5 h.

Prognostic Markers of Outcome in Patients Undergoing Infra-inguinal Revascularisation: A Prospective Observational Pilot Study.

OBJECTIVES: The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value. METHODS: A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE). RESULTS: The 1 year mortality rate was 6%, the overall complications rate was 23%, and the combined incidence of MACE and 1 year mortality was 10%. Cycle ergonometry peak VO2 14 mL/kg/min (RR 5.5, 95% CI 1.4-22.4, p = .007) and AT < 10mL/kg/min (RR 3.0, 95% CI 1.1-7.0, p = .03) were predictors of post-operative complications. Pre-operative NT-proBNP > 320 ng/L (RR 18, 95% CI 2.5-140 p = .0003) was the sole predictor of 1 year mortality or MACE. CONCLUSION: The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.

Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio).

Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment.

Autoimmune encephalitis.

Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides.

The effects of sex and neonatal stress on pituitary adenylate cyclase-activating peptide expression.

NEW FINDINGS: What is the central question of this study? Does sex or neonatal stress affect the expression of pituitary adenylate cyclase-activating peptide or its receptors? What is the main finding and its importance? Neonatal-maternal separation stress has little long-lasting effect on the expression of pituitary adenylate cyclase-activating peptide or its receptors, but sex differences exist in these genes between males and females at baseline. Sex differences in classic stress hormones have been studied in depth, but pituitary adenylate cyclase-activating peptide (PACAP), recently identified as playing a critical role in the stress axes, has not. Here we studied whether baseline levels of PACAP differ between sexes in various stress-related tissues and whether neonatal-maternal separation stress has a sex-dependent effect on PACAP gene expression in stress pathways. Using quantitative RT-PCR, we found sex differences in PACAP and PACAP receptor gene expression in several respiratory and/or stress-related tissues, while neonatal-maternal separation stress did little to affect PACAP signalling in adult animals. We propose that sex differences in PACAP expression are likely to contribute to differences between males and females in responses to stress.

Methylxanthine reversal of opioid-induced respiratory depression in the neonatal rat: mechanism and location of action.

Methylxanthines like caffeine and theophylline have long been used to treat apnea of prematurity. Despite their success in stimulating neonatal breathing, their mechanism of action remains poorly understood. Methylxanthines can act as both non-specific adenosine receptor antagonists and inhibitors of cAMP-dependent phosphodiesterases, sarcoplasmic/endoplasmic reticulum calcium ATPases or receptor-coupled anion channels, depending on the dose used. Though there is evidence for methylxanthine action at the level of the carotid body, the consensus is that methylxanthines stimulate the respiratory centers of the brainstem. Here we used the in situ neonatal rat working heart-brainstem preparation and the ex vivo neonatal rat carotid body preparation to test the hypothesis that methylxanthines act at the level of the carotid body. We conclude that although the neonatal carotid body has active adenosine receptors, the effects of methylxanthine therapy are likely mediated centrally, predominantly via inhibition of cAMP-dependent phosphodiesterase-4.

Crystalloid or colloid for goal-directed fluid therapy in colorectal surgery.

BACKGROUND: Goal-directed fluid therapy has been shown to improve outcomes after colorectal surgery, but the optimal type of i.v. fluid to use is yet to be established. Theoretical advantages of using hydroxyethyl starch (HES) for goal-directed therapy include a reduction in the total volume of fluid required, resulting in less tissue oedema. Recent work has demonstrated that new generations of HES have a good safety profile, but their routine use in the perioperative setting has not been demonstrated to confer outcome benefit. METHODS: We randomly assigned 202 medium to high-risk patients undergoing elective colorectal surgery to receive either balanced 6% HES (130/0.4, Volulyte) or balanced crystalloid (Hartmann's solution) as haemodynamic optimization fluid. The primary outcome measure was the incidence of gastrointestinal (GI) morbidity on postoperative day 5. Secondary outcome measures included the incidence of postoperative complications, hospital length of stay, and the effect of trial fluids on coagulation and inflammation. RESULTS: No difference was seen in the number of patients who suffered GI morbidity on postoperative day 5 [30% in the HES group vs 32% in the crystalloid group; adjusted odds ratio=0.96 (0.52-1.77)]. Subjects in the crystalloid group received more fluid [median (inter-quartile ranges) 3175 (2000-3700) vs 1875 (1500-3000) ml, P<0.001] and had a higher 24 h fluid balance [+4226 (3251-5779) vs +3610 (2443-4519) ml, P<0.001]. No difference in the incidence of postoperative complications was seen between the groups. CONCLUSIONS: Goal-directed fluid therapy is possible with either crystalloid or HES. There is no evidence of a benefit in using HES over crystalloid, despite its use resulting in a lower 24 h fluid balance.

Stress peptide PACAP stimulates and stabilizes neonatal breathing through distinct mechanisms.

Pituitary adenylate cyclase-activating peptide (PACAP) is an important mediator of the stress response and is crucial in maintaining breathing in neonates. Here we investigate the role of exogenously applied PACAP in neonatal breathing using the neonatal rat in situ working heart-brainstem preparation. A 1-min bolus of 250 nM PACAP-38 caused an increased in respiratory frequency that was rapid and transient, but had no effect on neural tidal volume or neural minute ventilation. Denervation of the carotid body abolished this effect. PACAP had a persistent effect on breathing stability in both carotid body-intact and -denervated preparations, as shown by decreases in respiratory variability 5 min following application. These data suggest that PACAP released during stress acts via carotid body dependent and independent mechanisms to stimulate and stabilize breathing. These mechanisms may account for PACAP's critical role in defending neonatal breathing against environmental stress.

Neural activity and branching of embryonic retinal ganglion cell dendrites.

The shape of a neuron's dendritic arbor is critical for its function as it determines the number of inputs the neuron can receive and how those inputs are processed. During development, a neuron initiates primary dendrites that branch to form a simple arbor. Subsequently, growth occurs by a process that combines the extension and retraction of existing dendrites, and the addition of new branches. The loss and addition of the fine terminal branches of retinal ganglion cells (RGCs) is dependent on afferent inputs from its synaptic partners, the amacrine and bipolar cells. It is unknown, however, whether neural activity regulates the initiation of primary dendrites and their initial branching. To investigate this, Xenopus laevis RGCs developing in vivo were made to express either a delayed rectifier type voltage-gated potassium (KV) channel, Xenopus Kv1.1, or a human inward rectifying channel, Kir2.1, shown previously to modulate the electrical activity of Xenopus spinal cord neurons. Misexpression of either potassium channel increased the number of branch points and the total length of all the branches. As a result, the total dendritic arbor was bigger than for control green fluorescent protein-expressing RGCs and those ectopically expressing a highly related mutant non-functional Kv1.1 channel. Our data indicate that membrane excitability regulates the earliest differentiation of RGC dendritic arbors.

Fragmentation dynamics of frozen-thawed ram sperm DNA is modulated by sperm concentration.

This study investigated the hypothesis that post-thaw incubation of ram sperm at high concentrations results in a faster rate of DNA fragmentation than when sperm are incubated at a lower concentration. Ejaculates from 10 rams were frozen-thawed, prepared in sperm concentrations of 100, 50, 25, 12, and 6 × 106 sperm/mL, and incubated for 6 h at 37 °C. Sperm DNA fragmentation was assessed using the sperm chromatin dispersion test (Sperm-Halomax®) at 1, 3, 4, and 6 h of incubation at 37 °C. On fitting a binary logistic regression with a cubic over time and treating ram and dilution levels as factors, there were significant effects with respect to the ram, dilution and time (all P-values were very much smaller than 0.001). Therefore, DNA fragmentation dynamics of incubated frozen-thawed ram sperm were not only dependent on the inherent sperm DNA fragmentation expressed immediately after thawing, but also on the concentration of sperm incubated in the sample. Although there was evidence of individual ram variation in SDF during the incubation period, the general finding of the current study was that lower sperm concentrations resulted in a slower rate of DNA fragmentation These findings have important implications for the post-thaw manipulation of ram sperm used for AI and advanced reproductive procedures that use sperm at low concentrations. Our data also emphasised the highly dynamic nature of sperm DNA fragmentation and the importance of conducting the procedure in a standardised manner.