A study of cognitive skills in complex systems

A digital circuit usually comprises a controller and datapath. The time spent for determining a valid controller behavior to detect a fault usually dominates test generation time. A validation test set is used to verify controller behavior and, hence, it activates various controller behaviors. In this paper, we present a methodology wherein the controller behaviors exercised by test sequences in a validation test set are reused for detecting faults in the datapath. A heuristic is used to identify controller behaviors that can justify/propagate pre-computed test vectors/responses of datapath register-transfer level (RTL) modules. Such controller behaviors are said to be compatible with the corresponding pre-computed test vectors/responses. The heuristic is fairly accurate, resulting in the detection of a majority of stuck-at faults in the datapath RTL modules. Also, since test generation is performed at the RTL and the controller behavior is predetermined, test generation time is reduced. For microprocessors, if the validation test set consists of instruction sequences then the proposed methodology also generates instruction-level test sequences

In the behavioral approach, the stabilization problem is to find, for a given plant behavior, a controller behavior such that the manifest controlled behavior is stable. In this paper we will establish, for a given plant behavior, a parametrization of all stabilizing controller behaviors.

Executive function (EF) is a key cognitive process that emerges in early childhood and facilitates children's ability to control their own behavior. Individual differences in EF skills early in life are predictive of quality-of-life outcomes 30 years later (Moffitt etal., 2011). What changes in the brain give rise to this critical cognitive ability? Traditionally, frontal cortex growth is thought to underlie changes in cognitive control (Bunge & Zelazo, 2006; Moriguchi & Hiraki, 2009). However, more recent data highlight the importance of long-range cortical interactions between frontal and posterior brain regions. Here, we test the hypothesis that developmental changes in EF skills reflect changes in how posterior and frontal brain regions work together. Results show that children who fail a "hard" version of an EF task and who are thought to have an immature frontal cortex, show robust frontal activity in an "easy" version of the task. We show how this effect can arise via posterior brain regions that provide on-the-job training for the frontal cortex, effectively teaching the frontal cortex adaptive patterns of brain activity on "easy" EF tasks. In this case, frontal cortex activation can be seen as both the cause and the consequence of rule switching. Results also show that older children have differential posterior cortical activation on "easy" and "hard" tasks that reflects continued refinement of brain networks even in skilled children. These data set the stage for new training programs to foster the development of EF skills in at-risk children.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is caused by reduced or absent Fragile X messenger ribonucleoprotein (FMRP). Cognitive and adaptive skills widely vary among individuals with FXS, and these individual phenotypic differences are not fully accounted for by individual differences in FMRP expression. Social-environmental factors, including social determinants of health, may help further explain these individual differences, but these environmental factors have been under-studied in FXS. 175 participants with FXS (123 males; age range: 4-72 years) completed the Stanford-Binet, Fifth Edition to estimate IQ and a blood draw to quantify peripheral FMRP levels. Caregivers from a subset of participants also completed the Vineland Adaptive Behavior Scales. Neighborhood-level social-environmental information was extracted by linking participants' home addresses to rankings of neighborhood resources (e.g., household income, pollution, healthcare access) from the Child Opportunity Index (COI). We calculated the unique variance in IQ and adaptive behaviors accounted for by these neighborhood-level social-environmental factors from the COI while covarying for FMRP expression. Even after accounting for individual differences in FMRP, numerous neighborhood factors were associated with greater IQ in males with FXS, including social resources and indicators of healthcare access. Different social-environment factors were associated with stronger adaptive skills in males with FXS, including economic and educational resources. Almost no neighborhood factors were associated with clinical outcomes in females. Our finding of stronger links between neighborhood resources and clinical outcomes in males with FXS is consistent with previous work and may reflect increased reliance on social-environmental supports in males who typically have more significant intellectual and adaptive deficits than females. Consistent associations between greater social resources, higher IQ, and stronger adaptive skills suggest social support (e.g., social cohesion, resource and knowledge sharing) may be a particularly salient target for intervention. Associations between economic resources and adaptive communication skills also highlight the benefits of targeted economic supports for families affected by FXS. Together, our findings underscore the role of social determinants of health as key contributors to individual differences and the importance of considering these factors in clinical studies of FXS.

INTRODUCTION Many educational assessments are based on cognitive problem-solving tasks. Cognitive diagnostic assessments are designed to model examinees' cognitive performances on these tasks and yield specific information about their problem-solving strengths and weaknesses. Although most psychometric models are based on latent trait theories, a cognitive diagnostic assessment requires a cognitive information processing approach to model the psychology of test performance because the score inference is specifically targeted to examinees' cognitive skills. Latent trait theories posit that a small number of stable underlying characteristics or traits can be used to explain test performance. Individual differences on these traits account for variation in performance over a range of testing situations (Messick, 1989). Trait performance is often used to classify or rank examinees because these traits are specified at a large grain size and are deemed to be stable over time. Cognitive information processing theories require a much deeper understanding of trait performance, where the psychological features of how a trait can produce a performance become the focus of inquiry (cf. Anderson et al., 2004). With a cognitive approach, problem solving is assumed to require the processing of information using relevant sequences of operations. Examinees are expected to differ in the knowledge they possess and the processes they apply, thereby producing response variability in each test-taking situation. Because these knowledge structures and processing skills are specified at a small grain size and are expected to vary among examinees within any testing situation, cognitive theories and models can be used to understand and evaluate specific cognitive skills that affect test performance.

Identifying the set of cognitive processes (CPs) a student can go through during computer programming is an interesting research problem. It can provide a better understanding of the human aspects in computer programming process and can also contribute to the computer programming education in general. The study identified the presence of a set of 42 CPs in computer programming (C language). The study used Verbal Protocol Analysis (VPA) in identifying these CPs. It is a qualitative study on the Verbal Protocols (VPs) of 19 students. Some of the CPs have been inferred by referring to the literature and some have been additionally identified by this study. The additional CPs found are confusion, hypothesis, interrogation, iteration, monitoring, recollection, recurrence, and translation. It is observed that programming involves the interplay of lower and higher CPs and needs various cognitive skills, which increase the processing load on the brain and make the programming process difficult and complex to learn and practice. The same set of CPs was found in both the effective and ineffective subjects. The research results can provide deeper knowledge to teachers on cognitive aspects of programming and the cognitive behavior of students during the programming process.

Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.

Response assessment in advanced differentiated thyroid cancer.

BackgroundEnumeration of circulating tumor cells (CTC) from whole blood permits monitoring of patients with breast carcinoma. Analysis of apoptosis & Bcl-2 expression in CTC might add additional prognostic and predictive information. We estimated the degree of these markers in CTC from patients being treated for metastatic breast cancer. MethodsEighty-three evaluable patients initiating a new therapy for metastatic breast cancer were enrolled. Whole blood was collected at baseline, at one of three short term time windows (24, 48, or 72 h) after initiating treatment, and at first follow-up (3–5 weeks). CTC were isolated, enumerated, and expression of M30 and Bcl2 was determined using the CellSearch® System. ResultsAt baseline, window, and 3–5 weeks post-treatment, 41/80 (51%), 40/80 (50%) and 21/75 (28%) patients had ≥5 CTC, respectively. At baseline, the proportion of CTC-apoptosis (M30) was inversely correlated with CTC number, and modestly inversely correlated with CTC-Bcl-2. As expected, higher CTC levels at baseline or first follow-up were associated with worse prognosis. Surprisingly, in patients with elevated CTC, higher levels of CTC-apoptosis were associated with worse prognosis, while higher CTC-Bcl-2 levels correlated with better outcomes. ConclusionsCTC apoptosis and expression of Bcl-2 can be analytically determined in patients with metastatic breast cancer and may have biological and clinical implications. Characterization of CTC for these and other markers could further increase the utility of CTC monitoring patients in clinical investigations of new anti-neoplastic agents.

Human cytomegalovirus (HCMV) clinical isolates display genetic polymorphisms that are supposed to be implicated in HCMV-induced immunopathogenesis. Open reading frame UL73, encoding for the envelope glycoprotein N, shows four distinct genomic variants (gN-1, 2, 3, 4). This report analysed the distribution of glycoprotein N genotypes in 29 AIDS patients and 50 solid-organ transplant recipients compared with 111 immunocompetent individuals. HIV patients exhibited a prevalence of HCMV strains with the gN-1 genotype, which seem to replicate favourably in immunocompromised hosts.

Proteomic analysis uncovers biological diversity in molecularly defined endometrial carcinomas

Fine needle aspiration is an established diagnostic tool in breast carcinoma. Although the potential of using the same diagnostic aspirate material to provide additional cytomorphologic prognostic or predictive information has been investigated, no well-recognized, practical grading system has been established. Such system is necessary in guiding treatment, monitoring neoadjuvant chemotherapy effect and predicting outcome. We herein propose a new grading system, combining nuclear grade, cellular dyscohesion, and bare atypical nuclei to arrive at one cytoprognostic score. Cytoprognostic scores were compared with other known prognostic factors. Fine needle aspirations of breast diagnosed as adenocarcinoma from 55 patients were reviewed. The cytoprognostic score combined three features including nuclear grade (score 1-3), cellular dyscohesion (score 1-3), and bare atypical nuclei (score 0, 1). A cytoprognostic score of 3 and below was considered a low score, and a score of 4-7 was considered a high score. The cytoprognostic score was then compared to histologic grade, lymph node status, and expressions of estrogen receptor, progesterone receptor, Her2-Neu, Ki-67, and p53 in the subsequently excised tumor. A low cytoprognostic score predicted a low to intermediate grade carcinoma and a high score predicted an intermediate to high-grade carcinoma. A high cytoprognostic score also correlated with more positive lymph node metastasis, and poor expression of prognostic markers. In conclusion, cytoprognostic score is performed with ease and shows a great promise as a cost-effective way to predict biological behavior of breast carcinoma and guide clinical management.

The human epidermal receptor-2 (HER-2) is overexpressed or amplified in 15% to 25% of breast cancers. Determination of HER-2 tumor status offers clinically useful information, as it selects patients who may benefit from treatment with trastuzumab, the monoclonal antibody against HER-2. Currently approved methods for HER-2 testing include immunohistochemistry or fluorescent in situ hybridization using tumor tissue. A fragment of HER-2 composed of its extracellular domain (ECD) can also be detected in the serum of some patients with breast cancer. As an easily accessible tumor marker, it could offer additional useful prognostic or predictive information. This review will briefly address the biology of the circulating HER-2 ECD and discuss the evidence to support the role, if any, for measuring HER-2 ECD levels in women with breast cancer. In particular, we focus on the value and limitations of serum ECD in both early and advanced breast cancer in the following clinical contexts: as a marker of HER-2 tumor tissue status; clinical implications of raised levels in women who have a tumor not overexpressing HER-2; as a prognostic indicator and as a predictor of response to treatment; and as a monitoring tool for early recurrence. On the basis of our review of the literature, we conclude that there is currently insufficient evidence to support the use of serum HER-2 ECD in the routine management of individual patients with breast cancer. This conclusion is in agreement with the 2007 American Society of Clinical Oncology guidelines on the use of biomarkers in breast cancer.

Purpose: Sensitive and specific detection of circulating tumor cells (CTCs) in a blood sample is required for realizing the full potential of CTCs as prognostic and predictive factors. Current approaches of CTC detection are largely ineffective, and are dependent on the presence of differential epithelial protein markers or upon crude morphological characteristics like cell size differences between CTCs and blood cells. These combined approaches do not detect all relevant CTCs due to their significant heterogeneity. The objectives of this study are to develop and characterize a novel RNA in situ hybridization (ISH)-based CTC detection system called CTCscope, and to demonstrate its potential clinical utility in metastatic breast cancer patients. Experimental Design: Cultured cells of different cancer cell lines were spiked into whole blood, which was used as a model system for CTCscope development. A novel ultrasensitive fluorescent RNA-ISH method was used to detect mRNA transcripts of a multitude of tumor markers at single-cell resolution. To demonstrate feasibility of CTC detection in patient blood, duplicate blood samples were collected from 45 metastatic breast cancer patients with informed consent for CTC analysis by the newly developed CTCscope system and the CellSearch system. Association of CTCs with tumor marker CA15–3 and progression-free survival (PFS) was assessed. Results: CTCscope detected mRNA transcripts of 8 epithelial tumor markers and 3 epithelial-mesenchymal-transition (EMT) markers, and resulted in increased sensitivity for CTC detection. CTCscope was used to detect CTCs without enrichment, and did not result in false positives from detection of apoptotic or dead cells. In patient blood samples, CTCs detected by CellSearch but not CTCscope were positively correlated with CA15–3 levels. CTCs detected by either CTCscope or CellSearch predicted PFS, but only CTCs detected by CTCscope remained significantly associated with PFS (hazard ratio 2.01, 95% CI 1.14–3.92, p=0.038) after adjusting for CA15–3 levels. Conclusions: The CTCscope assay may offer unique advantages over existing CTC detection approaches. By enumerating and characterizing only viable CTCs, CTCscope may provide additional prognostic and predictive information. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C88.

In this chapter we discuss the importance of promoting cognitive skills during development. Mental skills are key to learning and socialization and predict success in a wide range of life outcomes. In the past years, a great bulk of research has examined the extent to which cognitive skills can be enhanced through training interventions during development. We present different approaches to training and the results of a sample of studies showing great promise to the goal of promoting children’s mental capacities. Many studies demonstrate that training cognitive skills, such as working memory, executive attention, and cognitive flexibility, leads to gains in performance of tasks that entail these very same skills (near transfer) and often extend to untrained domains (far transfer). Benefits of training seem to be larger for children with lower initial levels of cognitive skills. Although many questions remain to be answered about individual differences in training susceptibility, neural underpinnings, and generalization of training to life outcomes, we argue about the significance of this research for both school and clinic.