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The complexities underlying epilepsy in people with glioblastoma
Seizures are among the most common clinical signs in people with glioblastoma. Advances over the past 5 years, including new clinical trial data, have increased the understanding of why some individuals with glioblastoma are susceptible to seizures, how seizures manifest clinically, and what implications seizures have for patient management. The pathophysiology of epilepsy in people with glioblastoma relates to a combination of intrinsic epileptogenicity of tumour tissue, alterations in the tumour and peritumoural microenvironment, and the physical and functional disturbance of adjacent brain structures. Successful management of epilepsy in people with glioblastoma remains challenging; factors such as drug–drug interactions between cancer therapies and antiseizure medications, and medication side-effects, can affect seizure outcomes and quality of life. Advances in novel therapies provide some promise for people with glioblastoma; however, the effects of these therapies on seizures are yet to be fully determined. Looking forward, insights into electrical activity as a driver of tumour cell growth and the intrinsic hyperexcitability of tumour tissue might represent useful targets for treatment and disease modification. There is a pressing need for large randomised clinical trials in this field.
Journal Article
The Cambridge companion to Piers Plowman
\"Piers Plowman, written by William Langland, has long been considered one of the greatest poems of medieval England. Current scholarship on this alliterative masterpiece looks very different from that available even a decade ago. New information about the manuscripts of the poem, new historical discoveries, and new investigations of its literary, cultural and theoretical scope have fundamentally altered the very meaning of Langland's art. This Companion thus critically surveys traditional scholarship, with the aim of recuperating its best insights, and it ventures forth into newer areas of inquiry attuned to questions of social setting, institutional context, intellectual and literary history, theory, and the revitalized fields of codicology and paleography. By proceeding through chapters that offer cumulatively wider views as well as stand-alone analyses of topics most crucial to understanding Piers Plowman, this Companion gives serious students and seasoned scholars alike up-to-date knowledge of this intricate and beautiful poem\"-- Provided by publisher.
Book
Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease
Using intracranial electrode recordings in two individuals with Alzheimer's disease, Lam
et al
. discover hippocampal seizure activity that could not be detected by traditional EEG monitoring.
We directly assessed mesial temporal activity using intracranial foramen ovale electrodes in two patients with Alzheimer's disease (AD) without a history or EEG evidence of seizures. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when these abnormalities were most likely to interfere with memory consolidation. The findings in these index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.
Journal Article
Removing Constraints on the Biomass Production of Freshwater Macroalgae by Manipulating Water Exchange to Manage Nutrient Flux
Freshwater macroalgae represent a largely overlooked group of phototrophic organisms that could play an important role within an industrial ecology context in both utilising waste nutrients and water and supplying biomass for animal feeds and renewable chemicals and fuels. This study used water from the intensive aquaculture of freshwater fish (Barramundi) to examine how the biomass production rate and protein content of the freshwater macroalga Oedogonium responds to increasing the flux of nutrients and carbon, by either increasing water exchange rates or through the addition of supplementary nitrogen and CO2. Biomass production rates were highest at low flow rates (0.1-1 vol.day-1) using raw pond water. The addition of CO2 to cultures increased biomass production rates by between 2 and 25% with this effect strongest at low water exchange rates. Paradoxically, the addition of nitrogen to cultures decreased productivity, especially at low water exchange rates. The optimal culture of Oedogonium occurred at flow rates of between 0.5-1 vol.day-1, where uptake rates peaked at 1.09 g.m-2.day-1 for nitrogen and 0.13 g.m-2.day-1 for phosphorous. At these flow rates Oedogonium biomass had uptake efficiencies of 75.2% for nitrogen and 22.1% for phosphorous. In this study a nitrogen flux of 1.45 g.m-2.day-1 and a phosphorous flux of 0.6 g.m-2.day-1 was the minimum required to maintain the growth of Oedogonium at 16-17 g DW.m-2.day-1 and a crude protein content of 25%. A simple model of minimum inputs shows that for every gram of dry weight biomass production (g DW.m-2.day-1), Oedogonium requires 0.09 g.m-2.day-1 of nitrogen and 0.04 g.m-2.day-1 of phosphorous to maintain growth without nutrient limitation whilst simultaneously maintaining a high-nutrient uptake rate and efficiency. As such the integrated culture of freshwater macroalgae with aquaculture for the purposes of nutrient recovery is a feasible solution for the bioremediation of wastewater and the supply of a protein resource.
Journal Article
The Joneses
The Joneses, a seemingly perfect family, are the envy of their posh, suburban neighborhood filled with all the trappings of the upper middle class. They are the ultimate trend setters with an endless supply of high-tech toys, designer clothes, fast cars and the latest gadgets. But as the neighbors try to keep up with the Joneses, none are prepared for the truth about this all too perfect family.
DVD
Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1
Programmed death-ligand 1 is a glycoprotein expressed on antigen presenting cells, hepatocytes, and tumors which upon interaction with programmed death-1, results in inhibition of antigen-specific T cell responses. Here, we report a mechanism of inhibiting programmed death-ligand 1 through small molecule-induced dimerization and internalization. This represents a mechanism of checkpoint inhibition, which differentiates from anti-programmed death-ligand 1 antibodies which function through molecular disruption of the programmed death 1 interaction. Testing of programmed death ligand 1 small molecule inhibition in a humanized mouse model of colorectal cancer results in a significant reduction in tumor size and promotes T cell proliferation. In addition, antigen-specific T and B cell responses from patients with chronic hepatitis B infection are significantly elevated upon programmed death ligand 1 small molecule inhibitor treatment. Taken together, these data identify a mechanism of small molecule-induced programmed death ligand 1 internalization with potential therapeutic implications in oncology and chronic viral infections.
Programmed death-ligand 1 (PD-L1) is involved in the inhibition of antigen specific T cells via ligation of programmed death 1 (PD-1). Here, the authors show checkpoint inhibition by use of small molecule inhibition of PD-L1 which in a humanised mouse model was shown to restore T cell responses and reduced tumour burden.
Journal Article
Cost modelling rehabilitation in the home for reconditioning in the Australian context
Background
Inpatient rehabilitation services are challenged by increasing demand. Where appropriate, a shift in service models towards more community-oriented approaches may improve efficiency. We aimed to estimate the hypothetical cost of delivering a consensus-based rehabilitation in the home (RITH) model as hospital substitution for patients requiring reconditioning following medical illness, surgery or treatment for cancer, compared to the cost of inpatient rehabilitation.
Methods
Data were drawn from the following sources: the results of a Delphi survey with health professionals working in the field of rehabilitation in Australia; publicly available data and reports; and the expert opinion of the project team. Delphi survey data were analysed descriptively. The costing model was developed using assumptions based on the sources described above and was restricted to the Australian National Subacute and Non-Acute Patient Classification (AN-SNAP) classes 4AR1 to 4AR4, which comprise around 73% of all reconditioning episodes in Australia. RITH cost modelling estimates were compared to the known cost of inpatient rehabilitation. Where weighted averages are provided, these were determined based on the modelled number of inpatient reconditioning episodes per annum that might be substitutable by RITH.
Results
The cost modelling estimated the weighted average cost of a RITH reconditioning episode (which mirrors an inpatient reconditioning episode in intensity and duration) for AN-SNAP classes 4AR1 to 4AR4, to be A$11,371, which is 28.1% less than the equivalent weighted average public inpatient cost (of A$15,820). This represents hypothetical savings of A$4,449 per RITH reconditioning substituted episode of care.
Conclusions
The hypothetical cost of a model of RITH which would provide patients with as comprehensive a rehabilitation service as received in inpatient rehabilitation, has been determined. Findings suggest potential cost savings to the public hospital sector. Future research should focus on trials which compare actual clinical and cost outcomes of RITH for patients in the reconditioning impairment category, to inpatient rehabilitation.
Journal Article