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Guselkumab effectively treats moderate-to-severe psoriasis.To evaluate the cumulative safety experience of guselkumab using pooled data from the VOYAGE 1 and 2 studies through 5 years.Patients were randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-to-guselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264.Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed.No direct treatment comparisons were possible after week 52.The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis.

With the busy life of modern people, more and more consumers are preferring to shop online. This change on shopping behavior results in large volumes of packages must be transported, and thus research on logistics planning considering real constraints has increased. To solve this problem, several heuristics or evolutionary methods with expert knowledge were proposed previously, but they are usually inefficient or need a large amount of memory. In this paper, we propose a hybrid approach called Iterative Logistics Solution Planner (ILSP) for not only quickly finding a nice logistics solution but also iteratively improving the solution quality while meeting the real logistics constraints. ILSP contains two main phases including initial logistics solution generation and iterative logistics solution improvement based on the intelligence and knowledge from domain experts. Several algorithms and strategies are designed in ILSP for package partitioning, route planning and quality improvement. From the view of expert systems, the significance and impact of ILSP are simultaneously taking both computational efficiency and iterative quality improvement based on the expert knowledge into account on logistics planning problem with pickup and delivery. Through the rigorous experimental evaluations of real logistics data, the results demonstrated the excellent performance of ILSP.

Drawn from theories in group diversity and group performance, this study examines the association between board diversity, measured in both relation-oriented dimension (i.e., gender, race, and age) and task-oriented dimension (i.e., tenure and expertise), and board performance in corporate investment oversight. We assess suboptimal investment by measuring how much firms deviate from the expected level of capital expenditures, R&D expenses, and acquisition spending within their industry. Using a sample of 15,125 firm-year across 1898 firms from 1998 to 2014, we find that task-oriented diversity attributes, such as tenure and expertise, are negatively associated with suboptimal investment, suggesting that diverse boards in terms of firm specific experience and functional expertise are more effective in overseeing corporate investment activities than homogeneous boards. Our results shed light on the recent regulatory requirements on board diversity and recommend greater task-oriented diversity in corporate boardrooms.

Accumulating data has revealed a rapidly rising incidence of pancreatic cancer in Western countries, but convincing evidence from the East remains sparse. We aimed to quantify how the incidence and mortality rates of pancreatic malignancy changed over time in Taiwan, and to develop future projection for the next decade.This nationwide population-based study analyzed the Taiwan National Cancer Registry and the National Cause of Death Registry to calculate the annual incidence and mortality rates of pancreatic malignancy from 1999 to 2012 in this country. The secular trend of the incidence was also examined by data from the National Health Insurance Research Database.A total of 21,986 incident cases of pancreatic cancer and 20,720 related deaths occurred during the study period. The age-standardized incidence rate increased from 3.7 per 100,000 in 1999 to 5.0 per 100,000 in 2012, with a significant rising trend (P0.01). The increase was nationwide, consistently across subgroups stratified by age, gender, geographic region, and urbanization. Data from the National Health Insurance Research Database corroborated the rise of incident pancreatic cancer. Mortality also increased with time, with the age-standardized rate rising from 3.5 per 100,000 in 1999 to 4.1 per 100,000 in 2012 (P0.01). In accordance with the incidence, the mortality trend was consistent in all subgroups. Both the incidence and mortality were projected to further increase by approximately 20% from 2012 to 2027.The incidence and mortality of pancreatic cancer have been rapidly rising and presumably will continue to rise in Taiwan.

A tumor-mapping algorithm was proposed to identify the same regions in different passes of automated breast ultrasound (ABUS). A total of 53 abnormal passes with 41 biopsy-proven tumors and 13 normal passes were collected. After computer-aided tumor detection, a mapping pair was composed of a detected region in one pass and another region in another pass. Location criteria, including the radial position as on a clock, the relative distance and the distance to the nipple, were used to extract mapping pairs with close regions. Quantitative intensity, morphology, texture and location features were then combined in a classifier for further classification. The performance of the classifier achieved a mapping rate of 80.39% (41/51), with an error rate of 5.97% (4/67). The trade-offs between the mapping and error rates were evaluated, and Az = 0.9094 was obtained. The proposed tumor-mapping algorithm was capable of automatically providing location correspondence information that would be helpful in reviews of ABUS examinations.

Objectives Oral cancer is the fourth most common cancer among men in Taiwan. Betel nut consumption is a major risk factor for oral cancer, but the association between betel nut chewing and the long-term secular trend of oral cancer incidence is unclear. Materials and methods We conducted an age-period-cohort analysis to examine the incidence rates of oral cancer among men in Taiwan from 1997 to 2016. Results The oral cancer incidence rate among men doubled between 1997 and 2009, but the trend leveled off thereafter. Oral cancer incidence rates in the oldest age group (80–84 y) were approximately 85 times those of the youngest group (25–29 y). The period effect was weak, and the cohort effect exhibited a drastically increasing trend from 1917 (midyear for 1913–1921) to 1972 (1968–1976) birth cohorts and then a decreasing trend afterward. The Spearman rank correlation coefficient between the cohort effects on oral cancer incidence among men and the average consumption of betel nut with a lag time of 30 years had a significant and extremely high value of 0.993. Conclusions Our findings suggest that betel nut chewing is the main driver of the cohort effect for oral cancer incidence rates among men in Taiwan. In addition to reduced betel nut consumption, a decrease in smoking prevalence may also have contributed to the reduction in oral cancer incidence after the 1972 birth cohort; moreover, the increasing prevalence of alcohol consumption in Taiwan is unlikely to be the reason for the cohort effect for oral cancer.

This study examines the association between board diversity and corporate risk taking. Research on board diversity has focused on gender diversity, leaving board diversity beyond gender diversity largely unexplored. We construct diversity indexes to measure board diversity in multiple dimensions, including gender, race, age, experience, tenure, and expertise. We use five variables to proxy for corporate risk taking: capital expenditures, R&D expenses, acquisition spending, the volatility of stock returns, and the volatility of accounting returns. We find that firms with more diverse boards are more risk averse, spending less on capital expenditure, R&D, and acquisitions, and exhibiting lower volatilities of stock returns and accounting returns than those with less diverse boards. Our additional analysis shows that firms with more diverse boards are more likely to pay dividends, as well as pay greater amount of dividend per share than their counterparts, confirming that board diversity is negatively associated with risk taking. We also find strong evidence that board diversity significantly curbs excessive risk taking for firms with above industry median risk taking activities. Our results shed light on the desirability of recent legal and disclosure requirements to enhance board diversity and provide implications that nominating and governance committees should consider in forming the best practices for board composition.

Drawing from institutional isomorphism, gender socialization theory, the ethics of care, and social identity theory, we examine the impact of geographic locality, product market competitions, and owners’ demographic characteristics on a firm’s decision to be a certified B Corporation. Using two sets of data: a hand-collected sample of 743 small businesses receiving a B Corporation certification between 2007 and 2014 and a sample of 902 firms participating in a B Lab survey from 2011 to 2013, we examine factors that influence firms’ decision to obtain the B Corporation and their environment, social, and governance (ESG) performance. Firms in states that are Democratic-leaning, have a lower hourly wage rate, or have a greater religious population are more likely to be early adopters and leaders of the B Corporation movement than those in other states. On average, states with a higher unemployment rate and more democratic-leaning voters have more B Corporation certified firms in each year and over the years. Additionally, product market competition is positively associated with firms’ likelihood of obtaining B Corporation certification and their ESG scores.

BackgroundElastography is a new sonographic imaging technique to acquire the strain information of tissues and transform the information into images. Radiologists have to observe the gray-scale distribution of tissues on the elastographic image interpreted as the reciprocal of Young's modulus to evaluate the pathological changes such as scirrhous carcinoma. In this study, a computer-aided diagnosis (CAD) system was developed to extract quantitative strain features from elastographic images to reduce operator-dependence and provide an automatic procedure for breast mass classification. MethodThe collected image database was composed of 45 malignant and 45 benign breast masses. For each case, tumor segmentation was performed on the B-mode image to obtain tumor contour which was then mapped to the elastographic images to define the corresponding tumor area. The gray-scale pixels around tumor area were classified into white, gray, and black by fuzzy c-means clustering to highlight stiff tissues with darker values. Quantitative strain features were then extracted from the black cluster and compared with the B-mode features in the classification of breast masses. ResultsThe performance of the proposed strain features achieved an accuracy of 80% (72/90), a sensitivity of 80% (36/45), a specificity of 80% (36/45), and a normalized area under the receiver operating characteristic curve, Az=0.84. Combining the strain features with the B-mode features obtained a significantly better Az=0.93, p-value

We examine the association between product market competition and earnings management activities. We use the Herfindahl-Hirschman Index (HHI), a widely used measure for market concentration, as a proxy for product market competition. We examine two forms of earnings management: accrual-based and real activity-based. Our results are mixed, but generally suggest that both income-increasing accrual manipulation and real activity-based manipulation are more prevalent among firms in low competition industries than those in high competition industries. Our findings are robust to various measures of earnings management, alternative measures of product market competitions, and different subsamples. We further explore the reasons why firms in low competition industries are more inclined to manage earnings and find that the market consequences of missing important earnings targets are more severe among firms in low competition industries than those in high competition industries.

Pemphigus is a potentially life-threatening autoimmune blistering disease. However, little is known about the all-cause and cause-specific mortality among patients with pemphigus compared with the general population. The incidence of pemphigus in Taiwan has not been described previously. The objective of this study was to estimate the incidence of pemphigus in Taiwan and to investigate the overall mortality, causes of death, and cause-specific mortality in a nationwide population-based cohort of pemphigus patients. The study cohort included 853 patients newly diagnosed with pemphigus between 2002 and 2009 in the National Health Insurance Research Database. Survival status, date of death, and cause of death were ascertained by linking the study cohort with the National Register of Deaths Database of Taiwan. All-cause and cause-specific standardized mortality ratios (SMRs) were estimated. The incidence of pemphigus in Taiwan was 4.7 (95% confidence interval (CI), 3.2–6.2) per million per year. Overall, 88 deaths were observed during a mean follow-up period of 3.8 years, which was more than two times the number expected (SMR, 2.36; 95% confidence interval, 1.92–2.91). In the analysis of causes of death, the SMRs for death due to pneumonia (3.64; 95% CI, 1.30–10.21), septicemia (11.57; 95% CI, 2.95–45.34), cardiovascular disease (2.69; 95% CI, 1.18–6.12), and peptic ulcer disease (8.44; 95% CI, 1.22–58.21) were significantly higher than expected. We concluded that the incidence of pemphigus is not low in Taiwan, and the overall mortality among pemphigus patients is two times greater than that of the general population. In particular, patients with pemphigus have higher risk of mortality from systemic and respiratory tract infections, cardiovascular disease, and peptic ulcer disease.

Previous studies have shown awareness of uremic dysfunction in end-stage renal disease (ESRD) patients. Dysautonomia in ESRD patients may be reversible after renal transplantation. We used a power spectral analysis (PSA) of heart rate variability (HRV) to assess alterations of autonomic activity in 14 controls and 14 nondiabetic hemodialysis ESRD patients who had undergone renal transplantation. Compared with matched control subjects, the power frequency determinations of low frequency (LF; 3.42 ln(ms(2)) vs 6.38 ln(ms(2)); P < .05 high frequency (HF; 2.29 ln(ms(2)) vs 5.27 ln(ms(2)); P < .05)), and total power (TP; 5.39 ln(ms(2)) vs 7.53 ln(ms(2)); P < .05) were significantly suppressed in ESRD patients undergoing hemodialysis. ESRD patients showed significantly improved HRV after renal transplantation. After renal transplantation, there was no significant difference in the TP (6.82 ln(ms(2)) vs 7.53 ln(ms(2)); P = .15) component between measurements in both patient subgroups. We further divided the ESRD patients into 2 groups based on their pretransplantation HRV, observing alterations in HRV after renal transplantation. Patients with significantly improved HRV were those with more suppressed HRV before transplantation (HF

This study examines whether nonfinancial patent information is useful to investors in assessing and valuing biotech firm's long-term financial performance. Using six patent variables measuring both quantity and quality aspects of patents, I find that patent information is associated with biotech firm's subsequent financial performance. In addition, I derive a return model to test whether patent information adds incremental value-relevance over traditional accounting measures to the market valuation in the biotech industry. The result suggests that nonfinancial patent information captures the biotech firms’ value not valued by traditional accounting measures.

Hsu et al. recently pointed out that the Ku-Wang scheme is vulnerable to modification attack and further proposed an improvement on their scheme. However, this article will show the improvement which they claim is still vulnerable by off-line password guessing attack.

The coral-inhabiting snails, Coralliophila violacea (Lamarck), are widely distributed in the Indo–Pacific region. It has been inferred from field data that sex changes have occurred and might be influenced by neighbors. In this study, we designed a field experiment with 2 treatments, i.e. `single males' and `male–female pairings' to test the hypothesis of sex changes as well as the role of neighbors on sex changes. Snails were collected by SCUBA diving from the surface of massive coral Porites lobata in shallow waters (

Many firms define their fiscal quarters as 13-week periods. For these firms each fiscal year contains 52 weeks, which leaves out one/two day(s) a year. To compensate, one extra week is added to every fifth/sixth year; consequently, one quarter therein comprises 14 weeks. We find evidence of predictable stock returns and forecast errors in 14-week quarters, which suggests that investors and analysts do not, on average, adjust their expectations for the extra week. The ease with which 14-week quarters can be predicted, and expectations adjusted, suggests a surprising lack of effort on the part of investors and analysts.

SYNOPSIS: This study evaluates the extent to which the FASB and IASB convergence projects and the EU-wide adoption of IFRS have impacted the differences between firms’ financial results under U.S. GAAP and IFRS. Using 2004 to 2006 reconciliation disclosures of 75 EU cross-listed firms, we find that the average gap between U.S. GAAP and IFRS income and between U.S. GAAP and IFRS shareholders’ equity declined from 2004 to 2006, consistent with convergence, though the net income gap remains significant. Although both pensions and goodwill are included in the convergence projects, these adjustments appear to be the dominant reconciliation items. Across the EU, net income and shareholders’ equity reconciliation amounts differ significantly by industry and by legal origin of the firm’s home country, raising questions about the homogeneity of IFRS as implemented. Furthermore, most firms report IFRS net income (shareholders’ equity) higher (lower) than U.S. GAAP net income (shareholders’ equity), with the result that 28 percent of the sample firms’ 2006 ROE under IFRS is more than 5 percentage points higher than under U.S. GAAP, whereas fewer than 10 percent of the sample report ROE more than 5 percentage points lower. Finally, shareholders’ equity reconciliations and income reconciliations appear value-relevant, although results are somewhat sensitive to model specification. Overall, our findings indicate that significant numerical differences still exist between results under IFRS and U.S. GAAP, despite convergence. In light of the SEC’s elimination of the requirement for reconciliations between the two sets of standards and the potential adoption of provisions allowing U.S. firms to choose between the standards, investors and other financial statement users should be aware of the significant numerical differences.

The purpose of this paper is to investigate the impact on pay-performance sensitivity of a commitment by regulatory bodies to monitor the auditing of managers' financial reporting. We approach our investigation first by modeling the effects of an imposed mandatory audit of the auditor. We suggest that in a more rigorous audit environment, the reliability of performance measures increases. In motivating employees to work to their maximum potential, investors can rely on these performance measures to better effect. We then test our model in an empirical setting by comparing managers' pay-performance sensitivity before and after the passage of the Sarbanes-Oxley Act of 2002 (SOX). Our model reveals that both managerial effort levels and pay-performance sensitivity increase from a laissez-faire environment with the introduction of a regulatory commitment to auditing. Consistent with the model's prediction, our empirical tests of the impact on managerial incentive schemes after SOX reveal that pay-performance sensitivity did in fact increase.

Question: A 55-year-old woman with a history of hysterectomy for uterine myoma 2 yeas ago was referred to our hospital with a 2-month history of intermittent lower abdominal pain. Weight loss of about 5– 6 kg in 1 year was noted. Abdominal examination was unremarkable except for low abdominal tenderness. Whole blood analysis and biochemical parameters were within normal limits. Contrast-enhanced computed tomography revealed a large, round mass with enhanced rim, which contained entrapped gas bubbles at the pouch of Douglas (Figure A, arrow). What is the most likely diagnosis? See the GASTROENTEROLOGY web site (www. gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

We have performed light-induced modulation of absorption spectroscopy, thermally stimulated current spectroscopy, capacitance measurements as a function of temperature and frequence, and electron spin resonance experiments on reactively sputtered a-Si:H films. We find evidence for seven different localized gap states in a range of ±0.4 eV around the midgap region. The possible origin of these states is discussed.