Detecting temporal and spatial effects of epithelial cancers with Raman spectroscopy.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Hindawi Publishing Corporation via the DOI in this record.Epithelial cancers, including those of the skin and cervix, are the most common type of cancers in humans. Many recent studies have attempted to use Raman spectroscopy to diagnose these cancers. In this paper, Raman spectral markers related to the temporal and spatial effects of cervical and skin cancers are examined through four separate but related studies. Results from a clinical cervix study show that previous disease has a significant effect on the Raman signatures of the cervix, which allow for near 100% classification for discriminating previous disease versus a true normal. A Raman microspectroscopy study showed that Raman can detect changes due to adjacent regions of dysplasia or HPV that cannot be detected histologically, while a clinical skin study showed that Raman spectra may be detecting malignancy associated changes in tissues surrounding nonmelanoma skin cancers. Finally, results of an organotypic raft culture study provided support for both the skin and the in vitro cervix results. These studies add to the growing body of evidence that optical spectroscopy, in this case Raman spectral markers, can be used to detect subtle temporal and spatial effects in tissue near cancerous sites that go otherwise undetected by conventional histology.The authors acknowledge the financial support of the NCI/NIH (R01-CA95405 and R21-CA95995), as well as the Howard Hughes Medical Institute (pre-doctoral fellowship for MK). We would also like to thank the doctors and staff at Vanderbilt University Medical Center and Tri-state Women’s Health for all their assistance

Using item response theory to explore the psychometric properties of extended matching questions examination in undergraduate medical education

BACKGROUND: As assessment has been shown to direct learning, it is critical that the examinations developed to test clinical competence in medical undergraduates are valid and reliable. The use of extended matching questions (EMQ) has been advocated to overcome some of the criticisms of using multiple-choice questions to test factual and applied knowledge. METHODS: We analysed the results from the Extended Matching Questions Examination taken by 4th year undergraduate medical students in the academic year 2001 to 2002. Rasch analysis was used to examine whether the set of questions used in the examination mapped on to a unidimensional scale, the degree of difficulty of questions within and between the various medical and surgical specialties and the pattern of responses within individual questions to assess the impact of the distractor options. RESULTS: Analysis of a subset of items and of the full examination demonstrated internal construct validity and the absence of bias on the majority of questions. Three main patterns of response selection were identified. CONCLUSION: Modern psychometric methods based upon the work of Rasch provide a useful approach to the calibration and analysis of EMQ undergraduate medical assessments. The approach allows for a formal test of the unidimensionality of the questions and thus the validity of the summed score. Given the metric calibration which follows fit to the model, it also allows for the establishment of items banks to facilitate continuity and equity in exam standards

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Neglect patients exhibit egocentric or allocentric neglect for the same stimulus contingent upon task demands

Hemispatial Neglect (HN) is a failure to allocate attention to a region of space opposite to where damage has occurred in the brain, usually the left side of space. It is widely documented that there are two types of neglect: egocentric neglect (neglect of information falling on the individual?s left side) and allocentric neglect (neglect of the left side of each object, regardless of the position of that object in relation to the individual). We set out to address whether neglect presentation could be modified from egocentric to allocentric through manipulating the task demands whilst keeping the physical stimulus constant by measuring the eye movement behaviour of a single group of neglect patients engaged in two different tasks (copying and tracing). Eye movements and behavioural data demonstrated that patients exhibited symptoms consistent with egocentric neglect in one task (tracing), and allocentric neglect in another task (copying), suggesting that task requirements may influence the nature of the neglect symptoms produced by the same individual. Different task demands may be able to explain differential neglect symptoms in some individuals

Turbulence and galactic structure

Interstellar turbulence is driven over a wide range of scales by processes including spiral arm instabilities and supernovae, and it affects the rate and morphology of star formation, energy dissipation, and angular momentum transfer in galaxy disks. Star formation is initiated on large scales by gravitational instabilities which control the overall rate through the long dynamical time corresponding to the average ISM density. Stars form at much higher densities than average, however, and at much faster rates locally, so the slow average rate arises because the fraction of the gas mass that forms stars at any one time is low, ~10^{-4}. This low fraction is determined by turbulence compression, and is apparently independent of specific cloud formation processes which all operate at lower densities. Turbulence compression also accounts for the formation of most stars in clusters, along with the cluster mass spectrum, and it gives a hierarchical distribution to the positions of these clusters and to star-forming regions in general. Turbulent motions appear to be very fast in irregular galaxies at high redshift, possibly having speeds equal to several tenths of the rotation speed in view of the morphology of chain galaxies and their face-on counterparts. The origin of this turbulence is not evident, but some of it could come from accretion onto the disk. Such high turbulence could help drive an early epoch of gas inflow through viscous torques in galaxies where spiral arms and bars are weak. Such evolution may lead to bulge or bar formation, or to bar re-formation if a previous bar dissolved. We show evidence that the bar fraction is about constant with redshift out to z~1, and model the formation and destruction rates of bars required to achieve this constancy.Comment: in: Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning Fork strikes a New Note, Eds., K. Freeman, D. Block, I. Puerari, R. Groess, Dordrecht: Kluwer, in press (presented at a conference in South Africa, June 7-12, 2004). 19 pgs, 5 figure

Quantum oscillations of nitrogen atoms in uranium nitride

The vibrational excitations of crystalline solids corresponding to acoustic or optic one phonon modes appear as sharp features in measurements such as neutron spectroscopy. In contrast, many-phonon excitations generally produce a complicated, weak, and featureless response. Here we present time-of-flight neutron scattering measurements for the binary solid uranium nitride (UN), showing well-defined, equally-spaced, high energy vibrational modes in addition to the usual phonons. The spectrum is that of a single atom, isotropic quantum harmonic oscillator and characterizes independent motions of light nitrogen atoms, each found in an octahedral cage of heavy uranium atoms. This is an unexpected and beautiful experimental realization of one of the fundamental, exactly-solvable problems in quantum mechanics. There are also practical implications, as the oscillator modes must be accounted for in the design of generation IV nuclear reactors that plan to use UN as a fuel.Comment: 25 pages, 10 figures, submitted to Nature Communications, supplementary information adde