Long cavity photonic crystal laser in FDML operation using an akinetic reflective filter.

A novel configuration of a Fourier domain mode locked (FDML) laser based on silicon photonics platform is presented in this work that exploits the narrowband reflection spectrum of a photonic crystal (PhC) cavity resonator. Configured as a linear Fabry-Perot laser, forward biasing of a p-n junction on the PhC cavity allowed for thermal tuning of the spectrum. The modulation frequency applied to the reflector equalled the inverse roundtrip time of the long cavity resulting in stable FDML operation over the swept wavelength range. An interferometric phase measurement measured the sweeping instantaneous frequency of the laser. The silicon photonics platform has potential for very compact implementation, and the electro-optic modulation method opens the possibility of modulation speeds far beyond those of mechanical filters.

Solid phase synthesis of peptides containing backbone-fluorinated amino acids.

Backbone-fluorinated amino acids exhibit unique conformational behaviour, and have potential utility as components of bioactive shape-controlled peptides. However, methods for the elaboration of backbone-fluorinated amino acids have thus far been limited to solution phase peptide coupling reactions. In this paper, protocols are developed that allow the successful manipulation of backbone-fluorinated amino acids using Fmoc-strategy solid phase peptide synthesis. To exemplify this strategy, several fluorinated RGD peptide analogues were synthesised in moderate to good overall yields.

High-Q asymmetrically cladded silicon nitride 1D photonic crystals cavities and hybrid external cavity lasers for sensing in air and liquids.

In this paper we show a novel design of high Q-factor silicon nitride (SiN) 1D photonic crystal (PhC) cavities side-coupled to curved waveguides, operating with both silica and air cladding. The engineering of the etched 1D PhC cavity sidewalls angle allows for high Q-factors over a wide range of upper cladding compositions, and the achievement of the highest calculated Q-factor for non-suspended asymmetric SiN PhC structures. We show the employment of these type of SiN PhC cavities in hybrid external cavity laser (HECL) configuration, with mode-hop free single mode laser operation over a broad range of injected currents (from 25 mA to 65 mA), milliwatts of power output (up to 9 mW) and side-mode suppression ratios in the range of 40 dB. We demonstrate the operation of these devices as compact and energy efficient optical sensors that respond to refractive index changes in the surrounding medium the measurement of sodium chloride (from 0% to 25%) and sucrose (from 0% to 25%) in aqueous solution. In HECL configuration, the RI sensor exhibits a 2 orders of magnitude improvement in detection limit compared to the passive microcavity. We also discuss the possibility for applying these devices as novel transducers for refractive index changes that are induced by analyte specific absorption of infrared radiation by the target analytes present in gas or liquid phase.

Long term outcome of thermal anterior capsulotomy for chronic, treatment refractory depression.

BACKGROUND: There is very limited evidence for the efficacy of any specific therapeutic intervention in chronic, treatment refractory major depression. Thermal anterior capsulotomy (ACAPS) is a rarely performed but established therapeutic procedure for this patient group. While benefit has been claimed, previous ACAPS reports have provided limited information. Detailed prospective reporting of therapeutic effects and side effects is required. OBJECTIVE: To report a prospective study of therapeutic effect, mental status, quality of life, social functioning and neurocognitive functioning in individuals with chronic treatment refractory major depression, treated with ACAPS. METHOD: A prospective case series of 20 patients treated with ACAPS between 1992 and 1999 were reassessed at a mean follow-up of 7.0±3.4 years. Data were collected preoperatively and at long term follow-up. Structural MRI was performed in 14 participants. RESULTS: According to a priori criteria, at long term follow-up, 50% were classified as 'responders' and 40% as 'remitters'. Fifty-five per cent were classified as 'improved'; 35% were 'unchanged'; and 10% had 'deteriorated'. Neurocognitive and personality testing were not significantly different at follow-up. A trend towards improvement in some aspects of executive neuropsychological functioning was observed. Significant adverse effects were infrequent and there were no deaths. CONCLUSIONS: ACAPS may represent an effective intervention for some patients with chronic, disabling, treatment refractory major depression that has failed to respond to other therapeutic approaches. The adverse effect burden within this population was modest, with no evidence of generalised impairment of neurocognitive functioning.

The identification of novel orally active mGluR5 antagonist GSK2210875.

The identification of novel orally active mGluR5 antagonist GSK2210875 is described.

Aryl sulphonyl amides as potent agonists of the growth hormone secretagogue (ghrelin) receptor.

As part of an on-going lead optimisation effort, a cross screening exercise identified an aryl sulphonyl amide hit that was optimised to afford a highly potent series of ghrelin receptor agonists.

Discovery of an Orally Bioavailable Pan αv Integrin Inhibitor for Idiopathic Pulmonary Fibrosis.

The heterodimeric transmembrane αv integrin receptors have recently emerged as potential targets for the treatment of idiopathic pulmonary fibrosis. Herein, we describe how subtle modifications of the central aromatic ring of a series of phenylbutyrate-based antagonists of the vitronectin receptors αvß3 and αvß5 significantly change the biological activities against αvß6 and αvß8. This resulted in the discovery of a pan αv antagonist (compound 39, 4-40 nM for the integrin receptors named above) possessing excellent oral pharmacokinetic properties in rats (with a clearance of 7.6 mL/(min kg) and a bioavailability of 97%).

Identification of small molecule agonists of the motilin receptor.

High-throughput screening resulted in the identification of a series of novel motilin receptor agonists with relatively low molecular weights. The series originated from an array of biphenyl derivatives designed to target 7-transmembrane (7-TM) receptors. Further investigation of the structure-activity relationship within the series resulted in the identification of compound (22) as a potent and selective agonist at the motilin receptor.

Potent achiral agonists of the growth hormone secretagogue (ghrelin) receptor. Part 2: Lead optimisation.

A series of small molecule orally bioavailable ghrelin receptor agonists have been identified through systematic optimisation of a high throughput screening hit.

Potent achiral agonists of the ghrelin (growth hormone secretagogue) receptor. Part I: Lead identification.

High throughput screening combined with efficient datamining and parallel synthesis led to the discovery of a novel series of indolines showing potent in vitro ghrelin receptor agonist activity and acceleration of gastric emptying in rats.

Utilizing a 'systems' approach to improve the management of waste from healthcare facilities: best practice case studies from England and Wales.

Changes in environmental legislation and standards governing healthcare waste, such as the Hazardous Waste Regulations are expected to have a significant impact on healthcare waste quantities and costs in England and Wales. This paper presents findings from two award winning case study organizations, the Cardiff and Vale NHS Trust and the Cornwall NHS Trust on 'systems' they have employed for minimizing waste. The results suggest the need for the development and implementation of a holistic range of systems in order to develop best practice, including waste minimization strategies, key performance indicators, and staff training and awareness. The implications for the sharing of best practice from the two case studies are also discussed.