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Ngeow W.C.,University of Sheffield | Ngeow W.C.,University of Malaya | Atkins S.,University of Sheffield | Morgan C.R.,University of Sheffield | And 4 more authors.
Neuroscience | Year: 2011

We have investigated the effect of three potential scar-reducing agents applied at a sciatic nerve repair site in C57-black-6 mice. Under anaesthesia the nerve was transected, repaired using four epineurial sutures, and 100 μl of either triamcinolone acetonide (1 mg/100 μl), an interleukin-10 peptide fragment (125 ng/100 μl or 500 ng/100 μl) or mannose-6-phosphate (M6P, 200 mM or 600 mM) was injected into and around the nerve. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2 mm distal or proximal to the repair site. The conduction velocity of the fastest components in the CAP was also calculated. The percentage area of collagen staining (PAS) at the repair site was analysed using Picrosirius Red and image analysis. Comparisons were made with a placebo group (100 μl of phosphate buffered saline) and sham-operated controls. The median CAP modulus ratio in the 600 mM M6P group was 0.44, which was significantly higher than in the placebo group (0.24, P=0.012: Kruskal-Wallis test). Conduction velocities were also faster in the 600 mM M6P group (median 30 m s -1) than in the placebo group (median 27.8 m s -1; P=0.0197: Kruskal-Wallis test). None of the other treated groups were significantly different from the placebo, and all had significantly lower CAP ratios than the sham controls (P<0.05). All repair groups had a significantly higher PAS for collagen than sham controls. We conclude that the administration of 600 mM mannose-6-phosphate to a nerve repair site enhances axonal regeneration. © 2011 IBRO.


Moore R.W.,University of Wisconsin - Madison | Fritz W.A.,University of Wisconsin - Madison | Fritz W.A.,Covance | Schneider A.J.,University of Wisconsin - Madison | And 5 more authors.
Toxicology and Applied Pharmacology | Year: 2016

It is well established that the prototypical aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can both cause and protect against carcinogenesis in non-transgenic rodents. But because these animals almost never develop prostate cancer with old age or after carcinogen exposure, whether AHR activation can affect cancer of the prostate remained unknown. We used animals designed to develop this disease, Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, to investigate the potential role of AHR signaling in prostate cancer development. We previously reported that AHR itself has prostate tumor suppressive functions in TRAMP mice; i.e., TRAMP mice in which Ahr was knocked out developed neuroendocrine prostate carcinomas (NEPC) with much greater frequency than did those with both Ahr alleles. In the present study we investigated effects of AHR activation by three different xenobiotics. In utero and lactational TCDD exposure significantly increased NEPC tumor incidence in TRAMP males, while chronic TCDD treatment in adulthood had the opposite effect, a significant reduction in NEPC incidence. Chronic treatment of adult TRAMP mice with the low-toxicity selective AHR modulators indole-3-carbinol or 3,3′-diindolylmethane did not significantly protect against these tumors. Thus, we demonstrate, for the first time, that ligand-dependent activation of the AHR can alter prostate cancer incidence. The nature of the responses depended on the timing of AHR activation and ligand structures. © 2016 Elsevier Inc.


Dalbeth N.,University of Auckland | Milligan A.,Auckland District Health Board | Doyle A.J.,University of Auckland | Clark B.,Grafton Group | McQueen F.M.,University of Auckland
Arthritis Research and Therapy | Year: 2012

Introduction: Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and tophus.Methods: Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed.Results: The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous tophus were more likely to have NBF; if tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001.Conclusions: This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, tophus, and formation of new bone during the process of joint remodelling in gout. © 2012 Dalbeth et al.; licensee BioMed Central Ltd.


Beliaev A.M.,Auckland City Hospital | Marshall R.J.,University of Auckland | Gordon M.,Grafton Group | Smith W.,Auckland City Hospital | Windsor J.A.,University of Auckland
Vox Sanguinis | Year: 2012

Background It is well known that blood transfusion is life-saving, but also that it carries a serious risk of transmitting viral infections. Introduction of new methods of testing for transmissible diseases, blood banking and dispatch regulations has considerably increased the cost of blood products. However, the clinical benefits and cost-effectiveness of allogeneic red-blood-cell (ARBC) transfusion remain assumed yet undetermined. We assessed the clinical benefits and cost-effectiveness of ARBC transfusion in severe anaemia. Methods This was a multicenter observational study comparing Jehovah's Witness (JW) patients with matched ARBC-transfused patients. Inclusion criteria were age ≥15years and severe anaemia (haemoglobin≤80g/l). Two JW patients with palliative care cancer and five JW patients with haemoglobin (Hb) concentration between 70·1 and 80g/l, mild symptoms of anaemia and Auckland Anaemia Mortality Risk Score of 0-3 were excluded. Results The entry criteria were met by 103 JW patients and the same number of patients treated with ARBC transfusion. ARBC transfusion reduced mortality by 94%, shock by 88%, gastrointestinal bleeding by 81%, infective complications by 81%, cardiac arrhythmia by 96%, angina by 86%, ischaemic myocardial injury by 81%, acute/acute on chronic renal failure by 66%, neurologic complications by 92%, delirium by 76%, depression by 91% and syncopal episodes by 95%. The incremental cost-effectiveness ratio of ARBC transfusion was 2011 US$22515 for death prevented. Conclusion ARBC transfusion in anaemic patients is clinically beneficial and cost-effective. © 2011 International Society of Blood Transfusion.


Cadirci M.,University of Manchester | Masala O.,Grafton Group | Pickett N.,Grafton Group | Binks D.,University of Manchester
Chemical Physics | Year: 2014

Colloidal CuInS2 quantum dots have been synthesised and characterised using absorption and photoluminescence spectroscopy, X-ray diffraction, inductive-coupled plasma atomic emission spectroscopy and thermogravimetric analysis. The ultrafast charge dynamics of these dots have been studied using transient absorption spectroscopy. Cooling of hot photo-generated carriers to the band edge occurred within 3-5 ps. Significant de-population of the band-edge was found to occur on a sub-nanosecond time-scale, and was attributed to hole-trapping. © 2014 Elsevier B.V. All rights reserved.


Bignell E.,Grafton Group | Cairns T.C.,TU Berlin | Throckmorton K.,University of Wisconsin - Madison | Nierman W.C.,J. Craig Venter Institute | Keller N.P.,University of Wisconsin - Madison
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Aspergillus fumigatus is a versatile fungus able to successfully exploit diverse environments from mammalian lungs to agricultural waste products. Among its many fitness attributes are dozens of genetic loci containing biosynthetic gene clusters (BGCs) producing bioactive small molecules (often referred to as secondary metabolites or natural products) that provide growth advantages to the fungus dependent on environment. Here we summarize the current knowledge of these BGCs—18 of which can be named to product—their expression profiles in vivo, and which BGCs may enhance virulence of this opportunistic human pathogen. Furthermore, we find extensive evidence for the presence of many of these BGCs, or similar BGCs, in distantly related genera including the emerging pathogen Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats, and suggest such BGCs may be predictive of pathogenic potential in other fungi. © 2016 The Author(s) Published by the Royal Society. All rights reserved.


Marjoribanks J.,Grafton Group | Proctor M.,Grafton Group | Farquhar C.,Grafton Group | Derks R.S.,Grafton Group
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea versus placebo, versus paracetamol and versus each other, to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the following databases to May 2009: Cochrane Menstrual Disorders and Subfertility Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science. The National Research Register and the Clinical Trials Register were also searched. Abstracts of major scientific meetings and the reference lists of relevant articles were checked. SELECTION CRITERIA: All randomised controlled comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). Inverse variance methods were used to combine data. MAIN RESULTS: Seventy-three randomised controlled trials were included. Among women with primary dysmenorrhoea, NSAIDs were significantly more effective for pain relief than placebo (OR 4.50, 95% CI: 3.85, 5.27). There was substantial heterogeneity for this finding (I(2) statistic =53%): exclusion of two outlying studies with no or negligible placebo effect reduced heterogeneity, resulting in an odds ratio of 4.14 (95% CI: 3.52, 4.86, I(2)=40%). NSAIDs were also significantly more effective for pain relief than paracetamol (OR 1.90, 95% CI:1.05 to 3.44). However, NSAIDS were associated with significantly more overall adverse effects than placebo (OR 1.37, 95% CI: 1.12 to 1.66). When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain-relief or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. AUTHORS' CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.


BIRMINGHAM, England--(BUSINESS WIRE)--SCC* has announced its annual results for year ending March 2015, with Services revenue reaching £159m, up 22% and accounting for 24% of its total income. · Services revenue up 22% to £159m, now 24% of total revenue; · Gross Profit (GP) increase of 15% and margin rate up 3.7% in the year to 15.5%; · Share of GP from Services up 11% in the year to 55% of overall GP; · EBITDA up 25% on prior year to £19.4m; · PBT at £12.4m up 20% on prior year; · M2 print business contributes turnover of £27m and EBITDA of £1.6m. The transition has seen dramatic changes in the underlying business and hyper growth in Cloud Delivered Managed Services (CDMS – DCS & Connectivity), as SCC moves the business away from low margin product sales. Key to SCC EMEA’s strategy to reach £50m EBITDA by FY17 is its Services division, which saw an overall GP growth of 22% in FY15. This was supported by key new business wins with Kier Group, Samworth Brothers, Grafton Group, McDonald Hotels, United Utilities, Department for Work and Pensions, and WHSmith. SCC’s Professional Services business grew 11% versus last year, with Managed Services up 13% and growth from the new Flexible Resourcing service. As SCC continues to invest heavily in its Data Centre Services (DCS) – most recently taking a majority share in Fluidata, the Data Delivery Network – it enjoyed another year of accelerated growth, up 87% on FY14. DCS closes the year on £26m, with an Annualised Run Rate (ARR) of £34m. March 2015 alone saw Monthly Recurring Revenue (MRR) increase 100% compared to last year. As SCC’s Cloud platforms enter maturity, DCS GP closed the year at 44% from 25%, with ARR closing on £29.4m, 96% ahead of the previous year. Monthly DCS EBITDA closes 220% ahead of FY14, at an annualised EBITDA of £12m (pre-central costs). Following SCC’s acquisition of SSE’s Tier 3+ Data Centre in Fareham and our recent 2nd phase 360 rack Birmingham investment, our total rack capacity is over 1,800 and 14Mv of power, the business closes the year on 67% occupancy and annual rack growth of 145%. Looking ahead to FY16 for the combined UK business, turnover for Services business is expected to top £200m with Cloud Services set to close next March on £55m and an ARR of £70m. EBITDA is estimated to grow 30% to £25m, with stable Product revenues of £500m and overall revenues of £700m. SCC Chief Executive James Rigby said: “The business is firmly on track to achieve its 3-year target of £50m EBITDA. We now have a sizeable Services business to further our growth and margins through recurring revenues. “Cloud Delivered Managed Services is the way forward for SCC. We have already started our next phase with a £10m investment in our own Data Centres, building additional data halls at Birmingham and Fareham facilities to increase capacity to 3,000 racks in FY16 to cater for CDMS growth of up to 60%. “SCC has always been a company with vision and an ability to deliver. We have an exciting year ahead as we grow our Services business organically and through further investments.” In Europe, SCC France recorded its best year of EBITDA for a second consecutive year, up 5.4% to £15.7m. Overall revenue in France closed on £812m a 3% improvement in constant currency terms. SCC Spain increased its revenue by £8m to £48m versus FY14 – a constant currency increase of 30%, with EBITDA of £0.6m, up 123%, as it continues its own transition to a services led business. And SCC Romania saw revenues of £9.2m, while the business delivered a 103% increase of EBITDA to £1.2m. During the year, headcount grew to 711 people at the facilities in Iasi and Bacau. During FY16, it is expected to grow to more than 1,200 people. SCC EMEA closed the year on £1.55bn revenue and EBITDA of £35.2m; an increase of 10% over the prior year. People do business, we make it work. We enable people to do business by planning, supplying, integrating and managing their IT. We make IT work through partnership, knowledge and passion: trusted to run IT infrastructure and services for leading business across Europe for 40 years. This information was brought to you by Cision http://news.cision.com


BIRMINGHAM, England--(BUSINESS WIRE)--SCC* has announced its annual results for year ending March 2015, with Services revenue reaching £159m, up 22% and accounting for 24% of its total income. · Services revenue up 22% to £159m, now 24% of total revenue; · Gross Profit (GP) increase of 15% and margin rate up 3.7% in the year to 15.5%; · Share of GP from Services up 11% in the year to 55% of overall GP; · EBITDA up 25% on prior year to £19.4m; · PBT at £12.4m up 20% on prior year; · M2 print business contributes turnover of £27m and EBITDA of £1.6m. The transition has seen dramatic changes in the underlying business and hyper growth in Cloud Delivered Managed Services (CDMS – DCS & Connectivity), as SCC moves the business away from low margin product sales. Key to SCC EMEA’s strategy to reach £50m EBITDA by FY17 is its Services division, which saw an overall GP growth of 22% in FY15. This was supported by key new business wins with Kier Group, Samworth Brothers, Grafton Group, McDonald Hotels, United Utilities, Department for Work and Pensions, and WHSmith. SCC’s Professional Services business grew 11% versus last year, with Managed Services up 13% and growth from the new Flexible Resourcing service. As SCC continues to invest heavily in its Data Centre Services (DCS) – most recently taking a majority share in Fluidata, the Data Delivery Network – it enjoyed another year of accelerated growth, up 87% on FY14. DCS closes the year on £26m, with an Annualised Run Rate (ARR) of £34m. March 2015 alone saw Monthly Recurring Revenue (MRR) increase 100% compared to last year. As SCC’s Cloud platforms enter maturity, DCS GP closed the year at 44% from 25%, with ARR closing on £29.4m, 96% ahead of the previous year. Monthly DCS EBITDA closes 220% ahead of FY14, at an annualised EBITDA of £12m (pre-central costs). Following SCC’s acquisition of SSE’s Tier 3+ Data Centre in Fareham and our recent 2nd phase 360 rack Birmingham investment, our total rack capacity is over 1,800 and 14Mv of power, the business closes the year on 67% occupancy and annual rack growth of 145%. Looking ahead to FY16 for the combined UK business, turnover for Services business is expected to top £200m with Cloud Services set to close next March on £55m and an ARR of £70m. EBITDA is estimated to grow 30% to £25m, with stable Product revenues of £500m and overall revenues of £700m. SCC Chief Executive James Rigby said: “The business is firmly on track to achieve its 3-year target of £50m EBITDA. We now have a sizeable Services business to further our growth and margins through recurring revenues. “Cloud Delivered Managed Services is the way forward for SCC. We have already started our next phase with a £10m investment in our own Data Centres, building additional data halls at Birmingham and Fareham facilities to increase capacity to 3,000 racks in FY16 to cater for CDMS growth of up to 60%. “SCC has always been a company with vision and an ability to deliver. We have an exciting year ahead as we grow our Services business organically and through further investments.” In Europe, SCC France recorded its best year of EBITDA for a second consecutive year, up 5.4% to £15.7m. Overall revenue in France closed on £812m a 3% improvement in constant currency terms. SCC Spain increased its revenue by £8m to £48m versus FY14 – a constant currency increase of 30%, with EBITDA of £0.6m, up 123%, as it continues its own transition to a services led business. And SCC Romania saw revenues of £9.2m, while the business delivered a 103% increase of EBITDA to £1.2m. During the year, headcount grew to 711 people at the facilities in Iasi and Bacau. During FY16, it is expected to grow to more than 1,200 people. SCC EMEA closed the year on £1.55bn revenue and EBITDA of £35.2m; an increase of 10% over the prior year. People do business, we make it work. We enable people to do business by planning, supplying, integrating and managing their IT. We make IT work through partnership, knowledge and passion: trusted to run IT infrastructure and services for leading business across Europe for 40 years. This information was brought to you by Cision http://news.cision.com

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