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PubMed1995

Systematic analysis of coding and noncoding DNA sequences using methods of statistical linguistics.

We compare the statistical properties of coding and noncoding regions in eukaryotic and viral DNA sequences by adapting two tests developed for the analysis of natural languages and symbolic sequences. The data set comprises all 30 sequences of length above 50 000 base pairs in GenBank Release No. 81.0, as well as the recently published sequences of C. elegans chromosome III (2.2 Mbp) and yeast chromosome XI (661 Kbp). We find that for the three chromosomes we studied the statistical properties of noncoding regions appear to be closer to those observed in natural languages than those of coding regions. In particular, (i) a n-tuple Zipf analysis of noncoding regions reveals a regime close to power-law behavior while the coding regions show logarithmic behavior over a wide interval, while (ii) an n-gram entropy measurement shows that the noncoding regions have a lower n-gram entropy (and hence a larger "n-gram redundancy") than the coding regions. In contrast to the three chromosomes, we find that for vertebrates such as primates and rodents and for viral DNA, the difference between the statistical properties of coding and noncoding regions is not pronounced and therefore the results of the analyses of the investigated sequences are less conclusive. After noting the intrinsic limitations of the n-gram redundancy analysis, we also briefly discuss the failure of the zeroth- and first-order Markovian models or simple nucleotide repeats to account fully for these "linguistic" features of DNA. Finally, we emphasize that our results by no means prove the existence of a "language" in noncoding DNA.

Animals↗
PubMed1998

Systematic analysis and controlling of health care organisations lead to numerical health care improvements.

The EFQM model for organisational excellence is used in the health care sector as a tool to diagnose and assess the starting position for the effective QM programme. Feedback reports cover the fields of acute medical care, rehabilitation and ambulant care and contain strengths areas for improvement. Building on the EFQM feedback reports, the Modular Concept for Quality in Health Care ("Heidelberg Model") improves QM both holistically and specifically by implementing so-called "Modules for Excellence". The implementation process follows principles of project management covering medical, nursing and managing issues and the performance is periodically evaluated against targets. QM projects that are designed in the dichotomic way follow three goals. Organisational diagnosis and therapy lead to numerical health care improvements in "Prevention of nosocomial infections" and "Optimising out-patient treatment". Different assessment approaches lead to a diagnosing feedback report for QM in health care. The Modular Concept for Quality in Health Care ("Heidelberg Model") clusters, priorities, implements and evaluates the organisation's key areas for improvement.

Ambulatory Care↗
PubMed2001

Systematic analysis of a conserved region of the aminoglycoside 6'-N-acetyltransferase type Ib.

Alanine-scanning mutagenesis was applied to the aminoglycoside 6'-N-acetyltransferase type Ib conserved motif B, and the effects of the substitutions were analyzed by measuring the MICs of kanamycin (KAN) and its semisynthetic derivative, amikacin (AMK). Several substitutions resulted in no major change in MICs. E167A and F171A resulted in derivatives that lost the ability to confer resistance to KAN and AMK. P155A, P157A, N159A, L160A, I163A, K168A, and G170A conferred intermediate levels of resistance. Y166A resulted in an enzyme derivative with a modified specificity; it conferred a high level of resistance to KAN but lost the ability to confer resistance to AMK. Although not as pronounced, the resistance profiles conferred by substitutions N159A and G170A were related to that conferred by Y166A. These phenotypes, taken together with previous results indicating that mutant F171L could not catalyze acetylation of AMK when the assays were carried out at 42 degrees C (D. Panaite and M. Tolmasky, Plasmid 39:123-133, 1998), suggest that some motif B amino acids play a direct or indirect role in acceptor substrate specificity. MICs of AMK and KAN for cells harboring the substitution C165A were high, suggesting that the active form of the enzyme may not be a dimer formed through a disulfide bond. Furthermore, this result indicated that the acetylation reaction occurs through a direct mechanism rather than a ping-pong mechanism that includes a transient transfer of the acetyl group to a cysteine residue. Deletion of fragments at the C terminus demonstrated that up to 10 amino acids could be deleted without a loss of activity.

Acetyltransferases↗
PubMed1996

A systematic analysis of the mutations of the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) or Günther's disease is an inborn error of heme biosynthesis, transmitted as an autosomal recessive trait and characterized by a profound deficiency of uroporphyrinogen III synthase activity (UROIIIS). The molecular defects observed in CEP are mainly heterogeneous, except for one missense mutation, C73R (Cys to Arg substitution at codon 73) which represents nearly 40% of the disease alleles. A convenient strategy was designed to establish a rapid diagnosis at the genetic level in samples from patients with CEP. As a first step, the most frequent mutation is searched for by restriction analysis from genomic. DNA amplified by PCR. Next, the nine coding exons and intron-exon boundaries are sequenced from genomic DNA. As an alternative, the mutation can be determined by sequencing the UROIIIS cDNA of the patient, using the RT-PCR technique on RNAs when a lymphoblastoid cell line can be established. Finally, for each new mutation in UROIIIS coding sequence, the corresponding mutant protein is expressed in Escherichia coli, in order to demonstrate the pathological significance of the mutation. This work describes the analysis of UROIIIS gene mutations in 10 new families with CEP and summarizes the data from 20 unrelated families studied in our laboratory. Three new missense mutations of UROIIIS coding sequence (H173Y, Q187P and P248Q) have been observed together with 8 known mutations. The significance of three intronic base changes (476 -31 T-->C; 562 -4 A-->T; 562 -23 A-->G) is discussed. In 6 alleles out of 40 (15%), the mutation remains undetermined.

Adolescent↗
PubMed2001

Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.

One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.

Adrenergic beta-Antagonists↗
PubMed1979

Neurotic depressions: a systematic analysis of multiple criteria and meanings.

Neurotic depression, the most commonly used psychiatric diagnosis, has multiple meanings that are often used interchangeably in clinical practice. The authors identify six different meanings of neurotic depression and present data from a study of 90 depressed inpatients to determine how many patients met several different criteria; 16 patients met four sets of criteria. The overlap that exists between the different meanings is higher than chance alone but not sufficiently high to allow complete interchangeability. Until new diagnostic classes are developed, the authors recommend that the term "neurotic depression" no longer be used clinically because of its vagueness.

Adjustment Disorders↗
PubMed1998

Systematic analysis of snoring in women.

Nineteen percent of women are habitual snorers, yet most snoring studies report only on male snorers. The aim of this study was to identify the factors responsible for habitual snoring in women. Twenty-four snorers and 16 controls were studied prospectively in a special snoring clinic. Snorers were shorter (p = .005) and heavier (p = .001), and with greater body mass index (BMI: p < .001), collar size (p = .002), and submental skinfold thickness (p = .001) than controls. The area of the posterior pharyngeal wall visible on oral examination was smaller in snorers (p = .005). Acoustic rhinometry areas and volumes were similar in the two groups. Nasal flow-volume loops showed reduced expiratory (p = .01) and inspiratory (p = .07) flow in snorers. Inspiratory flow correlated inversely with nasal symptoms (p < .05). The factors that best predict habitual snoring in women are a high BMI, a high nasal symptom score, and heavy weight. Of these, BMI is the most powerful.

Adolescent↗
PubMed2002

Identifying functional relationships among human genes by systematic analysis of biological literature.

BACKGROUND: The availability of biomedical literature in electronic format has made it possible to implement automatic text processing methods to expose implicit relationships among different documents, and more importantly, the functional relationships among the molecules and processes that these documents describe. RESULTS: A computational strategy that identifies functionally related human genes by detecting the implicit relationships among the publications cited under each gene in the Online Mendelian Inheritance in Man (OMIM) was implemented. The implementation was based on a substantially modified version of the kernel document method. The improvements include assigning a calculated weight for a document to indicate its importance in establishing the relationship between two documents, and using multiple kernel documents to reflect the multiple functions of the same gene. An example of using this strategy to identify genes related to the apoptosis pathway in human was given. CONCLUSIONS: The results showed that this method can indeed produce meaningful results when applied to human genes.

Apoptosis↗
PubMed2003

Haplotypes and the systematic analysis of genetic variation in genes and genomes.

Haplotypes have been used in various fields of genetics for a long time, in a variety of contexts, and for different purposes. Now, haplotype-based approaches to the analysis of candidate genes and genome-wide linkage disequilibrium (LD) mapping have gained center stage. It is time to explicitly distinguish the different concepts implied in the present haplotype approaches: haplotypes are not haplotypes, after all. The distinction of three different categories, ancestral, common haplotypes or haplotype blocks, gene-based haplotypes as complex genetic markers and gene-based functional haplotypes, is proposed. These categories serve as framework to review and analyze in particular the recent work suggesting evidence for a haplotype block structure of the human genome and the body of comparative sequencing studies addressing haplotype and LD structures at the gene level. Haplotype approaches will be evaluated along the dimensions preselection of variants versus complete DNA sequence information, role of LD and stages in the process of disease gene identification. Overall, the content of haplotypes is conceived as a function of available technologies to evaluate genetic variation and general advances in human genome research.

Genetic Predisposition to Disease↗
PubMed1998

Systematic analysis of STD control: an operational model.

BACKGROUND: Sexually transmitted diseases (STDs) enhance HIV transmission, and improved management of STD in primary health care decreases HIV incidence. In resource poor countries, those responsible for planning and managing STD control programmes need to be able to analyse the STD situation in their setting and the interventions which are therefore likely to be most cost effective. However, the data required for such decision making are often not available in developing countries. This paper presents an operational model, developed as a practical tool to support planning, monitoring, and evaluation of STD intervention strategies in settings where data are unavailable or inadequate. METHOD: The operational model is based on the approach developed for estimating the effectiveness of control measures in tuberculosis programmes. Using available data, the model takes a step by step approach. It begins with analysis of the total male and female population, the proportion of men and women aged 15-49 years, and the proportion of these who are sexually active. Subsequent steps analyse numbers with STDs, and loss of cases to the health system at each stage between infection and cure. The model was tested in Nairobi, Kenya using available demographic, epidemiological, and public health data; no original data were collected. Data for the total population of Nairobi were not available to illustrate all the steps in the model. For these steps, relevant information was taken where available from a specific study population using a large STD referral centre. RESULTS: Despite the lack of precise data for Nairobi, the model highlighted sex imbalances in population, which has potential implications for STDs. It also showed significant disparities in terms of public health policy--for example, between the number of people infected with STDs and the number who have symptoms, and between the number with symptoms and those who seek treatment from public health facilities. It also showed differences between the numbers who attend a health facility, and those that are correctly diagnosed and treated, and, of these, the proportion that are cured. CONCLUSION: Even where data are incomplete or not available, the model can be a useful tool for analysis. Application of the model, as the Nairobi example illustrates, provides a useful starting point in terms of determining both general and specific determinants of STDs, identifying problems, highlighting significant sex differences, and indicating where it might be appropriate to focus interventions. The model showed that, in Nairobi, only a small proportion of STD cases are removed from the reservoir of infection in the community through curative services, that cases are lost to the health services at every step, and therefore that interventions are required at every step to achieve comprehensive STD control. It highlights the need for strategies to prevent infections, to identify and treat those with and without symptoms, to motivate those who are aware of their infection to seek treatment, and to improve the effectiveness of partner notification and treatment. Finally, the model points to areas where data are inadequate and where STD control programmes need to concentrate information collection efforts.

Adolescent↗
PubMedDate not supplied

[The concept of nursing. A systematic analysis].

Nursing is a field which employs numerous people whose formation and professional roles are regulated by a wide set of rules and norms, and one which benefits innumerable patients. A paradox exists when, upon consulting various dictionaries, one of these the Royal Academy Dictionary (Diccionario de la Real Academia), the term nursing is defined as a physical space/set of nurses without any reference whatsoever to nurses' role in the health and educational systems. The definition we find in a dictionary should correspond to the concept the general public holds and reflect the true meaning of the profession. During a three year period, academic years 1994-96, on the first day of class, we asked each student to define or describe what he/she understood nursing to be. We consider that their responses, in a large sense, should correspond to the idea which the general public holds about nursing. An analysis of the content of these definitions allowed us to establish that there is a clear confrontation between what dictionaries state and what students, as a sample of society as a whole, think. Our results permit us to offer a definition for nursing which may be incorporated into new dictionary editions for the purpose of completing the already existing ones.

Attitude of Health Personnel↗
PubMed1999

A systematic analysis of secondary DNA transfer.

The Nature letter by R. van Oorschot and M. Jones (1) addressed two topics: the primary transfer of DNA from person to person or to various objects, and the secondary transfer of DNA through an intermediary. Forensic scientists have described the primary transfer of DNA and other biological evidence for many years. However, the authors also reported detecting secondary transfer of DNA from an object to a person's hands, which could adversely affect DNA typing in the forensic context. The prospect of secondary transfer raises questions of interest to both the legal and forensic communities. Therefore, we sought to evaluate parameters potentially leading to secondary DNA transfer. Our data do not support the conclusion that secondary transfer will compromise DNA typing results under typical forensic conditions.

DNA↗