Internal control reporting by non-accelerated filers

I examine three issues related to internal control reporting by non-accelerated filers. Motivation for the three studies comes from the fact that Section 404 of the Sarbanes-Oxley Act (SOX) continues to be controversial, as evidenced by the permanent exemption from Section 404(b) of SOX granted to non-accelerated filers by the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010. The Dodd-Frank Act also requires the SEC to study compliance costs associated with smaller accelerated filers. In the first part of my dissertation, I document that the audit fee premium for non-accelerated filers disclosing a material weakness in internal controls (a) is significantly lower than the corresponding premium for accelerated filers, and (b) declines significantly over time. I also find that in the case of accelerated filers remediating clients pay lower fees compared to clients continuing to report internal control problems; however, such differences are not observed in the case of non-accelerated filers. The second essay focuses on audit report lag. The results indicate that presence of material weaknesses are associated with increased audit report lags, for both accelerated and non-accelerated filers. The results also indicate that the decline in report lag following remediation of problems is greater for accelerated filers than for non-accelerated filers. The third essay examines early warnings (pursuant to Section 302 disclosures) for firms that subsequently disclosed internal control problems in their 404 reports. The analyses indicate that non-accelerated firms with shorter CFO tenure, presence of accounting experts on the audit committee, and more frequent audit committee meetings are more likely to provide prior Section 302 warnings. Overall the results suggest that there are differences in internal control reporting between the accelerated and non-accelerated filers. The results provide empirical grounding for the ongoing debate about internal control reporting by non-accelerated filers.

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

GPU Acceleration of Partial Differential Equation Solvers

Differential equations are often directly solvable by analytical means only in their one dimensional version. Partial differential equations are generally not solvable by analytical means in two and three dimensions, with the exception of few special cases. In all other cases, numerical approximation methods need to be utilized. One of the most popular methods is the finite element method. The main areas of focus, here, are the Poisson heat equation and the plate bending equation. The purpose of this paper is to provide a quick walkthrough of the various approaches that the authors followed in pursuit of creating optimal solvers, accelerated with the use of graphical processing units, and comparing them in terms of accuracy and time efficiency with existing or self-made non-accelerated solvers.

Développement et validation de méthodes visant une utilisation optimale d'antennes réceptrices en imagerie par résonance magnétique

Différentes méthodes ayant pour objectif une utilisation optimale d'antennes radio-fréquences spécialisées en imagerie par résonance magnétique sont développées et validées. Dans un premier temps, il est démontré qu'une méthode alternative de combinaison des signaux provenant des différents canaux de réception d'un réseau d'antennes mène à une réduction significative du biais causé par la présence de bruit dans des images de diffusion, en comparaison avec la méthode de la somme-des-carrés généralement utilisée. Cette réduction du biais engendré par le bruit permet une amélioration de l'exactitude de l'estimation de différents paramètres de diffusion et de diffusion tensorielle. De plus, il est démontré que cette méthode peut être utilisée conjointement avec une acquisition régulière sans accélération, mais également en présence d'imagerie parallèle. Dans une seconde perspective, les bénéfices engendrés par l'utilisation d'une antenne d'imagerie intravasculaire sont étudiés. Suite à une étude sur fantôme, il est démontré que l'imagerie par résonance magnétique intravasculaire offre le potentiel d'améliorer significativement l'exactitude géométrique lors de mesures morphologiques vasculaires, en comparaison avec les résultats obtenus avec des antennes de surface classiques. Il est illustré qu'une exactitude géométrique comparable à celle obtenue grâce à une sonde ultrasonique intravasculaire peut être atteinte. De plus, plusieurs protocoles basés sur une acquisition de type balanced steady-state free-precession sont comparés dans le but de mettre en évidence différentes relations entre les paramètres utilisés et l'exactitude géométrique obtenue. En particulier, des dépendances entre la taille du vaisseau, le rapport signal-sur-bruit à la paroi vasculaire, la résolution spatiale et l'exactitude géométrique atteinte sont mises en évidence. Dans une même optique, il est illustré que l'utilisation d'une antenne intravasculaire permet une amélioration notable de la visualisation de la lumière d'une endoprothèse vasculaire. Lorsque utilisée conjointement avec une séquence de type balanced steady-state free-precession utilisant un angle de basculement spécialement sélectionné, l'imagerie par résonance magnétique intravasculaire permet d'éliminer complètement les limitations normalement engendrées par l'effet de blindage radio-fréquence de l'endoprothèse.

Model - data comparison of western African rainfall evolutions during the Last Interglacial (130-115 ka)

This dataset characterizes the evolution of western African precipitation indicated by marine sediment geochemical records in comparison to transient simulations using CCSM3 global climate model throughout the Last Interglacial (130-115 ka). It contains (1) defined tie-points (age models), newly published stable isotopes of benthic foraminifera and Al/Si log-ratios of eight marine sediment cores from the western African margin and (2) annual and seasonal rainfall anomalies (relative to pre-industrial values) for six characteristic latitudinal bands in western Africa simulated by CCSM3 (two transient simulations: one non-accelerated and one accelerated experiment).

Transient simulations for present and last interglacials using a comprehensive coupled climate model CCSM3 (Community Climate System Model 3.0), links to model result files in NetCDF format

Transient simulations are widely used in studying the past climate as they provide better comparison with any exisiting proxy data. However, multi-millennial transient simulations using coupled climate models are usually computationally very expensive. As a result several acceleration techniques are implemented when using numerical simulations to recreate past climate. In this study, we compare the results from transient simulations of the present and the last interglacial with and without acceleration of the orbital forcing, using the comprehensive coupled climate model CCSM3 (Community Climate System Model 3). Our study shows that in low-latitude regions, the simulation of long-term variations in interglacial surface climate is not significantly affected by the use of the acceleration technique (with an acceleration factor of 10) and hence, large-scale model-data comparison of surface variables is not hampered. However, in high-latitude regions where the surface climate has a direct connection to the deep ocean, e.g. in the Southern Ocean or the Nordic Seas, acceleration-induced biases in sea-surface temperature evolution may occur with potential influence on the dynamics of the overlying atmosphere. The data provided here are from both accelerated and non-accelerated runs as decadal mean values.

A comparison between accelerated hypofractionation and stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC): Results of a propensity score-matched analysis

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) has become standard for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is no randomized evidence demonstrating benefit over more fractionated radiotherapy. We compared accelerated hypofractionation (AH) and SABR using a propensity score-matched analysis.

MATERIALS AND METHODS: From 1997-2007, 119 patients (T1-3N0M0 NSCLC) were treated with AH (48-60Gy, 12-15 fractions). Prior to SABR, this represented our institutional standard. From 2008-2012, 192 patients (T1-3N0M0 NSCLC) were treated with SABR (48-52Gy, 4-5 fractions). A total of 114 patients (57 per cohort) were matched (1:1 ratio, caliper: 0.10) using propensity scores.

RESULTS: Median follow-up (range) for the AH cohort was 36.3 (2.5-109.1) months, while that for the SABR group was 32.5 (0.3-62.6)months. Three-year overall survival (OS) and local control (LC) rates were 49.5% vs. 72.4% [p=0.024; hazard ratio (HR): 2.33 (1.28, 4.23), p=0.006] and 71.9% vs. 89.3% [p=0.077; HR: 5.56 (1.53, 20.2), p=0.009], respectively. On multivariable analysis, tumour diameter and PET staging were predictive for OS, while the only predictive factor for LC was treatment cohort.

CONCLUSIONS: OS and LC were improved with SABR, although OS is more closely related to non-treatment factors. This represents one of the few studies comparing AH to SABR for early-stage lung cancer.

Comparison of non-Ohmic accelerated ageing of the ZnO- and SnO2-based voltage dependent resistors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effectiveness of non-conventional methods for accelerated orthodontic tooth movement: a systematic review and meta-analysis.

OBJECTIVES To assess the available evidence on the effectiveness of accelerated orthodontic tooth movement through surgical and non-surgical approaches in orthodontic patients. METHODS Randomized controlled trials and controlled clinical trials were identified through electronic and hand searches (last update: March 2014). Orthognathic surgery, distraction osteogenesis, and pharmacological approaches were excluded. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Eighteen trials involving 354 participants were included for qualitative and quantitative synthesis. Eight trials reported on low-intensity laser, one on photobiomodulation, one on pulsed electromagnetic fields, seven on corticotomy, and one on interseptal bone reduction. Two studies on corticotomy and two on low-intensity laser, which had low or unclear risk of bias, were mathematically combined using the random effects model. Higher canine retraction rate was evident with corticotomy during the first month of therapy (WMD=0.73; 95% CI: 0.28, 1.19, p<0.01) and with low-intensity laser (WMD=0.42mm/month; 95% CI: 0.26, 0.57, p<0.001) in a period longer than 3 months. The quality of evidence supporting the interventions is moderate for laser therapy and low for corticotomy intervention. CONCLUSIONS There is some evidence that low laser therapy and corticotomy are effective, whereas the evidence is weak for interseptal bone reduction and very weak for photobiomodulation and pulsed electromagnetic fields. Overall, the results should be interpreted with caution given the small number, quality, and heterogeneity of the included studies. Further research is required in this field with additional attention to application protocols, adverse effects, and cost-benefit analysis. CLINICAL SIGNIFICANCE From the qualitative and quantitative synthesis of the studies, it could be concluded that there is some evidence that low laser therapy and corticotomy are associated with accelerated orthodontic tooth movement, while further investigation is required before routine application.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Accelerated induction of experimental allergic encephalomyelitis in PL/J mice by a non-V beta 8-specific superantigen.

Superantigens such as the staphylococcal enterotoxins can play an important role in exacerbation of autoimmune disorders such as experimental allergic encephalomyelitis (EAE) in mice. In fact, superantigens can reactivate EAE in PL/J mice that have been sensitized to rat myelin basic protein (MBP). The T-cell subset predominantly responsible for disease in PL/J mice bears the V beta 8+ T-cell antigen receptor (TCR). The question arises as to whether T cells bearing other V beta specificities are involved in induction or reactivation of EAE with superantigen. Thus, we have investigated the ability of a non-V beta 8-specific superantigen, staphylococcal enterotoxin A (SEA) (V beta specificities 1, 3, 10, 11, and 17), to induce EAE in PL/J mice that have been previously protected from disease by anergy and deletion of V beta 8+ T cells. PL/J mice were first pretreated with the V beta 8-specific superantigen staphylococcal enterotoxin B (SEB) and then immunized with MBP. These mice exhibited V beta 8-specific anergy and depletion and did not develop EAE, even when further treated with SEB. However, administration of SEA to these same mice induced an initial episode of EAE which was characterized by severe hindleg paralysis and accelerated onset of disease. In contrast to SEB pretreatment, PL/J mice pretreated with SEA did develop EAE when immunized with MBP, and after resolution of clinical signs of disease these mice were susceptible to relapse of EAE induced by SEB but not by SEA. Thus, superantigens can activate encephalitogenic MBP-specific non-V beta 8+ T cells to cause EAE in PL/J mice. These data suggest that superantigens can play a central role in autoimmune disorders and that they introduce a profound complexity to autoimmune diseases such as EAE, akin to the complexity seen in multiple sclerosis.

Asset life prediction and maintenance decision-making using a non-linear non-Gaussian state space model

Estimating and predicting degradation processes of engineering assets is crucial for reducing the cost and insuring the productivity of enterprises. Assisted by modern condition monitoring (CM) technologies, most asset degradation processes can be revealed by various degradation indicators extracted from CM data. Maintenance strategies developed using these degradation indicators (i.e. condition-based maintenance) are more cost-effective, because unnecessary maintenance activities are avoided when an asset is still in a decent health state. A practical difficulty in condition-based maintenance (CBM) is that degradation indicators extracted from CM data can only partially reveal asset health states in most situations. Underestimating this uncertainty in relationships between degradation indicators and health states can cause excessive false alarms or failures without pre-alarms. The state space model provides an efficient approach to describe a degradation process using these indicators that can only partially reveal health states. However, existing state space models that describe asset degradation processes largely depend on assumptions such as, discrete time, discrete state, linearity, and Gaussianity. The discrete time assumption requires that failures and inspections only happen at fixed intervals. The discrete state assumption entails discretising continuous degradation indicators, which requires expert knowledge and often introduces additional errors. The linear and Gaussian assumptions are not consistent with nonlinear and irreversible degradation processes in most engineering assets. This research proposes a Gamma-based state space model that does not have discrete time, discrete state, linear and Gaussian assumptions to model partially observable degradation processes. Monte Carlo-based algorithms are developed to estimate model parameters and asset remaining useful lives. In addition, this research also develops a continuous state partially observable semi-Markov decision process (POSMDP) to model a degradation process that follows the Gamma-based state space model and is under various maintenance strategies. Optimal maintenance strategies are obtained by solving the POSMDP. Simulation studies through the MATLAB are performed; case studies using the data from an accelerated life test of a gearbox and a liquefied natural gas industry are also conducted. The results show that the proposed Monte Carlo-based EM algorithm can estimate model parameters accurately. The results also show that the proposed Gamma-based state space model have better fitness result than linear and Gaussian state space models when used to process monotonically increasing degradation data in the accelerated life test of a gear box. Furthermore, both simulation studies and case studies show that the prediction algorithm based on the Gamma-based state space model can identify the mean value and confidence interval of asset remaining useful lives accurately. In addition, the simulation study shows that the proposed maintenance strategy optimisation method based on the POSMDP is more flexible than that assumes a predetermined strategy structure and uses the renewal theory. Moreover, the simulation study also shows that the proposed maintenance optimisation method can obtain more cost-effective strategies than a recently published maintenance strategy optimisation method by optimising the next maintenance activity and the waiting time till the next maintenance activity simultaneously.

Transferring a successful strategy for supporting accelerated nursing students from a small to a large cohort

In 2009 and 2010, withdrawal rates from a Pharmacology unit of accelerated QUT nursing students in the first year of their degree, were higher than for continuing students. The cohort of 216 accelerated students in 2011 had university or non-university qualification or equivalent experience and included domestic and international students. A previously tested intervention was introduced in 2011 to improve retention rates and support all Pharmacology students in their first year of nursing. The intervention involved a community website, on-line tutors and an “O week” workshop comprising information about library resources, effective learning strategies and learning tips from a previous student as well as review anatomy, physiology and microbiology lectures. Withdrawal rates for accelerated students in the Pharmacology unit improved and all students found the workshop and review lectures to be informative and valuable. The intervention was therefore successfully transferred to a large, diverse cohort of accelerated nursing students.