bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arginine 595 is duplicated in patients with acute leukemias carrying internal tandem duplications of FLT3 and modulates its transforming potential
Authors: Vempati Sridhar , Reindl Carola , Kaza Seshu Kumar , Kern Ruth , Malamoussi Theodora , Dugas Martin , Mellert Gudrun , Schnittger Susanne , Hiddemann Wolfgang , Spiekermann Karsten 
Published: March 2007

Abstract
FLT3–internal tandem duplications (FLT3-ITDs) comprise a heterogeneous group of mutations in patients with acute leukemias that are prognostically important. To characterize the mechanism of transformation by FLT3-ITDs, we sequenced the juxtamembrane region (JM) of FLT3 from 284 patients with acute leukemias. The length of FLT3-ITDs varied from 2 to 42 amino acids (AAs) with a median of 17 AAs. The analysis of duplicated AAs showed that in the majority of patients, the duplications localize between AAs 591 to 599 (YVDFREYEY). Arginine 595 (R595) within this region is duplicated in 77% of patients. Single duplication of R595 in FLT3 conferred factor-independent growth to Ba/F3 cells and activated STAT5. Moreover, deletion or substitution of the duplicated R595 in 2 FLT3-ITD constructs as well as the deletion of wild-type R595 in FLT3-ITD substantially reduced the transforming potential and STAT5 activation, pointing to a critical role of the positive charge of R595 in stabilizing the active confirmation of FLT3-ITDs. Deletion of R595 in FLT3-WT nearly abrogated the ligand-dependent activation of FLT3-WT. Our data provide important insights into the molecular mechanism of transformation by FLT3-ITDs and show that duplication of R595 is important for the leukemic potential of FLT3-ITDs.
Construction of the Femoral Neck During Growth Determines Its Strength in Old Age
Authors: Zebaze Roger M D , Jones Anthony , Knackstedt Mark , Maalouf Ghassan , Seeman Ego 
Published: March 2007

Abstract
Study of the design of the FN in vivo in 697 women and in vitro in 200 cross-sections of different sizes and shapes along each of 13 FN specimens revealed that strength in old age was largely achieved during growth by differences in the distribution rather than the amount of bone material in a given FN cross-section from individual to individual.
Introduction: We studied the design of the femoral neck (FN) to gain insight into the structural basis of FN strength in adulthood and FN fragility in old age.
Materials and Methods: Studies in vivo were performed using densitometry in 697 women and in vitro using high-resolution μCT and direct measurements in 13 pairs of postmortem specimens.
Results: The contradictory needs of strength for loading yet lightness for mobility were met by varying FN size, shape, spatial distribution, and proportions of its trabecular and cortical bone in a cross-section, not its mass. Wider and narrower FNs were constructed with similar amounts of bone material. Wider FNs were relatively lighter: a 1 SD higher FN volume had a 0.67 (95% CI, 0.61–0.72) SD lower volumetric BMD (vBMD). A 1 SD increment in height was achieved by increasing FN volume by 0.32 (95% CI, 0.25–0.39) SD with only 0.15 (95% CI, 0.08–0.22) SD more bone, so taller individuals had a relatively lighter FN (vBMD was 0.13 [95% CI, 0.05–0.20 SD] SD lower). Greater periosteal apposition constructing a wider FN was offset by even greater endocortical resorption so that the same net amount of bone was distributed as a thinner cortex further from the neutral axis, increasing resistance to bending and lowering vBMD. This was recapitulated at each point along the FN; varying absolute and relative degrees of periosteal apposition and endocortical resorption focally used the same amount of material to fashion an elliptical FN of mainly cortical bone near the femoral shaft to offset bending but a more circular FN of proportionally more trabecular and less cortical bone to accommodate compressive loads adjacent to the pelvis. This structural heterogeneity was largely achieved by adaptive modeling and remodeling during growth—most of the variance in FN volume, BMC, and vBMD was growth related.
Conclusions: Altering structural design while minimizing mass achieves FN strength and lightness. Bone fragility may be the result of failure to adapt bone's architecture to loading, not just low bone mass.
Identification of Sex-Specific Associations Between Polymorphisms of the Osteoprotegerin Gene, TNFRSF11B, and Paget's Disease of Bone
Authors: Beyens Greet , Daroszewska Anna , de Freitas Fenna , Fransen Erik , Vanhoenacker Filip , Verbruggen Leon , Zmierczak Hans-Georg , Westhovens René , Van Offel Jan , Ralston Stuart H , Devogelaer Jean-Pierre , Van Hul Wim 
Published: March 2007

Abstract
We studied the role of TNFRSF11B polymorphisms on the risk to develop Paget's disease of bone in a Belgian study population. We observed no association in men, but a highly significant association was found in women, and this was confirmed in a population from the United Kingdom.
Introduction: Juvenile Paget's disease has been shown to be caused by mutations in TNFRSF11B encoding osteoprotegerin. Although mutations in this gene have never been found in patients with typical Paget's disease of bone (PDB), there are indications that polymorphisms in TNFRSF11B might contribute to the risk of developing PDB.
Materials and Methods: We recruited a population of 131 Belgian patients with sporadic PDB and 171 Belgian controls. By means of the HapMap, we selected 17 SNPs that, in combination with four multimarker tests, contain most information on common genetic variation in TNFRSF11B. To replicate the findings observed in the Belgian study population, genotyping data of SNPs generated in a UK population were reanalyzed.
Results: In our Belgian study population, associations were found for two SNPs (rs11573871, rs1485286) and for one multimarker test involving rs1032129. When subsequently analyzing men and women separately, these associations turned out to be driven by women (56 cases, 78 controls). In addition, three other tagSNPs turned out to be associated in women only. These were rs2073617 (C950T), rs6415470, and rs11573869. Reanalysis of genotyping data from a UK study population indicated that the associations found for C950T and C1181G were also exclusively driven by women (146 cases, 216 controls). Meta-analysis provided evidence for risk increasing effects of the T allele of C950T and the G allele of C1181G in the female population (p = 0.002 and 0.003, respectively). The haplotypes formed by the SNPs associated in the Belgian population were also distributed differentially between female cases and controls.
Conclusions: We showed for the first time that SNPs influencing the risk to develop PDB could be sex-specific. Further research is necessary to identify the causative variants in TNFRSF11B and to elucidate the molecular pathogenic mechanism.
Accounting Discretion and Managerial Conservatism: An Intertemporal Analysis*
Authors: Lin Haijin 
Published: March 2007

AbstractAccounting discretion and the principle of conservatism are two salient features embedded in financial reporting systems. Arguably, the practice of conservative accounting choices can never be well understood without incorporating their effect on future periods (the intertemporal effect). This paper provides one explanation for managerial conservatism in a two‐period agency model with hidden information (a binary project type) and hidden actions (the agent's efforts). A piece‐wise linear incentive scheme with accounting earnings as the performance measure is employed. The agent's discretion is the choice of a depreciation method. Discretion is valuable if and only if the agent's marginal productivity of a “bad” project is greater than that of a “good” project, but not to an extreme degree. A conservative depreciation method decreases current compensation in exchange for a “bet” on future compensation and, hence, serves as a commitment device for the agent to signal that the prospect is indeed good. The accounting mechanism replicates the performance of the optimal direct mechanism.
Auditor Reputation, Auditor Independence, and the Stock‐Market Impact of Andersen's Indictment on Its Client Firms*
Authors: Krishnamurthy Srinivasan , Zhou Jian , Zhou Nan 
Published: March 2007

AbstractIn this paper, we study a broad sample of Arthur Andersen clients and investigate whether the decline in Andersen's reputation, due to its criminal indictment on March 14, 2002, adversely affected the stock market's perception of its audit quality. Because these reputa‐tional concerns are more of an issue if an auditor's independence is impaired, we investigate the relationship between the abnormal market returns for Andersen clients around the time of the indictment announcement and several fee‐based measures of auditor independence. Our results suggest that when news about Andersen's indictment was released, the market reacted negatively to Andersen clients. More importantly, we find that the indictment period abnormal return is significantly more negative when the market perceived the auditor's independence to be threatened. We also examine the abnormal returns when firms announced the dismissal of Andersen as an auditor. Consistent with the audit quality explanation, we document that when firms quickly dismissed Andersen, the announcement returns are significantly higher when firms switched to a Big 4 auditor than when they either switched to non‐Big 4 auditors or did not announce the identity of the replacement auditor. Our empirical results support the notion that auditor reputation and independence have a material impact on perceived audit quality and the credibility of audited financial statements, and that the market prices this.
Forces Leading to the Adoption of Accrual Accounting by the Canadian Federal Government: An Institutional Perspective*/ LES FORCES AYANT MENÉ L'ADMINISTRATION FÉDÉRALE CANADIENNE À ADOPTER LA COMPTABILITÉ D'EXERCICE: UNE PERSPECTIVE INSTITUTIONNELLE
Authors: BAKER RON , RENNIE MORINA D. 
Published: March 2007

ABSTRACTIn 1995, the federal government of Canada announced that it would adopt full accrual accounting. The change was fully implemented at the department level in 2001 and for government‐wide financial reporting in 2003. Using the perspective of institutional theory, we examine several factors that had the potential to influence the federal government's decision to adopt full accrual accounting, including two royal commissions, the Office of the Auditor General of Canada, the Canadian Institute of Chartered Accountants, credit markets, and the practices of other national governments. We find that the decision to change to accrual accounting can be largely attributed to coercive and normative influences of the Office of the Auditor General of Canada (supported by the normative influence of the Canadian Institute of Chartered Accountants' Public Sector Accounting Board) and mimetic isomorphism with other members of the federal government's organizational field.
Nonaudit Services and Earnings Conservatism: Is Auditor Independence Impaired?*
Authors: Ruddock Caitlin , Taylor Sarah J. , Taylor Stephen L. 
Published: March 2007

AbstractWe examine whether the provision of nonaudit services (NAS) by incumbent auditors is associated with a reduction in the extent to which earnings reflect bad news on a timely basis (that is, news‐based conservatism). Reduced conservatism is expected to occur if relatively high levels of NAS result in reduced auditor independence and, ultimately, lower‐quality auditing. Because client‐specific demand for NAS is expected to vary, our proxy for the auditor‐client economic bond is the extent to which NAS purchases (relative to audit fees) are greater or less than expected. Using several different methods for identifying news‐based conservatism, we consistently find that higher than expected levels of NAS are not associated with reduced conservatism. This result is robust to allowing for endogenous NAS demand, as well as several explicit factors that may be associated with differences in conservatism. Similar conclusions arise from tests that use alternative measures of the economic bond between auditors and their clients, as well as in tests confined to either the Big 6 or non‐Big 6 audit firms. Our results are consistent with factors such as market‐based incentives, the threat of litigation, and alternative governance mechanisms offsetting any expected benefits to the audit firm from reducing its independence. We therefore conclude that recent legislative intervention aimed at restricting the supply of NAS is unlikely to result in increased independence in fact, although independence in appearance may be improved.
Conservative Accounting and Linear Information Valuation Models*
Authors: Choi Young‐Soo , O'Hanlon John F. , Pope Peter F. 
Published: March 2007

AbstractPrior research using the residual income valuation model and linear information models has generally found that estimates of firm value are negatively biased. We argue that this could result from the way in which accounting conservatism effects are reflected in such models. We build on the conservative accounting model of Feltham and Ohlson 1995 and the Dechow, Hutton, and Sloan 1999 (DHS) methodology to propose a valuation model that includes a conservatism‐correction term, based on the properties of past realizations of residual income and “other information”. “Other information” is measured using analyst‐forecast‐based predictions of residual income. We use data comparable to the DHS sample to compare the bias and inaccuracy of value estimates from our model and from models similar to those used by DHS and Myers 1999. Valuation biases are substantially less negative for our model, but valuation inaccuracy is not markedly reduced.
Earnings Quality and the Equity Risk Premium: A Benchmark Model*
Authors: Yee Kenton K. 
Published: March 2007

AbstractThis paper solves a model that links earnings quality to the equity risk premium in an infinite‐horizon consumption capital asset pricing model (CAPM) economy. In the model, risk‐averse traders hold diversified portfolios consisting of risk‐free bonds and shares of many risky firms. When constructing their portfolios, traders rely on noisy reported earnings and dividend payments for information about the risky firms. The main new element of the model is an explicit representation of earnings quality that includes hidden accrual errors that reverse in subsequent periods.The model demonstrates that earnings quality magnifies fundamental risk. Absent fundamental risk, poor earnings quality cannot affect the equity risk premium. Moreover, only the systematic (undiversified) component of earnings‐quality risk contributes to the equity risk premium. In contrast, all components of earnings‐quality risk affect earnings capitalization factors. The model ties together consumption CAPM and accounting‐based valuation research into one price formula linking earnings quality to the equity risk premium and earnings capitalization factors.
CAP Forum on Forensic Accounting in the Post‐Enron World: Audit Committees and Misappropriation of Assets: Publicly Held Companies in the United States*/LES COMITÉS DE VÉRIFICATION ET LE DÉTOURNEMENT DE BIENS: LES SOCIÉTÉS OUVERTES AUX ÉTATS‐UNIS
Authors: MUSTAFA SAMEER T. , MEIER HEIDI HYLTON 
Published: March 2007

ABSTRACTThe majority of previous studies investigating the different risk factors associated with financial fraud have focused on investigating misreporting. A few studies have provided only a limited descriptive analysis of cases involving misappropriation of assets without investigating the corporate governance structure and its role in reducing the incidence of misappropriation. Only Beasley (1996) has examined financial fraud and corporate governance structure by combining cases of misreporting and misappropriation of assets by top management.This study investigates the relationship between the incidence of misappropriation of assets by employees, including management, and the effectiveness of the audit committee. Using LEXIS‐NEXIS Research Software 7.1, Business/Finance News to find relevant articles, we identified publicly held companies suffering misappropriation of assets by employees during the period from 1987 to 2000. The study investigated 81 companies experiencing misappropriation and two control samples: 81 random‐control companies and 81 matched‐control companies.The results extend the previous literature related to financial fraud and corporate governance. The percentage of independent members in audit committees and the average tenure of audit committee members were significantly and negatively related to the incidence of misappropriation of assets in publicly held companies in both the random and the matched models, while the number of audit committee meetings was not significant.
Auditor Independence in Canada: A Historical Perspective — From Shareholder Auditors to Modern‐Day Audit Committees*
Authors: GREEN DUNCAN L. 
Published: March 2007

ABSTRACTThis paper uses the theoretical framework of Goldman and Barlev (1974) to examine auditor independence in Canada. It traces the historical development of the auditor's role in the 19th century and the beginning of the auditor's relationship with shareholders and management. It shows how, following the separation of management from shareholding, management's ability to influence auditors undermined auditor independence. The paper traces attempts by legislators and regulatory bodies to limit management's influence over auditors and to correct the asymmetry of their relationship. It notes that recent changes to legislation and rules of professional conduct are no longer proactive, but are reactions to corporate scandals in Canada and the United States. The paper argues that although future changes will occur to redress the imbalance, only structural changes are likely to provide a real solution to auditor independence problems. However, it is likely that such changes will be resisted by the accounting profession.
Recognition versus Disclosure of Stock Option Compensation: An Analysis of Judgements and Decisions of Nonprofessional Investors*/CONSTATER OU PRÉSENTER PAR VOIE DE NOTE LA RÉMUNÉRATION SOUS FORME D'OPTIONS D'ACHAT D'ACTIONS: UNE ANALYSE DES JUGEMENTS ET DES DÉCISIONS DES INVESTISSEURS NON PROFESSIONNELS
Authors: BELZILE RÉJEAN , FORTIN ANNE , VIGER CHANTAL 
Published: March 2007

ABSTRACTGiven the importance of stock options in the aggregate compensation of chief executive officers and other firm employees in the 1990s and early 2000s, the International Accounting Standards Board issued an International Financial Reporting Standard on stock‐based payments on February 19, 2004, requiring that all share‐based payment transactions be recognized at fair value in entities' financial statements. The Canadian Institute of Chartered Accountants' Accounting Standards Board had already agreed to this principle and amended section 3870 of the CICA Handbook (stock‐based compensation) for financial periods beginning on or after January 1, 2004, making Canada the first major jurisdiction to require all public companies to expense employee stock‐based compensation awards. The revised section eliminated the possibility of disclosing pro forma net income and earnings per share only by way of a note.This research, conducted as a between‐subjects experiment with executive MBA students as nonprofessional investors, examines whether changes in the way stock option compensation is reported (recognition as an expense in the income statement or note disclosure of pro forma net income and earnings per share) affect financial statement users' judgements and investment decisions. Our results indicate that, consistent with the functional fixation hypothesis, the reporting method does indeed significantly influence subjects' judgement of the expected stock price direction, but has no material influence on their investment decisions.
The Importance of Account Relations when Responding to Interim Audit Testing Results*
Authors: Vandervelde Scott D. 
Published: March 2007

AbstractAuditors are expected to plan and adapt audit programs in response to changes in risk associated with each client. Results in the existing research have been mixed regarding whether auditors respond to changes in risk. Two possible explanations for the lack of responsiveness to changes in risk found in the existing research are that auditors succumb to profit pressure, and that researchers only analyze responses in the risky accounts without considering related accounts. This paper experimentally tests how auditors respond to changes in risk of material misstatement identified by means of interim audit testing results. The response to changes in risk of material misstatement is analyzed using planned audit hours across related financial statement accounts and at varying levels of profit pressure. Results indicate the following primary findings: (a) auditors respond to changes in risk of material misstatement by increasing planned audit hours in accounts related to the risky account, and (b) profit pressure does not affect the auditor's response to changes in risk. These results indicate that the relations between accounts must be considered in order to identify the auditors' response to changes in risk of material misstatement. In addition, the results are consistent with audit firms decreasing the emphasis on profit pressure due to the current importance that the market places on audit quality.
The Efficacy of Third‐Party Consultation in Preventing Managerial Escalation of Commitment: The Role of Mental Representations*
Authors: KADOUS KATHRYN , SEDOR LISA M. 
Published: March 2007

AbstractAvoiding continued investment in poorly performing projects is an important function of management control systems. However, prior research suggests that managers fail to use accounting information indicating that a project is performing poorly to discontinue it; that is, they escalate commitment to the project. We perform two experiments to investigate the efficacy of a potential control mechanism, third‐party consultation, in preventing managerial escalation of commitment. We hypothesize that the information‐processing objective (that is, purpose) assigned to consultants influences the mental representations they construct to process and store information, which ultimately influences their recommendations regarding the continuation of a poorly performing project. Results suggest that consultants will not construct mental representations amenable to making high‐quality project‐continuation recommendations unless they are assigned that specific purpose. Results further suggest that applying additional effort likely will not overcome the adverse effects of having inappropriate mental representations when making project‐continuation recommendations. An implication of our study is that third‐party consultants likely will not prevent managerial escalation of commitment unless consultants have a specific mandate of making a project‐continuation recommendation in mind when they encounter relevant accounting information.