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PubMed2001

Multiple sclerosis treatment 2001.

Trials of new MS drugs now require MR imaging and clinical data and entail enormous expense. Therefore, science can ask and answer only a limited number of questions, so physicians must use their clinical acumen to judge (or conjecture) the best treatments for their patients. The drugs discussed earlier will dominate MS therapy in the next few years, but further advances may come from one of the more than forty new agents now under investigation for alleviating MS. It is an exciting time for patients and their doctors.

Adjuvants, Immunologic↗
PubMed1997

Variational Approach to Unsupervised Learning Algorithms of Neural Networks.

Variational approach in pattern recognition basing on a mean risk functional is applied to unsupervised learning algorithms for neural networks. The paper summarizes main statements and results of the approach: a structure of mean risk functionals relevant for the problem of grouping the multivariate data; optimum conditions; recurrent algorithms of stochastic approximation type for minimization of the functionals; and conditions ensuring convergence of the algorithms to appropriate solutions. Basing on this theory a general scheme is proposed and it allows to obtain neural networks whose adaptation laws arise as the recurrent unsupervised learning algorithms for suitably selected mean risk functionals. The well known Grossberg networks, counter-propagation networks, and Kohonen self-organizing networks are among them. Moreover the new variants of unsupervised-learning neural structures can be derived as it is demonstrated in the paper. The developed mathematical means can serve for theoretical justification of using such neural networks in data processing systems. Copyright 1997 Elsevier Science Ltd. All Rights Reserved.

Journal Article↗
PubMed1997

Associative List Memory.

This paper introduces an Associative List Memory (ALM) that has high recall fidelity with low memory and low processing requirements. This permits a simple implementation in software on a personal computer or space instrument microprocessor. Associative List Memory has a performance comparable with Sparse Distributed Memory (SDM) but differs from SDM in that convergence occurs during learning, rather than on recall, and in that the memory is in the form of a dynamic list rather than static randomly distributed locations. Associative List Memory is suitable for unsupervised finding of classes of phenomena in large databases. In particular, all of the class exemplars deduced can be easily accessed at any time to provide a summary of current database knowledge, being essentially the contents of the list. Examples are given where patterns of 1000 bits length with > 30% noise can be learned unsupervised to deduce the original pattern's noise free. A second pass through the data in recall mode can be used to assign to each input the appropriate original pattern, effectively removing all noise from the input data. At large input bit sizes the recall fidelity approaches closely to the maximum possible value. Associative List Memory compares well in recall fidelity with SDM and other associative memories. Its processing times on a personal computer are found to be practical for database applications. Implemented within a space instrument processor, ALM would greatly reduce downlink data transmission rates. Copyright 1997 Elsevier Science Ltd.

Journal Article↗
PubMed1998

Internet information sources for the identification of emerging health technologies. A starting point.

The basis of an early warning system for new and emerging health technologies is information, and in particular, information that has been selectively extracted from the huge quantity of data in the fields of medicine, science, and biobusiness. The information will be useful only if presented in a format suitable to the needs of health care decision makers and produced at the time most likely to influence the introduction or diffusion of new technologies. In 1997 the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) began a one-year pilot project to identify and provide information on developments in medical technologies that may have a significant impact on health care in Canada. We began by examining the information available to us through the Internet, based on the assumption that electronic sources can offer more timely access to a greater range of information, often with little or no cost involved. It was important to identify the sites that offered the most relevant information in the least amount of time.

Canada↗
PubMed1995

Determination of the three-dimensional solution structure of noxiustoxin: analysis of structural differences with related short-chain scorpion toxins.

The 3D structure of noxiustoxin, the first identified scorpion toxin acting on K+ channels, has been elucidated by NMR and molecular modeling. Thirty-nine solution structures were calculated using 572 distance and 42 dihedral restraints. The average atomic rms deviation between the refined structures and the mean structure is 0.75 A for the backbone atoms. Noxiustoxin adopts a alpha/beta scaffold constituted of a three-stranded beta-sheet (residues 2-3, 25-30, 33-38) linked to a helix (residues 10-20) through two disulfide bridges. A comparison between the 3D structure of noxiustoxin and those of other structurally and functionally related scorpion toxins (charybdotoxin, PO5-NH2, kaliotoxin) revealed a bending capacity of the helix and a variability in the relative orientations between the helix and the beta-sheet. These two features highlight the plasticity of the alpha/beta scaffold and offer a structural explanation for the capacity of the fold to accommodate an additional alanine residue in the Gly-x-Cys pattern of a previously proposed consensus sequence [Bontems et al. (1991) Science 254, 1521-1523]. Our structural data also emphasize the possibility that the beta-sheet of NTX is implicated in the capacity of NTX to recognize voltage-dependent K+ channels.

Amino Acid Sequence↗
PubMed1992

Solution conformation of a deoxynucleotide containing tandem G.A mismatched base pairs and 3'-overhanging ends in d(GTGAACTT)2.

We have used 31P and 1H NMR spectroscopy and circular dichroism to define the solution conformation of d(GTGAACTT)2 which contains tandem G.A mismatched base pairs and 3'-overhanging TT ends. Measurements of coupling constants and NOE intensities show that the sugar puckers of the nucleotides are predominantly in the south domain (i.e., near C2'-endo) and that the glycosidic torsion angles are anti. The sequential NOE intensities indicate the presence of a right-handed helix. Analysis of the 31P and 1H NMR spectra of the duplex shows that the tandem mismatch forms a block in which there are unusual backbone torsion angles (i.e., in the BII state), within an otherwise B-like structure. The chemical shift of the N1H of the mismatched guanosine and NOEs between the mismatched base pairs and their nearest neighbors are inconsistent with the imino pairing present in single A.G mismatches or in the X-ray structure of a tandem mismatch [Privé, G. G., et al. (1987) Science 238, 498-503] but the data are consistent with the amino pairing found by Li et al. (1991) [Li, Y., et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 26-30]. The strong base-base stacking both within the tandem G.A block and between the G.A mismatches and their other nearest neighbors offsets the intrinsic destabilizing effects of the mismatch. Further, the 3'-TT overhangs stack onto the ends of the helix and stabilize the duplex against fraying, which accounts for the observed increase in the melting temperature compared with the flush-ended duplex.

Adenine↗
PubMed2003

The disabled throwing shoulder: spectrum of pathology Part I: pathoanatomy and biomechanics.

PROLOGUE: Several years ago, when we began to question microinstability as the universal cause of the disabled throwing shoulder, we knew that we were questioning a sacrosanct tenet of American sports medicine. However, we were comfortable in our skepticism because we were relying on arthroscopic insights, clinical observations, and biomechanical data, thereby challenging unverified opinion with science. In so doing, we assembled a unified concept of the disabled throwing shoulder that encompassed biomechanics, pathoanatomy, kinetic chain considerations, surgical treatment, and rehabilitation. In developing this unified concept, we rejected much of the conventional wisdom of microinstability-based treatment in favor of more successful techniques (as judged by comparative outcomes) that were based on sound biomechanical concepts that had been scientifically verified. Although we have reported various components of this unified concept previously, we have been urged by many of our colleagues to publish this information together in a single reference for easy access by orthopaedic surgeons who treat overhead athletes. We are grateful to the editors of Arthroscopy for allowing us to present our view of the disabled throwing shoulder. Part I: Pathoanatomy and Biomechanics is presented in this issue. Part II: Evaluation and Treatment of SLAP Lesions in Throwers will be presented in the May-June issue. Part III: The "SICK" Scapula, Scapular Dyskinesis, the Kinetic Chain, and Rehabilitation will be presented in the July-August issue. We hope you find it thought-provoking and compelling.

Adolescent↗
PubMed1999

Identification of kinase-phosphatase signaling modules composed of p70 S6 kinase-protein phosphatase 2A (PP2A) and p21-activated kinase-PP2A.

A growing body of evidence indicates that regulation of protein-serine/threonine phosphatase 2A (PP2A) involves its association with other cellular and viral proteins in multiprotein complexes. PP2A-containing protein complexes may exist that contribute to PP2A's important regulatory role in many cellular processes. To identify such protein complexes, PP2A was partially purified from rat brain soluble extracts following treatment with a reversible cross-linker to stabilize large molecular size forms of PP2A. Compared with native (uncross-linked) PP2A, cross-linked PP2A revealed an enrichment of p70 S6 kinase and two p21-activated kinases (PAK1 and PAK3) in the PP2A complex, indicating these kinases may associate with PP2A. The existence of protein kinase-PP2A complexes in rat brain soluble extracts was further substantiated by the following results: 1) independent immunoprecipitation of the kinases revealed that PP2A co-precipitated with p70 S6 kinase and the two PAK isoforms; 2) glutathione S-transferase fusion proteins of p70 S6 kinase and PAK3 each isolated PP2A; and 3) PAK3 and p70 S6 kinase bound to microcystin-Sepharose (an affinity resin for PP2A-PP1). Cumulatively, these findings provide evidence for association of PP2A with p70 S6 kinase, PAK1, and PAK3 in the context of the cellular environment. Moreover, together with the recent reports describing associations of PP2A with Ca2+/calmodulin-dependent protein kinase IV (Westphal, R. S., Anderson, K. A., Means, A. R., and Wadzinski, B. E. (1998) Science 280, 1258-1261) and casein kinase IIalpha (Heriche, J. K., Lebrin, F., Rabilloud, T., Leroy, D., Chambaz, E. M., and Goldberg, Y. (1997) Science 276, 952-955), the present data provide compelling evidence for the existence of protein kinase-PP2A signaling modules as a new paradigm for the control of various intracellular signaling cascades.

Amino Acid Sequence↗
PubMed1993

Measurement of the range and coupled movements observed in the lumbar spine.

The aim of this study was to set up a data base, using the Polhemus Navigation Sciences 3Space Isotrak system, of the range and coupled movements expected to be seen in the lumbar spine of people not experiencing spinal problems. Measurements were taken from groups of volunteers who had not previously experienced any form of serious back pain and who were not suffering from any pathology known to affect the spine. The 'normal' group was split into sections determined by age an dsex. Age was split into five categories, those aged 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years. Range of motion was seen to be affected by both the age and sex of subjects. Lateral bend and axial rotation, flexion and lateral bend and flexion and axial rotation were all strongly coupled. The younger age groups tested exhibited a greater degree of coupled movement than the older groups.

Adult↗
PubMed2004

The U.S. Environmental Protection Agency's assessment of risks from indoor radon.

The U.S. Environmental Protection Agency has updated its assessment of health risks from indoor radon, which has been determined to be the second leading cause of lung cancer after cigarette smoking. This risk assessment is based primarily on results from a recent study of radon health effects (BEIR VI) by the National Academy of Sciences. In BEIR VI, the National Academy of Sciences fit empirical risk models to data from 11 cohorts of miners, and estimated that each year about 20,000 lung cancer deaths in the U.S. are radon related. A summary, abstracted from the technical report, is given of the EPA's risk assessment results and methods, including some modifications and extensions to the approach used in BEIR VI. Results include numerical estimates of lung cancer deaths per unit exposure, which had not been provided in BEIR VI.

Adolescent↗
PubMed1997

Evolution and revolution in child psychiatry: ADHD as a disorder of adaptation.

Current knowledge about early plasticity and children's responsiveness to environmental modifications as well as the atheoretical nature of current nosological systems necessitate alternative models to explain the phenomena of childhood behavioral and emotional disturbances. Evolutionary biology provides one such framework. It organizes data from the behavioral and cognitive sciences and parallels similar efforts in other areas of medicine and biology. Through an evolutionary biological lens, some mental disorders are better viewed as an adaptive response to early pathogenic environments and/or reflect the optimization of brain function to some environments at the cost of poorer response to the demands of other environments. As an example, the authors examine attention-deficit/hyperactivity disorder (ADHD) in relation to evolutionary theories of psychology and biology and clarify the potentially adaptive nature of characteristics of inattention, impulsivity, and motoric hyperactivity, depending on the nature of child's environments. Reframing ADHD characteristics according to evolutionary theory has important treatment implications for clinicians and offers researchers opportunities for novel scientific discoveries.

Adaptation, Psychological↗
PubMed1997

Measurement of 2,4-toluenediamine in urine and serum samples from women with Même or Replicon breast implants.

The objective of this matched case-control study was to determine whether women with Même or Replicon polyurethane-covered silicone breast implants are exposed to clinically significant levels of free 2,4-TDA from biodegradation of the polyurethane foam. Urine and serum samples were obtained from 61 patients with Même or Replicon breast implants and 61 controls on two separate occasions separated by 10 +/- 3 days. Free TDA was analyzed by gas chromatography combined with negative chemical ionization mass spectrometry with lower limit of quantitation in both urine and serum of 10 pg/ml. The results were correlated with the length of time since implantation. No patients or controls had detectable free 2,4-TDA in their sera. Thirty patients had quantifiable levels of free 2,4-TDA, and 18 had detectable levels in their urine. Controls had no quantifiable levels, but 7 subjects had detectable levels. The biodegradative half-life of the polyurethane foam was estimated to be 2 years. A risk assessment using the cancer potency estimate calculated by the FDA from rat data and the National Academy of Sciences methodology provided a theoretical lifetime risk of approximately one in one million. It was concluded that the polyurethane foam cover on the Même and Replicon breast implants biodegrades. The risk assessment of approximately one in one million derived from this study strengthens earlier conclusions by the Health Protection Branch (Canada) that there is no significant risk of cancer from exposure to the 2,4-TDA formed from this biodegradation.

Adult↗
PubMed2004

Association between ocular herpes simplex virus and topical ocular hypotensive therapy.

PURPOSE: To evaluate whether use of particular topical hypotensive therapies is associated with ocular herpes simplex virus (OHSV). MATERIALS AND METHODS: This population-based, retrospective, cohort study used claims records from the Protocare Sciences managed care database (United States). Data were extracted from September 1, 1996 through June 30, 2002. An OHSV event was either a medical claim from the utilization database coded with an International Classification of Diseases Ninth Revision (ICD-9) code for OHSV (ICD-9 = 054.4, 054.40-054.44, 054.49) or a pharmacy claim for vidarabine or trifluridine ophthalmic solution. RESULTS: A total of 93,869 eligible glaucoma patients, 21 different ocular hypotensive agents, and 192,840 agent-utilizing patient combinations were identified. In all, 411 patients had an OHSV event; 272 of 411 patients had at least 1 ocular hypotensive agent dispensed prior to the OHSV event but not preceding the event by less than 7 days. Of these, 219 had only 1 ocular hypotensive agent dispensed on the last fill date prior to the OHSV event, yielding an overall OHSV event rate of 0.11%. There was no significant association between OHSV event rates and agent use for either the set of 21 agents (P = 0.260; chi2) or when 14 products having < 5% usage were combined (P = 0.058). Prevalence rates were estimated as 161 per 100,000 population for 2000 to 2001 and 165 per 100,000 for 1999 to 2001. CONCLUSIONS: Ocular herpes simplex virus is extremely rare in patients treated with ocular hypotensive therapies, and its prevalence is similar to that found in the general population. The current analysis revealed no association between the use of particular topical ocular hypotensive therapies and OHSV.

Adult↗
PubMed2004

Preferential exchange: strengthening connections in complex networks.

Many social, technological, and biological interactions involve network relationships whose outcome intimately depends on the structure of the network and on the strengths of the connections. Yet, although much information is now available concerning the structure of many networks, the strengths are more difficult to measure. Here we show that, for one particular social network, notably the e-mail network, a suitable measure of the strength of the connections can be available. We also propose a simple mechanism, based on positive feedback and reciprocity, that can explain the observed behavior and that hints toward specific dynamics of formation and reinforcement of network connections. Network data from contexts different from social sciences indicate that power-law, and generally broad, distributions of the connection strength are ubiquitous, and the proposed mechanism has a wide range of applicability.

Journal Article↗
PubMed2002

Quantum tunneling of Bose-Einstein condensates in optical lattices under gravity.

We investigate the quantum tunneling of Bose-Einstein condensates in optical lattices under gravity in the "Wannier-Stark localization" regime and "Landau-Zener tunneling" regime. Our results agree with experimental data [B. P. Anderson et al., Science 282, 1686 (1998); F. S. Cataliotti et al., Science 293, 843 (2001)]. We obtain the total decay rate which is valid over the entire range of temperatures, and show how it reduces to the appropriate results for the classical thermal activation at high temperatures, the thermally assisted tunneling at intermediate temperatures, and the pure quantum tunneling at low temperatures. We design an experimental protocol to observe this new phenomenon in further experiments.

Journal Article↗
PubMed2005

Forensic analysis of nonlinear collusion attacks for multimedia fingerprinting.

Digital fingerprinting is a technology for tracing the distribution of multimedia content and protecting them from unauthorized redistribution. Unique identification information is embedded into each distributed copy of multimedia signal and serves as a digital fingerprint. Collusion attack is a cost-effective attack against digital fingerprinting, where colluders combine several copies with the same content but different fingerprints to remove or attenuate the original fingerprints. In this paper, we investigate the average collusion attack and several basic nonlinear collusions on independent Gaussian fingerprints, and study their effectiveness and the impact on the perceptual quality. With unbounded Gaussian fingerprints, perceivable distortion may exist in the fingerprinted copies as well as the copies after the collusion attacks. In order to remove this perceptual distortion, we introduce bounded Gaussian-like fingerprints and study their performance under collusion attacks. We also study several commonly used detection statistics and analyze their performance under collusion attacks. We further propose a preprocessing technique of the extracted fingerprints specifically for collusion scenarios to improve the detection performance.

Algorithms↗