Strong Dynamo Action in Rapidly Rotating Suns

Stellar dynamos are driven by complex couplings between rotation and turbulent convection, which drive global-scale flows and build and rebuild stellar magnetic fields. When stars like our sun are young, they rotate much more rapidly than the current solar rate. Observations generally indicate that more rapid rotation is correlated with stronger magnetic activity and perhaps more effective dynamo action. Here we examine the effects of more rapid rotation on dynamo action in a star like our sun. We find that vigorous dynamo action is realized, with magnetic field generated throughout the bulk of the convection zone. These simulations do not possess a penetrative tachocline of shear where global-scale fields are thought to be organized in our sun, but despite this we find strikingly ordered fields, much like sea-snakes of toroidal field, which are organized on global scales. We believe this to be a novel finding.Comment: 8 pages, 4 figs. Published in conference proceedings "Unsolved Problems in Stellar Physics", held July 2-6 2007 Cambridge, Englan

Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types

Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature

Ultrasound Mediated Gemcitabine Delivery Reduces the Normal-Tissue Toxicity of Chemoradiation Therapy in a Muscle-Invasive Bladder Cancer Model

Purpose: Chemoradiation is the standard of care in muscle-invasive bladder. While agents such as gemcitabine can enhance tumour radiosensitisation, their side effects can limit patient eligibility and treatment efficacy. Here we investigate ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal tissue toxicity in a murine orthotopic MIBC model. Materials and Methods: CD1-nude mice were injected orthotopically with RT112 bladder tumour cells. Conventional chemoradiation involved injecting gemcitabine (10 mg/kg) before 6 Gy targeted irradiation of the bladder area using a Small Animal Radiation Research Platform (SARRP). Ultrasound-mediated gemcitabine delivery (10 mg/kg gemcitabine) involved either co-administration of microbubbles with gemcitabine or conjugating gemcitabine onto microbubbles followed by exposure to ultrasound (1.1 MHz centre frequency, 1 MPa peak negative pressure, 1% duty cycle and 0.5 Hz pulse repetition frequency), prior to SARRP irradiation. The effect of ultrasound and microbubbles alone was also tested. Tumour volumes were measured by 3D ultrasound imaging. Acute normal tissue toxicity from 12 Gy to the lower bowel area was assessed using an intestinal crypt assay in mice culled. 3.75 days post-treatment. Results: Significant tumour growth delay was observed with conventional chemoradiation and both microbubble groups (p Conclusions: Ultrasound and microbubbles offer a promising new approach for improving chemoradiation therapy in muscle-invasive bladder cancer, maintaining tumour growth delay but with reduced acute intestinal toxicity compared to conventional chemoradiation therapy.</p

Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC. We identify candidate driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for therapeutic interventions. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The observations that higher T-cell infiltration is associated with better overall survival and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients

Self-Reported Head Injury and Risk of Late-Life Impairment and AD Pathology in an AD Center Cohort

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer\u27s disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 for the transition from MCI to dementia. Without respect to age, head injury increased the odds of mortality (OR = 1.54). Moreover, it increased the odds of a pathological diagnosis of AD for men (OR = 1.47) but not women (OR = 1.18). Men with a head injury had higher mean amyloid plaque counts in the neocortex and entorhinal cortex than men without. Conclusions: Self-reported head injury is associated with earlier onset, increased risk of cognitive impairment and dementia, increased risk of mortality, and AD-type pathological changes

Data-driven recommendations for enhancing real-time natural hazard warnings, communication, and response

The effectiveness and adequacy of natural hazard warnings hinges on the availability of data and its transformation into actionable knowledge for the public. Real-time warning communication and emergency response therefore need to be evaluated from a data science perspective. However, there are currently gaps between established data science best practices and their application in supporting natural hazard warnings. This Perspective reviews existing data-driven approaches that underpin real-time warning communication and emergency response, highlighting limitations in hazard and impact forecasts. Four main themes for enhancing warnings are emphasised: (i) applying best-practice principles in visualising hazard forecasts, (ii) data opportunities for more effective impact forecasts, (iii) utilising data for more localised forecasts, and (iv) improving data-driven decision-making using uncertainty. Motivating examples are provided from the extensive flooding experienced in Australia in 2022. This Perspective shows the capacity for improving the efficacy of natural hazard warnings using data science, and the collaborative potential between the data science and natural hazards communities

The Methodology of Modern Macroeconomics and the Descriptive Approach to Discounting

Critics of modern macroeconomics often raise concerns about unwarranted welfare conclusions and data mining. This paper illustrates these concerns with a thought experiment, based on the debate in environmental economics about the appropriate discount rate in climate change analyses: I set up an economy where a social evaluator wants to determine the optimal time path of emission levels, and seeks advice for this from an old-style neo-classical macroeconomist and a new neo-classical (modern) macroeconomist; I then describe how both economists analyze the economy, their policy advice, and their mistakes. I then use the insights from this thought experiment to point out some pitfalls of the modern macroeconomic methodology

Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66102/1/j.1469-7793.2001.t01-1-00141.x.pd

The Life-Cycle Model of Consumption and Saving

The life-cycle framework is the standard way that economists think about the intertemporal allocation of time, e¤ort and money. The framework has a venerable history in the economics profession with roots in the in…nite horizon models of Ramsey (1926) and Friedman (1957) and the …nite horizon models of Fisher (1930) and Modigliani and Brumberg (1956). Developments since the 1950’s have considerably increased the breadth, depth and coherence of the framework so that the modern version provides a guide to thinking about the modeling of many life-cycle choices (such as consumption, saving, education, human capital, marriage, fertility and labor supply) while taking account of uncertainty in a rigorous way. However, the life-cycle framework is held in increasing disrepute within the profession. We believe that reports of the demise - or even ill health - of the theory are much exaggerated. In this article we provide a defence of the life-cycle framework as a source of models that can be taken to the data. We emphasize this distinction between the life-cycle framework (or tradition) and particular models with empirical content. The life-cycle framework is a conceptual framework within which we can develop useful models; in this view, there is no such thing as the life-cycle model, only particular life-cycle models