Improving access to psychological therapy: The Doncaster demonstration site organisational model

Reproduced with permission of the publisher

Response to commentaries on ‘Improving access to psychological therapy: the Doncaster demonstration site organisational model'

Reproduced with permission of the publisher

Blocked dihydropteridines as nitric oxide synthase activators

It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings

Methyl 2-amino-5-iso­propyl-1,3-thia­zole-4-carboxyl­ate

The title compound, C8H12N2O2S, forms a supramolecular network based on N-HN hydrogen-bonded centrosymmetric dimers that are linked in turn by N-HO contacts

Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur

Slow waves caused by cuts perpendicular to a single subwavelength slit in metal

Copyright © 2007 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. This is the published version of an article published in New Journal of Physics Vol. 9, article 1. DOI: 10.1088/1367-2630/9/1/001Resonant transmission of microwaves through a subwavelength slit in a thick metal plate, into which subwavelength cuts have been made, is explored. Two orientations of the cuts, parallel and perpendicular to the long axis of the slit, are examined. The results show that the slits act as though filled with a medium with anisotropic effective relative permeability which at low mode numbers has the two values ~(1, 9.1), increasing to ~(1, 14.4) for higher mode numbers

Remarkable Zeroth-Order Resonant Transmission of Microwaves through a Single Subwavelength Metal Slit

James R. Suckling, J. Roy Sambles, and Christopher R. Lawrence, Physical Review Letters, Vol. 95, article 187407 (2005). "Copyright © 2005 by the American Physical Society."A slit in a thick metal plate that is extremely subwavelength will not transmit microwaves polarized parallel to it. It is shown here that cuts perpendicular to the slit allow parallel polarized radiation to resonantly transmit. Furthermore, a zero-order mode may be excited within the slit, the frequency of which, to first order, is independent of the plate depth. Remarkably, for this novel type of resonance, the field in the slit oscillates with a constant phase and little amplitude variation throughout the plate depth, while the resonant wavelength tends to infinity as the slit width approaches zero

Resonant transmission of microwaves through a hexagonal array of holes in a thin metal layer

Copyright © 2007 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. This is the published version of an article published in New Journal of Physics Vol. 9, article 101. DOI: 10.1088/1367-2630/9/4/101Resonant transmission of microwaves through a hexagonal array of holes in a very thin aluminium layer is studied. The array of holes, with diameter much less than the incident wavelength, leads to a strong transmission peak at a frequency just lower than the diffraction limit of the array. The results are well-modelled using a finite element package. The effect of metal depth on transmission intensity and the maximum efficiency of the hole array is also explored. Further experimental data are presented for the transmission of microwaves as a function of angle of incidence. It is shown that strong transmission occurs at frequencies just lower than the diffraction edges of the array. Incidentally, it is also shown that less than 0.01% of normally incident microwave radiation is transmitted through a continuous metal layer of thickness only 40% of the skin depth

Improving access to psychological therapy: Initial evaluation of two UK demonstration sites

Copyright © 2009 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Behaviour Research and Therapy, 2009, Vol. 47, Issue 11, pp. 910 – 920 DOI: http://dx.doi.org/10.1016/j.brat.2009.07.010Recently the UK Government announced an unprecedented, large-scale initiative for Improving Access to Psychological Therapies (IAPT) for depression and anxiety disorders. Prior to this development, the Department of Health established two pilot projects that aimed to collect valuable information to inform the national roll-out. Doncaster and Newham received additional funds to rapidly increase the availability of CBT-related interventions and to deploy them in new clinical services, operating on stepped-care principles, when appropriate. This article reports an evaluation of the new services (termed ‘demonstration sites’) during their first thirteen months of operation. A session-by-session outcome monitoring system achieved unusually high levels of pre to post-treatment data completeness. Large numbers of patients were treated, with low-intensity interventions (such as guided self-help) being particularly helpful for achieving high throughput. Clinical outcomes were broadly in line with expectation. 55–56% of patients who had attended at least twice (including the assessment interview) were classified as recovered when they left the services and 5% had improved their employment status. Treatment gains were largely maintained at 10 month follow-up. Opening the services to self-referral appeared to facilitate access for some groups that tend to be underrepresented in general practice referrals. Outcomes were comparable for the different ethnic groups who access the services. Issues for the further development of IAPT are discussed

The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma