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PubMed2003

[Naltrexone in the treatment of addiction].

BACKGROUND: Naltrexone is a well-known opioid antagonist that has attracted increased attention with respect to new techniques in detoxification, methods for improving compliance, and new indications. Naltrexone 50 mg Revia recently obtained registration in Norway as a pharmaceutical product. A review of its pharmacological properties and documentation of clinical use is merited. METHODS: Basic neurobiological descriptions are cited from review publications. In addition, Medline, Embase and the Cochrane library have been searched for evidence-based evaluations. RESULTS AND INTERPRETATION: The basic antagonist effect is proven beyond doubt. Clinical dosages give few and moderate side effects. The drug's two properties, blocking for exogenic opioid and modulating the endogenic opioid system, are both therapeutically useful. Its use in the treatment of heroin addiction is hampered by poor compliance; this might be improved by formulations with prolonged duration or by special therapeutic techniques. Usefulness in treatment of alcohol problems is documented but effect size is moderate and partly dependent on psychosocial therapeutic techniques. There is interesting but undocumented reports on usefulness with nicotine and cocaine addiction, with gambling problems, in impulsive behaviour and in several other areas.

Adult↗

PubMed1986

[Rib notchings in Cooley's anemia].

In 3 cases of Cooley's anemia rib notchings were found. In the first case the clinical pattern did not allow to exclude postductal type of aortic coarctation and thus was performed a venous digital aortography (SVC) showing the integrity of the aortic arch and the absence of intercostal arterial collateral circulation. Only two previous descriptions of rib notchings in thalassemia were found in literature, and the authors shortly describe the 3 observed cases and suggest some possible pathogenetic interpretations either of rib notchings in thalassemia or of the relatively late appearance (adolescence) of rib notchings.

Adolescent↗

PubMed1993

The epidemiology of thyroid carcinoma.

Thyroid cancer is one of the rarest forms of cancer, yet there are wide variations in the degree of malignancy, ranging from the most rapidly fatal to the relatively benign. This is almost entirely dependent on the histological type. Generally speaking, data available on changing trends of incidence and mortality are subject to reservation, dependent on the degree to which they have been influenced by changing diagnostic criteria and the precision of histopathological description. Nevertheless, there is evidence that mortality is slowly decreasing, while incidence is slowly increasing. The purpose of this review is to try to interpret the temporal trends of incidence and mortality rates for thyroid carcinoma in the last 3 decades in light of the problems arising from changes in diagnostic standards and histological classification regarding thyroid neoplasms. Attention is also drawn to the implications, from a public health viewpoint, of the present intensive detection and treatment of occult thyroid carcinomas.

Causality↗

PubMed2006

Names in frames: infants interpret words in sentence frames faster than words in isolation.

In child-directed speech (CDS), adults often use utterances with very few words; many include short, frequently used sentence frames, while others consist of a single word in isolation. Do such features of CDS provide perceptual advantages for the child? Based on descriptive analyses of parental speech, some researchers argue that isolated words should help infants in word recognition by facilitating segmentation, while others predict no advantage. To address this question directly, we used online measures of speech processing in a looking-while-listening procedure. In two experiments, 18-month-olds were presented with familiar object names in isolation and in a sentence frame. Infants were 120 ms slower to interpret target words in isolation than when the same words were preceded by a familiar carrier phrase, suggesting that the sentence frame facilitated word recognition. Familiar frames may enable the infant to 'listen ahead' more efficiently for the focused word at the end of the sentence.

Eye Movements↗

PubMed1998

Hepatic clearance models: comparison of the dispersion and Goresky models in outflow profiles from multiple indicator dilution rat liver studies.

The multiple indicator dilution (MID) technique is often used for investigation of the kinetic behavior of substrates and metabolites in eliminating organs. The present study was a systematic comparison of the utility of the Goresky model (GM) (a structural model) and the mixed-boundary dispersion model (DM) (a stochastic model) in the interpretation of influx, efflux, and removal (sequestration) coefficients, with data generated from rat liver-perfusion/MID studies. Although the GM and the DM are equivalent in their descriptions of membrane transport, they differ in their classifications of the dispersion of blood-borne elements. For the DM, the dispersion is an inverse Gaussian distribution of vascular transit times; for the GM, it is accounted for by the dispersion observed among noneliminated reference indicators (e.g. labeled red blood cells, albumin, sucrose, and H2O) or the derived reference. In this study, previously published rat liver-perfusion/MID data obtained for the glutathione conjugate of bromosulfophthalein and hippuric acid, compounds that exhibit saturable carrier-mediated transport, with the GM were reanalyzed with the two-compartment DM. When the fitted values for volume and transfer coefficients were compared, good correlation was found between the fitted vascular volume for the DM and the vascular volume for the reference indicator for the GM. The influx coefficients were generally similar between the models, but improved correspondence was observed when the DM was modified to include the large-vessel transit time. In contrast, the efflux and sequestration coefficients obtained for the DM did not correspond well to those from the GM. The disagreement was due, in part, to differences in the interpretation of the late-in-time component of the reference transit time distribution curve, which was not described well by the DM. Consequently, the residence time distribution and the relative dispersion were underestimated by the DM.

Animals↗

PubMed2001

Methods and measures for the description of epidemiologic contact networks.

This article describes new methods to characterize epidemiologic contact networks that involve links that are being dynamically formed and dissolved. The new social network measures are designed with an epidemiologic interpretation in mind. These methods are intended to capture dynamic aspects of networks related to their potential to spread infection. This differs from many social network measures that are based on static networks. The networks are formulated as transmission graphs (TGs), in which nodes represent relationships between two individuals and directed edges (links) represent the potential of an individual in one relationship to carry infection to an individual in another relationship. Network measures derived from transmission graphs include "source counts," which are defined as the number of prior relationships that could potentially transmit infection to a particular node or individual.

Contact Tracing↗

PubMed1994

Protein folding classes: a geometric interpretation of the amino acid composition of globular proteins.

The amino acid composition of globular proteins of known tertiary structures is analyzed for the classification of the folding classes of protein structures and for a description of their relationship which can be useful in the determination of the folding type of a protein. For each of the folding classes, an ellipsoid in the multidimensional space was constructed from the 20-D vectors of amino acid composition of its member proteins according to standard analytical geometry methods. From this representation, an ellipsoid-based scheme is then presented for determining the folding type of a protein on the basis of its elliptically scaled radial distances from ellipsoid centroids (rather than the conventional Euclidean distances) in a definitive and analytical manner. Among the 132 basis set proteins from which the ellipsoid representations were derived, locations of their individual vectors give correct assignment of the folding type for 127 proteins; this success rate of 96%, though better than those in previous studies, is established to be the theoretical upper limit only for the basis set proteins. Moreover, the geometrical description of the relationship between amino acid composition and protein folding types derived from this analytical (rather than statistical) method indicates that amino acid composition alone cannot determine the protein folding type in all cases. The high success rate for the basis set proteins nevertheless suggests that the ellipsoid representation and the elliptically scaled distances can be more successful in determining the folding type of a protein from its amino acid composition than other analytical approaches reported previously.

Amino Acids↗

PubMed1991

Flow cytometric DNA analysis of human solid tumors: a review of the interpretation of DNA histograms.

A survey of over 225 recent studies examining the relationship between the flow cytometric DNA analysis of solid tumors and clinical prognosis indicates that criteria used to classify DNA histograms are variable and often inconsistent with the recommendations proposed by the Convention on Nomenclature for DNA Cytometry. Numerous reports not only lack unambiguous descriptions of the histogram features used to differentiate diploid from aneuploid DNA distributions, but also inadequately describe the technical aspects of data acquisition, standardization, and inclusion or exclusion of subpopulations by gating. In many cases, the coefficient of variation of the diploid and aneuploid G0/1 peaks, which would allow an assessment of histogram quality, is not reported. Because of the differences in DNA histogram interpretation, extrapolation of the results among laboratories may be difficult and is probably not reliable. This review summarizes the criteria that have been used to classify the DNA histograms and illustrates the effects of these different classifiers on DNA ploidy analysis and clinical conclusions.

DNA, Neoplasm↗

PubMed2001

What is the quality of drug therapy clinical practice guidelines in Canada?

BACKGROUND: The Canadian Medical Association maintains a national online database of clinical practice guidelines developed, endorsed or reviewed by Canadian organizations within 5 years of the current date. This study was designed to identify and describe guidelines in the database that make recommendations related to the use of drug therapy, and to assess their quality using a standardized guideline appraisal instrument. METHODS: Drug therapy guidelines in the database were identified with the use of search terms and hand searching. Descriptive information about the developers, endorsement by other organizations, publication status, disease and drug focus was abstracted. Each guideline was independently assessed by 3 appraisers (a physician, a pharmacist and a methodologist) with the use of the Appraisal Instrument for Clinical Guidelines. Conditions were classified according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems. RESULTS: We identified 217 drug therapy guidelines produced or reviewed from 1994 to 1998. Guideline developers included national organizations (47.0%), paragovernment organizations (39.6%) and professional associations (30.9%); 31.3% of the guidelines were published, and 10.6% stated drug company sponsorship. The most common conditions addressed by the guidelines were infections and parasitic diseases (39.6%), neoplasms (11.5%) and diseases of the circulatory system (11.5%). Drugs most commonly cited were anti-infective agents (42.9%), antiviral agents (15.2%) and cardiovascular drugs (16.1%). Eleven organizations produced 176 (81.1%) of the guidelines. In all, 14.7% of the guidelines met half or more of the 20 items assessing rigour of guideline development on the appraisal instrument (mean quality score 30.0% [95% confidence interval (CI) 27.5%-32.6%]), 61.8% met half or more of the 12 items assessing guideline context and content (mean score 57.0% [95% CI 54.6%-59.3%]), and none met half or more of the 5 items assessing guideline application (mean score 5.6% [95% CI 4.7%-6.5%]). Overall, 64.6% of the guidelines were recommended with modification by at least 2 of the 3 appraisers, 9.2% were recommended without change, and 26.3% were not recommended. The quality of the guidelines assessed varied significantly by developer, publication status and drug company sponsorship. No substantial improvement in guideline quality was observed over the 5-year study period. INTERPRETATION: Developers of Canadian drug therapy guidelines are producing guidelines that are often perceived to be clinically useful to physicians and pharmacists, although the methods (or the description of the methods) by which they are developed need to be more rigorous and thorough.

Canada↗

PubMed2005

Variation in periodontal diagnosis and treatment planning among clinical instructors.

Consistency in clinical decision making may be necessary for reliable assessment of student performance and teaching effectiveness, yet little has been done to examine variation in periodontal diagnosis and treatment planning among dental school faculty. The purpose of this investigation was to examine variation among faculty in diagnosis and management of common periodontal diseases. Twenty-seven clinical instructors (periodontists, general dentists, dental hygienists, and first- and second-year periodontal graduate students) reviewed three web-based cases and answered a brief questionnaire focusing on radiographic interpretation, periodontal diagnosis, and treatment planning. Response rates for the three cases ranged from 62 percent to 70 percent. Clinical instructors' rating of percent bone loss in the majority of cases varied between three descriptive categories for the same tooth. Greater consistency in periodontal diagnosis was noted within the graduate student group as compared to periodontal and dental hygiene faculty groups. Diagnoses offered for one of the three patients varied between gingivitis and chronic and aggressive periodontitis. Six to nineteen different treatment plans (many with subtle differences) were submitted for each of the three cases. Inter-rater variation was qualitatively more prevalent than intra-rater variation. To our knowledge, this is the first study to document substantial variation among instructors in radiographic interpretation, diagnosis, and treatment planning for common periodontal diseases. Qualitative judgments speculating on the impact of variability among dental school faculty on student performance and patient care can be made but as yet remain unknown. Consistent use of accepted practice guidelines and greater consensus-building opportunities may decrease variation among faculty and enhance dental education.

Adult↗

PubMed2026

AI-enabled viral genomics: from virus discovery to host prediction and emerging variant forecasting.

The rapid expansion of metagenomic sequencing has generated vast repositories of viral sequence data that far outpace our capacity to interpret them using conventional approaches. Highly divergent sequences, sparse functional annotation, and taxonomically uneven sampling present fundamental challenges for reference-dependent methods, which lose sensitivity precisely for novel and understudied viruses with high public health relevance. Artificial intelligence (AI) provides a new avenue to address these challenges by enabling predictive inference from viral genomes and proteins while reducing dependence on sequence similarity. In this Review, we discuss representative advances in AI for virus discovery, taxonomic classification and functional annotation, prediction of host range and zoonotic potential, and efforts toward forecasting emerging variants. These advances are transforming viral genomics from a largely descriptive discipline into one with increasing predictive capability. We also critically assess the major challenges that constrain current approaches, including the availability of high-quality and representative datasets, rigorous model evaluation, biological interpretability and responsible governance for increasingly capable AI models.

Artificial Intelligence↗

PubMed1985

Magnetic relaxation of solvent protons by Cu2+- and VO2+-substituted transferrin: theoretical analysis and biochemical implications.

Measurements of the magnetic field dependence of the longitudinal nuclear magnetic relaxation rates of solvent protons (NMRD profiles) in solutions of paramagnetic proteins have contributed significantly to the elucidation of the physical biochemistry of a number of metalloprotein systems. In many cases, NMRD profiles were used as indicators of chemical state, both static and dynamic [cf. Brewer, C. F., Brown, R. D., III, & Koenig, S. H. (1983) J. Biomol. Struct. Dyn. 1, 961-997], in part because a proper theoretical description of the data, with realistic assumptions for a model system, was computationally intractable. This has been particularly true for Cu2+-protein complexes, attributable in part to the S = 1/2 ground-state configuration of the Cu2+ ions; significant progress in interpreting such data has been made only recently [Bertini, I., Briganti, F., Luchinat, C., Mancini, M., & Spina, G. (1985) J. Magn. Reson. 63, 41-55]. We report NMRD profiles for solutions of Cu2+ - and VO2+-substituted human transferrin, both S = 1/2 ions, as well as computations that include the effects of the anisotropic hyperfine interactions of the paramagnetic ions with their respective nuclei. The description of the data that results from these computations is quite good, sufficiently so that one can say with confidence that the protons that contribute to the relaxation are rather distant (approximately 3.5 A) from the ions and in rapid exchange (approximately 10(8) s-1) with solvent. A possible view, consistent with what is known of the biochemistry of these substituted transferrins, is that relaxation occurs in the second coordination sphere: the exchanging entity is a water molecule hydrogen bonded to a donor atom of the metal ion complex.

Copper↗

PubMed1999

Aspects of fluid dynamics applied to the larger arteries.

A review is given of some of the ideas from fluid mechanics which are considered essential background for researchers in cardiovascular flows. The paper links the topics discussed at a fundamental level with real problems which, in the experience of the author, occur in research. In particular, approximate equations governing the principal phenomena, and which help with understanding, are introduced. A description is given of the equations of motion and the significance of similarity parameters is discussed: it is shown how Reynolds number and the Womersley parameter arise from dimensionless forms of the equations. Steady flow equations and approximations are commented on, including illustrations of their use. Unsteady flow phenomena are introduced and it is shown how Stokes' first and second problems illustrate key aspects of unsteady viscous diffusion and boundary layers in the circulation. Important features of pulsatile pipe flow, as analysed by both Uchida and Womersley, are discussed and linked to Stokes' two-dimensional results. Entrance effects in steady and unsteady pipe flow are compared and contrasted. Other phenomena discussed include the effects of bends in vessels, transition to turbulence and the different time-scales associated with unsteady flows. Computational methods, which are assuming increasing importance in biological fluid mechanics, also receive a brief description. Finally, comments are made on pressure and other measurements and the need for an understanding of various fluid flow phenomena when planning measurements and interpreting the resulting data.

Animals↗

PubMed1987

Effect of protein concentration on the binding of gold(I) to human serum albumin.

The binding of aurothiosulphate, gold(I), by human serum albumin has been studied by equilibrium dialysis at four different albumin concentrations, 37 degrees, pH 7.2-7.4 and ionic strength 0.15 M. The results show that the interaction of aurothiosulphate with albumin depends on albumin concentration. This observation is linked with the previous observation that the usual independent site description cannot be used to represent the clinically important low concentration data. All the observed dependences are satisfactorily accounted for by assuming that gold(I) competes with a highly bound contaminant for the high affinity (Cys(34)-SH) site. This description is supported by the experimental observation that a fraction of this site is originally blocked both in vivo and in in vitro. The present interpretation yields a high affinity binding constant 100 times larger than found previously and provides an explanation for the lack of correlation between dose and therapeutic and toxic effects in chrysotherapy.

Gold↗

PubMed1983

Mechanical properties of a single equivalent muscle producing forearm supination.

Muscles involved in forearm supination in man were analyzed in terms of a two component muscle model. The properties of the contractile component and series elastic component were determined by a series of dynamic contractions at four levels of perceived exerted effort. Generally characteristics were found to be highly non-linear, however at submaximal effort levels mechanical relationships contained long linear segments. This was interpreted as an attempt to make muscle behaviour more linear and thus more predictable. The outlined method is not limited to forearm supination, and allows description not only of muscle properties, but also of strategies employed in the use of muscles. When determined muscle characteristics were used in a validated muscle model, accurate prediction of contractions for individual subjects was possible.

Biomechanical Phenomena↗

PubMed1993

The hand of the musician: the kinematics of the bidigital finger system with anatomical restrictions.

Tendons of the fingers are frequently interconnected by anatomic structures that limit the displacements of these tendons relative to each other. In this paper a bidigital finger system in which such interconnections between tendons are present is kinematically modelled. Using this model, an exhaustive description of the effects on finger movement of connections between the different tendons of the fingers is given. The study provides a context for the interpretation of typical difficulties of finger coordination in musicians, especially in pianists and string players.

Finger Joint↗

PubMed2006

Chromatography as Lévy stochastic process.

The Stochastic Theory of Chromatography has been revised in light of some of the most relevant Lévy's findings in Theory of Probability, including the so-called Lévy's distance, the characteristic function and the theory of infinitesimally divisible distributions. These concepts represent the key to exploit and understand, at a molecular basis, phenomena typical of chromatographic separations under linear conditions, such as peak tailing and splitting. In particular, Lévy's distance has been used to quantify the degree of convergence of real peaks towards an ideal Gaussian shape; the characteristic function properties, introduced by Lévy to deal with the problem of the addition of independent random variables, have been employed to solve a wide variety of chromatographic models (including adsorption on heterogeneous surfaces) and to interpret mobile phase dispersion from a probabilistic point of view. Finally, Lévy's studies concerning infinitesimally divisible distributions have allowed to introduce in the stochastic description of chromatography, effects associated to dispersion in mobile phase. It has been demonstrated that, according to Lévy's canonical representation of stochastic processes, the basis of chromatography is a mobile phase Poisson Process. Represented as a Lévy's process, the microscopic-probabilistic model of chromatography permits the establishment of a connection between single-molecule properties and their statistical fluctuations and shapes of real chromatographic peaks allowing, at the same time, for the constitution of a link between different branches of physical sciences.

Chromatography↗

PubMed2003

Negative self-imagery blocks inferences.

Previous research has shown that, unlike non-anxious individuals, people with social phobia fail to generate non-threatening inferences when ambiguous social information is first encountered (i.e. 'on-line'; Hirsch and Mathews Journal of Abnormal Psychology, 109 (2000) 705-712). Patients with social phobia also report negative self-imagery in social situations, while individuals without high social anxiety do not. The negative self-imagery in social phobia may prevent the generation of non-threatening inferences. If so, then training non-anxious individuals to hold in mind a negative self-image should remove the 'on-line' non-threat inferential bias normally evident in this population. In the present study, low anxious volunteers were allocated to negative image training or a control task that did not manipulate self-imagery. Following negative image training, or the control task, volunteers read descriptions of job interviews and at certain points during the text performed lexical decisions. Some decisions were made after ambiguous text that could have been interpreted in both a threatening and a non-threatening manner. In a baseline condition, decisions were made following the text for which there was only one possible inference (either threat or non-threat). The results for the control group replicated earlier findings of a non-threat inferential bias for non-anxious individuals. In contrast, and as predicted, non-anxious volunteers who were trained to hold a negative image in mind lacked any non-threatening inferential bias, and also experienced higher levels of state anxiety.

Adult↗