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PubMed2005

A managed clinical network for cardiac services: set-up, operation and impact on patient care.

PURPOSE: To investigate the set up and operation of a Managed Clinical Network for cardiac services and assess its impact on patient care. METHODS: This single case study used process evaluation with observational before and after comparison of indicators of quality of care and costs. The study was conducted in Dumfries and Galloway, Scotland and used a three-level framework. Process evaluation of the network set-up and operation through a documentary review of minutes; guidelines and protocols; transcripts of fourteen semi-structured interviews with health service personnel including senior managers, general practitioners, nurses, cardiologists and members of the public. Outcome evaluation of the impact of the network through interrupted time series analysis of clinical data of 202 patients aged less than 76 years admitted to hospital with a confirmed myocardial infarction one-year pre and one-year post, the establishment of the network. The main outcome measures were differences between indicators of quality of care targeted by network protocols. Economic evaluation of the transaction costs of the set-up and operation of the network and the resource costs of the clinical care of the 202 myocardial infarction patients from the time of hospital admission to 6 months post discharge through interrupted time series analysis. The outcome measure was different in National Health Service resource use. RESULTS: Despite early difficulties, the network was successful in bringing together clinicians, patients and managers to redesign services, exhibiting most features of good network management. The role of the energetic lead clinician was crucial, but the network took time to develop and 'bed down'. Its primary "modus operand" was the development of a myocardial infarction pathway and associated protocols. Of sixteen clinical care indicators, two improved significantly following the launch of the network and nine showed improvements, which were not statistically significant. There was no difference in resource use. DISCUSSION AND CONCLUSIONS: The Managed Clinical Network made a difference to ways of working, particularly in breaching traditional boundaries and involving the public, and made modest changes in patient care. However, it required a two-year "set-up" period. Managed clinical networks are complex initiatives with an increasing profile in health care policy. This study suggests that they require energetic leadership and improvements are likely to be slow and incremental.

Journal Article↗
PubMed2000

Regulation of type I collagen genes expression.

Type I collagen is the major component of many extracellular matrices, and its accumulation characterizes most fibrotic processes. It is synthesized by a small number of discrete cell types, including fibroblasts, osteoblasts and odontoblasts. Analysis of transgenic mice harbouring different segments of the promoters of the mouse pro-alpha1 (I) and pro-alpha2 (I) genes has led to the conclusion that this tissue-specific expression is controlled by different cis-acting elements which are responsible for the expression of type I collagen genes in different type I collagen-producing cells. Transacting factors which bind to these different tissue-specific elements are still unknown, but they probably act by modifying the chromatin structure. In fibroblastic cells, various soluble molecules can modulate the transcription of type I collagen genes. Analysis of the pro-alpha1 (I) and pro-alpha2 (I) proximal promoters has led to the identification of different cis-acting elements which can modulate the expression of reporter genes, in transfection experiments. Among these cis-acting elements, a sequence located between -378 and -183 bp in the human pro-alpha2 (I) promoter appears to mediate the transcriptional effects of transforming growth factor-beta. It binds a large multimeric complex which contains Sp1, as well as AP1 and other DNA-binding proteins which have not yet been identified.

Animals↗
PubMed2006

Functional analysis of transcription factors by microparticle bombardment.

This chapter describes a method for rapid gene expression assays in Arabidopsis. Three distinct plasmids are codelivered into leaves by microparticle bombarment. The first one carries a transacting factor gene driven by the cauliflower mosaic virus (CaMV) 35S promoter. The second plasmid includes a reporter luciferase (LUC) gene transcribed from a promoter containing the TF binding site(s). The third plasmid contains a reference beta-glucuronidase (GUS) gene transcribed from the 35S-CaMV promoter, which is used to normalize data derived from independent experiments. This method could be applied to study systematically the functional properties of Arabidopsis transcription factors as well as to identify promoters and control region(s) regulated by specific transcription factors.

Arabidopsis↗
PubMed1997

c-Jun/AP-1, but not NF-kappa B, is a mediator for oxidant-initiated apoptosis in glomerular mesangial cells.

Oxidant stress is a trigger of cell death in various cell types. Hydrogen peroxide (H2O2) induced mesangial cell death with nuclear condensation and DNA fragmentation typical of apoptosis. To explore molecular mechanisms involved in this process, redox-sensitive transacting molecules, activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B), have been brought into focus. Northern blot analysis and transient transfection assays using reporter plasmids showed that H2O2 activated both AP-1 and NF-kappa B. Downregulation of c-Jun/AP-1 using a transdominant negative mutant of c-jun, an antisense c-jun, or a pharmacologic inhibitor curcumin inhibited the H2O2-initiated apoptosis. In contrast, inhibition of the NF-kappa B activation using a transdominant negative mutant of the p50 NF-kappa B subunit did not affect the H2O2-triggered cellular death. These data elucidated that c-Jun/AP-1, but not NF-kappa B, is involved in the oxidant-initiated cell death program in glomerular mesangial cells.

Animals↗
PubMed1999

DNA sequence and expression of a defective mer operon from Pseudomonas K-62 plasmid pMR26.

pMRB01 cloned from Pseudomonas K-62 plasmid pMR26 conferred bacterial hypersensitivity to organomercurials. DNA sequence analysis of a 2.3-kb SacI-Aor51HI fragment encompassing the whole region required for expression of the hypersensitive phenotype, revealed three open reading frames. The DNA sequence of these frames had 82.5%, 99.2% and 97.0% homology with the pDU1358 merR, merB and merD, respectively. The pMRB01 mer operon differs from the already known mer operon by the absence of the merT, merP and merA genes in this plasmid. An inverted repeat-like sequence upstream from the predicted merR was observed suggesting that this defective mer operon could be part of a transposon-like structure. Induction experiments and maxicell analysis of the mer-polypeptide showed that the lyase enzyme encoded by pMRB01 merB gene is mercurial-inducible and regulated by the transacting product of the merR gene. These results suggest that the hypersensitivity to organomercurials resulted from the expression of lyase activity encoded by the defective mer operon in the absence of reductase activity. The lyase enzyme encoded by pMRB01 merB catalyzes the protonolysis of the C-Hg bond of both arylmercury and alkylmercury compounds.

Amino Acid Sequence↗
PubMed2004

A behavior genetic investigation of the relationship between leadership and personality.

Phenotypic research on leadership style has long considered the importance of individual differences in personality when identifying the behaviors associated with good leaders. Although leadership and many personality traits have been separately shown to be heritable, these constructs have not been examined with genetically informative data to identify common sources of heritability in the two domains. A logical extension to current research, therefore, is to examine the extent to which factors of personality are predictive of leadership dimensions and the extent to which unique genetic contributions to the relationship between personality and leadership style may be identified. Adult twin pairs (183 MZ and 64 same-sex DZ) completed the Multifactor Leadership Questionnaire (MLQ) and the Personality Research Form (PRF). Univariate analyses indicated that both leadership factors (transformational and transactional leadership) and all five of the "Big Five" factors (openness, conscientiousness, extraversion, disagreeableness, and neuroticism) were best fit by genetic models. Multivariate genetic analyses suggest that transformational leadership shows a statistically significant positive genetic correlation with conscientiousness, extraversion, and openness to experience. Transactional leadership shows a significant negative genetic correlation with conscientiousness and extraversion, and a significant positive genetic correlation with disagreeableness. These results underscore the importance of conscientiousness and extraversion in predicting leadership style, and illustrate important differences between transformational and transactional leaders.

Adult↗
PubMed1996

Review of statistics usage in the American Journal of Obstetrics and Gynecology.

OBJECTIVE: Our purpose was an assessment of statistical analysis in studies published in the American Journal of Obstetrics and Gynecology, as well as documentation of appropriate and inappropriate statistical application. STUDY DESIGN: All papers included in the Clinical Articles section and transactions of societies sections of the January through June 1994 issues of the American Journal of Obstetrics and Gynecology (volume 170, numbers 1 to 6) were reviewed for statistical usage. Each paper was given a rating for the thoroughness of the listing of applied statistics and a rating for the appropriateness of statistical usage, when possible. RESULTS: Of the 190 available articles, 53 consisted of studies void of statistics, 8 of which required statistics or claimed significance without the use of statistics. Therefore 145 articles were included in the final analysis. Because of inappropriate or incomplete descriptions of statistics used within the article (52.6%), the ability to assess the appropriateness of usage was severely limited. However, 44 articles (30.3%) could be classified as having appropriate usage of statistics, whereas 46 articles (31.7%) were deemed to have inappropriate usage of statistics. Furthermore, 27 of these 46 articles were noted to have serious flaws. CONCLUSION: The lack of complete and detailed listings of applied statistics made it difficult to assess the appropriateness of more than half the studies examined, suggesting a need for more detailed guidelines as to the listing of statistical procedures used. Despite this fact, nearly one third of the articles contained examples of statistics used inappropriately. These findings suggest that a policy of statistical review be instituted.

Publishing↗
PubMed1996

Long-range chromatin analysis of the human MYC locus by pulsed-field gel electrophoresis.

The identification of cis-acting regulatory elements has been greatly facilitated by the perception that nonnucleosomal regions of chromatin, including sites where transacting factors are bound, are hypersensitive to cleavage by nucleases. Hence, mapping of DNaseI-hypersensitive sites (HSs) has become particularly valuable for the detection of transcriptional control elements. The utility of this technique, however, may be constrained by the huge size of some eukaryotic gene domains or by the nonavailability of genomic probes. Apparently, both of these drawbacks hold true for the human protooncogene MYC. To overcome these limitations, we investigated the feasibility of mapping DNaseI-HSs in large restriction fragments. By using MYC-amplified cell lines, we devised a simple protocol that allowed for the detection of DNaseI-HSs at a distance of several hundred kb. In an attempt to identify additional regulatory elements required for MYC expression, we used this method to establish the long-range chromatin structure of four MYC amplicons. This method has potential benefits and applications.

Chromatin↗
PubMed1999

[Functional analysis of human A gamma-globin gene promoter with-173 T-->C mutation].

OBJECTIVE: To investigate the effect of the human A gamma-globin gene-173 T-->C mutation on the binding of transacting factors to the promoter and the activity of the promoter. METHODS: Electrophoretic mobility shift assay and transient transfection assay were used in this study. RESULTS: The A gamma-globin gene-173 T-->C mutation decreased the affinity of GATA-1 to the mutant promoter fragment (-201(-)-158) 96% (P < 0.01) and the binding of Oct-1 to the same DNA fragment 55% (P < 0.05). The activity of the mutant promoter was 2-fold (P < 0.05) as strong as that of the normal one in MELGM979 cells. The mutant and the normal promoters exhibited basically same activities in K562 and Hela cells. CONCLUSIONS: The -173 T-->C mutation decreased dramatically the binding of GATA-1, implicating that GA-TA-1 may act as a negative regulator of A gamma-globin gene in adults. The -173 T-->C mutation may enhance the activity of A gamma-globin gene promoter in the adult erythroid cell environment.

Adult↗
PubMed2001

Identification of a positive regulatory element in the myelin-specific promoter of the PMP22 gene.

Over- and under expression of the 22 kDa peripheral myelin protein (PMP22) results in dysmyelinating peripheral neuropathies, such as Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy, with the liability to pressure palsies (HNPP). Expression of the PMP22 gene is driven by two alternative promoters, P1 and P2, with transcripts originating from P1 associated with peripheral nerve myelination by Schwann cells. Transient transfections of constructs containing P1 (3.5 kb) or P2 (2.5 kb) resulted in high levels of reporter gene expression in the RT4-D6P2T schwannoma cell line. Serial deletions of P1 revealed that region P1-A (-105 to -43), situated upstream of the minimal promoter, contained a positive regulatory element. The 62 bp P1-A region conferred in cis a sevenfold increase in expression of luciferase driven by a heterologous promoter in an orientation-dependent manner. Interspecies comparison of the P1-A region revealed a 98% degree of identity between the human, mouse, and rat sequences. A prominent sequence-dependent DNA-protein complex (C-I) was detected in electrophoretic mobility shift assays with P1-A using RT4-D6P2T nuclear extract and was localized to a minimal 21 bp region within P1-A. Site-directed mutagenesis of this region revealed nucleotides at positions -46 to -43 as being necessary for formation of C-I. Functional analysis of the mutated P1-A element indicated that positions -46 and -45 were essential for transactivation mediated by this element. Characterization of the transacting factor(s) interacting with this key regulatory element will shed light on its role in regulating peripheral nerve myelination.

Base Sequence↗
PubMed2003

The process of sharing social support in cyberspace.

Mutual support is an interactional communication process. Taking an interactional approach to support requires group participants be viewed not only as targets and recipients but also as sources and providers of various types of support. An analysis was performed on the interactions of a group listserve and model of online interactional support. The aim was to explore the communication process children follow. The analysis revealed self-disclosure was used in the support group in three distinct ways. Its function for the support recipient is to initiate a transactional relationship with another member for the purpose of attracting social support through the open expression of concerns and frustrations. It is then used by the support provider to demonstrate that coping is possible for the recipient through the reciprocal self-disclosure of similar concerns and situations with which the member has successfully dealt. The third use of self-disclosure was to share reciprocal social companionship relationships.

Adolescent↗
PubMedDate not supplied

[Effects of selective vegetative denervation on the urinary bladder of the adult rat].

The present work is a study of the plastic capacity of the peripheral nervous system subjected to different aggressions in the case of 28 rats of the Wistar breed. They were divided into four groups: 1) sympathetic deafness (n=9); 2) parasympathetic deafness (n=9); 3) evaluation of regeneration (n=9); 4) control group (n=5). An image analyser was used to study the acetylcholinesterase (AChE) and Tyrosine Hydroxylase (TH) positive ganglionic neurones of the pelvic ganglion (GP) as well as the dorsal ganglions (GRD) compared with the control group. With group 3 a study was also made of the possible plasticity of the transacted axons using a wheat germ agglutinin conjugated-horseradish peroxidase (WGA-HRP) neurotracer. The statistical study was carried out by means of the analysis of variance (ANOVA), Fisher test and Scheffe method, with a p<0.05 taken as significant. The results show the predominant role of the pelvic nerve in the modulation of the plastic changes produced at the ganglionic level, with a lesser influence of the hypogastric nerve. Further studies are needed in order to define the specific role of each of these in the act of miction.

English Abstract↗
PubMed1978

Family practice in Virginia: a comparative analysis of two years' data.

Data representing Fiscal Years 1975 and 1976 as well as the aggregate 1975--1976 data set are reviewed in this paper. Information on 92,410 discrete patients and the 333,709 transactions they generated is studied. The transactions per patient rate of 3.6 varies greatly among the eight practices under investigation. This interpractice variation is complemented by remarkable year-to-year consistency within each practice. Age and the percent of continuing patients are presented as possible explanations for this variation. These data are useful to the physician in identifying the high-use patients and to the health planner for manpower and funding appropriations.

Adolescent↗
PubMedDate not supplied

Physician practice management companies: a failed concept.

Is there a lesson? Famed investor Warren Buffet claims he never buys a company unless he personally understands the business. He admits he has missed a few real opportunities in the high technology sector. However, he is pleased to have avoided many disasters. Many physicians entered into PPMC deals without completely understanding the concept. Perhaps the lesson is to simply avoid a deal that does not make sense. Understand the market. Understand the business. If you, as a buyer, seller or partner cannot clearly understand how a transaction creates value that you can capture, walk away.

Bankruptcy↗
PubMed2004

On traits, situations, and their integration: a developmental perspective.

The question of whether the person or the situation is largely responsible for behavior has plagued psychology intermittently for the last half century. Studies of the heritability, stability, and consensual validity of traits have clearly demonstrated the existence of traits. However, there is continuing controversy about the role of traits and situations in the enterprise of personality psychology. The goal of this article is to describe how insights yielded from adopting a developmental approach can foster the successful integration of the person and the situation across the life span. Five key lessons are described: (a) age matters--studying different age groups can lead to biases for and against traits and situations; (b), if age matters, time matters more--longitudinal and within-participant designs demonstrate that traits and situations are reciprocally related; (c) examine multiple types of change--focusing on one type, such as mean-level change, can lead to inappropriate conclusions about the merits of persons or situations; (d) be sensitive to levels of analysis--the relative breadth of persons and situations may determine the relative influence of the two; (e) pay attention to process--process models lead inextricably to transactional explanations.

Age Factors↗
PubMed1986

[Estimation of 99mTc-dimercaptosuccinic acid renal uptake using single photon emission computed tomography].

Renal function was assessed by measurement of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidney based on the transsectional tomographic image obtained by single photon emission computed tomography (SPECT). The renal uptake was expressed as percentage of the total radioactivity detected in the kidney, the volume of which was measured by convolution method, against the amount dosed. Absorption was corrected by GE-STAR method using cut off level of 42%. In order to determine normal range, measurement was made for 40 kidneys of each of 10 male and female volunteers confirmed of having normal kidneys both morphologically and functionally. The average volume of the kidney was 220.4 ml for the right and 239.3 ml for the left for males, and 205.9 ml and 236.5 ml, respectively for females. The renal uptake of radioactivity (at 2 h after injection), was 26.8% for the right and 27.6% for the left for males, with corresponding figures for females being 26.4% and 27.9%, respectively. Distribution range of renal volume and renal uptake was obtained by bivariate analysis with 90% and 95% probability. From these results, our method of renal function determination based on renal uptake of 99mTc-DMSA obtained from renal transactional tomogram by SPECT is considered to be accurate and potentially useful for clinical purpose.

Adult↗
PubMed1992

[Developmental structures in children with perinatal risk factors].

This longitudinal study focuses on the improvement of understanding the development of infants with perinatal complications. 38 infants with perinatal complications requiring intensive care for at least two weeks and their parents were examined shortly after birth and up to the age of 3 years. A number of biological and psychosocial data were collected. By means of cluster analysis based on data collected from children and families during the first three month three groups were obtained. After three years, children differed significantly in many developmental areas according to this grouping. A second cluster analysis based on three years follow-up data yielded four clusters which were characteristically related to the original ones. The results are discussed using a transactional perspective.

Adaptation, Psychological↗