Paired box protein Pax-6 (oculothrombin) is a transcription factor that plays an important regulatory role in ocular, brain, and pancreatic development. Mutations of the PAX6 gene cause aniridia and Peters anomaly. Reduction in Pax-6 protein is also associated with ocular diseases such as dry eye. An electrochemiluminescence immunoassay method using the Meso Scale Discovery platform was developed to measure Pax-6 protein levels in corneal epithelial cells obtained by impression cytology. Impression cytology involves harvesting ocular epithelial cells by applying a polyethersulfone membrane patch briefly to the ocular surface using a commercially available EYEPRIM™ device. The epithelial cells that adhere to the membrane patch of the EYEPRIM™ device provide a biological sample which can be assayed for Pax-6 protein levels. Assay development identified an antibody pair capable of detecting purified recombinant Pax-6 protein produced in mammalian cells. The optimized assay has a dynamic range of 24 pg mL-1 to 100,000 pg mL-1 and a lower limit of quantification of 24 pg mL-1. Assay selectivity was demonstrated using either HeLa or HEK293 cells transfected with inhibitory RNA. Finally, the method was validated by measuring Pax-6 protein levels in impression cytology acquired samples obtained using the EYEPRIM™ device from rabbit cornea.
This paper provides results of an experiment designed to investigate how mandatory rotation or retention of auditors may affect auditor reporting. Repeat audit engagements are believed to be a source of economic rents to auditors, and as such they are believed to pose a threat to auditor independence. Our study examines under controlled experimental conditions whether mandatory rotation would materially increase auditors' independence compared to similar settings in which the requirement is not imposed on auditor-client relationships. Our experimental design includes four settings. The first setting has neither mandatory retention nor mandatory rotation and is a benchmark for comparing the other three. The second setting has mandatory retention, without a rotation requirement. The third has mandatory rotation but not retention, and the fourth has both retention and rotation. We find that in the setting without mandatory retention or rotation, managers made investments at levels higher than predicted by our model, and auditors issued a high frequency of reports that favored management. In the retention setting, auditors reported more conservatively than in the baseline setting. Once the retention period ended, however, auditors and managers converged to the same type of cooperative behavior observed in the base setting. In the setting with a rotation requirement, auditors reported more conservatively than they did in the previous two settings. The lower frequency of favorable reports was also observed in the non-rotation periods of the rotation setting. This outcome was not predicted by our model, and it suggests a spillover effect of the rotation requirement to non rotation periods. Our fourth setting included both retention and rotation requirements. We found that this setting had the highest level of conservative reporting but only nominally so relative to the setting with only mandatory rotation. Investment levels were also relatively high, but only in the retention periods and in the period of mandatory rotation; dropping materially in the one period in which the manager had the choice of dismissing the auditor. This result is consistent with the model's predictions since the manager could lower the investment in that one period and still expect the auditor to provide a favorable report.
Abstract Abstract A common theme in discussions of auditors' independence is the concern that provision of nonaudit services may compromise auditors' independence. We use a simple model to show that although the latter argument applies in some cases, it is false in others. Specifically, we show that the presence of contingent economic rents is not sufficient for auditors to compromise their independence, nor is the lack of contingent rents sufficient to imply auditors' independence. We also show that contingent rents could increase audit quality and strengthen independence when the risk of misstatements is less than 50 per cent. Our paper provides definitions of independence in appearance and independence in fact. Although the issue of independence relates to the dual notion of appearance and fact, regulations generally focus on appearance. In contrast, the literature on auditors' independence has focused on independence in fact. We bridge the gap by formalising a definition of independence in fact, and a definition of independence in appearance. JEL Classifications: M42N22Keywords: auditors' independenceaudit qualitysecurities regulation
329 Background: Penile squamous cell carcinoma (PSCC) is a disfiguring and deadly disease. US cancer registry reports a higher incidence in certain minority communities including those over-represented at LAC-USC. Human papilloma virus (HPV) infection is strongly associated with PSCC. This study examined correlations of HPV presence and subtype with PSCC patient clinicopathological variables. Methods: After IRB approval, a retrospective review of PSCC patients at LAC-USC between 1996-2010 was completed. HPV presence and genotype was detected from primary tumors of 33 patients by DNA amplification followed by reverse line blot hybridization. Associations with patient and tumor characteristics were examined by contingency analyses. Results: 20 (60.6%) patients were HPV+, and 85% of all HPV+ cases harbored at least one high-risk viral strain (80% of all positive cases had HPV 16, 5% HPV 31, 10% HPV 66). 20% of all positive cases harbored low-risk HPV 11; HPV strains 6 or 35 were not detected in any specimen. 3 patients were positive for multiple strains. Overall median age at diagnosis was 53 (range: 24-77) yrs. Median age was 56 yrs and 49 yrs for HPV+ and HPV- patients, respectively. HPV infection showed a trend towards being more prevalent in patients beyond the fifth decade of life, although this did not reach statistical significance (p=0.10). 22 (66.7%) patients were Hispanic; this ethnicity comprised 60% and 77% of HPV+ and HPV- cases, respectively (p=0.31). This cohort included Stage 0 (n= 1, n= 0), Stage 1 (n= 4, n=2), Stage 2 (n= 4, n= 4), Stage 3 (n=5, n= 1), and Stage 4 (n= 4, n= 5) HPV+ and HPV- patients, respectively. Neither HPV status nor presence of nodal metastasis was significantly associated with stage (p=0.50, p=0.52 respectively). Tumor grade was available for 30 (90.9%) cases; while HPV+ cases tended to have higher proportion of moderately-poorly differentiated tumors than HPV- cases (77.8% vs. 58.3%), this was not statistically significant (p=0.32). Conclusions: An overwhelming majority of HPV+ cases harbored at least one high-risk viral strain. Several interesting associations of HPV status with age and grade were noted, although the study was underpowered to show significance.
e15016 Background: Penile cancer is uncommon but can be disfiguring and aggressive. We explored specific molecular changes in PSC and their relationship to outcomes. Methods: After IRB approval, 52 patients were identified from 1995 and 2010 with tissue specimens and clinical data available. ERCC1 and EGFR expression were evaluated by RT-PCR plus IHC for a subgroup; TS expression was by RT-PCR only. RNA results represent a ratio of the gene of interest to internal reference gene β-actin. Immunohistochemistry (IHC) was graded 0-2+ by an experienced pathologist. Results: Median age is 52 (36-80) and 72% are Hispanic, 15% white, 6.5% each Asian and African-American. 6 had stage Tis, 10 had T1, 23 had T2, 12 had T3; 19 had pathologic documentation of lymph node involvment. With a median follow-up of 1.8 years the (longest 16.3 yrs) median survival is 4.9 years. 17 men received neoadjuvant chemotherapy for >N2 disease or for distant metastases; 7 had disease progression on chemo, 8 (47%) had objective response including 1 pathologic CR. EGFR over-expression was common both by RNA amplification (median 5.09, range 1.92-104.5) and immunohistochemistry (IHC); 7/22 had 2+ staining. EGFR expression >7 correlated significantly with more advanced T stage and poor differentiation (p=0.01 and 0.034 by Fisher’s exact test, respectively); it did not correlate with survival or lymph node involvement in multivariate analysis. ERCC1 expression was less common, median RNA expression 0.65 and range 0.21-1.87 with only 4/22 2+ by IHC. TS expression was intermediate, median 1.88 (range 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage or survival. There were no KRAS mutations identified. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (RR) to chemotherapy; 67% RR in EGFR<7 vs. 33% in EGFR>=7, p=0.31) and the trend was similar using IHC scores with no responses seen in thsoe wtih 2+ EGFR expression (p=0.16). Conclusions: We did not find a significant correlation between survival and EGFR, ERCC1, or TS expression in penile SCC. EGFR expression showed a trend for inverse relationship with chemotherapy response. The lack of KRAS mutation may predict a good likelihood of response to EGFR-targeted therapy.
The U.S. accounting graduate education has evolved considerably over the last few years and offers a plethora of accounting master’s programs. The Department of Accountancy at the Gies College of Business at the University of Illinois has a rich tradition of excellence in graduate accounting education, awarding its first master’s degree in 1922, and remaining at the forefront of accounting education ever since. Gies is a top-three business school for graduate accounting, and the accounting faculty is #1 in the BYU accounting research ranking. It is one of the largest suppliers of leaders of the accounting profession and among its graduates are legions of CFOs, accounting firm partners, and entrepreneurs. Graduates of Gies accounting programs have tremendously successful careers, and the STEM designation provides international students an opportunity to work in the U.S. for 36 months after graduation, and a competitive advantage.
As the academic director of the MSA program at Gies, and faculty members with many years of experience in the graduate accounting field, we are in a unique position to share our knowledge and observations with you. Our goal is to guide you through the process of assessing US accounting master's programs, explain the general admission requirements, and provide tips for a successful application. We conclude the editorial with an example of graduate accounting programs offered by the Gies College of Business at the University of Illinois.
It has been suggested that autoimmunity to the proteoglycan (PG) component of cartilage plays a major role in the etiology of adjuvant arthritis (AA), which occurs in rats, but not in mice, after injection of CFA. In order to more directly investigate this role, bovine and human cartilage PG were used to modulate AA, and immunity to PG was assessed. Immunization of rats or mice with PG by itself does not induce arthritis. However, in rats, a single i.v. injection of soluble PG, given 1 wk before injection of CFA, results in a significant increase in incidence and severity of the arthritis induced. Rats injected with CFA have both antibody and delayed type hypersensitivity (DTH) to PG. Upon pretreatment of rats with PG i.v., both DTH and antibody titers to PG are increased. Rats immunized with PG in IFA have high titers of anti-PG and strong DTH to PG, which are also enhanced by pretreatment with PG i.v., although none of these animals develops arthritis. In contrast to these findings in rats, when mice are pretreated with PG i.v., DTH to PG induced by injection of CFA is lower, whereas anti-PG titers are higher than in unpretreated controls. The results presented here show that, in rats, i.v. injection of PG synergizes with CFA in the induction of AA, and enhances both humoral and cellular immunity to PG. The findings support the hypothesis that immunity to PG is of importance in AA, although under the conditions of these experiments immunity induced by PG alone is clearly not sufficient for the induction of arthritis.
