The Effect of Chance Variability in Blood Pressure Readings on the Decision Making of General Practitioners: An Internet-Based Case Vignette Study

Background

Guidelines for the management of blood pressure (BP) in primary care generally suggest that decisions be made on the basis of specific threshold values (e.g. BP 140/90 mmHg); but this fails to adequately accommodate a common cause of variation – the play of chance.

Objective

To determine the impact of chance variability in BP readings on the clinical decision making of general practitioners (GPs) regarding anti-hypertensive treatment and cardiovascular risk management.

Method

We used an internet based study design, where 109 GPs were assigned to manage one of eight case vignettes (guidelines would recommend treatment for only one of the eight) and presented with blood pressure readings that were randomly selected from an underlying population.

Results

Seventeen (15.6%, 17/109) GPs consulted the vignette for whom treatment was recommended, but only 7/17 (41.2%) GPs prescribed treatment, whereas 14/92 (15.2%) GPs prescribed medication to the other vignettes. When deciding to follow-up a vignette GPs were influenced by threshold values for systolic and diastolic BP, but not by the overall cardiovascular risk. If the first reading was a low BP (systolic <140, diastolic <90) GPs were highly likely to discharge the vignette and follow-up a high BP reading (diastolic >90 or systolic BP≥140). Similar factors predicted the decision to prescribe a drug, although the vignette’s cardiovascular risk (>20%) was now statistically significant (p = 0.03).

Conclusions

GP decision making, whilst generally consistent with guidelines, appears to be compromised by chance variation leading to under and over treatment. Interventions to adequately accommodate chance variability into clinical decision making are required.     

A high‐resolution radiation hybrid map of the river buffalo major histocompatibility complex and comparison with BoLA

The major histocompatibility complex (MHC) in mammals codes for antigen‐presenting proteins. For this reason, the MHC is of great importance for immune function and animal health. Previous studies revealed this gene‐dense and polymorphic region in river buffalo to be on the short arm of chromosome 2, which is homologous to cattle chromosome 23. Using cattle‐derived STS markers and a river buffalo radiation hybrid (RH) panel (BBURH₅₀₀₀), we generated a high‐resolution RH map of the river buffalo MHC region. The buffalo MHC RH map (cR₅₀₀₀) was aligned with the cattle MHC RH map (cR₁₂₀₀₀) to compare gene order. The buffalo MHC had similar organization to the cattle MHC, with class II genes distributed in two segments, class IIa and class IIb. Class IIa was closely associated with the class I and class III regions, and class IIb was a separate cluster. A total of 53 markers were distributed into two linkage groups based on a two‐point LOD score threshold of ≥8. The first linkage group included 32 markers from class IIa, class I and class III. The second linkage group included 21 markers from class IIb. Bacterial artificial chromosome clones for seven loci were mapped by fluorescence in situ hybridization on metaphase chromosomes using single‐ and double‐color hybridizations. The order of cytogenetically mapped markers in the region corroborated the physical order of markers obtained from the RH map and served as anchor points to align and orient the linkage groups.     

Association analysis for agronomic traits in wheat under terminal heat stress

Terminal heat stress causes irreversible damage to wheat crop productivity. It reduces the vegetative growth and flowering period that consequently declines the efficiency to capture available stem reserves (carbohydrates) in grains. Markers associated with thermotolerant traits ease in marker assisted selection (MAS) for crop improvement. It identifies the genomic regions associated with thermotolerant traits in wheat, but the scarcity of markers is the major hindrance in crop improvement. Therefore, 158 wheat genotypes were subjected to genotyping with 165 simple sequence repeat markers dispersed on three genomes (A, B and D). Allelic frequency and polymorphic information content values were highest on genome A (5.34 (14% greater than the lowest value at genome D) and 0.715 (3% greater than the lowest value at genome D)), chromosome 4 (5.40 (16% greater than the lowest value at chromosome 2) and 0.725 (5% greater than the lowest value at chromosome 6)) and marker xgwm44 (13.0 (84% greater than the lowest value at marker xbarc148) and 0.916 (46% greater than the lowest value at marker xbarc148)). Bayesian based population structure discriminated the wheat genotypes into seven groups based on genetic similarity indicating their ancestral origin and geographical ecotype. Linkage disequilibrium pattern had highest significant (P < 0.001) linked loci pairs 732 on genome A at r² > 0.1 whereas, 58 on genome B at r² > 0.5. Linkage disequilibrium decay (P < 0.01 and r² > 0.1) had larger LD block (5–10 cM) on genome A. Highly significant MTAs (P < 0.000061) under heat stress conditions were identified for flag leaf area (xwmc336), spikelet per spike (xwmc553), grains per spike (cxfa2147, xwmc418 and xwmc121), biomass (xbarc7) and grain yield (xcfa2147 and xwmc671). The identified markers in this study could facilitate in MAS and gene pyramiding against heat stress in wheat.     

Climate change and coastal waterbird populations – past declines and future impacts

Considerable attention has been given to the impact of climate change on avian populations over the last decade. In this paper we examine two issues with respect to coastal bird populations in the UK: (1) is there any evidence that current populations are declining due to climate change, and (2) how might we predict the response of populations in the future? We review the cause of population decline in two species associated with saltmarsh habitats. The abundance of Common Redshank Tringa totanus breeding on saltmarsh declined by about 23% between the mid-1980s and mid-1990s, but the decline appears to have been caused by an increase in grazing pressure. The number of Twite Carduelis flavirostris wintering on the coast of East Anglia has declined dramatically over recent decades; there is evidence linking this decline with habitat loss but a causal role for climate change is unclear. These examples illustrate that climate change could be having population-level impacts now, but also show that it is dangerous to become too narrowly focused on single issues affecting coastal birds. Making predictions about how populations might respond to future climate change depends on an adequate understanding of important ecological processes at an appropriate spatial scale. We illustrate this with recent work conducted on the Icelandic population of Black-tailed Godwits Limosa limosa islandica that shows large-scale regulatory processes. Most predictive models to date have focused on local populations (single estuary or a group of neighbouring estuaries). We discuss the role such models might play in risk assessment, and the need for them to be linked to larger-scale ecological processes. We argue that future work needs to focus on spatial scale issues and on linking physical models of coastal environments with important ecological processes.     

Attempted Transformation of Wheat (Triticum aestivum) and Tobacco (Nicotiana tabacum) by Plasmid DNA Uptake Via the Pollen-tube Pathway

Plasmid DNA (CaMVGUS, containing β-glucuronldase gene) was used to transform developing seed of wheat and tobacco through pollen-tube pathway. The DNA was applied on the ovule end of excised styles and stigmas of wheat and tobacco after pollination. None of the 272 wheat and 13,567 tobacco plants obtained after application of the isolated DNA showed β-glucuronidase activity suggesting that the pollen-tube pathway may not be effective for transformation of plants.     

Cytogenetic studies in Cochlearia L. (Cruciferae). The origins of C. officinalis L. and C. micacea Marshall

Genome analysis has been used to investigate the evolutionary relationships of the tetraploid species in the genus Cochlearia. The results indicate that both C. officinalis L. (2n=24) and C. micacea Marshal (2n=26) are essentially autotetraploid in origin and that C. scotica Druce is simply a morphological variant of C. officinalis. The chromosomal relationships of the tetraploids to each other and to the diploids in the genus are discussed and the possible routes for the formation of all the species from a single, 2n=12, basic taxon are given. Evidence for the existence of a genic mechanism causing C. officinalis to form only bivalents is given and the mode of evolution of such a mechanism discussed.     

Visualization of protoplast fusion and quantitation of recombination in fused protoplasts of auxotrophic strains of Escherichia coli

Protoplast fusion has been used to combine genes from different organisms to create strains with desired properties. A recently developed variant on this approach, genome shuffling, involves generation of a genetically heterogeneous population of a single organism, followed by recursive protoplast fusion to allow recombination of mutations within the fused protoplasts. These are powerful techniques for engineering of microbial strains for desirable industrial properties. However, there is a prevailing opinion that it will be difficult to use these methods for engineering of Gram-negative bacteria because the outer membrane makes protoplast fusion more difficult. Here we describe the successful use of protoplast fusion in Escherichia coli. Using two auxotrophic strains of E. coli, we obtained prototrophic strains by recombination in fused protoplasts at frequencies of 0.05-0.7% based on the number of protoplasts subjected to fusion. This frequency is three-four orders of magnitude better than those previously reported for recombination in fused protoplasts of Gram-negative bacteria such as E. coli and Providencia alcalifaciens.     

Cytolytic activity and immunological similarity of the Bacillus thuringiensis subsp. israelensis and Bacillus thuringiensis subsp. morrisoni isolate PG-14 toxins.

The parasporal bodies of the mosquitocidal isolates of Bacillus thuringiensis subsp. israelensis and B. thuringiensis subsp. morrisoni isolate PG-14 were compared with regard to their hemolytic and cytolytic activities and the immunological relatedness of the 28- and 65-kilodalton (kDa) proteins that occur in both subspecies. The alkali-solubilized parasporal bodies of B. thuringiensis subsp. israelensis caused 50% lysis of human erythrocytes at 1.14 micrograms/ml, whereas those of B. thuringiensis subsp. morrisoni caused similar lysis at 1.84 micrograms/ml. Preincubation of solubilized parasporal bodies with dioleolyl phosphatidylcholine significantly inhibited the hemolytic activity of both supspecies. In cytolytic assays against Aedes albopictus cells, the toxin concentrations causing 50% lysis for B. thuringiensis subsp. israelensis and B. thuringiensis subsp. morrisoni were 1.87 and 11.98 micrograms/ml, respectively. Polyclonal antibodies raised separately against the 25-kDa protein (a tryptic digest of the 28-kDa protein) or the 65-kDa protein of B. thuringiensis subsp. israelensis cross-reacted, respectively, with the 28- and the 65-kDa proteins of B. thuringiensis subsp. morrisoni. However, neither of these antibodies cross-reacted with the 135-kDa protein of either subspecies. These results indicate that the mosquitocidal and hemolytic properties of B. thuringiensis subsp. israelensis and B. thuringiensis subsp. morrisoni isolate PG-14 are probably due to the biologically related proteins that are present in the parasporal bodies of both subspecies. The lower hemolytic activity of the B. thuringiensis subsp. morrisoni may be due to the presence of lower levels of the 28-kDa protein in that subspecies.(ABSTRACT TRUNCATED AT 250 WORDS)