Search

Leveraging information in aggregate data from external sources to improve estimation efficiency and prediction accuracy with smaller scale studies has drawn a great deal of attention in recent years. Yet, conventional methods often either ignore uncertainty in the external information or fail to account for the heterogeneity between internal and external studies. This article proposes an empirical likelihood-based framework to improve the estimation of the semiparametric transformation models by incorporating information about the t-year subgroup survival probability from external sources. The proposed estimation procedure incorporates an additional likelihood component to account for uncertainty in the external information and employs a density ratio model to characterize population heterogeneity. We establish the consistency and asymptotic normality of the proposed estimator and show that it is more efficient than the conventional pseudopartial likelihood estimator without combining information. Simulation studies show that the proposed estimator yields little bias and outperforms the conventional approach even in the presence of information uncertainty and heterogeneity. The proposed methodologies are illustrated with an analysis of a pancreatic cancer study.

Methylated cell-free DNA (cfDNA) has been deemed a promising biomarker for ovarian cancer (OvCa) prognosis and therapy selection. However, exploring the methylation profiles of tumor suppressor genes in cfDNA remains a challenge due to their extremely low concentrations and complicated protocols, as well as methodological constraints. In this study, an integrated microfluidic system was developed to automatically (1) capture methylated cfDNA in plasma by magnetic beads coated with the methyl-CpG-binding domain and (2) quantify the methylation level of tumor suppressor genes by on-chip quantitative polymerase chain reaction (qPCR). For capturing methylated cfDNA from a very small amount of plasma, samples along with beads were mixed in a new micromixer to enhance the capture rate. With a high capture rate (72%) and a limit of quantification of 0.1 pg/μL (3 orders of magnitude lower than that of the benchtop method), the compact system could detect the methylated cfDNA from only 20 μL of plasma sample in 2 h. Furthermore, the dynamic range, from 0.1 to 2000 pg/μL of methylated cfDNA, spans the physiological range in plasma, signifying that this device has great potential for personalized medicine in OvCa.

Methylated cell-free DNA (cfDNA) has been regarded as a novel indicator for early diagnosis and prognosis of ovarian cancer. However, analysis the methylation status of tumor suppressor genes in cfDNA remains challenging due to its extremely low concentration and lengthy, labor-intensive processes. In this study, an integrated microfluidic chip was reported to use beads coated with methyl CpG binding proteins and functional microfluidic devices which could implement (1) capture of methylated cfDNA in plasma and (2) semi-quantitative methylation-status analysis of tumor suppressor genes. The limit of detection could be as low as 2 pg/µL, which is two orders of magnitude lower than the previous work. Moreover, a dynamic range from 2 to 200 pg/µL of methylated cfDNA could be achieved. The whole process could be automated in 2 hr while only required 20 µL of plasma, indicating that this integrated microfluidic system may be utilized for early diagnosis and prognosis of ovarian cancer by using liquid biopsy.

In multivariate recurrent event data regression, observation of recurrent events is usually terminated by other events that are associated with the recurrent event processes, resulting in informative censoring. Additionally, some covariates could be measured with errors. In some applications, an instrumental variable is observed in a subsample, namely a calibration sample, which can be applied for bias correction. In this article, we develop two non-parametric correction approaches to simultaneously correct for the informative censoring and measurement errors in the analysis of multivariate recurrent event data. A shared frailty model is adopted to characterize the informative censoring and dependence among different types of recurrent events. To adjust for measurement errors, a non-parametric correction method using the calibration sample only is proposed. In the second approach, the information from the whole cohort is incorporated by the generalized method of moments. The proposed methods do not require the Poisson-type assumption for the multivariate recurrent event process and the distributional assumption for the frailty. Moreover, we do not need to impose any distributional assumption on the underlying covariates and measurement error. Both methods perform well, but the second approach improves efficiency. The proposed methods are applied to the Nutritional Prevention of Cancer trial to assess the effect of selenium treatment on the recurrences of basal cell carcinoma and squamous cell carcinoma.

Benzofuranyl benzene incorporating naphthyl (phenothiazinyl or dimesitylboryl) entities via meta-conjugation have been synthesized. These compounds exhibit bipolar transport characteristic with mobilities in the range of 10−5 to 10−4 cm2/V s at an electric field of 4 × 105 V/cm. The compounds with two naphthyl or dimesitylboryl substituents emit in the violet region with good solution quantum yields. The OLEDs fabricated from the benzofuranyl/dimethylboryl, benzofuranyl/naphthyl and benzofuranyl/dimethylboryl/phenathiazine derivatives have maximum external efficiencies of 1.01%, 1.41% and 3.14%, respectively.

New bipolar transport compounds containing a meta-conjugated phenothiazine/dimesitylborane hybrid have been synthesized and three of them were characterized via single crystal structural determination. The compounds exhibited emission from blue to green, and one of them has a dual emission behavior. Organic light-emitting diodes using the compounds as the host for the red-emitting guest, Ir(pq)2(acac) (bis(2-phenylquinoline)(acetylacetonate)iridium), have external quantum efficiencies in the range of 6.3–15.5%. Some devices have a negligible efficiency roll-off up to 1000 cd m−2.

In multivariate recurrent event data regression, observation of recurrent events is usually terminated by other events that are associated with the recurrent event processes, resulting in informative censoring. Additionally, some covariates could be measured with errors. In some applications, an instrumental variable is observed in a subsample, namely a calibration sample, which can be applied for bias correction. In this article, we develop two non-parametric correction approaches to simultaneously correct for the informative censoring and measurement errors in the analysis of multivariate recurrent event data. A shared frailty model is adopted to characterize the informative censoring and dependence among different types of recurrent events. To adjust for measurement errors, a non-parametric correction method using the calibration sample only is proposed. In the second approach, the information from the whole cohort is incorporated by the generalized method of moments. The proposed methods do not require the Poisson-type assumption for the multivariate recurrent event process and the distributional assumption for the frailty. Moreover, we do not need to impose any distributional assumption on the underlying covariates and measurement error. Both methods perform well, but the second approach improves efficiency. The proposed methods are applied to the Nutritional Prevention of Cancer trial to assess the effect of selenium treatment on the recurrences of basal cell carcinoma and squamous cell carcinoma.

Objective: The purpose of this study was to determine the efficacy of the Lidopat® 5% skin patch in relieving rib fracture pain. Subjects and Methods: From June 2009 to May 2011, 44 trauma patients with isolated rib fractures were enrolled in this study and randomized in a double-blind method into 2 groups. The experimental group (group E: 27 patients) used a Lidopat® 5% skin patch at the trauma site and took an oral analgesic drug for pain relief. The placebo group (group P: 17 patients) used a placebo vehicle patch and an oral analgesic drug. Results: The mean age, weight and hospital stay of patients were 56.8 ± 13.8 years, 67.4 ± 12.6 kg and 6.34 ± 1.3 days, respectively. In the first 4 days, there were no significant differences in pain scores between the groups (p > 0.05). After the 5th day, the average pain score was significantly less in group E (mean 1.5) than in group P (mean 3.10; p < 0.05). There was no significant difference in the number of fractured ribs between groups (p = 0.904). The use of meperidine and the length of hospital stay (6.0 vs. 6.9 days) were both significantly less in group E (p = 0.043 and 0.009, respectively). Conclusion: In this study, the use of the Lidopat® 5% skin patch in patients with isolated rib fractures alleviated pain and shortened the hospital stay, and a lower dose of pain-relieving medication was used.

This paper develops methods and inference for causal estimation in semiparametric transformation models for prevalent survival data. Through estimation of the transformation models and covariate distribution, we propose analytical procedures to estimate the causal survival function. As the data are observational, the unobserved potential outcome (survival time) may be associated with the treatment assignment, and therefore there may exist a systematic imbalance between the data observed from each treatment arm. Further, due to prevalent sampling, subjects are observed only if they have not experienced the failure event when data collection began, causing the prevalent sampling bias. We propose a unified approach which simultaneously corrects the bias from the prevalent sampling and balances the systematic differences from the observational data. We illustrate in the simulation study that standard analysis without proper adjustment would result in biased causal inference. Large sample properties of the proposed estimation procedures are established by techniques of empirical processes and examined by simulation studies. The proposed methods are applied to the Surveillance, Epidemiology, and End Results (SEER) and Medicare linked data for women diagnosed with breast cancer.

A three-dimensional (3D) porous supramolecular architecture, {[Zn(bdc)(dpds)]·0.62(MeOH)·2H2O}n (1) (bdc2− = dianion of benzenedicarboxylic acid and dpds = 4,4′-dipyridyldisulfide), has been synthesized and structurally characterized. Single-crystal X-ray diffraction analysis reveals that each [Zn2(dpds)2]4+ macrocycle is connected by bdc2− ligands to form a two-dimensional (2D) layered metal–organic framework (MOF). Adjacent layers are further assembled via two interlayer π–π interactions in sandwich-type πpyridyl–πbenzene–πpyridyl and πpyridyl–πpyridyl fashions to afford a 3D porous supramolecular architecture. Controlled heating of the as-synthesized crystal 1 at ~120 °C causes de-solvated species of {[Zn(bdc)(dpds)]}n (1a). The structural determination of the de-solvated compound shows the same structural characterization as that of 1 with the only difference of the nonexistence of solvated MeOH and water molecules. The de-solvated 1a generates the re-hydrated crystal of {[Zn(bdc)(dpds)]·1.1(H2O)}n (1b) upon exposure to water vapor. The water ab-/de-sorption phenomenon by cyclic TG measurement suggests the complete reversibility upon re-/de-hydration between 1a and 1b, associated with reversible temperature-dependent emission properties. Such a reversible switching process of 1 at RT to 120 °C can proceed for at least 20 cycles, implying good thermoluminescence reversibility of 1 during the heating–cooling processes. After removal of the solvent molecules, compound 1a exhibits permanent porosity verified by the N2 sorption isotherm with a Langmuir surface area of 530.0 m2 g−1 and a Brunauer–Emmett–Teller (BET) surface area of 429.4 m2 g−1 and also exhibits significant gas storage capacities of 1.09 wt% for H2 at 77 K and 17 wt% for CO2 at 195 K. Moreover, 1a also displays interesting reversible water, methanol and ethanol vapor ad-/de-sorption behavior correlated with the polarity of the pore surface in 1a to the corresponding adsorbate molecules.

In biomedical studies involving survival data, the observation of failure times is sometimes accompanied by a variable which describes the type of failure event (Kalbeisch and Prentice, 2002). This paper considers two specific challenges which are encountered in the joint analysis of failure time and failure type. First, because the observation of failure times is subject to left truncation, the sampling bias extends to the failure type which is associated with the failure time. An analytical challenge is to deal with such sampling bias. Second, in case that the joint distribution of failure time and failure type is allowed to have a temporal trend, it is of interest to estimate the joint distribution of failure time and failure type nonparametrically. This paper develops statistical approaches to address these two analytical challenges on the basis of prevalent survival data. The proposed approaches are examined through simulation studies and illustrated by using a real data set.

Adjuvant chemotherapy is commonly given to surgically treated non-small-cell lung cancer (NSCLC) patients. However, the prerequisite for chemotherapy needs to be scrutinized in order to maximize the benefits to patients. In this study, we observed that NSCLC cells with high Id1 protein expression were vulnerable to the treatment of paclitaxel and cisplatin. In addition, paclitaxel and cisplatin caused Id1 protein degradation through ubiquitination. In the nude mice xenograft model, the tumor growth was reduced to a large degree in the Id1-overexpressing group upon treatment with paclitaxel and cisplatin. Furthermore, immunohistochemical staining for Id1 followed by Kaplan-Meier survival analysis showed that surgically treated NSCLC patients with high Id1 expression in primary tumor tissues had better disease-free and overall survivals after adjuvant paclitaxel and cisplatin chemotherapy. In summary, our current data suggest that Id1, a generally negative prognostic factor, predicts a favorable prognosis in the case of surgically treated NSCLC patients receiving the definitive adjuvant chemotherapy. The distinct role of Id1 reported in this study may arise from the phenomenon of Id1 dependence of NSCLC cells for survival, which renders the cancer cells additionally susceptive to the adjuvant chemotherapy with paclitaxel and cisplatin.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

Summary Survival data are subject to length-biased sampling when the survival times are left-truncated and the underlying truncation time random variable is uniformly distributed. Substantial efficiency gains can be achieved by incorporating the information about the truncation time distribution in the estimation procedure [Wang (1989) Journal of the American Statistical Association 84, 742–748; Wang (1996) Biometrika 83, 343–354]. Under the semiparametric transformation models, the maximum likelihood method is expected to be fully efficient, yet it is difficult to implement because the full likelihood depends on the nonparametric component in a complicated way. Moreover, its asymptotic properties have not been established. In this article, we extend the martingale estimating equation approach [Chen et al. (2002) Biometrika 89, 659–668; Kim et al. (2013) Journal of the American Statistical Association 108, 217–227] and the pseudo-partial likelihood approach [Severini and Wong (1992) The Annals of Statistics 4, 1768–1802; Zucker (2005) Journal of the American Statistical Association 100, 1264–1277] for semiparametric transformation models with right-censored data to handle left-truncated and right-censored data. In the same spirit of the composite likelihood method [Huang and Qin (2012) Journal of the American Statistical Association 107, 946–957], we further construct another set of unbiased estimating equations by exploiting the special probability structure of length-biased sampling. Thus the number of estimating equations exceeds the number of parameters, and efficiency gains can be achieved by solving a simple combination of these estimating equations. The proposed methods are easy to implement as they do not require additional programming efforts. Moreover, they are shown to be consistent and asymptotically normally distributed. A data analysis of a dementia study illustrates the methods.

Background Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARβ2) and long interspersed nuclear elements (LINE-1) in different stages of esophageal squamous cell carcinoma (ESCC). Method The tumor and adjacent normal esophageal tissues from 125 male ESCC patients who underwent primary surgery were analyzed for the methylation status of RARβ2 promoter and LINE-1 through methylation-specific polymerase chain reaction and pyrosequencing. Results RARβ2 hypermethylation was detected in 20% of the tumor samples, but not in the normal counterparts. The methylation frequency of LINE-1 was significantly lower in the tumor than in the normal parts (median: 67.7% vs. 80%, P

Objective Development of flavonoids as potential chemotherapeutic agents for cervical cancer may open new avenues in anticancer drug design. In this study, the cytotoxic activity and anti-migration/invasion/angiogenesis efficiency of the synthetic flavonoid WYC02-9 on cervical cancer and the underlying mechanisms are explored. Methods XTT cell viability assay, apoptosis assays, cell cycle analysis, and immunoblotting analysis were applied to study the biologic activity of WYC02-9. Anchorage independent soft agar assay and xenograft nude mouse model were applied to study the anti-tumor effect of WYC02-9 in vivo . Wound healing assay, transwell invasion assay, and gelatin zymography analysis were applied to study the effect of WYC02-9 on cancer cell migration and invasion. Tube formation analysis, zebrafish angiogenesis model, and nude mice Matrigel plug angiogenesis assay were applied to study the effect of WYC02-9 on angiogenesis. Results WYC02-9 induced cytotoxicity on cervical cancer cells by promoting apoptosis and G2/M cell cycle arrest. WYC02-9 inhibited cervical cancer cell migration/invasion and angiogenesis in vitro and in vivo via MAPK14 pathway. Conclusion WYC02-9 significantly inhibited cervical cancer cell proliferation/migration/invasion and angiogenesis in vitro and in vivo . WYC02-9 may be a promising drug candidate for cervical cancer chemotherapy.

In high-speed differential signal transmission, signal integrity at the receiving end is mainly determined by high quality of the differential-mode signal and good suppression of the common-mode noise. In this paper, an innovative circuit with dual function of the differential-mode equalizer and common-mode filter (DME-CMF) is proposed. The differential-mode and common-mode characteristics of the proposed structure are discussed separately with their corresponding half-circuit model. Based on the proposed design methodology for the DME-CMF and the presented structure realizing the DME-CMF with a two-layer printed circuit board, a set of design parameters are determined for 8-Gb/s differential transmission and utilized in the fabrication of test boards. The frequency-domain and time-domain measurements of the test board successfully demonstrate the effectiveness of the proposed structure.

This article develops semiparametric approaches for estimation of propensity scores and causal survival functions from prevalent survival data. The analytical problem arises when the prevalent sampling is adopted for collecting failure times and, as a result, the covariates are incompletely observed due to their association with failure time. The proposed procedure for estimating propensity scores shares interesting features similar to the likelihood formulation in case-control study, but in our case it requires additional consideration in the intercept term. The result shows that the corrected propensity scores in logistic regression setting can be obtained through standard estimation procedure with specific adjustments on the intercept term. For causal estimation, two different types of missing sources are encountered in our model: one can be explained by potential outcome framework; the other is caused by the prevalent sampling scheme. Statistical analysis without adjusting bias from both sources of missingness will lead to biased results in causal inference. The proposed methods were partly motivated by and applied to the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data for women diagnosed with breast cancer.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC 90 s) from 2006-2007 (0.06 μg/ml) to 2008–2010 (0.12 μg/ml). The MIC 90 s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ( n = 602), ESBL-producing Klebsiella pneumoniae ( n = 736), and Acinetobacter baumannii ( n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC 90 values of tigecycline against MRSA, VRE, ESBL-producing E. coli , ESBL-producing K. pneumoniae , and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii . Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were E. coli . For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER)-α have been found to be associated with various diseases at significantly different frequencies. However, whether any relationship exists between ER-α polymorphisms and lung cancer remains to be determined. In this study, 84 non-smoking, female, non-small cell lung cancer patients with various stages of disease and 234 cancer-free reference controls were enrolled to examine the association of ER-α polymorphisms in lung cancer. Two restriction SNP sites, PvuII and XbaI, in the first intron of the ER-α gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the PvuII-XbaI haplotypes and genotypes in a Taiwanese population were revealed for the first time. Although the genotypic frequencies of two polymorphic sites of ER- α were in linkage disequilibrium for the lung cancer group (χ(2)=50.013, d.f.=4) and reference controls (χ(2)=60.797, d.f.=4); and 7 and 8 combined genotypes were present, respectively, the distribution and the major genotypes are different in the two groups (p

BackgroundStudies have criticized the low level of agreement between the various methods of personality disorder (PD) assessment. This is an important issue for research and clinical purposes.MethodSeven hundred and forty-two participants in the Hopkins Epidemiology of Personality Disorders Study (HEPS) were assessed on two occasions using the Personality Disorder Schedule (PDS) and the International Personality Disorder Examination (IPDE). The concordance between the two diagnostic methods for all DSM-IV PDs was assessed using standard methods and also two item response analytic approaches designed to take account of measurement error: a latent trait-based approach and a generalized estimating equations (GEE)-based approach, with post-hoc adjustment.ResultsRaw criteria counts, using the intraclass correlation coefficient (ICC), κ and odds ratio (OR), showed poor concordance. The more refined statistical methods showed a moderate to moderately high level of concordance between the methods for most PDs studied. Overall, the PDS produced lower prevalences of traits but higher precision of measurement than the IPDE. Specific criteria within each PD showed varying endorsement thresholds and precision for ascertaining the disorder.ConclusionsConcordance in the raw measurement of the individual PD criteria between the two clinical methods is lacking. However, based on two statistical methods that adjust for differential endorsement thresholds and measurement error in the assessments, we deduce that the PD constructs themselves can be measured with a moderate degree of confidence regardless of the clinical approach used. This may suggest that the individual criteria for each PD are, in and of themselves, less specific for diagnosis, but as a group the criteria for each PD usefully identify specific PD constructs.

Medical Education 2011: 45: 835–842 CONTEXT The occupational health literature has long been dominated by stress-related topics. A more contemporary perspective suggests using a positive approach in the form of a health model focused on what is right with people, such as feelings of well-being and satisfaction. OBJECTIVES Using a positive perspective and multi-source data collection, this study investigated the inter-relationships among emotional intelligence (EI), patient satisfaction, doctor burnout and job satisfaction. METHODS In this observational study, 110 internists and 2872 out-patients were surveyed in face-to-face interviews. RESULTS Higher self-rated EI was significantly associated with less burnout (p

The improvement of current injection efficiency in organic light emitting diodes is demonstrated with incorporation of lithium fluoride (LiF) mixed with subphthalocyanine (SubPc) as electron injection layers. The photoemission spectra indicate that the lithium released from LiF would remove chlorine atoms from SubPc molecules and create large density of gap states at the interfaces. These gap states, resulted from the addition of SubPc in conventional aluminum/LiF/ tris-(8-Hydroxyquinoline)-aluminum (Alq3) cathode structures, further enhance the electron injection efficiency in OLEDs. The results demonstrate a relatively unique feature of SubPc which can be used to improve both electron and hole injection efficiency.

Objective Preclinical and human family studies clearly link monoamine oxidase A (MAOA) to aggression and antisocial personality (ASP). The 30–base pair variable number tandem repeat in the MAOA promoter regulates MAOA levels, but its effects on ASP in humans are unclear. Methods We evaluated the association of the variable number tandem repeat of the MAOA promoter with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , ASP disorder (ASPD) traits in a community sample of 435 participants from the Hopkins Epidemiology of Personality Disorders Study. Results We did not find an association between the activity of the MAOA allele and ASPD traits; however, among whites, when subjects with a history of childhood physical abuse were excluded, the remaining subjects with low-activity alleles had ASPD trait counts that were 41% greater than those with high-activity alleles ( P Conclusion The high-activity MAOA allele is protective against ASP among whites with no history of physical abuse, lending support to a link between MAOA expression and antisocial behavior.

High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions. It is involved in invasion and metastasis in various human malignancies. However, the role of HMGB1 in non-small cell lung cancer (NSCLC) is unclear. We hypothesized that HMGB1 expression is a determinant of cellular invasiveness and metastasis in lung cancer. We examined HMGB1 expression in 48 NSCLC specimens by quantitative real-time PCR. High HMGB1 expression was significantly associated with clinically advanced stages (stage III-IV) (P < 0.05) and was correlated to expression of matrix metalloproteinase-9 (MMP-9) (P < 0.05). Patients with high levels of HMGB1 expression had poorer clinical prognosis. The expression level of MMP-9 and metastatic ability in vitro were significantly higher in an HMGB1-overexpressing human NSCLC cell lines (A549 and H23). The treatment with HMGB1 small interfering RNA reduced MMP-9 expression and the cellular metastatic ability in NSCLC cells. We also demonstrated that phosphoinositide 3-kinase/Akt and NF-κB-related pathways contributed to the HMGB1-induced MMP-9 expression and cellular metastatic ability.

A total of 393 isolates of A. baumannii were collected from patients treated at 19 teaching hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibitory zone diameters for tigecycline were determined by the broth microdilution method and the disk diffusion method, respectively. The MIC results were interpreted using the US FDA tigecycline susceptibility breakpoints for Enterobacteriaceae (susceptible [S]or=2 microg/mL; intermediate [I] 4 microg/mL; resistant [R]or=8 microg/mL). The disk diffusion results were interpreted by criteria recommended by Jones et al. (Sor=16 mm; I 13-15 mm; Ror=12 mm) and also by those recommended by the US FDA for Enterobacteriaceae (Sor=19 mm; I 15-18 mm; Ror=14 mm). The percentages of susceptible, intermediate and resistant isolates determined by the broth microdilution method were 80.9%, 12.2%, and 6.9%, respectively. The rates of susceptible, intermediate and resistant isolates by the disk diffusion method using the criteria of Jones et al. were 88.3%, 9.9% and 1.8% and using the US FDA criteria were 44.0%, 51.7% and 4.3%. Using the criteria recommended by Jones et al., the total error rate of the disk diffusion method in comparison with the broth microdilution method was 14.2% (56/393). For routine susceptibility testing of tigecycline against A. baumannii the broth microdilution method, not the disk diffusion method, should be used due to the poor correlation of results between these two methods interpreted either by the Jones et al. or US FDA criteria.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria in Taiwan. This study, part of TIST-2006 study, aimed to compare the in-vitro activity of tigecycline against clinical isolates of Gram-positive bacteria. A total of 805 isolates of Gram-positive bacteria were collected from patients treated at 20 teaching hospitals. Minimum inhibitory concentrations (MICs) of tigecycline for these isolates were determined by the broth microdilution method according to the guidelines of the Clinical and Laboratory Standards Institute, and by the Etest as per the manufacturer's instructions. Susceptibility results were interpreted by the MIC criteria recommended by the US FDA. Agreement between the two methods was low: 80.7% for methicillin-resistant Staphylococcus aureus (MRSA), 27.2% for Streptococcus pneumoniae, 22.8% for other Streptococcus spp., and 30.8% for vancomycin-resistant E. faecium (VRE). There were no very major or major errors noted. Tigecycline exhibited excellent in-vitro activity against Gram-positive cocci, including MRSA, VRE, S. pneumoniae and other Streptococcus spp. isolates in Taiwan. Correlation between MIC values determined using the broth microdilution and Etest methods for these organisms was poor.

OBJECTIVES. The effects of a computer kiosk intervention on parents' child safety seat, smoke alarm, and poison storage knowledge and behaviors were evaluated in a pediatric emergency department serving predominantly low-income, urban families. The effects of parent anxiety and the reason for the child's emergency department visit also were examined. METHODS. A randomized, controlled trial of a Safety in Seconds program with a 2- to 4-week follow-up interview was conducted with 759 parents of young children (4–66 months of age). The intervention group received a personalized report containing tailored, stage-based safety messages based on the precaution adoption process model. The control group received a report on other child health topics. RESULTS. The intervention group had significantly higher smoke alarm, poison storage, and total safety knowledge scores. The intervention group was more likely to report correct child safety seat use. Neither parent anxiety nor the reason for the emergency department visit was related to the safety behaviors. Virtually all (93%) intervention parents read at least some of the report; 57% read it all, and 68% discussed it with others. Lower-income intervention parents who read all of the report and discussed it with others were more likely than control parents to practice safe poison storage. Higher-income intervention parents were more likely than control parents to report correct child safety seat use. CONCLUSIONS. These results bode well for widespread applicability of computer technology to patient education in busy emergency departments and other child health care settings. Reducing financial barriers to certain safety behaviors should continue to be a high priority.

The inclusion criteria were established for a videothoracoscopic resection of early-stage thymoma. We retrospectively evaluated the validity of these criteria in the treatment of early-stage thymoma.The computed tomography (CT) image characteristics and clinical information comprised these criteria. The image considerations included the location of the tumor in the anterior mediastinum, a distinct fat plane between the tumor and vital organs, unilateral tumor predominance, tumor encapsulation, the existence of residual normal-appearing thymic tissue, and no mass compression effect. All enrollees were expected to be free of pleural effusion, pericardial effusion, paralysis of the hemidiaphragm, and the encasement of great vessels. An elevation of either the serum alpha-fetoprotein or beta-human chorionic gonadotropin levels, severe chest pain, superior vena cava syndrome, hoarseness, and age less than 20 years excluded the patient from enrollment. The heterogeneous content of the tumor was not an exclusion criterion, and the tumor size was not considered important. According to the above criteria, 44 patients were enrolled between November 1999 and November 2005.Twenty-seven patients had stage I thymoma and 17 had stage II thymoma. All patients successfully underwent a complete tumor resection using a three-port endoscopic technique. There was no open conversion.Based on these criteria, we can select suitable patients to confidently perform a thoracoscopic resection of early-stage thymoma.

// I-Chen Wu 1, 2, * , Yu-Kuei Chen 3, * , Chun-Chieh Wu 4 , Yu-Jen Cheng 5 , Wei-Chung Chen 6 , Huey-Jiun Ko 1 , Yu-Peng Liu 7, 8 , Chee-Yin Chai 4 , Hung-Shun Lin 9 , Deng-Chyang Wu 1, 2 , Ming-Tsang Wu 7, 10, 11 1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 2 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan 4 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 5 Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan 6 Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 7 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Laboratory Medicine & Department of Research, Education & Training, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 11 Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Ming-Tsang Wu, email: 960021@ms.kmuh.org.tw Keywords: ATPase Na+/K+ transporting alpha 1 polypeptide, microarray-based screening, arecoline, F344, esophageal squamous cell carcinoma Received: December 30, 2015 Accepted: October 14, 2016 Published: November 10, 2016 ABSTRACT This study aims to identify new upregulated genes related to secretory or membranous proteins to help detect esophageal squamous cell carcinoma (ESCC). First, we performed microarray-based screening of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and seventeen human ESCC specimens. Candidate genes were validated by quantitative PCR (qPCR) and immunohistochemical (IHC) staining of ESCC tissues. Among the paired cancer and adjacent normal tissues from 14 ESCC patients, 10 pairs (71.4%) had overexpression of ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) by qPCR (P = 0.0052). ATP1A1 protein expression was re-confirmed by tissue arrays in 243 ESCC tissues and 126 adjacent normal tissues and by ELISA in 78 serum specimens of ESCC patients. ATP1A1 was 12.3 times (adjusted odds ratio=12.3, 95% CI = 7.2-21.0) more likely to be overexpressed in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to tumor stage. Patients with higher serum ATP1A1 levels had a 2.9-fold (95% CI = 1.1-7.4) risk of late-stage disease (stages III-IV vs . I-II). Downregulation of ATP1A1 expression inhibited the migration and invasion ability of ESCC cell lines in vitro . We concluded that the overexpression of ATP1A1 is strongly associated with the presence and severity of ESCC.

Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244–amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan–Meier survival analysis showed that patients with low adiponectin expression ratio (1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future.

Primary mediastinal germ-cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk-sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor-marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.

Extensive researches have found that the mutation of p53 tumor suppressor gene is the most frequent event in many human cancers and associated with a poor clinical outcome in lung cancer patients. Because the p53 molecular mutation involved in tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the aim of this study was to assess the p53 mutation spectrum and possible etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC). Cancer specimens were obtained surgically from 61 patients with pathologically proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We also performed immunohistochemistry (IHC) to detect p53 protein expression. Our results provided that 34 mutations of p53 gene were found in 27 cases with a mutation rate of 44% (27/61). There were six cases having more than two p53 mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted of a majority of missense mutations including transversion (13/19, 68%) and transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence. One of the most important finding in our study was the high frequency of frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at codon181 and codon 185 seemed to have more advanced clinical outcome with survival time less than 6 months. In addition, there were two recurring mutations at codon 168 and three at condon193. The different mutation spectrum in our series, including a high frequency of frameshift mutations and distinctly novel hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in Taiwan.

Summary Objective Angiogenesis is essential for tumor growth and metastasis. Angiogenesis regulators, which are controlled by ovarian hormones, play an important role during endometrial carcinogenesis. The study evaluated the relationship between angiogenesis and clinicopathologic parameters, and the possible regulatory roles of estrogen receptor (ER) and progesterone receptor (PR) status in the angiogenesis of endometrial carcinoma. Materials and Methods Twenty patients undergoing surgery for endometrial carcinoma were enrolled. The microvessel density (MVD) of the excised tumor was assessed immunohistochemically. The relationships between the tumor MVD (MVD-T) and tumor/normal counterpart MVD ratio (MVD T/N ratio) and clinicopathologic parameters, including histologic grade, myometrial invasion, cervical involvement, lymph node involvement, lymphovascular space involvement, menopausal status, histologic type, stage, and ER and PR status, were analyzed. Results The relationships between MVD (× 200 fields) and clinicopathologic parameters were not significantly different in the 20 patients when only tumor lesions were counted. However, several clinicopathologic parameters were significantly different when MVD was measured as the T/N ratio. The MVD T/N ratios were significantly higher in tumors of histologic grades 2 and 3, with lymphovascular space involvement, and of serous type, when compared, respectively, with tumors of histologic grade 1 (1.31 vs 1.07, p = 0.010), with no lymphovascular space involvement (1.32 vs 1.13, p = 0.029), and of endometrioid type (1.48 vs 1.13, p = 0.021). MVD T/N ratios were higher in ER-negative, PR-negative and both receptor-negative tumors compared with ER- positive, PR-positive and both receptor-positive tumors (1.33 vs 1.02, p = 0.002). Conclusion There was a better correlation between MVD T/N ratios and clinicopathologic parameters, even taking into account the inborn heterogeneity characteristics of endometrial cancer and the limited case number. Anti-angiogenesis factors may have a close relationship with ovarian hormone receptor status in the different pathogeneses of endometrial carcinoma.