Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by interleukin (IL)-1b. Canakinumab inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 wk double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150mg divided in doses every 4 wks (50þ50þ25þ25mg [q4wk]) or colchicine 0.5mg p.o. daily for 16 wks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to number of flares occurring during first 16 wks. Secondary outcomes included number of patients with flares and C-reactive protein (CRP) levels during the first 16 wks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine couldn't be determined. Based on a negative binomialmodel, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25mg 0.60, 50mg 0.34, 100mg 0.28, 200mg 0.37, 300mg 0.29, q4wk 0.38; p_0.05). Percentage of patients with flares was lower for all canakinumab groups (25mg 27.3%, 50mg 16.7%, 100mg 14.8%, 200mg 18.5%, 300mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p_0.05 for all). Median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN¼3 mg/L) throughout the 16 wk period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg), 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. 1 fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusions: In this randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine and was well tolerated.Disclosure statement: U.A., A.B., G.K., D.R. and P.S. are employees of and have stock options or bold holdings with Novartis Pharma AG. E.M. is a principal investigator for Novartis Pharmaceuticals Corporation. E.N. has received consulting fees from Roche. N.S. has received research grants from Novartis Pharmaceuticals Corporation. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Assistance circulatoire chronique: le point en 2013 [Long-term mechanical circulatory support: where do we stand in 2013?].

With the advent of new technologies, experience with long-term mechanical circulatory support (MCS) is rapidly growing. Candidates to MCS are selected based on concepts, strategies and classifications that are specific to this indication. As results drastically improve, supported by stronger scientific evidence, the trend is towards earlier implantation. An adequate pre-implant follow-up is mandatory in order to avoid missing the best window of opportunity for implantation. While on chronic support, the hemodynamic profile of patients with continuous-flow ventricular assist devices is unique and remarkably influenced by the hydration status. Optimal management of these patients from the pre-implant phase to the long-term support phase requires a multidisciplinary approach that is similar to that already long validated for organ transplantation.

Anatomie du foie: ce qu'il faut savoir [Anatomy of the liver: what you need to know]

A precise knowledge of arterial, portal, hepatic and biliary anatomical variations is mandatory when a liver intervention is planned. However, only certain variations must be searched when a precise intervention is planned. The basic liver anatomy as well as the most relevant malformations will be precised.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements.

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Psychological transformations in kidney transplantation: A prospective qualitative study

The aim of this IRB-approved study was to prospectively analyze psychological transformations in ESRD patients before and after transplantation (KT). Semi-structured interviews were conducted in 30 patients (mean age = 53±10) after their inclusion on the waiting-list (Gr. A). Follow-up interviews were performed 6 months later in 15 patients still awaiting KT (Gr. B6), and in 15 patients 6 months (Gr. C6) and 12 months (Gr. C12) after KT. Qualitative analysis was performed. Gr: A:All patients underlined loss of freedom, 87% devoted much energy to maintain normality, 57% modified medical directives. All reported emotional fragility related to dialysis and loss of quality of life (QOL), negative (43%) or suicidal thoughts (20%). Professional stigma was underlined (26%). Gr: B6:40% reported no change, 60% mentioned increase of illness intrusiveness, 46% dialysis side-effects, 40% communication problems, 33% tension with medical staff and waiting list handling. Fear of emotional breakdown (40%), couple problems (47%) and worsened professional difficulties (20%) were reported. Gr: C6:All patients mentioned improved QOL and freedom recovery (87%). All expressed concerns about possible acute rejection, 73% were anxious about laboratory results, 93% experienced dependence to immunosuppressants, 47% reported difficulties in handling medication, 21% feared to forget them, 47% were concerned about side-effects, 67% had resumed work but medical constraints led to professional tension (40%). Gr: C12:All mentioned recovered QOL. Medical controls were accepted as a routine (87%) and adherence to medication was mandatory (100%). All mentioned the limited long-term graft survival and 47% were anxious about possible return to dialysis, especially younger patients (27%). Positive identity and existential changes were reported (60%). This prospective qualitative study identifies psychological modifications in the course of KT. It provides a basis to adequately address concerns, but it shows also that KT is clearly associated with positive psychological transformations.

MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma.

Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and the leading cause of cancer related deaths in childhood between the age of 1 to 4 years. NBL may behave in very different ways, from the less aggressive stage 4S NBL or congenital forms that may resolve without treatment in up to 90% of the children, to the high-risk disseminated stage 4 disease in older children with a cure rate of 35 to 40%. Initial staging is crucial for effective management and radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool with a sensitivity around 90% and a specificity close to 100% for the diagnosis of NBL. MIBG scintigraphy is used routinely and is mandatory in most investigational clinical trials both for the initial staging of the disease, the evaluation of the response to treatment, as well as for the detection of recurrence during follow-up. With respect to outcome of children presenting disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been investigated by several groups but so far there is no consensus whereas a complete or very good partial response as assessed by MIBG may be of prognostic value. NBL needs a multimodality approach at diagnosis and during follow-up and MIBG scintigraphy keeps its pivotal role, in particular with respect to bone marrow involvement and/or cortical bone metastases.

State of Iowa Employee Handbook, Revised October 2003

This is your employee handbook. This information is based on Iowa Department of Administrative Services – Human Resources Enterprise (DAS-HRE) rules and policies. Much of the information in this handbook is also covered in the State’s collective bargaining agreements. Where there are differences between a collective bargaining agreement and this handbook, the collective bargaining agreement prevails for employees covered by the agreement. Where there are differences between this handbook and DAS-HRE rules and policies, DAS-HRE rules and policies prevail. Some of the employee benefit plans described in this handbook are subject to legal requirements concerning reporting and disclosure. This handbook contains highlights of those plans. For complete details about benefit plans, consult the benefit handbooks and the official plan documents. In case of any discrepancy, the official plan documents prevail. Of course, changes in laws may affect the benefit programs described in this handbook. The State of Iowa reserves the right to amend the contents of this handbook at any time without prior notice. The provisions of this handbook and other policies do not establish contractual rights or conditions of employment between the State and its employees.

Gross – to – Net Payroll Calculation Program Human Resources Information System (HRIS), 2000

Gross-to-Net is a payroll calculator modeled after the actual payroll calculation used for state employees’ paychecks. This calculator can be used to project changes in net pay when there are changes in pay amounts, hours worked, mandatory and voluntary deductions, including all pre-tax deductions such as retirement, insurances, deferred compensation or flexible spending plans. Federal and state tax withholding, retirement rates, OASDI and Medicare (FICA) are calculated using current rates.

OS CONTRACTOS DE CONCESSÃO NO CONTEXTO DO SISTEMA DE NORMALIZAÇÃO CONTABILÍSTICA E DE RELATO FINANCEIRO

A mudança do normativo contabilístico ocorrido em 2009, alterou o paradigma de reconhecimento e mensuração de activos. Embora a natureza das operações contínua presente no processo contabilístico, muitas coisas foram alteradas tendo em conta a substância da informação e a sua realidade económica. O caso dos contratos de concessão é disto um bom exemplo. Há casos em que no normativo anterior eram reconhecidos como activos fixos tangíveis e actualmente são reconhecidos como intangíveis. O estudo em causa tem como objetivo principal analisar o conceito dos contratos de concessão, bem como os procedimentos para o reconhecimento, mensuração e divulgação nas demonstrações financeiras. Considerados activos intangíveis (de facto a entidade acaba por ter um “Direito” de explorar um determinado activo), o processo contabilístico é feito a luz do disposto na Norma de Relato Financeiro nº6 – Activos Intangíveis. Os contractos de concessão apresentam especificidades próprias e por esta razão o IASB emitiu uma IFRIC (nº 12) com o objectivo de clarificar o tratamento contabilístico desta problemática. Não existindo no normativo nacional tal norma interpretativa as empresas nacionais que convivem com esta realidade vêem-se na contingência de, supletivamente, recorrer às normas internacionais de contabilidade para resolver o assunto. É o caso da ELECTRA para os activos afectos a distribuição. Neste sentido, o estudo debruça sobre esta problemática, apresenta um enquadramento teórico, analisar os principais aspectos de reconhecimento a luz dos dois normativos contabilísticos nacionais (o antigo Plano Nacional de Contabilidade e o actual Sistema de Normalização Contabilística e de Relato Financeiro) e termina utilizando as informações da ELECTRA, SARL para ilustrar este processo de reconhecimento contabilístico. The change of a the accounting regulatory occurred in 2009, changed the paradigm for recognizing and measuring assets. Although the continuous nature of the operations in this accounting process, many things have changed in view of the substance of information and its economic reality. The case of concession contracts, it is a good example. There are cases where the former were recognized as legal and tangible fixed assets are currently recognized as intangible assets. The study is aimed to analyzing the concept of concession contracts, as well as procedures for the recognition, measurement and disclosure in the financial statements. Considered intangible assets (in fact the entity turns out to have a “right” to exploit a particular asset) the accounting process is done in light of the provisions of Financial Reporting Standard No. 6 – Intangible Assets. The concession contracts have specific characteristics and for this reason the IASB issued IFRIC one (Ner. 12 ) in order to clarify the accounting treatment of this problem. In the absence of such a standard national regulatory interpretative national companies that live with this reality find themselves in contingency, additionally, make use of international accounting standards to resolve the matter. ELECTRA is the case of the assets connected to the distribution. In this sense, the study focuses on this issue, presents a theoretical framework to analyze the main aspects of recognition light of both national accounting standards (formerly the National Accounting Standards and the current system of accounting and financial reporting) and ends up using the information the Electra SARL to illustrate this process of accounting recognition.

Efficacy of brief motivational intervention at army conscription to address alcohol use and related problems: a randomized controlled trial

Objectives: The aim of this study was to evaluate the efficacy of brief motivational intervention (BMI) in reducing alcohol use and related problems among binge drinkers randomly selected from a census of 20 year-old French speaking Swiss men and to test the hypothesis that BMI contributes to maintain low-risk drinking among non-bingers. Methods: Randomized controlled trial comparing the impact of BMI on weekly alcohol use, frequency of binge drinking and occurrence of alcohol-related problems. Setting: Army recruitment center. Participants: A random sample of 622 men were asked to participate, 178 either refused, or missed appointment, or had to follow military assessment procedures instead, resulting in 418 men randomized into BMI or control conditions, 88.7% completing the 6-month follow-up assessment. Intervention: A single face-to-face BMI session exploring alcohol use and related problems in order to stimulate behaviour change perspective in a non-judgmental, empathic manner based on the principles of motivational interviewing (MI). Main outcome measures: Weekly alcohol use, binge drinking frequency and the occurrence of 12 alcohol-related consequences. Results: Among binge drinkers, we observed a 20% change in drinking induced by BMI, with a reduction in weekly drinking of 1.5 drink in the BMI group, compared to an increase of 0.8 drink per week in the control group (incidence rate ratio 0.8, 95% confidence interval 0,66 to 0,98, p = 0.03). BMI did not influence the frequency of binge drinking and the occurrence of 12 possible alcohol-related consequences. However, BMI induced a reduction in the alcohol use of participants who, after drinking over the past 12 months, experienced alcohol-related consequences, i.e., hangover (-20%), missed a class (-53%), got behind at school (-54%), argued with friends (-38%), engaged in unplanned sex (-45%) or did not use protection when having sex (-64%). BMI did not reduce weekly drinking in those who experienced the six other problems screened. Among non-bingers, BMI did not contribute to maintain low-risk drinking. Conclusions: At army conscription, BMI reduced alcohol use in binge drinkers, particularly in those who recently experienced alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is an interesting preventive option in young binge drinkers, particularly in countries with mandatory army recruitment.

Does direct democracy reduce the size of government? New evidence from historical data, 1890-2000

Using historical data for all Swiss cantons from 1890 to 2000, we estimate the causal effect of direct democracy on government spending. The main innovation in this paper is that we use fixed effects to control for unobserved heterogeneity and instrumental variables to address the potential endogeneity of institutions. We find that the budget referendum and lower costs to launch a voter initiative are effective tools in reducing canton level spending. However, we find no evidence that the budget referendum results in more decentralized government or a larger local government. Our instrumental variable estimates suggest that a mandatory budget referendum reduces the size of canton spending between 13 and 19 percent. A 1 percent lower signature requirement for the initiative reduces canton spending by up to 2 percent.

Turismo Rural na Ilha de Santo Antão como factor de Desenvolvimento das Aldeias de Fontaínhas, Corvo e Formiguinhas

Santo Antão é uma ilha onde a oferta turística passa pelo turismo de natureza, e pretendese criar um projecto ligado ao Turismo Rural nas aldeias de Fontaínhas, Corvo e Formiguinhas. As aldeias são rurais e enfrentam vários constrangimentos e é necessário implementar um leque de infra-estruturas como alojamento, estradas, postos de saúde, saneamento para o suporto do Turismo e optar por uma alternativa do desenvolvimento local. O objectivo é criar uma proposta de desenvolvimento do Turismo Rural que seja viável para estas aldeias. Numa segunda fase pretende-se também envolver as famílias rurais no desenvolvimento do turismo. As aldeias em questão reúnem condições naturais para o Turismo Rural, mas pretende apostar na valorização cultura, história e nos produtos locais. Having in mind that Santo Antão is an island where the offer is almost mandatory for nature tourism, it intends to develop a project connected to the Rural Tourism in the following villages of “Fontaínhas,” “Corvo” and “Formiguinhas”. These villages are rural and face various constraints, so it is necessary to implement a range of infrastructures to support Tourism and opt for an alternative that promotes local development. The aim is to create a model of development of Rural Tourism practicable to these villages. We also intend to involve local families in rural tourism development. The villages in question have natural conditions for Rural Tourism, but we want to focus on enhancing products like cultural and historical sites.

Risk of cardiovascular disease in a traditional African population with a high infectious load: a population-based study.

BACKGROUND: To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. METHODOLOGY/PRINCIPAL FINDINGS: Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%). CONCLUSIONS/SIGNIFICANCE: Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

Early Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

Purpose/Objective(s): Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas, and 4-5% of all extranodal lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with stage I and II PBL.Materials/Methods: Between 1987 and 2008, 116 consecutive patients with PBL treated in 13 RCNinstitutions were included in this study. Inclusion criteriawere: age.17 yrs, PBLin stage I and II, andminimum6months follow-up. The median agewas 51 yrs (range: 17-93).Diagnosticwork-up included plain boneXray (74%of patients), scintigraphy (62%), CT-scan (65%),MRI (58%), PET (18%), and bone-marrow biopsy (84%).All patients had biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). The histopathological type was predominantly diffuse large B-cell lymphoma (78%) and follicular lymphoma (6%), according to theWHOclassification. One hundred patients had a high-grade, 7 intermediate and 9 low-gradeNHL. Ninety-three patients had anAnn-Arbor stage I, and 23 had a stage II. Seventy-seven patients underwent chemoradiotherapy (CXRT), 12 radiotherapy (RT) alone, 10 chemotherapy alone (CXT), 9 surgery followed by CXRT, 5 surgery followed by CXT, and 2 surgery followed by RT. One patient died before treatment.Median RT dosewas 40Gy (range: 4-60).Themedian number ofCXTcycleswas 6 (range, : 2-8).Median follow-upwas 41months (range: 6-242).Results: Following treatment, the overall response rate was 91% (CR 74%, PR 17%). Local recurrence was observed in 12 (10%) patients, and systemic recurrence in 17 (15%) patients. Causes of death included disease progression in 16, unrelated disease in 6, CXT-related toxicity in 1, and secondary cancer in 2 patients. The 5-yr overall survival (OS), disease-free survival (DFS), lymphoma- specific survival (LSS), and local control (LC) were 76%, 69%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for survival were: age\50 years (p = 0.008), IPI score #1 (p = 0.009), complete response (p\0.001), CXT (p = 0.008), number of CXT cycles $6 (p = 0.007), and RT dose . 40 Gy (p = 0.005). In multivariate analysis age, RT dose, complete response, and absence of B symptoms were independent factors influencing the outcome. There were 3 patients developing grade 3 or more (CTCAE.V3.0) toxicities.Conclusions: This large multicenter study, confirms the relatively good prognosis of early stage PBL, treated with combined CXRT. Local control was excellent, and systemic failure occurred infrequently. A sufficient dose of RT (. 40 Gy) and completeCXT regime (. 6 cycles) were associated with a better outcome. Combined modality appears to be the treatment of choice.Author Disclosure: L. Cai, None; M.C. Stauder, None; Y.J. Zhang, None; P. Poortmans, None; Y.X. Li, None; N. Constantinou, None; J. Thariat, None; S. Kadish, None; M. Ozsahin, None; R.O. Mirimanoff, None.

Earnings management and audit adjustments: An empirical study of IBEX 35 constituents

Doubts about the reliability of a company's qualitative financial disclosure increase market participant expectations from the auditor's report. The auditing process is supposed to serve as a monitoring device that reduces management incentives to manipulate reported earnings. Empirical research confirms that it could be an efficient device under some circumstancesand recognizes that our estimates of the informativeness of audit reports are unavoidably biased (e.g., because of a client's anticipation of the auditing process). This empirical study supports the significant role of auditors in the financial market, in particular in the prevention of earnings management practice. We focus on earnings misstatements, which auditors correct with anadjustment, using a sample of past and current constituents of the benchmark market index in Spain, IBEX 35, and manually collected audit adjustments reported over the 1997-2004 period (42 companies, 336 annual reports, 75 earnings misstatements). Our findings confirm that companies more often overstate than understate their earnings. An investor may foresee earningsmisreporting, as manipulators have a similar profile (e.g., more leveraged and with lower sales). However, he may receive valuable information from the audit adjustment on the size of earnings misstatement, which can be significantly large (i.e., material in almost all cases). We suggest that the magnitude of an audit adjustment depends, other things constant, on annual revenues and free cash levels. We also examine how the audit adjustment relates to the observed market price, trading volume and stock returns. Our findings are that earnings manipulators have a lower price and larger trading volume compared to their rivals. Their returns are positively associated with the magnitude of earnings misreporting, which is not consistent with the possible pricing of audit information.