Welwyn Garden City Research Articles

A randomized, double-blind, negatively controlled pilot study to determine whether the use of emollients or calcipotriol alters the sensitivity of the skin to ultraviolet radiation during phototherapy with narrowband ultraviolet B

There is contradictory evidence suggesting that emollients increase, decrease or have no effect on minimal erythema dose (MED) or minimal phototoxic dose values prior to phototherapy. Few studies have looked at the in vivo use of emollients or calcipotriol prior to narrowband ultraviolet (UV) B (NB-UVB) treatment. To investigate whether emollients or calcipotriol alter MED readings of skin on the back of healthy subjects prior to NB-UVB irradiation. Topical agents were applied to the backs of 20 healthy volunteers for 30 min prior to MED testing. These agents were aqueous cream, 50:50 white soft paraffin and liquid paraffin, Diprobase(®) (Schering-Plough, Welwyn Garden City, U.K.), Epaderm(®) (Medlock, Oldham, U.K.) and calcipotriol ointment and cream. A control MED strip was used with no topical agent applied prior to testing. MED readings were recoded as integer steps between 1 and 9 (one is lowest MED dose for skin type; eight is highest; nine is no response, i.e. a higher MED). The median MED was between step 5 and 6 for all treatments and control. There was no significant difference at the 5% level between control and each topical agent. The study was powered to detect a median difference of approximately 0·4-0·6 steps. This has important implications at a practical level when advising patients not to apply creams prior to treatment with NB-UVB. Studies where agents are applied immediately prior to phototherapy have been more likely to show that emollients block transmission of UV radiation. If they are applied at least 30 min prior to treatment, they have no effect.

Plasticity in human motor cortex is in part genetically determined

Brain plasticity refers to changes in the organization of the brain as a result of different environmental stimuli. The aim of this study was to assess the genetic variation of brain plasticity, by comparing intrapair differences between monozygotic (MZ) and dizygotic (DZ) twins. Plasticity was examined by a paired associative stimulation (PAS) in 32 healthy female twins (9 MZ and 7 DZ pairs, aged 22.6±2.7 and 23.8±3.6 years, respectively). Stimulation consisted of low frequency repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with a single pulse transcranial magnetic stimulation (TMS) for activation of the abductor pollicis brevis muscle (APB). Corticospinal excitability was monitored for 30 min following the intervention. PAS induced an increase in the amplitudes of the motor evoked potentials (MEP) in the resting APB, compared to baseline. Intrapair differences, after baseline normalization, in the MEP amplitudes measured at 25-30 min post-intervention, were almost double for DZ (1.25) in comparison to MZ (0.64) twins (P =0.036). The heritability estimate for brain plasticity was found to be 0.68. This finding implicates that genetic factors may contribute significantly to interindividual variability in plasticity paradigms. Genetic factors may be important in adaptive brain reorganization involved in motor learning and rehabilitation from brain injury.

Focus on photonics and biomedical optics

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Recurrence of kyphosis and its functional implications after surgical stabilization of dorsolumbar unstable burst fractures

Background context Treatment of unstable burst fractures in the dorsolumbar spine still remains controversial. Surgical stabilization has been aimed to prevent long-term back pain and progression of deformity. Purpose This study was aimed to analyze the degree of loss of correction of the angle of kyphosis with pedicle screw instrumentation in place and the components responsible for the recurrence of kyphosis after surgical stabilization of dorsolumbar A3 fractures and to assess the return of functional capacity in these patients. Study design Retrospective study. Patient sample This study involves 26 patients who had dorsolumbar unstable burst fractures (Arbeitsgemeinschaft für Osteosynthesefragen type A3). Outcome measures Radiological assessment at injury, immediate postoperative period, and most recent follow-up along with functional assessment using short form 36 (SF-36) and return to work. Methods All the patients had posterior pedicle screw instrumentation without fusion for unstable dorsolumbar burst compression (A3) fractures. The mean follow-up period was 25.5 months. All of them had their fractures stabilized with Universal Spinal System (Synthes, Welwyn Garden City, UK) Fracture System. Serial standing lateral radiographs were taken from the immediate postoperative period to the most recent follow-up. The angle of kyphosis; the heights of the discs above and below the fractured vertebra; and the heights of the vertebral bodies above, at, and below the fractured level were measured. The height at each level was measured in three segments (anterior, middle, and posterior). The values were normalized to avoid discrepancies while comparing radiographs. The difference in the height of each segment measured between the immediate postoperative period and the most recent follow-up was computed. Results The mean angle of kyphosis was 6.3±8.9 in the immediate postoperative period and 15.7±6.7 at the most recent follow-up (p<.001). The mean patient function score from SF-36 was 52.3%, and the mean pain score was 44.9%. There was no relationship to the loss of correction angle of kyphosis to the patient function score (r=0.06, p=.76) and the pain score (r=0.11, p=.58). The correlation between the corresponding difference in the height of each segment and the degree of loss of correction of the angle of kyphosis showed positive correlation to the decrease in the anterior and middle segment heights at the fractured vertebral level. Conclusion There is a progressive loss of correction of the angle of kyphosis after posterior stabilization with instrumentation even without implant removal that mainly corresponds to the decrease in the anterior segment height of the fractured vertebral body.

Conference Scene - Nanotoxicology: Health and Environmental Impacts

The conference on Nanotoxicology: Health & Environmental Impacts was organized by Euroscicon (Welwyn Garden City, UK), a team of professionals working towards the continuous improvement of technical knowledge transfer for all scientists, and hosted by 'BioPark', a research and development center in Welwyn Garden City, UK, on the 27th February 2009. The 1-day conference was chaired by SH Doak, Senior Lecturer and Research Councils UK Academic Fellow in Nanomedicine at Swansea University (Wales, UK) and brought together eminent scientists from seven different countries to interact and discuss the latest developments in the rapidly proliferating field of nanotechnology.

Biosimilarity of HX575 (human recombinant epoetin alfa) and epoetin beta after multiple subcutaneous administration

To compare the steady-state pharmacokinetics and pharmacodynamics following multiple subcutaneous administration of a new erythropoiesis stimulating agent (HX575, Binocrit, Sandoz GmbH, Holzkirchen, Germany) with that of epoetin beta (NeoRecormon, Roche Ltd., Welwyn Garden City, UK). An open, randomized, parallel group study was conducted in 80 healthy adult males. Subjects were randomized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or epoetin beta three-times-weekly for 4 weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratios of hematological characteristics were used as surrogate parameters for efficacy evaluation. The pharmacokinetic profiles after multiple doses were similar for both treatments. HX575 was bioequivalent to epoetin beta with respect to the rate and extent of exposure of exogenous epoetin, as indicated by the ratios (90% confidence intervals) of AUC(tau) (96.1 (86.4 - 106.9)) and C(max,ss) (98.5 (85.2 - 113.9)). The hematological profiles of both treatments were similar as determined from the population mean curves and the AUEC(Hb) ratio (90% confidence interval] (99.2 (97.7 - 100.7)), the primary endpoint of this study. Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected at any time. HX575 and epoetin beta were bioequivalent with respect to their steady-state pharmacokinetic profile and pharmacodynamic action. These results support the conclusion that HX575 and epoetin beta will be equally efficacious and may be interchangeable as therapy.

Piggyback intraocular lens implant to correct severe refractive error after penetrating keratoplasty in pseudophakes

This letter describes two cases in which severe refractive error after penetrating keratoplasty (PK) in pseudophakes was corrected with piggyback intraocular lens (IOL) implantation. A 65-year-old woman had bilateral phacoemulsification...

Molecular Farming – Plant Biologicals, EuroSciCon (http://www.euroscicon.com). BioPark Hertfordshire, Welwyn Garden City, 29 January 2008

Molecular Farming – Plant Biologicals, EuroSciCon (http://www.euroscicon.com). BioPark Hertfordshire, Welwyn Garden City, 29 January 2008

Iodine Deficiency Induces a Thyroid Stimulating Hormone-Independent Early Phase of Microvascular Reshaping in the Thyroid

Expansion of the thyroid microvasculature is the earliest event during goiter formation, always occurring before thyrocyte proliferation; however, the precise mechanisms governing this physiological angiogenesis are not well understood. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry to measure gene expression and laser Doppler to measure blood flow in an animal model of goitrogenesis, we show that thyroid angiogenesis occurred into two successive phases. The first phase lasted a week and involved vascular activation; this process was thyroid-stimulating hormone (TSH)-independent and was directly triggered by expression of vascular endothelial growth factor (VEGF) by thyrocytes as soon as the intracellular iodine content decreased. This early reaction was followed by an increase in thyroid blood flow and endothelial cell proliferation, both of which were mediated by VEGF and inhibited by VEGF-blocking antibodies. The second, angiogenic, phase was TSH-dependent and was activated as TSH levels increased. This phase involved substantial up-regulation of the major proangiogenic factors VEGF-A, fibroblast growth factor-2, angiopoietin 1, and NG2 as well as their receptors Flk-1/VEGFR2, Flt-1/VEGFR1, and Tie-2. In conclusion, goiter-associated angiogenesis promotes thyroid adaptation to iodine deficiency. Specifically, as soon as the iodine supply is limited, thyrocytes produce proangiogenic signals that elicit early TSH-independent microvascular activation; if iodine deficiency persists, TSH plasma levels increase, triggering the second angiogenic phase that supports thyrocyte proliferation.

Galectin-3 Expression and Secretion Links Macrophages to the Promotion of Renal Fibrosis

Macrophages have been proposed as a key cell type in the pathogenesis of renal fibrosis; however, the mechanism by which macrophages drive fibrosis is still unclear. We show that expression of galectin-3, a beta-galactoside-binding lectin, is up-regulated in a mouse model of progressive renal fibrosis (unilateral ureteric obstruction, UUO), and absence of galectin-3 protects against renal myofibroblast accumulation/activation and fibrosis. Furthermore, specific depletion of macrophages using CD11b-DTR mice reduces fibrosis severity after UUO demonstrating that macrophages are key cells in the pathogenesis of renal fibrosis. Disruption of the galectin-3 gene does not affect macrophage recruitment after UUO, or macrophage proinflammatory cytokine profiles in response to interferon-gamma/lipopolysaccharide. In addition, absence of galectin-3 does not affect transforming growth factor-beta expression or Smad 2/3 phosphorylation in obstructed kidneys. Adoptive transfer of wild-type but not galectin-3(-/-) macrophages did, however, restore the fibrotic phenotype in galectin-3(-/-) mice. Cross-over experiments using wild-type and galectin-3(-/-) macrophage supernatants and renal fibroblasts confirmed that secretion of galectin-3 by macrophages is critical in the activation of renal fibroblasts to a profibrotic phenotype. Therefore, we demonstrate for the first time that galectin-3 expression and secretion by macrophages is a major mechanism linking macrophages to the promotion of renal fibrosis.

Peripheral retinal shape measurements, using the IOLMaster, in myopia and hyperopia

Purpose: When measuring peripheral retinal shape using the IOLMaster, measurements have been taken with the instrument in a fixed position and the subjects rotating their eye to measure peripherally. However, eye rotation could affect the peripheral ocular shape measures. The aim of this experiment is to determine the effect of eye rotation upon the measurement of peripheral retinal shape in myopic and hyperopic subjects using the IOLMaster.Methods: 20 subjects participated with informed consent in the experiment [10 myopes (MYO) and 10 hyperopes (HYP)]. All subjects were visually normal with visual acuity of 0.0 logMAR or better. The mean age of the subjects was 21.4 ± 2.2 years, and all were students in the University. Cycloplegia and mydriasis were induced using 1.0% cyclopentolate and the measurements were taken 30 min after instillation of the eyedrops. Peripheral retinal dimensions were measured with the IOLMaster (Carl Zeiss Ltd., Welwyn Garden City, UK) which measures axial length using partial coherence interferometry. 5 measures of axial length were taken at 10 degree intervals from 0–40 degree nasally and temporally using two different experimental paradigms. Experiment 1: Subjects rotated their eye to view an LED target array, attached to the front of the instrument. Experiment 2: Subjects maintained fixation upon a stationary target in the primary position while the IOL‐Master was rotated about the centre of rotation of the eye. The data was fitted with second order polynomials with separate curves being fitted to the temporal and nasal profiles to take into account any retinal asymmetry.Results: A significant difference (p &lt; 0.01) was found in the mean second order coefficients for the temporal and nasal retinal profiles in the MYO subjects, with the temporal retina having the lower coefficient. There was no significant difference between temporal and nasal second order coefficients in the HYP subjects. Eye rotation produced a significant shift in the second order coefficients for both temporal (p &lt; 0.01) and nasal (p &lt; 0.01) retinal profiles in the MYO group, with the coefficients becoming smaller with ocular rotation. No significant effect of eye rotation was found in the HYP group.Conclusions: Asymmetry between the temporal and nasal retinal profiles is more pronounced in the myopic eye. Ocular rotation has a substantial and measurable effect on the shape of the myopic eye, but no measurable effect is found in the hyperopic eye. These results are indicative of substantial structural differences between the eyes of subjects with myopia and hyperopia. When measuring peripheral retinal shape these factors should be taken into account.

Protein Kinase Cδ Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein

Mucin hypersecretion is a major pathological feature of many respiratory diseases, yet cellular mechanisms regulating secretion of mucin have not been fully elucidated. Previously, we reported that mucin hypersecretion induced by human neutrophil elastase involves activation of protein kinase C (PKC), specifically the delta-isoform (PKC delta). Here, we further investigated the role of PKC delta in mucin hypersecretion using both primary human bronchial epithelial cells and the human bronchial epithelial 1 cell line as in vitro model systems. Phorbol-12-myristate-13-acetate (PMA)-induced mucin hypersecretion was significantly attenuated by rottlerin, a PKC delta-selective inhibitor. Rottlerin also reduced PMA- or human neutrophil elastase-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) protein in these cells. Both secretion and MARCKS phosphorylation were significantly enhanced by the PKC delta activator bryostatin 1. A dominant-negative PKC delta construct (pEGFP-N1/PKC delta K376R) transfected into human bronchial epithelial 1 cells significantly attenuated both PMA-induced mucin secretion and phosphorylation of MARCKS, whereas transfection of a wild-type construct increased PKC delta and enhanced mucin secretion and MARCKS phosphorylation. Similar transfections of a dominant-negative or wild-type PKC epsilon construct did not affect either mucin secretion or MARCKS phosphorylation. The results suggest that PKC delta plays an important role in mucin secretion by airway epithelium via regulation of MARCKS phosphorylation.

Assaying Chemokines and Chemotaxis

The EuroSciCon [1] meeting on Assaying Chemokines and Chemotaxis took place on 8th June 2007, and was held at the Biopark, Welwyn Garden City, Hertfordshire, UK. The aim of this meeting was to disc...

Imperial City. Rome, Romans and Napoleon, 1796-1815 (review)

Reviewed by Tommaso Astarita Georgetown University Imperial City. Rome, Romans and Napoleon, 1796-1815. By Susan Vandiver Nicassio. (Welwyn Garden City, UK: Ravenhall Books, Linden Publishing Limited. 2005. Pp. 255. $34.95.) This book is evidently intended for a broad readership intrigued by the recreation of a picturesque and occasionally dramatic past. The author surveys the life of the inhabitants of Rome in the extraordinary decades when the Eternal City experienced traumatic events such as the short-lived Jacobin Republic of 1798, the restoration of papal government, the French hegemony in Italy, absorption into the French Empire in 1809, and the fall of Napoleon's reign in 1814-15. The book does not pretend to offer any particular analysis of these events; rather, they serve as the background for a skillful evocation of what life in Rome was like at that time. The look of the city, the character and social organization of its inhabitants, their daily and ordinary experiences, are recreated with the help of travelers' accounts, occasional vignettes of specific well-documented individuals, memoirs, and some visual sources. Though the striking developments of those years receive attention, the emphasis is on what the ordinary lives of ordinary Romans were like, and on how they survived the disruptions caused by the French. A first chapter recounts the overall historical narrative of these decades. Then follow chapters on the city and its appearance, the society and mores of the Romans, the "joys" and "sorrows" of their lives (from marriages and popular entertainments to violence and dirt), the features and feasts of the Catholic ritual year, and the economy, education, and work. Two late chapters more closely track the deteriorating relationship between French occupiers and resisting Romans, which mirrored the increasingly bitter fight between Napoleon and the papacy. A final chapter surveys the restoration of papal government and ends the book with an overview of the fate of Napoleon's family, many of whom ended up in Rome. The book is enjoyable to read, and its larger story and individual vignettes are often captivating. None of it adds up to much in the way of interpretation, although Professor Nicassio affects a tone of nostalgia for the happiness of old-regime life, which appears for instance in a constant—and eventually, to this reviewer, grating - sarcasm toward reform attempts: suffice it to say that the Jacobin Republic is almost always referred to as the "Ridiculous Republic," an epithet apparently used at the time, but obviously far from an unbiased one. Even when writing an engaging book for a general audience, a professional author ought to be more careful with her facts and editing. The book is quite simply riddled with errors and typos. There are many instances in which little facts or details are repeated, sometimes in the same few pages (e.g., pp. 45-46); many, many of the numerous terms and expressions in Italian, French, or Latin are misspelled; often the same foreign names or words appear with different spellings [End Page 977] even in the same two or three lines (e.g., in the "cast of characters," p. 10, where the name of one of Napoleon's brothers-in-law is also misspelled, or on pp. 99-100), or events are dated to different years (such as the death of Napoleon's mother, pp. 226 and 232); and the bibliography, which includes a useful introductory essay, is filled with misspelled names of authors and mistaken titles, including one of the classics on the topic, David Silvagni's La corte e la società romana (a single footnote on p. 160 includes five typos in Italian names and titles). The book has no full index (only proper names); a few quotes have no references, and many of the pretty illustrations are not identified or credited. Then, there are errors of fact: the dates of the Civil Constitution of the Clergy (p. 17) and of the Treaty of Amiens (p. 27) are off by one year...

The CB1 Cannabinoid Receptor Mediates Excitotoxicity-induced Neural Progenitor Proliferation and Neurogenesis

Endocannabinoids are lipid signaling mediators that exert an important neuromodulatory role and confer neuroprotection in several types of brain injury. Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and differentiation as an attempt of neuroregeneration after damage. Here we investigated the mechanism of hippocampal progenitor cell engagement upon excitotoxicity induced by kainic acid administration and the putative involvement of the CB1 cannabinoid receptor in this process. Adult NPs express kainate receptors that mediate proliferation and neurosphere generation in vitro via CB1 cannabinoid receptors. Similarly, in vivo studies showed that excitotoxicity-induced hippocampal NPs proliferation and neurogenesis are abrogated in CB1-deficient mice and in wild-type mice administered with the selective CB1 antagonist rimonabant (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide; SR141716). Kainate stimulation increased basic fibroblast growth factor (bFGF) expression in cultured NPs in a CB1-dependent manner as this response was prevented by rimonabant and mimicked by endocannabinoids. Likewise, in vivo analyses showed that increased hippocampal expression of bFGF, as well as of brain-derived neurotrophic factor and epidermal growth factor, occurs upon excitotoxicity and that CB1 receptor ablation prevents this induction. Moreover, excitotoxicity increased the number of CB1+ bFGF+ cells, and this up-regulation preceded NP proliferation. In summary, our results show the involvement of the CB1 cannabinoid receptor in NP proliferation and neurogenesis induced by excitotoxic injury and support a role for bFGF signaling in this process.

Bevacizumab as a Potent Inhibitor of Inflammatory Corneal Angiogenesis and Lymphangiogenesis

To analyze whether bevacizumab can inhibit inflammatory angiogenesis and lymphangiogenesis in the cornea. Bevacizumab (Avastin; Roche, Welwyn Garden City, UK) is a recombinant, humanized, monoclonal antibody against VEGF-A that has been approved by the U.S. Food and Drug Administration for the treatment of colon carcinomas. The mouse model of suture-induced corneal neovascularization was used to assess the antihemangiogenic and antilymphangiogenic effect of bevacizumab by systemic and topical application. Corneal flatmounts were stained with LYVE-1 as a specific lymphatic vascular endothelial marker and CD31 as a pan-endothelial marker, and blood and lymph vascularized areas were analyzed morphometrically. The inhibitory effect of bevacizumab on lymphatic endothelial cells (LECs) was analyzed with a colorimetric (BrdU) proliferation ELISA. The binding ability of bevacizumab to murine VEGF-A was analyzed by Western blot, ELISA, and surface plasmon resonance. The systemic and topical applications of bevacizumab significantly inhibited the outgrowth of blood (P < 0.006 and P < 0.0001, respectively) and lymphatic (P < 0.002 and P < 0.0001, respectively) vessels. Inhibition of the proliferation of LECs was also significant (P < 0.0001). Western blot analysis, ELISA, and the surface plasmon resonance assay showed that bevacizumab binds murine VEGF-A. Topical or systemic application of bevacizumab inhibits both inflammation-induced angiogenesis and lymphangiogenesis in the cornea. This finding suggests an important role of VEGF-A in corneal lymphangiogenesis. Bevacizumab may be useful in preventing immune rejections after penetrating keratoplasty or tumor metastasis via lymphatic vessels.

Eradication of Methicillin-Resistant Staphylococcus aureus (MRSA) and Clostridium difficile in Hospital Mops and Wiping Cloths by Ozone Cold Water Laundering in the United Kingdom – Comparison of Ozone and Standard Laundering Procedures

BACKGROUND/OBJECTIVES: Both MRSA and C. difficile are resistant to many cleaners, disinfectants and institutional laundering techniques. One route of continued transmission of these microorganisms is the laundering system for hospital/nursing facility linens and bed clothing. An evaluation of cold water (ambient temperature) ozone laundering was conducted at the Queen Elizabeth II Hospital in Welwyn Garden City, Herts., UK during 2005.

Optimizing Aerosol Gene Delivery and Expression in the Ovine Lung

We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

Failure of humeral fracture fixation plate in a young patient using the Philos system: Case report

A range of methods have been described for treating fractures of the proximal neck of the humerus. These have included both intramedullary and extracortical devices.4 Among the problems with plates applied to the lateral surface are irritation of overlying tissues and migration of the head fragment, when the screws may cut through the bone or move in the holes in the plate.3 To reduce the occurrence of these problems, a low-profile titanium alloy plate (Philos; Stratec, Welwyn Garden City, Hertfordshire, UK) has been marketed since 2001.

Pharmacologic Strategies for Treatment-resistant OCD: A Review of the Evidence

&lt;P&gt;Although most patients with obsessive-compulsive disorder (OCD) respond well to first-line treatment with serotonin reuptake inhibitors (SRIs), or to exposure and response prevention (ERP), for many the treatment response is not complete. Arguably, in about 30% of cases, residual symptoms remain in spite of prolonged treatment, although some have suggested a higher proportion. The clinical management of treatment-resistant OCD is an area that has not yet been thoroughly investigated, although there is much interest in the area, and studies indicating promising treatment strategies are starting to appear in the scientific literature.&lt;/P&gt; &lt;H4&gt;ABOUT THE AUTHORS&lt;/H4&gt; &lt;P&gt;Dr. Fineberg is consultant psychiatrist, Hertforshire Partnership NHS Trust, and visiting professor, University of Hertfordshire, Herts, England. Dr. Nigam is specialist registrar, West London Mental Health NHS Trust, London, England, and honorary research fellow, Hertforshire Partnership NHS Trust. Miss Sivakumaran is senior research fellow, Hertfordshire Partnership NHS Trust. &lt;/P&gt; &lt;P&gt;Address reprint requests to: Naomi A Fineberg, MA, MBBS, MRCPsych, Mental Health Unit, Queen Elizabeth II Hospital, Howlands, Welwyn Garden City, Hertfordshire AL7 4HQ; or e-mail &lt;a href="mailto:naomi.fineberg@btinternet.com"&gt;naomi.fineberg@btinternet.com&lt;/a&gt;.&lt;/P&gt; &lt;P&gt;Dr. Fineberg disclosed relevant financial relationships with Lundbeck, AstraZeneca, GlaxoSmithKline, and Bristol Myers Squibb. Dr. Nigam and Ms. Sivakumaran disclosed no relevant financial relationships.&lt;/P&gt;