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[Regional variations in health services: various methodological problems].

Many studies show strong variation of health consumption between regions, suggesting that theses variations are related to the uncertainty of medical practice or to other factors related to health services or patients attitude. However the statistical interpretation of these variations is far from easy: apart from usual and specific information bias, there are statistical problems when observing incidence of events like health care consumption: it is in fact a rare event, which is observed within small population, and among regions with unequal number of person. Therefore, most of the variation reported might be well explained by a purely statistical phenomenon. This paper presents some aspects of this variability for three common indicators of variation, and suggest the use of ad hoc simulation to get statistical criteria.

Bias↗

The effects of variation in climatic temperature (1980-2001) on breeding activity and tadpole stage duration in the common toad, Bufo bufo.

The effects of variation in climatic temperature on breeding behaviour and tadpole growth were investigated using data collected during a 22-year study of a single population of common toads, Bufo bufo, in southern England. Although the start of the breeding season each year, taken as the day when adult toads first arrived at their breeding pond in large numbers, showed no trend over time (1980-2001) it was highly correlated with climatic temperature. Thus, toads started breeding approximately 50 days earlier in the year following very mild winters (1993: February 2nd) compared with very cold ones (1986: March 23rd). Regression analysis of the relationship between the mean temperature of the 40 days immediately preceding the main arrival of toads at the breeding pond revealed that for every 1 degrees increase (or decrease) the toads arrived 12 days earlier (or later). Although the duration of the tadpole stage was longer when spawning was early, toadlets still emerged from the pond earlier than when spawning was late. The increased length of the tadpole stage, in years when spawning was early, was due to an increase in the proportion of cold days when the minimum ground temperature was at or below 0 degrees C. Thus, the tadpole stage was approximately 6 days longer (or shorter) for every 5% increase (or decrease) in the proportion of cold days the tadpoles were exposed to.

Animals↗

Genetic variation in susceptibility to Trypanoplasma borreli infection in common carp (Cyprinus carpio L.).

Gynogenetic reproduction of homozygous females, or crossbreeding two homozygous animals, results in fish lines without genetic variation. Hybrid crosses are expected to express a more stable development than homozygous lines, the latter may have an important value for gaining insight into genetic components of host resistance to parasite infection. We examined the antibody response of carp (Cyprinus carpio L.) to infection with Trypanoplasma borreli. Outbred carp responded with a production of specific antibodies, but highly susceptible isogenic hybrid carp did not. This suggests an apparent relationship between susceptibility and the lack of specific antibody production. This relation was partially confirmed by the passive transfer of immunity with immune plasma. In addition, two isogenic homozygous carp lines were highly susceptible to the trypanoplasm (100% mortality), in contrast with outbred carp, the majority of which survived infection. None of the carp in either homozygous carp line produced an antibody response to parasite-unrelated antigen (DNP-KLH). This suggests that the low antibody response was not entirely due to a poor state of health, but that these carp have a genetically predetermined low antibody response.

Animals↗

Body composition and skin temperature variation.

Temperature variations near four common torso skin temperature sites were measured on 17 lightly clad subjects exposed to ambient temperatures of 28, 23, and 18 degrees C. Although variations in skin temperature exceeding 7 degrees C over a distance of 5 cm were observed on individuals, the mean magnitude of these variations was 2-3 degrees C under the coolest condition and less at the warmer temperatures. There was no correlation between the temperature variation and skinfold thickness at a site or with estimations of whole body fat content. These findings imply that errors in mean skin temperature measurement could arise from probe mislocation and/or subcutaneous fat distribution and that the problem becomes more acute with increasing cold stress. However, the magnitudes of these errors cannot be easily predicted from common anthropometric measurements.

Adipose Tissue↗

Methicillin-resistant Staphylococcus aureus: acquisition and risk of death in patients in the intensive care unit.

OBJECTIVE: To evaluate the risk of patients in intensive care units (ICU) of becoming infected with methicillin-resistant Staphylococcus aureus (MRSA) and to assess the mortality during a six week follow-up period, compared with patients who developed methicillin-sensitive S. aureus (MSSA) infection. DESIGN: Point prevalence survey. SETTING: 1417 ICU in 17 Western European countries. SUBJECTS: 10038 patients in ICU who were part in the EPIC (European Prevalence of Infection in Intensive Care) Study. MAIN OUTCOME MEASURES: Prevalence of MRSA and MSSA ICU-acquired infections, risk factors, and mortality. RESULTS: On the study day 21% of patients had ICU-acquired infections. The most commonly reported pathogen was Staphylococcus aureus (30%). Overall, 60% of strains of S. aureus were resistant to methicillin (with a wide intercountry variation). The most commonly reported MRSA infections were pneumonia and lower respiratory tract infections. The most important risk factor for MRSA was the length of stay in the ICU. MRSA infection reduced the chance of survival, particularly when it was found in lower respiratory tract infections: the risk of mortality was three times higher in patients with MRSA than in those with MSSA. CONCLUSION: Patients in ICU are at high risk of becoming infected with MRSA. The longer they stay, the higher the risk. Patients with MRSA infections are less likely to survive than those with MSSA.

Cross Infection↗

Family level inbreeding depression and the evolution of plant mating systems.

Variation in the magnitude of inbreeding depression (ID) among families may have important consequences for mating system evolution. Experimental studies have shown that such variation is a common feature of natural plant populations. Unfortunately, the genetic and evolutionary significance of family level estimates remains obscure. Almost any kind of genetic variation will generate differences in ID among families, and as a consequence, a non-zero variance in family level ID is not sufficient to distinguish genetic architectures with wholly different implications for mating system evolution. Quantitative genetic methods provide a means to extract more information from ID experiments. Estimates of quantitative genetic variance components directly inform questions about the genetic basis of ID and should ultimately allow tests of alternative theories of mating system evolution.

Biological Evolution↗

Preliminary report on the results of the second phase of a round- robin endotoxin assay study using cotton dust.

In an on-going endotoxin assay study, a two-part interlaboratory endotoxin assay study has been completed. The purpose of the study was to compare the variation in assay results between different laboratories, and, if the variation was high, to see if a common protocol would reduce the variation. In both parts of the study, membrane filters laden with the same approximate amount and type of cotton dust were sent for analysis to laboratories that "routinely" perform endotoxin analyses. First, each of these laboratories performed the analysis using the methodology common to its laboratory. In the second part of the study, membrane filters with cotton dust were again sent to the same laboratories where the analyses were performed as before but with a common extraction protocol. The preliminary results from the first phase of the study have been collected and showed that intra-laboratory variations were small, but large and significant interlaboratory variation was observed. The results were reported elsewhere. The preliminary results from the second part of the study consisting of the data currently collected are presented here. Again, intra-laboratory variations were small, but, also again, large and significant inter-laboratory variation was observed. However, in this part of the study, the range between the highest and lowest average results was narrower than in the first part of the study. Influence of the assay kit type was examined. The variation within assay kit type was small but significant differences in results were observed between assay kit types. The findings suggest that endotoxin concentration in samples can be ranked within laboratories, but not necessarily between laboratories. However, some of the variation between laboratories has been reduced by a common extraction protocol which suggests the possibility of further standardization that may lead to better comparability between laboratories.

Air Pollution, Indoor↗

The incidence of anatomic variations and sinus opacities in pediatric patients with chronic sinonasal symptoms.

OBJECTIVES: In this study, our purpose was to determine the incidence of paranasal sinus anatomic variations and their relationship with sinus opacities in pediatric patients. PATIENTS AND METHODS: A total of 44 children (age range 3 to 16 years) unresponsive to maximum medical therapy were evaluated with coronal paranasal sinus computed tomography. RESULTS: Computed tomographic evaluations revealed that 70.5% (31/44) of the patients had at least one anatomic variation, the most common being septal deviation, followed by concha bullosa and agger nasi cells. Sinus opacities were found in 81.8% (36/44) of the patients, of whom 9 had single and 27 had multiple involvement of sinus groups. The most commonly involved sinuses were anterior ethmoids and maxillary sinuses, followed by posterior ethmoids, sphenoid and frontal sinuses. Patients with single, multiple, and no anatomic variations had 78.9% (15/19), 83.3% (10/12), and 84.6% (11/13) opacities, respectively. CONCLUSION: The incidence of anatomic variations was found to be similar to that reported for adults in the literature except for nasal septal deformity which was found lower. Our results showed no correlation between bony anatomic variations and sinus opacities in children.

Adolescent↗

High-throughput identification of proteins and unanticipated sequence modifications using a mass-based alignment algorithm for MS/MS de novo sequencing results.

With the increasing availability of de novo sequencing algorithms for interpreting high-mass accuracy tandem mass spectrometry (MS/MS) data, there is a growing need for programs that accurately identify proteins from de novo sequencing results. De novo sequences derived from tandem mass spectra of peptides often contain ambiguous regions where the exact amino acid order cannot be determined. One problem this poses for sequence alignment algorithms is the difficulty in distinguishing discrepancies due to de novo sequencing errors from actual genomic sequence variation and posttranslational modifications. We present a novel, mass-based approach to sequence alignment, implemented as a program called OpenSea, to resolve these problems. In this approach, de novo and database sequences are interpreted as masses of residues, and the masses, rather than the amino acid codes, are compared. To provide further flexibility, the masses can be aligned in groups, which can resolve many de novo sequencing errors. The performance of OpenSea was tested with three types of data: a mixture of known proteins, a mixture of unknown proteins that commonly contain sequence variations, and a mixture of posttranslationally modified known proteins. In all three cases, we demonstrate that OpenSea can identify more peptides and proteins than commonly used database-searching programs (SEQUEST and ProteinLynx) while accurately locating sequence variation sites and unanticipated posttranslational modifications in a high-throughput environment.

Algorithms↗

VSD: a database for schizophrenia candidate genes focusing on variations.

Schizophrenia is a common mental disease characterized by delusions, hallucinations, and formal thought disorder. It has been demonstrated with genetic evidence that the disease is a polygenic disorder. Pharmacological, neurochemical, and clinical studies have suggested a number of schizophrenia susceptibility loci. In order to systematically search for genes with small effect in the development of schizophrenia, a database called VSD was established to provide variation data for publicly available candidate genes. Most of the genes encode neurotransmitter receptors, neurotransmitter transporters, and the enzymes involved in their metabolism. Other candidate genes extracted from published literature are also included. The variation information has been collected from publicly available mutation and polymorphism databases such as dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the most abundant form of collected variations. Reference sequences from NCBI's RefSeq database are used as references when positioning variation at transcript and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid changes in the functional sites or domains of proteins are distinguished since they are more likely to affect protein function and would be target SNPs for association studies. In addition to variation data, gene descriptions, enzyme information, and other biological information for each gene locus are also included. The latest version of VSD contains 23,648 variations assigned to a total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be accessed via the World Wide Web (www.chgb.org.cn/vsd.htm) and will be developed as an up-to-date and comprehensive locus-specific resource for identifying susceptibility genes for schizophrenia.

Databases, Nucleic Acid↗

The origin of gonadal arteries in human fetuses: anatomical variations.

Testicular arterial anatomy has been well studied because of its importance in testicular physiology, as well as testicular and renal surgery. In contrast to classical anatomical descriptions, it may originate from the suprarenal or lumbar arteries or a high-positioned origin, course behind the inferior vena cava or be doubled or arise from an inferior polar renal artery. Different developmental patterns as variations in relation to origin, course and number of the renal and gonadal arteries have been reported and discussed. This study was performed on 90 spontaneously aborted fetuses obtained from two different hospitals in Konya. The study was carried out on the testicular or ovarian arteries of fetuses fixed by immersion in 10% formalin. In all, 180 gonadal arteries were studied and 16 of them were found to have variations in their origin (8.8%). The variations of the gonadal artery origins could be classified into four types. The gonadal artery variations were more commonly found in male than the female fetuses and on the right side rather than the left. In the present study, it is clear that these variations are important not only from the developmental point of view or research interest, but they also may explain some pathological conditions. Knowledge of these variations may help to avoid the clinical complications especially during radiological examinations and/or surgical approaches in this region.

Abortion, Spontaneous↗

Hotspots for copy number variation in chimpanzees and humans.

Copy number variation is surprisingly common among humans and can be involved in phenotypic diversity and variable susceptibility to complex diseases, but little is known of the extent of copy number variation in nonhuman primates. We have used two array-based comparative genomic hybridization platforms to identify a total of 355 copy number variants (CNVs) in the genomes of 20 wild-born chimpanzees (Pan troglodytes) and have compared the identified chimpanzee CNVs to known human CNVs from previous studies. Many CNVs were observed in the corresponding regions in both chimpanzees and humans; especially those CNVs of higher frequency. Strikingly, these loci are enriched 20-fold for ancestral segmental duplications, which may facilitate CNV formation through nonallelic homologous recombination mechanisms. Therefore, some of these regions may be unstable "hotspots" for the genesis of copy number variation, with recurrent duplications and deletions occurring across and within species.

Animals↗

The prevalence of skin diseases in the elderly: analysis of 4099 geriatric patients.

BACKGROUND: The geriatric population is composed of persons over 65 years of age, and few studies are available on the dermatologic diseases in this group. METHODS: Data on a total of 4099 geriatric patients admitted between the years 1999-2003 were analyzed. Hospital-based patient registry records were used for data collection. The data were analyzed according to age, sex, and time of admittance. RESULTS: The five most frequently encountered diseases in elderly patients were eczematous dermatitis, fungal infections, pruritus, and bacterial and viral infections. The most common disorders in males were fungal, bacterial, and viral infections, disorders of the feet, cutaneous ulcers, and vesiculo-bullous diseases, whereas, in females, they were immune-rheumatologic diseases and disorders of the mucous membranes. The five most frequently encountered diseases were significantly different in geriatric age subgroups. In the younger age group, pruritus, disorders due to sun exposure, and precancerous lesions and skin carcinomas were less common, whereas eczematous dermatitis was more common. The frequencies of some diseases showed significant seasonal variations. Infestations were more common in spring and summer, fungal infections were more common in summer but less so in winter, pruritus was more common in autumn but less so in spring, disorders due to sun exposure were more common in spring, and benign neoplasia were more common in autumn. In 2003, benign neoplasia, precancerous lesions and skin carcinomas, and immune-rheumatic disorders were more common, but vesicular and bullous diseases, fungal infections, and cutaneous lymphomas were less common when compared with the year 1999. CONCLUSIONS: This study provides important data on the frequency of dermatologic diseases in elderly patients, and shows variations in the frequency depending on age, gender, and season. We believe that this study will create awareness about the extent and patterns of dermatologic problems in geriatric patients.

Aged↗

Variation in the use of red blood cell transfusions. A study of four common medical and surgical conditions.

This study assessed variation in red cell transfusion practice among adult patients hospitalized with ulcer disease (ULCER), and those undergoing coronary artery bypass grafting (CABG), hip surgery (HIP), or total knee replacement (KNEE). The study design was a retrospective analysis of the 1989 MedisGroups Hospital Comparative Database, and the participants were adult patients presenting for their first admission with ULCER (N = 4,664), CABG (N = 6,812), HIP (N = 4,131) or KNEE (N = 3,042) in the MedisGroups Hospital Comparative Database. Outcome measures were whether a patient was transfused, and the number of units transfused. Logistic regression was used to analyze the decision to transfuse, and linear regression to analyze the number of units transfused. In these analyses, patient characteristics, hospital characteristics, and unique hospital identity were used as independent variables. The percentage of patients transfused was ULCER 50%, CABG 81%, HIP 69%, and KNEE 51%. The range among hospitals in the percentage of patients transfused was ULCER 11% to 76%, CABG 51% to 100%, HIP 36% to 95%, and KNEE 9% to 97%. When only patient characteristics were entered in the linear regression analyses, the R2 values were ULCER 0.33, CABG 0.11, HIP 0.11, and KNEE 0.07. When hospital was added, the R2 increased to ULCER 0.38, CABG 0.29, HIP 0.19, and KNEE 0.20 (P < 0.0001 for the change for all analyses). The results of the logistic regression analyses of the probability of transfusion were similar. There is substantial interhospital variation in the proportion of patients transfused and number of units transfused in the four conditions studied. Patient demographic and clinical characteristics explain a substantial proportion of the variation in transfusion practices for ulcer patients, but little of the variation in the three surgical conditions.

Adult↗

Colony variations in Candida species.

One hundred isolates of seven Candida species and three isolates of Saccharomyces cerevisiae were plated on phloxine B agar and examined for variations in the morphology or colour of colonies that developed. Colony variations were found in 9 of 12 C. parapsilosis isolates, 8 of 13 C. tropicalis isolates, 4 of 9 C. krusei isolates and 12 of 30 C. albicans isolates. None of 23 C. glabrata isolates grew on the test medium. Variant colonies often generated further different colony forms on secondary subculture. The rate of production of fimbriate and rhizoid colonies by two C. albicans isolates varied with agar thickness and the nutrient content of the medium. These results suggest that colony variation is a common property among isolates of many Candida species and that strict control of agar medium thickness and composition is essential for reproducible screening of isolates for colony variations.

Candida↗

The evolution of the phenotypic covariance matrix: evidence for selection and drift in Melanoplus.

Phenotypic variation in trait means is a common observation for geographically separated populations. Such variation is typically retained under common garden conditions, indicating that there has been evolutionary change in the populations, as a result of selection and/or drift. Much less frequently studied is variation in the phenotypic covariance matrix (hereafter, P matrix), although this is an important component of evolutionary change. In this paper, we examine variation in the phenotypic means and P matrices in two species of grasshopper, Melanoplus sanguinipes and M. devastator. Using the P matrices estimated for 14 populations of M. sanguinipes and three populations of M. devastator we find that (1) significant differences between the sexes can be attributed to scaling effects; (2) there is no significant difference between the two species; (3) there are highly significant differences among populations that cannot be accounted for by scaling effects; (4) these differences are a consequence of statistically significant patterns of covariation with geographic and environmental factors, phenotypic variances and covariances increasing with increased temperature but decreasing with increased latitude and altitude. This covariation suggests that selection has been important in the evolution of the P matrix in these populations Finally, we find a significant positive correlation between the average difference between matrices and the genetic distance between the populations, indicating that drift has caused some of the variation in the P matrices.

Animals↗

Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+ response in patients with chronic hepatitis C.

Hepatitis C virus (HCV) variation in specific T-cell epitopes may represent a mechanism of viral persistence in chronic infection. We examined the HCV non-structural protein 3 (NS3), including the immunologically relevant epitopes HCV NS3-2 KLVALGINAV (human leukocyte antigen [HLA]-A2-restricted) and HCV NS3-1391 LIFCHSKKK (HLA-A3-restricted), in 22 HLA-A2+ patients with chronic infection. Significant amino acid variation was found in HCV NS3-2 epitope sequences when compared to the HCV-1 prototype virus. Six of the nine different HCV NS3-2 peptide variants were identified in patients with HCV NS3-2-specific CD8+ cells, detected with an HLA-A2 tetramer made with the HCV-1 prototype peptide. Phylogenetic analysis, including HCV reference sequences other than HCV-1, suggested however that most of the variations in the HCV NS3-2 epitope could be related to genetic heterogeneity between HCV reference subtypes. Variation was less common when comparing HCV NS3-2 epitope sequences from the clinical isolates to the most-closely related HCV reference subtype in each case. Some subtype-independent variations were found in epitopic residues probably important for T-cell receptor interaction. In contrast, no significant variation was found in HLA primary anchor sites, flanking regions, or in the contiguous HLA A3-restricted CD8+ T-cell epitope. Ongoing variation was not evident in two selected patients with follow-up. In conclusion, (i) the HCV NS3-2 epitope is not conserved between different HCV strains/subtypes, and (ii) an HLA-A2 tetramer loaded with the HCV-1 prototype NS3-2 peptide may still detect NS3-specific CD8+ cells in some patients with variant viruses. These data may be useful to improve T-cell assays using HCV NS3 peptides, taking into account the genetic diversity of this virus.

Adult↗