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PubMed2004

Gaps, conflicts, and consensus in the ethics statements of professional associations, medical groups, and health plans.

BACKGROUND: Patients today interact with physicians, physician groups, and health plans, each of which may follow distinct ethical guidelines. METHOD: We systematically compared physician codes of ethics with ethics policies at physician group practices and health plans, using the 1998-99 policies of 38 organisations-18 medical associations (associations), nine physician group practices (groups), and 12 health plans (plans)-selected using random and stratified purposive sampling. A clinician and a social scientist independently abstracted each document, using a 397-item health care ethics taxonomy; a reconciled abstraction form was used for analysis. This study focuses on ethics policies regarding professional obligation towards patients, resource allocation, and care for the vulnerable in society. RESULTS: A majority in all three groups mention "fiduciary obligations" of one sort or another, but associations generally address physician/patient relations but not health plan obligations, while plans rarely endorse physicians' obligations of advocacy, beneficence, and non-maleficence. Except for occasional mentions of cost effectiveness or efficiency, ethical considerations in resource allocation rarely arise in the ethics policies of all three organisational types. Very few associations, groups, or plans specifically endorse obligations to vulnerable populations. CONCLUSIONS: With some important exceptions, we found that the ethics policies of associations, groups, and plans are narrowly focused and often ignore important ethical concerns for society, such as resource allocation and care for vulnerable populations. More collaborative work is needed to build integrated sets of ethical standards that address the aims and responsibilities of the major stakeholders in health care delivery.

Conflict, Psychological↗
PubMed1996

On evolutive systems and the initial evolution of structure and function.

As an instrument for the study of the early stages of evolution, we introduce evolutive systems, defined as systems that have the capacity to evolve given appropriate conditions in their environment. They consist of building blocks (e.g. monomers) that are either stable or in steady supply, and of transient assemblies (e.g. polymers) that are entities of great variety, some of which are capable of function. Evolution leads to the accumulation of structure within the transient assemblies during repeated cycles of disintegration (partial or total) and reassembly, on account of the selective advantages associated with transient assembly functions. Transient assemblies must be either inherently unstable or subject to disintegration by agents in their environment. Evolutive systems must have access to a negentropy input in the form of energy in packets larger than typical thermal energies. Reproduction, although not a prerequisite, greatly affects the capacity of evolutive systems to evolve, and thus can be expected to appear in an evolutive system if at all possible. Similarly, functions that require the expenditure of negentropy (for example mobility, breathing, circulation, sensing, communicating, etc.) are not prerequisites for evolution, but can be expected to become established in evolutive systems during evolution through the selective advantages that they confer. A computer-based evolutive automaton is used to explore possible evolutionary scenarios. In the presence of spatial and temporal inhomogeneities, one can construct a multitude of evolutionary scenarios through which various functions, such as the operation of genetic code, can become established within the evolutive automaton. This variety of possible evolutionary scenarios is all the more remarkable because the automaton does not include many important physical processes that would be present in a real system and would greatly multiply the number of possible evolutionary mechanisms and scenarios. Some evolutionary mechanisms are based on survival related selection, while others are based on generation related selection. Previously explored scenarios for the initiation of life have been based mostly on generation related selection. In this paper, we give particular emphasis to survival related selection which is more general in that it does apply to structures and functions related to reproduction but, unlike generation related selection, it is not limited to them. Some of the most basic features of terrestrial living systems can be seen either as prerequisite features of an evolutive system (such as the mortality of living organisms, instability of biological polymers, imperfect reproduction caused by mutations, and the need for a negentropy input) or as features that one can reasonably expect to become established in an evolutive system (such as reproduction and the multitude of living functions that require expenditure of negentropy). This suggests the possibility that an independent definition of living systems may not be necessary if features of living systems substantially overlap with features that one may expect to find in evolutive systems.

Animals↗
PubMedDate not supplied

[Prospects and achievements of genetic engineering in development of antiviral vaccines].

Proceeding from the known data various theoretical and experimental approaches to the construction of gene-engineering vaccines are considered. Gene-engineering subunit vaccines of the first generation are based on isolation of the genes coding for the synthesis of full length capsid proteins with the main antigenic determinants and their subsequent expression in suitable recipient cells. Initial idea of the microbiological synthesis as the main way for production of any antiviral vaccines was not confirmed by the later development. Now for this type of vaccines eucaryotic systems are widely employed using the animal virus vectors and the animal cell cultures. Gene-engineering subunit vaccine of the second generation appears to be a chimeric protein with built-in antigenic determinants of different viruses and maximal immunogenicity in monomeric form. The last point reopens the perspective to use a microbiological synthesis for the production of antiviral vaccines. Besides that the chemically synthesized polypeptide antiviral vaccine will be used widely. In gene-engineering subunit vaccines of the third generation it is possible to use not the natural antigenic determinants which often are characterized by high level of the primary structure changes but artificial (non-natural) antigens, that are the capsid protein conservative regions which under natural conditions of infection or immunization do not induce the protective antiviral antibodies. The recombinant DNA technology in addition to subunit type vaccine allows to construct living vaccines which represent a DNA-containing attenuated virus with build-in natural or synthetic gene of the capsid or chimeric protein with antigenic determinants of another viral species.

Animals↗
PubMed2003

Extensive gene gain associated with adaptive evolution of poxviruses.

Previous studies of genome evolution usually have involved one or two genomes and have thus been limited in their ability to detect the direction and rate of evolutionary change. Here, we use complete genome data from 20 poxvirus genomes to build a robust phylogeny of the Poxviridae and to study patterns of genome evolution. We show that, although there has been little gene order evolution, there are substantial differences between poxviruses in terms of genome content. Furthermore, we show that the rate of gene acquisition is not constant over time and that it has increased in the orthopox lineage (which includes smallpox and vaccinia). We also tested for positive selection on 204 groups of genes and show that a disproportionately high proportion of genes in the orthopox clade are under positive selection. The association of an increased rate of gene gain and positive selection is indicative of adaptive genome evolution. Many of the genes involved in these processes are likely to be associated with host-parasite coevolution.

Animals↗
PubMed2001

Conformational analysis of putative regulatory subunit D of the toluene/o-xylene-monooxygenase complex from Pseudomonas stutzeri OX1.

A gene cluster isolated from Pseudomonas stutzeri OX1 genomic DNA and containing six ORFs codes for toluene/o-xylene-monooxygenase. The putative regulatory D subunit was expressed in Escherichia coli and purified. Its protein sequence was verified by mass spectrometry mapping and found to be identical to the sequence predicted on the basis of the DNA sequence. The surface topology of subunit D in solution was probed by limited proteolysis carried out under strictly controlled conditions using several proteases as proteolytic probes. The same experiments were carried out on the homologous P2 component of the multicomponent phenol hydroxylase from Pseudomonas putida CF600. The proteolytic fragments released from both proteins in their native state were analyzed by electrospray mass spectrometry, and the preferential cleavage sites were assessed. The results indicated that despite the relatively high similarity between the sequences of the two proteins, some differences in the distribution of preferential proteolytic cleavages were detected, and a much higher conformational flexibility of subunit D was inferred. Moreover, automatic modeling of subunit D was attempted, based on the known three-dimensional structure of P2. Our results indicate that, at least in this case, standard modeling procedures based on automatic alignment on the structure of P2 fail to produce a model consistent with limited proteolysis experimental data. Thus, it is our opinion that reliable techniques such as limited proteolysis can be employed to test three-dimensional models and highlight problems in automatic model building.

Amino Acid Sequence↗
PubMed2005

Role of the N terminus in enzyme activity, stability and specificity in thermophilic esterases belonging to the HSL family.

A superposition between the structures of Alicyclobacillus acidocaldarius esterase 2 (EST2) and Burkholderia cepacia lipase, the latter complexed with a phosphonate inhibitor, allowed us to hypothesize for the EST2 N terminus a role in restricting the access to the active site and therefore in modulating substrate specificity. In order to test this hypothesis we generated by site-directed mutagenesis some truncated versions of EST2 and its double mutant M211S/R215L (S/L) at the N terminus. In parallel, an analysis of the Sulfolobus solfataricus P2 genome allowed us to identify a gene coding for a putative esterase of the HSL family having a natural deletion of the corresponding region. The product of this gene and the above-mentioned EST2 mutants were expressed in Escherichia coli, purified and characterised. These studies support the notion that the N terminus affects substrate specificity other than several other enzyme parameters. Although the deletions afforded a tenfold and 550-fold decrease in catalytic efficiency towards the best substrate pNP-hexanoate at 50 degrees C for EST2 and S/L, respectively, the analysis of the specific activities with different triacylglycerols with respect to pNP-hexanoate showed that their ratios were higher for deleted versus non-deleted enzymes, on all tested substrates. In particular, the above ratios for glyceryl tridecanoate were 30-fold and 14-fold higher in S/L and EST2 deleted forms, respectively, compared with their full-length versions. This behaviour was confirmed by the analysis of the S.solfataricus esterase, which showed similar specific activities on pNP-hexanoate and triacylglycerols; in addition, higher activities on the latter substrates were observed in comparison with EST2, S/L and their deleted forms. Finally, a dramatic effect on thermophilicity and thermostability in the EST2 deleted forms was observed. This is the first report highlighting the importance of the "cap" domain in the HSL family, since the N terminus partly contributes to the building up of this structure.

Amino Acid Sequence↗
PubMed2005

A quantitative determination of multi-protein interactions by the analysis of confocal images using a pixel-by-pixel assessment algorithm.

MOTIVATION: Recent advances in confocal microscopy have allowed scientists to assess the expression, and to some extent, the interaction/colocalization of multiple molecules within cells and tissues. In some instances, accurately quantifying the colocalization of two or more proteins may be critical. This can require the acquisition of multiple Z plane images (Z stacks) throughout a specimen and, as such, we report here the successful development of a freeware, open-source image analysis tool, IMAJIN_COLOC, developed in PERL (v. 5.8, build 806), using the PERLMagick libraries (ImageMagick). Using a pixel-by-pixel analysis algorithm, IMAJIN_COLOC can analyze images for antigen expression (any number of colors) and can measure all possible combinations of colocalization for up to three colors by analyzing a Z stack gallery acquired for each sample. The simultaneous (i.e. in a single pass) analysis of three-color colocalization, and batch analysis capabilities are distinctive features of this program. RESULTS: A control image, containing known individual and colocalized pixel counts, was used to validate the accuracy of IMAJIN_COLOC. As further validation, pixel counts and colocalization values from the control image were compared to those obtained with the software packaged with the Zeiss laser-scanning microscope (LSM AIM, version 3.2). The values from both programs were found to be identical. To demonstrate the applicability of this program in addressing novel biological questions, we examined the role of neurons in eliciting an immune reaction in response to viral infection. Specifically, we successfully examined expression of the chemokine RANTES in measles virus (MV) infected hippocampal neurons and quantified changes in RANTES production throughout the disease period. The resultant quantitative data were also evaluated visually, using a gif image created during the analysis. AVAILABILITY: PERL (ActivePerl, version 5.8) is available at activestate.com; the PERLMagick libraries are available at imagemagick.org, and IMAJIN_COLOC, the source code and user documentation can be downloaded from http://www.fda.gov/cber/research/imaging/imageanalysis.htm.

Algorithms↗
PubMed1994

Building a computer-supported quality improvement system in one year: the experience of a large state psychiatric hospital.

BACKGROUND: G. Pierce Wood Memorial Hospital, a large state psychiatric hospital, implemented a data-intensive quality improvement (QI) program as part of its efforts to attain Joint Commission accreditation. EARLY STEPS OF QI IMPLEMENTATION: With the December 1993 Joint Commission survey date in mind, the Executive QI Committee started weekly meetings in December 1992 to plan initiatives and establish a viable information management system for the QI process. A QI coach was hired to help plan all phases of the QI program, and a 40-hour training program on statistics and QI principles was provided to key middle managers. SOFTWARE CHOICE ISSUES: Software options can be examined in terms of data cleaning, data manipulation, statistical flexibility, graphics strength, word processor compatibility, and utility strength. SOFTWARE CONFIGURATION: The present configuration of our statistical software is relatively elaborate. Organizations new to using statistical software should start off modestly to avoid being overwhelmed by the infinite possibilities that large numbers of interlinked modules present. DATA NETWORK CONFIGURATION: The technical core of the computerized QI system and how it operates are discussed. The data interface between the local area network (LAN) and statistical system data is described in three stages: (1) the creation of the "system" file; (2) the generation of the raw data; and (3) the transference of the raw data into the system file. QI ACTIONS: A QI reporting form was developed on which each report user states his/her analysis of the monthly indicator data report and identifies root causes, describes the actions taken to resolve the problems, or evaluates the effectiveness of prior actions taken. In addition, each indicator manager presents a quarterly verbal report to the Executive QI Committee on QI occurrences in his/her area of responsibility. CASE STUDIES: A nursing department indicator revealed an insufficient amount of supplies being placed in the code-blue ambulance. Determination of root causes led to the identification of a breakdown in the process whereby each shift adds and reviews supplies. As another example, the initiation of the stat IM (use of intramuscular injections or tranquilizing medications to restrain persons) indicator report led to a decrease in the number of IMs ordered. CONCLUSIONS: If we could have developed this statistical software-based QI program in only one year, then virtually any organization, large or small, can attain the technical capability to conduct "state of the art" QI.

Data Interpretation, Statistical↗
PubMed2006

Perceived barriers to care and attitudes about vision and eye care: focus groups with older African Americans and eye care providers.

PURPOSE: To identify by using focus group methods the perceived barriers to eye care and attitudes about vision and eye care among older African Americans as well as among ophthalmologists and optometrists serving their communities. METHODS: Seventeen focus groups of older African Americans residing in the Birmingham or Montgomery, Alabama, areas were led by an experienced facilitator. Discussion was stimulated by a semistructured script focused on their perceived barriers to eye care and attitudes about vision and eye care. Six focus groups of ophthalmologists and optometrists who practiced in this geographic region addressed the same topics. Discussion was audiotaped and transcribed. Comments were coded using a multistep content analysis protocol. RESULTS: One hundred nineteen African Americans (age range, 59-97 years) and 35 eye care providers (51% ophthalmologists, 49% optometrists) participated. The barrier-to-care problem most frequently cited by both African Americans and eye care providers was transportation. The next most common problems mentioned by African Americans were trusting the doctor, communicating with the doctor, and the cost of eye care; and for eye care providers, the next most common problems were cost, trust, and insurance. With respect to older African Americans' comments on their attitudes about vision and eye care, these comments were predominantly positive (69%), highlighting the importance of eye care and behavior in their lives and attitudes that facilitated care. However, when eye care providers relayed their impressions of African Americans' attitudes about vision and eye care, their comments were largely negative (74%) centering on concerns and frustrations that older African Americans did not have attitudes or engage in behavior that facilitate eye care. CONCLUSIONS: These results provide some guidance for the design of interventions to increase the use of routine eye care in this population. At a societal level, there is a need for affordable and accessible transportation services for older African Americans seeking eye care. For ophthalmologists, optometrists, and their staffs, there is a need for continuing education that imparts culturally sensitive and age-appropriate communication and trust-building skills for interactions with this population. In addition to reinforcing the generally positive attitudes of older African Americans toward the importance of eye care, community-based educational programs should be focused on strategies for overcoming the common barriers to care.

Black or African American↗
PubMed2003

Beyond individual rights and freedoms: metaethics in social work research.

Increasingly, social workers are called on to demonstrate the efficacy of their interventions and to contribute to knowledge building in the social sciences. Although social workers have a long tradition of practice ethics, less attention has been given to the unique dimensions of research ethics for social workers. A social work model of research ethics would consider how to balance highly valued ethical principles that are individually focused, such as self-determination and nonmalfeasance (the obligation to do no harm), with equally important values that have a collective focus, such as justice and beneficence (the obligation to bring about good). This article reviews current principles guiding research ethics, such as autonomy, beneficence, nonmalfeasance, and justice and provides an outline of the salient issues for social workers as they strive to address individual and collective interests in research endeavors, such as a greater emphasis on the social justice mission and the need to ensure that social justice objectives do not obscure individual rights and freedoms. The article concludes with preliminary recommendations for developing a social work perspective in research ethics.

Codes of Ethics↗
PubMed2006

Modularity of the transcriptional response of protein complexes in yeast.

A comprehensive study is performed on the condition-dependent expression of genes coding for the components of hand curated multi-protein complexes of the yeast Saccharomyces cerevisiae, in order to identify coherent transcriptional modules within these complexes. Such modules are defined as groups of genes within complexes whose expression profiles under a common set of experimental conditions allow us to discriminate them from random sets of genes. Our analysis reveals that complexes such as the cytoplasmic ribosome, the proteasome and the respiration chain complexes previously characterized as "stable" or "permanent" represent transcriptional modules that are coherently up or down-regulated in many different conditions. Overall however, some level of coherent expression is detected only in 71 out of the total of 113 complexes with at least five different protein components that could be reliably analyzed. Of these, 26 behave as coherently expressed transcriptional modules encompassing all the components of the complex. In another 15, at least half of the components make up such modules and in ten, few or no modules are detected. In an additional 20 complexes coherent expression is detected, but in too few conditions to enable reliable module detection. Interestingly, the transcriptional modules, when detected, often correspond to one or more known sub-complexes with specific functions. Furthermore, detected modules are generally consistent with transcriptional modules identified on the basis of predicted cis-regulatory sequence motifs. Also, groups of genes shared between complexes that carry out related functions tend to be part of overlapping transcriptional modules identified in these complexes. Together these findings suggest that transcriptional modules may represent basic functional and evolutionary building blocs of protein complexes.

Cluster Analysis↗
PubMed2006

The dismantling of end-of-life vehicles in Estonia before putting into effect the Directive 2000/53/EC.

BACKGROUND, AIMS AND SCOPE: When joining the European Union on 1st May 2004, Estonia had to conform its legislation to the European Union legislation. In relation with that, also the treatment requirements on end-of-life vehicles proceeding from Directive 2000/53/EC of the European Parliament and of the Council of 18 September 2000 were established in Estonia for the first time. Since this area was not regulated with law beforehand, there was not any information available about it. The aim of the current survey was to ascertain the condition of scrap yards in mid 2004. In addition to that, also to identify the number of scrap yards operating in Estonia, to classify these by the number of dismantled vehicles and the potential environmental hazard, and to map the locations of car dismantling companies and evaluate their compliance with the valid requirements. METHODS: The companies that have been registered in the Commercial Registry under the activity code 503090-end-of-life vehicle dismantling were visited and visually reviewed. During the visits, the compliance of scrap yards with the existing requirements was evaluated and it was also attempted to identify how environmentally sound the dismantling technology of every scrap yard owner is. RESULTS AND DISCUSSION: Altogether, 63 scrap yards operated in Estonia by mid 2004. Twelve of them dismantled more than 100 vehicles, 13 of them 51-99 vehicles and 38 up to 50 vehicles a year. The total annual market capacity on dismantling of vehicles in Estonia is considered to be approx. 10,000 units. There are very few companies dealing only with car dismantling as the main business. Most scrap-yard owners also offer side services, e.g. haulage, car repair and maintenance. The dismantlers are interested in the selling of second-hand spare parts and scrap metal. Only one company out of 63 complied with all the requirements enacted by the relevant decision of the Estonian Minister of Environment. The rest of the scrap yards did not meet the requirements on the site on storage and treatment nor did they have the hazardous waste handling licence or the waste permit. Of the requirements established for the site for storage of end-of-life vehicles, 97% of the scrap yards were surrounded with a fence, 67% had a 24-hour guard, 45% had covered the areas with waterproof cover, but only 3% had an oil trap. Sites for treatment were in a somewhat better condition, these were mostly situated inside the buildings, where floors were covered with waterproof covers. Most of the dismantlers collected the waste oil and waste fluids into separate vessels, but there were a number of dismantlers who did not know of existence of polychlorinated biphenyls (PCB) in car air conditioning systems and the availability of mercury in sensors belonging in passenger safety systems. Proceeding from the general condition of the scrap yard, the rest of 62 scarp yards were distributed between two empirical parameters--'rather environmentally hazardous' or 'rather not environmentally hazardous'. As a matter of fact, 17% of scrap yards turned out 'rather environmentally hazardous'. CONCLUSION: Out of the scrap yards operating in Estonia, only one is compliant with the requirements set up by Directive 2000/53/EC. Another 62 appeared during the review to be sites of potential environmental pollution. In order to comply with environmental requirements and get the hazardous waste treatment license, the scrap yard owners have to invest into state-of-the-art dismantling and environment protection equipment. The main obstacle to reach the environmentally sound scrap-yard is the high investment cost and the black market for spare parts. RECOMMENDATION AND OUTLOOK: As the correction of the market in end-of-life vehicle treatment started after the adoption of Directive 2000/53/EC, the environmental authorities have to look after the ongoing correction. It is because there is still a demand for cheap spare parts and it makes it attractive to dismantle the vehicles out of scrap-yards by licensees.

Automobiles↗
PubMed2002

Mutational analysis of the Uukuniemi virus (Bunyaviridae family) promoter reveals two elements of functional importance.

We have performed an extensive mutational analysis of the proposed promoter region of the phlebovirus Uukuniemi (UUK), a member of the Bunyaviridae family. This was achieved by using a recently developed RNA polymerase I (Pol I)-driven reverse genetics system (R. Flick and R. F. Pettersson, J. Virol. 75:1643-1655, 2001). Chimeric cDNAs containing the coding region for the reporter chloramphenicol acetyltransferase (CAT) in an antisense orientation were flanked by the 5'- and 3'-terminal nontranslated regions of the UUK virus-sense RNA (vRNA) derived from the medium-sized (M) RNA segment. The chimeric cDNAs (Pol I expression cassettes) were cloned between the murine Pol I promoter and terminator, and the plasmids were transfected into BHK-21 cells. CAT activity was determined after cotransfection with viral expression plasmids encoding the RNA-dependent RNA polymerase (L) and the nucleoprotein (N) or, alternatively, after superinfection with UUK virus helper virus. Using oligonucleotide-directed mutagenesis, single point mutations (substitutions, deletions, and insertions) were introduced into the viral promoter region. Differences in CAT activities were interpreted to reflect the efficiency of mRNA transcription from the mutated promoter and the influence on RNA replication. Analysis of 109 mutants allowed us to define two important regulatory regions within the proximal promoter region (site A, positions 3 to 5 and 2 to 4; site B, positions 8 and 8, where underlined nucleotides refer to positions in the vRNA 3' end). Complementary double nucleotide exchanges in the proximal promoter region, which maintained the possibility for base pairing between the 5' and 3' ends, demonstrated that nucleotides in the two described regions are essential for viral polymerase recognition in a base-specific manner. Thus, mere preservation of panhandle base pairing between the 5' and 3' ends is not sufficient for promoter activity. In conclusion, we have been able to demonstrate that both ends of the M RNA segment build up the promoter region and are involved in the specific recognition by the viral polymerase.

Animals↗
PubMed2026

The SARS-CoV-2 Integrated Genomic Epidemiology Database (IGED): Linking viral genomes with patient-level metadata to advance statewide genomic surveillance in California.

In July 2021, the California Code of Regulations Title 17 required all laboratories performing SARS‑CoV‑2 whole genome sequencing (WGS) to report their sequencing results to the California Department of Public Health (CDPH). These viral genomic data and patient metadata were compiled into the Integrated Genomic Epidemiology Database (IGED). Linking anonymized viral sequences with patient‑level information enabled monitoring of infectiousness, pathogenicity, transmission dynamics, evolution, and vaccine evasion among emerging SARS‑CoV‑2 lineages. Laboratories performing SARS-CoV-2 WGS transmitted sequencing results to CDPH through Electronic Laboratory Reporting (ELR) and non-ELR pathways. CDPH applied uniform reporting requirements but allowed flexibility in specific data formats to accommodate diverse data systems. To preserve data quality and interoperability across heterogeneous sources, CDPH implemented standardization, validation, and deduplication protocols. Snowflake, a cloud‑based data storage and analytics platform, and Posit Connect, a cloud deployment and automation platform, supported the management, processing, and integration of data within the IGED. The IGED established links between SARS‑CoV‑2 WGS data and epidemiologic metadata for 801,418 sequences, representing 81.7% of all sequences reported in California. Lineages reported to the IGED showed strong concordance with lineage proportions in GISAID. Sequences reported to the IGED had average turnaround times longer than one month, and the majority of sequencing was performed in Southern California and Los Angeles. The IGED enhanced genomic surveillance through predictive modeling and monitoring concerning evolutionary trends such as recombination and saltations in persistent infections. Development of the IGED highlighted the need for standardized data requirements, sustained funding for sequencing, incentives for data submission, and interdisciplinary collaboration to build an effective genomic surveillance system. This framework for linking genomic and epidemiologic data has not only generated critical insights for SARS‑CoV‑2 but also provided the foundation for CDPH and other public health organizations to develop similar IGED‑like systems for other priority pathogens as genomic surveillance expands.

Journal Article↗
PubMed2004

[Data of the morbidity and mortality index of the acute coronary syndrome in the South Trans-Danubian Region between 1999 and 2002].

Data of the morbidity and mortality index of the acute coronary heart disease in the South Trans-Danubian Region between 1999 and 2002. South Trans-Danubian Regional Acute Coronary Registry. Based on GYOGYINFOK database, the authors' purpose was to monitor the morbidity and mortality of acute coronary heart diseases (acute coronary syndrome, acute myocardial infarction) in the approximately one million people inhabiting the South Trans Danubian Region. Data were obtained using the financing data sheets reported to GYOGYINFOK by 15 in-patient health care institutions located in the region. The regional data were compared nation-wide ones as well. The observed diagnoses correspond to diseases the codes of which range from I 20.00 to I 22.90, according to BNO classification. The data of years 1999, 2000, 2001 and 2002 have already been processed and categorized by gender and age-groups. Hospital mortality, therapeutical procedures (thrombolysis, GP IIb/IIIa receptor blocker) as well as the parameters of progressive care have all been evaluated. Of the processed 4 years, the data of 8431 patients are already recorded in the registry. The rate of the thrombolytic therapy reached patients was decreased from 26.01% (which was detailed in 1999) to 7.39% into 2002 in our region, but the rate was nearly constant 16.1% in 1999 and 13.28% in 2002 in the country. The rate of the GP IIb/IIIa therapy reached patients was increased from 2.15% to 6.66% in our region, while it was increased from 0.66% to 3.96% between 2000 and 2002 in the country. Mortality in the hospitals decreased in the case of male from 14.44% to 8.7% in the region, and from 20.28% to 16.18% in the female. At the same time the hospital mortality was constant in the country, in males it was 14.39% in 1999, and 13.11% in 2002, and in females it was 20.00% in 1999, and 18.81 in 2002. As regards the therapeutical procedures--based on the data processed up to the present--it can be observed that classic thrombolytic therapy becomes de-emphasized while treatments with GP IIb/IIIa receptor blockers as well as the intervention coupled to these gain ground. The authors consider the creation of this registry a very important beginning step in building the cardiological map of the region.

Acute Disease↗
PubMed2006

Nature and frequency of exchanges on medications during primary care encounters.

OBJECTIVE: To describe the exchanges, related to discussion of all medications during primary care medical consultations. METHODS: Descriptive study of audio recordings of 422 medical encounters. Coding was done with MEDICODE, a validated instrument developed to analyse verbal exchanges on medications. The unit of analysis is the medication. RESULTS: An average of 3.9 medications (S.D.=2.8; range 1-21) are discussed per interview and 4.2 themes are broached for each drug (S.D.=2.6; range 1-17). "Active Discussed", "Represcribed" and "Newly Prescribed" drugs account for 43.1, 16.3 and 10.6%, respectively of all medications discussed. Themes most often discussed are Name, Instructions, Observed Main Effect, Class, Reasons for Taking the Drug, General Use of the Medication, Expected Effect on Symptoms, Form of the Medication, Indications Another Consultation Needed, and Alternative Medication. The least often discussed themes include clinically significant ones such as Possible Adverse Effects, Observed Adverse Effects, Expression of Attitudes and Emotions with regard to the medication, Compliance and Warnings. The average number of themes discussed differed between medications that were prescribed during the encounter, either New prescriptions or Represcribed drugs, compared to medications that were only discussed during the encounter. CONCLUSION: Our results show that medication discussions are heterogeneous and vary with the status of the medication and the theme. Also, the nature and extent of the discussions about medications do not support the shared-decision making model. PRACTICE IMPLICATIONS: Though it is too soon to make specific recommendations about discussions on medications, it seems clear that information-sharing about medications during medical encounters is a process that extends beyond any single encounter. Although communication skills are now part of most medical curriculums, there is an obvious need to put forth the concept of patient medication knowledge-building over multiple physician-patient encounters and to better prepare physicians to use the specific content and process skills necessary to revisit issues related to medications that seem necessary to support their patients' medication-taking practices.

Abstracting and Indexing↗
PubMed2002

Metabolic efficiency and amino acid composition in the proteomes of Escherichia coli and Bacillus subtilis.

Biosynthesis of an Escherichia coli cell, with organic compounds as sources of energy and carbon, requires approximately 20 to 60 billion high-energy phosphate bonds [Stouthamer, A. H. (1973) Antonie van Leeuwenhoek 39, 545-565]. A substantial fraction of this energy budget is devoted to biosynthesis of amino acids, the building blocks of proteins. The fueling reactions of central metabolism provide precursor metabolites for synthesis of the 20 amino acids incorporated into proteins. Thus, synthesis of an amino acid entails a dual cost: energy is lost by diverting chemical intermediates from fueling reactions and additional energy is required to convert precursor metabolites to amino acids. Among amino acids, costs of synthesis vary from 12 to 74 high-energy phosphate bonds per molecule. The energetic advantage to encoding a less costly amino acid in a highly expressed gene can be greater than 0.025% of the total energy budget. Here, we provide evidence that amino acid composition in the proteomes of E. coli and Bacillus subtilis reflects the action of natural selection to enhance metabolic efficiency. We employ synonymous codon usage bias as a measure of translation rates and show increases in the abundance of less energetically costly amino acids in highly expressed proteins.

Amino Acids↗
PubMed2004

A nearest-neighboring-end algorithm for genetic mapping.

MOTIVATION: High-throughput methods are beginning to make possible the genotyping of thousands of loci in thousands of individuals, which could be useful for tightly associating phenotypes to candidate loci. Current mapping algorithms cannot handle so many data without building hierarchies of framework maps. RESULTS: A version of Kruskal's minimum spanning tree algorithm can solve any genetic mapping problem that can be stated as marker deletion from a set of linkage groups. These include backcross, recombinant inbred, haploid and double-cross recombinational populations, in addition to conventional deletion and radiation hybrid populations. The algorithm progressively joins linkage groups at increasing recombination fractions between terminal markers, and attempts to recognize and correct erroneous joins at peaks in recombination fraction. The algorithm is O (mn3) for m individuals and n markers, but the mean run time scales close to mn2. It is amenable to parallel processing and has recovered true map order in simulations of large backcross, recombinant inbred and deletion populations with up to 37,005 markers. Simulations were used to investigate map accuracy in response to population size, allelic dominance, segregation distortion, missing data and random typing errors. It produced accurate maps when marker distribution was sufficiently uniform, although segregation distortion could induce translocated marker orders. The algorithm was also used to map 1003 loci in the F7 ITMI population of bread wheat, Triticum aestivum L. emend Thell., where it shortened an existing standard map by 16%, but it failed to associate blocks of markers properly across gaps within linkage groups. This was because it depends upon the rankings of recombination fractions at individual markers, and is susceptible to sampling error, typing error and joint selection involving the terminal markers of nearly finished linkage groups. Therefore, the current form of the algorithm is useful mainly to improve local marker ordering in linkage groups obtained in other ways. AVAILABILITY: The source code and supplemental data are http://www.iubio.bio.indiana.edu/soft/molbio/qtl/flipper/ CONTACT: ccrane@purdue.edu.

Algorithms↗