An alternative water transport system in land plants.

The evolution of vascular tissue is a key innovation enabling plants to inhabit terrestrial environments. Here, we demonstrate extra-vascular water transport in a giant, prop-rooted monocot from Lord Howe Island. Pandanus forsteri (Pandanaceae) produces gutter-like leaves that capture rainwater, which is then couriered along a network of channels to the tips of aerial roots, where it is stored by absorptive tissue. This passive mechanism of water acquisition, transport and storage is critical to the growth of aerial prop roots that cannot yet attain water via vascular conduction. This species therefore sheds light on the elaborate means by which plants have evolved to attain water.

Ecological speciation in sympatric palms: 2. Pre- and post-zygotic isolation.

We evaluated reproductive isolation in two species of palms (Howea) that have evolved sympatrically on Lord Howe Island (LHI, Australia). We estimated the strength of some pre- and post-zygotic mechanisms in maintaining current species boundaries. We found that flowering time displacement between species is consistent across in and ex situ common gardens and is thus partly genetically determined. On LHI, pre-zygotic isolation due solely to flowering displacement was 97% for Howea belmoreana and 80% for H. forsteriana; this asymmetry results from H. forsteriana flowering earlier than H. belmoreana and being protandrous. As expected, only a few hybrids (here confirmed by genotyping) at both juvenile and adult stages could be detected in two sites on LHI, in which the two species grow intermingled (the Far Flats) or adjacently (Transit Hill). Yet, the distribution of hybrids was different between sites. At Transit Hill, we found no hybrid adult trees, but 13.5% of younger palms examined there were of late hybrid classes. In contrast, we found four hybrid adult trees, mostly of late hybrid classes, and only one juvenile F1 hybrid in the Far Flats. This pattern indicates that selection acts against hybrids between the juvenile and adult stages. An in situ reciprocal seed transplant between volcanic and calcareous soils also shows that early fitness components (up to 36 months) were affected by species and soil. These results are indicative of divergent selection in reproductive isolation, although it does not solely explain the current distribution of the two species on LHI.

Ecological speciation in sympatric palms: 1. Gene expression, selection and pleiotropy.

Ecological speciation requires divergent selection, reproductive isolation and a genetic mechanism to link the two. We examined the role of gene expression and coding sequence evolution in this process using two species of Howea palms that have diverged sympatrically on Lord Howe Island, Australia. These palms are associated with distinct soil types and have displaced flowering times, representing an ideal candidate for ecological speciation. We generated large amounts of RNA-Seq data from multiple individuals and tissue types collected on the island from each of the two species. We found that differentially expressed loci as well as those with divergent coding sequences between Howea species were associated with known ecological and phenotypic differences, including response to salinity, drought, pH and flowering time. From these loci, we identified potential 'ecological speciation genes' and further validate their effect on flowering time by knocking out orthologous loci in a model plant species. Finally, we put forward six plausible ecological speciation loci, providing support for the hypothesis that pleiotropy could help to overcome the antagonism between selection and recombination during speciation with gene flow.

A comparative analysis of the mechanisms underlying speciation on Lord Howe Island.

On Lord Howe Island, speciation is thought to have taken place in situ in a diverse array of distantly related plant taxa (Metrosideros, Howea and Coprosma; Proc. Natl Acad. Sci. USA 108, 2011, 13188). We now investigate whether the speciation processes were driven by divergent natural selection in each genus by examining the extent of ecological and genetic divergence. We present new and extensive, ecological and genetic data for all three genera. Consistent with ecologically driven speciation, outlier loci were detected using genome scan methods. This mechanism is supported by individual-based analyses of genotype-environment correlations within species, demonstrating that local adaptation is currently widespread on the island. Genetic analyses show that prezygotic isolating barriers within species are currently insufficiently strong to allow further population differentiation. Interspecific hybridization was found in both Howea and Coprosma, and species distribution modelling indicates that competitive exclusion may result in selection against admixed individuals. Colonization of new niches, partly fuelled by the rapid generation of new adaptive genotypes via hybridization, appears to have resulted in the adaptive radiation in Coprosma - supporting the 'Syngameon hypothesis'.

What is associated with being active in arthritis? Analysis from the Obstacles to Action study.

BACKGROUND: Many adults with arthritis do not achieve physical activity levels recommended for good health. This study aimed to identify factors associated with physical activity participation in people with arthritis. METHODS: 1106 out of 8163 adults with self-reported arthritis were identified from the 2003 Obstacles to Action study. Participants were classified as active if they reported 30 min of moderate activity > or = 5 days a week or 20 min of vigorous activity > or = 3 days a week (n = 613), or insufficiently active if they did not (n = 438). Sociodemographic factors, attitudes, self-efficacy, motivators and barriers to being active were analysed. RESULTS: Active people with arthritis had a lower burden of chronic disease than insufficiently active people (18% with three or more chronic medical conditions vs 33%, P < 0.0001). Active participants believed more strongly in the benefits of physical activity, reported higher levels of encouragement from others and had greater overall levels of self-efficacy when compared with the less active participants (P for all <0.0001). Arthritis, fatigue and discomfort were ranked by both groups as the top three barriers. However, the active participants reported lower impact scores for these barriers than the inactive group (P for all <0.0001). These findings persisted after adjusting for occupational status, body mass index and comorbidities. CONCLUSION: Active adults with arthritis have lower levels of chronic disease, greater self-efficacy and fewer psychosocial barriers. Recognition of such barriers and motivators may be useful when designing intervention programmes to help people with arthritis initiate or intensify physical activity participation.

Using simulation models to teach junior doctors how to insert chest tubes: a brief and effective teaching module.

BACKGROUND: Pleural procedures may cause serious complications when incorrectly carried out. There is a need to find effective methods for teaching how to insert a chest drain safely. AIM: To assess the effectiveness of a programme for teaching chest tube insertion using a simulation model (SuperAnnie). METHODS: Groups of four to six junior doctors were enrolled in a 2-h teaching session, covering both theoretical knowledge and practical chest tube insertion techniques using a simulation model. Before the teaching module, participants completed a questionnaire about their confidence and skill levels and were videotaped inserting a standard chest tube in the model. The assessments were repeated 1 month after the teaching module. The video clips were scored by two independent assessors using an 18-point scoring system that was blinded to whether the taping was pre- or post-teaching. RESULTS: Forty-nine doctors completed the study. Baseline video assessment scores were low (median score 4 (maximum possible score 18), interquartile range (IQR) 2-7.5) and were not associated with past experience, the doctor's self-confidence level or their self-assessed skill rating. After teaching, video assessment scores improved significantly (mean score 13, IQR 10.5-15). Doctors with the lowest baseline scores showed the most improvement. There were also improvements in doctors' self-confidence and self-assessed skill levels, although there remained no association between these measures and video assessment scores. CONCLUSIONS: A brief teaching module using a simulation model is effective in improving confidence and skill in chest tube insertion.

Introduction of a Simple Second Tier Screening Test for C5 Isobars in Dried Blood Spots: Reducing the False Positive Rate for Isovaleric Acidaemia in Expanded Newborn Screening.

In 2015 the English Newborn Screening programme expanded to include Isovaleric Acidaemia (IVA). Screening is performed by flow injection analysis tandem mass spectrometry of isovalerylcarnitine. Isovalerylcarnitine is isobaric with pivaloylcarnitine which can be present in blood due to the use of pivalic ester pro-drugs or pivalic acid derivatives used as emollients in some nipple creams; the potential for false positives (FP) is well documented. A pilot study in England screened 438,164 babies, 18 had presumptive positive results but only 4 were confirmed as true positives (TP). We developed a simple test to separate the isobaric compounds and investigate these samples further.We studied newborn screening blood spots from 122 randomised controls and 34 infants with an initial raised C5 result. Dried blood spots were eluted with 30% acetonitrile (150 µL) and injected into a Waters Acquity UPLC coupled to a Waters Premier XE tandem mass spectrometer operating in positive ion mode. Isocratic separation of isovalerylcarnitine, pivaloylcarnitine, valerylcarnitine and 2-methylbutyrylcarnitine was achieved within 8 min. Assay performance characteristics were acceptable and non-parametric reference ranges (n = 122) were determined for each analyte.If this method had been used as a second tier test for the 34 presumptive positive samples, the number of FP's would have reduced from 24 to 8 and the positive predictive value of the screening test would have increased from 29 to 56%. Introduction of this test into the screening protocol has the potential to significantly reduce FP results for IVA and prevent unnecessary anxiety.

The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling.

Influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact dogs with prolonged coronary artery occlusion.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact, unsedated dogs with myocardial infarction resulting from chronic occlusion of the proximal left anterior descending coronary artery was studied. tmannitol given to increase serum osmolality 20 mOsm increased regional myocardial blood flow to that portion of the left ventricle supplied by the occluded left anterior descending coronary artery by 22 +/- 2.8% (1.06 +/- 0.19 to 1.36 +/- 0.23 ml/min with g-1) without changing the inner:outer wall flow ratio. Mannitol also significantly increased regional myocardial blood flow to other areas of the left ventricle and the ventricular septum. Mean aortic pressure, maximal LV dP/dt, LV dP/dt/P, and cardiac output also increased significantly after mannitol. Thus hypertonic mannitol increases regional myocardial blood flow and ventricular performance in the awake, unsedated dog with prolonged occlusion of the proximal left anterior descending coronary artery. The increase in regional myocardial blood flow after mannitol under these circumstances probably is at least in part secondary to the increase in blood pressure and contractility. The increases in regional myocardial blood flow after mannitol in this study are less impressive than those that have been previously reported in the setting of either no myocardial ischaemia or acute myocardial ischaemia; this is probably due to the vasodilatation that chronic myocardial ischaemia itself produces in the canine heart.

Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.

Comparison of Doppler ultrasound velocity measurements with pressure differences across bioprosthetic valves in a pulsatile flow model.

Continuous wave Doppler ultrasound was used in vitro to assess the pressure differences across four different cardiac bioprosthetic valves in a pulsatile flow test apparatus. Valves were tested under four different flow conditions. Pressure differences were calculated from the maximum flow velocity measured by Doppler ultrasound and correlated well with the pressure differences measured directly in the flow model (r = 0.98). Thus Doppler ultrasound can accurately measure pressure differences across bioprosthetic valves in vitro.

Changes in regional coronary blood flow with hypertonic mannitol in conscious dogs.

Systemic haemodynamics and regional myocardial blood flow responses to hypertonic mannitol were studied in 10 conscious and 23 anaesthetized dogs. Mannitol infusion significantly increased regional myocardial blood flow in the conscious, intact dogs. Mannitol increased total coronary flow 20% in anasethetized animals compared to 80% in the awake ones. In both groups mannitol exerted a significant positive inotropic effect as evidenced by increases in maximal LV dp/dt and dp/dt/p. These studies have also demonstrated that the intact conscious dog that has not received any sedation has an inner:outer wall left ventricular flow ratio greater than 1-0.

Gated xenon scans for right ventricular function.

The complex geometry of the right ventricle makes the use of radionuclides an attractive method for assessing right ventricular function. The use of the gated 133Xe technique for this purpose offers several advantages. A short i.v. infusion over 20 sec of 133Xe permits scans to be obtained, gated to the electrocardiogram at rest and during maximal exercise using a standard gamma camera. The method is both reproducible (3.5%) and repeatable (2.8%), and because of the short half-life within the patient with most of the radioisotope being excreted by the lungs, scans may be repeated within a few minutes and the radiation dose to the patient is small. Right ventricular ejection fraction obtained from gated xenon scans is shown to correlate well with measurements obtained from both standard gated technetium scans and first-pass studies.

Acylated streptokinase--plasminogen complex in patients with acute myocardial infarction.

BRL 26921 is the p- anisoyl derivative of the primary streptokinase-human plasminogen complex in which the acyl group is specifically located at the catalytic centre of the enzyme. Doses of BRL 26921 ranging from 5 mg to 25 mg were given intravenously or into a coronary artery to 12 patients with acute myocardial infarction. The complex was well tolerated and produced no serious bleeding. Coronary artery reperfusion was demonstrated angiographically in three patients. In most patients, fibrinogen, plasminogen, alpha 2 antiplasmin and alpha 2 macroglobulin levels fell and the level of fibrinogen degradation products increased acutely post treatment indicating systemic fibrinolytic activation. The degree of this activation was variable but was profound in some. It appeared to be dose related and modified by the presence of streptokinase antibodies. BRL 26921 appears less "selectively" thrombolytic in patients than had been expected from animal models.

The effects of propranolol and acebutolol on left ventricular function and coronary haemodynamics in the conscious dog with myocardial ischaemia.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.

The effects of a new beta-adrenoceptor blocking compound, tolamolol, on haemo-dynamics and myocardial function in man.

1 The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.2 The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 +/- 7 to 62 +/- 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 +/- 0.9 to 3.5 +/- 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.3 There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dt(max)) and the derived index of the left ventricular contractile state (V(max)).4 These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.

Planning for coronary angioplasty: guidelines for training and continuing competence. British Cardiac Society (BCS) and British Cardiovascular Intervention Society (BCIS) working group on interventional cardiology.

The following recommendations are made: 1 Existing centres undertaking angioplasty should increase their activity, and the target figure of 400 PTCA procedures per million of the United Kingdom population should be achieved by the end of 1996-97, or immediately thereafter. 2 Angioplasty centres should be appropriately equipped to undertake PTCA safely and effectively and provide a reliable emergency service. They should have a minimum of two trained PTCA operators jointly undertaking a minimum of 200 procedures per year at that centre, and have regular meetings to share experience. 3 Angioplasty operators should ensure that where the need arises patients undergoing PTCA can receive immediate attention from a trained operator at any time until discharge from hospital. 4 Trained operators should undertake at least 1-2 PTCA procedures per week (> 60 procedures per year) to maintain competence, and those undertaking so few procedures should increase their activity over the next three years to more than 100 a year. 5 Trainers should have performed at least 500 procedures before formally training others and should undertake a minimum of 125 procedures a year to maintain accreditation as a trainer. 6 Surgical cover for PTCA procedures should be mandatory and on site cover remains the strongly preferred option. Where surgical cover is provided off site, this should be at a centre less than 30 minutes away by road. Whether provided on or off-site it should be possible to establish cardiopulmonary bypass within 90 minutes of the decision being made to refer the patient for surgery. 7 All operators and interventional centres should audit their activity and results, review these data locally with colleagues, and provide regular audit returns to the national database run by BCIS. This will allow future recommendations concerning standards to take more account of risk stratification and actual outcomes, and not place such emphasis merely on volumes of activity. 8 These recommendations should be reviewed in three years.

Breathlessness in microvascular angina.

In patients with microvascular angina (MA), there is some evidence from studies of plethysmography, that there are widespread microvascular abnormalities. In addition to exertional chest pain, all these patients complain of breathlessness, with no evidence of airways obstruction or resting left ventricular dysfunction. Progressive exercise testing was performed in 12 age and sex matched controls and 12 patients (three males), in whom the diagnosis of MA was established on the basis of exertional chest pain, abnormal thallium scans, and an attenuated myocardial flow response to a vasodilator challenge, with angiographically entirely normal epicardial vessels. Symptom limited exercise was performed with on line ventilation and expired gas analysis, measuring minute ventilation, oxygen consumption and carbon dioxide production and arterial blood gas values using a transcutaneous system. Anaerobic threshold was calculated by curve fitting a plot of oxygen consumption against carbon dioxide production. Compared to controls (49.7 +/- 7.3 SD% predicted maximum VO2) in patients with MA, the anaerobic threshold was reduced (41.6 +/- 5.82; P < 0.02) although still within accepted normal limits. Maximal (symptom limited) oxygen consumption, as a percentage of predicted, was reduced 60.73 +/- 16.51 compared to 87.21 +/- 5.2 (P < 0.003). The ventilatory response (VE/VCO2 l l-1 CO2 output) was significantly increased in the MA patients compared to controls (35.9 +/- 8.01 and 27.5 +/- 3.08, respectively; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Long term haemodynamic, pulmonary function and symptomatic effects of pirbuterol in COPD.

Haemodynamic studies at rest and during exercise together with radionuclide ventriculography, pulmonary function and clinical well-being assessment were evaluated in ten patients with COPD and secondary pulmonary hypertension (mean PAP 25 mm Hg), before and after 6 months therapy with pirbuterol 20 mg thrice daily. Despite the continued pharmacological action of pirbuterol on the heart and systemic circulation during peak pirbuterol levels at 6 months, no significant effect on the pulmonary circulation was observed. Seven patients reported an improvement in the level of fatigue, the partial pressure of carbon dioxide fell significantly (6.5 +/- 0.9 to 6.1 +/- 0.9 kPa: P less than 0.01) and there was a slight bronchodilator effect [forced expiratory volume in 1s (FEV1) 0.60 +/- 0.18 to 0.71 +/- 0.2 1s-1: P less than 0.02] after 6 months. The drug was generally well tolerated but three patients with pre-existing biliary tract disease developed obstructive jaundice.

Lung uptake of thallium-201: a marker of defect reversibility?

High lung uptake of thallium-201 at stress is reported to be associated with a large number of perfusion defects and poor prognosis. This study was performed to assess whether the reversibility of stress perfusion defects was related to lung uptake. Gated planar thallium scans at stress and at redistribution from 102 consecutive patients with essentially normal left ventricular ejection fraction (using 99mTc gated blood pool ventriculography) were graded in terms of defect size. Lung and myocardial uptake of thallium were quantitated by region of interest methods relative to the given activity in a previously validated method. There was no significant correlation (non-parametric) between lung uptake and degree of redistribution (p = ns, rs = 0.140). There was a weak but positive correlation between lung uptake and defect size (p < 0.05, rs = 0.188). Both exercise time and double product showed a negative correlation with lung uptake (e.g. for double product, p < 0.0005, rs = -0.541). In conclusion, contrary to our expectation, lung uptake is not related to the degree of redistribution. High lung uptake seems to reflect poor cardiovascular reserve.