Research Ltd Research Articles

The potential of current european light duty CNG-fuelled vehicles to meet Euro 6 requirements

Natural gas is one of the most promising alternative fuels to meet the new stringent Euro 6 emissions regulations in the European Union, as well as the planned CO2 emissions reductions. For spark-ignition (SI) engines, bi-fuel fuelling equipment is widely available and engine conversion technology for European automobiles is well established, thereby facilitating usage of CNG in this engine type. This study investigates the implications of natural gas fuelling of a passenger car featuring a spark-ignition engine regarding the possibility of meeting Euro 6 emissions limits for gaseous pollutants. This paper presents an analysis of CO, THC, NMHC, NOx and CO2 emissions during testing of a vehicle on a chassis dynamometer, fuelled with CNG, in the context of the new Euro 6 emissions requirements. The analyses were performed on a Euro 5 bi-fuel vehicles with an SI engine equipped with an MPI feeding system operating in closed-loop control, a typical three-way-catalyst, and a heated oxygen sensor. The vehicles had been adapted by their manufacturer for fuelling with CNG by using additional special equipment mounted onto the existing petrol fuelling system. The vehicles tested featured a multipoint gas injection system latest generation. The tests subject to the analyses presented here were performed in the Engine Research Department of BOSMAL Automotive Research and Development Institute Ltd in Bielsko-Biala, Poland, within a research programme investigating the influence of alternative fuels on exhaust emissions from automotive vehicles with spark-ignition and compression-ignition engines.

286 TELEMETRY-BASED OXYGEN SENSOR TO CONTINUOUSLY MONITOR KIDNEY OXYGENATION IN CONSCIOUS RATS; A NEW PLATFORM FOR EXPLORING DEVELOPMENT OF RENAL DISEASE

Objectives: Disturbed kidney oxygenation, i.e. renal hypoxia, may contribute to initiation and progression of both chronic kidney disease and acute kidney injury. A critical barrier to investigate this is the lack of available technology to chronically measure kidney tissue oxygenation. We have developed a novel solution for chronic measurement of oxygen concentration in the kidney. Methods: Using a telemetry-based carbon paste oxygen electrode we continuously recorded oxygen concentration in the inner medulla for 6 weeks in rats, unhindered by anaesthesia or restraint. The implantable potentiostat allows for potentially lifetime monitoring through the use of inductive powering of the implanted telemeter (Telemetry Research Ltd, Auckland, New Zealand). Results: Oxygen concentration values were stable over time and comparable between animals. Within an animal the level of tissue oxygen slightly increased over time from 7 days after implantation until 3 weeks. When the average of day 5, 6 and 7 is considered as baseline, oxygen concentration increased by 6-66% with a coefficient of variation of 22%. We observed a reproducible response to repeatedly applied changes in inspired oxygen. Hypoxia (10% oxygen) decreased medullary oxygen concentration by 48 ± 7% while hyperoxia (100% oxygen) increased it by 76 ± 5%. Three weeks after implantation, there was little fibrosis around the implanted electrodes. Conclusions: These findings illustrate the possibility of monitoring renal tissue oxygen concentration in conscious animals. This technology provides a platform for the investigation of the role of tissue hypoxia in development of kidney disease.

Clinical evaluation of a new multi-purpose disinfecting solution in symptomatic wearers of silicone hydrogel contact lenses

Correspondence: Renee Garofalo Alcon Research Ltd, 6201 South Freeway, TC-44, Fort Worth, TX 76134, USA Tel +1 817 615 2712 Fax +1 817 615 4602 Email renee.garofalo@alconlabs.com Background: The purpose of this study was to evaluate the safety and efficacy of a new multi-purpose disinfecting solution containing a diblock copolymer, poly(oxyethylene)poly(oxybutylene), designed to improve the wetting properties of silicone hydrogel lenses in patients with symptoms of discomfort. Methods: This 30-day, randomized, concurrently controlled, double-masked, multi-site study involved 589 subjects at 42 investigational sites in the US. Existing symptomatic lens wearers were randomly assigned to either regimen 1 (OPTI-FREE PureMoist, Alcon Laboratories Inc,) a newly developed formulation containing the diblock copolymer), or regimen 2 (renu freshTM multi-purpose solution Bausch + Lomb, Inc). On days 0, 14 and 30, subjects assessed acceptability and comfort using seven Likert-type questions, rated the intensity of ocular symptoms (comfort, dryness, irritation, scratchiness, burning, stinging) on a visual analog scale (0–100), as well as reported lens wearing time, comfortable lens wearing time, and rewetting drop frequency. The investigators assessed slitlamp findings (including circumlimbal conjunctival lissamine green staining and corneal fluorescein staining), on-eye lens surface wettability and deposits, visual acuity, and adverse events. Results: Differences favoring regimen 1 were noted on Day 30 for the primary Likert statement “I can comfortably wear my lenses” (P = 0.047) and for comfortable lens wear time (P = 0.041). Symptoms of ocular scratchiness, ocular burning, and ocular stinging were all rated lower after 30 days of use by subjects using regimen 1 compared with those using regimen 2 (P # 0.024). Circumlimbal conjunctival staining (sum score) was significantly lower with regimen 1 (P , 0.0001). Other parameters did not show any difference between the two treatment regimens. Conclusion: This study shows that the new multi-purpose disinfecting solution is safe and effective when used by symptomatic silicone hydrogel contact lens wearers. By improving symptoms of scratchiness, burning, stinging, and comfortable wear time, and decreasing circumlimbal conjunctival staining, the new multi-purpose disinfecting solution enhances the patient’s wearing experience and helps maintain optimal lens performance.

Progress in Blueberry Research in New Zealand

Blueberries were first introduced to New Zealand in the 1950s from North America and by 1970 around 30 cultivars had been imported. Selection for new material better suited to the New Zealand climate then began using F1 seedlings and open pollinated crosses. The Plant & Food Research Ltd blueberry breeding program (led by Dr. Jessica Scalzo) is currently run at three sites: at Hamilton and Motueka on the North and South Island, respectively, of New Zealand, and a smaller program at Dierking's Nursery in Germany. Plant & Food Research Ltd's breeding targets are to improve yield, ripening season, and disease resistance, as well as fruit quality traits, such as fruit size, firmness, flavor, color, and grittiness. Areas of research include molecular genetics, functional genomics, biochemical composition, and health, and in 2008, we joined the Speciality Crop Research Initiative project to generate genomic tools for blueberry improvement, led by Dr. Lisa Rowland. We present a summary of the microsatellite and single nucleotide polymorphism-based markers we have developed as part of the Speciality Crop Research Initiative program, as well as an update on other blueberry research undertaken at Plant & Food Research Ltd. This will include anthocyanin composition studies, research into polyphenolics and skeletal muscle damage, as well as work on our expressed sequence tag library and candidate genes within the anthocyanin pathway. We will also discuss the impact of this research on the future of blueberry breeding at Plant & Food Research Ltd.

Evaluation of nepafenac in prevention of macular edema following cataract surgery in patients with diabetic retinopathy

BackgroundThe purpose of this study was to evaluate nepafenac ophthalmic suspension 0.1% (Nevanac®; Alcon Research Ltd) in the prevention of macular edema following cataract surgery in diabetic retinopathy patients.MethodsThis was a multicenter, randomized, double-masked, vehicle-controlled study of 263 adult diabetic patients with nonproliferative diabetic retinopathy requiring cataract surgery. Patients were randomized (1:1) to instill nepafenac or vehicle three times daily beginning 1 day prior to surgery through day 90. Efficacy included the percentage of patients who developed macular edema (≥30% increase in central subfield macular thickness from baseline) and the percentage of patients with decreases of more than five letters in best-corrected visual acuity from day 7 to 90.ResultsA significantly lower percentage of patients in the nepafenac group developed macular edema relative to patients in the vehicle group (3.2% versus 16.7%; P < 0.001). A significantly lower percentage of patients in the nepafenac group had best-corrected visual acuity decreases of more than five letters relative to patients in the vehicle group on day 30 (P < 0.001), day 60 (P = 0.002), and day 90 (P = 0.006). The mean central subfield macular thickness and mean percent change from baseline in macular volume were also significantly lower in the nepafenac group versus the vehicle group at days 14 through 90 (P ≤ 0.005). No safety issues or trends were identified when dosing was increased to 90 days that negatively impacted the favorable benefit/risk profile of nepafenac.ConclusionNepafenac demonstrated statistically significant and clinically relevant advantages compared with vehicle in preventing macular edema and maintaining visual acuity in diabetic patients following cataract surgery. These advantages were seen at multiple time points over the course of the 90-day therapy period. There was no clinically relevant increase in risk from 90 days dosing compared with 14 days. Therefore, with a similar safety profile and benefit in preventing macular edema and maintaining vision, the risk/benefit to the diabetic patient undergoing cataract surgery appears to be positive.

Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the interaction of thrombin-conjugated iron oxide magnetic nanoparticles with fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF) was achieved by the covalent and physical conjugation of the growth factor to the magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in the transparent fibrin scaffolds in the absence or presence of the free or conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced significantly the growth and differentiation of the NOM cells in the fibrin scaffolds, compared to the same or even five times higher concentration of the free bFGF. In the presence of the bFGF-conjugated magnetic nanoparticles, the cultured NOM cells proliferated and formed a three-dimensional interconnected network composed mainly of tapered bipolar cells. The magnetic properties of these matrices are due to the integration of the thrombin- and bFGF-conjugated magnetic nanoparticles within the scaffolds. The magnetic properties of these scaffolds may be used in future work for various applications, such as magnetic resonance visualization of the scaffolds after implantation and reloading the scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to the iron oxide magnetic nanoparticles.

Visual performance in cataract patients with low levels of postoperative astigmatism: full correction versus spherical equivalent correction

PurposeTo evaluate whether visual performance could be improved in pseudophakic subjects by correcting low levels of postoperative astigmatism.MethodsAn exploratory, noninterventional study was conducted using subjects who had been implanted with an aspheric intraocular lens and had 0.5–0.75 diopter postoperative astigmatism. Monocular visual performance using full correction was compared with visual performance using spherical equivalent correction. Testing consisted of high- and low-contrast visual acuity, contrast sensitivity, and reading acuity and speed using the Radner Reading Charts.ResultsThirty-eight of 40 subjects completed testing. Visual acuities at three contrast levels (100%, 25%, and 9%) were significantly better using full correction than when using spherical equivalent correction (all P < 0.001). For contrast sensitivity testing under photopic, mesopic, and mesopic with glare conditions, only one out of twelve outcomes demonstrated a significant improvement with full correction compared with spherical equivalent correction (at six cycles per degree under mesopic without glare conditions, P = 0.046). Mean reading speed was numerically faster with full correction across all print sizes, reaching statistical significance at logarithm of the reading acuity determination (logRAD) 0.2, 0.7, and 1.1 (P < 0.05). Statistically significant differences also favored full correction in logRAD score (P = 0.0376), corrected maximum reading speed (P < 0.001), and logarithm of the minimum angle of resolution/logRAD ratio (P < 0.001).ConclusionsIn this study of pseudophakic subjects with low levels of postoperative astigmatism, full correction yielded significantly better reading performance and high- and low-contrast visual acuity than spherical equivalent correction, suggesting that cataractous patients may benefit from surgical correction of low levels of preoperative corneal astigmatism.

Standardisation and harmonisation boost the credibility of nuclear medicine procedures

The results of diagnostic procedures in nuclear medicine may be heavily influenced by the equipment used and factors related to the investigator. The freedom of physicists, technicians and physicians to discretely compose the camera set-up and the protocols for acquisition, reconstruction and post-processing, including various techniques of quantification, not surprisingly results in a heterogeneous outcome of procedures that are in principle the same. One might debate whether these issues play a role in the diagnostic work-up of a certain patient; it is quite evident, however, that scientific investigations, e.g. in the setting of multicentre trials, may be greatly compromised by these factors. Procedural guidelines published by professional associations in our field, such as the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine (SNM) or the local societies in various European countries are an important milestone to provide a basic framework. However, it is in the nature of such guidelines that they leave space for interpretation and layout. Particularly for scientific purposes but also in the clinical context standardisation and harmonisation of procedures needs to be further pursued and developed to improve the comparability of results between institutions. The credibility of reported findings depends largely on their validity. The latter is a crucial point, because nuclear medicine procedures increasingly have to prove both benefit for the patient and economic benefit before they are accepted and recognized by health insurance and authorities. In this context procedural guidelines have to be further narrowed with the aim of providing harmonised, wellaccepted results. An example of how these theoretical considerations can be successfully realised is supplied by John Dickson and co-workers. They report in this issue of the European Journal of Nuclear Medicine and Molecular Imaging a proposal for the standardisation of SPECT investigations of the brain for multicentre trials [1]. This proposal is the first logical step of a remarkable programme launched and developed under the umbrella of the recently founded EANM Research Ltd (EARL) and aims to standardise investigations with I-123-FP-CIT (DaTSCAN) SPECT in Europe. FP-CIT is a diagnostically valuable tracer for assessment of presynaptic dopaminergic function, particularly in neurodegenerative Parkinsonian syndromes. Unfortunately however, even though this radiopharmaceutical has been approved for more than a decade in Europe in clinical practice as well as in clinical trials, the quality spectrum of scans has ranged from excellent to rather poor, mostly due to the lack of standardised acquisition, processing, and quantification and of a generally available reference database. Realising these problems, the Neuroimaging Committee of the EANM decided to initiate a programme to overcome these limitations by setting up an investigatorinitiated multicentre trial using EARL as a platform. The aims of the trial, performed at 15 highly experienced centres in ten European countries, were threefold: first, to provide a framework to acquire high-quality multicentre SPECT studies by proposing a standardised set-up and qualityassurance regime; second, to perform anthropomorphic phantom measurements for cross-calibration of gamma camera systems; and third, to build up a comprehensive K. Tatsch (*) Klinik fur Nuklearmedizin, Stadtisches Klinikum Karlsruhe, Moltkestr. 90, 76133 Karlsruhe, Germany e-mail: Klaus.Tatsch@klinikum-karlsruhe.de

Antioxidant and &amp;#x2018;Natural Protective&amp;#x2019; Properties of Kiwifruit

Kiwifruit are nutrient-dense fruit with a reputation for promoting good health. Although this could be attributed to the high vitamin C content of kiwifruit, other phytochemicals could also provide health benefits. Kiwifruit are commonly reported to be a good source of vitamin E and in addition contain phenolics and carotenoids. The antioxidant properties of kiwifruit have received attention as possible mechanisms for their health-promoting effects. In this review, the antioxidant capacity of kiwifruit is discussed in the context of biologically relevant in vitro assays for predicting antioxidant activity in a biological setting compared with chemical antioxidant assays, and the ability of kiwifruit to protect cells from dying after exposure to an oxidative insult by hydrogen peroxide (cytoprotection). Some recent data are included, where extracts from twenty kiwifruit genotypes, derived from germplasm held at The New Zealand Institute for Plant & Food Research Ltd, were compared for their cellular antioxidant activity and cytoprotection, using human gut-derived epithelial cell lines. Our knowledge of how this type of result is currently reflected in vivo is summarised, together with the 'naturally protective' properties of kiwifruit that involve modulating immune responses in a positive way. Finally, the ways in which these antioxidant and natural protective properties of kiwifruit may influence human health and wellness are discussed.

Abstract 4478: Discovery of AZD5363, an orally bioavailable, potent ATP-competitive inhibitor of AKT kinases

Abstract AKT is a key node in the most frequently de-regulated signaling pathway in human cancer and has been shown to mediate resistance to a range of cytotoxic, anti-hormonal and targeted therapies. We decided to explore inhibitors of AKT as potential new anti-cancer therapeutics. Here we disclose for the first time the discovery and structure of AZD5363, an orally bioavailable, potent ATP-competitive inhibitor of AKT. We evaluated a range of chemical starting points arising from our previous collaboration with the Institute of Cancer Research and Astex Therapeutics Ltd. Ultimately AZD5363 was discovered following a long journey that started from a pyrrolopyrimidine series of compounds. Our first challenge was to improve potency and a second challenge was to improve ROCK selectivity. ROCK is an AGC kinase like AKT but is involved in regulation of vascular tone and thus blood pressure. Extensive SAR studies exploring the series revealed that achieving selectivity over ROCK while retaining AKT potency was quite challenging. Eventually we discovered ways which could improve both selectivity and potency. However, these compounds had significant activity against the hERG ion channel which is implicated in the development of Torsades de Pointes and cardiac death. The next phase of work therefore had to focus on reducing hERG activity, while at the same time not adversely impacting either AKT potency or ROCK selectivity. Finally we discovered that introduction of a key substituent group provided a compound that achieved reduced hERG potency and, surprisingly, also achieved a further small improvement in both AKT potency and ROCK selectivity. This compound was AZD5363. A crystal structure of AZD5363 bound to AKT has revealed some of the key interactions that may contribute to its potency. For example, the pyrrolopyrimidine appears to form hydrogen bonds to the hinge region of the kinase. AZD5363 inhibits all known AKT isoforms with a potency of &amp;lt;10 nM and inhibits phosphorylation of the AKT substrate, PRAS40 in BT474c cells with a potency of 0.31 μM. Activity in in vivo pharmacodynamic and xenograft models has also been demonstrated. A synthetic route suitable for scale-up has been developed. In conclusion, AZD5363 is a potent inhibitor of AKT in vitro and in cells. It has good hERG and ROCK selectivity. It has pharmacodynamic and xenograft activity in vivo. AZD5363 has potential in cancer therapy and is currently in phase 1 clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4478. doi:10.1158/1538-7445.AM2011-4478

Reply: Patient Assessments of Scarring: Patient-Reported Impact of Scars Measure or Patient Scar Assessment Questionnaire?

Reply: Patient Assessments of Scarring: Patient-Reported Impact of Scars Measure or Patient Scar Assessment Questionnaire?

Application of PIP data in health economic models for market access

Correspondence: Nadine van Dongen van Dongen Research Ltd, London, UK Tel +44 75 4522 3534 email nadine.vandongen@vandresearch.com Abstract: Cost-effectiveness data from a state of the art health economic analysis should permit reliable, reproducible, and verifiable insights into the effectiveness of a drug and the possible savings that might be achieved relative to other drugs and/or treatments. The data for a model may come from a variety of sources and are subject to varying degrees of uncertainty. The reliability of the estimates depends on the choice of the data sources. Data sources for the variables being used in a model may be clinical trials, databases, medical records, and Delphi panels. A limitation of these data sources is that they often lack the input from the patient’s perspective. Patient Intelligence applications can provide data to be used in health economic models for any given situation regarding treatment of persons suffering from a disorder, disease, or complaint. The objective of this paper to explore the opportunity of integrating patient data generated by Patient Intelligence applications as an alternative data source for a Delphi panel and databases in health economic models.

Tidal influences on fish distributions on tropical eastern Pacific rocky shores (Colombia)

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 416:241-254 (2010) - DOI: https://doi.org/10.3354/meps08768 Tidal influences on fish distributions on tropical eastern Pacific rocky shores (Colombia) Gustavo Adolfo Castellanos-Galindo1,2,*, Uwe Krumme1, Trevor J. Willis3 1Leibniz Center for Tropical Marine Ecology (ZMT), Fahrenheitstr. 6, 28359 Bremen, Germany 2Grupo de Investigación en Ecología Animal, Departamento de Biología, Universidad del Valle, A.A. 25360, Cali, Colombia 3National Institute of Water and Atmospheric Research Ltd, PO Box 893, Nelson 7040, New Zealand *Email: gustavoa80@yahoo.com ABSTRACT: On coasts with high tidal ranges, fishes regularly establish linkages between subtidal and intertidal habitats via tidal movements, such that the home range incorporates habitat that is only intermittently available. To examine the responses of shallow-water reef fish assemblages to tidal water level changes in a macrotidal area of the tropical eastern Pacific, daytime underwater visual fish surveys were carried out in intertidal and subtidal zones at different tidal stages in Utría National Park, Colombia. Labridae and Pomacentridae were the most abundant families, but species within these families changed between intertidal and subtidal zones. Of 106 species, >70% used the rocky intertidal zone. Benthic opportunistic reef species comprised ca. 85% of the intertidal migrant species, whereas the remaining 15% corresponded to ubiquitous reef and pelagic species. Little variation in subtidal and intertidal fish assemblages was observed between spring and neap tides, but there were large changes detected over the tidal cycle that were attributed to species-specific use of the intertidal zone at high tide. Intertidal fish assemblages comprised a defined subset of species that differed significantly from those of subtidal areas. Rocky intertidal habitats are used only haphazardly by most reef fishes, but a few common species shifted more than 90% of their population into intertidal habitats during high tide, indicating that for those taxa, intertidal habitats provide important foraging opportunities. This may introduce a significant source of local-scale bias to density estimates of subtidal reef fishes, and reef fish monitoring programmes should specifically factor tidal state as a controlling influence in macrotidal areas. KEY WORDS: Tidal migrations · Rocky intertidal · Reef fishes · Tropical eastern Pacific · Utría Full text in pdf format PreviousNextCite this article as: Castellanos-Galindo GA, Krumme U, Willis TJ (2010) Tidal influences on fish distributions on tropical eastern Pacific rocky shores (Colombia). Mar Ecol Prog Ser 416:241-254. https://doi.org/10.3354/meps08768 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 416. Online publication date: October 14, 2010 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2010 Inter-Research.

First-in-human study evaluating safety and pharmacokinetics of endoxifen, a potent estrogen-receptor antagonist for breast cancer.

3087 Background: Endoxifen is an active metabolite of tamoxifen, a widely used breast cancer drug. Treatment of breast cancer directly with endoxifen may eliminate tamoxifen metabolism associated variability and avoid a potential serious drug-drug interaction. In this study, the safety, tolerability, and pharmacokinetics (PK) of endoxifen at escalating single doses were assessed in healthy, adult, male and female human subjects. Methods: An open label, single oral dose, randomized, dose escalating parallel study was conducted in 40 healthy male and female fasting subjects. Eight subjects received a single dose of 0.5, 1, 2, or 4 mg endoxifen tablets. Tamoxifen (Nolvadex) 20 mg tablets were administered to eight subjects as reference. Blood samples were collected at predose and up to 528 hours postdose for PK. Results: Single oral dose of endoxifen at 0.5, 1, 2, or 4 mg was safe and well tolerated. Adverse events were not found and no clinically significant changes in laboratory or other safety variables were noted. Endoxifen displays near dose-proportional pharmacokinetics, and small deviations from dose. The drug at all doses was rapidly absorbed with Tmax 6±2.9 h and half-life (t3/4) of 54.9±8.6. Increase in Cmax and AUC appeared proportional to dose when consecutive dose increments were compared. Endoxifen administered at 0.5, 1, 2, or 4 mg resulted in 1.36, 3.8, 5.5, and 14.5 ng/mL Cmax and 99.1, 231, 330, 763 ng.h/mL AUC0-inf, respectively. When compared with endoxifen levels in 20 mg tamoxifen administered subjects, 0.5, 1, 2, and 4 mg endoxifen showed 228%, 804%, and 1,216%, 3,385% higher Cmax, respectively, while Tmax was significantly lower in endoxifen treated subjects. Conclusions: This is the first ever report on human trial demonstrating escalating single oral dose of endoxifen. The results indicated that oral administration of endoxifen is safe and systemically bioavailable in healthy adult human subjects and exhibited linear pharmacokinetics over the dose range of 0.5-4 mg. The drug continues in clinical development as a potentially new therapeutic agent in patients with breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Intas Pharmaceuticals, Jina Pharmaceuticals, Lambda Therapeutic Research Ltd

OR consultancy in the early years: The story of Business Operations Research Ltd

In the post-war years most newly nationalised industries in the United Kingdom had OR groups. Many were run by members of the armed forces who had been involved in OR work during World War II. Although much of the work done by these groups was successful, a lot of it was hampered by politics and, in some cases, a general reluctance to accept new ideas. The author and some colleagues recognised there was an opportunity to spread the word of OR to a much wider audience by setting up a consultancy. This article explains how this came about and details some of their successes.

Evaluating the health benefits of fruits for physical fitness: A research platform

To evaluate the health promoting attributes of fruits and their compounds the New Zealand Institute for Plant & Food Research Ltd (PFR) is using exercise as a model for oxidative stress and immune depression. Regular exercise has health benefits believed to be derived from adaptive responses to moderate oxidative stress. However, following exhaustive or unaccustomed exercise, excessive and prolonged oxidative stress and inflammation can be detrimental and the right balance of modulation from nutritional support via fruit phytochemicals (and vitamins) may prevent damage, aid recovery, and/or enhance muscular and immune function. We have developed a research platform to evaluate physical health, performance and recovery to position new fruit varieties in this area. Utilising compositional analysis of fruit extracts, in vitro screening of muscle cells, electrically stimulated muscle ex vivo, and animal and human intervention and exercise trials, we are evaluating the physical health-promoting effects of polyphenolic phytochemicals derived from fruit, particularly berry fruits. Our research demonstrates that certain fruits may complement the benefits of regular exercise through appropriate modulation of excessive oxidative stress and inflammation.

Eddy covariance methane measurements at a Ponderosa pine plantation in California

Abstract. Long term methane flux measurements have been mostly performed with plant or soil enclosure techniques on specific components of an ecosystem. New fast response methane analyzers make it possible to use the eddy covariance (EC) technique instead. The EC technique is advantageous because it allows continuous flux measurements integrating over a larger and more representative area including the complete ecosystem, and allows fluxes to be observed as environmental conditions change naturally without disturbance. We deployed the closed-path Fast Methane analyzer (FMA) from Los Gatos Research Ltd and demonstrate its performance for EC measurements at a Ponderosa pine plantation at the Blodgett Forest site in central California. The fluctuations of the CH4 concentration measured at 10 Hz appear to be small and their standard deviation is comparable to the magnitude of the signal noise (±5 ppbv). Consequently, the power spectra typically have a white noise signature at the high frequency end (a slope of +1). Nevertheless, in the frequency range important for turbulent exchange, the cospectra of CH4 compare very well with all other scalar cospectra confirming the quality of the FMA measurements are good for the EC technique. We furthermore evaluate the complications of combined open and closed-path measurements when applying the Webb-Pearman-Leuning (WPL) corrections (Webb et al., 1980) and the consequences of a phase lag between the water vapor and methane signal inside the closed path system. The results of diurnal variations of CH4 concentrations and fluxes are summarized and compared to the monthly results of process-based model calculations.

Let&amp;rsquo;s be effective, let the patients talk! Does &amp;lsquo;patient intelligence&amp;rsquo; have an effect on improvements in quality within the healthcare environment?

Let&rsquo;s be effective, let the patients talk! Does &lsquo;patient intelligence&rsquo; have an effect on improvements in quality within the healthcare environment? Nadine van DongenVan Dongen Research Ltd, London, UKAbstract: This paper examines the interaction of patients within the context of efficiency in the pharmaceutical environment. Measurements of quality standards in healthcare are reviewed with an emphasis on the question of whether &lsquo;patient intelligence&rsquo; can improve quality standards in healthcare. Something given particular consideration is the ethical point of view versus the business point of view, in relation to the integration of patients into the decision-making process of a healthcare organization. The paper focuses on the formal and informal reasons for involvement of patients in corporate and/or market access strategies for healthcare organizations.Keywords: healthcare, decision-making process, efficiency, patient intelligence, patients

News and Notes

News and Notes

Crystal Structure of the LG1-3 Region of the Laminin α2 Chain

Laminins are large heterotrimeric glycoproteins with many essential functions in basement membrane assembly and function. Cell adhesion to laminins is mediated by a tandem of five laminin G-like (LG) domains at the C terminus of the α chain. Integrin binding requires an intact LG1-3 region, as well as contributions from the coiled coil formed by the α, β, and γ chains. We have determined the crystal structure at 2.8-Å resolution of the LG1-3 region of the laminin α2 chain (α2LG1-3). The three LG domains adopt typical β-sandwich folds, with canonical calcium binding sites in LG1 and LG2. LG2 and LG3 interact through a substantial interface, but LG1 is completely dissociated from the LG2-3 pair. We suggest that the missing γ chain tail may be required to stabilize the interaction between LG1 and LG2-3 in the biologically active conformation. A global analysis of N-linked glycosylation sites shows that the β-sandwich faces of LG1 are free of carbohydrate modifications in all five laminin α chains, suggesting that these surfaces may harbor the integrin binding site. The α2LG1-3 structure provides the first atomic view of the integrin binding region of laminins.