bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep‐water Corallium rubrum (L., 1758) from the Mediterranean Sea: preliminary genetic characterisation
Authors: Costantini Federica , Taviani Marco , Remia Alessandro , Pintus Eleonora , Schembri Patrick J. , Abbiati Marco
Published: September 2009

The precious red coral Corallium rubrum (L., 1758) lives in the Mediterranean Sea and adjacent Eastern Atlantic Ocean on subtidal hard substrates. Corallium rubrum is a long‐lived gorgonian coral that has been commercially harvested since ancient times for its red axial calcitic skeleton and which, at present, is thought to be in decline because of overexploitation. The depth distribution of C. rubrum is known to range from c. 15 to 300 m. Recently, live red coral colonies have been observed in the Strait of Sicily at depths of c. 600–800 m. This record sheds new light on the ecology, biology, biogeography and dispersal mechanism of this species and calls for an evaluation of the genetic divergence occurring among highly fragmented populations. A genetic characterization of the deep‐sea red coral colonies has been done to investigate biological processes affecting dispersal and population resilience, as well as to define the level of isolation/differentiation between shallow‐ and deep‐water populations of the Mediterranean Sea. Deep‐water C. rubrum colonies were collected at two sites (south of Malta and off Linosa Island) during the cruise MARCOS of the R/V Urania. Collected colonies were genotyped using a set of molecular markers differing in their level of polymorphism. Microsatellites have been confirmed to be useful markers for individual genotyping of C. rubrum colonies. ITS‐1 and mtMSH sequences of deep‐water red coral colonies were found to be different from those found in shallow water colonies, suggesting the possible occurrence of genetic isolation among shallow‐ and deep‐water populations. These findings suggest that genetic diversity of red coral over its actual range of depth distribution is shaped by complex interactions among geological, historical, biological and ecological processes.
All‐terrain vehicle crashes and associated injuries in north Queensland: Findings from the Rural and Remote Road Safety Study
Authors: O'Connor Teresa , Hanks Heather , Steinhardt Dale
Published: September 2009

Objective:  To define characteristics of all‐terrain vehicle (ATV) crashes occurring in north Queensland from March 2004 till June 2007 with the exploration of associated risk factors.

Design:  Descriptive analysis of ATV crash data collected by the Rural and Remote Road Safety Study.

Setting:  Rural and remote north Queensland.

Participants:  Forty‐two ATV drivers and passengers aged 16 years or over hospitalised at Atherton, Cairns, Mount Isa or Townsville for at least 24 hours as a result of a vehicle crash.

Main outcome measures:  Demographics of participants, reason for travel, nature of crash, injuries sustained and risk factors associated with ATV crash.

Results:  The majority of casualties were men aged 16–64. Forty‐one per cent of accidents occurred while performing agricultural tasks. Furthermore, 39% of casualties had less than one year's experience riding ATVs. Over half the casualties were not wearing a helmet at the time of the crash. Common injuries were head and neck and upper limb injuries. Rollovers tended to occur while performing agricultural tasks and most commonly resulted in multiple injuries.

Conclusions:  Considerable trauma results from ATV crashes in rural and remote north Queensland. These crashes are not included in most general vehicle crash data sets, as they are usually limited to events occurring on public roads. Minimal legislation and regulation currently applies to ATV use in agricultural, recreational and commercial settings. Legislation on safer design of ATVs and mandatory courses for riders is an essential part of addressing the burden of ATV crashes on rural and remote communities.
Pilot study on confocal endomicroscopy for determination of the depth of squamous cell esophageal cancer in vivo
Authors: Iguchi Youichi , Niwa Yasumasa , Miyahara Ryoji , Nakamura Masanao , Banno Kakunori , Nagaya Toshihiko , Nagasaka Tetsuro , Watanabe Osamu , Ando Takafumi , Kawashima Hiroki , Ohmiya Naoki , Itoh Akihiro , Hirooka Yoshiki , Goto Hidemi
Published: September 2009

Background and Aim:  Confocal endomicroscopy is ultra‐high‐magnification endoscopy with histological observation during ongoing endoscopy. We planned a pilot study of the diagnosis of the depth of esophageal cancer using confocal endomicroscopy for treatment strategies.

Methods:  Patients had 14 superficial esophageal cancers and one dysplasia. The depth of neoplasms in 15 lesions was confirmed by endoscopic mucosal resection or surgery.

We examined the rate of delineation and compared results of confocal imaging with histological findings. We classified two cellular and three microvascular patterns on confocal endomicroscopic images: CP‐N for normal squamous mucosa and CP‐Ca for cancerous lesion; VP‐type A for normal squamous mucosa; VP‐type B for T1a‐EP and T1a‐LPM cancers; and VP‐type C for T1a‐MM or a more invasive cancer pattern. We measured diameters of microvessels for the three patterns of confocal endomicroscopic images and histological specimens.

Results:  The rate of delineation was 73.3% (11/15) for esophageal cancer. The results of confocal imaging coincided well with microvessel distribution on horizontal histology. Two endoscopists blindly diagnosed the two types by cellular pattern and the three types by vascular pattern: their overall accuracies were 96% and 89% for the cellular pattern and 85% and 85% for the vascular pattern, respectively. The k value of the cellular pattern and the vascular pattern diagnosis was 0.84 and 0.75, respectively.

Conclusion:  Scoring and quantification of confocal endomicroscopic images may be useful for the differential diagnosis and diagnosis of superficial invasion by squamous cell carcinoma.
RIFLE classification as predictive factor of mortality in patients with cirrhosis admitted to intensive care unit
Authors: Cholongitas Evangelos , Calvaruso Vincenza , Senzolo Marco , Patch David , Shaw Steve , O'Beirne James , Burroughs Andrew K.
Published: September 2009

Background and Aim:  To evaluate the association of the Risk, Injury, Failure, Loss and End‐stage renal failure (RIFLE) score on mortality in patients with decompensated cirrhosis admitted to intensive care unit (ICU).

Methods:  A cohort of 412 patients with cirrhosis consecutively admitted to ICU was classified according to the RIFLE score. Multivariable logistic regression analysis was used to evaluate the factors associated with mortality. Liver‐specific, Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) and RIFLE scores on admission, were compared by receiver–operator characteristic curves.

Results:  The overall mortality during ICU stay or within 6 weeks after discharge from ICU was 61.2%, but decreased over time (76% during first interval, 1989–1992 vs 50% during the last, 2005–2006, P < 0.001). Multivariate analysis showed that RIFLE score (odds ratio: 2.1, P < 0.001) was an independent factor significantly associated with mortality. Although SOFA had the best discrimination (area under receiver–operator characteristic curve = 0.84), and the APACHE II had the best calibration, the RIFLE score had the best sensitivity (90%) to predict death in patients during follow up.

Conclusions:  RIFLE score was significantly associated with mortality, confirming the importance of renal failure in this large cohort of patients with cirrhosis admitted to ICU, but it is less useful than other scores.
Ease of early gastric cancer demarcation recognition: A comparison of four magnifying endoscopy methods
Authors: Kadowaki Shigenori , Tanaka Kyosuke , Toyoda Hideki , Kosaka Ryo , Imoto Ichiro , Hamada Yasuhiko , Katsurahara Masaki , Inoue Hiroyuki , Aoki Masatoshi , Noda Tomohiro , Yamada Tomomi , Takei Yoshiyuki , Katayama Naoyuki
Published: September 2009

Background and Aim:  Various techniques using magnifying endoscopy (ME) have been developed to enhance images of early gastric cancer (EGC) demarcations, which are often obscure. We investigated four ME methods to determine which is most effective in enhancing the recognition of EGC demarcations: conventional ME (CME), ME with narrow band imaging (NBI‐ME), enhanced‐magnification endoscopy with acetic acid (EME), and ME with NBI and acetic acid (NBI‐EME).

Methods:  Thirty‐seven successive patients having a total of 40 EGCs participated in the investigation. The endoscope was fixed and magnification images of EGC demarcations in each patient were recorded using four different ME methods (CME, NBI‐ME, EME and NBI‐EME). Eight experts and eight non‐experts scored each of the four images of each lesion for ease of recognition of demarcation (1 to 4, with 4 being easiest).

Results:  The mean scores of expert and non‐expert judges, respectively, for images acquired using each technique were: CME 1.23, 1.24; NBI‐ME 2.61, 2.95; EME 2.62, 2.32 and NBI‐EME 3.54, 3.50. There were significant differences between the mean scores for the four techniques (P < 0.0001) using one‐way repeated‐measures anova. In a Bonferroni's multiple comparison, the average scores (expert and non‐expert) of images acquired using NBI‐EME were significantly higher than those acquired using other methods; images acquired by NBI‐ME or EME also scored significantly higher than those by CME. Non‐experts also scored NBI‐ME images significantly higher than CME and EME images.

Conclusions:  Early gastric cancer demarcations were recognized most easily using NBI‐EME, and more easily using EME or NBI‐ME than CME.
Lymph node staging in esophageal squamous cell carcinoma: A comparative study of endoscopic ultrasonography versus computed tomography
Authors: Takizawa Kohei , Matsuda Takahisa , Kozu Takahiro , Eguchi Takako , Kato Hoichi , Nakanishi Yukihiro , Hijikata Atsushi , Saito Daizo
Published: September 2009

Background and Aim:  Endoscopic ultrasonography (EUS) is established as a standard approach for locoregional staging of esophageal cancer. However, only a few published studies have attempted to correlate the station of the abnormal lymph nodes detected by EUS with the definitive histology. We compared EUS and computed tomography (CT) in the initial staging of esophageal squamous cell carcinoma.

Methods:  Consecutive patients with esophageal cancer undergoing EUS were evaluated. EUS findings and patient data including histopatology were collected prospectively and analyzed retrospectively. Lymph node locations were divided into three groups; abdominal (A), paraesophageal (B), and thoracic paratracheal (C).

Results:  A total of 365 consecutive patients underwent EUS and 159 patients underwent esophagectomy without neoadjuvant chemotherapy. Thirty‐eight patients were excluded (insufficient EUS, etc.), and 121 patients were enrolled. The overall accuracy of EUS was 64% (sensitivity 68%, specificity 58%, positive predictive value [PPV] 68%), CT was 51% (sensitivity 33%, specificity 75%, PPV 64%), and CT + EUS was 64% (sensitivity 74%, specificity 50%, PPV 66%). The accuracy of EUS was higher than CT in Groups A and C. Sensitivity of CT was lower than that of EUS alone and CT + EUS.

Conclusions:  This study has demonstrated that EUS is a more accurate technique than contrast‐enhanced CT for detecting abnormal lymph nodes. Sensitivity of CT was lower than that of EUS alone and CT + EUS. But some metastatic lymph nodes in neck and abdominal fields are only detectable by CT. Therefore, both EUS and CT should be undertaken for routine examination prior to treatment of esophageal cancer.
Feasibility of individualized treatment for hepatitis C patients in the real world
Authors: Chen Tsung‐Ming , Huang Pi‐Teh , Lin Ching‐Heng , Tsai Ming‐Hung , Lin Lien‐Fu , Liu Chung‐Cheng , Ho Ka‐Sic , Tung Jai‐Nien
Published: September 2009

Background and Aim:  Individualized treatment with a combination of peg‐interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real‐life clinical setting.

Methods:  A total of 253 naïve patients with HCV infection who received peg‐interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non‐1 (HCV non‐1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV‐1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV‐1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24‐week treatment for HCV‐1 patients who achieved a rapid virological response, otherwise patients received a 48‐week course of treatment. Early termination of treatment at week 16 was recommended for non‐responders.

Results:  A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non‐1 infection. Among the HCV‐1‐infected patients, 53.5% of patients who underwent standard 24‐week treatment, 66.7% of patients who underwent standard 48‐week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV‐1 and treated by individualized therapy had a similar efficacy response compared with the standard 48‐week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220–2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189–6.855, P = 0.019) or standard 48‐week treatment (adjusted OR 3.733, 95% CI 1.073–12.986, P = 0.038) had significantly higher odds of SVR compared with HCV‐1 patients treated by standard 24‐week course.

Conclusion:  Individualized therapy is feasible in the real world, especially for patients with HCV‐1 infection.
N‐Acetylcysteine improves disturbed ileal contractility following partial hepatectomy in rats
Authors: Okay Erdem , Mutlu Oguz , Gocmez Semil S , Oz Sarpkaya , Utkan Tijen
Published: September 2009

Background and Aims:  It is well known that disturbed intestinal motility and bacterial overgrowth may occur following partial hepatectomy. These events have been followed by the translocation of enteric bacteria that play a major role in the development of infections. We designed the present study to evaluate the effect of N‐acetylcysteine (NAC) on ileal muscle contractility as an indication of intestinal motility.

Methods:  Sprague–Dawley rats were divided into four groups (n = 6): sham, sham plus preoperative intraperitoneal NAC injection, hepatectomy, and hepatectomy plus preoperative intraperitoneal NAC injection. Contractile and relaxant responses in isolated ileal smooth muscle strips were determined using an in vitro muscle technique. Statistical analyses were performed by Kruskal–Wallis and Mann–Whitney U‐tests.

Results:  Contractile responses to KCl and carbachol were significantly decreased in the ileal strips of the hepatectomy group when compared to the sham‐operated control group. The impaired contraction of strips was markedly improved by preoperative NAC treatment. However, neither the electrical field stimulation nor the sodium nitroprusside‐mediated relaxant responses changed in any of the groups.

Conclusions:  Our data indicated that disturbed ileal contractility after partial hepatectomy was remedied by preoperative NAC treatment, which in turn might cause attenuation of bacterial translocation.
Evaluation of esophageal function in patients with gastroesophageal reflux disease using transnasal endoscopy
Authors: Yasaka Shigeaki , Murakami Kazunari , Abe Takashi , Anan Juro , Mizukami Kazuhiro , Tanahashi Jin , Okimoto Tadayoshi , Kodama Masaaki , Kudo Yoshikuni , Kawasaki Hisanori , Fujioka Toshio
Published: September 2009

Background and Aims:  To investigate the utility of a new method of carrying out esophageal manometry using a narrow gauge manometry catheter via a transnasal endoscope.

Methods:  The Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a GERD‐specific questionnaire, was given to 45 subjects. Subjects 

underwent transnasal endoscopy with three dry and three wet (3 mL water) swallows. Direct observations of the primary peristaltic wave and peristaltic pressure measurement were conducted simultaneously.

Results:  Endoscopic observation of lower esophageal motility associated with swallowing revealed dilatation of the esophageal lumen after swallowing, followed by contraction in association with the primary peristaltic wave. The peristaltic pressure was significantly lower with increased FSSG scores for dry swallows (r = −0.347, P = 0.0212), but no significant correlation was seen for wet swallows.

Conclusions:  The significant negative correlation between reflux symptoms and peristaltic pressure in dry swallows was thought to be that reduced pressure immediately rostral to the lower esophageal sphincter leads to decreased clearance following gastric acid reflux, playing a large part in the onset of symptoms.
Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice
Authors: Larter Claire Z , Yeh Matthew M , Van Rooyen Derrick M , Teoh Narci C , Brooling John , Hou Jing Yun , Williams Jacqueline , Clyne Matthew , Nolan Christopher J , Farrell Geoffrey C
Published: September 2009

Background and Aims:  We previously reported that steatohepatitis develops in obese, hypercholesterolemic, diabetic foz/foz mice fed a high‐fat (HF) diet for 12 months. We now report earlier onset of steatohepatitis in relation to metabolic abnormalities, and clarify the roles of dietary fat and bodily lipid partitioning on steatosis severity, liver injury and inflammatory recruitment in this novel non‐alcoholic steatohepatitis (NASH) model.

Methods:  Foz/foz (Alms1 mutant) and wild‐type (WT) mice were fed a HF diet or chow, and metabolic characteristics and liver histology were studied at 2, 6, 12 and 24 weeks.

Results:  After 12 weeks HF‐feeding, foz/foz mice were obese and diabetic with approximately 70% reduction in serum adiponectin. Hepatomegaly developed at this time, corresponding to a plateau in adipose expansion and increased adipose inflammation. Liver histology showed mild inflammation and hepatocyte ballooning as well as steatosis. By 24 weeks, HF‐fed foz/foz mice developed severe steatohepatitis (marked steatosis, alanine aminotransferase elevation, ballooning, inflammation, fibrosis), whereas dietary and genetic controls showed only simple steatosis. While steatosis was associated with hepatic lipogenesis, indicated by increased fatty acid synthase activity, steatohepatitis was associated with significantly higher levels of CD36, indicating active fatty acid uptake, possibly under the influence of peroxisome proliferator‐activated receptor‐γ.

Conclusion:  In mice genetically predisposed to obesity and diabetes, HF feeding leads to restriction of adipose tissue for accommodation of excess energy, causing lipid partitioning into liver, and transformation of simple steatosis to fibrosing steatohepatitis. The way in which HF feeding ‘saturates’ adipose stores, decreases serum adiponectin and causes hepatic inflammation in steatohepatitis may provide clues to pathogenesis of NASH in metabolic syndrome.
Bone marrow stem cells and the liver: Are they relevant?
Authors: Eckersley‐Maslin Mélanie A , Warner Fiona J , Grzelak Candice A , McCaughan Geoffrey W , Shackel Nicholas A
Published: September 2009

The contribution of bone marrow stem cell responses to liver homeostasis, injury and malignancy is discussed in this review. Pluripotent stem cells or their more committed progenitor progeny are essential to tissue development, regeneration and repair and are widely implicated in the pathogenesis of malignancy. Stem cell responses to injury are the focus of intense research efforts in the hope of future therapeutic manipulation. Stem cells occur within tissues, such as the liver, or arise from extrahepatic sites, in particular, the bone marrow. As the largest reservoir of stem cells in the adult, the bone marrow has been implicated in the stem cell response associated with liver injury. However, in liver injury, the relative contribution of bone marrow stem cells compared to intrahepatic progenitor responses is poorly characterized. Intrahepatic progenitor responses have been recently reviewed elsewhere. In this review, we have summarized liver‐specific extrahepatic stem cell responses originating from the bone marrow. The physiological relevance of bone marrow stem cell responses to adult liver homeostasis, injury and malignancy is discussed with emphasis on mechanisms of bone marrow stem cell recruitment to sites of liver injury and its contribution to intrahepatic malignancy.
Rapid risk assessment using probability of fracture nomographs
Authors: PENMETSA R. , TUEGEL E. , SHANMUGAM V.
Published: September 2009

Traditional risk‐based design process involves designing the structure based on risk estimates obtained during several iterations of an optimization routine. This approach is computationally expensive for large‐scale aircraft structural systems. Therefore, this paper introduces the concept of risk‐based design plots that can be used for both structural sizing and risk assessment for fracture strength when maximum allowable crack length is available. In situations when crack length is defined as a probability distribution the presented approach can only be applied for various percentiles of crack lengths. These plots are obtained using normalized probability density models of load and material properties and are applicable for any arbitrary load and strength values. Risk‐based design plots serve as a tool for failure probability assessment given geometry and applied load or they can determine geometric constraints to be used in sizing given allowable failure probability. This approach would transform a reliability‐based optimization problem into a deterministic optimization problem with geometric constraints that implicitly incorporate risk into the design. In this paper, cracked flat plate and stiffened plate are used to demonstrate the methodology and its applicability.
Some issues on structural integrity analysis of P91 welds in power plants subjected to high temperature creep*
Authors: HYDE T. H. , SUN W. , YAGHI A. H. , LEEN S. B.
Published: September 2009

Welds are metallurgically complex, with heterogeneous structures within the weld metal and heat‐affected zones. In order to carry out a structural integrity assessment, it is important to have knowledge of the initial metallurgical features and the associated material property variations so that it is possible to accurately model all the possible failure modes of welds using, for example, numerical techniques. This paper describes some fundamental issues concerning a holistic process for high temperature performance and failure prediction assessment of power plant welds. This includes welding process simulation and residual stress determination, microstructural evolution and the formulation of creep damage mechanics constitutive equations including weld metal anisotropy. Typical examples, from specific case studies for P91 welds, are used to illustrate the application. Future requirements for development of high temperature assessment methods for welds are suggested.
Future perspectives for insulinotropic agents in the treatment of type 2 diabetes–DPP‐4 inhibitors and sulphonylureas
Authors: Gallwitz B. , Häring H.‐U.
Published: September 2009

The introduction of dipeptidyl‐peptidase IV inhibitors (DPP‐4 inhibitors) brought a novel class of insulinotropic agents into the treatment options for type 2 diabetes. This paper compares the actions, clinical efficacy and safety of sulphonylureas with those of the DPP‐4 inhibitors. First, the mode of action of both classes of antidiabetic agents is described. Then clinical studies for both substances in monotherapy and combination therapies are compared concerning their effects on glycaemic parameters and long‐term duration of action. Hypoglycaemia incidence and other adverse effects are compared and data on cardiovascular parameters and endpoints are summarized. The effects of sulphonylureas and DPP‐4 inhibitors on beta‐cell function and beta‐cell mass are highlighted. The present and future indications for both sulphonylureas and DPP‐4 inhibitors are discussed.
Multiple molecular targets underlie the antidiabetic effect of Nigella sativa seed extract in skeletal muscle, adipocyte and liver cells
Authors: Benhaddou‐Andaloussi A. , Martineau L. C. , Vallerand D. , Haddad Y. , Afshar A. , Settaf A. , Haddad P. S.
Published: September 2009

Aim:
Nigella sativa (N. sativa) is a plant widely used in traditional medicine of North African countries. During the last decade, several studies have shown that extracts from the seeds of N. sativa have antidiabetic effects.

Methods: Our group has recently demonstrated that N. sativa seed ethanol extract (NSE) induces an important insulin‐like stimulation of glucose uptake in C2C12 skeletal muscle cells and 3T3‐L1 adipocytes following an 18 h treatment. The purpose of the present study was to elucidate the pathways mediating this insulin‐like effect and the mechanisms through which these pathways are activated.

Results: Results from western immunoblot experiments indicate that in C2C12 cells as well as in H4IIE hepatocytes, but not in 3T3‐L1 cells, NSE increases activity of Akt, a key mediator of the effects of insulin, and activity of AMP‐activated protein kinase (AMPK), a master metabolic regulating enzyme. To test whether the activation of AMPK resulted from a disruption of mitochondrial function, the effects of NSE on oxygen consumption were assessed in isolated liver mitochondria. NSE was found to exhibit potent uncoupling activity.

Conclusion: Finally, to provide an explanation for the effects of NSE in adipocytes, PPARγ stimulating activity was tested using a reporter gene assay. Results indicate that NSE behaves as an agonist of PPARγ. The data supports the ethnobotanical use of N. sativa seed oil as a treatment for diabetes, and suggests potential uses of this product, or compounds derived thereof, against obesity and the metabolic syndrome.
The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes
Authors: Luzio S. D. , Dunseath G. , Lockett A. , Broke‐Smith T. P. , New R. R. , Owens D. R.
Published: September 2009

Aim: Randomized, open, single‐centre, two‐way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin).

Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m2, haemoglobin A1c (HbA1c) 7.4% (1.1). Two 6‐h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C‐peptide concentrations were determined throughout each 6‐h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self‐monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days.

Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280–330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC0–6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat‐dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA1c, weight and triglycerides were observed.

Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.
THE TEN COMMANDMENTS FOR OPTIMIZING VALUE‐AT‐RISK AND DAILY CAPITAL CHARGES
Authors: McAleer Michael
Published: September 2009

Abstract Credit risk is the most important type of risk in terms of monetary value. Another key risk measure is market risk, which is concerned with stocks and bonds, and related financial derivatives, as well as exchange rates and interest rates. This paper is concerned with market risk management and monitoring under the Basel II Accord, and presents Ten Commandments for optimizing value‐at‐risk (VaR) and daily capital charges, based on choosing wisely from (1) conditional, stochastic and realized volatility; (2) symmetry, asymmetry and leverage; (3) dynamic correlations and dynamic covariances; (4) single index and portfolio models; (5) parametric, semi‐parametric and non‐parametric models; (6) estimation, simulation and calibration of parameters; (7) assumptions, regularity conditions and statistical properties; (8) accuracy in calculating moments and forecasts; (9) optimizing threshold violations and economic benefits; and (10) optimizing private and public benefits of risk management. For practical purposes, it is found that the Basel II Accord would seem to encourage excessive risk taking at the expense of providing accurate measures and forecasts of risk and VaR.
UNDERSTANDING LABOUR MARKET FRICTIONS: AN ASSET PRICING APPROACH
Authors: Basu Parantap
Published: September 2009

Labour market friction is viewed in terms of the market value of an employed worker as opposed to the position of the Beveridge curve. This market value of an installed worker, which I call Tobin's Q of a worker, is inversely proportional to the average quality of the match between employers and workers. Based on this measure, I find that the labour market friction rises during a period of productivity boom. This phenomenon is indirectly supported by the data where it is found that the relative value of a worker with respect to tangible capital shows a positive association with the total factor productivity. The model suggests that firms may be compromising the quality of a skill match during a period of tight labour market conditions.
Time‐Adaptive Lines for the Interactive Visualization of Unsteady Flow Data Sets
Authors: Cuntz N. , Pritzkau A. , Kolb A.
Published: September 2009

The quest for the ideal flow visualization reveals two major challenges: interactivity and accuracy. Interactivity stands for explorative capabilities and real‐time control. Accuracy is a prerequisite for every professional visualization in order to provide a reliable base for analysis of a data set. Geometric flow visualization has a long tradition and comes in very different flavors. Among these, stream, path and streak lines are known to be very useful for both 2D and 3D flows. Despite their importance in practice, appropriate algorithms suited for contemporary hardware are rare. In particular, the adaptive construction of the different line types is not sufficiently studied. This study provides a profound representation and discussion of stream, path and streak lines. Two algorithms are proposed for efficiently and accurately generating these lines using modern graphics hardware. Each includes a scheme for adaptive time‐stepping. The adaptivity for stream and path lines is achieved through a new processing idea we call ‘selective transform feedback’. The adaptivity for streak lines combines adaptive time‐stepping and a geometric refinement of the curve itself. Our visualization is applied, among others, to a data set representing a simulated typhoon. The storage as a set of 3D textures requires special attention. Both algorithms explicitly support this storage, as well as the use of precomputed adaptivity information.
Geometry Images of Arbitrary Genus in the Spherical Domain
Authors: Gauthier M. , Poulin P.
Published: September 2009

While existing spherical parameterization algorithms are limited to genus‐0 geometrical models, we believe a wide class of models of arbitrary genus can also benefit from the spherical domain. We present a complete and robust pipeline that can generate spherical geometry images from arbitrary genus surfaces where the holes are explicitly represented. The geometrical model, represented as a triangle mesh, is first made topologically equivalent to a sphere by cutting each hole along its generators, thus performing genus reduction. The resulting genus‐0 model is then parameterized on the sphere, where it is resampled in a way to preserve connectivity between holes and to reduce the visual impact of seams due to these holes. Knowing the location of each pair of boundary components in parametric space, our novel sampling scheme can automatically choose to scale down or completely eliminate the associated hole, depending on geometry image resolution, thus lowering the genus of the reconstructed model. We found our method to scale better than other geometry image algorithms for higher genus models. We illustrate our approach on remeshing, level‐of‐detail rendering, normal mapping and topology editing.
Sediment Transport via Dam‐Break Flows over Sloping Erodible Beds
Authors: Emmett M. , Moodie T. B.
Published: September 2009

When a semi‐infinite body of homogeneous fluid initially at rest behind a vertical retaining wall is suddenly released by the removal of the barrier the resulting flow over either a horizontal or a sloping bed is referred to as a dam‐break flow. When resistance to the flow is neglected the exact solution, in the case of a stable horizontal bed with or without “tail water,” may be obtained on the basis of shallow‐water theory via the method of characteristics and the results are well known. Discrepancies between these shallow‐water based solutions and experiments have been partially accounted for by the introduction of flow resistance in the form of basal friction. This added friction significantly modifies the wave speed and flow profile near the head of the wave so that the simple exact solutions no longer apply and various asymptotic or numerical approaches must be implemented to solve these frictionally modified depth‐averaged shallow‐water equations. When the bed is no longer stable so that solid particles may be exchanged between the bed and the water column the dynamics of the flow becomes highly complex as the buoyancy forces vary in space and time according to the competing rates of erosion and deposition. It is our intention here to study dam‐break flows over erodible sloping beds as agents of sediment transport taking into account basal friction as well as the effects of particle concentrations on flow dynamics including both erosion and deposition. We consider shallow flows over initially dry beds and investigate the effects of changes in the depositional and erosional models employed as well as in the nature of the drag acting on the flow. These models include effects hitherto neglected in such studies and offer insights into the transport of sediment in the worst case scenario of the complete and instantaneous collapse of a dam.
Tranching and Rating
Authors: Brennan Michael J. , Hein Julia , Poon Ser‐Huang
Published: September 2009

In this paper we analyse the source and magnitude of marketing gains from selling structured debt securities at yields that reflect only their credit ratings, or specifically at yields on equivalently rated corporate bonds. We distinguish between credit ratings that are based on probabilities of default and ratings that are based on expected default losses. We show that subdividing a bond issued against given collateral into subordinated tranches can yield significant profits under the hypothesised pricing system. Increasing the systematic risk or reducing the total risk of the bond collateral increases the profits further. The marketing gain is generally increasing in the number of tranches and decreasing in the rating of the lowest rated tranche.
Social Capital Investment and Immigrant Economic Trajectories: A Case Study of Punjabi American Taxi Drivers in New York City
Authors: Mitra Diditi
Published: September 2009

Although the scholarship on social capital and immigrant economic incorporation has sufficiently documented how immigrants mobilize social capital in their search for employment which often leads to the formation of immigrant niches, how social capital is processed after immigrants acquire employment and its significance for the preservation of immigrant employment niches is less well explored. This paper addresses this gap in the literature with a case study of immigrant Punjabi taxi drivers in the New York metropolitan area. In particular, this study shows how a group of immigrant Punjabi taxi drivers mobilized social capital via embeddedness in co‐ethnic social networks and improved their working conditions – a process that must be considered in explanations of the Punjabi niche in the taxi industry for more than two decades. The study has implications for the relationship between social capital and the structure of the workplace or industry where immigrants are incorporated and its subsequent impact on immigrant economic trajectories. Further, this study contributes to the debate on the usefulness of ethnic communities for the adaptation of immigrant groups. Additionally, this research is relevant to the scholarship on the economic adaptation of South Asian (a subset of Asian Americans) immigrants, an understudied immigrant group in the United States.
NEUTRON TOMOGRAPHY AS A VALUABLE TOOL FOR THE NON‐DESTRUCTIVE ANALYSIS OF HISTORICAL BRONZE SCULPTURES
Authors: LEHMANN E. H. , DESCHLER‐ERB E. , FORD A.
Published: September 2009

This paper explains, with the example of a Roman object (the ‘Mars from Oberweningen’, Switzerland), why neutrons can be used preferentially for the non‐destructive analysis of metallic objects of relatively large size. This method is superior to the conventional X‐ray tomography method due to the higher penetration ability in metals such as copper, tin and even lead. With this method, differing materials can also easily be differentiated. In this way, the inner and outer structures of objects can be observed with the help of tools based on mathematical algorithms. Slices at arbitrary positions and segmentation of different material clusters aid the understanding of manufacturing processes and can describe the present preservation status. This helps in selecting optimal and additional conservation measures in museums for further preservation. Beside the qualitative overview on structure and inner properties of the objects, quantitative information can be derived about material content and composition. This method and the subsequently needed facilities for this method are available at PSI for similar studies on demand.
Drug transporters in the human blood‐placental barrier
Authors: Vähäkangas Kirsi , Myllynen Päivi
Published: September 2009

Studies on the increasing number of transporters found in the placental barrier are gaining momentum, because of their tissue‐specific expression, significance in physiology and disease, and the possible utilization of the emerging knowledge in pharmacology. In the placenta, both syncytiotrophoblast and fetal capillary endothelium express transporters. Fetal exposure is determined by the net effect of combination of transporters, their nature and localization in relation to placental cells and their substrate specificity. Although the significance of placental transporters on human fetal drug exposure is almost an unstudied field so far, their potential use to design drugs that do not cross the placenta is already being pursued. It is thus of interest to review the existing knowledge of human placental transporters. Transporters in all groups which take part in drug transport are found in human placenta. Especially, ATP‐binding cassette transporters ABCG2/breast cancer resistance protein, ABCB1/P‐glycoprotein and ABCC2/MRP2 are all expressed at the apical surface of syncytiotrophoblast facing maternal blood and are putatively important protective proteins both for placental tissue and the fetus, because they are efflux transporters and their substrates include many drugs and also environmental chemicals. Such protective effect has been shown in animals, but these results cannot be directly extrapolated to humans due to interspecies differences in placental structure and function. Experimental models utilizing human placental tissue, especially human placental perfusion, offer valuable possibilities, which have been insufficiently studied so far.
The NADPH oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+pump
Authors: Tazzeo T , Worek F , Janssen LJ
Published: September 2009

Background and purpose: Diphenyleneiodonium (DPI) is often used as an NADPH oxidase inhibitor, but is increasingly being found to have unrelated side effects. We investigated its effects on smooth muscle contractions and the related mechanisms.

Experimental approach: We studied isometric contractions in smooth muscle strips from bovine trachea. Cholinesterase activity was measured using a spectrophotometric assay; internal Ca2+pump activity was assessed by Ca2+uptake into smooth muscle microsomes.

Key results: Contractions to acetylcholine were markedly enhanced by DPI (10−4 M), whereas those to carbachol (CCh) were not, suggesting a possible inhibition of cholinesterase. DPI markedly suppressed contractions evoked by CCh, KCl and 5‐HT, and also unmasked phasic activity in otherwise sustained responses. Direct biochemical assays confirmed that DPI was a potent inhibitor of acetylcholinesterase and butyrylcholinesterase (IC50∼8 × 10−6 M and 6 × 10−7 M, respectively), following a readily reversible, mixed non‐competitive type of inhibition. The inhibitory effects of DPI on CCh contractions were not mimicked by another NADPH oxidase inhibitor (apocynin), nor the Src inhibitors PP1 or PP2, ruling out an action through the NADPH oxidase signalling pathway. Several features of the DPI‐mediated suppression of agonist‐evoked responses (i.e. suppression of peak magnitudes and unmasking of phasic activity) are similar to those of cyclopiazonic acid, an inhibitor of the internal Ca2+pump. Direct measurement of microsomal Ca2+uptake revealed that DPI modestly inhibits the internal Ca2+pump.

Conclusions and implications: DPI inhibits cholinesterase activity and the internal Ca2+pump in tracheal smooth muscle.
Vasodilator efficacy of nitric oxide depends on mechanisms of intracellular calcium mobilization in mouse aortic smooth muscle cells
Authors: Van Hove CE , Van der Donckt C , Herman AG , Bult H , Fransen P
Published: September 2009

Background and purpose: Reduction of intracellular calcium ([Ca2+]i) in smooth muscle cells (SMCs) is an important mechanism by which nitric oxide (NO) dilates blood vessels. We investigated whether modes of Ca2+mobilization during SMC contraction influenced NO efficacy.

Experimental approach: Isometric contractions by depolarization (high potassium, K+) or α‐adrenoceptor stimulation (phenylephrine), and relaxations by acetylcholine chloride (ACh), diethylamine NONOate (DEANO) and glyceryl trinitrate (GTN) and SMC [Ca2+]i(Fura‐2) were measured in aortic segments from C57Bl6 mice.

Key results: Phenylephrine‐constricted segments were more sensitive to endothelium‐derived (ACh) or exogenous (DEANO, GTN) NO than segments contracted by high K+solutions. The greater sensitivity of phenylephrine‐stimulated segments was independent of the amount of pre‐contraction, the source of NO or the resting potential of SMCs. It coincided with a significant decrease of [Ca2+]i, which was suppressed by sarcoplasmic reticulum (SR) Ca2+ATPase (SERCA) inhibition, but not by soluble guanylyl cylase (sGC) inhibition. Relaxation of K+‐stimulated segments did not parallel a decline of [Ca2+]i. However, stimulation (BAY K8644) of L‐type Ca2+influx diminished, while inhibition (nifedipine, 1–100 nM) augmented the relaxing capacity of NO.

Conclusions and implications: In mouse aorta, NO induced relaxation via two pathways. One mechanism involved a non‐cGMP‐dependent stimulation of SERCA, causing Ca2+re‐uptake into the SR and was prominent when intracellular Ca2+was mobilized. The other involved sGC‐stimulated cGMP formation, causing relaxation without changing [Ca2+]i, presumably by desensitizing the contractile apparatus. This pathway seems related to L‐type Ca2+influx, and L‐type Ca2+channel blockers increase the vasodilator efficacy of NO.
Alleviation of Both Water and Nutrient Limitations is Necessary to Accelerate Ecological Restoration of Waste Rock Tips
Authors: Williamson Julie C. , Rowe Ed C. , Hill Paul W. , Nason Mark A. , Jones David L. , Healey John R.
Published: September 2009

Hard rock quarries are commonly located close to national parks and special areas of conservation and are generally regarded as visually intrusive. Consequently, restoration strategies that effectively accelerate natural plant regeneration processes are required. Slate waste tips present extreme conditions for plant establishment with multiple potential limiting factors (e.g., lack of organic matter, nutrients, and poor water retention). In this study, we investigated ecological strategies to accelerate natural regeneration at the largest slate quarry in Europe. A field experiment was conducted to assess ecosystem restoration using a contrasting set of native woody species. Treatments included amendments of waste tips with: polyacrylamide gel to increase water‐holding capacity; mineral fertilizer to increase nutrient supply; and two treatments that increased both (organic waste or boulder clay addition). Ecosystem recovery was evaluated through above‐ and below‐ground productivity (plant and microbial, respectively) and soil analyses. Neither increasing nutrient supply (with mineral fertilizer) nor water‐holding capacity (with polyacrylamide gel) was sufficient, alone, to improve plant establishment. However, both boulder clay and organic waste amendment significantly enhanced plant growth. There was a marked positive interaction in the effects on tree growth of the amendment with organic waste and boulder clay. Large interactions occurred between tree species and substrate amendments. The growth of N2‐fixing species was strongly favored over non‐fixers where there was no addition of material increasing soil nitrogen supply, whereas the growth advantage of pioneer species over non‐pioneers was greatest with fertilizer, organic waste, or clay additions. Organic waste addition had the greatest positive impact on soil processes.