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Background Liquid biopsy using cell-free DNA (cfDNA) presents new opportunities for solid tumor genotyping. While studies have demonstrated the utility of cfDNA from plasma, cfDNA from other body fluids remains underexplored. Methods We evaluated the molecular features and clinicopathologic correlates of cfDNA from serous body cavity fluids by performing hybrid capture-based next-generation sequencing (NGS) on cfDNA isolated from residual effusion supernatants. Twenty-one serous effusions from pleural (n = 15), peritoneal (n = 5), and pericardial (n = 1) cavity were analyzed. Results The supernatants provided a median cfDNA concentration of 10.3 ng/µL. Notably, all effusions were sequenced successfully to a median depth >1000×, revealing a broad range of genetic alterations including single nucleotide variants, small insertions and deletions, amplifications, and fusions. Specifically, pathogenic alterations were identified in all malignant fluids (13/13), all fluids suspicious for malignancy (2/2), and 1 benign fluid (1/6) from a patient with metastatic cancer. To validate our findings, we examined matching results from 11 patients who underwent additional testing using formalin-fixed, paraffin-embedded (FFPE) specimens. In 8 patients, the paired results between FFPE and supernatant testing were concordant, whereas in the remaining 3 patients, supernatant analysis identified additional variants likely associated with resistance to targeted therapies. Additional comparison between FFPE and supernatant testing showed no difference in DNA concentration (P = .5), depth of coverage (P = .6), or allele frequency of pathogenic mutations (P = .7). Conclusion cfDNA isolated from serous body cavity fluids represents a promising source of genomic input for targeted NGS.

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.

Squamous cell carcinoma (SCC) of the prostate is a rare and clinically aggressive entity that may arise de novo or through transformation of prostatic adenocarcinoma, typically following hormonal or radiation therapy. Confirmation of prostatic origin, especially when evaluating a metastatic focus, often requires correlation with clinical and imaging findings, as the morphologic and immunohistochemical features of SCC are not organ-specific. Comprehensive genomic profiling (CGP) may provide additional information useful for confirming the primary site and for identifying potential targeted therapy options. CGP data may also contribute to our understanding of the molecular basis of squamous differentiation in prostatic malignancies. However, these data are limited, and to our knowledge, there are only three previously published cases of prostatic SCC with reported CGP findings. Herein, we report a case of metastatic keratinizing SCC diagnosed by core needle biopsy in a 68-year-old man with a history of prostatic adenocarcinoma status post radical prostatectomy and androgen deprivation therapy (ADT). NKX3.1 immunohistochemistry was negative. CGP was performed, and a TMPRSS2-ERG fusion, among other genetic alterations, was detected, supporting a diagnosis of metastatic SCC transformed from prostatic adenocarcinoma following ADT. This case supports the use of CGP or other molecular techniques not only to query potential targeted therapy options but also to refine the diagnosis and confirm the primary site of disease in cases with non-specific morphologic and immunophenotypic features, such as SCC.

Background Fine‐needle aspiration with flow cytometry (FNA‐FC) is routinely used in the evaluation of lymph nodes suspicious for lymphoma, yet data comparing immunophenotype distributions and outliers in benign lymph nodes sampled by fine‐needle aspiration (FNA) versus excision are lacking. Methods Flow cytometry data from 289 benign lymph node FNA cases were assessed for the overall antigen distribution, with a focus on outliers relevant to the diagnosis of lymphoma. Distributions and outlier proportions were compared with those of a separate cohort of 298 excisional biopsies. Results Compared with excisional biopsies, FNA specimens overrepresented CD3+ events (72% vs 63%), underrepresented CD19+ events (22% vs 29%), and had 25% fewer large cell–gated events. Normalized antigen distributions in FNA were equivalent to those in excisional biopsy. Twenty‐three percent of FNA‐FC cases exhibited an outlier, including a skewed kappa:lambda light‐chain ratio, increased CD5+ or CD10+ B‐cell events, a skewed CD4:CD8 ratio, and increased CD7 loss on T cells, with no significant differences in frequency or type in comparison with excisional specimens. Outliers for the light‐chain ratio and T‐cell antigens were enriched among older patients and included patients with a variety of autoimmune/rheumatologic conditions. Conclusions Benign lymph node FNA yields flow immunophenotypes remarkably similar to those from excisional biopsies. Outlier flow immunophenotypes are identified in benign lymph nodes sampled by FNA at a frequency similar to that with excisional biopsies. Older patients, who have a higher baseline risk of lymphoma, are more likely to exhibit lymphoma‐mimicking outliers such as a light‐chain predominance on B cells and skewed CD4:CD8 ratios or increased CD7 loss on T cells, and they warrant additional diagnostic caution., Fine‐needle aspiration–based flow cytometry of lymph nodes is comparable to excisional biopsy and exhibits similar outliers. The reference ranges provided in this study can aid pathologists and contribute in the long term to computational flow analysis and biomedical research.

Recognition of the inverted faces (compared to upright faces) becomes much more difficult, this phenomenon is known as “facial inversion effect”. The role of face inversion on the eye-movement patterns is still under debate. In the current research, we aimed to investigate the effects of face inversion and the number of feature differences on eye-movement patterns during judgement of similarity between two faces. The participants were asked to judge the pairs of faces similarity by a 4-point Likert scale. Eye-movements were recorded during similarity ratings. The faces were presented either upright or inverted. The pairs of the faces were either the same or different. The different pairs of faces were manipulated via the number of feature differences (i.e., one feature or two features). As expected, we found that the inversion of the faces resulted in a higher level of estimated similarity in overall. However, when only the hairs were different between two faces, the inversion of the faces resulted in a lower level of estimated similarity. Surprisingly, the inversion of the faces resulted in a significant decrease of transitions between the pairs of inverted faces. The less eye gaze transitions during similarity rating of inverted pairs suggested that the feature-based processing strategy of inverted faces was less likely to be used in our rating task that presumably exerts no memory load. In conclusion, our findings suggested that both face inversion and the number of feature differences influence the eye-movement patterns during the similarity rating of two simultaneously presented faces.

Associative recognition requires discriminating between old items and conjunction lures constructed by recombining elements from two different study items. This task can be solved not only by recollection but also by familiarity if the to-be-remembered stimuli are perceived as a unitized representation. In two event-related potential (ERP) studies, we provide evidence for the integration of internal and external facial features by showing that the early frontal old-new effect (considered a correlate of familiarity) is modulated by the specific combination of facial features. Participants studied faces consisting of internal features (eyes, eyebrows, nose, and mouth) paired with external features (hair, head shape, and ears). During the testing phase, intact, recombined, and new faces were presented. Recombined faces consisted of internal and external features taken from two different studied faces. The results showed that at the frontal sites, during the time window from 300 to 500 ms, ERPs to intact faces were more positive than those to new and recombined faces; the latter two did not differ from one another. The late parietal effect was observed only after a more extended study phase in Experiment 2. We take the modulation of the early frontal old-new effect as evidence for the contribution of familiarity to associative recognition for combinations of internal and external facial features.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69 y), and the M:F ratio was 2.2:1. Median tumor size was 6.5 cm (range, 2.5 to 28 cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118 mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9 y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.

The relevance of human papillomavirus (HPV)-related features in cutaneous, non-anogenital SCC is not known and not incorporated into current diagnostic categories and treatment algorithms. Here, we describe the case of a 78-year-old male with bilateral inguinal warty-basaloid carcinoma, which is an HPV-related SCC that, in men, has been described only in a penile location. The patient underwent surgical excision without lymphadenectomy and declined radiation therapy due to concerns of poor wound healing. Adjuvant chemotherapy was not offered given the patient's Stage IV chronic kidney disease and undefined degree of benefit in the absence of concurrent radiotherapy. We therefore opted for close follow up and surveillance with PET/CT imaging and full body skin exams. The patient also received HPV vaccination. No clinical evidence of recurrence or metastasis was apparent at 6 months following initial excision. The identification of HPV-associated cutaneous SCC and correlation with patient outcomes is necessary to evaluate the prognostic significance of these features and to clarify the role of different treatment strategies in this setting.

BACKGROUND The classification of renal neoplasms is essential for oncologic risk stratification and clinical management, and an accurate pretreatment pathologic diagnosis can provide useful guidance for active surveillance, minimally invasive ablative therapy, or surgical resection and can reduce the incidence of overtreatment. Previous studies evaluating the diagnostic accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for renal masses are limited and show variable results. METHODS Two hundred forty-seven renal FNA cases with or without concurrent CNB performed and/or reviewed at the Stanford University School of Medicine over the course of 20 years were identified. Cytohistopathologic correlation was performed for 77 cases with subsequent resection specimens. All available case materials were reviewed, and select cases were worked up further and reclassified as necessary. RESULTS Cytohistopathologic correlation showed 96% diagnostic specificity and 83% sensitivity for renal FNA with or without concurrent CNB. Discordant cases were mostly attributed to sampling errors or suboptimal specimens (79%) and also included 2 non-renal cell carcinoma entities (1 case of angiomyolipoma and 1 case of a benign peripheral nerve sheath tumor) and 1 case involving misclassification of the renal cell carcinoma subtype. CONCLUSIONS There is considerable value in FNA/CNB for the initial diagnosis of renal masses because of the high diagnostic specificity and sensitivity. Sensitivity is predominantly dependent on sufficient sampling, and additional potential diagnostic pitfalls include nonepithelial and rare entities. Judicious use of ancillary techniques is encouraged, especially when one is presented with a limited specimen, and this article presents a practical algorithmic approach to the diagnosis of renal masses using salient morphologic features and results from ancillary studies. Fine-needle aspiration is an accurate method for the diagnosis of renal masses. A practical diagnostic algorithm, based on salient morphologic and ancillary findings, is presented.

Previous studies have shown that we need to distinguish between means and end information about actions. It is unclear how these two subtypes of action information relate to each other with theoretical accounts postulating the superiority of end over means information and others linking separate means and end routes of processing to actions of differential meaningfulness. Action meaningfulness or familiarity differs between cultures. In a cross-cultural setting, we investigated how action familiarity influences recognition memory for means and end information. Object directed actions of differential familiarity were presented to Chinese and German participants. Action familiarity modulated the representation of means and end information in both cultures in the same way, although the effects were based on different stimulus sets. Our results suggest that, in the representation of actions in memory, end information is superordinate to means information. This effect is independent of culture whereas action familiarity is not.

In this training study, we aimed to selectively train participants' filtering mechanisms to enhance visual working memory (WM) efficiency. The highly restricted nature of visual WM capacity renders efficient filtering mechanisms crucial for its successful functioning. Filtering efficiency in visual WM can be measured via the lateralized change detection task with distractors. From an array of items, only a subsample must be memorized (targets), whereas distractors must be filtered out. From the EEG recorded while items are maintained in memory, slow potentials over posterior recording sides can be extracted. In addition, the contralateral delay activity (CDA) can be calculated as the difference wave between contralateral and ipsilateral slow potentials. As the amplitudes of contralateral slow potentials and CDA reflect the number of remembered items, one can infer if distractors were filtered out. Efficient filtering mechanisms are also highly important in multiple object tracking (MOT). We trained participants' filtering ability with the aid of this latter task. Filtering in both tasks is assumed to happen via allocation of selective attention. We observed large training-induced improvements in MOT. However, these improvements did not transfer to improved filtering mechanisms in the change detection task. Instead, we obtained suggestive evidence for an overall improvement in filtering mechanisms in the change detection task for both the training and control group. Apparently, there exist differences in the exact nature of filtering mechanisms that operate in change detection and MOT.

The effects of action complexity and familiarity on preschooler's imitation performance were investigated. Thirty-two tool-use action video clips were imitated by 32 German and 32 Chinese preschoolers. Preschoolers' imitation performance was better for familiar as compared to unfamiliar actions and for simple as compared to complex actions. Furthermore, imitation errors were classified as means (action steps to reach the goal) errors and ends (action outcomes) errors. When imitating simple actions children made more means than ends errors, whereas more ends errors were made for complex actions. We explain this by the higher demands of processing complex actions on cognitive resources. This result highlights the important role of action complexity in children's representation of the means and ends of tool-use actions. Performances showed a high cross-cultural stability, which indicates that imitation is a basic learning mechanism thereby uninfluenced by cultures.

SUMMARY Public Company Accounting Oversight Board (PCAOB) Concept Release No. 2011-003 (PCAOB 2011a) proposes changes that may require auditors to disclose qualitative information about management and the audit. While there is evidence that a change may be necessary, it is unclear how the proposed changes would impact auditors. Based on our practitioner and educational experiences, we discuss potential impacts of these proposed changes on the current audit environment. We provide insights and recommend that the PCAOB perform additional research concerning this proposed standard prior to implementation to gain a more thorough understanding of all relevant issues.

Small and medium-sized enterprises play an important role in the US economy, yet they're often beset by financial woes. Financial professionals can help their executives and managers convert the vision, mission, and strategic goals of their enterprises to provide timely information; assist with pricing and cost analysis for bids or orders; and assist these enterprises with meeting regulatory requirements. © 2011 Wiley Periodicals, Inc.

The time taken to decide whether a character is shown in its mirror or normal version has been shown to increase approximately linearly with the angular departure from an up-right position. Additionally, in some studies, decisions took longer for clockwise tilted characters than for counterclockwise tilted ones. Other studies do not report the latter effect. We argue that inconsistencies across studies are caused by variance in participants' strategies. The task employed here was specifically designed to bring these strategies and thereby the direction of rotation under experimental control. From the EEG recorded during the rotation period, we extracted an event-related slow potential whose amplitude is sensitive to the amount of mental rotation. In both strategy conditions, the slow potential's amplitude was lower for clockwise than for counterclockwise rotations. We take this as evidence that mental rotation of alphanumeric characters is easier in a clockwise than in a counterclockwise direction.

Research on the effects of perceptual manipulations on recognition memory has suggested that (a) recollection is selectively influenced by task-relevant information and (b) familiarity can be considered perceptually specific. The present experiment tested divergent assumptions that (a) perceptual features can influence conscious object recollection via verbal code despite being task-irrelevant and that (b) perceptual features do not influence object familiarity if study is verbal-conceptual. At study, subjects named objects and their presentation colour; this was followed by an old/new object recognition test. Event-related potentials (ERP) showed that a study-test manipulation of colour impacted selectively on the ERP effect associated with recollection, while a size manipulation showed no effect. It is concluded that (a) verbal predicates generated at study are potent episodic memory agents that modulate recollection even if the recovered feature information is task-irrelevant and (b) commonly found perceptual match effects on familiarity critically depend on perceptual processing at study.

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib.

Within dual-process accounts of recognition memory, familiarity (as opposed to recollection) is often referred to as a rather automatic and context-free process. Thus, in episodic object recognition, familiarity and its electrophysiological ERP signature are supposed to index prior occurrence of an object independent of the context the object was originally encountered in, e.g., [Ecker, U.K.H., Zimmer, H.D., Groh-Bordin, C., in press. Color and context: An ERP study on intrinsic and extrinsic feature binding in episodic memory. Mem. Cogn.]). Yet, contextual sensitivity of familiarity has also been reported (e.g., [Tsivilis, D., Otten, L.J., Rugg, M.D., 2001. Context effects on the neural correlates of recognition memory: An electrophysiological study. Neuron 31, 497-505.]). We argue that considering attentional and perceptual factors of target processing is vital in understanding these conflicting results. Presenting target objects on contextual landscape scenes, we introduced a cueing technique designed to focus subjects' attention on target processing. We demonstrate that context effects on familiarity are diminished if the attentional impact of contextual stimuli is experimentally controlled, arguing that contextual influences on object familiarity are indirect and mediated by factors such as salience and attentional capture. Results suggest that salient context stimuli may elicit an independent familiarity signal instead of directly impacting on the familiarity signal of the target object. We conclude that (a) object familiarity is in principle a rather automatic and context-free process, and that (b) the study of episodic memory can profit substantially from adopting a dynamic processing perspective.

PurposeCoronary artery aneurysms (CAA) may remain silent after Kawasaki disease (KD) until adulthood when myocardial ischemia can lead to sudden death. We postulated that there would be young adults with sudden, unexpected death due to CAA from KD who would have a state-mandated autopsy performed by the San Diego County Medical Examiner's Office (SDCMEO).MethodsWe reviewed all autopsy cases

It is argued that explicit remembering is based on so-called episodic tokens binding together all perceptual features of a visual object. In episodic recognition, these features are collectively reactivated. In support of this view, it has been shown that changing sensory features of a stimulus from study to test decreases subject's performance in an episodic recognition task, even though the changed features are irrelevant for the recognition judgment. On the other hand, repetition priming is unaffected by such manipulations of perceptual specificity. Implicit memory performance is therefore thought to depend on structural representations, so-called types, comprising only invariant perceptual features, but no exemplar-specific details. Event-related potentials (ERPs) in our study revealed electrophysiological evidence for the differential involvement of these perceptual memory traces in explicit and implicit memory tasks. Participants attended either a living-nonliving task or an episodic recognition task with visually presented objects. During test both groups of participants processed new objects and old objects, which were repeated either identically or in a mirror-reversed version. In the implicit task ERPs showed an occipitoparietal repetition effect, which was the same for identically repeated items and mirror reversals. In contrast, in the explicit task an early mid-frontal old/new effect for identical but not for mirror-reversed old objects was observed indicating involuntary access to perceptual information during episodic retrieval. A later portion of the old/new effect solely differentiated both types of old items from new ones.

If configurations of objects are presented in a S1-S2 matching task for the identity of objects a spatial mismatch effect occurs. Changing the (irrelevant) spatial layout lengthens response times. We investigated what causes this effect. We observed a reliable mismatch effect that was not influenced by a secondary task during maintenance. Neither articulatory suppression (Experiment 1), nor unattended (Experiments 2 and 6) or attended visual material (Experiment 3) reduced the effect, and this was independent of the length of the retention interval (Experiment 6). The effect was also rather independent of the visual appearance of the local elements. It was of similar size with color patches (Experiment 4) and with completely different surface information when testing was cross modal (Experiment 5), and the name-ability of the global configuration was not relevant (Experiments 6 and 7). In contrast, the figurative similarity of the configurations of S1 and S2 systematically influenced the size of the spatial mismatch effect (Experiment 7). We conclude that the spatial mismatch effect is caused by a mismatch of the global shape of the configuration stored together with the objects of S1 and not by a mismatch of templates of perceptual records maintained in a visual cache.

In three experiments, we investigated the influence of the overt performance of signs on memory. Deaf and hearing participants studied lists of action phrases (Experiment 1) or nouns (Experiment 2) under standard verbal instruction, under the instructions to sign the verbal phrase, to symbolically perform the denoted action, or to carry out a prototypical action corresponding to each noun. Higher recall and recognition performances were observed when actions were performed than in the verbal encoding condition, and signing was as effective for memory as was enactment. Thus, overt signing can induce an enactment effect. In contrast, Experiment 3 demonstrated that performing an unrelated action did not. A unique but unrelated action was not memory efficient.

In three experiments we investigated the perceptual specificity of explicit (old-new object recognition) and implicit memory (word-picture matching) for colour. In order to enhance the impact of co...

A new approach was taken to study the question whether the free recall advantage of enacting actions (SPT), over only listening to their verbal descriptions (VT), is due to better relational encoding of SPTs than of VTs. The approach consisted of studying related lists and manipulating the degree of relational encoding by repeated list presentation in Experiment 1 and by presenting the list items at random or blocked in Experiment 2. In both experiments, free recall and adjusted ratio of clustering (ARC) scores increased as to be expected with repeated list presentation and blocking. However, these effects proved to be independent of the type of encoding. There was a clear SPT effect in free recall, but in contrast a slight though nonsignificant advantage of VTs over SPTs in ARC scores. Altogether, the experiments show that the SPT effect in free recall is not due to better relational encoding in SPTs than in VTs, in line with the assumption that this effect is due to good item-specific encoding.

Working memory capacity (WMC) and reasoning abilities—as assessed by figural matrices tests—are substantially correlated. It is controversially discussed whether this correlation is only caused by controlled attention or also by storage capacity. This study aims at investigating storage of partial solutions as a possible mechanism by which storage capacity may contribute to solving figural matrices tests. For this purpose, we analyzed how an experimental manipulation of storage demands changes the pattern of correlations between WMC and performance in a matrix task. We manipulated the storage demands by applying two test formats: one providing the externalization of partial solutions and one without the possibility of externalization. Storage capacity was assessed by different types of change detection tasks. We found substantial correlations between storage capacity and matrices test performance, but they were of comparable size for both test formats. We take this as evidence that the necessity to store partial solutions is not the limiting factor which causes the association between storage capacity and matrices test. It is discussed how this approach can be used to investigate alternative mechanisms by that storage may influence performance in matrices tests.

We investigated the impact of perceptual processing demands on visual working memory of coloured complex random polygons during change detection. Processing load was assessed by pupil size (Exp. 1) and additionally slow wave potentials (Exp. 2). Task difficulty was manipulated by presenting different set sizes (1, 2, 4 items) and by making different features (colour, shape, or both) task-relevant. Memory performance in the colour condition was better than in the shape and both condition which did not differ. Pupil dilation and the posterior N1 increased with set size independent of type of feature. In contrast, slow waves and a posterior P2 component showed set size effects but only if shape was task-relevant. In the colour condition slow waves did not vary with set size. We suggest that pupil size and N1 indicates different states of attentional effort corresponding to the number of presented items. In contrast, slow waves reflect processes related to encoding and maintenance strategies. The observation that their potentials vary with the type of feature (simple colour versus complex shape) indicates that perceptual complexity already influences encoding and storage and not only comparison of targets with memory entries at the moment of testing.

In memory for subject-performed tasks (SPTs), subjects encode a list of simple action phrases (e.g., thumb through a book, knock at the door) by performing these actions during learning. In three experiments, we investigated the size of the levels-of-processing effects in SPTs as compared with those in standard verbal learning tasks (VTs). Subjects under SPT and VT conditions learned lists of action phrases in a surface or a conceptual orienting task. Under both encoding conditions, the subjects recalled fewer items with surface orienting tasks than with conceptual orienting tasks, but the levels-of-processing effects were strongly reduced in the SPT condition. In the SPT condition, items that were encoded in a surface orienting task were still substantially recalled. The items were recalled almost as well as the conceptually encoded items in the VT condition. The distinct reduction of the levels-of-processing effect is caused by the fact that, in SPT encoding even with a verbal surface orienting task, subjects process conceptual information in order to perform the denoted action. We attribute the small conceptual advantage, which remains with SPT despite the conceptual processing for performing, to the fact that items are not as well integrated into memory as they are when conceptual processing is focused on the action component, rather than on the semantic contexts. This lower integration reduces the accessibility of items in the verbal surface task, even with SPT encoding.

This paper uses an organizational science framework to evaluate the present status of the public accounting profession and make recommendations for a systematic process to influence long‐term effective change. Historically, the profession has implemented short‐term responses to environmental events such as corporate merger mania, globalization of the economy, or demographic changes in the workforce. This paper suggests establishment of a joint long‐term effort among the Big Six firms as well as major national and regional firms to influence long‐term changes to the way the profession manages its human resources, develops and maintains businesses, and operates as a legal entity.

Background Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future. Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus. Methods/Design In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus. This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment. The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment. The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes. Patients are randomised by central fax randomisation. Primary endpoint is mean HbA1c after 24 months of treatment. Secondary endpoints are change in FEV1% predicted and change in BMI-Z-score. Discussion There is only one prospective study comparing oral antidiabetic drugs to insulin in the treatment of CFRD without fasting hyperglycaemia. The results regarding BMI after 6 months and 12 months showed an improvement for the insulin treated patients and were inconsistent for those treated with repaglinide. HbA1c and lung function (FEV1%pred) were unchanged for either group. The authors compared the changes -12 months to baseline and baseline to +12 months separately for each group. Therefore a direct comparison of the effect of repaglinide versus insulin on BMI, HbA1c and FEV1%pred was not presented. According to our protocol, we will directly compare treatment effects (HbA1c, BMI, FEV1%pred) in between both groups. The actual Cochrane report regarding “Insulin and oral agents for managing CFRD” stated that further studies are needed to establish whether there is clear benefit for hypoglycemic agents. We expect that the results of our study will help to address this clinical need. Trial registration ClinicalTrials.gov Identifier: NCT00662714

In three experiments, people learned descriptions of layouts and were then tested on the locations of objects in the layouts. Learning occurred either by using arrow-keys (a pointing-like procedure) or naming directions (front, back, right, left) to explore the layout, and testing involved either arrow-keys or verbal responses. In Experiment 1a, using arrow keys during learning and testing, right/left judgments were made faster than front/back judgments (reverse pattern). In Experiment 2a, direction labels were used during learning and testing, and front/back judgments were made faster than right/left, replicating the standard pattern obtained by Franklin & Tversky (1990). In Experiment 3 subjects learned the layout using direction labels and were tested with arrow-keys and the reverse pattern was found again. Response biases (Experiments 1b and 1c) and phonological biases (Experiment 2b) were ruled out as explanations for the patterns obtained. The pragmatics and requirements involved in each modality accounts for the accessibility patterns obtained with pointing and verbal labeling.

Pharmaceutical companies have received a tremendous amount of attention in the media regarding increases in drug prices at rates much in excess of the rate of inflation. Synthesizes the numerous issues affecting drug pricing and the role that the auditor should play in determining a “fair” price. Evaluates the role of the auditor with regard to the call from investors for additional information in the annual report and more in‐depth analysis of management′s ethical and operational practices. The pharmaceuticals industry represents a unique area for consideration, given ethical and regulatory pressures and the nature of the drug development and distribution process. With the complexities of this process, considers the auditor′s responsibility to understand unfair pricing practices along with the ability to detect such practices.

Proposes a new model for fraud detection that goes beyond internal accounting controls. Historically, internal and external auditors focus on internal controls and management integrity as the key components to determine the propensity for irregularities. This new paradigm focuses on gaining an understanding of the corporate culture in order to understand better the opportunity for fraud or illegal acts to occur. Corporate culture provides a more holistic and comprehensive view of the overall management philosophy and control environment. Various sources from practitioners, corporate executives to government agencies estimate that the annual cost of fraud exceeds $100 billion. Recognizes the economic impact of fraud and the historical problems associated with fraud detection. Offers recommendations and discussion for a new model to evaluate organizational behaviour as an alternative method to fight the social and economic cost of fraud.

There is ongoing debate concerning the mechanisms of feature binding in working memory. In particular, there is controversy regarding the extent to which these binding processes are automatic. The present article demonstrates that binding mechanisms differ depending on whether the to-be-integrated features are perceived as forming a coherent object. We presented a series of experiments that investigated the binding of color and shape, whereby color was either an intrinsic feature of the shape or an extrinsic feature of the shape's background. Results show that intrinsic color affected shape recognition, even when it was incidentally studied and irrelevant for the recognition task. In contrast, extrinsic color did not affect shape recognition, even when the association of color and shape was encoded and retrievable on demand. This strongly suggests that binding of intrinsic intra-item information but not extrinsic contextual information is obligatory in visual working memory. We highlight links to perception as well as implicit and explicit long-term memory, which suggest that the intrinsic-extrinsic dimension is a principle relevant to multiple domains of human cognition.

Seeks to compare the three auditor attributes of brand name or reputation, concentration and structure to determine how they collectively influence the auditor selection process. The methodology for this study involves a comparison of the financial characteristics of the client base of Big Eight and non‐Big Eight firms. Overall, this study finds that comparison of client financial characteristics reveals significant differences in auditor brand name. In addition, the analysis indicates that differences also exist, based on audit structure and auditor reputation. Concludes that the auditor selection process, as proxied by a client′s systematic risk, is influenced by a joint combination of auditor attributes. Therefore the results of the study appear to support the theory that clients and auditors seek to match on desired traits.

Recognition and cued recall of ordinary action phrases (e.g. “open the book”) and bizarre ones (e.g. “plant the hammer”) were compared under two encoding conditions: in verbal tasks (VTs), subjects learned the phrases by simply listening to them; in subject-performed tasks (SPTs), subjects learned the phrases by performing the denoted actions (without real objects). Memory performance was better after SPTs than after VTs in recognition and cued recall. In addition to this already established finding, it was observed that recognition was better for bizarre phrases than for ordinary ones after VTs and that bizarreness was unrelated to recognition after SPTs. Cued recall, on the other hand, depended on bizarreness after VTs as well as after SPTs and, in contrast to the recognition findings, ordinary phrases were recalled better than bizarre phrases. This pattern of findings was explained by the assumptions that lexical and conceptual information is encoded after VTs and motor information is addition...

We investigated the electrophysiological correlates of the processing of subject's own name (SON) in comparison to familiar and unfamiliar names in the Chinese language. The three types of names were the deviants in an oddball paradigm among lexical and non-lexical phrases. All items consisted of three characters, and the non-lexical items were the targets. All names caused a clear N170 component of identical size which we take as a correlate of structural encoding. Only SON elicited a large N250 component, reflecting attentional capturing of SON. Additionally, SON caused a larger but later peaking P300 than the other two name stimuli which we interpret as a correlate of access to self-reference information.

Visual working memory (VWM) consolidation is the process to transfer a fleeting perpetual representation into a durable WM representation that can survive the presentation of new sensory inputs. It is investigated by post-exposure of a mask shortly after offset of memory array (S1). The memory performance increases as stimulus onset asynchrony (SOA) between S1 and mask array increases and finally reaches a asymptote level not influenced by the mask. It is considered that masks interfere the memory items representation into VWM in short SOA and that causes the consolidation phenomenon. Nevertheless, the question leaves open: how do masks interfere with this consolidation process. In this study, we tested whether masks overwrote the perceptual representation of memory items or competed with them for VWM representation. Masks interfered only when they appeared in the same location as memory items. We concluded that “overwriting”, not “competing”, characterized the VWM consolidation. Using the model “boost and bounce theory of temporal attention”[1], we gave the explanation to that conclusion.

In an assistance scenario, a computer provides purposive information supporting a human user in an everyday situation. Wayfinding with navigation assistance is a prototypical assistance scenario. The present chapter analyzes the interplay of the resources of the assistance system and the resources of the user. The navigation assistance system provides geographic knowledge, positioning information, route planning, spatial overview information, and route commands at decision points. The user’s resources encompass spatial knowledge, spatial abilities and visuo-spatial working memory, orientation strategies, and cultural habit. Flexible adaptations of the assistance system to available resources of the user are described, taking different wayfinding goals, situational constraints, and individual differences into account. Throughout the chapter, the idea is pursued that the available resources of the user should be kept active.

The above quote, which recently appeared in the Management Accounting newsletter, characterises the state of affairs for the profession. Presently, academic research and instruction have made very few contributions to the body of knowledge for management accounting. To date, a definitive explanation or theory supporting management accounting does not exist. Practitioners view the field as a multidimensional discipline which integrates managerial, financial, social, and political skills. However, academics generally focus only on the financial skills of management accountants. This is evident in the many behavioural studies that address budgeting or decision making topics rather than a broader set of characteristics.

A major house‐building corporation in the United States employed an organizational change and development (OCD) strategy during the early 1970s to assist its transformation to a mega‐corporation. The outcome was the development of an autocratic, machiavellian, coercive management style. Initial financial success during a growth phase in the construction industry masked the deficiencies of the approach, which only became apparent during an economic slump. Provides a lesson for managers who ignore the participant needs of employees.

Episodic memory for intrinsic item and extrinsic context information is postulated to rely on two distinct types of representation: object and episodic tokens. These provide the basis for familiarity and recollection, respectively. Electrophysiological indices of these processes (ERP old-new effects) were used together with behavioral data to test these assumptions. We manipulated an intrinsic object feature (color; Experiment 1) and a contextual feature (background; Experiments 1 and 2). In an inclusion task (Experiment 1), the study-test manipulation of color affected object recognition performance and modulated ERP old-new effects associated with both familiarity and recollection. In contrast, a contextual manipulation had no effect, although both intrinsic and extrinsic information was available in a direct feature (source memory) test. When made task relevant (exclusion task; Experiment 2), however, context affected the ERP recollection effect, while still leaving the ERP familiarity effect uninfluenced. We conclude that intrinsic features bound in object tokens are involuntarily processed during object recognition, thus influencing familiarity, whereas context features bound in episodic tokens are voluntarily accessed, exclusively influencing recollection. Figures depicting all the electrodes analyzed are available in an online supplement at www.psychonomic.org/archive.

The present study used multiple repetitions of meaningless pictorial stimuli to examine the electrophysiological correlates of the creation of a new stimulus representation. Study participants judged whether preexperimentally unfamiliar figures (meaningless line drawings) that were repeated up to four times contained a crossover in their contour. Stimulus repetition thereby led to a reduction of the visual N1 component in event-related potentials as well as to a late (430-600 ms), successively increasing positivity over posterior electrodes. In particular, the size of this latter event-related potential effect highly correlated with and thus predicted participants' performance in a subsequent recognition memory test. It can therefore be interpreted as neural correlate of the creation of a new memory-effective stimulus representation.

It is shown that visuo-spatial working memory is better characterized as processes operating on sensory information (visual appearance) and on spatial location (environmental coordinates) in a distributed network than as unitary slave system. Results from passive (short-term) and active memory tasks (imagery) disclose the properties (capacity, content) and the components of this network. The prefrontal cortex is a control structure (dorsal prefers active, ventral passive tasks) and it contributes to spatial memory by a prospective spatial code (eye movements). Visual appearance (including dynamic aspects) is represented as features and object files (bound features) within content-specific areas in the ventral occipital cortex. Spatial coordinates are represented in the parietal cortex (modality-unspecific), when used in spatio-temporal tasks (Corsi) they are closely related to attention. Imagery of objects activates occipito-temporal structures, spatial transformations and mental rotation the parietal cortex (specifically the intraparietal sulcus). Perception, working memory, and imagery use the same neural network. Differences between the tasks are explained by different demands and states of the neural network, and differences in the configuration of the anterior-posterior neural circuits.

In a recognition memory experiment, the claim was tested that intrinsic object features contribute to familiarity, whereas extrinsic context features do not. We used the study-test manipulation of color to investigate the perceptual specificity of ERP old-new effects associated with familiarity and recollection. Color was either an intrinsic surface feature of the object or a feature of the surrounding context (a frame encasing the object); thus, the same feature was manipulated across intrinsic/extrinsic conditions. Subjects performed a threefold (same color/different color/new object) decision, making feature information task-relevant. Results suggest that the intrinsic manipulation of color affected the mid-frontal old-new effect associated with familiarity, while this effect was not influenced by extrinsic manipulation. This ERP pattern could not be explained by basic behavioral performance differences. It is concluded that familiarity can be perceptually specific with regard to intrinsic information belonging to the object. The putative electrophysiological signature of recollection - a late parietal old-new effect - was not present in the data, and reasons for this null effect are discussed.

The incidental acquisition of spatial orientation knowledge when using a pedestrian navigation assistance system for wayfinding was compared to incidental learning during map-based wayfinding. First-time visitors to a real environment (a zoo) took a guided tour. In the navigation assistance conditions, users were provided with direction information and view-based pictures of the current intersection at each decision point, presented on a hand-held computer. In the map-based condition, participants derived route segments from a map (each segment comprising three or four intersections), and then walked the partial routes from memory. After walking, unexpected tests on route memory and survey knowledge were administered. Navigation assistance users showed good route knowledge and poor survey knowledge. In contrast, map users showed better survey knowledge and nearly perfect route knowledge. Variations of information presentation within navigation assistance conditions (auditory vs. visual direction command, additional presentation of allocentric spatial information) was not effective. Results are explained with an active encoding principle. Only information that is actually encoded, transformed, and/or memorized during the primary wayfinding activity, is incidentally learned. Since navigation assistance systems do not require users to encode, transform, and memorize spatial information, the spatial orientation knowledge of navigation assistance users is poor.

In this paper we report results of an experiment that investigates the effects of mobile pedestrian navigation systems on the development of route and survey knowledge acquired by the users. In the experiment directions were presented incrementally step-by-step in different modalities (i.e. audio, graphics) and through different media (PDA, clip-on display). The experiment has been carried out in the field in a Wizard-of-Oz like study. Results show that as expected all subjects had problems in building up survey knowledge of the environment. In contrast, route knowledge was learned much better. We also observed a slight gender effect showing that women had an advantage of a visual presentation condition, whereas for men the presentation mode didn’t matter. Finally, we discuss some implications on the design of pedestrian navigation systems.

Dear Editor, During the early part of the 21 Century, AT&T and Verizon noted that revenue from traditional residence based land lines had been surpassed by wireless revenues. Likewise, Amazon noted just a few years ago a similar milestone when e-books surpassed paper books’ revenues. PC manufacturers such as HP are seeking declines in sales while mobile phone manufactures such as Samsung experience significant sales increase as more consumers globally access the internet via mobile connections. Similarly more and more of the millions of students enrolled around the world today take courses in some form of online education or Massive Online Open Courses (MOOCs). When I was working on my doctorate at Texas A&M University I represented my department at the annual accounting doctoral student symposium hosted by Deloitte in 1991. During that symposium the late Alvin Arens noted that the emergence of information technology was closing the gap between larger and smaller academic institutions. Arens notes that the inherent resource difference is mitigated by technology such as electronic databases with journal articles or financial information. Thereby, allowing faculty and doctoral students to conduct similar lines of inquiry despite the size of the institution. My co-author in a recently published book “Giraffes of Technology: The Making of the Twenty-First Leader” notes that technology provides a democratization of information. In other words from the most rural and lower socio economic level to the most developed and affluent groups, information is equally available. Finally, I recall submitting a proposal regarding the consolidation of university resources into one central electronic database and the elimination of paper subscriptions in 1994 at my first academic institution. The proposal was soundly rejected as it was premature. However, today, many colleges have reorganized their libraries to be part of the their information resources group, eliminated or greatly reduced paper based subscriptions and replaced with enterprise or bulk electronic subscriptions and access to mainstream and proprietary databases are a priority if not the norm. The economy has become clearly global as the recession that began in 2007 had an effect throughout the world as markets due to technology and trade are interconnected as never before. Just look at the US stock markets that ebb and flow on the economic reports from China to Greece. Today more than 100 companies have adopted International Financial Reporting Standards (IFRS) and many more will adopt in the future. The former G2 is now G20 and growing. Our scholarly activities should mirror the global market trends. I have sat on the boards of the American Institute of Certified Public Accountants (AICPA) and Institute of Management Accountants (IMA) who now have significant global strategies. I am also serving on the finance committee for the American Accounting Association (AAA) which has more than a third of its membership is international. Thus, I am excited about the latest trend in academic publishing which is open access. Some of our leading and prolific business scholars are now paying for open access to their articles. Despite their publication in tier one journal, I asked one of these leading scholars in accounting why he elected to pay thousands for open access and he noted “our goal is to advance the profession by contributing to the body of knowledge... hence it is essential that as many as possible access this contribution to generate an organic and dynamic response....” The launching of the Open Journal of Accounting is an innovative step to facilitating the requisite exchange of ideas, contributions to the body of knowledge and the access to best practices in research, pedagogy and other key issues facing our profession. Leading scholars are willing to expend financial re