Generation of ultrabright beams in high energy Nd:glass and KrF laser systems

The development of ultrabright lasers is progressing rapidly particularly in the direction of table-top-terawatt systems operating at high pulse repetition rate with relatively low pulse energy. The highest pulse energies and highest absolute powers are being generated by the adaptation of larger-scale high energy laser systems operating in single pulse mode. The maximum focused intensity from either type of laser is determined by the beam brightness B which can be expressed in units of Watts cm where P is the power, lambda the wavelength and S the Strehl ratio, quantifying the ratio of brightness in a beam with less than diffraction limited quality to that in a diffraction limited beam

Report on ISCTM consensus meeting on clinical assessment of response to treatment of cognitive impairment in schizophrenia

Funding for this manuscript was provided by the International Society for CNS Clinical Trials and Methodology.Dr Keefe currently or in the past 3 years has received investigator-initiated research funding support from the Department of Veteran's Affair, Feinstein Institute for Medical Research, GlaxoSmithKline, National Institute of Mental Health, Novartis, Psychogenics, Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. He currently or in the past 3 years has received honoraria, served as a consultant, or advisory board member for Abbvie, Akebia, Amgen, Asubio, AviNeuro/ChemRar, BiolineRx, Biogen Idec, Biomarin, Boehringer-Ingelheim, Eli Lilly, EnVivo/FORUM, GW Pharmaceuticals, Janssen, Lundbeck, Merck, Minerva Neurosciences, Inc., Mitsubishi, Novartis, NY State Office of Mental Health, Otsuka, Pfizer, Reviva, Roche, Sanofi/Aventis, Shire, Sunovion, Takeda, Targacept, and the University of Texas South West Medical Center. Dr Keefe receives royalties from the BACS testing battery, the MATRICS battery (BACS Symbol Coding), and the Virtual Reality Functional Capacity Assessment Tool. He is also a shareholder in NeuroCog Trials, Inc. and Sengenix. Dr Haig is a full-time employee of Abbvie. Dr Marder has received consulting fees from Abbvie, Genentech, Roche, Lundbeck, Pfizer, Otsuka, Takeda, and Boeringer Ingelheim. He has received research support from Amgen, Sunovion, and Synchroneuron. Dr Harvey has received consulting fees from Abbvie, Boehringer Ingelheim, Forest Labs, Forum Pharma, Genentech, Otsuka America, Roche Pharma, Sunovion Pharma, and Takeda Pharma during the past year. He also received contract research support from Genentech. Dr Dunayevich for the past 3 years has been a full-time employee and stockholder of Amgen. Dr Medalia in the past 3 years has received research funding support from Sunovion. Dr Medalia has also currently or in the past 3 years received honoraria or served as consultant for Dainippon Sumitomo Pharma Co., Ltd., Otsuka, and Takeda Pharmaceuticals U.S.A., Inc. Dr Davidson has received research grant support and/or travel support and/or speaker fees and/or consultancy fees from Lundbeck, Eli Lilly, Servier, Abbott, Minerva and holds stocks in CTR and BiolineRx. Dr Lombardo is a full-time employee of FORUM Pharmaceuticals. Dr Bowie reports receiving grant support from Pfizer. He has also been a consultant for Lundbeck, Otsuka, Abbvie, and Takeda. Dr Buchanan reports: Advisory Board: Abbvie, Amgen, EnVivo, Roche; Consultant: Abbvie, Amgen, Bristol Myers Squibb, EnVivo, Omeros; DSMB member: Pfizer. Dr Bugarski -Kirola is a full-time employee of Hoffmann-La Roche Ltd. Dr Carpenter in the past 2 years has been a consultant to Roche/Genetech. Dr Dago in the last 3 years has received honoraria from Lundbeck, Forest Pharmaceuticals, Otsuka, Pam Labs, and Astra Zeneca for lectures given in promotion of their psychotropic medications. Dr Durand in the past year has been a consultant and received honoraria from Teva Pharmaceuticals. Dr Gold receives royalty payments from the BACS. He also has served as a consultant for Amgen, Hoffman LaRoche, and Lundbeck. Dr Hooker has served as a consultant and is currently a Co-Investigator on an NIH SBIR grant with PositScience Corporation. Dr Loebel is an employee of Sunovion Pharmaceuticals. Dr McGurk reports receiving consulting fees from Abbvie and EnVivo Pharmaceuticals. Dr Pinkham in the past year has received consulting fees from Otsuka America Pharmaceutical, Inc.The following authors have declared that there are no conflicts of interest in relation to the subject of this study: Drs Csernansky, Frese, Goff, Kopelowic, Opler, and Stern. (International Society for CNS Clinical Trials and Methodology; Department of Veteran's Affair; Feinstein Institute for Medical Research; GlaxoSmithKline; National Institute of Mental Health; Novartis; Psychogenics; Research Foundation for Mental Hygiene, Inc.; Singapore National Medical Research Council; Abbvie; Genentech; Roche; Lundbeck; Pfizer; Otsuka; Takeda; Boeringer Ingelheim; Amgen; Sunovion; Synchroneuron; Boehringer Ingelheim; Forest Labs; Forum Pharma; Otsuka America; Roche Pharma; Sunovion Pharma; Takeda Pharma; Eli Lilly; Servier; Abbott; Minerva; BACS; EnVivo Pharmaceuticals; Otsuka America Pharmaceutical, Inc.)Published versio

Episodic fire, runoff and deposition at the Palaeocene-Eocene boundary

Qualitative and quantitative coal petrological analyses have been undertaken on the laminated lignite at the base of the Cobham Lignite Bed, from Scalers Hill, Kent, England. The maximum negative carbon isotope excursion, which marks the beginning of the Palaeocene–Eocene thermal maximum (PETM), occurs near the top of the laminated lignite. The lignite contains inertinite, a petrographic term used to describe charcoal. The laminated lignite has inertinite-rich and inertinite-poor layers indicative of episodic fires and post-fire erosion. Charcoal clasts are derived from living or recently senesced plants and are dominated by the leaf stalks of herbaceous ferns and wood fragments from flowering plants. The charcoal assemblage reflects a low-diversity flora, possibly adapted to disturbance by fire, derived from a source vegetation subjected to seasonal surface wildfires. The environmental conditions leading up to and across the onset of the PETM are, therefore, interpreted as incorporating a persistent fire regime with episodic wildfires followed by rainfall and runoff events. Abundant charcoal indicates near-modern oxygen levels whereas the absence of charred peat in this area calls into question previous suggestions that burning of Palaeocene peats might have contributed to the short-lived negative carbon isotope excursion at the Palaeocene–Eocene boundary

The glycosylation heterogeneity of recombinant human IFN-gamma

The cloning of the cDNA for human interferon-gamma (IFN-gamma) has resulted in its expression in Escherichia coli, baculovirus-infected insect cells, Chinese hamster ovary (CHO) cells, and the mammary gland of transgenic mice. Large quantities of highly purified recombinant IFN-gamma have been generated, aided by the use of highly specific neutralizing monoclonal antibodies, with a view to its production as a human therapeutic protein. The primary source of structural heterogeneity for IFN-gamma during its production in mammalian expression systems is glycosylation, which can profoundly affect the three-dimensional structure of a glycoprotein and its biological function. A number of analytical approaches have been developed recently to allow a detailed analysis of the carbohydrate structures associated with IFN-gamma, the principal advances being in the areas of capillary electrophoresis and mass spectrometry, The implementation of these high-resolution analytical tools to determine the glycosylation profile of IFN-gamma makes it one of the best characterized recombinant glycoproteins, Recombinant human IFN-gamma acts as a model secretory glycoprotein, typifying the intrinsic glycosylation processing events associated with production of a potential therapeutic glycoprotein

‘I am not someone who gets skin cancer’: Risk, time and malignant melanoma

‘Delay’ is a term used in the cancer literature since the 1930s to describe the period between self-detection of a concerning sign of possible disease and presentation to a health professional. This linguistic choice carries an implication of blame for apparent failure to manage a risk appropriately, drawing attention away from the contemporaneous perspectives of those who respond to suspicious indicators more or less quickly. We present findings from a grounded theory study of accounts given by 45 patients about their slower or quicker journeys to a diagnosis of cutaneous malignant melanoma, a cancer which can ‘hide in plain sight’. There has been little research exploring in qualitative detail patients’ perspectives on their decision-making about what subsequently turn out to have been signs of this most risky of skin cancers. The findings frame referral time-lapses in terms of normalisation of symptoms, sometimes buttressed by reassurance derived from health promotion messages, disconfirmation of patients’ concerns by their general practitioners and prioritisation of other life concerns. We argue that a shared sense of urgency surrounding melanoma self-referral derives from a clinical representation of current knowledge which conceals numerous evidential uncertainties