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PubMed2005

Incipient offending among schizophrenia patients after first contact to the psychiatric hospital system.

The study examines how age, sex and substance use disorder are associated with the risk of committing a criminal offence. The study explicitly examines the risk after the first contact to the psychiatric hospital system and after the diagnosis of schizophrenia for those with no previous criminal record; the association between previous non-violent criminality and later violent criminality is also analysed. The study sample comprised 4619 individuals ever diagnosed with schizophrenia. All solved offences were accessible. Data were analysed using Cox's regression. Schizophrenic men had twice the risk of schizophrenic women of committing both violent and non-violent offences. A registered substance use disorder increased the risk 1.9- to 3.7-fold, depending on the starting point for the analyses, while increasing age on first contact or when diagnosed with schizophrenia diminished the risk. Previous non-violent criminality increased the risk for later violent criminality 2.5- to 2.7-fold, depending on the starting point for the analyses. The results suggest that the psychiatric treatment system can play an active role in preventing criminality among individuals with schizophrenia. The preventive measures should be based on a thorough assessment including criminal history at intake and alertness toward young psychotic men with substance use disorders and especially if they also have a criminal history.

Adolescent↗

PubMed2006

The United Nations Process Indicators for emergency obstetric care: Reflections based on a decade of experience.

OBJECTIVE: The paper reviews the experience with the EmOC process indicators, and evaluates whether the indicators serve the purposes for which they were originally created - to gather and interpret relatively accessible data to design and implement EmOC service programs. METHOD: We review experience with each of the 6 process indicators individually, and monitoring change over time, at the level of the facility and at the level of a region or country. We identify problems encountered in the field with data collection and interpretation. RESULT: While they have strengths and weaknesses, the process indicators in general serve the purposes for which they were developed. The data are easily collected, but some data problems were identified. We recommend several relatively minor modifications to improve data collection, interpretation and utility. CONCLUSIONS: The EmOC process indicators have been used successfully in a wide variety of settings. They describe vital elements of the health system and how well that system is functioning for women at risk of dying from major obstetric complications.

Data Collection↗

PubMed2005

Laser flash photolysis of hydrogen peroxide to oxidize protein solvent-accessible residues on the microsecond timescale.

Footprinting of proteins by hydroxyl radicals generated on the millisecond to minute timescales to probe protein surfaces suffers from the uncertainty that radical reactions cause the protein to unfold, exposing residues that are protected in the native protein. To circumvent this possibility, we developed a method using a 248 nm KrF excimer laser to cleave hydrogen peroxide at low concentrations (15 mM, 0.04%), affording hydroxyl radicals that modify the protein in less than a microsecond. In the presence of a scavenger (20 mM glutamine), the radical lifetimes decrease to approximately 1 microsecond, yet the reaction timescales are sufficient to provide significant oxidation of the protein. These times are arguably faster than super-secondary protein structure can unfold as a result of the modification. The radical formation step takes place in a nanoliter flow cell so that only one laser pulse irradiates each bolus of sample. The oxidation sites are located using standard analytical proteomics, requiring less than a nanomole of protein. We tested the method with apomyoglobin and observed modifications in accord with solvent accessibility data obtained from the crystal structure of holomyoglobin. Additionally, the results indicate that the F-helix is conformationally flexible in apomyoglobin, in accord with NMR results. We also find that the binding pocket is resistant to modifications, indicating that the protein pocket closes in the absence of the heme group-conclusions that cannot be drawn from current structural methods. When developed further, this method may enable the determination of protein-ligand interfaces, affinity constants, folding pathways, and regions of conformational flexibility.

Amino Acids↗

PubMed2006

The publication process itself was the major cause of publication bias in genetic epidemiology.

OBJECTIVES: How do scientists in the field of genetic epidemiology see the problem of publication bias, what are the possible solutions and what particular pressures are they under that might either promote or prevent publication and other biases? STUDY DESIGN AND SETTING: An exploratory study of beliefs and practices among scientists working in the field of genetic epidemiology. A purposive sample of senior, genetic scientists was selected (N=6) and informants were interviewed face to face. RESULTS: There was some consensus that the issue of nonreplication might be particularly problematic in genetic epidemiology, and that publication bias could contribute to this. The informants suggested that the problem lay mainly with the publication process. Publication of negative results was seen as important but fraught with difficulties. CONCLUSION: Possible solutions included education of editors, and reviewers, dissemination of negative findings through Web sites or accessible data archives and pooling of data. However, none of these were perceived to be straightforward given the current pressures on the research industry.

Culture↗

PubMed2005

Compressed representations of macromolecular structures and properties.

We introduce a new and unified, compressed volumetric representation for macromolecular structures at varying feature resolutions, as well as for many computed associated properties. Important caveats of this compressed representation are fast random data access and decompression operations. Many computational tasks for manipulating large structures, including those requiring interactivity such as real-time visualization, are greatly enhanced by utilizing this compact representation. The compression scheme is obtained by using a custom designed hierarchical wavelet basis construction. Due to the continuity offered by these wavelets, we retain very good accuracy of molecular surfaces, at very high compression ratios, for macromolecular structures at multiple resolutions.

Computational Biology↗

PubMed2004

Hemosoft: a new software for blood bank and apheresis management.

BACKGROUND: Blood banks (BB) generate large volumes of information relating to patients and blood products sometimes stored indefinitely. Today computers are the main keys used to manage this task. BB information systems are developed mainly to assist BB specialists. MATERIALS AND METHODS: We developed a new software, Hemosoft, in our blood bank. We have carried out a great deal of research into BB programs around the world in terms of program features. Using the latest technology, Hemosoft has been designed to run on a multi-user platform on the basis of a modular structure, and high security levels. RESULTS: Hemosoft's structural advantages are: (1) its modular structure and client/server architecture reduce initial hardware costs. (2) Relational database structure provides consistent and secure data access, (3) user-friendly graphical interface, (4) according to operational needs, Hemosoft can be expanded and transferred on to different platforms. As a MS Windows based program with graphical user interfacing, Hemosoft has all the functions and advantages of windows based applications. Barcode printing is available to ISBT 128 standard. Hemosoft's integrated modules are: blood donation, transfusion, product management, administrative follow-up, apheresis, stock management, staff-management, inter-center communication, statistics, archive, internet and video-conferencing systems, accounts, integration and security. CONCLUSION: It fulfills international transfusion medicine requirements, legislative measures and guidelines. We believe that Hemosoft is a high quality, competitive program developed to meet international standards. It is our hope that it will enforce transfusion medicine and blood banking nationwide.

Blood Banks↗

PubMed2002

Blood flow patterns in an anatomically realistic coronary vessel: influence of three different reconstruction methods.

Many clinical studies suggest that local blood flow patterns are involved in the location and development of atherosclerosis. In coronary diseases, this assumption should be corroborated by quantitative information on local hemodynamic parameters such as pressure, velocity or wall shear stress. Nowadays, computational fluid dynamics (CFD) algorithms coupled to realistic 3-D reconstructions of such vessels make these data accessible. Nevertheless, they should be carefully analysed to avoid misinterpretations when the physiological parameters are not all considered. As an example, we propose here to compare the flow patterns calculated in a coronary vessel reconstructed by three different methods. In the three cases, the vessel trajectory respected the physiology. In the simplest reconstruction, the coronary was modelled by a tube of constant diameter while in the most complex one, the cross-sections corresponded to the reality. We showed that local pressures, wall shear rates and velocity profiles were severely affected by the geometrical modifications. In the constant cross-section vessel, the flow resembled to that of Poiseuille in a straight tube. On the contrary, velocity and shear rate exhibited sudden local variations in the more realistic vessels. As an example, velocity could be multiplied by 5 as compared to Poiseuille's flow and area of very low wall shear rates appeared. The results obtained with the most complex model clearly outlined that, in addition to a proper description of the vessel trajectory, the section area changes should be carefully taken into account, confirming assumptions already highlighted before the rise of commercially available and efficient CFD softwares.

Arteries↗

PubMed2003

Cell wall-associated enzymes in fungi.

This review compiles and discusses previous reports on the identity of wall-associated enzymes (WAEs) in fungi and addresses critically the widely different terminologies used in the literature to specify the type of bonding of WAEs to other entities of the cell wall compartment, the extracellular matrix (ECM). A facile and rapid fractionation protocol for catalytically active WAEs is presented, which uses crude cell walls as the experimental material, a variety of test enzymes (including representatives of polysaccharide synthases and hydrolases, phosphatases, gamma-glutamyltransferases, pyridine-nucleotide dehydrogenases and phenol-oxidising enzymes) and a combination of simple hydrophilic and hydrophobic extractants. The protocol provides four fully operationally defined classes of WAEs, with constituent members of each class displaying the same basic type of physicochemical interaction with binding partners in situ. The routine application of the protocol to different species and cell types could yield easily accessible data useful for building-up a general objective information retrieval system of WAEs, suitable as an heuristic basis both for the unravelling of the role and for the biotechnological potentialities of WAEs. A detailed account is given of the function played in the ECM by WAEs in the metabolism of chitin (chitin synthase, chitinase and beta-N-acetylhexosaminidase) and of phenols (tyrosinase).

Cell Wall↗

PubMed2000

Atmospheric nitrogen in the Mississippi River Basin--emissions, deposition and transport.

Atmospheric deposition of nitrogen has been cited as a major factor in the nitrogen saturation of forests in the north-eastern United States and as a contributor to the eutrophication of coastal waters, including the Gulf of Mexico near the mouth of the Mississippi River. Sources of nitrogen emissions and the resulting spatial patterns of nitrogen deposition within the Mississippi River Basin, however, have not been fully documented. An assessment of atmospheric nitrogen in the Mississippi River Basin was therefore conducted in 1998-1999 to: (1) evaluate the forms in which nitrogen is deposited from the atmosphere; (2) quantify the spatial distribution of atmospheric nitrogen deposition throughout the basin; and (3) relate locations of emission sources to spatial deposition patterns to evaluate atmospheric transport. Deposition data collected through the NADP/NTN (National Atmospheric Deposition Program/National Trends Network) and CASTNet (Clean Air Status and Trends Network) were used for this analysis. NOx Tier 1 emission data by county was obtained for 1992 from the US Environmental Protection Agency (Emissions Trends Viewer CD, 1985-1995, version 1.0, September 1996) and NH3 emissions data was derived from the 1992 Census of Agriculture (US Department of Commerce. Census of Agriculture, US Summary and County Level Data, US Department of Commerce, Bureau of the Census. Geographic Area series, 1995:1b) or the National Agricultural Statistics Service (US Department of Agriculture. National Agricultural Statistics Service Historical Data. Accessed 7/98 at URL, 1998. http://www.usda.gov/nass/pubs/hisdata++ +.htm). The highest rates of wet deposition of NO3- were in the north-eastern part of the basin, downwind of electric utility plants and urban areas, whereas the highest rates of wet deposition of NH4+ were in Iowa, near the center of intensive agricultural activities in the Midwest. The lowest rates of atmospheric nitrogen deposition were on the western (windward) side of the basin, which suggests that most of the nitrogen deposited within the basin is derived from internal sources. Atmospheric transport eastward across the basin boundary is greater for NO3- than NH4+, but a significant amount of NH4+ is likely to be transported out of the basin through the formation of (NH4)2SO4 and NH4NO3 particles--a process that greatly increases the atmospheric residence time of NH4+. This process is also a likely factor in the atmospheric transport of nitrogen from the Midwest to upland forest regions in the North-East, such as the western Adirondack region of New York, where NH4+ constitutes 38% of the total wet deposition of N.

Air Pollutants↗

PubMed1999

Construction and analysis of arrayed cDNA libraries.

For any attempt to understand the biology of an organism the incorporation of a cDNA-based approach is unavoidable, because it is a major approach to studying gene function. The complete sequence of the genome alone is not sufficient to understand any organism; its gene regulation, expression, splice variation, posttranslational modifications, and protein-protein interactions all need to be addressed. Because the majority of vertebrate genes have probably been identified as ESTs the next stage of the Human Genome Project is attributing functional information to these sequences. In most cases hybridization-based approaches on arrayed pieces of DNA represent the most efficient way to study the expression level and splicing of a gene in a given tissue. Similar technology, now being applied at the protein level using protein expression libraries, high-density protein membranes, and antibody screening, should allow studies of protein localization and modifications. Coupled to these approaches is the use of technologies, which although lacking the highly parallel nature of hybridization, can potentially characterize large numbers of samples individually and with high accuracy. Automated gel-based DNA sequencing is an example of such a technique; protein sequencing and mass fingerprinting are further examples. In the case of mass spectroscopic analysis, the speed and sensitivity are vastly superior to that of gel-based approaches; however, the preparation of samples is more tedious. Our laboratory is developing a system to characterize DNA samples by mass spectrometry, allowing more rapid genotyping than is currently possible using gel-based technologies ([symbol: see text]. Gut, [symbol: see text]. Berlin and H. Lehrach, personal communication, 1998). Such technology would make information on gene polymorphisms widely accessible. Data generated using all of these techniques at the DNA and protein level will be connected by both protein expression libraries and database comparisons; finally, two hybrid library screens will identify many of the protein-protein interactions, linking genes together. In this way we will start to understand the interplay between genes on a global scale, both at the level of molecular interaction and the biological processes they regulate.

Alternative Splicing↗

PubMed1996

RNAs mediating cotranslational insertion of selenocysteine in eukaryotic selenoproteins.

Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. Its biosynthesis and cotranslational insertion into selenoproteins is performed by an outstanding mechanism, implying the participation of several gene products. The tRNA(Sec) is one of these. In eukaryotes, its transcription mode by RNA polymerase III differs from that of classical tRNA genes, both at the level of the promoter elements and transcription factors involved. In addition, enhanced transcription is afforded by a newly characterized zinc finger activator. Not only transcription of the gene, but also the tRNA(Sec) itself is atypical since its 2D and 3D structures exhibit features which set it apart from classical tRNAs. Decoding of eukaryotic selenocysteine UGA codons requires a stem-loop structure in the 3'UTR of mRNAs, the selenocysteine insertion sequence (SECIS) element. Structure probing and sequence comparisons led us to propose a 2D structure model for the SECIS element, containing a novel RNA motif composed of four consecutive non-Watson-Crick base-pairs. A 3D model, rationalizing the accessibility data, was elaborated by computer modeling. It yields indicative or suggestive evidence for the role that could play some conserved residues and/or structural features in SECIS function. These might act as signals for interaction with SBP, the SECIS binding protein that we have characterized.

Animals↗

PubMed2002

An overview of the epidemiology and epizootology of brucellosis in selected countries of Central and Southeast Europe.

The objective of this paper is to give an overview of the epidemiologic and epizootic status of brucellosis in selected countries of Central and Southeast Europe (Balkan region). Based on dimension of the disease problem, there is a need to establish collaboration in the eradication and prevention of brucellosis between all countries in the region. Although there were no readily accessible data concerning epidemiology and epizootology of brucellosis in these countries, the limited official and published data were analyzed. The incidence of brucellosis caused by Brucella melitensis in sheep, goats and humans is a very significant problem in Macedonia and Greece. In Greece, cattle are also affected either by B. melitensis or B. abortus. The disease is an endemic problem in some regions of Yugoslavia and includes B. suis biovar 2 in pigs and in Croatia, B. melitensis in sheep, goats and human is found occasionally. No problem appears to exist with brucellosis in Bulgaria. Financial well-supported brucellosis control programs of the European Union that will include all countries, regardless of the magnitude of brucellosis incidence, are needed for eradication and control of brucellosis.

Animals↗

PubMed2001

Applications of population approaches in toxicology.

Many experimental or observational studies in toxicology are best analysed in a population framework. Recent examples include investigations of the extent and origin of intra-individual variability in toxicity studies, incorporation of genotypic information to address intra-individual variability, optimal design of experiments, and extension of toxicokinetic modelling to the analysis of biomarker studies. Bayesian statistics provide powerful numerical methods for fitting population models, particularly when complex mechanistic models are involved. Challenges and limitations to the use of population models, in terms of basic structure, computational burden, ease of implementation and data accessibility, are identified and discussed.

Animals↗

PubMed1999

Improved bidirectional retrieval of sparse patterns stored by Hebbian learning.

The Willshaw model is asymptotically the most efficient neural associative memory (NAM), but its finite version is hampered by high retrieval errors. Iterative retrieval has been proposed in a large number of different models to improve performance in auto-association tasks. In this paper, bidirectional retrieval for the hetero-associative memory task is considered: we define information efficiency as a general performance measure for bidirectional associative memory (BAM) and determine its asymptotic bound for the bidirectional Willshaw model. For the finite Willshaw model, an efficient new bidirectional retrieval strategy is proposed, the appropriate combinatorial model analysis is derived, and implications of the proposed sparse BAM for applications and brain theory are discussed. The distribution of the dendritic sum in the finite Willshaw model given by Buckingham and Willshaw [Buckingham, J., & Willshaw, D. (1992). Performance characteristics of associative nets. Network, 3, 407-414] allows no fast numerical evaluation. We derive a combinatorial formula with a highly reduced evaluation time that is used in the improved error analysis of the basic model and for estimation of the retrieval error in the naive model extension, where bidirectional retrieval is employed in the hetero-associative Willshaw model. The analysis rules out the naive BAM extension as a promising improvement. A new bidirectional retrieval algorithm - called crosswise bidirectional (CB) retrieval - is presented. The cross talk error is significantly reduced without employing more complex learning procedures or dummy augmentation in the pattern coding, as proposed in other refined BAM models [Wang, Y. F., Cruz, J. B., & Mulligan, J. H. (1990). Two coding strategies for bidirectional associative memory. IEEE Trans. Neural Networks, 1(1), 81-92; Leung, C.-S., Chan, L.-W., & Lai, E. (1995). Stability, capacity and statistical dynamics of second-order bidirectional associative memory. IEEE Trans. Syst. Man Cybern., 25(10), 1414-1424]. The improved performance of CB retrieval is shown by a combinatorial analysis of the first step and by simulation experiments: it allows very efficient hetero-associative mapping, as well as auto-associative completion for sparse patterns - the experimentally achieved information efficiency is close to the asymptotic bound. The different retrieval methods in the hetero-associative Willshaw matrix are discussed as Boolean linear optimization problems. The improved BAM model opens interesting new perspectives, for instance, in information retrieval it allows efficient data access providing segmentation of ambiguous user input, relevance feedback and relevance ranking. Finally, we discuss BAM models as functional models for reciprocal cortico-cortical pathways, and the implication of this for a more flexible version of Hebbian cell-assemblies.

Journal Article↗

PubMed2004

A software application for multiattribute utility models.

RATIONALE AND OBJECTIVES: A software application for the building of preference-weighted quality of life instruments was constructed. The purpose of this application is to make the process of building such instruments with multiattribute utility (MAU) methods more accessible to physician investigators. Our application, "multiattribute outcomes evaluator" or "MOE," could facilitate the use of such methods for constructing disease-specific instruments for assessing the cost-effectiveness of new treatments. MOE could also be useful for building outcomes measures that are intended to aid individual decision making, assessment of patient satisfaction with care, or measuring of multiattribute outcomes that do not need to be scaled for cost-effectiveness analysis. MATERIALS AND METHODS: MOE was programmed in Visual Basic and runs atop a Microsoft Access data base. Data from groups or individuals can be stored, and valuations of health states can be performed using standard gambles and rating scale methods. Solutions to MAU models with multiplicative or additive utility independence are possible with this application. RESULTS: Initial tests of the program algorithms have been successful. CONCLUSION: We anticipate The MOE approach to MAU modeling will be a useful tool for health services researchers.

Humans↗

PubMedDate not supplied

[Costs of psychiatric services: a study performed at a public mental center in the Lombardy Region, Italy].

OBJECTIVE: The implementation of a simple methodology to estimate full costs of services provided by a public mental health centre. SETTING: CPS (NHS Mental Centre) Ussl 35, Magenta, Lombardy Region. METHOD: To estimate full costs of 16 types of service we followed a two step procedure. The first step was to estimate all costs attributable to the CPS. In the second one, we allocated this estimate to each type of service provided. We attributed to the CPS the following cost items: personnel, utilities (telephone, electricity, water, heating and cleaning), land & building, transports (for services provided outside the clinic) and a share of general cost of the USSL to which the CPS belongs. Full cost of each service was then calculated on the base of the yearly number of services provided and the time spent by each health professional. RESULTS: In 1995, the CPS provided 14,562 services. Total costs amounted to L 1,356 million, and more than three quarters of this amount was attributable to the personnel working at the CPS. Unit costs ranged from L 5,300 (drug administration) to L 442,400 (family therapy involving two professionals for 90 minutes) The unit cost of psychiatric visits, psychologist consultations and nurse domiciliary visits were L 105,300, L 106,600 and L 78,000, respectively. CONCLUSIONS: This approach requires accessible data and is relatively simple to manage. Some refinements are required, especially to improve the methodology for the determination and the allocation of overheads. However, we are convinced that this cost accounting procedure provides acceptable estimates of the services provided by the CPS. These estimates suggest that charges to be used to fund NHS providers may be too low, especially if fee-for-service will be the main funding source.

Costs and Cost Analysis↗

PubMed2005

Functional probing of arginine residues in proteins using mass spectrometry and an arginine-specific covalent tagging concept.

The reactivity of arginine residues in model proteins (ubiquitin, cytochrome c, myoglobin, ribonuclease A, lysozyme) was examined using a selective tagging reaction in combination with on-line monitoring of the reaction progress by electrospray ionization mass spectrometry (ESI-MS). The kinetics of this reaction, based on the cyclization of the guanidine group of arginine with 2,3-butanedione and phenylboronic acid at pH 8-10, allow the grouping of arginines in "exposed" or "partially buried" residues, because they differ substantially in their reaction rate constants for the conversion of the guanidine groups. The method allows one to differentiate between different protein conformations as shown for myoglobin and its apo form and native and reduced ribonuclease A: Removal of the heme group in myoglobin resulted in an increased reactivity for the two partially buried arginines. For RNAse A, quantitative reduction of the disulfide bonds lead to the exposure of an additional arginine residue and two different conformations of the reduced protein were observed by ESI-MS that could be distinguished according to their charge-state distribution. Experimentally obtained accessibilities were compared with solvent-accessibility data calculated from 3D structures and substantial agreement between both techniques was observed.

Affinity Labels↗

PubMed1995

Mapping light-dependent structural changes in the cytoplasmic loop connecting helices C and D in rhodopsin: a site-directed spin labeling study.

All 20 single cysteine substitution mutants in the sequence Y136-M155 of bovine rhodopsin have been prepared and modified with a sulfhydryl-specific nitroxide reagent. This sequence contains the C-D interhelical loop, a transducin interaction site. The accessibilities of the attached nitroxides to collisions with paramagnetic probes in solution were determined, and the electron paramagnetic resonance spectra were analyzed, both in the dark and after photoexcitation. Accessibility data show that the rhodopsin polypeptide crosses an aqueous/hydrophobic boundary near V138 and H152. The nitroxide mobilities inferred from the spectra are consistent with a model where the C helix extends to at least residue C140, with much of the helix surface in contact with protein rather than lipid near the cytoplasmic surface of the membrane. Upon photoexcitation, electron paramagnetic resonance spectral changes are observed at sites on the putative C helix surface that are in contact with the protein and at specific sites in the C-D interhelical loop. A simple interpretation of these results is that photoexcitation involves a rigid body movement of the C helix relative to the others in the helix bundle.

Amino Acid Sequence↗