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1.  Patient safety skills in primary care: a national survey of GP educators 
BMC Family Practice  2014;15(1):206.
Background
Clinicians have a vital role in promoting patient safety that goes beyond their technical competence. The qualities and attributes of the safe hospital doctor have been explored but similar work within primary care is lacking. Exploring the skills and attributes of a safe GP may help to inform the development of training programmes to promote patient safety within primary care.
This study aimed to determine the views of General Practice Educational Supervisors (GPES) regarding the qualities and attributes of a safe General Practitioner (GP) and the perceived trainability of these ‘safety skills’ and to compare selected results with those generated by a previous study of hospital doctors.
Methods
This was a two-stage study comprising content validation of a safety skills questionnaire (originally developed for hospital doctors) (Stage 1) and a prospective survey of all GPES in Scotland (n = 691) (Stage 2).
Results
Stage 1: The content-validated questionnaire comprised 66 safety skills/attributes across 17 broad categories with an overall content validation index of 0.92.
Stage 2: 348 (50%) GPES completed the survey. GPES felt the skills/attributes most important to being a safe GP were honesty (93%), technical clinical skills (89%) and conscientiousness (89%). That deemed least important/relevant to being a safe GP was leadership (36%). This contrasts sharply with the views of hospital doctors in the previous study. GPES felt the most trainable safety skills/attributes were technical skills (93%), situation awareness (75%) and anticipation/preparedness (71%). The least trainable were honesty (35%), humility (33%) and patient awareness/empathy (30%). Additional safety skills identified as relevant to primary care included patient advocacy, negotiation skills, accountability/ownership and clinical intuition (‘listening to that worrying little inner voice’).
Conclusions
GPES believe a broad range of skills and attributes contribute to being a safe GP. Important but subtle differences exist between what primary care and secondary care doctors perceive as core safety attributes. Educationalists, GPs and patient safety experts should collaborate to develop and implement training in these skills to ensure that current and future GPs possess the necessary competencies to engage and lead in safety improvement efforts.
Electronic supplementary material
The online version of this article (doi:10.1186/s12875-014-0206-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12875-014-0206-5
PMCID: PMC4275946  PMID: 25515429
General practice; Patient safety; Medical education; Skills
2.  Direct and indirect selection on flowering time, water-use efficiency (WUE, δ 13C), and WUE plasticity to drought in Arabidopsis thaliana 
Ecology and Evolution  2014;4(23):4505-4521.
Flowering time and water-use efficiency (WUE) are two ecological traits that are important for plant drought response. To understand the evolutionary significance of natural genetic variation in flowering time, WUE, and WUE plasticity to drought in Arabidopsis thaliana, we addressed the following questions: (1) How are ecophysiological traits genetically correlated within and between different soil moisture environments? (2) Does terminal drought select for early flowering and drought escape? (3) Is WUE plasticity to drought adaptive and/or costly? We measured a suite of ecophysiological and reproductive traits on 234 spring flowering accessions of A. thaliana grown in well-watered and season-ending soil drying treatments, and quantified patterns of genetic variation, correlation, and selection within each treatment. WUE and flowering time were consistently positively genetically correlated. WUE was correlated with WUE plasticity, but the direction changed between treatments. Selection generally favored early flowering and low WUE, with drought favoring earlier flowering significantly more than well-watered conditions. Selection for lower WUE was marginally stronger under drought. There were no net fitness costs of WUE plasticity. WUE plasticity (per se) was globally neutral, but locally favored under drought. Strong genetic correlation between WUE and flowering time may facilitate the evolution of drought escape, or constrain independent evolution of these traits. Terminal drought favored drought escape in these spring flowering accessions of A. thaliana. WUE plasticity may be favored over completely fixed development in environments with periodic drought.
doi:10.1002/ece3.1270
PMCID: PMC4264900  PMID: 25512847
Arabidopsis thaliana; drought; flowering time; plasticity; selection; water-use efficiency
3.  Harnessing genomics for delineating conservation units 
Trends in ecology & evolution  2012;27(9):489-496.
Genomic data have the potential to revolutionize the delineation of conservation units (CUs) by allowing the detection of adaptive genetic variation, which is otherwise difficult for rare, endangered species. In contrast to previous recommendations, we propose that the use of neutral versus adaptive markers should not be viewed as alternatives. Rather, neutral and adaptive markers provide different types of information that should be combined to make optimal management decisions. Genetic patterns at neutral markers reflect the interaction of gene flow and genetic drift that affects genome-wide variation within and among populations. This population genetic structure is what natural selection operates on to cause adaptive divergence. Here, we provide a new framework to integrate data on neutral and adaptive markers to protect biodiversity.
doi:10.1016/j.tree.2012.05.012
PMCID: PMC4185076  PMID: 22727017
4.  Natural Variation in Abiotic Stress Responsive Gene Expression and Local Adaptation to Climate in Arabidopsis thaliana 
Molecular Biology and Evolution  2014;31(9):2283-2296.
Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, “eSR”) to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, “eGEI”). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients.
doi:10.1093/molbev/msu170
PMCID: PMC4137704  PMID: 24850899
abiotic stress; landscape genomics; phenotypic plasticity; regulatory evolution; transcriptome
5.  Laboratory test ordering and results management systems: a qualitative study of safety risks identified by administrators in general practice 
BMJ Open  2014;4(2):e004245.
Objective
To explore experiences and perceptions of frontline administrators involved in the systems-based management of laboratory test ordering and results handling in general medical practice.
Design
Qualitative using focus group interviews.
Setting
West of Scotland general medical practices in three National Health Service (NHS) territorial board areas.
Participants
Convenience samples of administrators (receptionists, healthcare assistants and phlebotomists).
Methods
Transcript data were subjected to content analysis.
Results
A total of 40 administrative staff were recruited. Four key themes emerged: (1) system variations and weaknesses (eg, lack of a tracking process is a known risk that needs to be addressed). (2) Doctor to administrator communication (eg, unclear information can lead to emotional impacts and additional workload). (3) Informing patients of test results (eg, levels of anxiety and uncertainty are experienced by administrators influenced by experience and test result outcome) and (4) patient follow-up and confidentiality (eg, maintaining confidentiality in a busy reception area can be challenging). The key findings were explained in terms of sociotechnical systems theory.
Conclusions
The study further confirms the safety-related problems associated with results handling systems and adds to our knowledge of the communication and psychosocial issues that can affect the health and well-being of staff and patients alike. However, opportunities exist for practices to identify barriers to safe care, and plan and implement system improvements to accommodate or mitigate the potential for human error in this complex area.
doi:10.1136/bmjopen-2013-004245
PMCID: PMC3918986  PMID: 24503302
Qualitative Research
6.  Development of a next-generation NIL library in Arabidopsis thaliana for dissecting complex traits 
BMC Genomics  2013;14:655.
Background
The identification of the loci and specific alleles underlying variation in quantitative traits is an important goal for evolutionary biologists and breeders. Despite major advancements in genomics technology, moving from QTL to causal alleles remains a major challenge in genetics research. Near-isogenic lines are the ideal raw material for QTL validation, refinement of QTL location and, ultimately, gene discovery.
Results
In this study, a population of 75 Arabidopsis thaliana near-isogenic lines was developed from an existing recombinant inbred line (RIL) population derived from a cross between physiologically divergent accessions Kas-1 and Tsu-1. First, a novel algorithm was developed to utilize genome-wide marker data in selecting RILs fully isogenic to Kas-1 for a single chromosome. Seven such RILs were used in 2 generations of crossing to Tsu-1 to create BC1 seed. BC1 plants were genotyped with SSR markers so that lines could be selected that carried Kas-1 introgressions, resulting in a population carrying chromosomal introgressions spanning the genome. BC1 lines were genotyped with 48 genome-wide SSRs to identify lines with a targeted Kas-1 introgression and the fewest genomic introgressions elsewhere. 75 such lines were selected and genotyped at an additional 41 SNP loci and another 930 tags using 2b-RAD genotyping by sequencing. The final population carried an average of 1.35 homozygous and 2.49 heterozygous introgressions per line with average introgression sizes of 5.32 and 5.16 Mb, respectively. In a simple case study, we demonstrate the advantage of maintaining heterozygotes in our library whereby fine-mapping efforts are conducted simply by self-pollination. Crossovers in the heterozygous interval during this single selfing generation break the introgression into smaller, homozygous fragments (sub-NILs). Additionally, we utilize a homozygous NIL for validation of a QTL underlying stomatal conductance, a low heritability trait.
Conclusions
The present results introduce a new and valuable resource to the Brassicaceae research community that enables rapid fine-mapping of candidate loci in parallel with QTL validation. These attributes along with dense marker coverage and genome-wide chromosomal introgressions make this population an ideal starting point for discovery of genes underlying important complex traits of agricultural and ecological significance.
doi:10.1186/1471-2164-14-655
PMCID: PMC3849958  PMID: 24063355
2b-RAD; Fine-mapping; Quantitative trait loci; Stomatal conductance
7.  Applying the trigger review method after a brief educational intervention: potential for teaching and improving safety in GP specialty training? 
BMC Medical Education  2013;13:117.
Background
The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be tested. Current TRM training utilizes a workplace face-to-face session by a GP expert, which is not feasible. A less costly, more sustainable educational intervention is necessary to build capability at scale. We aimed to determine the feasibility and impact of TRM and a related training intervention in GP training.
Methods
We recruited 25 west of Scotland GP trainees to attend a 2-hour TRM workshop. Trainees then applied TRM to 25 clinical records and returned findings within 4-weeks. A follow-up feedback workshop was held.
Results
21/25 trainees (84%) completed the task. 520 records yielded 80 undetected PSIs (15.4%). 36/80 were judged potentially preventable (45%) with 35/80 classified as causing moderate to severe harm (44%). Trainees described a range of potential learning and improvement plans. Training was positively received and appeared to be successful given these findings. TRM was valued as a safety improvement tool by most participants.
Conclusion
This small study provides further evidence of TRM utility and how to teach it pragmatically. TRM is of potential value in GP patient safety curriculum delivery and preparing trainees for future safety improvement expectations.
doi:10.1186/1472-6920-13-117
PMCID: PMC3846442  PMID: 24000946
Patient safety; General practice; Primary care; Trigger tool; Clinical record review; GP training; Clinical audit
8.  The physiological basis for genetic variation in water use efficiency and carbon isotope composition in Arabidopsis thaliana 
Photosynthesis Research  2013;119(1-2):119-129.
Ecologists and physiologists have documented extensive variation in water use efficiency (WUE) in Arabidopsis thaliana, as well as association of WUE with climatic variation. Here, we demonstrate correlations of whole-plant transpiration efficiency and carbon isotope composition (δ13C) among life history classes of A. thaliana. We also use a whole-plant cuvette to examine patterns of co-variation in component traits of WUE and δ13C. We find that stomatal conductance (gs) explains more variation in WUE than does A. Overall, there was a strong genetic correlation between A and gs, consistent with selection acting on the ratio of these traits. At a more detailed level, genetic variation in A was due to underlying variation in both maximal rate of carboxylation (Vcmax) and maximum electron transport rate (Jmax). We also found strong effects of leaf anatomy, where lines with lower WUE had higher leaf water content (LWC) and specific leaf area (SLA), suggesting a role for mesophyll conductance (gm) in variation of WUE. We hypothesize that this is due to an effect through gm, and test this hypothesis using the abi4 mutant. We show that mutants of ABI4 have higher SLA, LWC, and gm than wild-type, consistent with variation in leaf anatomy causing variation in gm and δ13C. These functional data also add further support to the central, integrative role of ABI4 in simultaneously altering ABA sensitivity, sugar signaling, and CO2 assimilation. Together our results highlight the need for a more holistic approach in functional studies, both for more accurate annotation of gene function and to understand co-limitations to plant growth and productivity.
doi:10.1007/s11120-013-9891-5
PMCID: PMC3889294  PMID: 23893317
ABI4; Carbon isotope composition; Mesophyll conductance; Photosynthetic capacity; Stomatal conductance
9.  Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation 
An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, ‘antagonistic’ pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits ‘adaptive’ pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a ‘drought escape’ strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch.
doi:10.1098/rspb.2013.1043
PMCID: PMC3774242  PMID: 23698015
drought; Arabidopsis thaliana; water use efficiency; flowering time
10.  Combining QOF data with the care bundle approach may provide a more meaningful measure of quality in general practice 
Background
A significant minority of patients do not receive all the evidence-based care recommended for their conditions. Health care quality may be improved by reducing this observed variation. Composite measures offer a different patient-centred perspective on quality and are utilized in acute hospitals via the ‘care bundle’ concept as indicators of the reliability of specific (evidence-based) care delivery tasks and improved outcomes. A care bundle consists of a number of time-specific interventions that should be delivered to every patient every time. We aimed to apply the care bundle concept to selected QOF data to measure the quality of evidence-based care provision.
Methods
Care bundles and components were selected from QOF indicators according to defined criteria. Five clinical conditions were suitable for care bundles: Secondary Prevention of Coronary Heart Disease (CHD), Stroke & Transient Ischaemic Attack (TIA), Chronic Kidney Disease (CKD), Chronic Obstructive Pulmonary Disease (COPD) and Diabetes Mellitus (DM). Each bundle has 3-8 components. A retrospective audit was undertaken in a convenience sample of nine general medical practices in the West of Scotland. Collected data included delivery (or not) of individual bundle components to all patients included on specific disease registers. Practice level and overall compliance with bundles and components were calculated in SPSS and expressed as a percentage.
Results
Nine practices (64.3%) with a combined patient population of 56,948 were able to provide data in the format requested. Overall compliance with developed QOF-based care bundles (composite measures) was as follows: CHD 64.0%, range 35.0-71.9%; Stroke/TIA 74.1%, range 51.6-82.8%; CKD 69.0%, range 64.0-81.4%; and COPD 82.0%, range 47.9-95.8%; and DM 58.4%, range 50.3-65.2%.
Conclusions
In this small study compliance with individual QOF-based care bundle components was high, but overall (‘all or nothing’) compliance was substantially lower. Care bundles may provide a more informed measure of care quality than existing methods. However, the acceptability, feasibility and potential impact on clinical outcomes are unknown.
doi:10.1186/1472-6963-12-351
PMCID: PMC3523087  PMID: 23043262
11.  Maximising harm reduction in early specialty training for general practice: validation of a safety checklist 
BMC Family Practice  2012;13:62.
Background
Making health care safer is a key policy priority worldwide. In specialty training, medical educators may unintentionally impact on patient safety e.g. through failures of supervision; providing limited feedback on performance; and letting poorly developed behaviours continue unchecked. Doctors-in-training are also known to be susceptible to medical error. Ensuring that all essential educational issues are addressed during training is problematic given the scale of the tasks to be undertaken. Human error and the reliability of local systems may increase the risk of safety-critical topics being inadequately covered. However adherence to a checklist reminder may improve the reliability of task delivery and maximise harm reduction. We aimed to prioritise the most safety-critical issues to be addressed in the first 12-weeks of specialty training in the general practice environment and validate a related checklist reminder.
Methods
We used mixed methods with different groups of GP educators (n = 127) and specialty trainees (n = 9) in two Scottish regions to prioritise, develop and validate checklist content. Generation and refinement of checklist themes and items were undertaken on an iterative basis using a range of methods including small group work in dedicated workshops; a modified-Delphi process; and telephone interviews. The relevance of potential checklist items was rated using a 4-point scale content validity index to inform final inclusion.
Results
14 themes (e.g. prescribing safely; dealing with medical emergency; implications of poor record keeping; and effective & safe communication) and 47 related items (e.g. how to safety-net face-to-face or over the telephone; knowledge of practice systems for results handling; recognition of harm in children) were judged to be essential safety-critical educational issues to be covered. The mean content validity index ratio was 0.98.
Conclusion
A checklist was developed and validated for educational supervisors to assist in the reliable delivery of safety-critical educational issues in the opening 12-week period of training, and aligned with national curriculum competencies. The tool can also be adapted for use as a self-assessment instrument by trainees to guide patient safety-related learning needs. Dissemination and implementation of the checklist and self-rating scale are proceeding on a national, voluntary basis with plans to evaluate its feasibility and educational impact.
doi:10.1186/1471-2296-13-62
PMCID: PMC3418214  PMID: 22721273
12.  Barriers and attitudes influencing non-engagement in a peer feedback model to inform evidence for GP appraisal 
BMC Medical Education  2012;12:15.
Background
The UK general practitioner (GP) appraisal system is deemed to be an inadequate source of performance evidence to inform a future medical revalidation process. A long-running voluntary model of external peer review in the west of Scotland provides feedback by trained peers on the standard of GP colleagues' core appraisal activities and may 'add value' in strengthening the robustness of the current system in support of revalidation. A significant minority of GPs has participated in the peer feedback model, but a clear majority has yet to engage with it. We aimed to explore the views of non-participants to identify barriers to engagement and attitudes to external peer review as a means to inform the current appraisal system.
Methods
We conducted semi-structured interviews with a sample of west of Scotland GPs who had yet to participate in the peer review model. A thematic analysis of the interview transcriptions was conducted using a constant comparative approach.
Results
13 GPs were interviewed of whom nine were males. Four core themes were identified in relation to the perceived and experienced 'value' placed on the topics discussed and their relevance to routine clinical practice and professional appraisal: 1. Value of the appraisal improvement activity. 2. Value of external peer review. 3. Value of the external peer review model and host organisation and 4. Attitudes to external peer review.
Conclusions
GPs in this study questioned the 'value' of participation in the external peer review model and the national appraisal system over the standard of internal feedback received from immediate work colleagues. There was a limited understanding of the concept, context and purpose of external peer review and some distrust of the host educational provider. Future engagement with the model by these GPs is likely to be influenced by policy to improve the standard of appraisal and contractual related activities, rather than a self-directed recognition of learning needs.
doi:10.1186/1472-6920-12-15
PMCID: PMC3338401  PMID: 22443714
13.  Topical Azithromycin Therapy of Meibomian Gland Dysfunction: Clinical response and lipid alterations 
Cornea  2010;29(7):781-788.
Purpose
Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic behavior of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution.
Methods
Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid (ML) lipid-lipid interaction strength, conformation and phase transition parameters were measured using Fourier transform infrared spectroscopy (FTIR).
Results
In subjects with clinical evidence of MGD changes in ordering of the lipids and resultant alteration of phase transition temperature were identified. Topical therapy with azithromycin relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion towards normal.
Conclusions
Improvement in phase transition temperature of the meibomian gland lipid with the determined percent trans rotomer composition of the lipid strongly suggests that the ordering of the lipid molecules is altered in the disease state (MGD) and that azithromycin can improve that abnormal condition toward normal in a manner that correlates with clinical response to therapy.
doi:10.1097/ICO.0b013e3181cda38f
PMCID: PMC2893269  PMID: 20489573
14.  Verifying appraisal evidence using feedback from trained peers: views and experiences of Scottish GP appraisers 
Background
GP appraisal is currently considered inadequate because it lacks robustness. Objective assessment of appraisal evidence is needed to enable judgements on professional performance to be made.
Aim
To determine GP appraisers' views of the acceptability, feasibility, and educational impact of external peer feedback received on three core appraisal activities undertaken as part of this study.
Design of study
Independent peer review and cross-sectional postal questionnaire study.
Setting
NHS Scotland.
Method
One of three core appraisal activities (criterion audit, significant event analysis, or video of consultations) was undertaken by GP appraisers and subjected to peer review by trained colleagues. A follow-up postal questionnaire elicited participants' views on the potential acceptability, feasibility, and educational impact of this approach.
Results
Of 164 appraisers, 80 agreed to participate; 67/80 (84%) submitted one of three appraisal materials for peer review and returned completed questionnaires. For significant event analyses (n = 44), most responders believed the peer feedback method was feasible (100%) and fair (92.5%) and would add value to appraisal (95.5%). Peer feedback on criterion audits (n = 15) was believed to be acceptable and fair (93.3%) and it was thought it would be a useful educational tool (100%). Completing a consultation video (n = 8) was perceived to be feasible as part of normal general practice (n = 5). It was unanimously agreed that assessment of videos by peers has educational impact and would help improve appraisal.
Conclusion
This group of GP appraisers strongly supported the role of external and independent feedback by trained peers as one approach to strengthening the existing appraisal process.
doi:10.3399/bjgp09X453521
PMCID: PMC2702014  PMID: 19566997
appraisal; assessment; feedback; general practice; peer review
15.  Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons 
Annals of neurology  2009;65(6):742-748.
The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy(PML) and of JCV granule cell neuronopathy(JCV GCN). We present an HIV-negative patient who developed multiple cortical lesions, aphasia and progressive cognitive decline after chemotherapy for non-small-cell lung cancer. Brain biopsy and CSF PCR demonstrated JCV and she had a rapidly fatal outcome. Post-mortem analysis showed diffuse cortical lesions and areas of necrosis at the gray-white junction. Immunostaining revealed a productive JCV-infection of cortical pyramidal neurons, confirmed by electron microscopy, with limited demyelination. This novel gray matter syndrome expands the scope of JCV clinical presentation and pathogenesis.
doi:10.1002/ana.21619
PMCID: PMC2865689  PMID: 19557867
16.  The role of adaptive trans-generational plasticity in biological invasions of plants 
Evolutionary Applications  2010;3(2):179-192.
High-impact biological invasions often involve establishment and spread in disturbed, high-resource patches followed by establishment and spread in biotically or abiotically stressful areas. Evolutionary change may be required for the second phase of invasion (establishment and spread in stressful areas) to occur. When species have low genetic diversity and short selection history, within-generation phenotypic plasticity is often cited as the mechanism through which spread across multiple habitat types can occur. We show that trans-generational plasticity (TGP) can result in pre-adapted progeny that exhibit traits associated with increased fitness both in high-resource patches and in stressful conditions. In the invasive sedge, Cyperus esculentus, maternal plants growing in nutrient-poor patches can place disproportional number of propagules into nutrient-rich patches. Using the invasive annual grass, Aegilops triuncialis, we show that maternal response to soil conditions can confer greater stress tolerance in seedlings in the form of greater photosynthetic efficiency. We also show TGP for a phenological shift in a low resource environment that results in greater stress tolerance in progeny. These lines of evidence suggest that the maternal environment can have profound effects on offspring success and that TGP may play a significant role in some plant invasions.
doi:10.1111/j.1752-4571.2010.00118.x
PMCID: PMC3352481
annual plants; competitive ability; environmental stress; inclusive fitness; maternal environmental effects; phenotypic plasticity; propagule dispersal; resource patch; seed size; spatial heterogeneity
17.  A review of significant events analysed in general practice: implications for the quality and safety of patient care 
BMC Family Practice  2009;10:61.
Background
Significant event analysis (SEA) is promoted as a team-based approach to enhancing patient safety through reflective learning. Evidence of SEA participation is required for appraisal and contractual purposes in UK general practice. A voluntary educational model in the west of Scotland enables general practitioners (GPs) and doctors-in-training to submit SEA reports for feedback from trained peers. We reviewed reports to identify the range of safety issues analysed, learning needs raised and actions taken by GP teams.
Method
Content analysis of SEA reports submitted in an 18 month period between 2005 and 2007.
Results
191 SEA reports were reviewed. 48 described patient harm (25.1%). A further 109 reports (57.1%) outlined circumstances that had the potential to cause patient harm. Individual 'error' was cited as the most common reason for event occurrence (32.5%). Learning opportunities were identified in 182 reports (95.3%) but were often non-specific professional issues not shared with the wider practice team. 154 SEA reports (80.1%) described actions taken to improve practice systems or professional behaviour. However, non-medical staff were less likely to be involved in the changes resulting from event analyses describing patient harm (p < 0.05)
Conclusion
The study provides some evidence of the potential of SEA to improve healthcare quality and safety. If applied rigorously, GP teams and doctors in training can use the technique to investigate and learn from a wide variety of quality issues including those resulting in patient harm. This leads to reported change but it is unclear if such improvement is sustained.
doi:10.1186/1471-2296-10-61
PMCID: PMC2744665  PMID: 19723325
18.  Chloroplast genome sequencing analysis of Heterosigma akashiwo CCMP452 (West Atlantic) and NIES293 (West Pacific) strains 
BMC Genomics  2008;9:211.
Background
Heterokont algae form a monophyletic group within the stramenopile branch of the tree of life. These organisms display wide morphological diversity, ranging from minute unicells to massive, bladed forms. Surprisingly, chloroplast genome sequences are available only for diatoms, representing two (Coscinodiscophyceae and Bacillariophyceae) of approximately 18 classes of algae that comprise this taxonomic cluster.
A universal challenge to chloroplast genome sequencing studies is the retrieval of highly purified DNA in quantities sufficient for analytical processing. To circumvent this problem, we have developed a simplified method for sequencing chloroplast genomes, using fosmids selected from a total cellular DNA library. The technique has been used to sequence chloroplast DNA of two Heterosigma akashiwo strains. This raphidophyte has served as a model system for studies of stramenopile chloroplast biogenesis and evolution.
Results
H. akashiwo strain CCMP452 (West Atlantic) chloroplast DNA is 160,149 bp in size with a 21,822-bp inverted repeat, whereas NIES293 (West Pacific) chloroplast DNA is 159,370 bp in size and has an inverted repeat of 21,665 bp. The fosmid cloning technique reveals that both strains contain an isomeric chloroplast DNA population resulting from an inversion of their single copy domains. Both strains contain multiple small inverted and tandem repeats, non-randomly distributed within the genomes. Although both CCMP452 and NIES293 chloroplast DNAs contains 197 genes, multiple nucleotide polymorphisms are present in both coding and intergenic regions. Several protein-coding genes contain large, in-frame inserts relative to orthologous genes in other plastids. These inserts are maintained in mRNA products. Two genes of interest in H. akashiwo, not previously reported in any chloroplast genome, include tyrC, a tyrosine recombinase, which we hypothesize may be a result of a lateral gene transfer event, and an unidentified 456 amino acid protein, which we hypothesize serves as a G-protein-coupled receptor. The H. akashiwo chloroplast genomes share little synteny with other algal chloroplast genomes sequenced to date.
Conclusion
The fosmid cloning technique eliminates chloroplast isolation, does not require chloroplast DNA purification, and reduces sequencing processing time. Application of this method has provided new insights into chloroplast genome architecture, gene content and evolution within the stramenopile cluster.
doi:10.1186/1471-2164-9-211
PMCID: PMC2410131  PMID: 18462506
19.  Economic evaluation of a clinical protocol for diagnosing emergency patients with suspected pulmonary embolism 
Background
The objective of this paper is to estimate the amount of cost-savings to the Australian health care system from implementing an evidence-based clinical protocol for diagnosing emergency patients with suspected pulmonary embolism (PE) at the Emergency department of a Victorian public hospital with 50,000 presentations in 2001–2002.
Methods
A cost-minimisation study used the data collected in a controlled clinical trial of a clinical protocol for diagnosing patients with suspected PE. Thenumber and type of diagnostic tests in a historic cohort of 185 randomly selected patients, who presented to the emergency department with suspectedPE during an eight month period prior to the clinical trial (January 2002 -August 2002) were compared with the number and type of diagnostic tests in745 patients, who presented to the emergency department with suspected PE from November 2002 to August 2003. Current Medicare fees per test were usedas unit costs to calculate the mean aggregated cost of diagnostic investigation per patient in both study groups. A t-test was used to estimate the statistical significance of the difference in the cost of resources used for diagnosing PE in the control and in the intervention group.
Results
The trial demonstrated that diagnosing PE using an evidence-based clinical protocol was as effective as the existing clinical practice. The clinical protocol offers the advantage of reducing the use of diagnostic imaging, resulting in an average cost savings of at least $59.30 per patient.
Conclusion
Extrapolating the observed cost-savings of $59.30 per patient to the wholeof Australia could potentially result in annual savings between $3.1 million to $3.7 million.
doi:10.1186/1478-7547-4-12
PMCID: PMC1550258  PMID: 16803623
20.  Chronic cough 
BMJ : British Medical Journal  2003;326(7383):261.
PMCID: PMC140767  PMID: 12560280
21.  Ranitidine and duodenal ulceration: a short-term and maintenance study1 
Forty-eight patients successfully completed a six-week, double blind, placebo controlled trial of ranitidine hydrochloride 200mg twice daily for active duodenal ulceration. Following endoscopy 68% of the patients taking ranitidine had healed, compared to 35% of those who were taking placebo. Nineteen of the patients who had not healed then took a further six weeks of open active treatment; of these, 14 were successfully treated. Thirty-one of the patients who had healed duodenal ulcers then took ranitidine hydrochloride 100mg at night as a maintenance treatment for one year: 71% remained endoscopically and symptomatically in remission. No serious side effects were encountered.
PMCID: PMC1437798  PMID: 6122738

Results 1-21 (21)