Prospects for (non-SUSY) new physics with first LHC data

The ATLAS and CMS experiments will take first data soon. I consider here the prospects for new physics (excluding SUSY) with a few inverse fb of data. This means processes with signal cross sections of a few 100 fb or less, with clear and fairly simple signatures - precision comparison of data to Standard Model tails will take longer, needing more luminosity and very good understanding of detector calibrations, resolutions and trigger efficiencies. The approach I take here is signature rather than model based, but examples of models will be given.Comment: 4 pages, 1 figure. Contribution to 13th Annual Symposium of Particles, Strings and Cosmology (PASCOS 07), July 200

Out-of-pocket costs, primary care frequent attendance and sample selection : Estimates from a longitudinal cohort design

Acknowledgements: Thank you to the study participants, PATH Interviewers, Karen Maxwell and Trish Jacomb; and to the other PATH Chief Investigators: Kaarin Anstey, Helen Christensen, Anthony Jorm, Bryan Rodgers, Andrew Mackinnon, Simon Easteal and Nicolas Cherbuin. The PATH Through Life Study is funded by National Health and Medical Research Council Grants 973302, 179805 and 418039. Peter Butterworth is funded by ARC Future Fellowship FT13101444.Peer reviewedPostprin

Role of Nutrition in the Management of Hepatic Encephalopathy in End-Stage Liver Failure

Malnutrition is common in patients with end-stage liver failure and hepatic encephalopathy, and is considered a significant prognostic factor affecting quality of life, outcome, and survival. The liver plays a crucial role in the regulation of nutrition by trafficking the metabolism of nutrients, their distribution and appropriate use by the body. Nutritional consequences with the potential to cause nervous system dysfunction occur in liver failure, and many factors contribute to malnutrition in hepatic failure. Among them are inadequate dietary intake, malabsorption, increased protein losses, hypermetabolism, insulin resistance, gastrointestinal bleeding, ascites, inflammation/infection, and hyponatremia. Patients at risk of malnutrition are relatively difficult to identify since liver disease may interfere with biomarkers of malnutrition. The supplementation of the diet with amino acids, antioxidants, vitamins as well as probiotics in addition to meeting energy and protein requirements may improve nutritional status, liver function, and hepatic encephalopathy in patients with end-stage liver failure

Mild hypothermia prevents brain edema and attenuates up-regulation of the astrocytic benzodiazepine receptor in experimental acute liver failure

BACKGROUND/AIMS: Mild hypothermia has proven useful in the clinical management of patients with acute liver failure. Acute liver failure in experimental animals results in alterations in the expression of genes coding for astrocytic proteins including the "peripheral-type" (astrocytic) benzodiazepine receptor (PTBR), a mitochondrial complex associated with neurosteroid synthesis. To gain further insight into the mechanisms whereby hypothermia attenuates the neurological complications of acute liver failure, we investigated PTBR expression in the brains of hepatic devascularized rats under normothermic (37 degrees C) and hypothermic (35 degrees C) conditions. METHODS: PTBR mRNA was measured using semi-quantitative RT-PCR in cerebral cortical extracts and densities of PTBR sites were measured by quantitative receptor autoradiagraphy. Brain pregnenolone content was measured by radioimmunoassay. RESULTS: At coma stages of encephalopathy, animals with acute liver failure manifested a significant increase of PTBR mRNA levels. Brain pregnenolone content and [(3)H]PK 11195 binding site densities were concomitantly increased. Mild hypothermia prevented brain edema and significantly attenuated the increased receptor expression and pregnenolone content. CONCLUSIONS: These findings suggest that an attenuation of PTBR up-regulation resulting in the prevention of increased brain neurosteroid content represents one of the mechanisms by which mild hypothermia exerts its protective effects in ALF.CIH

Refining the definition of mandibular osteoradionecrosis in clinical trials: The cancer research UK HOPON trial (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis)

Introduction:Mandibular osteoradionecrosis (ORN) is a common and serious complication of head andneck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosisand classification of ORN have been inconsistently and imprecisely defined, even in clinical trials.Methods:A systematic review of diagnosis and classifications of ORN with specific focus on clinical trialsis presented. The most suitable classification was evaluated for consistency using blinded independentreview of outcome data (clinical photographs and radiographs) in the HOPON trial.Results:Of 16 ORN classifications found, only one (Notani) appeared suitable as an endpoint in clinicaltrials. Clinical records of 217 timepoints were analysed amongst 94 randomised patients in theHOPON trial. The only inconsistency in classification arose where minor bone spicules (MBS) were appar-ent, which occurred in 19% of patients. Some trial investigators judged MBS as clinically unimportant andnot reflecting ORN, others classified as ORN based on rigid definitions in common clinical use. When MBSwas added as a distinct category to the Notani classification this ambiguity was resolved and agreementbetween observers was achieved.Discussion:Most definitions and clinical classifications are based on retrospective case series and may beunsuitable for prospective interventional trials of ORN prevention or treatment. When ORN is used as aprimary or secondary outcome in prospective clinical trials, the use of Notani classification with the addi-tional category of MBS is recommended as it avoids subjectivity and enhances reliability and consistencyof reporting

Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle

The effects of chronic liver insufficiency resulting from end-to-side portacaval anastomosis (PCA) on glutamine synthetase (GS) activities, protein and gene expression were studied in brain, liver and skeletal muscle of male adult rats. Four weeks following PCA, activities of GS in cerebral cortex and cerebellum were reduced by 32\% and 37\% (p<0.05) respectively whereas GS activities in muscle were increased by 52\% (p<0.05). GS activities in liver were decreased by up to 90\% (p<0.01), a finding which undoubtedly reflects the loss of GS-rich perivenous hepatocytes following portal-systemic shunting. Immunoblotting techniques revealed no change in GS protein content of brain regions or muscle but a significant loss in liver of PCA rats. GS mRNA determined by semi-quantitative RT-PCR was also significantly decreased in the livers of PCA rats compared to sham-operated controls. These findings demonstrate that PCA results in a loss of GS gene expression in the liver and that brain does not show a compensatory induction of enzyme activity, rendering it particularly sensitive to increases in ammonia in chronic liver failure. The finding of a post-translational increase of GS in muscle following portacaval shunting suggests that, in chronic liver failure, muscle becomes the major organ responsible for the removal of excess blood-borne ammonia

Direct molecular and spectroscopic evidence for increased ammonia removal capacity of skeletal muscle in acute liver failure

BACKGROUND/AIMS: It has been proposed that, in acute liver failure, skeletal muscle adapts to become the principle organ responsible for removal of blood-borne ammonia by increasing glutamine synthesis, a reaction that is catalyzed by the cytosolic ATP-dependent enzyme glutamine synthetase. To address this issue, glutamine synthetase expression and activities were measured in skeletal muscle of rats with acute liver failure resulting from hepatic devascularization. METHODS: Glutamine synthetase protein and gene expression were investigated using immunoblotting and semi-quantitative RT-PCR analysis. Glutamine synthetase activity and glutamine de novo synthesis were measured using, respectively, a standard enzymatic assay and [13C]-nuclear magnetic resonance spectroscopy. RESULTS: Glutamine synthetase protein (but not gene) expression and enzyme activities were significantly up-regulated leading to increased de novo synthesis of glutamine and increased skeletal muscle capacity for ammonia removal in acute liver failure. In contrast to skeletal muscle, expression and activities of glutamine synthetase in the brain were significantly decreased. CONCLUSIONS: These findings demonstrate that skeletal muscle adapts, through a rapid induction of glutamine synthetase, to increase its capacity for removal of blood-borne ammonia in acute liver failure. Maintenance of muscle mass together with the development of agents with the capacity to stimulate muscle glutamine synthetase could provide effective ammonia-lowering strategies in this disorder

Increased expression of "peripheral-type" benzodiazepine receptors in human temporal lobe epilepsy: implications for PET imaging of hippocampal sclerosis

Increased binding sites for "peripheral-type" benzodiazepine receptor (PTBR) ligands have been described in a wide range of neurological disorders including both human and experimental epilepsy. This study was undertaken to assess PTBR expression in relation to the presence of hippocampal sclerosis in human temporal lobe epilepsy (TLE). For this purpose, hippocampal CA1 subfields were dissected from surgical samples from patients with therapy-refractive TLE with (n = 5) or without (n = 2) hippocampal sclerosis and from age-matched nonepileptic postmortem controls (n = 5). PTBR expression was assessed by immunohistochemistry and reverse-transcription polymerase chain reaction. Receptor sites were evaluated using an in vitro binding assay and the selective PTBR ligand [3H]PK11195. Epileptic patients with hippocampal sclerosis showed increases in PTBR binding sites, immunoreactivity, and mRNA expression compared to both nonsclerotic TLE patients and postmortem nonepileptic controls. Induction of PTBR expression and binding sites were directly correlated with the presence of hippocampal sclerosis and the accompanying reactive gliosis