Explosion Imminent: the appearance of Red Supergiants at the point of core-collapse

From the early radiation of type II-P supernovae (SNe), it has been claimed that the majority of their red supergiant (RSG) progenitors are enshrouded by large amounts of circumstellar material (CSM) at the point of explosion. The inferred density of this CSM is orders of magnitude above that seen around RSGs in the field, and is therefore indicative of a short phase of elevated mass-loss prior to explosion. It is not known over what time-scale this material gets there: is it formed over several decades by a ‘superwind’ with mass-loss rate M˙∼10−3M⊙yr−1⁠; or is it formed in less than a year by a brief ‘outburst’ with M˙∼10−1M⊙yr−1? In this paper, we simulate spectra for RSGs undergoing such mass-loss events, and demonstrate that in either scenario, the CSM suppresses the optical flux by over a factor of 100, and that of the near-IR by a factor of 10. We argue that the ‘superwind’ model can be excluded as it causes the progenitor to be heavily obscured for decades before explosion, and is strongly at odds with observations of II-P progenitors taken within 10 yr of core-collapse. Instead, our results favour abrupt outbursts < 1 yr before explosion as the explanation for the early optical radiation of II-P SNe. We therefore predict that RSGs will undergo dramatic photometric variability in the optical and infrared in the weeks-to-months before core-collapse

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson’s disease?

In Parkinson’s disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7 days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30 days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia

MRI of the cervical spinal cord predicts respiratory dysfunction in ALS

Abstract For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies