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1.  The Tie-dyed pathway promotes symplastic trafficking in the phloem 
Plant Signaling & Behavior  2013;8(6):e24540.
The tie-dyed1 (tdy1) and tdy2 mutants of maize exhibit leaf regions with starch hyperaccumulation and display unusual genetic interactions, suggesting they function in the same physiological process. Tdy2 encodes a putative callose synthase and is expressed in developing vascular tissues of immature leaves. Radiolabelling experiments and transmission electron microscopy (TEM) revealed symplastic trafficking within the phloem was perturbed at the companion cell/sieve element interface. Here, we show that as reported for tdy2 mutants, tdy1 yellow leaf regions display an excessive oil-droplet phenotype in the companion cells. Based on the proposed function of Tdy2 as a callose synthase, our previous work characterizing Tdy1 as a novel, transmembrane-localized protein, and the present findings, we speculate how TDY1 and TDY2 might interact to promote symplastic transport of both solutes and developmentally instructive macromolecules during vascular development at the companion cell/sieve element interface.
doi:10.4161/psb.24540
PMCID: PMC3909061  PMID: 23603956
callose synthase; companion cell; maize; oil droplet; phloem; plasmodesmata; sieve element; symplastic trafficking; tie-dyed; xylem
2.  Fusobacterium necrophorum in an Abdominal Aortic Aneurysm, Treated by Once Daily Ertapenem 
Inflammatory aneurysms may make up a small percentage of the total number of abdominal aortic aneurysms, but they present their own unique challenges. We present a case of a 65-year-old man whose aneurysm was found to be colonized by Fusobacterium necrophorum.
doi:10.1055/s-0032-1325169
PMCID: PMC3578632  PMID: 23997565
abdominal aortic aneurysm; aneurysm; C-reactive protein; infection; mycotic aneurysm; risk factors; repair
3.  Myocardial Function after Fetal Cardiac Bypass in an Ovine Model 
Objective
Fetal cardiac surgery may improve the prognosis of certain complex congenital heart defects that have significant associated mortality and morbidity in utero or after birth. An important step in translating fetal cardiac surgery is identifying potential mechanisms leading to myocardial dysfunction following bypass. The hypothesis was that fetal cardiac bypass results in myocardial dysfunction, possibly due to perturbation of calcium cycling and contractile proteins.
Methods
Mid-term sheep fetuses (n=6) underwent 30 minutes of cardiac bypass and 120 minutes of monitoring after bypass. Sonomicrometry and pressure catheters inserted in left (LV) and right ventricles (RV) measured myocardial function. Cardiac contractile and calcium cycling proteins, along with calpain, were analyzed by immunoblot.
Results
Preload recruitable stroke work (slope of the regression line) was reduced at 120 min after bypass (RV – baseline vs. 120 min after bypass, 38.6±6.8 vs. 20.4±4.8 (P=.01); LV – 37±7.3 vs. 20.6±3.9 (P=.01). Tau (msec), a measure of diastolic relaxation, was elevated in both ventricles (RV – baseline vs. 120 min after bypass, 32.7±4.5 vs. 67.8±9.4 (P<.01); LV – 26.1±3.2 vs. 63.2±11.2 (P=.01). Cardiac output was lower and end-diastolic pressures were higher in the RV, but not the LV, after bypass compared with baseline. RV troponin I was degraded by elevated calpain activity and protein levels of sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) were reduced in both ventricles.
Conclusions
Fetal cardiac bypass was associated with myocardial dysfunction and disruption of calcium cycling and contractile proteins. Minimizing myocardial dysfunction after cardiac bypass is important for successful fetal surgery to repair complex congenital heart defects.
doi:10.1016/j.jtcvs.2010.08.031
PMCID: PMC3032026  PMID: 20884028
4.  New relationships between breast microcalcifications and cancer 
British Journal of Cancer  2010;103(7):1034-1039.
Background:
Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state.
Methods:
A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue.
Results:
The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between microcalcification chemical composition (carbonate content and protein matrix : mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P<0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix : mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively.
Conclusions:
We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition.
doi:10.1038/sj.bjc.6605873
PMCID: PMC2965876  PMID: 20842116
breast cancer; calcifications; carbonate; DCIS; diagnose; FTIR; grade
5.  Acute Complete Heart Block in Dogs 
Circulation  1955;12(1):82-89.
A study has been conducted immediately and up to 18 days after the surgical production of complete heart block in dogs. Immediately after surgery cardiac output, coronary flow, and mean arterial pressure were reduced in rough proportion to the degree of bradycardia. In time, these measures began to return toward preoperative levels. Paralleling the diminished left ventricular work was a diminished left ventricular oxygen consumption with little consequent change in myocardial efficiency. Small rises were detected in central venous pressure. At autopsy, the only unequivocal abnormality was myocardial hypertrophy which became measurable between 2 and 18 days after operation.
PMCID: PMC2952508  PMID: 14390703
7.  Oral and Enteral Resuscitation of Burn Shock The Historical Record and Implications for Mass Casualty Care 
Eplasty  2010;10:e56.
In the aftermath of a mass disaster, standard care methods for treatment of burn injury will often not be available for all victims. A method of fluid resuscitation for burns that has largely been forgotten by contemporary burn experts is enteral resuscitation. We identified 12 studies with over 700 patients treated with enteral resuscitation, defined as drinking or gastric infusion of salt solutions, from the literature. These studies suggest that enteral resuscitation can be an effective treatment for burn shock under conditions in which the standard IV therapy is unavailable or delayed, such as in mass disasters and combat casualties. Enteral resuscitation of burn shock was effective in patients with moderate (10–40% TBSA) and in some patients with more severe injuries. The data suggests that some hypovolemic burn and trauma patients can be treated exclusively with enteral resuscitation, and others might benefit from enteral resuscitation as an initial alternative and a supplement to IV therapy. A complication of enteral resuscitation was vomiting, which occurred less in children and much less when therapy was initiated within the first postburn hour. Enteral resuscitation is contra-indicated when the patient is in “peripheral circulatory collapse”. The optimal enteral solution and regimen has not yet been defined, nor has its efficacy been tested against modern IV resuscitation. The oldest studies used glucose-free solutions of buffered isotonic and hypotonic saline. Studies that are more recent show benefit of adding glucose to electrolyte solutions similar to those used in the treatment of cholera. If IV therapy for mass casualty care is delayed due to logistical constraints, enteral resuscitation should be considered.
PMCID: PMC2933130  PMID: 20827301
8.  Patterns of Chromosomal Evolution in Sigmodon, Evidence from Whole Chromosome Paints 
Cytogenetic and Genome Research  2009;125(1):54-66.
Of the superfamily Muroidea (31 genera, 1578 species), the Sigmodontinae (74 genera, 377 species) is the second largest subfamily in number of species and represents a significant radiation of rodent biodiversity. Only 2 of the 74 genera are found in both North and South America (Sigmodon and Oryzomys) and the remainder are exclusively from South America. In recent molecular studies, the genus Sigmodon (Cricetidae, Sigmodontinae) has been considered sister to many other South American Sigmodontines [Steppan et al., 2004]. We examine the chromosomal evolution of 9 species of Sigmodon utilizing chromosomal paints isolated from S. hispidus, proposed to be similar to the ancestral karyotype [Elder, 1980]. Utilizing a phylogenetic hypothesis of a molecular phylogeny of Sigmodon [Henson and Bradley, 2009], we mapped shared chromosomal rearrangements of taxa on a molecular tree to estimate the evolutionary position of each rearrangement. For several species (S. hirsutus, S. leucotis, S. ochrognathus, S. peruanus, and S. toltecus), the karyotype accumulated few or no changes, but in three species (S. arizonae, S. fulviventer, and S. mascotensis) numerous karyotype rearrangements were observed. These rearrangements involved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as well as the addition of interstitial DNA not identified by chromosome paints or C-banding. The hypothesis that the ancestral karyotype for this complex had a diploid number of 52, a fundamental number of 52, and a G-band pattern of which most, if not all are similar to that present in modern day S. hispidus fails to be rejected. This hypothesis remains viable as an explanation of chromosomal evolution in Sigmodontine rodents.
doi:10.1159/000218747
PMCID: PMC2918645  PMID: 19617697
Ancestral karyotype; Comparative cytogenetics; DAPI banding; Karyotype conservation; Muroid rodents; Phylogeny; Sigmodontinae; Tandem fusions
9.  Breast calcification: the 'Cinderella' breast element? 
Breast Cancer Research : BCR  2010;12(Suppl 1):P36.
doi:10.1186/bcr2533
PMCID: PMC2875598
10.  The Adapter Protein SLP-76 Mediates “Outside-In” Integrin Signaling and Function in T Cells▿ †  
Molecular and Cellular Biology  2009;29(20):5578-5589.
The adapter protein SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an essential mediator of signaling from the T-cell antigen receptor (TCR). We report here that SLP-76 also mediates signaling downstream of integrins in T cells and that SLP-76-deficient T cells fail to support adhesion to integrin ligands. In response to both TCR and integrin stimulation, SLP-76 relocalizes to surface microclusters that colocalize with phosphorylated signaling proteins. Disruption of SLP-76 recruitment to the protein named LAT (linker for activation of T cells) inhibits SLP-76 clustering downstream of the TCR but not downstream of integrins. Conversely, an SLP-76 mutant unable to bind ADAP (adhesion and degranulation-promoting adapter protein) forms clusters following TCR but not integrin engagement and fails to support T-cell adhesion to integrin ligands. These findings demonstrate that SLP-76 relocalizes to integrin-initiated signaling complexes by a mechanism different from that employed during TCR signaling and that SLP-76 relocalization corresponds to SLP-76-dependent integrin function in T cells.
doi:10.1128/MCB.00283-09
PMCID: PMC2756887  PMID: 19667077
11.  Low level mercury speciation in freshwaters by isotope dilution GC-ICP-MS 
Environmental science & technology  2009;43(7):2463-2469.
Atmospheric deposition of anthropogenic Hg has led to increased Hg concentrations in many ecosystems. Modeling is an effective method for predicting the complex dynamics of Hg fate and transport in watersheds; such models require accurate concentrations for water column methylmercury, CH3Hg+, as input parameters, yet these concentrations are very difficult to measure precisely as they are so low. We developed a method for aqueous CH3Hg+ quantification in Lake Champlain VT, where ambient CH3Hg+ concentrations are < 0.04 ng l-1. The analysis utilized species specific isotope dilution, purge and trap, gas chromatography ICP-MS and provided instrument detection limits of ca 0.2 fM (0.04 pg l-1) and method detection limits of 15 fM (0.003 ng l-1) for CH3Hg+ which are amongst the lowest reported. Artifactual methylation of inorganic Hg2+ was shown to be minor and the precision of the isotope dilution method was generally < 5% relative standard deviation; much lower than would have been the case for an external calibration approach. The method is accurate even at low concentrations of ca. 0.025 ng l-1. This combination of precision, accuracy and low detection allow for quantification of significant differences in CH3Hg+ concentration between bays and over time within bays of Lake Champlain where mean CH3Hg+ concentrations differ by only 0.006 ng l-1 at concentrations as low as 0.014 ng l-1.
PMCID: PMC2692077  PMID: 19452902
12.  Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO2 levels* 
Experimental eye research  2008;88(2):286-292.
It has been proposed that disruption of normal vitreous humor may permit O2 to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto et al., 2004; Harocopos et al., 2004). In the present study, we injected enzymes intravitreally into guinea pigs (which possess an avascular retina) and rats (which possess a vascular retina) to produce either vitreous humor liquefaction plus a posterior vitreous detachment (PVD) (with use of microplasmin) or vitreous humor liquefaction only (with use of hyaluronidase), and 1–2 weeks later measured lens nuclear pO2 levels in vivo using a platinum-based fluorophore O2 sensor (Oxford-Optronix, Ltd.). Experiments were also conducted in which the animals were allowed to breathe 100% O2 following intravitreal injection with either microplasmin or hyaluronidase in order to investigate possible effects on O2 exchange within the eye. Injection of guinea pigs with either of the two enzymes produced no significant differences in lens pO2 levels 1–2 weeks later, compared to controls. However, for the rat, injection of microplasmin produced a 68% increase in O2 level in the center of the lens, compared to the controls (5.6 mmHg increasing to 9.4 mmHg, p<0.05), with no corresponding effect observed following similar use of hyaluronidase. Treatment of guinea pigs with microplasmin dramatically accelerated movement of O2 across the vitreal space when the animals were later allowed to breathe 100% O2 (for example, O2 traveled to a location directly behind the lens 5 times faster than control; p<0.01); however, the effect following treatment with hyaluronidase was significantly less. When microplasmin-injected rats breathed 100% O2, the time required for O2 to reach the center of the lens was 3 times faster than control (0.4 min compared to 1.4 min, p<0.01). The results have implication with regard to the occurrence of age-related PVD in the human, and a possible acceleration of maturity-onset nuclear cataract. In addition, enzymatic creation of a PVD to increase the rate of O2 exchange within the vitreal space may have potential application for treatment of retinal ischemic disease.
doi:10.1016/j.exer.2008.09.003
PMCID: PMC2694186  PMID: 18835558
guinea pig; lens; microplasmin; nuclear cataract; oxygen; posterior vitreous detachment; rat; vitreous humor
13.  Association between phosphodiesterase 4D gene and ischaemic stroke 
Background
An association between the phosphodiesterase 4D (PDE4D) gene and risk of ischaemic stroke in an Icelandic population has been suggested by the deCODE group.
Methods
A case–control study of 151 hospitalised patients with first‐ever ischaemic stroke and 164 randomly selected age‐matched and sex‐matched community controls was conducted. PDE4D genotypes for the six single‐nucleotide polymorphisms (SNPs) previously reported to be independently associated with stroke were determined, common haplotypes were inferred using the expectation‐maximisation algorithm, and SNP and haplotype associations with stroke were examined. A meta‐analysis of published studies examining the association between PDE4D and stroke was also carried out.
Results
Our study of Australian patients with stroke showed an independent association between ischaemic stroke and PDE4D SNP 89 (CC: odds ratio (OR) 5.55, 95% confidence interval (CI) 1.02 to 30.19; CA: OR 1.68, 95% CI 0.96 to 2.96; AA: OR 1 (reference)), SNP 87 (CC: OR 2.13, 95% CI 1.08 to 4.20; TC: OR 1.64, 95% CI 0.89 to 3.00; TT: OR 1 (reference)) and SNP 83 (TT: OR 2.16, 95% CI 1.08 to 4.32; TC: OR 1.37, 95% CI 0.77 to 2.43; CC: OR 1 (reference)), and between ischaemic stroke and PDE4D haplotypes at SNP 89–87–83 (A–C–C: OR 2.13, 95% CI 1.15 to 3.96; C–C–T: OR 2.25, 95% CI 1.29 to 3.92), but no association between ischaemic stroke and PDE4D SNP 56, SNP 45 or SNP 41, or with PDE4D haplotypes at SNP 56–45–41. A meta‐analysis of nine case–control studies (including our current results) of 3808 stroke cases and 4377 controls confirmed a significant association between stroke and PDE SNP 87 (pooled p = 0.002), SNP 83 (0.003) and SNP 41 (0.003). However, there was statistical heterogeneity (p<0.1) among the studies in the direction of association for each of the individual SNPs tested.
Conclusions
Our results and the pooled analyses from all the studies indicate a strong association between PDE4D and ischaemic stroke. This strengthens the evidence that PDE4D plays a key part in the pathogenesis of ischaemic stroke. Heterogeneity among the studies in the direction of association between individual SNPs and stroke suggests that the SNPs tested are in linkage disequilibrium with the causal allele(s).
doi:10.1136/jnnp.2006.092106
PMCID: PMC2077747  PMID: 16914755
14.  Impact of Single pMOSFET Dielectric Degradation on NAND Circuit Performance 
Microelectronics and reliability  2008;48(3):354-363.
Degradation of CMOS NAND logic circuits resulting from dielectric degradation of a single pMOSFET using constant voltage stress has been examined by means of a switch matrix technique. As a result, the NAND gate rise time increases by greater than 65%, which may lead to timing errors in high frequency digital circuits. In addition, the NAND gate DC switching point voltage shifts by nearly 11% which may be of consequence for analog or mixed signal applications. Experimental results for the degraded pMOSFET reveal a decrease in drive current by approximately 43%. There is also an increase in threshold voltage by 23%, a decrease in source to drain conductance of 30%, and an increase in channel resistance of about 44%. A linear relationship between the degradation of the pMOSFET channel resistance and the increase in NAND gate rise time is demonstrated, thereby providing experimental evidence of the impact of a single degraded pMOSFET on NAND circuit performance.
doi:10.1016/j.microrel.2007.09.002
PMCID: PMC2564826  PMID: 19255611
Gate oxide; dielectric degradation; pMOSFET; NAND logic gate; constant voltage stress; oxide wear out
15.  A syndromal analysis of neuropsychological outcome following coronary artery bypass graft surgery 
Background: Studies of neuropsychological outcome following coronary artery bypass graft surgery (CABG) have traditionally dichotomised patients as "impaired" or "unimpaired". This conceals the potential heterogeneity of deficits due to different mechanisms and sites of brain injury.
Objectives: To explore neuropsychological outcome following CABG and determine to what extent it conforms to prototypic cortical and/or subcortical neurobehavioral syndromes and whether different intraoperative physiologic measures are associated with different subtypes of neuropsychological outcome.
Methods: Neuropsychological tests were administered to 85 patients before and after elective CABG and to 50 matched normal control subjects. Pre- to postoperative change scores were computed using standardised regression based norms. Change scores on selected memory measures were subjected to cluster analysis to identify qualitatively distinct subtypes of memory outcome. Emergent clusters were compared on non-memory measures, intraoperative physiologic measures, and demographic variables.
Results: Three subtypes of memory outcome were identified: memory spared (48% of patients), retrieval deficit (35%), and encoding/storage deficit (17%). Contrary to expectation, the subgroups were indistinguishable on measures of confrontation naming and manual dexterity and on intraoperative cardiac surgical physiologic measures and demographic variables. The encoding/storage deficit subgroup exhibited executive dysfunction.
Conclusions: Heterogeneous profiles of neuropsychological dysfunction were found following CABG although they did not tightly conform to prototypic cortical and subcortical neurobehavioral syndromes. This challenges the value and appropriateness of the common practice of collapsing individual test scores to arrive at a single figure to define "impairment". Whether different subtypes of neuropsychological outcome are caused by different pathophysiologic mechanisms remains unknown.
doi:10.1136/jnnp.2004.047456
PMCID: PMC1739759  PMID: 16024891
16.  Tie-dyed1 and Sucrose export defective1 act independently to promote carbohydrate export from maize leaves 
Planta  2007;227(3):527-538.
tie-dyed1 (tdy1) and sucrose export defective1 (sxd1) are recessive maize (Zea mays) mutants with nonclonal chlorotic leaf sectors that hyperaccumulate starch and soluble sugars. In addition, both mutants display similar growth-related defects such as reduced plant height and inflorescence development due to the retention of carbohydrates in leaves. As tdy1 and sxd1 are the only variegated leaf mutants known to accumulate carbohydrates in any plant, we investigated whether Tdy1 and Sxd1 function in the same pathway. Using aniline blue staining for callose and transmission electron microscopy to inspect plasmodesmatal ultrastructure, we determined that tdy1 does not have any physical blockage or alteration along the symplastic transport pathway as found in sxd1 mutants. To test whether the two genes function in the same genetic pathway, we constructed F2 families segregating both mutations. Double mutant plants showed an additive interaction for growth related phenotypes and soluble sugar accumulation, and expressed the leaf variegation pattern of both single mutants indicating that Tdy1 and Sxd1 act in separate genetic pathways. Although sxd1 mutants lack tocopherols, we determined that tdy1 mutants have wild-type tocopherol levels, indicating that Tdy1 does not function in the same biochemical pathway as Sxd1. From these and other data we conclude that Tdy1 and Sxd1 function independently to promote carbon export from leaves. Our genetic and cytological studies implicate Tdy1 functioning in veins, and a model discussing possible functions of TDY1 is presented.
Electronic supplementary material
The online version of this article (doi:10.1007/s00425-007-0636-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s00425-007-0636-6
PMCID: PMC2249615  PMID: 17924136
Carbohydrate accumulation; Carbon partitioning; Maize; sucrose export defective1; tie-dyed1
17.  Getting to Grips with Clinical Governance 
doi:10.1136/qshc.2004.010512
PMCID: PMC1743908
18.  Implications of Harold Shipman for general practice 
Postgraduate Medical Journal  2004;80(944):303-306.
doi:10.1136/pgmj.2003.013110
PMCID: PMC1743029  PMID: 15192157
19.  Impact of the population at risk of diabetes on projections of diabetes burden in the United States: an epidemic on the way 
Diabetologia  2006;50(5):934-940.
Aims/hypothesis
The aim of this study was to make projections of the future diabetes burden for the adult US population based in part on the prevalence of individuals at high risk of developing diabetes.
Materials and methods
Models were created from data in the nationally representative National Health and Nutrition Examination Survey (NHANES) II mortality survey (1976–1992), the NHANES III (1988–1994) and the NHANES 1999–2002. Population models for adults (>20 years of age) from NHANES III data were fitted to known diabetes prevalence in the NHANES 1999–2002 before making future projections. We used a multivariable diabetes risk score to estimate the likelihood of diabetes incidence in 10 years. Estimates of future diabetes (diagnosed and undiagnosed) prevalence in 2011, 2021, and 2031 were made under several assumptions.
Results
Based on the multivariable diabetes risk score, the number of adults at high risk of diabetes was 38.4 million in 1991 and 49.9 million in 2001. The total diabetes burden is anticipated to be 11.5% (25.4 million) in 2011, 13.5% (32.6 million) in 2021, and 14.5% (37.7 million) in 2031. Among individuals aged 30 to 39 years old who are not currently targeted for screening according to age, the prevalence of diabetes is expected to rise from 3.7% in 2001 to 5.2% in 2031. By 2031, 20.2% of adult Hispanic individuals are expected to have diabetes.
Conclusions/interpretation
The prevalence of diabetes is projected to rise to substantially greater levels than previously estimated. Diabetes prevalence within the Hispanic community is projected to be potentially overwhelming.
Electronic supplementary material
Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00125-006-0528-5 and is accessible to authorized users.
doi:10.1007/s00125-006-0528-5
PMCID: PMC1849422  PMID: 17119914
Diabetes; Epidemiology; Projection
20.  Investigation of systems to prevent diversion of opiate drugs in general practice in the UK 
Background: Statutory regulations govern the procedures that must be followed by general practitioners (GPs) in the UK to minimise the risk of diversion of prescribed opiate drugs for illicit use. However, evidence presented at the trial of Harold Shipman, a GP convicted of murdering patients with diamorphine, suggests that the regulations and monitoring of GPs' prescribing are failing.
Aim: To assess the policies followed by general practices in Leicestershire and Rutland with regard to the controlled drugs regulations.
Methods: A semi-structured interview was administered to a purposeful sample of lead GPs to explore how their practices applied the regulations. The controlled drugs registers and drug storage facilities in these practices were inspected. A questionnaire was sent to all the remaining practices to seek information about their application of the regulations, any concerns they had about the regulations, and any suggestions for improving them.
Results: Of the 142 general practices in Leicestershire, the lead GP in 14 took part in the interviews. Respondents expressed dissatisfaction with current policies including the design of controlled drug registers, and generally supported the reintroduction of an inspection scheme. Ninety (70.9%) of the 127 practices to whom the questionnaire was sent responded and, of these, 31 (34.4%) no longer held a supply of controlled drugs. Those that did hold controlled drugs indicated concern about the regulations, confusion about some aspects including the return and disposal of unused drugs, and a desire for advice and support in the implementation of the regulations. Forty two of the 59 respondents who held a supply of controlled drugs (71.2%) would welcome regular inspection.
Conclusion: GPs are confused about the controlled drugs regulations and have little support in implementing them. The suspension of inspection schemes has reduced the amount of advice and support available to them and, in consequence, the regulations are interpreted differently in different practices. These findings are cause for concern about the risk of diversion of controlled drugs, and illustrate how patient safety systems can decay when they are not maintained.
doi:10.1136/qshc.2002.002485
PMCID: PMC1758056  PMID: 14757795
21.  Clinical Governance. 
Postgraduate Medical Journal  2003;79(938):715-716.
PMCID: PMC1742907
22.  Monitoring clinical outcomes in primary care 
Quality & safety in health care  2003;12(5):325-326.
doi:10.1136/qhc.12.5.325
PMCID: PMC1743764  PMID: 14532359
23.  Concerted changes in tropical forest structure and dynamics: evidence from 50 South American long-term plots. 
Several widespread changes in the ecology of old-growth tropical forests have recently been documented for the late twentieth century, in particular an increase in stem turnover (pan-tropical), and an increase in above-ground biomass (neotropical). Whether these changes are synchronous and whether changes in growth are also occurring is not known. We analysed stand-level changes within 50 long-term monitoring plots from across South America spanning 1971-2002. We show that: (i) basal area (BA: sum of the cross-sectional areas of all trees in a plot) increased significantly over time (by 0.10 +/- 0.04 m2 ha(-1) yr(-1), mean +/- 95% CI); as did both (ii) stand-level BA growth rates (sum of the increments of BA of surviving trees and BA of new trees that recruited into a plot); and (iii) stand-level BA mortality rates (sum of the cross-sectional areas of all trees that died in a plot). Similar patterns were observed on a per-stem basis: (i) stem density (number of stems per hectare; 1 hectare is 10(4) m2) increased significantly over time (0.94 +/- 0.63 stems ha(-1) yr(-1)); as did both (ii) stem recruitment rates; and (iii) stem mortality rates. In relative terms, the pools of BA and stem density increased by 0.38 +/- 0.15% and 0.18 +/- 0.12% yr(-1), respectively. The fluxes into and out of these pools-stand-level BA growth, stand-level BA mortality, stem recruitment and stem mortality rates-increased, in relative terms, by an order of magnitude more. The gain terms (BA growth, stem recruitment) consistently exceeded the loss terms (BA loss, stem mortality) throughout the period, suggesting that whatever process is driving these changes was already acting before the plot network was established. Large long-term increases in stand-level BA growth and simultaneous increases in stand BA and stem density imply a continent-wide increase in resource availability which is increasing net primary productivity and altering forest dynamics. Continent-wide changes in incoming solar radiation, and increases in atmospheric concentrations of CO2 and air temperatures may have increased resource supply over recent decades, thus causing accelerated growth and increased dynamism across the world's largest tract of tropical forest.
PMCID: PMC1693337  PMID: 15212094
24.  Pattern and process in Amazon tree turnover, 1976-2001. 
Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests.
PMCID: PMC1693333  PMID: 15212092
25.  Dupuytren's contracture unfolded 
BMJ : British Medical Journal  2006;332(7538):397-400.
PMCID: PMC1370973  PMID: 16484265

Results 1-25 (173)