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This case–control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α−308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Their gene–gene interaction was also investigated. We enrolled 200 pairs of age- and sex-matched patients with cirrhotic HBV-HCC and unrelated patients with HBV-cirrhosis alone. Polymorphisms of TNFα −308 and LTα +252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes ( TNFα −308 G/A and LTα +252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα −308 G/A (odds ratio [OR], 2.34) and LTα +252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child-Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα −308 G/A and LTα +252 G/G on risk of HCC (SI = 1.29). In conclusion: There are independent and additive interactions between TNFα −308 G/A and LTα +252 G/G on risk for HBV-HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC.

This case–control study aimed to assess the interactive effect between polymorphisms of lymphotoxin (LT) α +252 and habitual substance use on risk of hepatocellular carcinoma (HCC). We enrolled 150 pairs of sex- and age-matched HCC patients and unrelated healthy controls. LTα genotypes were detected with polymerase-chain reaction and restrictive fragment length polymorphisms. Information about habits of substance use was obtained through personal interview. Multivariate analysis indicated that LTα +252 G/G genotypes [odds ratio (OR) = 3.36], Hepatitis B surface antigen (OR = 16.68), antibodies to hepatitis C virus (OR = 34.88) and having at least two habits of substance use (OR = 2.50) were independent risk factors for HCC. There were additive interactions among LTα +252 G/G genotype, chronic viral hepatitis, and habit of each substance use. In conclusion: There are independent and additive interactions between LTα +252 G/G genotype, chronic viral hepatitis, and habits of substance use on risk of HCC.

Summary Background Peginterferon-α–based therapy frequently leads to neutropenia. It remains unclear whether neutropenia is associated with bacterial infection in chronic hepatitis C (CHC). Aim To evaluate the risk of bacterial infection and neutropenia in patients with CHC treated with peginterferon-α/ribavirin. Methods In all, 207 patients with CHC with (group A, n = 30) and without (group B, n = 177) baseline neutropenia were treated with peginterferon-α/ribavirin. Results Group A had significantly higher rates of moderate (

Observed spectra normally contain spurious features along with those of interest and it is common practice to employ one of several available algorithms to remove the unwanted components. Low frequency spurious components are often referred to as ‘baseline’, ‘background’, and/or ‘background noise’. Here we examine a cross-section of non-instrumental methods designed to remove background features from spectra; the particular methods considered here represent approaches with different theoretical underpinnings. We compare and evaluate their relative performance based on synthetic data sets designed to exemplify vibrational spectroscopic signals in realistic contexts and thereby assess their suitability for computer automation. Each method is presented in a modular format with a concise review of the underlying theory, along with a comparison and discussion of their strengths, weaknesses, and amenability to automation, in order to facilitate the selection of methods best suited to particular applications.

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and (log)AFP (r = -0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis.

This paper describes a system for the recognition of legal amounts on bank checks written in the Chinese language. It consists of subsystems that perform preprocessing, segmentation, and recognition of the legal amount. In each step of the segmentation and recognition phases, a list of possible choices are obtained. An approach is adopted whereby a large number of choices can be processed effectively and efficiently in order to achieve the best recognition result. The contribution of this paper is the proposal of a grammar checker for Chinese bank check amounts. It is found to be very effective in reducing the substitution error rate. The recognition rate of the system is 74.0%, the error rate is 10.4%, and the reliability is 87.7%.

In 1979, a mass poisoning of more than 2000 people occurred in central Taiwan due to consumption of rice-bran oil contaminated with PCBs and their heat-degraded byproducts. The incident was later referred to as Yucheng (oil disease). Serum samples from 56 women with the 1979 exposure were collected in February 1992 and analyzed for their contaminant content using sample enrichment and isotope dilution mass spectrometry. In most of the samples, levels of PCDFs and PCBs were detectable, and the median values of 2,3,4,7,8-PCDFs and 1,2,3,4,7,8-PCDFs were 1,030 and 2,220 ng/kg serum lipid, respectively. The median level of the total PCBs on a whole weight basis was 8,730 ng/kg. The PCB/PCDF concentrations in Yucheng women 14 years after the toxic exposure were still one to two orders of magnitude higher than controls. Concentrations of PCB levels in 1992 were positively correlated with the 1980-1981 measured PCB levels in these women and both PCBs and PCDFs were negatively correlated with the total duration when these women breast fed their children between 1979 and 1992. It is concluded that serum levels of congener-specific PCBs/PCDFs in exposed women are good indicators of previous exposure and may provide important information for more reliable estimation of dose-response relationship.

This case–control study aimed to evaluate the diagnostic application of urinary transforming growth factor (TGF) α and serum α-fetoprotein (AFP) in hepatocellular carcinoma (HCC). TGFα and AFP were determined in 90 pairs of age- and gender-matched patients with cirrhotic HCC and patients with cirrhosis alone and 60 healthy controls. The results indicated that TGFα and AFP levels in patients with HCC were higher than in those with cirrhosis alone or healthy controls (each P = 0.0001). Multivariate analysis indicated that TGFα (odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.05–1.16) and AFP (OR 1.03, 95 % CI 1.01–1.06) were closely associated, in a dose-related fashion, with the development of HCC. The optimal cutoff values, determined with the receiver operating characteristic (ROC) curves, were 29 μg/g creatinine for TGFα and 100 ng/ml for AFP, respectively. The areas under ROC curve (AUC) were 0.74 for TGFα and 0.78 for AFP, respectively. Both biomarkers showed the same sensitivity (52.2 %), high specificity, high positive predictive value, and moderate positive likelihood ratio. Determination of both markers in parallel significantly increased the AUC (0.91) and diagnostic accuracy (92.2 %), with a high sensitivity (86.7 %), specificity (97.8 %), positive predictive value (PPV; 97.5 %), and moderate positive likelihood ratio (PLR; 39.4). Among 31 cirrhotic HCC with AFP ≤ 20 ng/ml, the calculated AUC for TGFα was 0.79, with a sensitivity of 64.5 %, specificity of 96.7 %, PPV of 87.0 %, and PLR of 19.5. In conclusion, urinary TGFα and serum AFP are complementary tumor markers for detection of HCC with low AFP production.

In this communication, we present a study of tip artifacts in atomic force microscope images of nanometer-scale cellular structures created on germanium surfaces by ion bombardment. It is demonstrated that the appearance of a columnar/granular morphology is due to severe image distortion when the tip size is comparable with the mean cell/hole diameter. These tip artifacts can often be deconvoluted by inverting the image and the lateral extension of the cell/hole can be reproduced with reasonable accuracy.

Vibrational spectra often require baseline removal before further data analysis can be performed. Manual (i.e., user) baseline determination and removal is a common technique used to perform this operation. Currently, little data exists that details the accuracy and precision that can be expected with manual baseline removal techniques. This study addresses this current lack of data. One hundred spectra of varying signal-to-noise ratio (SNR), signal-to-baseline ratio (SBR), baseline slope, and spectral congestion were constructed and baselines were subtracted by 16 volunteers who were categorized as being either experienced or inexperienced in baseline determination. In total, 285 baseline determinations were performed. The general level of accuracy and precision that can be expected for manually determined baselines from spectra of varying SNR, SBR, baseline slope, and spectral congestion is established. Furthermore, the effects of user experience on the accuracy and precision of baseline determination is estimated. The interactions between the above factors in affecting the accuracy and precision of baseline determination is highlighted. Where possible, the functional relationships between accuracy, precision, and the given spectral characteristic are detailed. The results provide users of manual baseline determination useful guidelines in establishing limits of accuracy and precision when performing manual baseline determination, as well as highlighting conditions that confound the accuracy and precision of manual baseline determination.

Summary form only given. Highly miniaturized electron beam columns based on a field emission source and microfabricated electron optical components have been developed. A 1 keV microcolumn operating with a miniaturized Zr/O/W Schottky emitter has been successfully evaluated for the first time. This paper will present the results obtained with the new microcolumn and discuss present efforts to further improve column performance with respect to resolution, beam current, and deflection field size.

Background: Cerebrovascular disease is one of the leading causes of death worldwide. Hepatitis C virus (HCV) infection, a well-accepted causal agent for liver-related diseases, has been reported to increase the risk for atherothrombosis. However, the association between HCV infection and cerebrovascular diseases remains inconclusive and the dose-response relationship between serum HCVRNA levels and cerebrovascular death has never been elucidated. Methods: This study enrolled 23,665 residents aged between 30–65 years in community during 1991–1992. They were personally interviewed using structured questionnaires and provided blood samples for various serological and biochemical testing at study entry. Those who were seropositive for antibodies against HCV (anti-HCV) were examined for serum HCVRNA levels. HCV genotypes were determined in participants who had detectable serum HCVRNA. Cerebrovascular deaths of participants during follow-up were ascertained by computerized linkage with National Death Certification profiles from 1991 to 2007 (ICD-9: 430–438). Person-years at risk were calculated for each person as time from enrollment date to either the date of death, or to the end of 2007, whichever came first. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for magnitude of HCV after adjustment of other risk factors. Results: There were 240 cerebrovascular deaths with 361,171 person-years of follow-up, giving a mortality of 66.5 per 100,000 person-years in this population. The cumulative risks for cerebrovascular death were 1.0% and 2.7% for anti-HCV seronegatives and anti-HCV seropositives (p < 0.001). Participants seropositive for anti-HCV had increased risk of cerebrovascular death, with a multivariate-adjusted relative risk (95% confidence interval) of 2.27 (1.56–3.30). Elevated serum HCVRNA levels increased the risk for cerebrovascular death with dose-response trend (p < 0.001). The adjusted relative risks were 1.52 (0.67– 3.44), 1.73 (0.43–6.98), 2.31 (1.25–4.25), and 3.45 (1.76– 6.75) in corresponding to participants with serum HCVRNA level

A fully functional electron beam microcolumn, 3.5 mm in length, demonstrating a probe size of 10 nm and beam current >= 1 nA at 1 keV has been successfully developed. This paper presents its current status and future directions. Potential applications ranging from low cost scanning electron microscopy to arrays of such microcolumns for lithography, metrology, testing etc. will be discussed.

Photoemission has often been proposed as a promising approach for achieving arrays of independently modulated photocathodes for electron-beam lithography applications. In most such proposals the modulation of the photocurrent is assumed to be achieved by controlling the incident light energy reaching each photocathode. For many applications, however, the optical complexity of such a scheme limits the attractiveness of the photocathode approach. In this article we propose a novel gated photocathode structure which resolves this concern. It allows stable and reproducible electrical modulation of the photocurrent from each photocathode in a thin-film array under continuous optical illumination. In addition, by using illumination of the photocathodes through a transparent substrate, the position, the size, and the shape of each photocathode can be accurately determined during fabrication rather than being determined by the size of the optical illumination spot on the photocathode material. A number of structu...

A miniaturized 1 kV electron beam column with a 20×20 mm square footprint for application in arrayed lithography was developed. The actual beam forming optics measured from the electron emitter to the last electrode in the beam focusing Einzel lens is only 3.5 mm in length. The electron source is a miniaturized, high brightness (120 μA/sr), low heating power (

A miniature Schottky electron source has been developed and evaluated for applications in a new generation of scanning tunneling microscope aligned field emission microcolumns. Both the physical dimensions and the heating power of this source have been significantly reduced from a conventional source of the same kind. Operating parameters for such a source in a microcolumn environment in terms of emission characteristics, suppressor operating range, etc., have been evaluated. Test results show that very good emission stability at ≥100 μA emission current over several hours, and axial angular current densities in excess of 100 μA/sr can be obtained. Energy distributions have been measured using a carefully calibrated analyzer, and the results show a full width at half‐maximum of 0.4 to 0.76 eV for a 0.3 μm radius Schottky source operating over an angular current density range of 1 to over 100 μA/sr. A significant change in the shape of the energy distribution was observed over this range of operation, indi...

We have built and tested a 1 keV electron‐beam microcolumn that focuses 1 nA of beam current into a 10 nm full width half‐maximum beam diameter at a working distance of 1 mm. The electron source is a miniaturized Zr/O/W Schottky field emitter with 150 μA/sr angular emission current density operating at about 1800 K at a distance of only 100 μm from a silicon membrane extractor electrode. The actual microcolumn is 3.5 mm long assembled mainly from silicon membrane electrodes. Improved einzel lens design and fabrication allowed the operation of this beam focusing element in the accelerating mode. Spherical and chromatic aberrations were reduced by factors of about 2–3, respectively, as compared to the retarding lens mode. Excellent beam current stability with less than 1% variation over several hours has been observed.

Schottky emission tips have been evaluated with microlenses for applications in scanning tunneling microscope aligned field emission microcolumns. Operation of Zr/O/W 〈100〉 Schottky emission tips at 1800 K with an axial separation of 50–100 μm between the tip and a microlens has been successfully tested. The microlens consists of an extraction electrode with a 5‐μm‐diam hole in a 1‐μm‐thick silicon membrane. The preliminary results of this study show that thermal field emission tips can be operated continuously in close proximity to a microlens over a long period of time, and that good emission stability of less than 1% noise fluctuation over 10 h is achieved with emission currents up to at least 100 μA.

An oxygen induced sharpening process of field emitter tips, W〈111〉, for use in a scanning tunneling microscope aligned field emission microcolumn system has been developed. The sharpening process which depends on processing temperature and oxygen pressure can be used to control tip radius accurately with reliability and reproducibility. The measured tungsten removal rate was ∼13 A/min at a processing temperature of ≂1650 K and at an oxygen pressure of ≂4×10−5 Torr. The process is primarily intended for more accurate control of the tip radius and hence performance of newly etched tips, although damaged or blunt tips can also be resharpened in situ with this process. Favorable emission characteristics of the oxygen processed tips have been observed with microcolumn operation: (1) reasonably stable emission current, (2) low extraction voltage, (3) reproducible threefold symmetric emission patterns, and (4) small emission angle.

A new way to use Josephson junctions for parametric amplification with phase control is proposed. The dc current bias of the junction is adjusted such that the Josephson oscillation automatically synchronizes with the input signal and oscillates at twice the signal frequency with the proper relative phase. The impedance of the junction then has a negative resistive component which can be used for amplification. Extension to other phase sensitive circuits is also discussed.

The impact of diesel fuel sulfur reduction on directly-emitted and secondary atmospheric particulate is evaluated by experiment and analysis. Experimental evidence shows that fuel sulfur conversion rate to particulate sulfate is linear down to zero sulfur level. Analysis shows that sulfur-derived particulate accounts for the vast majority of atmospheric particulate from diesel engines. Consequently, fuel sulfur reduction would have a far greater impact in reducing atmospheric particulate burden than any other diesel engine particulate control strategy.