bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of electrical stimulation, delayed chilling and post‐mortem aging on the quality of M. longissimus dorsi and M. biceps femoris of grass‐fed steers
Authors: Razminowicz Regina H , Kreuzer Michael , Scheeder Martin RL
Published: March 2008

BACKGROUND: Roughage‐based low‐input beef production systems are gaining increasing interest owing to the perceived ecological advantages and potential health benefits associated with the favourable fatty acid composition of such beef. The low plane of nutrition may on the other hand yield less tender beef by affecting growth, carcass weight and fatness and therefore, indirectly, early post‐mortem (p.m.) proteolytic enzyme activity and sarcomere shortening. This study aimed to examine delayed chilling and electrical stimulation as promising techniques to control early p.m. muscle metabolism in a way that improves the tenderness of beef from purely grass‐fed steers in comparison with that from steers receiving a finishing diet with concentrates.

RESULTS: Electrical stimulation decreased the pH at 1.5 and 3 h p.m. in the M. longissimus dorsi (LD) and M. biceps femoris (BF) of the treated carcass sides as well as the maximum shear force in the LD, while delayed chilling had no effect on pH or texture. The interactions of carcass fatness with electrical stimulation (P = 0.025) and delayed chilling (P = 0.089) indicated more pronounced effects of the p.m. treatments on beef texture in leaner carcasses.

CONCLUSION: Electrical stimulation, but not delayed chilling, could markedly improve pasture beef texture and reduce the aging period needed for proper tenderisation. Copyright © 2008 Society of Chemical Industry
Comparative geometric analysis of diamond and hole techniques in end‐to‐side microvascular anastomosis
Authors: Sen Cenk , Hasanov Alemdar
Published: March 2008

Although microsurgical techniques have been accepted routinely in many plastic surgical operations, many experimental studies are currently being conducted to refine the results. Most of these studies are difficult to perform and evaluate and the results are not always free of bias. Many scientific disciplines recently use the mathematics for simulation and modeling to predict the results of difficult experiments. Slit and hole end‐to‐side microanastomosis techniques are frequently preferred by many microsurgeons. Diamond technique recently proposed by the senior author is also a technique of end‐to‐side anastomosis with some advantages. The authors used mathematical simulation and modeling to compare two end‐to‐side microanastomosis techniques namely hole and diamond. The authors measured cross sectional areas of anastomosis in both techniques with different input data. The results showed that for end‐to‐side anastomosis, at angles less than 60°, diamond technique yields a greater cross sectional area at anastomosis site compared with that of hole technique. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Thiel embalming technique: A valuable method for microvascular exercise and teaching of flap raising
Authors: Wolff Klaus‐D. , Kesting Marco , Mücke Thomas , Rau Andrea , Hölzle Frank
Published: March 2008

Because of its high requirements on dexterity and microsurgical skills and the need of complete understanding of flap anatomy, microvascular free flap transfer belongs to the most demanding surgical procedures. Therefore, courses for flap raising and microvascular exercise are considered a prerequisite to prepare for clinical practise. To achieve teaching conditions as realistic as possible we used a novel cadaver embalming method enabling tissue dissection comparable to the living body. Thirty cadavers which were offered to us by the Institute of Anatomy for the purpose of running flap raising courses were embalmed in the technique described by Thiel. On each cadaver, nine free flaps were dissected according to a structured protocol by each course participant and afterwards used for microvascular exercise. The conservation of fine vascular structures and the suitability of the embalmed tissue for microvascular suturing were observed and photographically documented. The Thiel embalming technique provided flap raising procedures to be performed under realistic conditions similar to the living body. Vessels and nerves could be exposed and dissected up to a diameter of 1 mm and allowed for microvascular suturing even after weeks like fresh specimens. The Thiel embalming method is a unique technique and ideally suited to teach flap raising and microvascular suturing on human material. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Functional evaluation of anterolateral thigh flap donor sites: Isokinetic torque comparisons for knee function
Authors: Tsuji Naoko , Suga Hirotaka , Uda Koichi , Sugawara Yasushi
Published: March 2008

Background: The anterolateral thigh flap is thought to have minor donor site morbidity, but muscle dissection is unavoidable when skin perforator vessels run through the vastus lateralis muscle. The purpose of this study was to investigate the functional problems associated with the anterolateral thigh flap donor site. Method: We evaluated 12 patients who underwent free anterolateral thigh flap transfer between March 2003 and November 2005. A questionnaire and dynamic functional evaluation of the knee joint using the Biodex System were performed preoperatively and 6 months postoperatively. Results: No patients reported any disturbance in their daily life. No significant differences were found between donor and normal thighs on isokinetic power tests of the quadriceps muscle. Conclusion: The function of the donor site after harvesting the anterolateral thigh flap was maintained. Damage to or functional disturbance of the donor site is minimal even if muscle is injured when harvesting the flap. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Repairing a 35‐mm‐long median nerve defect with a chitosan/PGA artificial nerve graft in the human: A case study
Authors: Fan Weimin , Gu Jianhui , Hu Wen , Deng Aidong , Ma Yimin , Liu Jie , Ding Fei , Gu Xiaosong
Published: March 2008

We have developed a chitosan/polyglycolic acid (PGA) artificial nerve graft which was previously used for bridge implantation of dog sciatic nerves across 30‐mm long defects. Here we describe a clinical trial of this graft for repairing a 35‐mm‐long median nerve defect at elbow of a human patient. During the 3‐year follow‐up period, functional recovery of the injured median nerve was assessed by pinch gauge test, hydraulic hand dynamometry, static two‐point discrimination and touch test with monofilaments, in couple with electrophysiological examinations. The motor and sensory function of the median nerve demonstrated an ongoing recovery postimplantation, reaching M4 and S3+ levels during the follow‐up period. The results indicate that the chitosan/PGA artificial nerve graft could be used for surgical repair of larger defects in major peripheral nerves at a higher level in the human. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Reliability of the superficial venous drainage of the radial forearm free flaps in oral and maxillofacial reconstruction
Authors: Liu Yuan , Jiang Xiaozhong , Huang Jiantao , Wu Yang , Wang Guodong , Jiang Lei , Li Wai , Zhao Yunfu
Published: March 2008

The aim of this article is to compare the superficial venous drainage system versus dual venous drainage system of radial forearm free flaps (RFFF) and its impact on flap survival. A total of 136 consecutive patients undergoing RFFF reconstruction for oral and maxillofacial surgical defects were reviewed retrospectively. In group l, both the superficial and deep veins were anastomosed to the neck recipient veins. In group 2, only the superficial vein was used for anastomosis. There were no statistical differences in venous problems between two groups (6/68 in group 1 vs. 5/68 in group 2, P = 0.75). The flap survival rate was 98.5% (66/68 in group 1 vs. 68/68 in group 2, P = 0.15). Although there are many theoretical advantages to dual venous drainage system anastomoses, they seem not to impact on flap survival in our experience. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Simultaneous coverage of two separate dorsal digital defects with a syndactylizing venous free flap
Authors: Trovato Matthew J. , Brooks Darrell , Buntic Rudolf F. , Buncke Gregory M.
Published: March 2008

We report a case of a 58‐year‐old patient who sustained multiple finger injuries on the right hand. After thorough debridement, two dorsal defects of the middle and ring fingers were covered simultaneously with a single arterialized venous free flap from the right forearm. The flap was used to create a dorsally syndactylized digit which survived completely and was subsequently divided longitudinally. With early flap division, excellent functional and cosmetic result was achieved. We consider the syndactylized venous free flap with early division as a useful option for simultaneous coverage of separate dorsal digital defects. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Protective effects of glucagon‐like peptide 2 on intestinal ischemia‐reperfusion rats
Authors: Zhang Wei , Zhu Weiming , Zhang Jian , Li Ning , Li Jieshou
Published: March 2008

Our objective was to evaluate the protective effects of glucagon‐like peptide 2 (GLP‐2) on intestinal ischemia/reperfusion (I/R) rats. Thirty‐two rats were randomly assigned to four experimental groups, each of 8: Group A, sham rats underwent laparotomy only, without superior mesenteric artery (SMA) occlusion; Group B, I/R animals underwent laparotomy and occlusion of the SMA for 60 minutes followed by 120 minutes of reperfusion; Group C, I/R animals underwent intestinal I/R, and received pretreatment with GLP‐2 for 3 days preoperatively; and Group D, I/R animals underwent intestinal I/R, received pretreatment with GLP‐2 as above, and during the reperfusion phase were injected intravenously with GLP‐2. After the reperfusion of intestinal ischemia, samples of intestinal mucosa, mesenteric lymph nodes (MLN) and blood were prepared for determination. In the pretreatment rats with GLP‐2 (group C), Chiu's scores, bacterial colony counts, serum D‐lactate, intestinal mucosal MDA and ET‐1, and serum endotoxin, TNF‐α and IL‐6 were significantly reduced compared with intestinal I/R rats (group B). Administration of GLP‐2 during the reperfusion phase following pretreatment (group D) showed further protective effects in comparison with the pretreatment rats (group C). We conclude that treatment with GLP‐2 attenuates intestinal I/R injury, reduces bacterial translocation, inhibits the release of oxygen free radicals and ET‐1, and may well inhibit the production of proinflammatory cytokines. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Transplantation of a vascularized rabbit femoral diaphyseal segment: Mechanical and histologic properties of a new living bone transplantation model
Authors: Giessler Goetz A. , Zobitz Mark , Friedrich Patricia F. , Bishop Allen T.
Published: March 2008

A new vascularized bone transplantation model is described, including the anatomy and surgical technique of isolating a rabbit femoral diaphyseal segment on its nutrient vascular pedicle. The histologic and biomechanical parameters of pedicled vascularized femoral autotransplants were studied following orthotopic reimplantation in the resulting mid‐diaphyseal defect. Vascularized femur segments were isolated in 10 rabbits on their nutrient pedicle, and then replaced orthotopically with appropriate internal fixation. Postoperative weightbearing and mobility were unrestricted, and the contralateral femora served as no‐treatment controls. After 16 weeks, the bone flaps were evaluated by x‐ray (bone healing), mechanical testing (material properties), microangiography (quantification of intraosseous vasculature), histology (bone viability), and histomorphometry (bone remodeling). Bone healing occurred by 2 weeks, with further callus remodeling throughout the survival period. Eight transplants healed completely, while two had a distal pseudarthrosis. Microangiography demonstrated patent pedicles in all transplants. Intraosseous vessel densities were comparable to nonoperated (control) femora. We found ultimate strength and elastic modulus to be significantly reduced when compared to normal controls. Viable bone, increased mineral apposition rate, and bone turnover were demonstrated in all transplants. The method described, and the data provided will be of value for the further study of isolated segments of living bone, and in particular, for investigations of reconstruction of segmental bone loss in weight‐bearing animal models. This study also provides important normative data on living autologous bone flap material properties, vascularity, and bone remodeling. We intend to use this method and data for comparison in subsequent studies of large bone vascularized allotransplantation. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Characterization of nonderivatized plant cell walls using high‐resolution solution‐state NMR spectroscopy
Authors: Yelle Daniel J. , Ralph John , Frihart Charles R.
Published: March 2008

A recently described plant cell wall dissolution system has been modified to use perdeuterated solvents to allow direct in‐NMR‐tube dissolution and high‐resolution solution‐state NMR of the whole cell wall without derivatization. Finely ground cell wall material dissolves in a solvent system containing dimethylsulfoxide‐d6 and 1‐methylimidazole‐d6 in a ratio of 4:1 (v/v), keeping wood component structures mainly intact in their near‐native state. Two‐dimensional NMR experiments, using gradient‐HSQC (heteronuclear single quantum coherence) 1‐bond 13C1H correlation spectroscopy, on nonderivatized cell wall material from a representative gymnosperm pinus taeda (loblolly pine), an angiosperm Populus tremuloides (quaking aspen), and a herbaceous plant Hibiscus cannabinus (kenaf) demonstrate the efficacy of the system. We describe a method to synthesize 1‐methylimidazole‐d6 with a high degree of perdeuteration, thus allowing cell wall dissolution and NMR characterization of nonderivatized plant cell wall structures. Copyright © 2008 John Wiley & Sons, Ltd.
Doubly compensated multiplicity‐edited HSQC experiments utilizing broadband inversion pulses
Authors: Hu Haitao , Krishnamurthy Krish
Published: March 2008

We propose a family of doubly compensated multiplicity‐edited heteronuclear single quantum coherence (HSQC) pulse sequences. The key difference between our proposed sequences and the compensation of refocusing inefficiency with synchronized inversion sweeps (CRISIS)‐HSQC experiments they are based on is that the conventional rectangular 180° pulses on the proton channel in the latter have been replaced by the computer‐optimized broadband inversion pulses (BIPs) with superior inversion performance as well as much improved tolerance to B1 field inhomogeneity. Moreover, all adiabatic carbon 180° pulses during the INEPT and reverse‐INEPT periods in the CRISIS‐HSQC sequences have also been replaced with the much shorter BIPs, while the adiabatic sweeps during the heteronuclear spin echo for multiplicity editing are kept in place in order to maintain the advantage of the CRISIS feature of the original sequences, namely J‐independent refocusing of the one‐bond 1H13C coupling constants. These modifications have also been implemented to the preservation of equivalent pathways (PEP)‐HSQC experiments. We demonstrate through a detailed comparison that replacing the proton 180° pulses with the BIPs provide additional sensitivity gain that can be mainly attributed to the improved tolerance to B1 field inhomogeneity of the BIPs. The proposed sequences can be easily adapted for 19F13C correlations. Copyright © 2008 John Wiley & Sons, Ltd.
NMR study of 5‐substituted pyrazolo[3,4‐c]pyridine derivatives
Authors: Tsikouris Orestis , Bartl Tomáš , Toušek Jaromír , Lougiakis Nikolaos , Tite Tony , Marakos Panagiotis , Pouli Nicole , Mikros Emmanuel , Marek Radek
Published: March 2008

Substituted pyrazolopyridines are potent inhibitors of phosphodiesterases and cyclin‐dependent kinases. In this study, NMR was used to investigate the potential N1‐H and N2‐H tautomerism of 5‐substituted pyrazolo[3,4‐c]pyridine derivatives. Six compounds were fully characterized by using 1H, 13C, and 15N chemical shifts and indirect 1H13C and 1H15N coupling constants. The 1H NMR spectra were measured over a broad range of temperatures. All of the compounds were shown to exist predominantly in the N1‐H tautomeric form. Complementary quantum‐chemical calculations of the chemical shieldings and indirect spin‐spin couplings support the structural conclusions drawn. Copyright © 2008 John Wiley & Sons, Ltd.
T1 relaxation measurement with solvent suppression
Authors: Hoffmann Markus M. , Sobstyl Hanna S. , Seedhouse Steven J.
Published: March 2008

Three solvent‐suppression pulse sequences of varying complexity were incorporated into the standard inversion recovery pulse program and experimentally evaluated. The least complex suppression sequence involves a composite 90° pulse. A more complex sequence utilizes an excitation sculpting sequence requiring pulsed field gradients, and the most complex sequence incorporates an excitation sculpting sequence with selective rf pulses and gradient pulses. The quality of the spectral data and the accuracy of T1 measurements of the investigated suppression schemes were evaluated using three aqueous samples with increasing proton content in the water solvent, i.e. by volume 100% D2O, 80/20% D2O/H2O, and 100% H2O. For lines removed from the water resonance the T1 values were generally very consistent between all pulse sequences tested. For lines less than about 200 Hz from the water signal the T1 measurements become less reliable but are still possible for most of the tested pulse programs. Copyright © 2008 John Wiley & Sons, Ltd.
119Sn NMR chemical shift tensors in anhydrous and hydrated Si8O20(SnMe3)8 crystals
Authors: Jiao Jian , Lee Ming‐Yung , Barnes Craig E. , Hagaman Edward W.
Published: March 2008

119Sn chemical shift tensors of crystalline trialkyltin functionalized octameric spherosilicates, Si8O20(SnMe3)8, have been determined by fitting sideband intensities in solid‐state magic angle spinning (MAS) NMR spectra. Tin chemical shift parameters are exquisitely sensitive to the presence of water of crystallization. Both hydrogen bonding and incipient oxygen–tin bonding from molecular water impact the local tin environment. Tin chemical shift tensors in the crystalline derivatives reflect the changes in geometry and coordination number at the tin centers. Chemical shift correlations on the crystalline derivatives, with known x‐ray structures, are used to infer the tin coordination environment in an amorphous sample. Copyright © 2008 John Wiley & Sons, Ltd.
Capacitated warehouse location model with risk pooling
Authors: Ozsen Leyla , Coullard Collette R. , Daskin Mark S.
Published: March 2008

In this article, we introduce the capacitated warehouse location model with risk pooling (CLMRP), which captures the interdependence between capacity issues and the inventory management at the warehouses. The CLMRP models a logistics system in which a single plant ships one type of product to a set of retailers, each with an uncertain demand. Warehouses serve as the direct intermediary between the plant and the retailers for the shipment of the product and also retain safety stock to provide appropriate service levels to the retailers. The CLMRP minimizes the sum of the fixed facility location, transportation, and inventory carrying costs. The model simultaneously determines warehouse locations, shipment sizes from the plant to the warehouses, the working inventory, and safety stock levels at the warehouses and the assignment of retailers to the warehouses. The costs at each warehouse exhibit initially economies of scale and then an exponential increase due to the capacity limitations. We show that this problem can be formulated as a nonlinear integer program in which the objective function is neither concave nor convex. A Lagrangian relaxation solution algorithm is proposed. The Lagrangian subproblem is also a nonlinear integer program. An efficient algorithm is developed for the linear relaxation of this subproblem. The Lagrangian relaxation algorithm provides near‐optimal solutions with reasonable computational requirements for large problem instances. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Warranty claims modeling
Authors: Kulkarni Vidyadhar , Resnick Sidney I.
Published: March 2008

A company wishes to estimate or predict its financial exposure in a reporting period of length T (typically one quarter) because of warranty claims. We propose a fairly general random measure model which allows computation of the Laplace transform of the total claim made against the company in the reporting interval due to warranty claims. When specialized to a Poisson process of both sales and warranty claims, statistical estimation of relevant quantities is possible. The methodology is illustrated by analyzing automobile sales and warranty claims data from a large car manufacturer for a single car model and model year. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
The building evacuation problem with shared information
Authors: Chen Lichun , Miller‐Hooks Elise
Published: March 2008

In this article, the Building Evacuation Problem with Shared Information (BEPSI) is formulated as a mixed integer linear program, where the objective is to determine the set of routes along which to send evacuees (supply) from multiple locations throughout a building (sources) to the exits (sinks) such that the total time until all evacuees reach the exits is minimized. The formulation explicitly incorporates the constraints of shared information in providing online instructions to evacuees, ensuring that evacuees departing from an intermediate or source location at a mutual point in time receive common instructions. Arc travel time and capacity, as well as supply at the nodes, are permitted to vary with time and capacity is assumed to be recaptured over time. The BEPSI is shown to be NP‐hard. An exact technique based on Benders decomposition is proposed for its solution. Computational results from numerical experiments on a real‐world network representing a four‐story building are given. Results of experiments employing Benders cuts generated in solving a given problem instance as initial cuts in addressing an updated problem instance are also provided. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Study of the process of secondary failure of sulphonylurea by a Markov model
Authors: Tang Wen‐Lu , Wang Yong‐Ming , Du Wen‐Min , Cheng Neng‐Neng , Chen Bin‐Yan
Published: March 2008

Purpose

The study was to reflect and forecast the evolutive tendency and influence factors of secondary failure of sulphonylurea (SFS) changing with time by using a Markov (MKV) model in the elderly diabetic population in Shanghai.

Methods

A total of 549 patients with elderly diabetes mellitus (DM) were enrolled and grouped in the study. A door‐to‐door retrospective epidemiological survey was used to collect data. The MKV model was used to assess the process and influence factors of SFS and the MKV process decision support system was adopted to calculate state probability of the MKV process.

Results

The rate of SFS in the group of all cases, FPG ≤ 10 mmol · L−1 before treatment and FPG > 10 mmol · L−1 before treatment, taking single type of sulphonylurea (SU) and taking two types of SU and over respectively was 9.11%, 3.55%, 11.03%, 8.54% and 11.21%. The years of changing into the state of secondary failure in half patients was 5 years, 11–12 years, 4 years, 5 years, 4 years, respectively in the following groups: all cases, FPG ≤ 10 mmol · L−1 before treatment and FPG > 10 mmol · L−1 before treatment, taking single type of SU and taking two types of SU and over.

Conclusions

A MKV model could predict the long‐term evolutive process of SFS by a short‐term observation; the speed of SFS was related to the degree of DM patients' condition, patients with higher glucose levels prior to treatment would develop SFS faster; but we cannot postpone the development of secondary failure by exchanging SU types. Copyright © 2008 John Wiley & Sons, Ltd.
Developing tools for the safety specification in risk management plans: lessons learned from a pilot project
Authors: Cooper Andrew J. P. , Lettis Sally , Chapman Charlotte L. , Evans Stephen J. W. , Waller Patrick C. , Shakir Saad , Payvandi Nassrin , Murray Alison B.
Published: March 2008

Purpose

Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use.

Methods

Archive data from a successful MAA were utilised. Methods were assessed for demonstrating the extent of clinical safety experience, evaluating the sensitivity of the clinical trial data to detect treatment differences and identifying safety signals from adverse event and laboratory data to define the extent of safety knowledge with the drug.

Results

The extent of clinical safety experience was demonstrated by plots of patient exposure over time. Adverse event data were presented using dot plots, which display the percentages of patients with the events of interest, the odds ratio, and 95% confidence interval. Power and confidence interval plots were utilised for evaluating the sensitivity of the clinical database to detect treatment differences. Box and whisker plots were used to display laboratory data.

Conclusions

This project enabled us to identify new evidence‐based methods for presenting and evaluating clinical safety data. These methods represent an advance in the way safety data from clinical trials can be analysed and presented. This project emphasises the importance of early and comprehensive planning of the safety package, including evaluation of the use of epidemiology data. Copyright © 2008 John Wiley & Sons, Ltd.
Indicators for preventable drug‐related morbidity. Practical application in home‐based care
Authors: Gianino M. M. , Foti G. , Borghese R. , Lorelli S. , Siliquini R. , Renga G.
Published: March 2008

Aim

The aim of this study is of evaluating Morris' PDRM indicator system in the Italian Health Care System, especially in the context of home‐based health care assistance, so as to assess the reliability of such a system to detect preventable events of drug‐related morbidity (DRM).

Methods

This is a pilot study which has been carried out on a control group of patients. The results, which have been obtained, have then been used to calculate the incidence of the preventable drug‐related morbidity (PDRM) in the entire population. The sample of patients was taken from the Health District of Chivasso (Local Health Unit 7 in Piedmont). The subjects had all been inserted in the Integrated Home Healthcare Assistance programme in the period from 1st January to 31st December 2004.

Results

The PDRM is equal to 32, with an incidence of 15.6% in the entire population (205). Seven indicators out of 19 were able to identify PDRM. Of these, the indicator which showed the best detection rate scored 72%.

Conclusions

The study revealed that this indicator system has the capability of detecting events of PDRM. In addition to this, the version of the system which has been approved by the expert panel has proved executable in the Italian healthcare system, especially in home‐based healthcare. Copyright © 2008 John Wiley & Sons, Ltd.
Risk of ischaemic cardiovascular events from selective cyclooxygenase‐2 inhibitors in osteoarthritis
Authors: Cunnington Marianne , Webb David , Qizilbash Nawab , Blum David , Mander Adrian , Funk Michele Jonsson , Weil John
Published: March 2008

Purpose

Most previous observational studies assessing cardiovascular risk associated with Cox‐2 inhibitors (Cox‐2is) used a case control approach, limiting the assessment of absolute risk by disease group and effect of duration of exposure. We conducted a retrospective cohort study in patients with osteoarthritis.

Methods

Using the Life‐link US claims database, all subjects had at least five years history in the database. Exposure was defined as the first chronic period of Cox‐2i (celecoxib, rofecoxib or valdecoxib) or naproxen use. Non‐users and non‐chronic users of non‐steroidal anti‐inflammatory drug (NSAID)/Cox‐2i within the osteoarthritis cohort served as the reference. The primary outcome was myocardial infarction and ischaemic stroke.

Results

A cohort of 16 580 subjects were chronically exposed to celecoxib, 9800 received rofecoxib, 2907 received naproxen and 51 539 were non‐chronically exposed controls. With a median follow up of 506 days, there were 2116 ischaemic events for the entire cohort. The strongest predictors of AMI/ ischaemic stroke risk were history of ischaemic stroke (HR 2.34, 2.12–2.59) and age 65+ years (HR 2.28, 2.07–2.52). For rofecoxib, (HR 1.25,1.04–1.50), the attributable risk varied from 3 per 1000 patients years in individuals aged under 65 years with no history of CVD to 19 per 1000 patients years in older individuals with a history of CVD. The hazard ratios did not change over time. Celecoxib and naproxen were not associated with increased risks.

Conclusions

The attributable risk for rofecoxib varied substantially with the underlying cardiovascular risk profile, being lower in clinical trial than in clinical practice populations. Copyright © 2008 John Wiley & Sons, Ltd.
The pattern of use of non‐steroidal anti‐inflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people
Authors: Fosbøl Emil Loldrup , Gislason Gunnar H , Jacobsen Søren , Abildstrom Steen Z , Hansen Morten Lock , Schramm Tina Ken , Folke Fredrik , Sørensen Rikke , Rasmussen Jeppe N , Køber Lars , Madsen Mette , Torp‐Pedersen Christian
Published: March 2008

Purpose

To describe the nationwide pattern of use of non‐steroidal anti‐inflammatory drugs (NSAIDs) in the Danish population.

Methods

All Danish citizens aged 10 or above 1 January 1997 were included in the study. The national prescription registry was used to identify all claimed prescriptions for NSAIDs by the cohort until 2005. By individual‐level‐linkage of nationwide registries, information was acquired concerning hospitalizations, comorbidity, concomitant pharmacotherapy and socioeconomic factors.

Results

The population consisted of 4 614 807 individuals, of which 2 663 706 (57.8%) claimed at least one prescription for NSAID from 1997 to 2005. Ibuprofen and diclofenac were the most frequently used non‐selective NSAIDs, whereas rofecoxib and celecoxib were the most frequently used selective cyclooxygenase‐2 (COX‐2) inhibitors. The usage was similar across all age groups. Female sex and increasing age was associated with increased use of NSAID. Factors predicting extensive NSAID use were: rheumatic disease (odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.69–1.90), gout agents (allopurinol) (OR = 2.54, CI: 2.44–2.64) and other pain medication (OR = 3.27, CI: 3.23–3.31). NSAIDs were most often prescribed for use for one distinct treatment interval and for a short period (overall inter‐quartile range [IQR]: 9–66 days). High doses were used in a relatively large proportion of the population (8.9% for etodolac to 19.5% for celecoxib) and 54 373 (2.0%) claimed prescriptions for more than one NSAID at the same time.

Conclusion

NSAIDs were commonly used in the Danish population. Since NSAIDs have been associated with increased cardiovascular risk, further research on the overall risk associated with these drugs on a national scale is needed. Copyright © 2008 John Wiley & Sons, Ltd.
Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000–2007
Authors: Walker Alexander M. , Koro Carol E. , Landon Joan
Published: March 2008

Background

The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices.

Objectives

To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas.

Methods

We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head‐to‐head comparisons using propensity‐score‐stratified Cox proportional hazards models, examining risks both on‐treatment and during total follow‐up before regimen switches.

Results

For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94–1.14) for total follow‐up and 1.05 (0.92–1.19) for on‐treatment time. For MI, the hazard ratios were 1.07 (0.89–1.27) for total follow‐up and 1.21 (0.95–1.54) for on‐treatment time.

Conclusions

The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on‐treatment time will require combination with the results of other studies to provide a reliable assessment. Copyright © 2008 John Wiley & Sons, Ltd.
Plasma Process. Polym. 3/2008
Authors: Xie Yong‐Bing , Liu Chang‐Jun
Published: March 2008

Cover: Using NMR and FTIR analyses it could be confirmed that ionic liquids can remain stable under the influence of glow discharge plasma. The novel combination of glow discharge and ionic liquids will lead to many potential applications including the formation of nano metal particles at around room temperature, like indicated in the cover picture. Further details can be found in the article by Y.‐B. Xie, and C.‐J. Liu* on page 239.
Pyrethroids, knockdown resistance and sodium channels
Authors: Soderlund David M
Published: March 2008

Knockdown resistance to DDT and the pyrethrins was first described in 1951 in the housefly (Musca domestica L.). This trait, which confers reduced neuronal sensitivity to these insecticides, was subsequently shown to confer cross‐resistance to all synthetic pyrethroid insecticides that have been examined to date. As a consequence, the worldwide commercial development of pyrethroids as a major insecticide class over the past three decades has required constant awareness that pyrethroid overuse has the potential to reselect this powerful resistance mechanism in populations that previously were resistant to DDT. Demonstration of tight genetic linkage between knockdown resistance and the housefly gene encoding voltage‐sensitive sodium channels spurred efforts to identify gene mutations associated with knockdown resistance and understand how these mutations confer a reduction in the sensitivity of the pyrethroid target site. This paper summarizes progress in understanding pyrethroid resistance at the molecular level, with particular emphasis on studies in the housefly. Copyright © 2008 Society of Chemical Industry
Synthesis and characterization of synthetic analogs of cinnacidin, a novel phytotoxin from Nectria sp.
Authors: Irvine Nicholas M , Yerkes Carla N , Graupner Paul R , Roberts Roben E , Hahn Don R , Pearce Cedric , Gerwick B Clifford
Published: March 2008

BACKGROUND: The novel natural product cinnacidin was isolated from a fungal fermentation extract of Nectria sp. DA060097. The compound was found to contain a cyclopentalenone ring system with an isoleucine subunit linked through an amide bond. Initial biological characterization of cinnacidin suggested promising herbicidal activity.

RESULTS: Two synthetic analogs, (2S,3S)‐2‐[(3RS,3aSR,6aRS)‐3‐methoxy‐4‐oxo‐3,3a,4,5,6,6a‐hexahydropentalen‐1‐ylcarbamoyl]‐3‐methylvaleric acid and benzyl (2S,3S)‐2‐[(3RS,3aSR,6aRS)‐3‐methoxy‐4‐oxo‐3,3a,4, 5,6,6a‐hexahydropentalen‐1‐ylcarbamoyl]‐3‐methylvalerate, were prepared for further characterization, and their herbicidal activities were compared with that of cinnacidin.

CONCLUSIONS: The synthetic compounds were highly phytotoxic on a range of weeds. Based on the symptoms in treated plants, the mode of action of these compounds is suggested to be similar to that of coronatine and jasmonic acid. Coronatine was more active against warm‐season grasses, while the cinnacidin benzyl ester analog was more effective on cool‐season grasses. In a seedling growth bioassay conducted on bentgrass, the cinnacidin analog was equivalent in activity to coronatine. Copyright © 2008 Society of Chemical Industry
Assessment of the suitability of Tinopal as an enhancing adjuvant in formulations of the insect pathogenic fungus Beauveria bassiana (Bals.) Vuillemin
Authors: Reddy Narasimha P , A Khan Pathan Akbar , Devi Koduru Uma , Victor John S , Sharma Hari C
Published: March 2008

BACKGROUND: Biopesticides based on Beauveria bassiana (Bals.) Vuillemin hold great promise for the management of a wide range of insect pests. The conidia in the biopesticide formulation require an adjuvant to protect them from photoinactivation by sunlight. The suitability of Tinopal, an optical brightener used as sunscreen for baculovirus formulations, for use with B. bassiana was assessed. The aim was to study the effect of Tinopal on the growth and photoprotection of B. bassiana, and its effect on the susceptibility of insects to B. bassiana.

RESULTS: Tinopal was found to have no adverse effect on the growth of B. bassiana. It was found to confer total protection (∼95% conidial germination at 10 g Tinopal L−1) from sunlight up to 3 h of exposure, and a better survival rate than controls even up to 4 h. Helicoverpa armigera Hübner larvae fed on diet with 5 g kg−1 Tinopal were found to have reduced growth. The duration of the larval stage increased by 3–4 days in 1 and 5 g kg−1 Tinopal treatments. Among the moths that emerged from larvae fed on diet with 5 g kg−1 Tinopal, a significantly high number were malformed compared with controls. The larvae that were fed diet with Tinopal showed quicker and higher mortality and required a lower effective lethal dose (LC50) than the controls. Tinopal was found to have a synergistic effect with B. bassiana in causing insect mortality.

CONCLUSIONS: Tinopal was found to be a suitable adjuvant for B. bassiana‐based biopesticide formulations. It conferred tolerance to sunlight and caused stress in the insect, leading to a synergistic effect with B. bassiana. Copyright © 2008 Society of Chemical Industry
Gerry Brooks and epoxide hydrolases: four decades to a pharmaceutical
Authors: Morisseau Christophe , Hammock Bruce D
Published: March 2008

The pioneering work of Gerry Brooks on cyclodiene insecticides led to the discovery of a class of enzymes known as epoxide hydrolases. The results from four decades of work confirm Brooks' first observations that the microsomal epoxide hydrolase is important in foreign compound metabolism. Brooks and associates went on to be the first to carry out a systematic study of the inhibition of this enzyme. A second role for this enzyme family was in the degradation of insect juvenile hormone (JH). JH epoxide hydrolases have now been cloned and expressed from several species, and there is interest in developing inhibitors for them. Interestingly, the distantly related mammalian soluble epoxide hydrolase has emerged as a promising pharmacological target for treating hypertension, inflammatory disease and pain. Tight‐binding transition‐state inhibitors were developed with good ADME (absorption, distribution, metabolism and excretion). These compounds stabilize endogenous epoxides of fatty acids, including arachidonic acid, which have profound therapeutic effects. Now EHs from microorganisms and plants are used in green chemistry. From his seminal work, Dr Brooks opened the field of epoxide hydrolase research in many directions including xenobiotic metabolism, insect physiology and human health, as well as asymmetric organic synthesis. Copyright © 2008 Society of Chemical Industry
Differences in the amount of lipolysis induced by atrial natriuretic peptide in small and large adipocytes
Authors: Yu Jiahua , Yu Hee‐Chul , Kim Kyung‐Ah , Kwon Kang‐Beom , Park Jin‐Woo , Kim Sung‐Zoo , Kim Suhn Hee , Park Byung‐Hyun
Published: March 2008

Atrial natriuretic peptide (ANP) is a 28‐amino acid polypeptide that is primarily secreted by the heart. ANP is believed to be a hormone that regulates cardiovascular dynamics and renal functions; however, studies conducted in the past few decades revealed that ANP is also a potent lipolytic agent in human adipocytes that functions through the cGMP‐dependent pathway. In this study, we separated human adipocytes within the same fat depot into small and large fractions using their floating properties and nylon filters of different pore sizes. Real‐time PCR revealed that large adipocytes expressed higher mRNA levels of natriuretic peptide receptor (NPR)‐A and hormone sensitive lipase, and binding studies showed that large adipocytes expressed more NPR‐A on the membrane than small adipocytes. This finding was confirmed by the increase in the amount of glycerol that was released from adipocytes as the cell size increased. Taken together, these results clearly suggest that adipocyte size is an important determinant of ANP‐stimulated lipolysis. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Microstructure, dielectric, and piezoelectric properties of Ce‐modified Na0.5Bi4.5Ti4O15 high temperature piezoceramics
Authors: Zhao Liang , Xu Jian‐Xiu , Yin Na , Wang Hong‐Chao , Zhang Cheng‐Ju , Wang Jin‐Feng
Published: March 2008

The cerium modified sodium bismuth titanate (Na0.5Bi4.5Ti4O15, NBT) piezoelectric ceramics have been prepared by using the conventional mixed oxide method. X‐ray diffraction analysis revealed that the cerium modified NBT ceramics have a pure four‐layer Aurivillius phase structure. The piezoelectric activity of NBT ceramics was found significantly improved by the modification of cerium. The Curie temperature Tc, and piezoelectric coefficient d33 for the NBT ceramics with 0.50 wt% cerium modification were found to be 655 °C, and 28 pC/N respectively. The Curie temperature gradually decreased from 668 °C to 653 °C with the increase of cerium modification. The dielectric spectroscopy showed that the samples possess stable piezoelectric properties, demonstrating practical potential that for high temperature applications. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A robust brain deformation framework based on a finite element model in IGNS
Authors: Liu Yixun , Song Zhijian
Published: March 2008

Background

Brain deformation plays an important role in causing inaccuracy in image‐guided neurosurgery. Three types of approaches have been proposed to solve this problem: intra‐operative imaging, deformation atlas and non‐rigid registration. By comparing these approaches, we here show that the non‐rigid registration approach, based on a linear elastic model, may be the most feasible method during clinical application.

Methods

Based on the non‐rigid registration model, we designed a framework used to correct the brain deformation. A laser range scanner (LRS) was introduced into this framework to obtain the intra‐operative brain surface. Using this device, we designed a novel surface‐tracking algorithm, which includes space transformation (rigid registration) and surface moving. We first transformed the point set from LRS space into image space by a series of transformations, then simulated the movement of the brain surface using a thin‐plate spline.

Results

We tested the framework using pigs. In these experiments, we segmented and meshed the pig's brain and transformed the initial surface (from a MRI scan) and deformed surface (from LRS) into the same coordinate system, using rigid registration. Using this method, the surfaces of pigs' brains were tracked accurately and the internal brain deformation was estimated. The pre‐operative images can be corrected accordingly.

Conclusions

Our animal experiments indicate that this framework can effectively capture the surface deformation and hence estimate the internal deformation of the brain. Copyright © 2008 John Wiley & Sons, Ltd.
Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir
Authors: Chou Sunwen
Published: March 2008

Mutations in the human CMV UL97 kinase gene are a major mechanism of viral resistance to two anti‐CMV drugs, ganciclovir (GCV) and maribavir (MBV). GCV, the most widely used and established therapy for CMV, is a substrate for the UL97 kinase. Well‐characterised GCV‐resistance mutations at UL97 codons 460, 520 and 590–607 impair the phosphorylation of GCV that is necessary for its antiviral activity, presumably by altering substrate recognition. In contrast, MBV is an inhibitor of the UL97 kinase and is the first new CMV therapy to reach later stage clinical trials in many years. No MBV‐resistant CMV isolates have yet been detected in clinical trials, but after culture propagation under drug, UL97 mutations that confer moderate to high‐level MBV resistance have been identified at codons 353, 397, 409 and 411. These mutations are located upstream of the GCV‐resistance mutations and are close to the ATP‐binding and catalytic domains common to all kinases, consistent with MBV acting as a small molecule ATP‐competitive kinase inhibitor. So far, no UL97 mutations are known to confer resistance to both GCV and MBV. Copyright © 2008 John Wiley & Sons, Ltd.
Host factors for replication and transcription of the influenza virus genome
Authors: Nagata Kyosuke , Kawaguchi Atsushi , Naito Tadasuke
Published: March 2008

For replication and transcription of the influenza virus genome of eight‐segmented and negative‐stranded RNAs, not only viral factors but also host‐derived cellular factors (host factors) are required. This paper focuses on the identification and characterisation of the host factors involved in replication and transcription of the influenza virus genome, reviewing recent progresses in the related molecular mechanisms. Functional assay systems for screening of host factors using cell‐free reconstitution systems and an yeast‐based influenza virus replicon system are highlighted. We have summarised the property of host factors comprehensively and provided a clue for the perspective in the determination mechanism of host range and virulence and the development of a new strategy to control the influenza virus. Copyright © 2008 John Wiley & Sons, Ltd.