Research fund for the control of infectious diseases: commissioned studies

Research Fund for the Control of Infectious Diseases: Research Dissemination Reportspublished_or_final_versio

Summary of research projects supported by the Health Services Research Fund (HSRF) and the Health Care and Promotion Fund (HCPF)

published_or_final_versio

Over-expression of c-Myc oncoprotein in oral squamous cell carcinoma in the South Indian population

Oral neoplasm constitutes a predominant class of cancer that is encountered in South India. This is in large part due to the elevated risk of oncogenesis as a result of the habit of chewing of quids containing betel leaves, areca nut and smokeless tobacco. An array of molecular events are induced during the transformation of the buccal epithelium, among them the over-expression of oncogene products plays a key role. The c-Myc protein, a regulator of a number of key cellular signalling pathways, plays a pivotal role in a number of malignancies. The present study was undertaken to evaluate expression of the c-Myc protein in tumours of the oral cavity from the South Indian population, predominantly oral squamous cell carcinoma (OSCC). The c-Myc protein was over-expressed in 80% of the cases studied. Taking into account the pivotal role demonstrated for c-Myc in tumourigenesis, our observations suggest a key role for Myc oncoprotein in the genesis of OSCC as well as its potential as a therapeutic target in this population

Mycotic aneurysm of the posterior tibial artery – a rare complication of bacterial endocarditis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Distal arterial embolisation and subsequent aneurysm formation are rare occurrences and most are secondary to trauma. We have found no case reports that describe posterior tibial aneurysm formation secondary to bacterial endocarditis.</p> <p>Case presentation</p> <p>We report the case of a 47-year-old Caucasian man who, 2 years after an episode of subacute bacterial endocarditis, presented with signs and symptoms consistent with posterior tibial aneurysm formation.</p> <p>Conclusion</p> <p>Posterior tibial aneurysm formation is a rare occurrence, most commonly occurring after trauma and, although other causes have been described, to our knowledge, endocarditis has not been implicated before, and as such should therefore be borne in mind when dealing with cases where no obvious aetiology is evident.</p

Size and shape constancy in consumer virtual reality

With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology

A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD)

<p>Abstract</p> <p>Background</p> <p>Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy.</p> <p>Methods</p> <p>Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for ADHD medication during the study period July2003 to June2004, and continuous enrollment 6 months prior to and throughout the study period. Dispensing events were grouped into 6 categories: atomoxetine (ATX), long-acting stimulants (LAS), intermediate-acting stimulants (IAS), short-acting stimulants (SAS), bupropion (BUP), and Alpha-2 Adrenergic Agonists (A2A). Events were assigned to calendar months, and months with combined use from multiple categories within patient were identified. Predictors of combination therapy for LAS and for ATX were modeled for patients covered by commercial plans using logistic regression in a generalized estimating equations framework to adjust for within-patient correlation between months of observation. Factors included age, gender, presence of the hyperactive component of ADHD, prior diagnoses for psychiatric disorders, claims history of recent psychiatric visit, insurance plan type, and geographic region.</p> <p>Results</p> <p>There were 18,609 patients identified representing a total of 11,886 months of therapy with ATX; 40,949 months with LAS; 13,622 months with IAS; 38,141 months with SAS; 22,087 months with BUP; and 1,916 months with A2A. Combination therapy was present in 19.7% of continuing months (months after the first month of therapy) for ATX, 21.0% for LAS, 27.4% for IAS, 23.1% for SAS, 36.9% for BUP, and 53.0% for A2A.</p> <p>For patients receiving LAS, being age 25–44 or age 45 and older versus being 18–24 years old, seeing a psychiatrist, having comorbid depression, or having point-of-service coverage versus a Health Maintenance Organization (HMO) resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD.</p> <p>For patients receiving ATX, being age 25–44 or age 45 and older versus being 18–24 years old, seeing a psychiatrist, having a hyperactive component to ADHD, or having comorbid depression resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD.</p> <p>Conclusion</p> <p>ATX and LAS are the most likely drugs to be used as monotherapy. Factors predicting combination use were similar for months in which ATX was used and for months in which LAS was used except that a hyperactive component to ADHD predicted increased combination use for ATX but not for LAS.</p

Two chemically similar stellar overdensities on opposite sides of the plane of the Galaxy

Our Galaxy is thought to have undergone an active evolutionary history dominated by star formation, the accretion of cold gas, and, in particular, mergers up to 10 gigayear ago. The stellar halo reveals rich fossil evidence of these interactions in the form of stellar streams, substructures, and chemically distinct stellar components. The impact of dwarf galaxy mergers on the content and morphology of the Galactic disk is still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups, which may have extragalactic origin. However, there is mounting evidence that stellar overdensities at the outer disk/halo interface could have been caused by the interaction of a dwarf galaxy with the disk. Here we report detailed spectroscopic analysis of 14 stars drawn from two stellar overdensities, each lying about 5 kiloparsecs above and below the Galactic plane - locations suggestive of association with the stellar halo. However, we find that the chemical compositions of these stars are almost identical, both within and between these groups, and closely match the abundance patterns of the Milky Way disk stars. This study hence provides compelling evidence that these stars originate from the disk and the overdensities they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.Comment: accepted for publication in Natur

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic