Human cortical perfusion and the arterial pulse: a near-infrared spectroscopy study

BACKGROUND: The pulsatile nature of the arterial pulse induces a pulsatile perfusion pattern which can be observed in human cerebral cortex with non-invasive near-infrared spectroscopy. The present study attempts to establish a quantitative relation between these two events, even in situations of very weak signal-to-noise ratio in the cortical perfusion signal. The arterial pulse pattern was extracted from the left middle finger by means of plethesmographic techniques. Changes in cortical perfusion were detected with a continuous-wave reflectance spectrophotometer on the scalp overlying the left prefrontal cortex. Cross-correlation analysis was performed to provide evidence for a causal relation between the arterial pulse and relative changes in cortical total hemoglobin. In addition, the determination of the statistical significance of this relation was established by the use of phase-randomized surrogates. RESULTS: The results showed statistically significant cross correlation between the arterial and perfusion signals. CONCLUSIONS: The approach designed in the present study can be utilized for a quantitative and continuous assessment of the perfusion states of the cerebral cortex in experimental and clinical settings even in situations of extremely low signal-to-noise ratio

The Quantum Geometric Phase between Orthogonal States

We show that the geometric phase between any two states, including orthogonal states, can be computed and measured using the notion of projective measurement, and we show that a topological number can be extracted in the geometric phase change in an infinitesimal loop near an orthogonal state. Also, the Pancharatnam phase change during the passage through an orthogonal state is shown to be either $\pi$ or zero (mod $2\pi$). All the off-diagonal geometric phases can be obtained from the projective geometric phase calculated with our generalized connection

Australian medical students’ and junior doctors' perceptions of gender discrepancies in obstetrics and gynaecology

Background: There is currently a gender imbalance 85:15 female/male in the intake into specialist training for the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). Aims: To determine the views and perceptions of Australian medical students, and junior doctors in the first five years of practice, toward obstetrics and gynaecology (O&G) as a career, including whether there are any perceived barriers to the pursuit of such a career. Materials and Methods: A semi-structured questionnaire was developed with members of the RANZCOG Gender Equity and Diversity Working Group There were two separate studies: the first involved telephone interviews of medical students across three campuses of a medical school in North Queensland. The second study surveyed junior doctors in Queensland who are members of the Australian Medical Association. Responses were analysed and compared using quantitative and qualitative methods. Results: Both studies found that experiences with O&G as a medical student influenced the decision to pursue O&G as a career. Exclusion from clinical scenarios and difficulty establishing good relationship with midwives within busy birthing suites were some reasons deterring male students from O&G. In addition, students felt poorly informed about the specialty in their preclinical years, affecting their early decisions in choice of specialty. Post-rotation, more female than male students reported positive experiences and were considering O&G as a career. Conclusions: Both groups see medical student experience as critical in attitudes toward the specialty as a possible career. This experience plays a significant role in encouraging female students toward a career in O&G and discouraging male students. More exposure to the specialty in the preclinical years, and attention to improving clinical rotations for all students, is required

Complications of Bezoar in Children: What Is New?

A bezoar is a mass found trapped in the gastrointestinal system. The condition may be associated with pica, especially in developmentally retarded children. Clinical manifestations are usually nonspecific. Endoscopic diagnosis and removal of the foreign materials is often indicated. Occasionally, severe complications may occur. We report two cases to illustrate the clinical features and complications in these children. In the first case, a reliable history was not obtained in the developmentally delayed girl which precluded prompt diagnosis, but the grossly dilated stomach on plain abdominal radiograph gave clues to an underlying insidious mechanical obstruction of upper gastrointestinal tract. In the second case of a normal child, the unrelenting symptoms and weight loss prompt further investigations which revealed the diagnosis. Literature on pediatric bezoar is reviewed. Oesophagoduodenoscopy is the investigation of choice for diagnostic confirmation, but surgical facilities must be available to deal with acute complications

In Vivo Response to Methotrexate Forecasts Outcome of Acute Lymphoblastic Leukemia and Has a Distinct Gene Expression Profile

William Evans and colleagues investigate the genomic determinants of methotrexate resistance and interpatient differences in methotrexate response in patients newly diagnosed with childhood acute lymphoblastic leukemia

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

Investigation of Inherited Noncoding Genetic Variation Impacting the Pharmacogenomics of Childhood Acute Lymphoblastic Leukemia Treatment

Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents