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The malaria cauldron of Southeast Asia: conflicting strategies of contiguous nation states.

The past half-century or so has witnessed dramatic failures but also some successes in control of malaria in the world at large. South and Southeast Asia have had their share of both outcomes, a scenario that reflects many variables in control programs: technology, management strategy, human and financial resources. However, at least equally culpable have been major wars and minor conflicts, economic growth and stagnation, inequity of opportunity, urbanisation, deforestation, changing transport and communications. The history of malaria is thus an integral part of the broader political and economic evolution of the region, as well as the story of the wisdom and unwisdom of malaria specialists. In positive reflection on the latter, systematic organisational effort using standard tools of trade has seen the gradual elimination of major malaria foci from central plain regions of a number of nations in this large region, with residual foci at forested border areas. In many cases there is good evidence of sustainability of elimination in defined areas but the differing success stories reflect in part conflicting strategies in neighboring nation states. On the other hand, physical conflicts, population migration, inequitable economic change, border instability and many other socio-economic variables can be clearly seen to undermine the most ingenuous strategies. Undoubtedly the single most important negative ingredient is the rise and spread of multi-drug resistant falciparum malaria that has its epicenter in Southeast Asia, from which it threatens the world in insidious fashion. Containment of this phenomenon has been the focus of attention for 30 years, more particularly the past decade, and represents the greatest challenge at this time in predicting the continuing impact of malaria globally on human history. So too does the compelling necessity to link malaria control with macro and micro economic planning. This challenge impinges on the sovereignty of individual nations in this region, for they exist in contiguity, so that successful applications of technology require collaborative political determination.

Animals↗

Review of studies on flight attendant health and comfort in airliner cabins.

BACKGROUND: A number of studies have examined the effect of the airliner cabin environment and other factors on the health and comfort of flight attendants (FAs), but no comprehensive review of such studies is available. METHODS: This paper reviews studies conducted after 1980 that addressed FA short-term health and comfort effects. Relevant literature was identified using the National Institute of Health's PUBMED database. RESULTS: Twenty-one studies were identified and classified into two types: in-flight surveys and surveys of general flight experiences. Most studies used questionnaires to obtain perceptions of the cabin environment, comfort, and health-related symptoms, but some included objective measurements. Only a few studies used a random sample or control groups. Effects of confounding variables generally have not been analyzed. DISCUSSION: Most studies shared some weaknesses such as poor response rate, significant response bias, exclusive reliance on questionnaires, or limited analysis. Taken together, the studies indicate that various complaints and symptoms reported by FAs appear to be associated with their job duties and with the cabin environment. Most notable are "dryness" symptoms attributable to low humidity and "fatigue" symptoms associated with factors such as disruption of circadian rhythm. Practically all symptoms are exacerbated by longer flight durations. Studies citing problems of "poor aircraft cabin air quality" tend to be weak in design and have addressed only general flight experiences of FAs. Although certain FA complaints are consistent with possible exposure to air pollutants, the relationship has not been proven and such complaints also are consistent with causes other than poor air quality.

Air Pollution, Indoor↗

Peripunctal melanocytic nevi. Distinctive clinical findings and differential diagnosis.

A peripunctal nevus is a rare lesion of the eyelid margin, six examples of which are included in this report. The lesions all involved the lower punctum and had been present for many years without producing epiphora. In addition to their variable clinical pigmentation and translucent appearance on biomicroscopy, all shared several other diagnostically useful clinical features: an overall dome-shape with a fine micronodularity; a prominent ramifying vascularity; and, most importantly, circumferentially swollen punctal lips that created a slit-like punctal orifice. Histopathologically, the lesions were predominantly or exclusively subepithelial melanocytic nevi and were demonstrated not to compress the punctum or canaliculus. Infiltration of the nevus cells within the orbicularis striated muscle fibers was a common finding owing to the latter's superficial location in the eyelids. If patients request excision for cosmetic reasons, these lesions are best managed by a horizontal circular shave excision with the temporary placement of a silicon punctual plug. The differential diagnosis includes cyst, papilloma, melanoma, and basal cell carcinoma.

Adolescent↗

Characteristics of national, divisional, and club male alpine ski racers.

Forty-two Canadian male alpine ski racers of either club, divisional, or national team status were studied by group to evaluate the physiological parameters that distinguish these athletes. Measurements of physical characteristics, flexibility, muscular power and endurance, aerobic and anaerobic power, and isokinetic leg strength were made. Correlations of the test variables were performed to evaluate the test battery for validity. While there were few physiological differences between the national and divisional skiers, club skiers scored consistently lower (P less than 0.01) in maximum number of sit-ups, vertical jump, anaerobic endurance, muscular power, 2-mile run time, isokinetic leg strength at 30 degrees X s-1, and hamstring-to-quadriceps strength ratio. However, no significant differences between groups were observed in sum of the skinfolds, flexibility, and isokinetic strength at 180 degrees X s-1. There were also no differences in VO2max between club and national team skiers. Highly-significant correlations were found between selected test variables, which indicated that some of the physiological parameters shared common variance. It seems that many of these physiological tests do not discriminate between national and divisional skiers. Club skiers would, however, appear to benefit from training programs designed to develop leg strength, power, and anaerobic endurance.

Humans↗

Antigen-specific receptor molecules isolated from murine T lymphocytes.

Hapten-specific receptor material can be isolated from sensitized murine T and B lymphocytes by the use of hapten-coupled nylon discs. The structural element shared between T and B cell receptors is the variable region of immunoglobulin heavy chains (VH), while known constant immunoglobulin domains appear not to be part of the T cell receptor molecule. The rules governing VH expression (i.e. NPb-idiotype expression) in the B and the T cell compartments are, however, different. Allotype-linked VH (idiotype) expression on T cell molecules was used in genetic reconstitution experiments to prove that the material under study is an endogenous T cell product. With the data available it seems reasonable to view the T cell molecules as representing surface receptors for antigen although this point needs further investigation.

Animals↗

Flexible maximum likelihood methods for assessing joint effects in case-control studies with complex sampling.

Case-control studies can often be made more efficient by using frequency matching, randomized recruitment, stratified sampling, or two-stage sampling. These designs share two common features: (1) some "first-stage" variables are ascertained for all study subjects, while complete variable ascertainment is carried out for only a selected subsample, and (2) the subsampling of subjects for "second-stage" variable ascertainment depends jointly on their disease status and their observed first-stage variables. Because first-stage variables alter the subsampling fractions, standard analyses require a multiplicative specification of any joint effects of a second- and a first-stage variable. We show that by making use of missing data methods, maximum likelihood estimates can be obtained for risk parameters of interest, even those characterizing interactions between first- and second-stage variables. Joint effects can thus be modelled flexibly, with allowance for both additive and multiplicative models. Preliminary data from a case-control study of lung cancer as related to age, sex, and smoking provide an example, leading to the suggestion that the combined effect of age and smoking is multiplicative.

Adult↗

Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients.

Gorlin syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, medulloblastomas, ovarian fibromas, and a variety of developmental defects. All affected individuals share certain key features, but there is significant phenotypic variability within and among kindreds with respect to malformations. The gene (NBCCS) maps to chromosome 9q22, and allelic loss at this location is common in tumors from Gorlin syndrome patients. Two recessive cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC) and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual, dominant mutations in these genes have been proposed as the cause of Gorlin syndrome. This study presents cytogenetic and molecular characterization of germ-line deletions in one patient with a chromosome 9q22 deletion and in a second patient with a deletion of 9q22-q3l. Both have typical features of Gorlin syndrome plus additional findings, including mental retardation, conductive hearing loss, and failure to thrive. That Gorlin syndrome can be caused by null mutations (deletions) rather than by activating mutations has several implications. First, in conjunction with previous analyses of allelic loss in tumors, this study provides evidence that associated neoplasms arise with homozygous inactivation of the gene. In addition, dominant mutations of the XPAC and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since the two patients described have null mutations. Finally, phenotypic features that show variable expression must be influenced by genetic background, epigenetic effects, somatic mutations, or environmental factors, since these two patients with identical alterations (deletions) of the Gorlin syndrome gene have somewhat different manifestations of Gorlin syndrome.

Adolescent↗

A European perspective on pediatric cochlear implantation, rehabilitation services, and their educational implications.

OBJECTIVE: To assess the educational implications of pediatric cochlear implantation from the perspective of the implant team. METHODS: Coordinators of pediatric cochlear implant teams throughout Europe took part in a survey using forced-choice questions. Fifty-four centers were originally sent the questionnaire; 41 centers replied. RESULTS: Of 504 children planned to receive cochlear implants in Europe during 1996, 54% (273/504) were aged 2-5 years and 12% (60/504) aged 0-2 years, indicating a trend toward pediatric implantation in younger children. There is a strong commitment to rehabilitation in the teams; 66% (27/41) employ a teacher of the deaf, the ratio of medical/audiological to rehabilitation personnel is 1:2, and 76% (31/41) of the implant teams visit local educators. Of all the children receiving implants to the date of this report, 23% were considered to be in unfavorable educational environments; these were environments where children were taught with an emphasis on sign language and little expectation from audition, and mainstream provision without support from experienced teachers of the deaf. CONCLUSION: There is a high staff input to children with cochlear implants from implant rehabilitation personnel over and above the input received in the educational environment. Hence, it is important for the school and the implant team to mutually agree on their shared responsibilities. Moreover, as the provision of service is variable and inconsistent, the development of guidelines for practice in each country should ensure consistency of rehabilitative and educational support to children with cochlear implants.

Adolescent↗

[Coevolutive mechanisms between retroviruses and their hosts. The murine mammary tumor model].

Mouse mammary tumor virus (MMTV) is a type B retrovirus that is transmitted as an infectious milk-borne particle and that causes mammary carcinomas by insertional activation of cellular protooncogenes. Germ line infections result in endogenous Mtv proviruses integrated in the genome of most mouse strains. These endogenous proviruses have been integrated into the genomes of mice for only the past 3-5 million years. The open reading frame present in the 3' long terminal repeat (LTR) of the provirus encodes a superantigen (SAg) which is able to stimulate a large proportion of T cells sharing a common T-cell receptor beta chain variable domain (v beta). Expression of this SAg is critical to the MMTV life cycle. After expression of the SAg in B cells a significant number of T cells are recruited to respond to these MMTV infected cells. As a consequence both the T cells expressing the relevant TCR V beta domain and the infected B cells become activated and start dividing. This would facilitate integration of MMTV and amplify the number of virus infected lymphocytes. Most likely during lactation the mammary glands become receptive to viral infection. The presence of endogenous Mtvs induces an early clonal deletion of reactive T cells. For this reason it has been argued that the presence of these proviruses confers a selective advantage to the mouse population by protecting the host from infection with an exogenous MMTV coding for a cross-reactive SAg. However, recent results discussed herein suggest that Mtv proviruses may also be detrimental to the mouse population by participating in recombinations with exogenous MMTVs, giving rise to highly tumorigenic recombinant particles. These results are discussed in the light of recent reports suggesting the involvement of viral sequences with a high homology to MMTV in human mammary tumorigenesis.

Animals↗

[Observer variability in the radiologic interpretation of interstitial lung disease].

OBJECTIVES: To study intra and interobserver variability of two pediatric neumologists in X-ray readings of interstitial lung disease (ILD), to determine the effect of clinical data on the readings, and to evaluate their interpretation in terms of the histopathology diagnosis. DESIGN: Prospective, cross sectional, comparative, blinded. SETTING: The Instituto Nacional de Pediatria of Mexico City. MATERIAL AND METHODS: Chest X-rays of 45 ILD pediatric patients with diagnosis confirmed by open lung biopsy were read by the two observers three times at two weeks intervals and in a randomized fashion. The observers were blinded to previous readings of both observers as well as to the diagnosis. The first two readings were done with no clinical information given to the observers, but some was given for the third reading (age of inception, length of evolution, and main symptoms at time of the X-rays). A classification in one of 5 patterns (lineal, reticular, reticulonodular, grounded glass, honeycomb) was established by the observers. Associations of patterns with anatomopathological diagnosis was explored. Weighted kappa was used in the statistical analysis. RESULTS: With one exception, good agreement (Kw 0.57-0.88) was found intra and interobservers. CONCLUSION: We believe the low variability is the result of the 15 years of shared experience of the two observers participating in this study.

Adolescent↗

The effects of genetic factors on selected indicators of the activity of the sympathoadrenal system and the renin-angiotensin-aldosterone system in twins.

BACKGROUND: There are numerous data indicating a significant role of the sympathoadrenal system and the reninangiotensin- aldosterone system in the regulation of blood pressure and the pathogenesis of essential hypertension. However, the genetic background of essential hypertension remains unclear. AIM: To determine the effects of genetic factors on selected indicators of the activity of the sympathoadrenal system and the renin-angiotensin-aldosterone system in twins. METHODS: We studied 39 monozygotic twin pairs (age 33+/-7 years) and 37 same-gender dizygotic twin pairs (age 36+/-7 years). We measured blood and urine adrenaline (A), noradrenaline (NA), dopamine (DA) and aldosterone (ALD) levels, as well as plasma renin activity (PRA) and serum angiotensin-converting enzyme (ACE) activity. Parameters of the genetic models for age- and gender-adjusted data were estimated by model fitting and path analysis technique using LISREL 8. RESULTS: The effects of genetic factors on the variability of blood and urine catecholamine levels were 69% and 65% for A, 42% and 76% for NA, and 58% and 40% for DA, respectively. We also found shared environmental components for blood NA (28%) and urine DA (17%). Genetic factors accounted for 36% of the variability of PRA and 80% of the variability of ACE. ALD levels were related only to environmental factors (including a shared environmental component, estimated at 25%, for urine ALD). CONCLUSIONS: We found significant effects of genetic factors on the activity of the sympathoadrenal system, as indicated by blood and urine catecholamine levels. We also found the effect of genetic factors on PRA and ACE, but not on aldosterone levels.

Adrenal Glands↗

Polymorphism in the immunoglobulin VH gene V1-69 affects susceptibility to rheumatoid arthritis in subjects lacking the HLA-DRB1 shared epitope.

OBJECTIVE: To investigate the contribution of polymorphism in the immunoglobulin heavy chain variable region V1-69 gene set to genetic susceptibility to rheumatoid arthritis (RA) in Czech and British patients. METHODS: We used V1-69 gene sequence-specific polymerase chain reaction (PCR) and restriction enzyme digestion to study polymorphism in the V1-69 gene set in germline DNA of 109 Czech and 159 British RA patients and 164 ethnically matched controls. Polymorphism was further studied by nucleotide sequencing of the V1-69 gene locus in germline DNA. RESULTS: We found that all patients and controls had at least one V1-69 gene copy. In the Czech RA cohort, the dimorphic nucleotide in codon 73 of V1-69 (GAA or AAA) was present in the homozygous form 73(A/A) in 31 of 109 (28.4%) RA patients vs 12 of 79 (15.2%) controls [odds ratio (OR)=2.22, P<0.001]. When the RA patients and controls were classified according to HLA shared epitope (SE) status, 73(A/A) was found in 18 of 76 (23.7%) SE(+) patients compared with 13 of 38 (34.2%) SE(-) patients, four of 12 (18.2) SE(+) controls and eight of 57 (14%) SE(-) controls. This suggests that homozygosity for the dimorphic sequence 73(A) contributed to susceptibility to RA in SE(-) Czech individuals (OR=3.2, P<0.001). The most striking observation was that none of the 38 SE(-) Czech patients, compared with 11 of 76 (14.5%) SE(+) RA patients, three of 22 (13.6%) SE(+) and 11 of 57 (19.3%) SE(-) ethnically matched controls, were homozygous for the alternative dimorphic sequence 73(G/G) (OR=9.1, P<0.05). These data, however, were not replicated in a Caucasoid British RA population. CONCLUSION: The dimorphic sequence at codon 73 (73(A/A)) of the V1-69 gene contributes to genetic susceptibility in SE(-) Czech RA patients.

Adult↗

HIV and hepatitis C virus risk in new and longer-term injecting drug users in Oslo, Norway.

Research has focused on understanding injecting drug use initiation in the era of HIV/AIDS. However, differences between new and longer-term injecting drug users (IDUs) have not received as much attention. This study examined injecting initiation experience, risk and risk reduction practices, and self-reported HIV and hepatitis C virus (HCV) testing practices and infection among new (injecting < or =4 years) and longer-term IDUs. Data from 3 cross-sectional surveys in 1992, 1994, and 1997 of syringe exchange program (SEP) users in Oslo, Norway, were used. Approximately one fifth of IDUs were new injectors. New IDUs were increasingly indistinguishable from longer-term IDUs in terms of socio-demographics, risk practices, and HIV and HCV testing. The prevalence of HIV infection remained low (5%); in contrast, approximately two thirds of all SEP users reported being HCV-infected. Known HCV infection status had no impact on syringe sharing; most HCV-infected SEP users reported sharing syringes, regardless of the duration of injecting. The only variable associated with HCV infection was injecting < or =4 years (adjusted odds ratio = 0.2; 95% confidence interval = 0.1-0.4). Increased similarity in age between new and longer-term IDUs may have contributed to the rapid spread of HCV infection by facilitating mixing patterns between HCV-infected and -susceptible IDUs.

Adolescent↗

Statistical detection of chromosomal homology using shared-gene density alone.

MOTIVATION: Over evolutionary time, various processes including point mutations and insertions, deletions and inversions of variable sized segments progressively degrade the homology of duplicated chromosomal regions making identification of the homologous regions correspondingly difficult. Existing algorithms that attempt to detect homology are based on shared-gene density and colinearity and possibly also strand information. RESULTS: Here, we develop a new algorithm for the statistical detection of chromosomal homology, CloseUp, which uses shared-gene density alone to fully exploit the observation that relaxing colinearity requirements in general is beneficial for homology detection and at the same time optimizes computation time. CloseUp has two components: the identification of candidate homologous regions followed by their statistical evaluation using Monte Carlo methods and data randomization. Using both artificial and real data, we compared CloseUp with two existing programs (ADHoRe and LineUp) for chromosomal homology detection and found that in general CloseUp compares favorably. AVAILABILITY: CloseUp and supplementary information are available at http://www.igb.uci.edu/servers/cgss.html CONTACT: pfbaldi@ics.uci.edu.

Algorithms↗

Antigenic variation by Borrelia hermsii occurs through recombination between extragenic repetitive elements on linear plasmids.

The relapsing fever agent Borrelia hermsii undergoes multiphasic antigenic variation through gene conversion of a unique expression site on a linear plasmid by an archived variable antigen gene. To further characterize this mechanism we assessed the repertoire and organization of archived variable antigen genes by sequencing approximately 85% of plasmids bearing these genes. Most archived genes shared with the expressed gene a <or= 62 nucleotide (nt) region, the upstream homology sequence (UHS), that surrounded the start codon. The 59 archived variable antigen genes were arrayed in clusters with 13 repetitive, 214 nt long downstream homology sequence (DHS) elements distributed among them. A fourteenth DHS element was downstream of the expression locus. Informative nucleotide polymorphisms in UHS regions and DHS elements were applied to the analysis of the expression site of relapse serotypes from 60 infected mice in a prospective study. For most recombinations, the upstream crossover occurred in the UHS's second half, and the downstream crossover was in the DHS's second half. Usually the closest archival DHS element was used, but occasionally a more distant DHS was employed. The downstream extragenic crossover site in B. hermsii contrasts with the upstream [corrected] extragenic crossover site for antigenic variation in African trypanosomes.

Antigenic Variation↗

Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor.

Two rat monoclonal antibodies (mAbs), 44-22-1 and 46-6B5, which recognize an alloreactive cytotoxic clone, 3F9, have been further tested on a panel of T hybridomas and cytotoxic T-cell clones for binding and functional activities. The mAbs recognized only those cells sharing the expression of the T-cell receptor beta-chain variable region gene V beta 6 with 3F9. All V beta 6+ cells were activated by these mAbs under cross-linking conditions and their antigen-specific activation was blocked by soluble mAb. Furthermore, depletion of 46-6B5+ normal lymph node T cells eliminated all cells expressing the epitope recognized by 44-22-1 and V beta 6 mRNA.

Animals↗

Models for the supply of pharmacists.

The BHPr (formerly Bureau of Health Professions) Supply Model for pharmacists is presented and analyzed. Recommendations are made for improvement of the supply model. Included are considerations of additional variables and improvement of tables of separation rates to more accurately reflect working patterns of male and female pharmacists. The supply model shares many features of supply models for other health professions such as nursing and medicine. The variables suggested for improvement of supply determinations parallel supply measures of other health professions also. The adoption of suggestions for improvement of the pharmacy supply model to other health professions' supply models is suggested.

Age Factors↗

Hereditary and environmental influences on the variation of thyroid hormones in normal male twins.

Heritability of the variation of the plasma total and unbound T4 (free T4), T3, T4-binding globulin (TBG), and TSH concentrations was investigated in 15 monozygotic and 15 dizygotic male twin pairs. The variability in plasma of total (58%) and free T4 (72%) concentrations was significantly less (P less than 0.01) in the twin pairs than in unrelated men. Half of the variability of T3 (P less than 0.05), TBG (P less than 0.05), and TSH (P less than 0.05) was affected by influences shared by the twin pairs in both monozygotic and dizygotic twin pairs. The heritability index for variability of the plasma total T4 and free T4 was greater than 28% (P less than 0.05), and it was 25% or less for T3 and TBG. Variation in TBG accounted for less than 20% (P less than 0.001) of the variation in thyroid hormone concentrations. The results indicate that familial factors, which are affected by genetic and/or environmental factors, influence the variation of plasma TBG, TSH, T4, free T4, and T3 concentrations among normal men. Genetic factors influenced the variation in plasma T4 and free T4 levels.

Humans↗