Arterial Oxygen Saturation During Ascent to 5010 m: Heart Rate and AMS Scores

The hypothesis here is that tissues exposed to the hypoxia of altitude have increased blood flow so that the rate of arrival of oxygen is as rapid as normal. If the ascent is too rapid, the system starts to fail. The study involves an ascent to high altitude (5010 m) during which 59 subjects recorded their resting arterial oxygen saturation (SaO2), heart rate (HR) and Lake Louise acute mountain sickness (AMS) scores, twice daily. During the major ascent SaO2 fell progressively. In 42 subjects, HR increased in a highly significant, negative, relationship to SaO2. In 10 subjects heart rate (HR) remained unchanged. Three subjects showed extreme HR variability. Data were incomplete in four subjects. For nine of the subjects, showing the progressive HR versus SaO2 correlation during ascent, the sequence terminated with a lower HR than would be expected from the correlation so far. Individual AMS scores showed no correlation with SaO2 but averaged values from 19 of the subjects from each ‘one night’ stopover; showed a strong, negative, correlation. Average stopover HR values correlated negatively with the average SaO2 values. Cardiac output (CO) is likely to have increased during ascent as HR increased, since there is a progressive relationship between HR and cardiac output (CO). Hence, despite the progressive fall in SaO2, tissue oxygen delivery (DO2) would have remained close to normal in the 42 subjects who showed the significant HR: SaO2 relationship

The On/Off Nature of Star-Planet Interactions

Evidence suggesting an observable magnetic interaction between a star and its hot Jupiter appears as a cyclic variation of stellar activity synchronized to the planet's orbit. In this study, we monitored the chromospheric activity of 7 stars with hot Jupiters using new high-resolution echelle spectra collected with ESPaDOnS over a few nights in 2005 and 2006 from the CFHT. We searched for variability in several stellar activity indicators (Ca II H, K, the Ca II infrared triplet, Halpha, and He I). HD 179949 has been observed almost every year since 2001. Synchronicity of the Ca II H & K emission with the orbit is clearly seen in four out of six epochs, while rotational modulation with P_rot=7 days is apparent in the other two seasons. We observe a similar phenomenon on upsilon And, which displays rotational modulation (P_rot=12 days) in September 2005, in 2002 and 2003 variations appear to correlate with the planet's orbital period. This on/off nature of star-planet interaction (SPI) in the two systems is likely a function of the changing stellar magnetic field structure throughout its activity cycle. Variability in the transiting system HD 189733 is likely associated with an active region rotating with the star, however, the flaring in excess of the rotational modulation may be associated with its hot Jupiter. As for HD 179949, the peak variability as measured by the mean absolute deviation for both HD 189733 and tau Boo leads the sub-planetary longitude by 70 degrees. The tentative correlation between this activity and the ratio of Mpsini to the planet's rotation period, a quantity proportional to the hot Jupiter's magnetic moment, first presented in Shkolnik et al. 2005 remains viable. This work furthers the characterization of SPI, improving its potential as a probe of extrasolar planetary magnetic fields.Comment: Accepted for publication in the Astrophysical Journa

WASP-80b has a dayside within the T-dwarf range

AHMJT is a Swiss National Science Foundation (SNSF) fellow under grant number P300P2-147773. MG and EJ are Research Associates at the F.R.S-FNRS; LD received the support the support of the F.R.I.A. fund of the FNRS. DE, KH, and SU acknowledge the financial support of the SNSF in the frame of the National Centre for Competence in Research ‘PlanetS’. EH and IR acknowledge support from the Spanish Ministry of Economy and Competitiveness (MINECO) and the ‘Fondo Europeo de Desarrollo Regional’ (FEDER) through grants AYA2012-39612-C03-01 and ESP2013-48391-C4-1-R.WASP-80b is a missing link in the study of exo-atmospheres. It falls between the warm Neptunes and the hot Jupiters and is amenable for characterisation, thanks to its host star's properties. We observed the planet through transit and during occultation with Warm Spitzer. Combining our mid-infrared transits with optical time series, we find that the planet presents a transmission spectrum indistinguishable from a horizontal line. In emission, WASP-80b is the intrinsically faintest planet whose dayside flux has been detected in both the 3.6 and 4.5 $\mu$m Spitzer channels. The depths of the occultations reveal that WASP-80b is as bright and as red as a T4 dwarf, but that its temperature is cooler. If planets go through the equivalent of an L-T transition, our results would imply this happens at cooler temperatures than for brown dwarfs. Placing WASP-80b's dayside into a colour-magnitude diagram, it falls exactly at the junction between a blackbody model and the T-dwarf sequence; we cannot discern which of those two interpretations is the more likely. Flux measurements on other planets with similar equilibrium temperatures are required to establish whether irradiated gas giants, like brown dwarfs, transition between two spectral classes. An eventual detection of methane absorption in transmission would also help lift that degeneracy. We obtained a second series of high-resolution spectra during transit, using HARPS. We reanalyse the Rossiter-McLaughlin effect. The data now favour an aligned orbital solution and a stellar rotation nearly three times slower than stellar line broadening implies. A contribution to stellar line broadening, maybe macroturbulence, is likely to have been underestimated for cool stars, whose rotations have therefore been systematically overestimated. [abridged]Publisher PDFPeer reviewe

Patient-reported outcomes data in patients with psoriatic arthritis from a randomised trial of etanercept and methotrexate as monotherapy or in combination.

OBJECTIVES: We examined patient-reported outcomes (PROs) in The Study of Etanercept And Methotrexate in Patients with Psoriatic Arthritis (PsA); a 48-week, phase 3, randomised controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept monotherapy, and MTX+ etanercept in patients with PsA. METHODS: Efficacy endpoints included: mean changes from baseline and proportion of patients who reported improvements≥minimal clinically important difference (MCID) at week 24 in treatment groups for Health Assessment Questionnaire-Disability Index, Patient Global Assessment (PtGA), Patient Global Assessment of Joint Pain (PtGAJP) and Medical Outcomes Study Short Form-36 Questionnaire (SF-36) Physical Component Summary (PCS), and Mental Component Summary, and eight domain scores. PROs were analysed as reported (observed), without multiplicity adjustment; therefore, p values are descriptive. RESULTS: At week 24, patients receiving etanercept monotherapy or MTX+ etanercept combination reported greater improvements (p≤0.05) in PtGA, PtGAJP and SF-36 PCS scores compared with those receiving MTX monotherapy. Compared with MTX monotherapy, higher proportions of patients receiving etanercept monotherapy and combination therapy reported improvements≥MCID in PtGA (etanercept vs MTX, p=0.005) and PtGAJP (MTX +etanercept vs MTX, p=0.038). Across PROs, proportions of patients reporting scores≥age and gender-matched normative values at week 24 ranged from 20.8% to 51.0% with MTX monotherapy, 30.9% to 48.8% with etanercept monotherapy, and 30.6% to 52.3% with MTX+ etanercept combination. CONCLUSIONS: Patients receiving etanercept monotherapy or MTX+ etanercept reported greater improvements from baseline in several PROs compared with those receiving MTX monotherapy. PROs should be incorporated in discussions between patients and clinicians regarding their treatment choices as they can help determine which treatments are more beneficial in patients with PsA

A two-phase model for smoothly joining disparate growth phases in the macropodid Thylogale billardierii

Generally, sigmoid curves are used to describe the growth of animals over their lifetime. However, because growth rates often differ over an animal's lifetime a single curve may not accurately capture the growth. Broken-stick models constrained to pass through a common point have been proposed to describe the different growth phases, but these are often unsatisfactory because essentially there are still two functions that describe the lifetime growth. To provide a single, converged model to age animals with disparate growth phases we developed a smoothly joining two-phase nonlinear function (SJ2P), tailored to provide a more accurate description of lifetime growth of the macropod, the Tasmanian pademelon Thylogale billardierii. The model consists of the Verhulst logistic function, which describes pouch-phase growth--joining smoothly to the Brody function, which describes post-pouch growth. Results from the model demonstrate that male pademelons grew faster and bigger than females. Our approach provides a practical means of ageing wild pademelons for life history studies but given the high variability of the data used to parametrise the second growth phase of the model, the accuracy of ageing of post-weaned animals is low: accuracy might be improved with collection of longitudinal growth data. This study provides a unique, first robust method that can be used to characterise growth over the lifespan of pademelons. The development of this method is relevant to collecting age-specific vital rates from commonly used wildlife management practices to provide crucial insights into the demographic behaviour of animal populations.Financial support was provided by the Tasmanian Community Forest Agreement: Alternatives to 1080 Programme. In-kind support was provided by the University of Tasmania

Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson\u27s Disease.

UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson\u27s disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson\u27s disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle. l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson\u27s disease and related disorders. SIGNIFICANCE STATEMENT: Dopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson\u27s disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson\u27s disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response to l-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson\u27s disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson\u27s disease and potentially other basal-ganglia-related disorders

Hepatic IKKε expression is dispensable for high-fat feeding-induced increases in liver lipid content and alterations in glucose tolerance

© 2020 the American Physiological Society. There are endocrine and immunological changes that occur during onset and progression of the overweight and obese states. The inhibitor of nuclear factor-κB kinase-ε (IKKε) was originally described as an inducible protein kinase; whole body gene deletion or systemic pharmaceutical targeting of this kinase improved insulin sensitivity and glucose tolerance in mice. To investigate the primary sites of action associated with IKKε during weight gain, we describe the first mouse line with conditional elimination of IKKε in the liver (IKKεAlb-/-). IKKεAlb-/- mice and littermate controls gain weight, show similar changes in body composition, and do not display any improvements in insulin sensitivity or whole body glucose tolerance. These studies were conducted using breeder chow diets and matched low- vs. high-fat diets. While glycogen accumulation in the liver is reduced in IKKεAlb-/- mice, lipid storage in liver is similar in IKKεAlb-/- mice and littermate controls. Our results using IKKεAlb-/-mice suggest that the primary action of this kinase to impact insulin sensitivity during weight gain lies predominantly within extrahepatic tissues