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Effective prevention of chronic postoperative pain is an important clinical goal, informed by a growing body of studies. Peri-operative regional anaesthesia remains one of the most important tools in the multimodal analgesic toolbox, blocking injury-induced activation and sensitisation of both the peripheral and central nervous system. We review the definition and taxonomy of chronic postoperative pain, its mechanistic basis and the most recent evidence for the preventative potential of multimodal analgesia, with a special focus on regional anaesthesia. While regional anaesthesia targets several important aspects of the mechanistic pathway leading to chronic postoperative pain, evidence for its efficacy is still mixed, possibly owing to the heterogeneity of risk profiles within the surgical patient, but also to variation in techniques and medications reported in the literature.

In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.

The purpose of the study was to evaluate the impact of single nucleotide polymorphisms (SNPs) of Cytochrome P450 (CYP) 3A5 and adenosine triphosphate-binding cassette B1 (ABCB1) genotypes on TAC pharmacokinetics in Chinese paediatric patients.A total of 136 Chinese paediatric liver recipients (R) and their donors (D) were divided into groups according to their CYP3A5 genotypes [expression of *1 allele: expressor (EX) or non-expressor (NEX)].Both recipient and donor CYP3A5*1 alleles had impacts on the TAC pharmacokinetics after liver transplantation. EX-R/EX-D recipients required a significantly higher TAC daily dose compared with NEX-R/NEX-D (0.24 ± 0.08 vs. 0.14 ± 0.06 mg/kg/day, p0.01). Age was also an independent factor on TAC requirement. Compared with EX-R/EX-D, non-expressor infants or recipients over 3-years old needed0.2 mg/kg/day. None of the ABCB1 SNPs (1236CT, 2677GA/T, 3435CT) had an impact on TAC pharmacokinetics. However, EX-R/EX-D recipients bearing the ABCB1 1236-CC genotype required a much higher TAC dose than those without this genotype (0.23 vs. 0.18 mg/kg/day, p0.01), who required a similar TAC dose to that of NEX-R/NEX-D children. Furthermore, EX-R/EX-D with ABCB1 1236-CC recipients exhibited an markedly higher incidence of acute rejection and transplant-related infections clinically.CYP3A5 and ABCB1-1236 genotyping, in addition to recipient age, are necessary for establishing a more accurate TAC dosage regimen in paediatric liver recipients. We should be cautious regarding the treatment of paediatric recipients with both CYP3A5-expressor and ABCB1 1236-CC genotypes with TAC, as these patients are more susceptible to acute rejection and infection.

Objectives To determine the risk of diabetes mellitus (DM) in patients with myasthenia gravis (MG) in a large cohort representing 99% of the Taiwan population. Methods Data from the Taiwan National Health Insurance Database were used to conduct retrospective cohort analyses. The study cohort comprised 1520 patients with MG who were four-fold frequency matched to those without MG by age and sex, and assigned the same index year. Cox proportional hazard regression analysis was conducted to estimate the risk of DM. Results The MG cohort had a 1.26-fold increased risk of developing DM compared with the comparison cohort (HR = 1.26, 95% CI = 1.04–1.53). MG patients without corticosteroids use had no increased risk of developing DM (HR = 1.05, 95% CI = 0.79–1.40), and MG patients with corticosteroids use had a 1.46-fold increased risk of developing DM (HR = 1.46, 95% = 1.15–1.86). In addition, patients with MG received aggressive treatment, associated thyroid diseases, and male patients had higher risk of DM. Conclusion This population-based retrospective cohort study demonstrates that MG is associated with a high risk of DM, which might be related to the adverse effect of corticosteroid and aggressive therapy.

The relationship between glutathione S-transferase M1 (GSTM1) genetic polymorphisms and lung cancer has been reported previously. However, the results are not consistent. Therefore, to clarify the association between GSTM1 polymorphisms and lung cancer, we performed a meta-analysis based on published studies. We used the Revman 5.0 software to perform literature retrieval, article selection, data collection, and statistical analysis. We utilized a random-effect model to pool the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible studies including 5737 lung cancer patients and 6843 cancer-free control subjects were analyzed. We found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.15, 95%CI = 0.98-1.36, P = 0.08). Including only Chinese individuals, we found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.13, 95%CI = 0.97-1.32, P = 0.13). In conclusion, we found that GSTM1 polymorphisms are not associated with lung cancer risk.

Even though a growing number of studies have found that patients with ankylosing spondylitis (AS) suffer from sexual problems, only very few studies have specifically addressed the relationship between AS and ED. Using a population-based data set, this case-control study aimed to examine the association of ED with a prior diagnosis of AS in Taiwan. We selected 2213 ED patients ≥40 years old and 17,704 matched controls. We considered the date of the first diagnosis of ED as the index date for cases. Multivariate logistic regression was performed to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between previously diagnosed AS and ED. A total of 224 out of the 19,917 sampled subjects (1.1%) had been diagnosed with AS before the index date. Prior AS was found in 42 (1.9%) cases and 182 (1.0%) controls. After adjusting for geographic location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, depressive disorder and alcohol abuse/alcohol-dependence syndrome, multivariate logistic regression revealed that cases were more likely to have been previously diagnosed with AS than controls (OR=1.58, 95% CI=1.09-2.19, P=0.019). There was an association between ED and AS. We suggest that physicians should be attentive to sexual complaints from AS patients in order to refer them to other specialists for multidisciplinary management.

The development and use of vaccines and their ability to prevent infection/disease is a shining example of the benefit of biomedical research. Modern vaccines often utilize subunit immunogens that exhibit minimal immunogenicity and require the use of adjuvants to maximize the induction of protective immune responses. We recently described a novel class of vaccine adjuvants, mast cell (MC) activators, that exhibit safe and effective vaccine adjuvant activity when administered by intranasal or intradermal routes. A compound library containing 580 functionalized benzopyrans, a structural motif found in a diverse array of natural and designed bioactive compounds, was screened using a MC degranulation assay to identify novel MC activating compounds for future evaluation as novel vaccine adjuvants. This approach identified 12 novel MC degranulating compounds. Therefore, MC degranulation can be used to reliably detect novel compounds for evaluation as adjuvants for use in mucosal vaccine strategies.

Background Numerous studies focus on intramuscular (i.m.) injection of hypertonic saline-induced muscle pain and nociception. The spatio-temporal characteristics and dynamic variation of spinal neuronal activities elicited by i.m. hypertonic saline remain unknown. Methods The spatio-temporal variations of c-Fos expression in the lumbar spinal cord exposed to i.m. injection of 5.8% saline were investigated in male rats. Results After a unilateral i.m. 5.8% saline injection, c-Fos expression in dorsal horn of spinal L4-6 segments was significantly enhanced bilaterally (p

Modern studies have shown that the X control charts with variable parameters (VPs) detect process shifts faster than the traditional X control charts. This article developed the economic design of the VP X control chart to determine the values of the design parameters of the chart. However, this study, different from previous studies, was focused on the process that is subject to a disturbing cause, and the occurrence of the cause can result in a fuzzy mean shift (ie the magnitude of the mean shift could not be recognized exactly). The issue of economically selecting the design parameters for the chart was firstly formulated as a mathematical programming model with a fuzzy objective function that could cope with fuzzy number type of mean shift. A fuzzy-simulation-based genetic algorithm was then employed to search for the optimal values of the design parameters from the model. An industrial example was provided to illustrate the solution procedure, and was used for comparison between the VP and the traditional X chart. Effects of model parameters on the solution of the economic design were also discussed.

A Monte-Carlo-based methodology is presented for physics-based probabilistic uncertainty analysis of aerothermodynamics and thermal protection system (TPS) material response modeling for aerocapture or direct entry missions. The objective of the methodology is to identify and quantify the most important sources of uncertainty in aeroheating and the resulting thermal protection material selection, design, and sizing based on inaccuracies in current knowledge of the parametric input modeling parameters. The resulting parametric modeling uncertainty would be combined with other uncertainty sources to determine the final aeroheating and TPS response modeling uncertainty for a given application, which can then be used to define appropriate margins and factors of safety that should be applied to the TPS. These techniques facilitate a risk-based probabilistic design approach, whereby the thermal protection system can be designed to a desired risk tolerance, and any remaining risk can be effectively compared to that of other subsystems via a system-level risk mitigation analysis. Modeling sensitivities, which are a byproduct of the uncertainty analysis, can be used to rank input uncertainty drivers. Key input uncertainties can then be prioritized and targeted for further analysis or testing. The strengths and limitations of this technique are discussed. Sample results are presented for two cases: Titan aerocapture and Mars Pathfinder. These cases demonstrate the utility of the methodology to quantify the uncertainty levels, rank sources of input uncertainty, and assist in the identification of structural uncertainties in the models employed.

Cutaneous vasculitis (CV) is a condition with cutaneous manifestations and possible systemic involvement. The causative factors or associated diseases are usually drugs, infection, collagen vascular disease, or malignancy. Syphilis as a cause of cutaneous vasculitis is rare. We report the case of a large cutaneous ulcer and small-vessel vasculitis associated with syphilis infection. We suggest that in apparently idiopathic CV or a chronic ulcer refractory to treatment, screening should be performed to detect any underlying infection such as syphilis. It is important to have a rapid and accurate diagnosis because the lesions are very contagious, but may be rapidly and completely cured by early administration of antibiotic treatment.

A configuration for aerocapture at Neptune is considered with an emphasis on reduction of the overall aeroshell thermal protection system mass. The biconic vehicle is assumed to be capable of bank angle as well as angle-of-attack modulation for guidance and optimal trajectory shaping. A methodology is presented for determining a nominal trajectory that robustly accommodates off-nominal flight conditions with relatively small dispersions in integrated heat load. Such a trajectory, termed nominal robust, is presented for bank-only guidance. A nominal-robust trajectory is also generated for guidance with both angle-of-attack and hank modulation. Simulation of a nominal-robust trajectory with angle-of-attack modulation in the presence of multiple stacked off-nominal conditions is described. The resulting reduction of maximum heat rate and heat load relative to the undershoot and overshoot trajectories is quantified. The thermal protection system response based on closed-loop trajectory simulations for worst-case off-nominal scenarios is calculated and compared with the traditional overshoot/undershoot thermal protection system design method. The results show that the use of the nominal-robust methodology results in a significant decrease in aeroshell mass, and that combined bank and angle-of-attack modulation further reduces trajectory dispersion and stagnation-point-integrated heat load as compared to pure bank-angle modulated trajectories.

Aim To present a case of adenoid cystic carcinoma (ACC) in the mandible, and manifesting as a periapical lesion. Summary A 56-year-old male suffered from pain around the right mandibular first molar for approximately 1 week. Oral examination revealed that the involved tooth was restored by a full coverage crown with no obvious abnormalities. A periapical radiograph revealed two ill-defined radiolucencies associated with the tooth, one over the mesial and another over the distal roots of the tooth; incomplete root filling and furcation involvement also being noted. The affected tooth was extracted based on the clinical impression of apical periodontitis. The surrounding tissue of the root apex was curetted and sent for histopathological examination, which revealed ACC. Key learning points • Adenoid cystic carcinoma affecting the mandible may mimic a periapical lesion. Proper diagnosis of such a lesion is dependent on thorough clinical, radiographic and microscopic examinations. • Such a case highlights the benefits of biopsy and histological examination of collected tissues. • Diagnosis of lesions in the mandible should include salivary gland tumours.

Since Reynolds et al. [1] proposed the variable sampling interval (VSI) X control chart, the statistical properties of the chart have been discussed and shown to be better than the traditional control chart in which the sampling intervals length are fixed. However, the VSI charts are, like the traditional charts, still costly when they are used for the prevention of defective products. For this reason, an appropriate design is necessary before it is used. In this paper, a VSI X control chart is used for monitoring non-normal process data, which is widely encountered in practice. Then, a cost-quality model based on the Burr distribution is proposed for constructing an economic-statistical design for the VSI X chart. The design of the chart has been developed considering the optimisation of the cost function in this model posed by statistical constraints. The design parameters can be derived through the evolutionary search method, and the overall finding indicates that the designed VSI chart always outperforms the traditional control chart with respect to the expected cost per unit time. This model is also suitable for normally distributed data; thus, it is suitable for a general application.

This paper reports an experimental method of measuring the colour change of wet paint when subject to a well-defined shear flow. Using a Multi-Pass Rheometer (MPR) and a modified colour spectrophotometer, the effect of shear on the colour changes of a red-pigmented paint were systematically studied. Substantial changes in paint colour during and after shear were observed for certain paint compositions. Additional direct optical observation on diluted paint samples strongly suggested that the key mechanism associated with the colour change was the state of pigment agglomerates during shear and the flocculation after shear. A model based on Mie scattering was developed to give a semi-quantitative prediction of the observed experimental trends.

We experimentally investigate a high output power L-band (1565–1605 nm) erbium-doped fiber amplified spontaneous emission (ASE) source using dual forward-pumping configuration. Such configuration allows high pumping-power operation and enhances the pumping efficiency. The high pumping efficiency of 36.1% is achieved for such ASE source with a mirror reflectance of 30%. The output power of about 72.2 mW and a linewidth of 40.8 nm with a power ripple of 0.7 dB are obtained without using any external spectral filters.

Y.-K. Chen, S.-S. Hsuen, L.-M. Lin: Increased expression of inducible nitric oxide synthase for human oral submucous fibrosis, verrucous hyperplasia, and verrucous carcinoma. Int. J. Oral Maxillofac. Surg. 2002; 31: 419-422. 2002 Published by Elsevier Science Ltd on behalf of the International Association of Oral and Maxillofacial Surgeons. Abstract. Three isoforms of nitric oxide synthase (NOS), endothelial, neuronal and inducible NOS (iNOS), have been identified in humans. Enhanced expression of iNOS protein has been previously reported for human oral epithelial dysplasias, a human oral premalignant epithelial lesion; however, this expression has not been demonstrated for other premalignant epithelial lesions, namely, oral submucous fibrosis (SF) and verrucous hyperplasia (VH). On the other hand, iNOS protein expression has not been reported in human oral verrucous carcinoma (VCa). The aim of this current study was to determine whether iNOS protein also occurs for oral SF, VH and VCa lesions. We found that membranous stainings were observed chiefly in oral SF lesions (17/20, 85%), whereas cytoplasmic stainings were mainly found in the VH variants (16/20, 80%). By contrast, cytoplasmic and/or nuclear stainings were observed in the specimens of verrucous carcinoma (17/20, 85%). Since no iNOS activity could be detected for any of our specimens of normal buccal mucosa in the present immunohistochemical study, this suggests that an NOS-dependent mechanism may be involved in the malignant transformation of these two premalignant oral epithelial lesions.

Since the introduction of endoscopic retrograde cholangiopancreatography (ERCP) by McCune et al. in 1968 (1) and endoscopic sphincterotomy (ES) in 1974 (2), there has been a rapid proliferation of endoscopic techniques for the diagnosis and treatment of benign and malignant biliary and pancreatic disorders. Although therapeutic ERCP has been a well-established modality for management of biliary tract disorders, its role in pancreatic diseases is still evolving (3-5). The limited number of randomized clinical trials and concern over potentially serious complications have prevented its widespread use in pancreatic disorders (6). Proper application of these therapeutic techniques and more randomized trials are needed to identify those patients with pancreatic disorders who will benefit most from endoscopic therapy. Various pancreatic disorders in which endoscopic therapy has been successfully applied are summarized in Table 1. Here we review the current status of endoscopic therapy in benign pancreatic disease.

An implicit ablation and thermal response program is presented for simulation of one-dimensional transient thermal energy transport in a multilayer stack of isotropic materials and structure which can ablate from a front surface and decompose in-depth. The governing equations and numerical procedures for solution are summarized. Solutions are compared with those of an existing code, the Aerotherm Charring Material Thermal Response and Ablation Program, and also with arcjet data Numerical experiments show that the new code is numerically more stable and solves a much wider range of problems compared with the older code. To demonstrate its capability, applications for thermal analysis and sizing of aeroshell heatshields for planetary missions, such as Stardust, Mars Microprobe (Deep Space n), Saturn Entry Probe, and Mars 2001, using advanced light-weight ceramic ablators developed at NASA Ames Research Center, are presented and discussed.

Barrett's epithelium is a risk factor for esophageal cancer. In this study we attempted to reverse Barrett's epithelium in an acid-reduced environment by using multipolar electrocoagulation.All patients had specialized columnar epithelium of at least 2 cm in length. Patients with dysplasia on successive screening examinations were excluded. Esophageal motility and 24-hour pH studies were performed before therapy and at 9 and 18 weeks. All patients received lansoprazole 30 mg twice a day regardless of pH study results. Multipolar electrocoagulation was applied to one side of the esophagus (2 to 3 cm per session) with the contralateral side serving as control. Biopsies were obtained from each 2 cm length at each endoscopy and reviewed by a single, blinded pathologist. At the 9-week evaluation of the treatment side, all patients elected to undergo multipolar electrocoagulation therapy for the control side.Twenty-seven patients completed the study: 21 men and 6 women, ages 33 to 81 years, length of specialized columnar epithelium 2 to 10 cm. Endoscopy at the 18-week follow-up showed normal mucosa (n = 16), residual small (3 mm) islands or tongue-shaped extensions of apparent specialized columnar epithelium (n = 7), untreated distal strips (5 mm) of apparent specialized columnar epithelium at the gastroesophageal junction (n = 3), and persistent specialized columnar epithelium (n = 1). Histologically, only 5 of 27 patients had residual specialized columnar epithelium at week 18. Of 16 patients with a normal endoscopic appearance, one still had specialized columnar epithelium on biopsy. While on lansoprazole, pH studies were normal in 15 of 26 patients at 9 weeks. Of 22 patients with histologic evidence of specialized columnar epithelium reversal, 10 had persistently abnormal 24-hour pH studies (pH4, 6.1% to 33.7% of total time). Four of five patients with residual specialized columnar epithelium on biopsy had persistent reflux. Side effects of multipolar electrocoagulation were transient, and treatment did not adversely alter motility patterns.Multipolar electrocoagulation therapy can induce re-epithelialization with normal squamous mucosa in most patients with specialized columnar epithelium and does not adversely affect esophageal motility. Adequate acid suppression is not mandatory for therapy to be effective in the short term.

Background: Flumazenil is an imidazobenzodiazepine that blocks the central effects of benzodiazepines by competitive interaction at the receptor level. In this study we assessed the impact of flumazenil use on postsedation observation time in outpatients undergoing endoscopy. Methods: Sixty outpatients received midazolam for conscious sedation and were randomized after endoscopy to receive intravenous flumazenil (0.1 mg/mL) or placebo until awake or a total of 10 mL was given. All patients were assessed using various psychomotor and cognitive tests at baseline and at 5, 15, 30, 45 and 60 minutes after flumazenil or placebo was administered. Results: The two groups were similar in age, gender, midazolam dose (mg/kg), vital signs, and baseline parameters. The average dose of flumazenil given was 0.41 mg. Sedation scores returned to presedation levels earlier in the flumazenil group, with significant differences compared to placebo at 5 minutes (84.6% vs. 24.2%), 15 minutes (88.5% vs. 57.6%) and 30 minutes (96.2% vs. 66.7%). Other parameters tested were not significantly different for patients receiving placebo compared to those given flumazenil. Sedation scores returned to baseline earlier than other psychomotor and cognitive tests in both groups. Flumazenil reduced the mean observation time from 23.5 minutes to 8.3 minutes (p < 0.0005), a difference of 15.2 minutes (64.7%) based on sedation score. Conclusions: Flumazenil significantly reduces postsedation observation time. Actual cost savings will vary depending on staff and facility capacity, patient volume, flumazenil cost, and unit cost of observation time. (Gastrointest Endosc 1999;49:573-9.)

We have fabricated InGaAs/InP based DHBTs for high speed circuit applications. A process involving both wet chemical and ECR plasma etching was developed. Carbon was employed as the p-type dopant of the base layer for excellent device stability. Both the emitter–base and base–collector regions were graded using quaternary InGaAsP alloys. The extrinsic emitter–base junction is buried for junction passivation to improve device reliability. The use of an InP collector structure with the graded region results in high breakdown voltages of 8-10 V, with no current blocking. The entire structure is encapsulated with spin-on-glass. These devices show no degradation in d.c. characteristics after operation at an emitter current density of 90 kA cm −2 and a collector bias, V CE , of 2 V at room temperature for over 500 h. Typical common emitter current gain was 50. An f t of 80 and f max of 155 GHz were achieved for 2×4 μ m 2 emitter size devices.

High performance semiconductor optoelectronic devices have powered coherent dense wavelength division multiplexing transceivers with a channel data rate from 100Gb/s to 1 Tb/s. As the coherent technology proliferates from the core network into metro and data center applications, higher integration level of these coherent optical components is highly desirable to reduced the cost of the coherent transceiver and optical port density. Recent advances in the semiconductor optoelectronic component technologies and the associated electro-optical integration platform, such as planar lightwave circuits, silicon photonics and compound semiconductor photonics integrated circuits, will be surveyed and discussed.

This empirical research is based on the relevant theoretical research and previous circumstances to develop a case study to explore in space planning for disaster prevention and relief. The research aims to establish a database system of disaster prevention and rescue sites for urban disaster prevention planning in Tainan metropolis, Taiwan. Historical data of Tainan metropolis were analyzed to construct a customized disaster information system. Through constructing a disaster prevention and rescue site system, a service size of fundamental refuge rings in Tainan metropolis was calculated, and influences on hazard sites and potentials of flood hazard toward refuge sites were evaluated. Using the software of MapInfo as an external platform for the database and MapBasis as internal system content, we develop a customized model for Tainan metropolis based on its refuge shelters, hazard sites, rescue locations, route system, and resources. The system provides city government officers and rescue sectors with space information, specific site inquiry, and detailed information of a particular site. This research also proposes some strategies for space planning on disaster prevention and rescue sites.

Background. Frontal lobe atrophy (FLA) is associated with late life depression. However, the role that FLA plays in the development of depression after stroke (DAS) remains unknown. This study thus examined the association between FLA and DAS.Methods. A convenience sample of 705 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. A psychiatrist administered the Structural Clinical Interview for DSM-IV to all patients and made a diagnosis of DAS three months after the index stroke.Results. Eighty-five (12.1%) patients were diagnosed with DAS. In univariate analysis, the DAS patients were more likely to have severe FLA (14.1% versus 5.6%). Severe FLA remained an independent predictor of DAS in multivariate analysis, with an odds ratio of 2.6 (95% confidence intervals = 1.2–5.9).Conclusions. The results suggest that FLA may play a role in the pathogenesis of DAS, which supports the hypothesis that cumulative vascular burden may be important in predicting DAS. Further investigations are needed to clarify the impact of FLA on the clinical presentation, treatment response, and outcome of DAS in stroke survivors.

Background and study aims Complete examination of the biliary tree and pancreatic duct may be difficult or unsuccessful using conventional imaging instruments. The purpose of this study was to evaluate the cannulation success rate, clinical utility, and safety of a new catheter-based ultrasound probe (CBUSP) used in the biliary tree and pancreas. Patients and methods The probes used in this study are manufactured by Microvasive (Watertown, MA, U.S.A.) and were 6.2 Fr in diameter, operated at 12.5 MHz. Thirty-six patients (11 with malignant bile-duct strictures, 12 with benign bile-duct strictures, two with bile duct stones, three with pancreatic duct strictures, one with a pancreatic cyst, one with pancreas divisum, three with sphincter of Oddi dysfunction, and three normal) underwent examination with a CBUSP. Results Cannulation was successful in all 36 patients. The hepatic artery and portal vein could be visualized with the probe in the proximal bile duct in 81% and 94% of the cases, respectively. The portal vein could not be adequately visualized in any patients when the probe was in the distal bile duct. The mean thickness of the normal bile duct wall was 0.17 cm, and the mean wall thicknesses proximal to a benign and malignant stricture were 0.16 and 0.17 cm, respectively. The mean thicknesses of benign and malignant biliary strictures were 0.32 cm and 0.31 cm, respectively (not significant). Eight of 12 benign biliary strictures (67%) and five of 11 malignant strictures (45%) were symmetrical. However, no obvious differences could be identified between benign and malignant biliary strictures. There were no catheter related complications. Conclusions Further catheter modifications are needed, but it appears to be feasible to assess vascular invasion in cholangiocarcinoma and to characterize biliary strictures in a way that may be able to influence therapy options in some patients. The currently available CBUSP cannot distinguish between benign and malignant strictures. However, with technical modifications, this may be possible in the future. The clinical usefulness of CBUSP in the pancreas awaits further investigation, but pancreatic imaging is feasible.

Dysthyroidism has been highlighted as a common endocrine disorder associated with erectile dysfunction (ED); however, to date, no large-scale population-based study has investigated the association between hyperthyroidism and ED. This case-control study aimed to explore the association between ED and hyperthyroidism using a population-based data set. In total, 6310 adult patients who received new diagnoses of ED were recruited as cases together with 18 930 matched enrollees with no history of ED who served as controls. Conditional logistic regressions were conducted to explore the association between ED and having been previously diagnosed with hyperthyroidism. In total, 569 (2.3%) of the 25 240 sampled subjects had been diagnosed with hyperthyroidism before the index date; hyperthyroidism was found in 207 (3.3%) cases and 362 (1.90%) controls. After adjusting for potential confounding factors, the odds ratio (OR) of prior hyperthyroidism among cases was 1.64 (95% confidence interval=1.37-1.96, P0.001) than that of controls. No association was detected between prior hyperthyroidism and ED for the 18-30, 30-39 and70 age groups. Subjects aged between 60 and 69 years had the highest ORs for prior hyperthyroidism among cases when compared to controls (OR=1.84; 95% confidence interval=1.20-2.84; P0.001). Our study further confirms the existence of an association between ED and prior hyperthyroidism.

In recent years, combination therapy has received growing popularity as a powerful therapeutic tactic for the treatment of diseases. The justifications and benefits of combination therapy are far-reaching, including but not limited to addressing unmet medical needs such as cancer, malaria, and HIV/AIDS, improved clinical efficacy and safety with reduced dosage of a single medication, understanding the underlying science of the disease, alleviating pharmaco-economic impacts, and better drug life-cycle management. Using the ezetimibe/simvastatin combination therapy as a case study, a comprehensive overview of the successful discovery and development of the single-pill combination, Vytorin, is presented in this review. A cursory introduction to combination therapy and the rationale for the ezetimibe/simvastatin combination for the treatment of hyperlipidemia provides an instructive entry point. The discovery and mode of action of simvastatin and ezetimibe monotherapies set the scene for a detailed discussion on the discovery and development of Vytorin, with emphasis on bioequivalency studies, clinical efficacy and safety profile studies, and the economic consequences of the single-pill combination therapy. Large-scale outcome clinical trials are also discussed to demonstrate the long-term effects of Vytorin.

In this tutorial review, recent advances in the synthesis of cyclopropane-containing natural products are discussed, highlighting the application of novel synthetic methodologies and innovative synthetic strategies in the construction of highly functionalized cyclopropanes. The examples showcased herein aim to inspire students and practitioners of organic synthesis to seek further advances in the chemical synthesis of cyclopropanes, both in the context of target-oriented syntheses and method developments.

Patients with giant duodenal ulcer (> 2 cm) have more ulcer complications (ie, bleeding) than patients with duodenal ulcer in the standard range (0.5-1.5 cm). To evaluate possible differences between patients with giant duodenal ulcer and those with duodenal ulcer in the standard range, we determined basal acid outputs by nasogastric suction, percentage of patients with daily nonsteroidal antiinflammatory drug (NSAID) use, and percentage of ulcer complications in 184 patients with endoscopically documented active duodenal ulcer. Seventeen patients had giant duodenal ulcer, and 167 patients had duodenal ulcer in the standard range. The mean basal acid outputs for the 17 patients with giant duodenal ulcer was 7.9 meq/hr (range 0.0-27.8 meq/hr) and for the 167 patients with duodenal ulcer in the standard range was 9.0 meq/hr (range 0.0-49.1 meq/hr), which were not significantly different. There was a significant difference in the percentages of ulcer complications between the 17 patients with giant duodenal ulcer and the 167 patients with duodenal ulcer in the standard range: 65% compared to 25% (P = 0.001), and in the percentages of patients with regular daily NSAID use, during the one month preceding the upper gastrointestinal endoscopy: 53% compared to 8% (P = 0.00001). However, a significant association between NSAID use and duodenal ulcer complication was not apparent. These results suggest that the development of giant duodenal ulcer and the significant increase in complications associated with giant duodenal ulcer are not attributable to increased basal acid output, however, they may be attributable to increased NSAID use.

A modular strategy leading to the salvileucalin B core structure has been accomplished. The developed synthetic strategy featured a bioinspired intramolecular Diels–Alder reaction to construct domain “A”, REDOX chemistry to functionalize domain “B”, and a palladium-mediated cross-coupling to install domain “C”. This flexible approach should facilitate further chemical and biological investigations of this fascinating class of compounds.

We review the recent development in real-time coherent optical OFDM (CO-OFDM) transmission for their algorithm and implementation. The unique challenge of real-time implementation of OFDM for high speed optical data transmission including relatively large phase noise, frequency offset and dynamically changing optical channels are discussed. The fundamental digital signal processing (DSP) architectures of transmitter and receiver are presented in the manner achievable in state of the art field-programmable gate arrays (FPGAs) or application-specific integrated circuits (ASICs). Primary DSP components' algorithms and implementations are presented and discussed. The successful demonstration of real-time CO-OFDM receivers includes a receiver with sampling rate of 2.5-Gsamples/s to receive a 3.55-Gb/s single channel and 53.3-Gb/s multi-band CO-OFDM signal.

We demonstrate the use of physically justified object constraints in x‐ray Fresnel coherent diffractive imaging on a sample of nanoporous gold prepared by dealloying. Use of these constraints in the reconstruction algorithm enabled highly reliable imaging of the sample’s shape and quantification of the 23‐ to 52‐nm pore structure within it without use of a tight object support constraint.

The objective of this study is to design aerobrakes for the Mars Environmental Survey (MESUR) vehicles. To contain cost, existing flight-certified materials are considered for the structure and heatshield. Since the probes enter the atmosphere directly, the heatshields had to survive entry during duststorm conditions. A slightly modified Viking forebody shape, consisting of a blunted 70-deg cone, is used. An aluminum honeycomb shell is used for the structure. For the nominal 7-km/s entry, the heatshield material used on the Vikings (a silicone elastomeric charring ablator, SLA-561) was found to be lightest, yielding an aerobrake mass fraction of 13.2%. For the extreme case of entry at 9 km/s, the stagnation region heatshield consisted of the medium-density ablator AVCOAT-5026, used on the Apollo capsules, and SLA-561 was used on the conical skirt. The aerobrake mass fraction for the 9-km/s entry was 18%. The penalty resulting if a single conservatively designed aerobrake were used for both entry velocities could reach 4.8% of the entry mass at 7 km/s. Therefore, it is recommended that separate aerobrakes be designed for probes entering at 7 km/s and at 9 km/s.

A modular strategy for the synthesis of hexacyclic dimeric resveratrol polyphenolic benzofurans is reported. The developed synthetic technology was applied to the total synthesis of malibatol A, shoreaphenol, and other biologically relevant poly-phenols.

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p

To evaluate whether the addition of enemas to oral electrolyte lavage is helpful for colonoscopic preparation, we conducted a prospective, randomized, observer-blinded trial to compare oral lavage plus enemas with oral lavage alone. The quality of preparation, mucosal visualization, and the volume of retained colonic fluid did not differ between the two groups. Twenty-two percent of the patients in the group who received oral lavage plus enemas compared with 12% of the patients in the group that only received oral lavage stated that they would refuse to repeat the preparation for future colonoscopic examination. Seventeen percent of the patients in the group that received oral lavage plus enemas demonstrated anorectal trauma or inflammation compared with only 5% in the group that received oral lavage alone (p = 0.09). These results indicate that the addition of enemas to oral lavage preparation for colonoscopic evaluation cannot be routinely recommended. However, enemas may be considered on an individual basis in the occasional patient unable to consume the complete oral lavage or in whom residual stool is found during colonoscopic evaluation after oral lavage preparation.

We have used solid-source molecular beam epitaxy (MBE) to grow InGaAs quantum-well lasers emitting at 980nm in a novel configuration of periodic index separate confinement heterostructure (PINSCH). Periodic multilayers (GaAs/AlGaAs) are utilized as optical confinement layers to reduce the transverse beam divergence as well as to increase the maximum output power. The multilayers are grown by temperature modulation MBE without any shutter operation. The heterointerfaces in the multilayers are linearly graded such that the energy barrier heights are greatly decreased. This has led to a drastic reduction in the series resistance which is essential in the performance of high output power. The 5μm × 750μm device has far-field angles of 10° by 20°, a threshold current of 45 mA, an external differential quantum efficiency of 1.15 mW/mA (90%), and an output power of 620 mW, all measured at room temperature under CW operation. A record high fiber coupling efficiency of 51% has been achieved and more than 130 mW of power is coupled into a 5μm-core single mode fiber.

In this paper, we present a highly efficient configuration by using the basic 4 × 4 active star coupler and the 2 × 2 3-dB fiber coupler as building blocks to construct larger reflective active N star couplers with the fewest erbium-doped fibers (EDFs) and pump lasers. This configuration saves about half the fibers and components used with the transmissive N × N active star. Moreover, this configuration provides advantages such as very low cost, high gain, and pump-wavelength independence for system applications.

Multilevel thin film processing, global planarization and advanced photolithography enables the ability to integrate complimentary materials and process sequences required for high index contrast photonic components all within a single CMOS process flow. Developing high performance photonic components that can be integrated with electronic circuits at a high level of functionality in silicon CMOS is one of the basic objectives of the EPIC program sponsored by the Microsystems Technology Office (MTO) of DARPA. Our research team consisting of members from: BAE Systems, Alcatel-Lucent, Massachusetts Institute of Technology, Cornell University and Applied Wave Research reports on the latest developments of the technology to fabricate an application specific, electronic-photonic integrated circuit (AS_EPIC). Now in its second phase of the EPIC program, the team has designed, developed and integrated fourth order optical tunable filters, both silicon ring resonator and germanium electro-absorption modulators and germanium pin diode photodetectors using silicon waveguides within a full 150nm CMOS process flow for a broadband RF channelizer application. This presentation will review the latest advances of the passive and active photonic devices developed and the processes used for monolithic integration with CMOS processing. Examples include multilevel waveguides for optical interconnect and germanium epitaxy for active photonic devices such as p-i-n photodiodes and modulators.

The purpose of this paper is to describe and demonstrate new capabilities in the two-dimensional implicit thermal response and ablation program. These expanded capabilities include grid options for flight and arcjet geometries, a sizing algorithm for the flight-type geometry, and an orthotropic thermal conductivity model. Applications to analysis of an orthotropic low-density carbon-phenolic material in arcjet and flight environments relevant to the Orion crew module are presented. For the arcjet environment, multidimensional conduction effects strongly influence the in-depth thermal response. For a lunar return flight environment, in the shoulder region of the crew module (where the radius of curvature is smallest), the thermal response is influenced by multidimensional conduction and by the orientation of the orthotropic material.

The complete integration of photonic devices into a CMOS process flow will enable low cost photonic functionality within electronic circuits. BAE Systems, Lucent Technologies, Massachusetts Institute of Technology, Cornell University, and Applied Wave Research are participating in a high payoff research and development program for the Microsystems Technology Office (MTO) of DARPA. The goal of the program is the development of technologies and design tools necessary to fabricate an application specific, electronic-photonic integrated circuit (AS-EPIC). The first phase of the program was dedicated to photonics device designs, CMOS process flow integration, and basic electronic functionality. We will present the latest results on the performance of waveguide integrated detectors, and tunable optical filters.

This paper demonstrates a Monte Carlo analysis technique to establish margins on sizing a thermal protection system and identifies the chief sources of uncertainty in the material response modeling. Monte Carlo sensitivity and uncertainty studies are performed for the thermal protection systems of the Stardust Sample Return Capsule, Mars Exploration Rovers, and X-37 wing leading edge, using the Fully Implicit Ablation and Thermal response code. The computation results are presented and discussed in detail. It shows that a Monte Carlo approach provides more insight than the traditional Root-Sum-Square method into the relationship between the thickness margin of a thermal protection system and the probability of maintaining the temperature of the underlying material within specified requirements. Nomenclature erfi = inverse error function N = total number of samples R = random number x = input parameters y = output of interests σ = standard deviation * σ = mean x

The optical components industry stands at the threshold of a major expansion that will restructure its business processes and sustain its profitability for the next three decades. This growth will establish a cost effective platform for the partitioning of electronic and photonic functionality to extend the processing power of integrated circuits. BAE Systems, Lucent Technologies, Massachusetts Institute of Technology, and Applied Wave Research are participating in a high payoff research and development program for the Microsystems Technology Office (MTO) of DARPA. The goal of the program is the development of technologies and design tools necessary to fabricate an application-specific, electronicphotonic integrated circuit (AS-EPIC). As part of the development of this demonstration platform we are exploring selected functions normally associated with the front end of mixed signal receivers such as modulation, detection, and filtering. The chip will be fabricated in the BAE Systems CMOS foundry and at MIT's Microphotonics Center. We will present the latest results on the performance of multi-layer deposited High Index Contrast Waveguides, CMOS compatible modulators and detectors, and optical filter slices. These advances will be discussed in the context of the Communications Technology Roadmap that was recently released by the MIT Microphotonics Center Industry Consortium.

We demonstrate a fully CMOS processed Ge p-i-n photodetector integrated with a Si waveguide on a SOI platform with a high responsivity of 1.0 A/W at lambda=1520 nm, and a 3 dB bandwidth of >4.5 GHz measured at lambda=1550 nm

We demonstrate a compact, fully tunable, narrowband (1GHz) 4thorder pole/zero optical filter that is fabricated in a silicon complementary metal oxide semiconductor foundry.

We report the demonstration of both enhancement-mode p - and n -channel GaAs metal oxide semiconductor field effect transistors (MOSFETs) on GaAs semi-insulating substrates using high quality Ga 2 O 3 (Gd 2 O 3 ) as the gate dielectric and the conventional ion-implant technology. The source and drain regions were selectively implanted with Zn or Si for low resistance ohmic contacts for p - or n -MOSFETs, respectively. AuBe/Pt/Au, Ge/Mo/Au-Ge/Mo/Au, and Ti/Pt/Au were deposited for p - and n -ohmic contacts and gate electrode, respectively. The devices, with a 4 × 50 μ m 2 gate geometry, exhibit an extrinsic transconductance of 0.18 and 0.1 mS/mm for p - and n -MOSFETs, respectively, and an excellent gate breakdown field greater than 3 MV cm −1 .

Pt/Ti/Pt/Au based Schottky contacts on HEMT devices were studied and shown to have better electrical characteristics than the standard Ti/Pt/Au Schottky contacts. The Pt-based Schottky has a higher relative barrier height and a higher turn-on voltage, 0.82 V compared to 0.72 V. The Schottky gate turn-on voltage and reverse breakdown voltages depended upon the Pt contact layer thickness. With 50 A of Pt metallization, the highest turn-on and reverse breakdown voltages were achieved. The Pt based metallization also provides good adhesion and thermal stability. This Pt-based Schottky contact can be used as a good replacement for the standard Ti based contact in FET processing.