Publications by authors named "Paul Stanley"

49 Publications

Diagnostic accuracy of the interferon-gamma release assay (IGRA) for cases of feline mycobacteriosis.

Prev Vet Med 2021 Aug 8;193:105409. Epub 2021 Jun 8.

The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom.

The aim of this study was to evaluate the sensitivity and specificity of the interferon-gamma release assay (IGRA) for diagnosing infections with members of the Mycobacterium (M.) tuberculosis-complex (MTBC) and non-tuberculous mycobacteria (NTM) in domestic cats, and to generate defined feline-specific cut-off values using receiver operating characteristic (ROC) curve analysis to improve test performance. Records of 594 cats that had been tested by IGRA were explored to identify individuals that had a culture and/or polymerase chain reaction (PCR)-confirmed case of mycobacterial disease, and those that had a final diagnosis of non-mycobacterial disease. A total of 117 cats - 80 with mycobacterial disease and 37 diagnosed with a condition other than mycobacteriosis - were identified for further detailed analysis. This population was used to estimate test sensitivity and specificity, as well as likelihood ratios for the IGRA to correctly identify a cat with or without mycobacterial disease. Agreement between IGRA results and culture/PCR using current and proposed new cut-off values was also determined. ROC analysis of defined confirmed infected and non-mycobacterial disease control cats allowed an adjustment of current test cut-offs that increased the overall test sensitivity for MTBC infections from 83.1 % (95 % confidence interval [CI]: 71.5-90.5 %) to 90.2 % (95 % CI: 80.2-95.4%), and M. bovis infection from 43 % (95 % CI: 28.2-60.7%) to 68 % (95 % CI: 51.4-82.1%) while maintaining high test specificity (100 % in both cases). Overall agreement between IGRA results and culture/PCR, while recognising that neither culture nor PCR tests have perfect sensitivity, improved from weak (κ = 0.57) to moderate (κ = 0.71) using new proposed IGRA test cut-off values. Application of these results, based upon the statistical analysis of accumulated test data, can improve the diagnostic performance of the feline IGRA, particularly for identifying infections with M. bovis, without compromising specificity.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105409DOI Listing
August 2021

Serial Interferon-Gamma Release Assay (IGRA) Testing to Monitor Treatment Responses in Cases of Feline Mycobacteriosis.

Pathogens 2021 May 26;10(6). Epub 2021 May 26.

The Royal (Dick) School of Veterinary Studies and The Roslin Institute, Easter Bush Campus, University of Edinburgh, Midlothian EH25 9RG, UK.

The interferon-gamma release assay (IGRA) is used to diagnose cases of feline mycobacteriosis, but the use of serial testing to monitor treatment responses has not been evaluated in this species. From a population of cats that underwent IGRA testing for diagnostic investigation, individuals were identified with a pre- and end-of-treatment IGRA that passed control thresholds. The number of cats which reverted to negative at the end-of-treatment IGRA, changes in paired antigen-specific optical density (OD) values and differences in the pre-treatment antigen-specific OD values for those which underwent reversion were compared. Factors to explain reversion or recurrence of disease post-treatment were explored. Four of 18 cats (22%) reverted to negativity at the point of clinical resolution ( = 0.33), there was no difference in paired antigen-specific OD values ( ≥ 0.12), and cats that reverted did not have a lower baseline OD value ( = 0.63). No statistically significant factors were identified to predict reversion ( ≥ 0.08). Remaining positive at the end of treatment IGRA was not associated with recurrence of disease post-treatment ( = 0.34). Overall, these data suggest there is limited value in the use of the IGRA to monitor treatment responses in cats.
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http://dx.doi.org/10.3390/pathogens10060657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226617PMC
May 2021

Anatomical location of the primary tumour and its relationship to regional lymph node metastasis in cutaneous head and neck melanoma: Is selective neck dissection appropriate?

J Plast Reconstr Aesthet Surg 2021 01 28;74(1):223-243. Epub 2020 Sep 28.

Royal Victoria Infirmary, Queen Victoria Rd, Newcastle upon Tyne NE1 4LP, United Kingdom.

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http://dx.doi.org/10.1016/j.bjps.2020.08.115DOI Listing
January 2021

Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site.

Sci Rep 2018 Jul 13;8(1):10617. Epub 2018 Jul 13.

La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.
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http://dx.doi.org/10.1038/s41598-018-28880-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045569PMC
July 2018

Evaluation of buccal swabs for pharmacogenetics.

BMC Res Notes 2018 Jun 14;11(1):382. Epub 2018 Jun 14.

GenXys Health Care Systems Inc., Vancouver, BC, Canada.

Objective: A simple, non-invasive sample collection method is key for the integration of pharmacogenetics into clinical practice. The aim of this study was to gain samples for pharmacogenetic testing and evaluate the variation between dry-flocked and sponge-tipped buccal swabs in yield and quality of DNA isolated.

Results: Thirty-one participants collected samples using dry-flocked swabs and sponge-tipped swabs. Samples were assessed for DNA yield, quality and genotyping performance on a qPCR OpenArray platform of 28 pharmacogenetic SNPs and a CYP2D6 TaqMan copy number variant. DNA from sponge-tipped swabs had a significantly greater yield compared to DNA collected with dry-flocked swabs (p = 4.4 × 10). Moreover, highest genotyping call rates across all assays and highest CNV confidence scores were observed in DNA samples collected from sponge-tipped swabs (97% vs. 54% dry-flocked swabs; 0.99 vs. 0.88 dry-flocked swabs, respectively). Sample collection using sponge-tipped swabs provides a DNA source of sufficient quantity and quality for pharmacogenetic variant detection using qPCR.
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http://dx.doi.org/10.1186/s13104-018-3476-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000964PMC
June 2018

Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guérin (BCG) Vaccine Confers Protection against Tuberculosis.

PLoS One 2017 25;12(1):e0168851. Epub 2017 Jan 25.

School of Veterinary Medicine, University College Dublin (UCD), Dublin, Ireland.

A field trial was conducted to investigate the impact of oral vaccination of free-living badgers against natural-transmitted Mycobacterium bovis infection. For a period of three years badgers were captured over seven sweeps in three zones and assigned for oral vaccination with a lipid-encapsulated BCG vaccine (Liporale-BCG) or with placebo. Badgers enrolled in Zone A were administered placebo while all badgers enrolled in Zone C were vaccinated with BCG. Badgers enrolled in the middle area, Zone B, were randomly assigned 50:50 for treatment with vaccine or placebo. Treatment in each zone remained blinded until the end of the study period. The outcome of interest was incident cases of tuberculosis measured as time to seroconversion events using the BrockTB Stat-Pak lateral flow serology test, supplemented with post-mortem examination. Among the vaccinated badgers that seroconverted, the median time to seroconversion (413 days) was significantly longer (p = 0.04) when compared with non-vaccinated animals (230 days). Survival analysis (modelling time to seroconversion) revealed that there was a significant difference in the rate of seroconversion between vaccinated and non-vaccinated badgers in Zones A and C throughout the trial period (p = 0.015). For badgers enrolled during sweeps 1-2 the Vaccine Efficacy (VE) determined from hazard rate ratios was 36% (95% CI: -62%- 75%). For badgers enrolled in these zones during sweeps 3-6, the VE was 84% (95% CI: 29%- 97%). This indicated that VE increased with the level of vaccine coverage. Post-mortem examination of badgers at the end of the trial also revealed a significant difference in the proportion of animals presenting with M. bovis culture confirmed lesions in vaccinated Zone C (9%) compared with non-vaccinated Zone A (26%). These results demonstrate that oral BCG vaccination confers protection to badgers and could be used to reduce incident rates in tuberculosis-infected populations of badgers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168851PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266210PMC
August 2017

Introducing pharmacogenetic testing with clinical decision support into primary care: a feasibility study.

CMAJ Open 2016 Jul-Sep;4(3):E528-E534. Epub 2016 Sep 21.

Department of Family Practice (M. Dawes); GenXys Health Care Systems (M. Dawes, Aloise, Ang, Cullis, D. Dawes, Fraser, Liknaitzky, Stanley, Suarez-Gonzalez, Katzov-Eckert); Personalized Medicine Initiative (Cullis, Fraser); Department of Physical Therapy (D. Dawes); Faculty of Pharmaceutical Sciences (Paterson); Clinicare Pharmacists Inc. (Paterson); Department of Botany (Suarez-Gonzalez); Department of Biochemistry and Molecular Biology (Cullis), University of British Columbia, Vancouver, BC.

Background: Inappropriate prescribing increases patient illness and death owing to adverse drug events. The inclusion of genetic information into primary care medication practices is one solution. Our aim was to assess the ability to obtain and genotype saliva samples and to determine the levels of use of a decision support tool that creates medication options adjusted for patient characteristics, drug-drug interactions and pharmacogenetics.

Methods: We conducted a cohort study in 6 primary care settings (5 family practices and 1 pharmacy), enrolling 191 adults with at least 1 of 10 common diseases. Saliva samples were obtained in the physician's office or pharmacy and sent to our laboratory, where DNA was extracted and genotyped and reports were generated. The reports were sent directly to the family physician/pharmacist and linked to an evidence-based prescribing decision support system. The primary outcome was ability to obtain and genotype samples. The secondary outcomes were yield and purity of DNA samples, ability to link results to decision support software and use of the decision support software.

Results: Genotyping resulted in linking of 189 patients (99%) with pharmacogenetic reports to the decision support program. A total of 96.8% of samples had at least 1 actionable genotype for medications included in the decision support system. The medication support system was used by the physicians and pharmacists 236 times over 3 months.

Interpretation: Physicians and pharmacists can collect saliva samples of sufficient quantity and quality for DNA extraction, purification and genotyping. A clinical decision support system with integrated data from pharmacogenetic tests may enable personalized prescribing within primary care. ClinicalTrials.gov, NCT02383290.
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http://dx.doi.org/10.9778/cmajo.20150070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047800PMC
September 2016

Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity.

Org Biomol Chem 2016 Aug 22;14(31):7585-93. Epub 2016 Jul 22.

School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues.
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http://dx.doi.org/10.1039/c6ob01160hDOI Listing
August 2016

Biomimetic Approaches Towards The Synthesis of Complex Dimeric Natural Products.

Curr Pharm Des 2016 ;22(12):1628-57

School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

We present a selection of elegant and diverse biomimetic syntheses of complex natural product dimers. The dimerisation pathways discussed encompass the most prevalent strategies, including: Diels-Alder, Aldol, Mannich, conjugate addition, oxidative, radical and photochemical approaches; each underpinned through rational biosynthetic speculation.
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http://dx.doi.org/10.2174/1381612822666160101123106DOI Listing
December 2016

Merkel cell carcinoma in East Yorkshire: A case series and literature review of current management.

J Plast Reconstr Aesthet Surg 2015 May 6;68(5):667-72. Epub 2015 Jan 6.

Department of Plastic Surgery, Castle Hill Hospital, Hull, United Kingdom.

Introduction: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumour of the skin. The incidence is rising and it is associated with sun exposure and immunosuppression. Our aim was to perform a 10-year retrospective review of MCC treated in East Yorkshire and to examine disease progression, surgical and adjuvant management, and outcomes.

Methods: A 10-year retrospective review was undertaken of patients identified through the histopathology database. Case notes and digital patient records were examined for patient demographics, disease characteristics, management and outcome. Disease stage was calculated using the 2010 AJCC TNM classification.

Results: Thirty-seven patients with complete records were included. Twenty-one patients were male and 16 female, with mean age 76.7 years at presentation. Pre-malignant or malignant skin changes were documented in 15 patients, and immunosuppression in 15 patients. Mean duration of lesion was 17.5 weeks. Following diagnosis 22/37 patients underwent further surgery with 11 patients undergoing sentinel lymph node (LN) biopsy. LN disease was palpable at presentation in 8 patients. Three year survival is 40%.

Conclusions: There is no standardised management of MCC and randomised trials are challenging due to relatively small numbers. There has been little progress made in terms of improving survival. Development of a national database for patients with this condition would allow prospective data collection and more accurate assessment of current treatment protocols and their efficacy.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.bjps.2014.12.021DOI Listing
May 2015

Soft tissue sarcoma - A review of presentation, management and outcomes in 110 patients.

Surgeon 2016 Jun 30;14(3):129-35. Epub 2014 Sep 30.

Department of Plastic and Reconstructive Surgery, Castle Hill Hospital, Cottingham, Hull, UK.

Unlabelled: Soft tissue sarcomas are a rare group of mesenchymal tumours the treatment of which poses oncological and reconstructive challenges. Limb-salvage surgery aims to balance adequate excision margins for disease control and preservation of important structures to retain function. Reported here is the review of the Hull Plastic surgery sarcoma service over a twelve year period.

Method: We performed a review of the Hull sarcoma database over a twelve year period between 1997 and 2009. Demographic data, tumour grade, operative details complications and outcomes were recorded.

Results: The database contained a total of 435 patients with a diagnosis of sarcoma. 110 were treated at the Plastic Surgery department over a period of 12 years between 1997 and 2009. The patients treated in our department consisted of 67 males and 43 females (median age 70 years). The most common histological type was leiomyosarcoma (n = 23). Distribution of anatomical sites affected were head and neck (n = 15), upper limb (n = 17), lower limb (n = 56), trunk (n = 22). Large tumours (greater than 8 cm) n = 30, deep tumours n = 48, and high grade (Trojani 3) n = 33. Patients were treated with surgical excision and postoperative radiotherapy in the high grade groups (2 and 3). A range of reconstructive procedures were required from skin grafting, functional muscle transfer and free flap reconstruction. Nine patients developed regional recurrence, six patients had grade 3 tumours. Three were not resectable. Fourteen patients developed distant metastases, seven had grade 3 tumours, six underwent chemotherapy, two were treated palliatively. There were twenty deaths in this group, of which sixteen were sarcoma related. Deaths in the high risk groups was seven (high grade), nine (deep tumours) and eight (tumour size >8 cm). There were six survivors from eleven in the group with all three of these risk factors.

Conclusion: This study summarises the management of sarcoma form one unit over a twelve year period and lends further evidence to the fact that the principles of limb-salvage surgery are applicable to a wide range of tumour-types and grades, to all patient age groups and anatomical sites with good functional results and that local and free flap reconstruction provides wound cover robust enough to withstand courses of radiotherapy. Early recurrence of high-grade disease and the development of metastasis carry a worse prognosis, especially if adjuvant therapy cannot be given.

Level Of Evidence: 4.
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http://dx.doi.org/10.1016/j.surge.2014.06.002DOI Listing
June 2016

Trends of melanoma presentation in Hull and East Yorkshire: 25 years of data (1988-2012).

J Plast Reconstr Aesthet Surg 2014 Oct 28;67(10):1445-6. Epub 2014 May 28.

Department of Histopathology, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, NHS Hull and East Yorkshire Trust, UK.

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http://dx.doi.org/10.1016/j.bjps.2014.05.034DOI Listing
October 2014

Leishmania donovani eukaryotic initiation factor 5A: molecular characterization, localization and homology modelling studies.

Microb Pathog 2014 Aug 6;73:37-46. Epub 2014 Jun 6.

Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar Mohali 160062, Punjab, India.

Eukaryotic translation initiation factor 5A (eIF5A) is a small acidic protein highly conserved from archaea to mammals. eIF5A is the only protein which undergoes a unique lysine residue modification to hypusine. Hypusinylation is important for the function of eIF5A which is reported to be essential for cell viability. eIF5A promotes formation of the first peptide bond at the onset of protein synthesis. However, its function in Leishmania donovani is unclear. The present study focuses on the characterization and localization of L. donovani eIF5A protein. The eIF5A gene contains an ORF of 501×bp encoding 166 amino acid residues with a predicted molecular mass and isoelectric point of 17.8 kDa and 4.83 respectively. A phylogenetic tree analysis revealed its close proximity to trypanosomes however it is distantly located from Trichomonas vaginalis and Plasmodium falciparum. The L. donovani eIF5A was expressed as a 6× His tagged protein whose identity was confirmed by western blot and MALDI. Biophysical investigation by CD revealed the predominant presence of 49% β sheet structure which correlated well with secondary structure prediction. To gain insight into the role of eIF5A in L. donovani, we investigated the subcellular distribution of eIF5A. A GFP-fusion of L. donovani eIF5A was found to be localized in cytoplasm as confirmed by subcellular fractionation. Our studies indicated that eIF5A is primarily localized to cytoplasm and is undetectable in nuclear fraction. The homology model of eIF5A of L. donovani was built and the resulting model showed acceptable Ramachandran statistics. The model is reliable and can be used to study eIF5A binding with its effector molecules.
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http://dx.doi.org/10.1016/j.micpath.2014.05.005DOI Listing
August 2014

Risk factors for complications following breast reduction: results from a randomized control trial.

Breast J 2014 May-Jun;20(3):274-8

General Surgery, London Deanery, London, UK.

Reduction mammoplasty has been shown to benefit physical, physiological, and psycho-social health. However, there are some recognized complications. It would be beneficial if one could identify and modify the factors which increase the rate of complications. To determine the effects of resection weight, BMI, age, and smoking on complication rates following reduction mammoplasty. Data were gathered as a part of randomized control trial (RCT) examining psycho-social & QOL benefits of reduction mammoplasty. Sixty-seven consecutive female patients referred to either the Hull Breast Unit or Hull Plastic and Reconstructive Surgery Unit and underwent Inferior pedicle reduction mammoplasty were recruited. Complications were recorded prospectively. Data gathered included resection weight, BMI, age, and smoking status. Smoking status was categorized into current; ex; and never. Prospective records of all complications were noted. SPSS was used for purposes of statistical analysis. Of the 67 patients, 16 (23.9%) had complications. Higher resection weight, increased BMI, and older age are associated with high rate of complications with significance reaching p-values of p < 0.001, p = 0.034, and p = 0.004, respectively. Among the 67 women who had surgery, nine (13.4%) were current smokers, 20 (29.9%) were ex-smokers, and 38 (56.7%) never smoked. The incidence of complications was highest among current smokers and lowest among those who had never smoked. When comparing the current smokers with those who are not currently smoking, there is a 37% difference in the occurrence of complication. The chi-squared test shows that this is a significant difference (p < 0.01) at the 99% confidence interval. Higher resection weight, increased BMI, older age, and smoking are risk factors for complications. Patients should be adequately counseled about losing weight and stopping smoking.
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http://dx.doi.org/10.1111/tbj.12256DOI Listing
May 2015

A man with a mass in the thigh.

BMJ 2014 Apr 10;348:g2483. Epub 2014 Apr 10.

Hull-York Medical School, Hull HU6 7RX, UK.

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http://dx.doi.org/10.1136/bmj.g2483DOI Listing
April 2014

Microvesicle-mediated release of soluble LH/hCG receptor (LHCGR) from transfected cells and placenta explants.

Reprod Biol Endocrinol 2011 May 15;9:64. Epub 2011 May 15.

Department of Clinical Biochemistry, Laboratory Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK.

Placental hCG and pitutary LH transduce signals in target tissues through a common receptor (LHCGR). We demonstrate that recombinant LHCGR proteins which include the hormone-binding domain are secreted from transfected cells and that natural LHCGR is also secreted from human placental explants. LHCGR recombinant proteins representing varying lengths of the N-terminal extracellular domain were expressed in Chinese Hamster Ovary cells in suspension culture. Secretion was minimal up to 72h but by 96h 24-37% of the LHCGR had been released into the culture medium. The secreted proteins were folded and sensitive to glycosidases suggesting N-linked glycosylation. Secretion was independent of recombinant size and was mediated via structurally defined membrane vesicles (50-150nm). Similarly cultured human early pregnancy placental explants also released LHCGR via microvesicles. These studies provide the first experimental evidence of the possible mechanistic basis of the secretion of LHCGR.
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http://dx.doi.org/10.1186/1477-7827-9-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112408PMC
May 2011

Sex differences in smoking cessation outcomes of a tailored program for individuals with substance use disorders and mental illness.

Addict Behav 2011 May 13;36(5):523-6. Epub 2011 Jan 13.

British Columbia Centre of Excellence for Women's Health, E311-4500 Oak Street, Vancouver, BC, Canada.

Tobacco use is highly prevalent among individuals with a history of substance use disorders (SUD) and/or mental illness (MI). Despite evidence of differences in smoking cessation (SC) outcomes between women and men, few studies have formally evaluated sex differences among SUD and/or MI populations. For 258 participants (62% male, mean age=48.6 years) with an SUD and/or MI enrolled in a tobacco dependence clinic (TDC) program, we examined SC outcomes and compared men's and women's predictors of end-of-treatment abstinence. Individuals with an MI, social support for quitting, and a greater number of visits to the TDC program were more likely to be female; whereas males were characterized by having an SUD, older age, smoking a greater number of cigarettes per day, and having higher confidence in quitting smoking. In the intent-to-treat analysis, end-of-treatment smoking cessation was 32.2% (females=35.4% vs males=30.2, χ(2)=0.74, df=1, p=.390). Among females, baseline expired carbon monoxide (CO) level and a greater number of visits to the program were significantly predictive of SC; among males, having a history of alcohol, heroin and other opioids, and marijuana use were predictive of unsuccessful SC, whereas baseline expired CO level and a greater number of visits to the program were predictive of SC. These factors may be important in the design of enhanced tailored treatments and development of future SC programs for individuals with SUD and MI.
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http://dx.doi.org/10.1016/j.addbeh.2010.12.029DOI Listing
May 2011

Application of NMR-based metabolomics to the investigation of salt stress in maize (Zea mays).

Phytochem Anal 2011 May-Jun;22(3):214-24. Epub 2010 Dec 29.

Computational Toxicology, Safety Assessment, AstraZeneca R&D Mölndal, SE-43183 Mölndal, Sweden.

Introduction: High salinity, caused by either natural (e.g. climatic changes) or anthropic factors (e.g. agriculture), is a widespread environmental stressor that can affect development and growth of salt-sensitive plants, leading to water deficit, the inhibition of intake of essential ions and metabolic disorders.

Objective: The application of an NMR-based metabolic profiling approach to the investigation of saline-induced stress in Maize plants is presented.

Methodology: Zea Maize seedlings were grown in either 0, 50 or 150 mM saline solution. Plants were harvested after 2, 4 and 6 days (n = 5 per class and time point) and (1) H NMR spectroscopy was performed separately on shoot and root extracts. Spectral data were analysed and interpreted using multivariate statistical analyses.

Results: A distinct effect of time/growth was observed for the control group with relatively higher concentrations of acetoacetate at day 2 and increased levels of alanine at days 4 and 6 in root extracts, whereas concentration of alanine was positively correlated with the shoot extracts harvested at day 2 and trans-aconitic acid increased at days 4 and 6. A clear dose-dependent effect, superimposed on the growth effect, was observed for saline treated shoot and root extracts. This was correlated with increased levels of alanine, glutamate, asparagine, glycine-betaine and sucrose and decreased levels of malic acid, trans-aconitic acid and glucose in shoots. Correlation with salt-load shown in roots included elevated levels of alanine, γ-amino-N-butyric acid, malic acid, succinate and sucrose and depleted levels of acetoacetate and glucose.

Conclusions: The metabolic effect of high salinity was predominantly consistent with osmotic stress as reported for other plant species and was found to be stronger in the shoots than the roots. Using multivariate data analysis it is possible to investigate the effects of more than one environmental stressor simultaneously.
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http://dx.doi.org/10.1002/pca.1268DOI Listing
August 2012

Sorafenib enhances the in vitro anti-endothelial effects of low dose (metronomic) chemotherapy.

Oncol Rep 2010 Oct;24(4):1049-58

Cancer Biology Proteomics Group, Postgraduate Medical Institute, University of Hull, Hull, UK.

Angiogenesis inhibitors may enhance the effects of low dose (metronomic) chemotherapy. However, there is a wide range of novel angiogenesis inhibitors which must be tested in combinations with oral chemotherapy agents to assess the anti-endothelial and anti-cancer effects. This preliminary testing is most suited to high throughput in vitro models, rather than clinical trials. We aimed to establish an in vitro model and test the anti-endothelial and anti-cancer effects of the multi-kinase inhibitor sorafenib when used as a single agent and in combination with oral chemotherapy agents used at low concentrations. Micro-vascular endothelial cells and 3 cancer cell lines were utilised and an extended treatment strategy (96 h) was employed in order to mimic a continuous low dose anti-angiogenic chemotherapy regimen. Sorafenib significantly enhanced the anti-endothelial effect of low dose etoposide, paclitaxel and temozolomide. Sorafenib also significantly enhanced the anti-cancer effect of low dose etoposide, paclitaxel and temozolomide in SK-MEL-2 melanoma cells, producing an additive effect on inhibition of cell growth in all cases. These combinations appear to be the most promising for in vivo pre-clinical studies, with a view to testing in melanoma patients as a continuous dosing strategy, due to the in vitro additive inhibitory effect on growth seen in both endothelial and cancer cells.
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http://dx.doi.org/10.3892/or.2010.1049DOI Listing
October 2010

The 'Butter Test' to guide effective tissue cleansing after high-pressure injection injury.

J Plast Reconstr Aesthet Surg 2010 Nov 4;63(11):e792-5. Epub 2010 Aug 4.

Castle Hill Hospital, Cottingham, UK.

A case of high-pressure fingertip injury with an unknown paint primer injectate, and the use of a simple test to determine whether it is water- or solvent-based in order to guide subsequent optimal debridement, is presented. The favourable outcome achieved was felt to have resulted, in part, from the effective single debridement thus achieved.
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http://dx.doi.org/10.1016/j.bjps.2010.07.005DOI Listing
November 2010

Radiography before lymphoscintigraphy to prevent artefact.

J Plast Reconstr Aesthet Surg 2010 Dec 28;63(12):2207. Epub 2010 Apr 28.

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http://dx.doi.org/10.1016/j.bjps.2010.03.057DOI Listing
December 2010

Quick reference dictionary for occupational therapy, 5th edition (2009).

Authors:
Stanley Paul

Occup Ther Health Care 2010 Apr;24(2):188-9

School of Allied Health Sciences Department of Occupational Therapy Medical College of Georgia Augusta, GA 30912-0700

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http://dx.doi.org/10.3109/07380570903344940DOI Listing
April 2010

Histologic and elemental microanalytical study of anorganic bovine bone substitution following sinus floor augmentation in humans.

J Periodontol 2008 Jul;79(7):1232-40

Dental School, University of Chieti-Pescara, Chieti, Italy.

Background: Histologic data regarding the use of anorganic bovine bone (ABB) in humans are scarce. This study was a histologic evaluation and an examination of the elemental composition of ABB particles and adjacent bone in humans.

Methods: Ten biopsies were retrieved 20 months after maxillary sinus augmentation in five patients. The investigation was carried out using light microscopy in brightfield, fluorescence, and circularly polarized light and scanning electron microscopy (SEM) with energy-dispersive x-ray spectroscopy.

Results: The regenerated tissue consisted of 38% +/- 2.1% newly formed bone, 36% +/- 1.3% marrow spaces, and 29% +/- 1.8% residual ABB particles. Under polarized light, the newly formed bone was characterized by randomly oriented collagen fibers. Under fluorescence, the biomaterial showed close apposition to bone; under SEM, several projections of newly formed bone were seen penetrating the ABB particles. ABB and bone were distinguished by the lighter gray color of the biomaterial in back-scattered electron images; ABB particles were surrounded and linked by newly formed bone. Elemental analysis gave average calcium/phosphorus ratios (atomic %) approximately 1.9 for ABB and 1.4 for bone. Relatively high concentrations of calcium and phosphorus in the biomaterial decreased gradually toward the interface with bone.

Conclusion: The persistence of ABB in the human tissue after 20 months might have been related to the relatively high calcium content of the biomaterial as well as the absence of proteins.
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http://dx.doi.org/10.1902/jop.2008.070504DOI Listing
July 2008

Preventing or accelerating emergency care for children with complex healthcare needs.

Arch Dis Child 2008 Jan;93(1):17-22

Emergency Department, Royal Children's Hospital, Melbourne, Victoria, Australia.

Objective: A subgroup of children with special health care needs (CSHCN) have chronic and complex medical conditions and frequently attend the emergency department (ED). Some of these ED visits could be prevented through appropriate clinician advice or, if an ED visit is unavoidable, the management time could be decreased. We set out to determine whether an ED-based advice and coordination programme was feasible and could prevent or accelerate ED care for these patients. METHODS, SETTING AND PATIENTS: We identified CSHCN who frequently attended the ED at a large tertiary children's hospital. These patients were enrolled in an ED-based coordination programme, the Accelerated Care through Emergency (ACE) programme providing 24-hour mobile-phone access to experienced ED nurses. We prospectively tracked usage patterns and determined the rate of ED visits after receiving phone advice and the waiting time for patients to be seen in ED. Parental satisfaction and cost of the programme were also assessed.

Results: After a pilot phase in 2002, enrollment in the programme increased from 125 in 2003 to 220 patients in 2006. Patients had a broad range of medical conditions. All had two or more and up to 22 medical services involved in their care. 80% of patients used a technical device or implant. Phone calls increased from an initial average of 31 per month in 2003 (0.24 calls per participant) to 66 per month in 2006 (0.3 calls per participant), 60% of which were after hours. The percentage of ED reviews per phone call dropped from an initial 74.2% (95% CI 55.2%-88.1%) in 2003 to 50.0% (95% CI 37.4%-62.5%) in 2006 (p = 0.02). However, decreases in ED visits and admissions as a percentage of enrolled patients and as a percentage of phone calls to ACE staff were not statistically significant. Mean waiting time for enrolled patients remained below 30 minutes. Parent satisfaction with the programme was rated 8.3 on a 0-10 scale (0 meaning poor, 10 meaning excellent). The approximate cost of the programme per child was AU$750 (292 pounds sterling) per year.

Conclusion: We have developed a coordinated approach towards the provision of healthcare for a group of families with diverse severe chronic medical conditions who frequently present to the ED. Through a comprehensive programme including the development of patient-care plans, care coordination and 24-hour mobile-phone access we were able to enhance families' capacities to manage their children's conditions in the community.
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http://dx.doi.org/10.1136/adc.2007.117960DOI Listing
January 2008

Superior gluteal artery perforator flap reconstruction for anterior thoracic hypoplasia.

Plast Reconstr Surg 2007 Dec;120(7):2125-2126

Department of Plastic and Reconstructive Surgery, Castle Hill Hospital, Hull, United Kingdom.

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http://dx.doi.org/10.1097/01.prs.0000264651.76047.73DOI Listing
December 2007

Avoiding donor-site complications with bilateral DIEP flaps in patients with subcostal scars.

Plast Reconstr Surg 2007 Jun;119(7):2337-2339

Department of Plastic and Reconstructive Surgery, Castle Hill Hospital, Hull, United Kingdom.

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http://dx.doi.org/10.1097/01.prs.0000261064.22785.74DOI Listing
June 2007

Bilateral free DIEP breast reconstruction using contralateral internal mammary and ipsilateral thoracodorsal vessels.

Plast Reconstr Surg 2007 Apr;119(4):1385-1386

Department of Plastic and Reconstructive Surgery, Castle Hill Hospital, Hull, United Kingdom.

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http://dx.doi.org/10.1097/01.prs.0000255180.17788.8cDOI Listing
April 2007

Botulinum toxin as a treatment for leg ulcers.

Plast Reconstr Surg 2007 Apr;119(5):1633

Department of Plastic and Reconstructive Surgery, Castle Hill Hospital, Hull, United Kingdom.

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http://dx.doi.org/10.1097/01.prs.0000256491.39590.56DOI Listing
April 2007

Macromastia and carpal tunnel syndrome: is there an association?

Aesthetic Plast Surg 2006 Sep-Oct;30(5):535-7

Academic Surgical Unit, University of Hull, Castle Hill Hospital, Castle Road, HU16 5JQ, Cottingham, UK.

Macromastia is a disorder commonly reported by women. The prevalence of electrophysiologically confirmed, symptomatic carpal tunnel syndrome is 3% among women. A consecutive series of 31 patients with macromastia requesting breast reduction between August 2002 and April 2003 was recruited. The physical characteristics recorded included age, body mass index, and breast size. Clinical and electrophysiologic assessments of the upper limb were performed. Electrophysiologic testing showed that 7 (22%) of the 31 women had a prolonged median nerve latency conduction time longer than 0.40 ms. Age, chest circumference, and the ratio of nipple-to-inframammary line to chest circumference was associated with carpal tunnel syndrome. The prevalence of carpal tunnel syndrome among patients with macromastia was shown to be higher than in previous epidemiologic studies investigating the prevalence of carpal tunnel syndrome among women. Age, chest circumference, and breast size, but not body mass index, have a positive correlation with the increased prevalence of carpal tunnel syndrome in macromastia cases.
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http://dx.doi.org/10.1007/s00266-005-0214-xDOI Listing
February 2007