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This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status. The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of non-urothelial recurrence (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and non-urothelial recurrence (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis. In Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted. [ABSTRACT FROM AUTHOR]

Five funnel-web spiders in the genus Macrothele are widely distributed to Taiwan. We herein reported the severe case of a woman bitten by a male Macrothele gigas who present with autonomic (i.e., profuse sweating and piloerection), cardiovascular (hypertension and tachycardia), and neurologic effects (perioral numbness) in addition to local tissue swelling and regional limb pain. Morphine and ampicillin/sulbactam were administered. Her cardiovascular, neurologic, and local symptoms gradually improved, and thus was discharged 24 h post-bite. However, persistent diaphoresis and piloerection lasted for at least 3 days, and pre-renal azotemia was suspected. Due to the risk of severity and death reported for the Australian funnel web spider bites, we suggest patients bitten by an Asian funnel-web spider be carefully monitored and resuscitation performed as indicated. • Information on the diagnosis and management of the Asian funnel-web spiders' bites remains limited. • The patient bitten by Macrothele gigas (Asian funnel-web spider) developed cardiovascular, neurologic, and autonomic effects. • Specific antivenom is unavailable in Taiwan. • Immediately applying pressure immobilization and transporting the patient to the emergency department are recommended. [ABSTRACT FROM AUTHOR]

Background/purpose: We aimed to identify the risk factors of first-time occurrence of non-variceal upper gastrointestinal bleeding (UGIB) among aspirin users after adjusting for confounding factors like age, gender, underlying co-morbidities, and medications.Methods: Using the National Health Insurance Research Database of Taiwan and matching age, gender, underlying co-morbidities and enrollment time by propensity score, 11105 aspirin users and 11105 controls were identified for comparison from a cohort dataset of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify independent risk factors for first-time occurrence of non-variceal UGIB in the study cohort and in the aspirin users after adjusting for age, gender, underlying co-morbidities, and medications (e.g., non-steroidal anti-inflammatory drugs [NSAIDs], cyclooxygenase-2 [COX-2] inhibitors, steroids, thienopyridines, selective serotonin reuptake inhibitors, warfarin, and dipyridamole).Results: By Cox proportional hazard regression analysis, aspirin use increased the risk of first-time occurrence of UGIB (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28-1.72). Age, male gender, Helicobacter pylori (H. pylori)infection, diabetes, chronic kidney disease (CKD), cirrhosis, history of uncomplicated peptic ulcer disease (PUD), and use of NSAIDs, COX-2 inhibitors, steroids, and thienopyridines were independent risk factors for UGIB among aspirin users.Conclusion: In addition to age, male gender, H. pylori infection, and concomitant use of NSAIDs, COX-2 inhibitors, steroids, and thienopyridines, underlying co-morbidities including diabetes, CKD, cirrhosis, history of PUD are also important risk factors for first-time occurrence of non-variceal UGIB in aspirin users. [ABSTRACT FROM AUTHOR]

The production of indium-tin oxide has increased in the past decades due to the increased manufacture of liquid crystal displays (LCD). Taiwan is one of the highest indium-consuming countries worldwide. After repeated inhalation, indium oxide (In2O3) particles would accumulate in the lungs, resulting in severe lung effects. We report two workers of an LCD producing facility with elevated serum indium level up to 149 and 73.8 μg/L (normal value <3.5 μg/L), which was much higher than that observed in previous case reports in Taiwan. We collected their detailed working history, symptoms, pulmonary function, radiologic findings, and followed up for more than one year. We also performed workplace evaluation of the facility. We observed that sandblasters who clean components of ITO thin-film production machinery by sandblasting with aluminum oxide tend to have higher indium exposure with worse pulmonary functions and HRCT findings. [ABSTRACT FROM AUTHOR]

Background: The updated prevalence of Helicobacter pylori (H. pylori) is lacking in Taiwan. We aimed to assess the accuracy of Vstrip® H. pylori Stool Antigen Rapid Test (Vstrip®HpSA) in the detection and surveillance of the updated prevalence of H. pylori in Taiwan.Methods: A total of 347 adult subjects including 152 volunteers and 195 symptomatic patients were recruited. Stool samples were collected for detection of H. pylori using Vstrip® HpSA, ImmunoCard STAT!® HpSA and Premier Platinum HpSA® PLUS. All subjects who have completed the stool sample collections were included in the ITT analysis. The sensitivity, specificity, and accuracy of Vstrip® HpSA were calculated compared to gold standard test with 13C-Urea breath test.Results: The un-adjusted prevalence of H. pylori infection was 22.5% (95% CI: 18.3-27%) in 2018. The age-standardized prevalence of H. pylori was 21.8% in asymptomatic adults in Taiwan. The sensitivity, specificity, and accuracy of the Vstrip® HpSA, and ImmunoCard STAT!® HpSA tests were 91% (95% CI: 82-96%) versus 76.9% (95% CI: 66-86%), 97% (95% CI: 94.1-98.6%) versus 97% (95% CI: 94.1-98.6%), and 95.7% (95% CI: 92-97%) versus 92.5% (95% CI: 89-95%), respectively.Conclusion: The age-standardized prevalence of H. pylori infection in Taiwan was 21.8% in asymptomatic adults in 2018. The Vstrip® HpSA had equivalent performance as the ImmunoCard STAT!® HpSA, and can be used in future mass screening of H. pylori infection for gastric cancer prevention. [ABSTRACT FROM AUTHOR]

Background/purpose: The trend of suicide rates among young adults has been increasing worldwide. The study aimed to identify the suicide risks and associated psychosocial factors in a large university in Taiwan.Methods: This is a mixed-methods study using both questionnaire survey and two open-ended questions for the exploration of qualitative data. An online survey was conducted between two periods of the same semester in 2018 to collect different sources of stress and other suicide correlates. The measurement scales included the 9-item Concise Mental Health Checklist, the University Stress Screening Tool in Taiwan and the Chinese Maudsley Personality Inventory. The participants were required to fulfill two open-ended questions about stress experience and depressive symptoms in the previous month in the end of the questionnaire, which was analyzed using thematic analysis.Results: A total of 857 university students were recruited (67.9% female participants). Over a quarter of participants were under poor mental health status and more than 60% experienced stressful events in the prior year. A higher suicide risk and neurotic trait was noticed compared to the general public. These results were consistent with the qualitative findings.Conclusion: While identifying several risk factors that cumulatively conduced to higher suicide risks, neuroticism served as a key element in the increased suicide risk among the university students. Suicide prevention strategies for university students should highlight stress management for those with neurotic trait and early suicide risk identification. [ABSTRACT FROM AUTHOR]

North America experienced life-threatening outbreaks of enterovirus D68 (EV-D68) in 2014. We retrospectively detected EV-D68 from a child with Wilson's disease in 2008 in Taiwan. After comparing this EV-D68/Taiwan/2008 strain with EV-D68 genomes obtained from the public domain, it was classified as genome type 1-B; it is phylogenetically related to the predominant EV-D68 viruses that circulated in 2009 in Vietnam. It is necessary to strengthen EV-D68 detection globally, including in children with acute liver failure. Moreover, harmonization of genomic analysis of EV-D68 is desirable to understand global evolution of EV-D68. [ABSTRACT FROM AUTHOR]

This case study presents the effect of spatial variability of soft clays on the geotechnical serviceability assessment of braced excavations. Finite element modeling is performed to predict the excavation-induced wall and ground movement. The spatial variations in two key soil parameters are modeled as two correlated lognormal random fields. The system reliability-based serviceability assessment conducted in this case study shows that the system probability of serviceability failure is greater than or equal to that for each single failure mode, indicating that serviceability assessment considering an individual failure mode can result in unsafe predictions. [ABSTRACT FROM AUTHOR]

New approach methodologies in toxicology, such as in vitro high-throughput screening (HTS), can minimize the use of experimental animals and allow mechanism-based predictions of in vivo toxicity. HTS data has been increasingly used in the regulatory context; however, only a few studies integrated dietary exposure and HTS data to foster chemical prioritization in food. Additionally, the endocrine-associated risk of veterinary drug residues in food is yet to be fully characterized. This study aims to systematically compare the translated HTS data with the acceptable daily intake (ADI) values and prioritize the pesticides and veterinary drug residues (n = 294) in food using the exposure-activity ratio (EAR) and Toxicological Prioritization index (ToxPi). The dietary exposure assessment was accomplished using a stochastic human exposure and dose simulation high-throughput model (SHEDS-HT). We selected 76 HTS assays from 12 nuclear receptors to represent the molecular initiating event (MIE) of endocrine-disrupting phenotypes. Chemical prioritization was achieved using 4 methods (i.e., EAR-OED, EAR-ADI, ToxPi-exposure + ADI, and ToxPi-exposure + endocrine score), where the consensus prioritized chemicals were fipronil, furazolidone, oxolinic acid, and oxytetracycline for the Taiwanese population. This case study demonstrates the utility of HTS data in fostering regulatory decisions on chemicals, especially for those lacking comprehensive toxicity data. • Characterize the aggregate exposure of pesticides and veterinary drugs in Taiwan. • Review the high-throughput screening data to assess the endocrine-active potentials. • Compare the in vitro point of departure data with the acceptable daily intake. • Combine exposure and in vitro HTS data to foster chemical prioritization. • A prioritization framework for endocrine-active chemicals was proposed. [ABSTRACT FROM AUTHOR]

Background/purpose: Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids.Methods: An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine.Results: For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine.Conclusion: This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose. [ABSTRACT FROM AUTHOR]

Background/purpose: Silicosis remains the most prevalent occupational disease worldwide. There have been no specific studies focusing on the association between exposure settings at work and the clinical severity in silicosis patients. In this study, we describe and compare the clinical characteristics and silicosis-associated exposure history at work among workers from several types of ceramic production facilities in Taiwan.Methods: We reviewed the medical records of 221 patients who were first diagnosed with silicosis at the Occupational Medicine Clinic of Northern Taiwan in 2012. For each patient, we collected data on demographic characteristics, smoking habits, working history, duration of exposure, and years on the first relevant job. We also retrieved clinical reports of the pulmonary function test and the baseline chest radiography used for silicosis staging.Results: As compared to other ceramic workers, sanitary ceramic workers had a worse X-ray type (p=0.044), more advanced age (p<0.001), longer working duration (p=0.029), and a higher proportion of starting the first relevant job prior to the year 1975 (p=0.003). However, after adjusting for age, work duration, and an initial occupational exposure prior to 1975, sanitary ceramic workers showed a comparable risk for worse X-ray findings to other ceramic workers (adjusted odds ratio=1.18, p=0.704). Results of multivariable regression models on individual lung function parameter also suggested comparably impaired lung function tests between sanitary and other ceramic workers (p>0.05).Conclusion: In this study, we found that sanitary ceramic workers were at a similar risk to other ceramic workers for moderate to severe silicosis when older age and longer working duration were accounted for. [ABSTRACT FROM AUTHOR]

Background/purpose: Pulmonary endarterectomy (PEA) is a potentially curative surgical procedure for patients with chronic thromboembolic pulmonary hypertension. The aim of this study is to review our institutional experience with this operation.Methods: We conducted a retrospective review of PEA performed at our institution between January 2005 and December 2013. The measured outcomes were inhospital complications, improvement in cardiac function and exercise capacity, and actuarial survival after PEA.Results: Ten consecutive patients (7 women, 3 men) underwent PEA with a mean age of 59.9 ± 12.9 years. The preoperative New York Heart Association functional class (NYHA FC) for these patients was either Class III (n = 6) or Class IV (n = 4). The period from symptom onset to diagnosis was 34.3 ± 37.9 months, and that from diagnosis to operation was 31.4 ± 46.8 months. After PEA, the duration of intensive care unit stay and hospital stay prior to discharge were 9.7 ± 5.7 days and 18.7 ± 7.4 days, respectively. Postoperative complications included reperfusion lung edema (n = 3) and pneumonia (n = 1), and all recovered with medical therapy. After a mean follow-up of 48.4 ± 35.1 months, all patients showed marked improvements in their clinical status and were still alive without evidence of disease recurrence.Conclusion: With proper patient selection, the cooperation of a multidisciplinary team, and meticulous postoperative management, PEA can be conducted safely with relatively low risk at a center with limited experience with the procedure. [ABSTRACT FROM AUTHOR]

The distribution patterns of foraminiferal assemblages in relation to trace metals, sediment grain size, and calcium carbonate were studied in 232 surface sediments collected from the northwestern Taiwan Strait. Multivariate analyses of biotic and abiotic data revealed a separation of near-shore, coastal, and deep-water zones. The modified degree of contamination suggested that the overall contamination was very low to low. Trace metals were enriched in the near-shore and outside bays. Their distribution was likely determined by sediment transport pathways and hydrodynamic conditions. High metal concentrations co-occurred with a low density and diversity of foraminiferal assemblages. Pb, Ba, organic carbon, Ga, Zn, Cu, and Co had a positive correlation with near-shore assemblage, whereas Cr and Ni positively related to the deep-water assemblages. Some calcareous foraminifera were favored by CaCO 3 , Sr, and sand. This study highlights species’ responses that are specific to environmental variables. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is the main cause of nosocomial infections, which are increasingly difficult to treat due to the emergence of carbapenem resistance. This study focused on major carbapenemase genes and explored the association between carbapenemase genes, sequence types (ST types), and capsular types (K types). A total of 98 carbapenem-resistant A. baumannii (CRAB) strains were collected from two hospitals, the Chang Gung Memorial Hospital-Lin Kou branch (LCGMH) in northern Taiwan and the CGMH-Kaohsiung branch (KCGMH) in southern Taiwan, from 2015 to 2017. Major carbapenemase genes of class A, B, and D β-lactamases were detected by polymerase chain reaction. All strains except 1 were positive for bla OXA-51-like , 76 strains (77.6%) carried bla OXA-23-like , and 25 strains (25.5%) carried bla OXA-24-like. The regional distribution showed that bla OXA-23-like was more common than bla OXA-24-like in both hospitals (85.3% and 60% in LCGMH and KCGMH, respectively); however, the percentage of bla OXA-24-like was much higher in KCGMH (46.7%) than in LCGMH (16.2%). Oxford multilocus sequence typing and global optimal eBURST analysis were conducted for 59 strains. The results of this study showed the association between bla OXA gene patterns, ST types, and K types and demonstrated that four major K types, KL2, KL10, KL22, and KL52, which were associated with specific ST types, were mainly clustered into clonal complexes CC208 and CC549 (a unique clonal complex found in Taiwan). These findings provide important information for monitoring the epidemiology and dissemination of this pathogen. [ABSTRACT FROM AUTHOR]

Abstract: Sun Moon Lake (SML) is located at 23°52′N, 120°55′E near the center of Taiwan Island. In 2009, deposition of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) in ambient air, water bodies and sediments were measured in SML in this study. The monthly atmospheric PCDD/F deposition ranged from 0.61 to 3.0pg I-TEQm−2 d−1 in the vicinity area of SML. Average PCDD/F concentrations (0.008–0.012pg I-TEQ L−1) in the surface water were uniform and sufficiently mixed at the center, outflow and south bay of SML. However, the PCDD/F content (2.42±0.5ng I-TEQ kg−1 d.w.) of surface sediments measured at the south bay of SML was significantly higher than the PCDD/F content at other sampling sites. To evaluate the anthropogenic pollution history in central Taiwan, PCDD/F concentrations were also analyzed at 1–2cm intervals in three dated sediment cores collected at different locations of SML. The year dating by the sediment cores at different depths was estimated from the sedimentation rate (0.47±0.13–1.35±0.22cmy−1) calculated by 210Pb and 137Cs analysis. Based on the results of isotope analysis of sediment cores collected from the center, outflow and south bay of SML, PCDD/F concentrations at different locations appeared to be quite similar. PCDD/F concentrations in sediment cores began to increase in 1964 and reached a peak (4.78ng I-TEQ kg−1 d.w.) in 1968. In addition, variation in PCDD/F content at different depth of the sediment cores appeared to correlate directly with the rate of organochlorine pesticides production in Taiwan. [Copyright &y& Elsevier]

Résumé: Objectifs: Peu d’études se sont intéressées à l’association entre goutte et cancer. Cette étude examine le risque relatif de cancers au sein d’une cohorte nationale. Méthodes: La base de données de l’assurance maladie nationale de Taïwan constituait la source de données primaires. Les données recueillies de 2000 à 2008 chez des sujets âgés de plus de 20ans et sans antécédent de cancer ont été inclues dans l’analyse. La définition des cas de la goutte correspondait aux dossiers mentionnant un diagnostic de goutte et les traitements adaptés (médicaments hypo-uricémiants, incluant allopurinol, benzbromarone, probénécide et sulfinpyrazone, ainsi que la colchicine). Un modèle de régression de Cox (modèle à risques proportionnels) a été utilisé pour estimer l’association entre goutte et cancer. Résultats: Un total de 694361 patients (355278hommes, 339083femmes) ont été inclus ; parmi eux, 25943présentaient un antécédent de goutte. L’âge moyen (±écart-type) était de 42,3±16,3ans. Pendant les 5471272années-patients de suivi, un cancer a été détecté chez 24088patients (1745 atteints de goutte et 22343 témoins). La plupart des cancers concernaient le foie, le poumon et le côlon. L’incidence globale du cancer était significativement plus élevée parmi les patients goutteux que parmi les témoins (8,7 vs 4,2 cas par 1000 années-patients, p <0,001). Après ajustement sur l’âge et le sexe, la goutte s’est révélée associée au cancer avec un « hazard ratio » (HR) (rapport des risques instantanés) de 1,15 (intervalle de confiance à 95 % [IC], 1,10–1,21 ; p <0,001). La goutte était associée dans la majeure partie des cas au cancer de la prostate, avec un HR ajusté sur l’âge et le sexe de 1,71 (1,45–2,02). D’un autre côté, la goutte tendait à une association inverse, bien que négligeable, avec le cancer du sein (HR ajusté, 0,81 ; IC 95 %, 0,63–1,04). Conclusion: La goutte était associée à un risque de cancer plus élevé, notamment celui de la prostate chez les hommes. [Copyright &y& Elsevier]

Purpose: To investigate parents’ views about new vaccines, we surveyed the attitudes and awareness toward immunization program among parents of children younger than 14 years in Taiwan. Methods: Parents of children were invited to complete a questionnaire in a tertiary referral medical center in Kaoshiung, southern Taiwan from 2006 to 2008. A total of 535 questionnaires were completed. We used descriptive data for the analysis of parents’ views and attitudes toward the current vaccination program in Taiwan. Results: Of the 535 respondents, most parents (93%) did not think the current vaccination program was satisfactory. Few (approximately 8%) preferred self-paid vaccines. About 63% of parents believed that the new (self-paid) vaccines provided more protection, whereas 48% deemed them too expensive. The most popular reason for preferring the new vaccines was greater protection (73%). One-half of parents considered the new vaccines to be expensive. Regarding parental awareness of side effect of vaccination, fever was the most well known and of greatest concern (91%). Most parents (68%) had good awareness of conjugated pneumococcal vaccines, and only few (13%) had heard of the human papilloma virus vaccine. Most parental information of vaccines came from pamphlets at the hospital (56%). Conclusion: We found the awareness of parents about new vaccines to be insufficient. They also considered the new vaccines to be expensive. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma is a rare tumor among the general population, but for people exposed to asbestos, the lifetime risk is high. A 58-year old man presented with suffering from chest pain, upper back pain, shortness of breath, and coughing that had continued for several months. A chest X-ray revealed right-side pleural effusion; however, pleural biopsy from drainage treatment confirmed a diagnosis of malignant mesothelioma. According to his occupational and environmental history, the patient had worked continuously in a porcelain factory for 30 years. The specific characteristics of his work, making asbestos wallboards and gaskets, entailed working in high-temperature conditions with a high fine-particle content in the atmosphere. The high working temperature caused asbestos debris and dust to fall down regularly from the wallboards, however, it was not until recently that the patient had started to wear personal protection. Asbestos is a significant source of hazardous exposure in old buildings, and this case serves as a reminder of the importance of asbestos-related exposure history, which facilitated the correct diagnosis of pulmonary malignant mesothelioma. Asbestos-containing materials that are now banned or regulated are still present in older buildings and remain an exposure hazard; they continue to be a serious health concern in many countries. [ABSTRACT FROM AUTHOR]

Polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), polychlorinated biphenyl (PCB) and heavy metal concentrations were analyzed at 1–2cm intervals in a sediment core collected from a reservoir to evaluate anthropogenic pollution history in central Taiwan. The age of the sediment core was estimated from the sedimentation rate (0.44–0.52cmyear−1, calculated by 210Pb and 137Cs analysis). The highest PCDD/F (4.10ng TEQWHO kg−1 d.w.) and PCB (0.345ngTEQWHO kg−1 d.w.) concentrations occurred around 1985 (i.e. at a downcore depth of 10–12cm). Our results also demonstrated that PCDD/F and PCB concentrations in the reservoir sediment core started to decrease at a depth of 8–10cm (estimated year: 1989). This may be attributed to the fact that the Taiwan Environmental Protection Administration (EPA) proposed the regulation of pentachlorophenol (PCP) production and PCB manufacture in 1983 and 1988, respectively. In addition, a linear increasing trend in metal content with time (towards the core top) was observed for several metals (Zn, Cr, Cu, Cd and Pb). Results of the enrichments rates of anthropogenic metals indicated that the metal/alumina (M/Al) ratios of Zn, Cd and Pb in sediment cores exceeded those in crust compositions by 47%, 59% and 78%, respectively. The results revealed that considerable amounts of heavy metals were carried into the reservoir following significant immigration during the Chinese civil war (1950). [Copyright &y& Elsevier]

Abstract: This work investigates atmospheric visibility by employing two statistical processes for high-frequency extraction: Sobel operator and fast Fourier transform (FFT). In replacing the traditional measurement methods for atmospheric visibility, the new approaches can provide accurate digital data urban visibility by establishing the numerical indices. The procedure is illustrated as follows. Digital images of urban areas in Kaohsiung, a city at the south of Taiwan, are analyzed according to brightness. High-frequency components of the image are extracted to calculate the index values by employing the Sobel operator and FFT. Finally, the correlation between each index and the visual range estimated by trained investigators are evaluated. A good correlation between two indices and the values obtained by visual investigation is affirmed by correlation coefficients (), 0.8139 and 0.7797, respectively. Furthermore, both indices are highly correlated with each other (). Convenient transmission and the exchangeability of digital images of the real-time landscape facilitate the publication of results on the world wide web (WWW). [Copyright &y& Elsevier]

In the paper machine vision, laser interferometer and coordinate measuring machine (CMM) are combined to develop a vision inspection system. The measurement capability of the developed system is investigated by measuring the distances between the lines on a standard line scale. The vision camera is used to replace the probe of the CMM to take the images of the interested lines on a line scale at two different positions. Meanwhile, the displacement of the CCD camera is measured using laser interferometer. Using subpixel edge localization and outlier-excluding least-squares regression, the distance between two interested lines is computed under an image plane coordinate system. By adding the displacement of the CCD camera measured using laser interferometer, the line space can be determined. Experiments have been performed repeatedly to measure the line space on the 1.00 and 300.0 mm line scales. Results indicate that the measured data only have a little fluctuation and are close to those obtained by the NML (National Measurement Laboratory, Taiwan). [Copyright &y& Elsevier]

A hospital-based quasi-experimental (pretest and post-test) study was conducted in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a continuing education program (CEP) on nurses'' practices of cancer pain assessment and their acceptance of patients'' pain reports with respect to four types of misconceptions. A questionnaire was sent to on-duty nurses or head nurses with patient care responsibilities before the implementation of CEP (n = 645) and six months after the program (n = 630). The response rates were 92.6% and 91.3% for pretest and post-test surveys, respectively. The CEP was implemented in 8 weeks with four-repeated sessions of 4-hour lectures. A one-day workshop focused on cancer pain assessment and treatment was held 3 months after the four-repeated sessions. Several educational strategies and teaching materials were used in the CEP. The results showed that CEP made statistically significant yet moderate improvement in nurses'' practices of pain assessment using pain rating scales (pretest 3.29±0.76 vs. post-test 3.48±0.75, P<0.001) and acceptance of patient''s pain reports without misconceptions on addiction (3.12±0.80 vs. 3.39±0.90, P<0.001), phantom pain (3.91±0.96 vs. 4.07±0.92, P = 0.005), and placebo testing (3.63±0.72 vs. 3.81±0.73, P<0.001), except on patient gender-age-related doubts (3.60±0.72 vs. 3.67±0.77, P = 0.109). In order to achieve further improvement, additional follow-up CEP combined with a hospital-wide institutionalization of pain assessment should be promoted and implemented in the future. [Copyright &y& Elsevier]

Aims: To determine the presence of Asp13-p21-ki-ras oncoprotein and p53 oncoprotein in the plasma of vinyl chloride monomer (VCM)-workers in Taiwan. Methods: We used enhanced chemiluminescence (ECL) western blotting to detect Asp13-p21-ki-ras and ELISA to detect mutant p53 protein (p53-Ag) and anti-p53 antibodies (p53-Ab) in the plasma of VCM-exposed workers. Results: Twenty-five out of 251 (10%) VCM-workers were positive for Asp13-p21-ki-ras in plasma, but 0 out of 36 controls were positive. There were 15 out of 95 (15.8%) plasma-positives among the more highly exposed (>480 ppm-month) workers and 10 out of 156 (6.4%) plasma-positives among the lesser exposed (≤480 ppm-month). Compared to the unexposed controls, age and drinking adjusted odds ratios (95% CI) were 1.2 (0.1, 9.8) in the lower exposed workers, and 4.8 (0.8, 28) in the higher exposed workers, and there was a significant linear trend between exposure and plasma positivity (P=0.001). Thirty-three out of 251 (13.2%) VCM-workers were positive for the p53 over-expression (10% with positive p53-Ag and 2.8% with positive p53-Ab). There was a significant association between cumulative VCM exposure concentration and positive p53 expression (P=0.032) among VCM-workers after adjusting for age, hepatitis, drinking and smoking status. Conclusions: Asp13-p21-ki-ras oncoprotein and p53 over-expression (p53-Ag or p53-Ab) can be found in the plasma of VCM-workers in Taiwan, and a significant dose–response relationship exists between plasma oncoproteins expression and VCM exposure. [Copyright &y& Elsevier]

• An end-to-end system for air quality monitoring in Taiwan is presented. • AirBox embeds social dimension within an IoT system for building resilient cities. • Effective ways of inclusion, collaboration and capacity building are discussed. Air pollution is a serious problem and has caused public health concerns all over the world. Despite the evidence, the preparedness and response of citizens has been limited. This underlines the importance of having sustainable air quality monitoring solutions that foster inclusion and multi-stakeholder partnerships for social-scientific interventions. This study illustrates how AirBox project has emerged in Taiwan, where makers and citizens use the sensors to sense air quality and provide the public with actionable data about their environments. The AirBox project includes elements of technology-innovation and citizen science: (1) Participatory Sensing – Static and mobile air quality sensing, (2) Open Data – Open hardware, software and access to data, (3) Co-creation Citizen Science – Citizen-led campaigns and forums, and (4) Outreach – Knowledge sharing, trust building and multi-stakeholder collaboration. The project uses a wide range of sensors to provide extendable solutions and data at fine spatio-temporal resolution. The results are highlighted using five cases studies that show how integrating social dimensions in an air quality monitoring framework can lead to public awareness, data-driven applications and environmentally sustainable cities. The multi-faceted approach highlights the effects of a bottom-up citizen science approach that considers local culture, practices and problems at grassroots. [ABSTRACT FROM AUTHOR]

Background: The recent demonstration of a vaginal biofilm in bacterial vaginosis and its postulated importance in the pathogenesis of recurrent bacterial vaginosis, including relative resistance to therapy, has led to the hypothesis that biofilms are crucial for the development of vulvovaginal candidiasis. The histopathology and microbial architecture of vulvovaginal candidiasis have not been previously defined; neither has Candida, containing biofilm been reported in situ. The present study aimed at clarifying the histopathology of vulvovaginal candidiasis including the presence or absence of vaginal biofilm.Study Design: In a cross-sectional study, vaginal tissue biopsies were obtained from 35 women with clinically, microscopically, and culture-proven vulvovaginal candidiasis and compared with specimens obtained from 25 healthy women and 30 women with active bacterial vaginosis. Vaginal Candida infection was visualized using fluorescent in situ hybridization with ribosomal gene-based probes.Results: Candida microorganisms were confirmed in 26 of 35 biopsies obtained from women with vulvovaginal candidiasis; however, Candida containing biofilm were not detected in any of the cases. Histopathological lesions were exclusively invasive and accompanied by co-invasion with Gardnerella or Lactobacillus species organisms.Conclusion: Histopathological lesions of vulvovaginal candidiasis are primarily invasive in nature and polymicrobial and do not resemble biofilms. The clinical significance of Candida tissue invasion is unknown. [ABSTRACT FROM AUTHOR]

There is little evidence about whether mammalian target of rapamycin (mTOR) inhibitor could prevent post–kidney transplant (KT) urothelial carcinoma (UC) or not. The aim of this study is to analyze the role of mTOR inhibitor add-on in tacrolimus-based kidney transplant recipients. The data were obtained from the Kaohsiung Chang Gung Memorial Hospital using the Chang Gung Research Database and retrospectively reviewed from January 2000 to December 2015. Patients then were categorized into 2 groups: group FK (more than 2-year tacrolimus [FK] prescription) and group FK + mTOR inhibitor (more than 2-year tacrolimus plus at least 6-month continued sirolimus prescription). The primary end point is post-KT UC development. The secondary end point is mTOR inhibitor add-on effect on renal function deterioration episode. There were 140 patients with tacrolimus-based immunosuppressant (group FK) and 82 patients with tacrolimus-based and add-on mTOR inhibitor regimen (group FK + mTOR inhibitor). The follow-up duration, sex distribution, and combined mycophenolate mofetil rate are similar in both groups. Younger age, lower tacrolimus trough level, lower UC incidence, and longer KT-to-UC interval were observed. Short- to intermediate-term results revealed noninferior graft outcome by creatinine level or creatinine deterioration. In our preliminary result, mTOR inhibitor add-on in patients with tacrolimus-based regimen revealed less post-KT UC occurrence. In addition, noninferior graft outcome was also observed. In Taiwan, a high UC prevalence area, mTOR inhibitor add-on strategy can be considered as a preventive strategy for UC after KT. • Less urothelial carcinoma (UC) incidence and better post–kidney transplant UC-free survival rate in mammalian target of rapamycin (mTOR) inhibitor add-on group. • Short- to intermediate-term results also revealed noninferior graft outcome in mTOR inhibitor add-on group • Tacrolimus trough level of first 1-year in mTOR inhibitor add-on group trended to be lower. • Preventive role of mTOR inhibitor in post–kidney transplant UC. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EV-A71), the major pathogen causing hand, foot, and mouth disease, affects young children in the Asia-Pacific region with cyclical epidemics. Numerous studies estimated seroprevalence of EV-A71 neutralizing antibodies. However, evidence of incidence rates from longitudinal studies is scarce. This study aims to examine age-specific incidence rates of EV-A71 infection, and to investigate dynamics of serum neutralizing antibody response to infection by following a birth cohort. We recruited 759 neonates in northern Taiwan from June 2006 to December 2009 and followed these children for 7 years. Study participants' sera were collected at birth, 6, 12, 24, 36, 48, 60, 72 and 84 months of age (m) for conducting neutralization test on EV-A71 to measure age-specific incidence rates and to observe reinfections at different ages. A total of 576 children returning for follow-up were analyzed from 2006 to 2013. The incidence rates increased gradually from 0.68 per 100 personyears at 6m to 19.33 at 60m, and reduced to 9.57 at 72m. The cumulative incidence rate of primary and secondary infections by 84m reached 37.97% and 6.96%, respectively. Of the 123 children with a primary infection, 43% were asymptomatic. The cumulative negative conversion rate of serum neutralizing antibody was 12%, 16.84%, and 23.51% in the first, second, and third year post primary infection, respectively. The decay rate of neutralizing antibody titer was estimated as 4.37% per month, and the half-life of infection-induced neutralizing antibody was estimated as 15.9 months. Our findings suggest that cumulative incidence of primary and secondary infections by 7 years of age was about 38% and 7% after experiencing 2 epidemics. We also characterized the dynamics of neutralizing antibody titers after EV-A71 infections. These findings provide critical information for designing efficacy trials of EV-A71 vaccines and formulating vaccination policy. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the authors present a probabilistic back-analysis of a recent slope failure at a site on Freeway No. 3 in northern Taiwan. Post-event investigations of this failure found uncertain strength parameters and deteriorating anchor systems as the most likely causes for failure. Field measurement after the event indicated an average slip surface of inclination 15°. To account for the uncertainties in input parameters, the probabilistic back analysis approach was adopted. First, the Markov Chain Monte Carlo (MCMC) simulation was used to back-calculate the geotechnical strength parameters and the anchor force. These inverse analysis results, which agreed closely with the findings of the post-event investigations, were then used to validate the maximum likelihood (ML) method, a computationally more efficient back-analysis approach. The improved knowledge of the geotechnical strength parameters and the anchor force gained through the probabilistic inverse analysis better elucidated the slope failure mechanism, which provides a basis for a more rational selection of remedial measures. [Copyright &y& Elsevier]

Abstract: Leaf succulence is common among drought-adapted plants, including many tropical and subtropical epiphytic species. A prominent anatomical feature of many such succulent leaves is a clear, water-storing tissue often referred to as “hydrenchyma” (water-storage parenchyma). Functionally, hydrenchyma appears to store water for use by the leaf during drought. Although this has been confirmed in several laboratory studies, field studies linking the amount of hydrenchyma in plants with availability of water in their environment are lacking. In this study, the relative amount of leaf hydrenchyma in one of the most widely distributed epiphytes in Taiwan, Pyrrosia lanceolata, was measured in plants growing along a gradient of annual mean precipitation from 2048 to 3688mm. In addition, because Pyrrosia lanceolata is a Crassulacean acid metabolism (CAM) plant, the amount of CAM activity was also examined in plants along the gradient. At each of seven sites along the precipitation gradient, leaves were collected, and, using thin mid-leaf slices, the relative areas of the leaf cross-sections occupied by hydrenchyma were determined. CAM, measured as diel changes in leaf acidity, was measured in plants from each site in the field, after 3 days of water-saturation in the greenhouse, and also after 14 days without water in the greenhouse. Regressions of relative hydrenchyma with ten environmental variables in the dry season revealed that the amount of hydrenchyma was significantly and positively correlated with monthly mean number of rainless days, monthly mean number of days with daily mean temperature over 30°C, and monthly mean temperature. During the wet season, relative hydrenchyma area correlated only with the amount of cloud cover, and the correlation was negative. All plants at all sites exhibited CAM acid fluctuations in the field, under water-saturated conditions, and after desiccation. The largest nocturnal acid accumulations were found when plants were well-hydrated in the field and in the greenhouse, although evidence of drought-induced elevations of CAM was found at the drier sites. The results of this study indicate that the amount of leaf hydrenchyma was greatest in areas with warmer, drier environments. Also, drought-induced elevation of CAM activity occurred in plants from drier sites. This may help to explain the wide range of environments inhabited by this epiphytic fern in Taiwan. [Copyright &y& Elsevier]

Abstract: This study analyzed fatal occupational injuries in Taiwan. One thousand eight hundred ninety work-related accident reports filed in the years 1996–1999 were extracted from the annual publication of the Council of Labor Affairs (CLA). These data were analyzed in terms of gender, age and work experience of the accident victim as well as accident type and the work-related source of injury to identify significant contributing factors. The CLA data showed that work-related falls were the leading cause of work-related fatalities in both male and female workers (38.2% of male victims and 39.2% of female victims). Gender differences were also noted in the accident type and age of the injured workers. Male workers had a significantly higher prevalence of fatal occupational injuries than female workers throughout the analyzed period (7.4 compared to 0.9 per 100,000 full-time workers). Young males aged 24 years or less had the highest rate of fatal occupational injuries. The finding that gender and age are major factors in occupational injuries is a significant finding in the field of occupational safety and may be helpful for developing accident prevention programs. [Copyright &y& Elsevier]

In addition, throat swabs of the participants who presented symptoms of HFMD or herpangina were collected for virus isolation and molecular tests to detect EV71 infections. This longitudinal cohort study contributes to precisely estimate incidence rates of EV71 infections via a long-term follow-up, and provides insights into clinical trial designs of EV71 vaccines. B Background: b Enterovirus A71 (EV-A71) is causing cyclical epidemics of fatal hand-foot-mouth disease (HFMD) in Taiwan and other Asian countries. [Extracted from the article]

The Ionospheric Dynamics Exploration and Attitude Subsystem Satellite (IDEASSat/ INSPIRESat-2) is a three-unit (U) CubeSat developed with the objective of providing in-situ measurements of the Earth's ionosphere in order to quantify both global scale ionospheric variability and small scale irregularities. The science payload is the Compact Ionospheric Probe (CIP) - an all in one in-situ plasma sensor developed at Taiwan National Central University (NCU), which is the miniaturized version of the larger Advanced Ionospheric Probe (AIP) that is carried and operational aboard the 450 kg FORMOSAT-5 spacecraft. The spacecraft has been developed by NCU in partnership with the International Satellite Program in Research and Education (INSPIRE) consortium, and is funded by the Taiwan National Space Organization (NSPO), Ministry of Science and Technology, and Ministry of Education as part of the first national effort to encourage small satellite development at Taiwan universities. The development of IDEASSat offers students a hands-on opportunity to learn about space science and technology and will work in conjunction with FORMOSAT-5 and INSPIRESat-1 to provide ionospheric observations spanning different altitudes and local times. The IDEASSat spacecraft subsystems are a combination of commercial off the shelf (COTS) and self-developed components designed by NCU in partnership with other INSPIRE member universities. IDEASSat is expected to be launched in late 2020. In this report, we describe the IDEASSat mission and spacecraft design, as well as unique lessons learned as part of the development process. [ABSTRACT FROM AUTHOR]

Isovaleric acidemia (IVA), a rare autosomal recessive disorder in leucine metabolism caused by defected IVD gene, is characterized by episodes of acute metabolic crisis and psychomotor development retardation. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with IVA from mainland China. Eight patients (three boys and five girls) from eight unrelated families were collected, IVD gene mutations and phenotypes were examined. The patients were admitted because of vomiting, feeding difficulty, psychomotor retardation and "dirty sock" odor. Elevated blood isovaleryl (C5)-carnitine and urine isovalerylglycine were detected from all our patients. Fourteen mutations of the IVD gene were detected, eight of them are novel, c.145C>T (p.Q49Ter), c.359G>A (p.R120Q), c.424C>T (p.R142C), c.458T>C (p.L153P), c.466-1G>T, c.676_677insA (p.T226Nfs*13), c.1039G>A (p.A347T) and c.1076A>G (p.D359G). With this study, a total of 34 alleles were studied in the Chinese population. c.1208A>G (p.Y403C), the common mutation in Taiwan, accounts for 9/34 alleles (7 in previous reports and 2 in this study). We described eight novel mutations detected from eight unrelated Chinese patients and provided evidence to support that the p.Y403C is the hotspot mutation in this population. • Fifteen mutations of the IVD gene were identified from eight Chinese IVA patients. • Eight novel mutations were found. • The mutation p.Y403C is the hotspot mutation in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4-86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7-88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6-92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters.Methods: This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879.Findings: Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% [15/127] to 66% [38/58] for T14, 7% [10/135] to 64% [28/44] for C10), cefazolin (13% [16/127] to 43% [25/58] for T14, 10% [13/135] to 41% [18/44] for C10), cefmetazole (8% [10/127] to 26% [15/58] for T14, 4% [5/135] to 18% [8/44] for C10), levofloxacin (8% [10/127] to 35% [20/58] for T14, 7% [10/135] to 32% [14/44] for C10), gentamicin (13% [19/146] to 47% [27/58] for T14, 15% [22/149] to 45% [20/44] for C10), and trimethoprim-sulfamethoxazole (33% [48/146] to 86% [50/58] for T14, 28% [42/148] to 86% [38/44] for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10.Interpretation: Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy.Funding: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder.Methods: Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring.Results: Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59).Conclusions: Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Background The literature on suicide mortality rates in patients with cardiovascular diseases (CVDs) is limited. Methods Taiwan National Health Insurance Research Database and Taiwan Death Registry were retrieved for patients with the 5 CVDs: congestive heart failure (CHF), acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke (HS), and pacemaker implantation (PMI) between January 1, 2001, and December 31, 2015. We excluded patients younger than 15 years old. The primary outcome was suicidal death. The standardized mortality ratio (SMR) was used to compare the risk of suicidal death in the 5 CVDs to the general population. Results From 2001 to 2015, there were 212,206 patients with CHF, 178,894 patients with AMI, 475,359 patients with IS, 189,555 patients with HS, and 64,173 patients with PMI. The suicide death rate per 100,000 person-year, 95% CI was 59.6 (54.5–64.8) for those with CHF, 44.6 (40.1–49.1) for AMI, 57.6 (54.7–60.5) for IS, 44.6 (40.2–49.0) for HS, 54.0 (45.9–62.0) for PMI, and 20.3 (20.1–20.4) for the general population. Patients with CHF patients had the highest SMR (2.10), followed by IS (1.96), PMI (1.86), HS (1.65), and AMI (1.46). The SMRs for patients with CVDs peaked at year 2 after the diagnosis, declined for patients with AMI, IS, and HS, increased and decreased for PMI alternately, and reached very similar values all five CVDs after 10th year after the diagnosis. Conclusions Patients with acute CVD with AMI, IS, and HS had suicide death rates peaked early after diagnosis, but patients with chronic CVD with CHF and PMI had suicide death rates that increased progressively. In addition, patients with PMI, CHF, IS had highest association with psychiatric illness and patients with PMI who were of young to middle age had highest suicide death rate. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Fritillaria cirrhosa D. Don bulbs contain alkaloids and are one of the most intensively exploited alpine Himalayan medicinal species. In terms of proprietary medicines, our study shows that 210 F. cirrhosa products are offered by 46 suppliers, most of which (44) are situated in China and two in Nepal. A widespread commercial use is as one of the main ingredients in cough syrups. A well known example is "Nin Jiom Pei Pa Koa Herbal Cough & Throat Syrup", which typically contains more F. cirrhosa than any other herbal ingredient in the formulation. The biggest market for F. cirrhosa bulbs is China, where demand exceeds supply of this wild harvested species for use in traditional Chinese medicine (TCM). Cross-border trade from Nepal to China occurs in significant quantities. Bhutan also imports F. cirrhosa bulbs from Nepal. In addition, F. cirrhosa is registered as an active ingredient in traditional herbal medicinal preparations in Australia, Canada, Hong Kong SAR, Malaysia, Republic of Korea, Singapore and Taiwan. There is also an export trade in F. cirrhosa to Europe. Assessing how much F. cirrhosa is traded is complex, however, due to a “look-alike” challenge, as nine Chinese Fritillaria species are traded in Europe ( Fritillaria cirrhosa, F. delavayi, F. hupehensis, F. pallidiflora, F. przewalskii, F. thunbergii, F. unibracteata, F. ussuriensis and F. walujewii ). Aims of the study The aims of this review were to assess the scale of the global trade in F. cirrhosa , and to synthesise studies of the impacts of wild harvest on F. cirrhosa populations and on the extent of emerging cultivation initiatives as an alternative to wild harvest. Methods Firstly, we reviewed published information on studies on impacts of wild F. cirrhosa harvest from across the geographic range of this species. Secondly, global trade data for F. cirrhosa were analysed. Results The principal demand for F. cirrhosa bulbs is in China, where hundreds of different companies produce Fritillaria preparations. Trade data also show that in 2013, China exported over 44 tonnes of F. cirrhosa bulbs to Taiwan and 26.7 tonnes to the Republic of Korea. Extensive commercial use and limited wild stocks result in a high price (2000 – 3800 CNY per kg (around US$ 303 –560 per kg in 2017)) for F. cirrhosa bulbs. Prices of cultivated Fritillaria bulbs are much lower (600–680 CNY per kg in 2017) than wild harvested bulbs. But due to very specific growth requirements of F. cirrhosa , cultivation is not yet able to meet total demand. The consequence is continued exploitation of wild stocks. At the same time, however, an increasing proportion of the demand is met by cultivation of alternative Fritillaria species that are easier to grow than F. cirrhosa . The air-dry mass of F. cirrhosa bulbs varies between 0.0917 and 0.1116 g per bulb. This represents 8960 – 10,900 bulbs/kg or 8.9 – 10.9 million bulbs per tonne. Current demand therefore represents billions of bulbs per year. Conclusions Demand for F. cirrhosa bulbs, particularly from China, makes this species one of the most intensively harvested alpine Himalayan medicinal bulbs. Although F. cirrhosa is listed as a Class III protected species in China, billions of these tiny, wild harvested bulbs are sold per year. Due to demand exceeding supply, the price of F. cirrhosa bulbs has increased dramatically. Between 2002 and 2017, for example, the price of wild harvested F. cirrhosa bulbs increased over nine-fold, from the equivalent of US$60 in 2002 to US$560 per kg in 2017. To date, cultivation has been unable to meet the entire market demand for F. cirrhosa bulbs, although other Fritillaria species are successfully cultivated on a larger scale. [ABSTRACT FROM AUTHOR]

Background: The incidence of nasopharyngeal carcinoma (NPC) is higher in Chinese than in Caucasian populations. Genetic, viral, and lifestyle factors may explain these ethnic differences in the incidence of NPC. In the present study, we examined the familial aggregation, heritability, and relative risks (RRs) of NPC using a nationwide database in Taiwan.Methods: A population-based family study was conducted using the Taiwan National Health Insurance Research Database. Participants included all individuals (N=23,422,955) registered with that database in 2013; of these, 17,653 had NPC. Among them, 47.45%, 57.45%, 47.29%, and 1.51% had a parent, child, sibling, and twin, respectively, with NPC.Results: Among the approximately 23 million Taiwan NHI beneficiaries in 2013, the relative risks (RRs) (95% confidence intervals) for NPC were 34.46 (5.12-231.77) for twins of the patients, 9.23 (6.34-13.43) for siblings, 3.80 (2.97-4.86) for parents, 3.74 (2.60-5.37) for offspring, and 1.78 (1.16-2.74) for spouses without genetic similarity. The mean age of onset in first-degree relative-affected NPC patients was 35.5years compared to 39.0years for NPC patients without affected first-degree relatives (p≤0.0001). Using a threshold liability model, the accountability for phenotypic variance of NPC was estimated to be 61.3% for genetic factors (heritability), 13.9% for shared environmental factors, and 24.8% for non-shared environmental factors. The probability of a patient with NPC to be sporadic was 82.8%.Conclusion: This population-based analysis suggested a strong familial tendency in the development of NPC. Screening of first-degree relatives of NPC patients is recommended, particularly in endemic regions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aspergillus luchuensis is a non-toxigenic fungus in fermentation of pu-erh tea. • The genome of A. luchuensis was sequenced and annotated. • Enzymes related to hydrolysis and O-methylation of phenolics were identified. • Knowledge of functions and mechanisms of A. luchuensis were advanced. Aspergillus fungi are extensively used in traditional food fermentation, so their functions, mechanisms, and safety risks are worth exploring. In this study, a dominant fungal strain (P1) was isolated from a fermented pu-erh tea and identified as A. luchuensis by phylogenetic analysis of fungal internally-transcribed spacer sequencing, partial β-tubulin and calmodulin genes. A pure-strain fermentation of tea leaves was developed, and tea compounds were analyzed by widely-targeted metabolomics, using high-performance liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LC-MS). The mycotoxins, aflatoxin (B1, B2, M1 and M2), fumonisin B1 and B2, ochratoxin A, citrinin, were not detected in fermented tea leaves using methods in the National Standard of the Peoples' Republic of China. The genome of 36.60 Mb with 11,836 protein-coding genes was sequenced by PacBio sequencing and annotated. Expression of fungal genes during fermentation was analyzed by Illumina HiSeq 2500; genes encoding enzymes including glycoside hydrolases, phenolic acid esterases, laccases, tyrosinases, dehydrogenases, peroxidases, dioxygenases, monooxygenases, decarboxylases and O-methyltransferases were identified. These enzymes catalyze hydrolysis, oxidation, ring cleavage, hydroxylation, decarboxylation and O-methylation of phenolic compounds , significantly (p < 0.05) changing the phenolic compound composition. While, phenolic compounds were degraded through degradation of aromatic compounds pathways and xenobiotics biodegradation and metabolism pathways. These findings advance knowledge of the functions and mechanisms of action of Aspergillus in traditional food fermentation. [ABSTRACT FROM AUTHOR]

Small abalone (Haliotis diversicolor) is an economically important shellfish in aquaculture, yet its sex determination mechanism remains unclear. Based on the re-sequencing data, candidate sexually dimorphic loci, including 281 SNPs and 21 InDels, were screened out in small abalone. The candidate sexually dimorphic SNPs were located on thirteen chromosomes but mainly on Chr. 3 (43.4%) and Chr. 9 (26.7%); while the candidate sexually dimorphic InDels were located on six chromosomes and also mainly on Chr. 3 (38.1%) and Chr. 9 (26.7%). After being checked with Integrative Genomic Viewer (IGV) and PCR, a dominant marker (SD3) based on three consecutive sexually dimorphic SNPs on Chr. 3 and a codominant marker (SC9) based on a male-specific deletion on Chr. 9 were developed to distinguish the genetic sex in small abalone. PCR validation gained 100% consistence for both sex-specific markers in the progenies of Taiwan population and an intra-hybrid variety with male parents originated from Tokyo population. The successful development of the male-specific markers suggested that small abalone has a male heterogametic sex determination and may have two sex-linked chromosomes, and also provided important tools and clues for further studies on mechanism of sex determination in small abalone. • Two sex-specific markers were developed. • A male heterogametic sex determination was revealed. • Two sex-linked chromosomes were preliminarily identified. [ABSTRACT FROM AUTHOR]

Summary Objectives To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors. Methods The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed. Results Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence interval (CI) 1.56–8.96); higher CD4 counts (aOR for per 50 cells/μl increase 1.51, 95% CI 1.12–2.03) and the concurrent use of trimethoprim/sulfamethoxazole (aOR 14.01, 95% CI 1.98–98.95) were associated with hepatotoxicity. Conclusions Abnormal liver function at baseline was significantly associated with skin rashes, while a higher CD4 count and the concurrent use of trimethoprim/sulfamethoxazole were associated with hepatotoxicity after the initiation of nevirapine-containing cART in HIV-infected Taiwanese patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] Winter monsoon not only brings cold air but also transports air pollutants to Taiwan. [•] Biomass burnings are important dioxin emission sources in Southeast Asia. [•] Typhoon events have a documented impact on the remobilization of dioxins. [Copyright &y& Elsevier]

Abstract: Objectives: Accumulating evidence suggests that gout is associated with increased overall and cardiovascular mortality. Using data from a large consecutive cohort of gout sufferers who were followed for 8 years, we investigated mortality among gout sufferers and compared the results with data from the general population of Taiwan. Methods: The study comprised 6631 people who had gout diagnosis at outpatient department of the Chang Gung Memorial Hospital in 2000. Survival status and cause of death were ascertained by examining the National Death Registry of Taiwan through 2008. Results: During 53,048 person-years of follow-up in 6631 gout patients, 1273 (male, 941; female, 332) deaths were identified, corresponding to the crude mortality rate was 21.3 (male, 20.0; female, 26.1) per 1000 patient-years, which was significantly higher than that of the national population. As compared with the national population of Taiwan in 2000, the all-cause standardized mortality ratio (95% confidence interval) was 1.29 (1.21–1.37) for men and 1.70 (1.53–1.89) for women. Both men and women in this cohort had higher standardized mortality ratios for death due to kidney diseases (men, 3.10; women, 3.54), endocrine and metabolic diseases (men, 2.24; women, 2.71), and cardiovascular diseases (men, 1.58; women, 1.81). Multivariate Cox regression showed no difference in mortality between genders. Discussion/Conclusions: Individuals with gout have increased mortality risk in both sexes; however, the extent of risk increment is higher in women. Kidney diseases, endocrine and metabolic diseases, and cardiovascular diseases are primary causes of death. [Copyright &y& Elsevier]

Résumé: Objectifs: De nombreuses données suggèrent que la goutte est associée à une augmentation de la mortalité globale et cardiovasculaire. Nous avons étudié la mortalité chez les patients goutteux au sein d’une importante cohorte de patients consécutifs atteints de goutte et suivis pendant huit ans, puis nous avons comparé les résultats avec les données de la population générale taïwanaise. Méthodes: Cette étude comportait 6631 patients qui avaient un diagnostic de goutte, issus des consultations du service de l’hôpital Chang Gung Memorial en 2000. La survie et la cause du décès ont été déterminées en examinant le registre national des décès de Taiwan jusqu’en 2008. Résultats: Pendant le suivi de 53 048 patients-années chez 6631 patients goutteux, 1273 (hommes, 941 ; femmes 332) décès ont été identifiés, ce qui correspond à un taux de mortalité brute de 21,3 (homme, 20,0 ; femme, 26,1) pour 1000 patients-années, taux significativement plus élevé que celui de la population nationale. En comparaison à la population nationale taïwanaise en 2000, le ratio de mortalité standardisés toutes causes (95 % de l’intervalle de confiance) était de 1,29 (1,21–1,37) pour les hommes et de 1,70 (1,53–1,89) pour les femmes. Dans cette cohorte, les hommes et les femmes avaient des ratios de mortalité standardisé plus élevés pour les décès liés aux maladies rénales (hommes, 3,10 ; femmes, 3,54), aux maladies métaboliques (hommes, 2,24 ; femmes, 2,71) et aux maladies cardiovasculaires (hommes, 1,58 ; femmes, 1,81). Une régression multivariée par modèle de Cox n’a pas mis en évidence de différence de mortalité entre les sexes. Discussion/Conclusions: Les patients taïwanais atteints de goutte ont un risque plus élevé de mortalité pour les deux sexes ; cependant, l’augmentation du risque est plus importante chez la femme. Les maladies rénales, endocriniennes et métaboliques ainsi que les maladies cardiovasculaires sont les principales causes de décès. [Copyright &y& Elsevier]

Abstract: Objective: Betel quid (BQ) components induce the secretion of tumour necrosis factor-alpha (TNF-α) in oral keratinocytes, which promotes oral mucosal inflammation and oral cancer. This study was carried out to evaluate the association of TNFA genetic variants (−308G>A and −238G>A) with the risk and prognosis of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC). Design: A total of 403 subjects (205 cancer cases and 198 healthy controls) who habitually chewed BQ were recruited. The genotypes were determined by TaqMan real-time assays. Results: G allele and G/G genotype at TNFA −308 were associated with a 1.95-fold (95%CI: 1.16–3.28, p corrected =0.024) and 2.28-fold (95%CI: 1.30–4.00, p corrected =0.008) increased risk of cancer as compared to those with A allele or A/A+A/G genotypes, respectively. In addition, G allele (p =0.080) and G/G genotype (p =0.076) at TNFA −238 were associated with a borderline but statistically significant increased risk of OPSCC. The combined G/G+G/G genotype at both loci had a 2.37-fold increased risk of OPSCC as compared to those with other combined genotypes (95%CI: 1.41–4.00, p =0.001). Interactions between combined genotypes and smoking status were also found to contribute to risk of BQ-related OPSCC. There was no association of TNFA genotypes with clinicopathologic findings or the survival of OPSCC patients. Conclusions: BQ-chewers who carry the G allele or G/G genotype in TNFA −308 may have an increased risk of OPSCC. The intensity of cigarette smoking modulates the effect of the combined TNFA genotypes on risk of BQ-related OPSCC. [Copyright &y& Elsevier]

Abstract: Aim of this study: The Xue-Fu-Zhu-Yu decoction (XFZYD) is a well-known traditional Chinese medicine for treating cardiovascular diseases. The therapeutic effects of this XFZYD have been well documented especially in treating of atherosclerosis and hyperlipidemia. Since this decoction can induce endothelial progenitor cell angiogenesis, it can provide experimental evidence for the treatment of ischemic diseases. Patients who are admitted to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging. Therefore, medical research has been devoted to finding an alternative and/or complementary therapy for ischemic stroke. In the present study, we evaluated the protective effect of the combination of XFZYD with or without rt-PA in a rat model of thromboembolic stroke. Materials and methods: A cerebral thromboembolic stroke animal model and immunoblotting analysis were used to assess the effects of XFZYD and rt-PA. Results: Treatment with rt-PA (8mg/kg) or XFZYD (1.5 and 3.0g/kg/day) alone showed slight reductions in the infarct volume compared to solvent-treated rats. However, XFZYD (1.5 and 3.0g/kg/day) obviously potentiated rt-PA-mediated reduction in the infarct volume in cerebral ischemic regions. In addition, treatment with rt-PA significantly reduced both tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) but not hypoxia-inducible factor (HIF)-1α or active caspase-3 expressions in ischemic regions, whereas treatment with XFZYD (3.0g/kg/day) significantly reduced all of these protein expressions in ischemic regions. Moreover, treatment with XFZYD (1.5 and 3.0g/kg/day) obviously potentiated rt-PA-mediated reductions in TNF-α, iNOS, HIF-1α, and active caspase-3 expressions. Conclusions: Results of this study suggest that XFZYD potentiated rt-PA-mediated neuroprotection against thromboembolic stroke in rats. This neuroprotection is probably mediated by the inhibition of HIF-1α and TNF-α, followed by the inhibition of inflammatory responses (i.e., iNOS) and apoptosis (active caspase-3). These results provide a better understanding of the scientific validation of the therapeutic value of the combination of XFZYD with rt-PA in ischemic stroke. [Copyright &y& Elsevier]

Abstract: In this work, a financial news headline agent is proposed to assisting the investors in deciding to buy and to sell stocks in Taiwan market after receiving the essential real-time news headline disseminated by the agent. Weighted association rules and text mining techniques are used to derive the significance degree of each newly arrived news headline on the fluctuation of Taiwan Stock Exchange Financial Price Index on the next trading day. The experimental results reveal that the proposed work indeed achieves significant performance and demonstrate its feasibility in the applications of real-time information dissemination, such as financial news headlines via Internet. [Copyright &y& Elsevier]

Background: Use of selective cyclooxygenase (COX)-2 inhibitors is associated with a better gastrointestinal (GI) safety profile than use of other NSAIDs. However, the risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications) in COX-2 inhibitor users have been rarely evaluated in the past. Objective: The aim of this study was to assess the annual incidence of and identify the risk factors for clinical upper GI events in chronic COX-2 inhibitor (celecoxib and etoricoxib) users. Methods: A prospective, hospital-based, observational cohort study was conducted in patients taking COX-2 inhibitors (celecoxib or etoricoxib) without comorbidity. COX-2 inhibitor prescription was conducted according to the guidelines issued by the Taiwan National Health Insurance and was identified by the computerized prescribing system of the Taipei Veterans General Hospital, Taipei, Taiwan. Patients with cardiovascular disease, pulmonary, hepatic or renal insufficiency, or malignancy were excluded. Patients received regular follow-up once a month. Between visits, patients were asked to report to the outpatient clinic if they had persistent ulcer or GI symptoms (dyspepsia, vomiting, nausea, heartburn, or acid regurgitation) not relieved by antacids for 1 week, or to the emergency department if they had evidence of GI bleeding or ulcer complications (melena, hematemesis, hematochezia, or sudden onset of severe epigastric pain). Endoscopy was performed to document any gastroduodenal ulcers with or without ulcer complications. The primary end point was the annual incidence and the significant risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications). Results: A total of 1158 COX-2 inhibitor users were identified; 96 refused to participate and 129 were excluded. The mean (SD) age of the remaining 933 COX-2 inhibitor users was 69 (15) years with 528 women (56.6%) and 405 men (43.4%). Mean time of follow-up was 12.4 months. The annual incidence of clinical upper GI events in these patients taking COX-2 inhibitors was 4.6% (44 events/959 patient-years), with symptomatic ulcers in 3.6% and ulcer complications in 1.0%. Multivariate logistic regression analysis found that a history of peptic ulcer disease (PUD) (odds ratio [OR = 4.61; 95% CI, 1.86–11.40; P = 0.001), concomitant use of steroids (OR = 2.99; 95% CI, 1.39–6.46; P = 0.005), aspirin (OR = 13.47; 95% CI, 5.89–30.82; P < 0.001), and other NSAIDs (OR = 60.49; 95% CI, 11.93–306.64; P < 0.001) were significant independent risk factors for clinical upper GI events in these patients taking COX-2 in-hibitors. Age >60 years was not found to be a risk factor. Conclusions: The annual incidence of clinical upper GI events was 4.6% in these Taiwanese patients without comorbidity taking COX-2 inhibitors. A history of PUD and concomitant use of steroids, aspirin, or other NSAIDs, were found to be significant risk factors for clinical upper GI events in these patients. [Copyright &y& Elsevier]

Summary: Background: Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. Methods: Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. Findings: 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6·5 months (95% CI 5·56–7·56) in patients treated with sorafenib, compared with 4·2 months (3·75–5·46) in those who received placebo (hazard ratio [HR] 0·68 [95% CI 0·50–0·93]; p=0·014). Median TTP was 2·8 months (2·63–3·58) in the sorafenib group compared with 1·4 months (1·35–1·55) in the placebo group (HR 0·57 [0·42–0·79]; p=0·0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10·7%]), diarrhoea (nine patients [6·0%]), and fatigue (five patients [3·4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11·4%]) and diarrhoea (11 patients [7·4%]); these adverse events rarely led to discontinuation. Interpretation: Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma. Funding: Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. [Copyright &y& Elsevier]