Analysis of satellite imagery using a simple algorithm supports evidence that Trichodesmium supplies a significant new nitrogen load to the GBR lagoon.

This work supports previous studies in the Great Barrier Reef lagoon that show the new nitrogen (N) load introduced by Trichodesmium is similar to or greater than that from riverine discharges. However, the current management programs aimed at improving the chronic eutrophic state of the GBR ignore the N load from Trichodesmium. These programs also ignore the evidence that Trichodesmium blooms could promote the bioavailability of heavy metals and be a source of toxins in the ciguatera food chain. Further work is urgently required to better quantify the potential impacts of Trichodesmium and develop management plans to reduce those impacts. A simple algorithm that uses MODIS imagery is developed for not only monitoring the spatial extent of Trichodesmium blooms but also for quantifying the concentration of those blooms. The algorithm is based on the readily available MODIS L2 data. A management plan that includes the harvesting of Trichodesmium is outlined.

Placental restriction in multi-fetal pregnancies and between-twin differences in size at birth alter neonatal feeding behaviour in the sheep.

Most individuals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON (n=14) and PR (n=12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (-15%, P=0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes (P=0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.

Conserved residues of the Pro103-Arg115 loop are involved in triggering the allosteric response of the Escherichia coli ADP-glucose pyrophosphorylase.

The synthesis of glycogen in bacteria and starch in plants is allosterically controlled by the production of ADP-glucose by ADP-glucose pyrophosphorylase. Using computational studies, site-directed mutagenesis, and kinetic characterization, we found a critical region for transmitting the allosteric signal in the Escherichia coli ADP-glucose pyrophosphorylase. Molecular dynamics simulations and structural comparisons with other ADP-glucose pyrophosphorylases provided information to hypothesize that a Pro103-Arg115 loop is part of an activation path. It had strongly correlated movements with regions of the enzyme associated with regulation and ATP binding, and a network analysis showed that the optimal network pathways linking ATP and the activator binding Lys39 mainly involved residues of this loop. This hypothesis was biochemically tested by mutagenesis. We found that several alanine mutants of the Pro103-Arg115 loop had altered activation profiles for fructose-1,6-bisphosphate. Mutants P103A, Q106A, R107A, W113A, Y114A, and R115A had the most altered kinetic profiles, primarily characterized by a lack of response to fructose-1,6-bisphosphate. This loop is a distinct insertional element present only in allosterically regulated sugar nucleotide pyrophosphorylases that could have been acquired to build a triggering mechanism to link proto-allosteric and catalytic sites.

Evidence of large-scale chronic eutrophication in the Great Barrier Reef: quantification of chlorophyll a thresholds for sustaining coral reef communities.

Long-term monitoring data show that hard coral cover on the Great Barrier Reef (GBR) has reduced by >70 % over the past century. Although authorities and many marine scientists were in denial for many years, it is now widely accepted that this reduction is largely attributable to the chronic state of eutrophication that exists throughout most of the GBR. Some reefs in the far northern GBR where the annual mean chlorophyll a (Chl a) is in the lower range of the proposed Eutrophication Threshold Concentration for Chl a (~0.2-0.3 mg m⁻³) show little or no evidence of degradation over the past century. However, the available evidence suggests that coral diseases and the crown-of-thorns starfish will proliferate in such waters and hence the mandated eutrophication Trigger values for Chl a (~0.4-0.45 mg m⁻³) will need to be decreased to ~0.2 mg m⁻³ for sustaining coral reef communities.

Should the size threshold for elective abdominal aortic aneurysm repair be lowered in the endovascular era? Yes.

According to current international guidelines, patients with infrarenal or juxtarenal abdominal aortic aneurysms (AAAs) measuring > or = 5.5 cm should undergo repair to reduce the risk of rupture. The 5.5-cm-diameter threshold is the size when the AAA rupture rate balances the mortality rates of elective open surgical AAA repair (3%). Endovascular AAA repair (EVAR) is associated with lower perioperative mortality and complication rates compared with open surgical repair. This debate addresses the issue whether the current size threshold for elective AAA repair needs to be lowered in the endovascular era. This paper supports the position that the size threshold for AAA repair should be lowered in the endovascular era.

The GALA trial: will it influence clinical practice?

The General Anesthesia vs. Local Anesthesia for Carotid Surgery (GALA) trial did not show a difference in 30-day postoperative stroke, myocardial infarction and death rates between patients undergoing carotid endarterectomy (CEA) under local vs. general anesthesia. The present article discusses some limitations of the GALA trial. Firstly, the expected stroke and death rates following CEA is so low, that it was unlikely that the GALA trial would show any significant difference between local and general anesthesia. Secondly, preoperative statin use was not recorded. Thirdly, intraoperative shunt usa ge rates (a possible parameter for the development of stroke) varied considerably between the 2 groups (43% vs. 14%, for general vs. local anesthesia, respectively; P < .0001), as well as between UK and non-UK surgeons who always (73.6% vs. 20.8%, respectively; P < .0001), never (4.2% vs. 26%, respectively; P < .0002), or selectively (22.2% vs. 53.2%, respectively; P < .0001) used a shunt. Furthermore, no information was provided regarding the type of shunts used; for example, atraumatic shunts may be associated with lower perioperative stroke rates. These limitations could influence the interpretation of the results of the GALA trial. Due to lack of differences between the 2 groups and the presence of the above limitations, it seems likely that this trial will have little effect on clinical practice.

Treatment of asymptomatic carotid disease with stenting: con.

The landmark trials of the 1980s established a powerful precedent for demanding that "evidence" rather than "intuitive reasoning" should determine practice regarding management of patients with carotid disease. Accordingly, for our opponents to succeed in this debate, they must first demonstrate that there is little remaining confusion regarding the optimal management of asymptomatic carotid disease and then provide compelling evidence that it is now reasonable to offer carotid angioplasty with stenting without the protection of randomized trials. It is our contention that neither can be demonstrated and that the motion cannot be sustained.

The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo.

BACKGROUND: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. METHODS: Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. RESULTS: Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. CONCLUSIONS: These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.

Repair of ruptured abdominal aortic aneurysms by endovascular techniques.

Emergency EVR for ruptured AAA is now technically feasible, and several reports with small numbers have appeared in the literature from major centers suggesting that the results may be the same as or better than seen with open repair. The immediate priority is avoidance of over-resuscitation together with the rapid transfer of the patient to CT and then to the operating theater. Because of the learning curve involved, these cases should be attempted only by major centers that have extensive elective endovascular experience. The requirement for 24-hour availability of surgeons and radiologists trained in endovascular techniques places an enormous strain on vascular and radiologic staff and is achievable only in major centers with large teams of doctors. These issues raise important questions about the delivery of vascular services and whether all cases of ruptured aortic aneurysm should be transferred to major vascular centers. The operating theater staff and other support persons need training in endovascular techniques and in rapid deployment of an aortic occlusion balloon. A wide selection of devices, guidewires, and catheters must be immediately available in the operating theater. The ideal way to establish the role of EVR for ruptured AAA would be a randomized trial, but there might be logistic difficulties in recruiting sufficient numbers in major vascular centers, particularly as screening for AAA becomes more common and reduces the number of cases. There also are ethical issues as to whether these patients can give informed consent for involvement in such a trial. The alternative is for major centers to continue to develop their endovascular programs, to do more cases, and to compare the results with historical controls undergoing open repair.

Reevaluation of ENCORE: support for the eutrophication threshold model for coral reefs.

The results from the multimillion dollar Enrichment of Nutrients on Coral Reefs Experiment (ENCORE) on One Tree Island Reef (OTIR) suggest that increased nutrient loads to coral reefs will have little or no effect on the algal growth rates and, hence, on the associated effects that increased algal growth might have on the functioning and stability of coral reefs. However, a comparison of the concentrations of nutrients within the OTIR lagoon with the proposed nutrient threshold concentrations (NTC) for coral reefs suggests that all sites, including the control sites, were saturated with nutrients during ENCORE, and, hence, one would not expect to get any differences between treatments in the algal-growth related measurements. Thus, ENCORE results provide strong support for the proposed NTCs and support the ecological principle that algal productivity and, consequently, the functioning of coral reefs are sensitive to small changes in the background concentrations of nutrients. The principal conclusion of ENCORE, namely that the addition of nutrients did not cause the "pristine" OTIR to convert from coral communities to algal dominated reefs, is contrary to the fact that there was prolific macroalgal growth on the walls and crests of the experimental microatolls by the end of ENCORE.

Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). METHODS AND RESULTS: Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. CONCLUSIONS: A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.

Using cognitive task analysis to facilitate the integration of decision support systems into the neonatal intensive care unit.

OBJECTIVE: New medical systems may be rejected by staff because they do not integrate with local practice. An expert system, FLORENCE, is being developed to help staff in a neonatal intensive care unit (NICU) make decisions about ventilator settings when treating babies with respiratory distress syndrome. For FLORENCE to succeed it must be clinically useful and acceptable to staff in the context of local work practices. The aim of this work was to identify those contextual factors that would affect FLORENCE's success. METHODS: A cognitive task analysis (CTA) of the NICU was performed. First, work context analysis was used to identify how work is performed in the NICU. Second, the critical decision method (CDM) was used to analyse how staff make decisions about changing the ventilator settings. Third, naturalistic observation of staff's use of the ventilator was performed. RESULTS: A. The work context analysis identified the NICU's hierarchical communication structure and the importance of numerous types of record in communication. B. It also identified important ergonomic and practical requirements for designing the displays and positioning the computer. C. The CDM interviews suggested instances where problems can arise if the data used by FLORENCE, which is automatically read, is not manually verified. D. Observation showed that most alarms cleared automatically. When FLORENCE raises an alarm, staff will normally be required to intervene and make a clinical judgement, even if the ventilator settings are not subsequently changed. CONCLUSIONS: FLORENCE must not undermine the NICU's hierarchical communication channels (A). The re-design of working practices to incorporate FLORENCE, reinforced through its user interface, must ensure that expert help is called on when appropriate (A). The procedures adopted with FLORENCE should ensure that the data the advice is based upon is valid (C). For example, FLORENCE could prompt staff to manually verify the data before implementing any suggested changes. FLORENCE's audible alarm should be clearly distinguishable from other NICU alarms (D); new procedures should be established to ensure that FLORENCE alarms receive attention (D), and false alarms from FLORENCE should be minimised (B, D). FLORENCE should always provide the data and reasoning underpinning its advice (A, C, D). The methods used in the CTA identified several contextual issues that could affect FLORENCE's acceptance. These issues, which extend beyond FLORENCE's capability to suggest changes to the ventilator settings, are being addressed in the design of the user interface and plans for FLORENCE's subsequent deployment.

An investigation into the cause of distal endoleaks: role of displacement force on the distal end of a stent-graft.

PURPOSE: To investigate if the forces developed by pulsatile flow on a stent-graft and dimensional changes of the graft material might contribute to distal endoleak and stent-graft kinking. METHODS: An in vitro experimental model was used to measure the peak displacement force developed by pulsatile flow pressure on the distal end of a stent-graft. Polytetrafluoroethylene (PTFE) graft material (110 mm long, 22 mm in diameter) was evaluated in a flow circuit, with water as the circulating liquid. In addition, the effect of internal pressure on PTFE graft dimensions was measured under nonpulsatile conditions in 3 configurations (1 bifurcated and 2 straight). RESULTS: Pressure in the PTFE graft did not cause a change in graft diameter but did increase the length of the graft. The mean load required to prevent retrograde displacement was 208.5+/-2.5 g. Peak retrograde displacement force developed on the distal end of the stent-graft by the pressure of pulsatile flow was strongly associated with the systolic phase of the cardiac cycle. CONCLUSIONS: The distal end of the stent-graft is subject to a retrograde displacement force by the pressure of pulsatile arterial flow. In addition, pressure inside the PTFE graft causes its length to increase. Both of these factors may be important in the development of late complications of stent-grafting.

Does carotid endarterectomy lead to a decline in cognitive function or health related quality of life?

Carotid endarterectomy has been shown to reduce the long-term risk of stroke in selected patients. The present study was designed to examine cognitive function and health related quality of life in a series of carotid endarterectomy patients. One hundred and nine patients undergoing carotid endarterectomy were assessed before surgery and at 6 months post op (n = 100) on standard cognitive function tests and quality of life surveys. Microembolisation was detected using transcranial Doppler ultrasonography. Multivariate repeated measures analysis if variance identified evidences of significant impairments on some tests. Further analysis revealed that particulate Microembolisation detected during the procedure was a significant risk factor associated with declining cognitive function. Patients' self-reported health related quality of life had not deteriorated at 6 month following surgery.

Anti-platelet effect of aspirin is substantially reduced after administration of heparin during carotid endarterectomy.

OBJECTIVES: Aspirin therapy is usually continued throughout the perioperative period to reduce the risk for thromboembolic stroke and myocardial infarction after carotid endarterectomy (CEA). Aspirin irreversibly binds cyclooxygenase-1, thereby reducing platelet aggregation for the lifetime of each platelet. However, recent research from this unit has shown that aggregation in response to arachidonic acid increases significantly, but transiently, during CEA, which suggests that the anti-platelet effect of aspirin is temporarily reversed. The purpose of the current study was to determine when this phenomenon occurs and to identify the possible mechanisms involved. METHODS: Platelet aggregation was measured in platelet-rich plasma from 41 patients undergoing CEA who were stabilized with 150 mg of aspirin daily. Blood was taken at 8 time points: before anesthesia, after anesthesia, before heparinization, 3 minutes after heparinization, 3 minutes after shunt insertion, 10 minutes after flow restoration, 4 hours postoperatively, and 24 hours postoperatively. Platelet aggregation was also measured at similar times in a group of 18 patients undergoing peripheral angioplasty without general anesthesia. RESULTS: All patient platelets were effectively inhibited by aspirin at the start of the operation. There was a significant intraoperative increase in platelet response to arachidonic acid in both groups of patients, which occurred within 3 minutes of administration of unfractionated heparin. In the CEA group this resulted in a greater than 10-fold increase in mean aggregation, to 5 mmol/L of arachidonic acid (5 mmol/L), rising from 3.9% +/- 2.2% preoperatively to 45.1% +/- 29.3% after administration of heparin ( P <.0001). This increased aggregation persisted into the early postoperative period, but by 24 hours post operation aggregation had returned to near preoperative values. Aggregation in response to other platelet agonists (adenosine diphosphate, thrombin receptor agonist peptide) showed only a small increase at the same time, which could be accounted for by a parallel increase in the level of spontaneous aggregation. CONCLUSION: Administration of heparin significantly increases platelet aggregation in response to arachidonic acid, despite adequate inhibition by aspirin administered preoperatively. This apparent reversal in anti-platelet activity persisted into the immediate early postoperative period, and could explain why a small proportion of patients are at increased risk for acute cardiovascular events after major vascular surgery, despite aspirin therapy.