Multi-site evaluation of a computer aided detection (CAD) algorithm for small acute intra-cranial hemorrhage and development of a stand-alone CAD system ready for deployment in a clinical environment

Timely detection of Acute Intra-cranial Hemorrhage (AIH) in an emergency environment is essential for the triage of patients suffering from Traumatic Brain Injury. Moreover, the small size of lesions and lack of experience on the reader's part could lead to difficulties in the detection of AIH. A CT based CAD algorithm for the detection of AIH has been developed in order to improve upon the current standard of identification and treatment of AIH. A retrospective analysis of the algorithm has already been carried out with 135 AIH CT studies with 135 matched normal head CT studies from the Los Angeles County General Hospital/ University of Southern California Hospital System (LAC/USC). In the next step, AIH studies have been collected from Walter Reed Army Medical Center, and are currently being processed using the AIH CAD system as part of implementing a multi-site assessment and evaluation of the performance of the algorithm. The sensitivity and specificity numbers from the Walter Reed study will be compared with the numbers from the LAC/USC study to determine if there are differences in the presentation and detection due to the difference in the nature of trauma between the two sites. Simultaneously, a stand-alone system with a user friendly GUI has been developed to facilitate implementation in a clinical setting. © 2010 Copyright SPIE - The International Society for Optical Engineering.published_or_final_versio

Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis

For the improved production of vaccines and therapeutic proteins, a detailed understanding of the metabolic dynamics during batch or fed-batch production is requested. To study the new human cell line AGE1.HN, a flexible metabolic flux analysis method was developed that is considering dynamic changes in growth and metabolism during cultivation. This method comprises analysis of formation of cellular components as well as conversion of major substrates and products, spline fitting of dynamic data and flux estimation using metabolite balancing. During batch cultivation of AGE1.HN three distinct phases were observed, an initial one with consumption of pyruvate and high glycolytic activity, a second characterized by a highly efficient metabolism with very little energy spilling waste production and a third with glutamine limitation and decreasing viability. Main events triggering changes in cellular metabolism were depletion of pyruvate and glutamine. Potential targets for the improvement identified from the analysis are (i) reduction of overflow metabolism in the beginning of cultivation, e.g. accomplished by reduction of pyruvate content in the medium and (ii) prolongation of phase 2 with its highly efficient energy metabolism applying e.g. specific feeding strategies. The method presented allows fast and reliable metabolic flux analysis during the development of producer cells and production processes from microtiter plate to large scale reactors with moderate analytical and computational effort. It seems well suited to guide media optimization and genetic engineering of producing cell lines

Perspectives of Patients with Insulin-Treated Type 1 and Type 2 Diabetes on Hypoglycemia: Results of the HAT Observational Study in Central and Eastern European Countries

INTRODUCTION: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. METHODS: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. RESULTS: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. CONCLUSION: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. FUNDING: Novo Nordisk

The cloud aerosol interaction and precipitation enhancement experiment (CAIPEEX): Overview and preliminary results

While the demand for enhancing rainfall through cloud seeding is strong and persistent in the country, considerable uncertainty exists on the success of such an endeavour at a given location. To understand the pathways of aerosol-cloud interaction through which this might be achieved, a national experiment named Cloud Aerosol Interaction and Precipitation Enhancement EXperiment (CAIPEEX) in two phases, was carried out. The rationale of CAIPEEX, the strategy for conducting the experiment, data quality and potential for path-breaking science are described in this article. Pending completion of quality control and calibration of the CAIPEEX phase-II data, here we present some initial results of CAIPEEX phase-I aimed at documenting the prevailing microphysical characteristics of aerosols and clouds and associated environmental conditions over different regions of the country and under different monsoon conditions with the help of an instrumented research aircraft. First-time simultaneous observations of aerosol, cloud condensation nuclei (CCN) and cloud droplet number concentration (CDNC) over the Ganges Valley during monsoon season show very high concentrations (> 1000 cm-3) of CCN at elevated layers. Observations of elevated layers with high aerosol concentration over the Gangetic valley extending up to 6 km and relatively less aerosol concentration in the boundary layer are also documented. We also present evidence of strong cloud- aerosol interaction in the moist environments with an increase in the cloud droplet effective radius. Our observations also show that pollution increases CDNC and the warm rain depth, and delays its initiation. The critical effective radius for warm rain initiation is found to be between 10 and 12 μm in the polluted clouds and it is between 12 and 14 μm in cleaner monsoon clouds

Adequacy of Diabetes Care for Older U.S. Rural Adults: A Cross-sectional Population Based Study Using 2009 BRFSS Data

Background: In the U.S. diabetes prevalence estimates for adults ≥ 65 years exceed 20%. Rural communities have higher proportions of older individuals and health disparities associated with rural residency place rural communities at risk for a higher burden from diabetes. This study examined the adequacy of care received by older rural adults for their diabetes to determine if older rural adults differed in the receipt of adequate diabetes care when compared to their non-rural counterparts. Methods: Cross-sectional data from the 2009 Behavioral Risk Factor Surveillance Survey were examined using bivariate and multivariate analytical techniques. Results: Logistic regression analysis revealed that older rural adults with diabetes were more likely to receive less than adequate care when compared to their non-rural counterparts (OR = 1.465, 95% CI: 1.454-1.475). Older rural adults receiving less than adequate care for their diabetes were more likely to be: male, non-Caucasian, less educated, unmarried, economically poorer, inactive, a smoker. They were also more likely to: have deferred medical care because of cost, not have a personal health care provider, and not have had a routine medical check-up within the last 12 months. Conclusion: There are gaps between what is recommended for diabetes management and the management that older individuals receive. Older adults with diabetes living in rural communities are at greater risk for less than adequate care when compared to their non-rural counterparts. These results suggest the need to develop strategies to improve diabetes care for older adults with diabetes and to target those at highest risk

Structure-based classification and ontology in chemistry

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving <it>relevant </it>results from the available information, and <it>organising </it>those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures), while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies.</p> <p>Results</p> <p>We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches.</p> <p>Conclusion</p> <p>Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational utilities including algorithmic, statistical and logic-based tools. For the task of automatic structure-based classification of chemical entities, essential to managing the vast swathes of chemical data being brought online, systems which are capable of hybrid reasoning combining several different approaches are crucial. We provide a thorough review of the available tools and methodologies, and identify areas of open research.</p

HP1 Recruitment in the Absence of Argonaute Proteins in Drosophila

Highly repetitive and transposable element rich regions of the genome must be stabilized by the presence of heterochromatin. A direct role for RNA interference in the establishment of heterochromatin has been demonstrated in fission yeast. In metazoans, which possess multiple RNA–silencing pathways that are both functionally distinct and spatially restricted, whether RNA silencing contributes directly to heterochromatin formation is not clear. Previous studies in Drosophila melanogaster have suggested the involvement of both the AGO2-dependent endogenous small interfering RNA (endo-siRNA) as well as Piwi-interacting RNA (piRNA) silencing pathways. In order to determine if these Argonaute genes are required for heterochromatin formation, we utilized transcriptional reporters and chromatin immunoprecipitation of the critical factor Heterochromatin Protein 1 (HP1) to monitor the heterochromatic state of piRNA clusters, which generate both endo-siRNAs and the bulk of piRNAs. Surprisingly, we find that mutation of AGO2 or piwi increases silencing at piRNA clusters corresponding to an increase of HP1 association. Furthermore, loss of piRNA production from a single piRNA cluster results in genome-wide redistribution of HP1 and reduction of silencing at a distant heterochromatic site, suggesting indirect effects on HP1 recruitment. Taken together, these results indicate that heterochromatin forms independently of endo-siRNA and piRNA pathways

Biogenesis and Dynamics of Mitochondria during the Cell Cycle: Significance of 3′UTRs

Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of β-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (ΔΨm) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of β-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3′UTR of the transcript. The 3′UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated β-F1-ATPase expression in human cancer

The Spread of Inequality

The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time