Occlusive Disease and Upright Activity in Acute Ischemic Stroke.

The impact of out-of-bed upright activity on outcomes in ischemic stroke patients with severe extra- and intracranial stenosis or occlusion is unknown. Using ultrasound findings from a cohort recruited to A Very Early Rehabilitation Trial (AVERT) which compared higher dose very early mobilisation (VEM) to usual care (UC), we aimed to explore the association between occlusive disease and 3-month outcomes and occlusive disease-by-mobilisation treatment interactions. Participants with ischemic stroke, with carotid and transcranial Doppler ultrasounds performed ≤1 week after admission, were included in this single centre substudy in Melbourne, Australia. Reports were retrospectively reviewed to determine the degree of stenosis or presence of occlusion in the relevant arterial territory. Stenosis ≥70% extracranial or ≥50% intracranial were classified as severe or occlusion. Overall, 19% (n = 36/191) had occlusive disease in the affected circulation. About 40% (n = 14/36) with occlusive disease and 51% (n = 79/155) without had a 3-month favourable outcome (mRS 0-2) (adjusted OR0.53, CI0.17-1.67). Fourteen percent (n = 5) with occlusive disease and 4% (n = 6) without died by 3 months (adjusted OR2.52, CI0.6-10.7). Fifty percent (n = 11/22) of UC (adjusted OR0.86, CI0.23-3.2) and 21% (n = 3/14) of VEM participants (adjusted OR0.16, CI0.01-2.7) with occlusive disease had a favourable outcome. Almost 30% (n = 4) VEM participants with occlusive disease died (adjusted OR3.99, CI0.69-22.9) compared to 5% (n = 1) UC participants with occlusive disease (adjusted OR0.45, CI0.02-8.6), however numbers were small. No stenosis-by-treatment interactions were found. High quality prospective studies are needed to help guide decision making about when patients with occlusive disease should commence upright activity in acute stroke.

Persistently Elevated Microvascular Resistance Postrecanalization.

Background and Purpose- Impaired microvascular reperfusion despite complete recanalization (no-reflow) represents a potential therapeutic target to improve outcomes after recanalization therapies. Although well documented in animal models, this phenomenon has not been demonstrated clinically. We investigated whether transcranial Doppler can detect acute microvascular changes postrecanalization as a biomarker of the no-reflow phenomenon in stroke patients. Methods- Consecutive patients with recanalized (Thrombolysis in Cerebral Infarction grade IIb/III) acute middle cerebral artery occlusion by thrombectomy at a Comprehensive Stroke Centre with a high-volume neurovascular laboratory were retrospectively identified. Sonographic measures of middle cerebral artery territory microvascular resistance (pulsatility index and resistive index) on days 1 to 3 follow-up transcranial Doppler were compared between patients and age/gender-matched controls. Results- In 53 patients, middle cerebral artery pulsatility index was significantly more likely to be asymmetrically increased on interside comparison (27.9% versus 4.9%; P=0.007) and abnormally elevated beyond normal reference ranges (46.7% versus 22.0%; P=0.016) in the symptomatic hemisphere. Middle cerebral artery pulsatility index elevation was associated with less hemorrhagic infarction (9.5% versus 45.8%; P=0.009) but worse functional outcome irrespective of infarct volume as assessed on 90-day modified Rankin Scale (score of ≤1, 18.2% versus 58.1%; P=0.035). Conclusions- Elevated microvascular resistance within the ischemic territory is commonly present after successful recanalization as measured by pulsatility index on transcranial Doppler and may be a readily available and clinically relevant biomarker of the no-reflow phenomenon.

Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.

BACKGROUND: Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. METHODS: The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. DISCUSSION: The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.

Complementary Microorganisms in Highly Corrosive Biofilms from an Offshore Oil Production Facility.

Offshore oil production facilities are frequently victims of internal piping corrosion, potentially leading to human and environmental risks and significant economic losses. Microbially influenced corrosion (MIC) is believed to be an important factor in this major problem for the petroleum industry. However, knowledge of the microbial communities and metabolic processes leading to corrosion is still limited. Therefore, the microbial communities from three anaerobic biofilms recovered from the inside of a steel pipe exhibiting high corrosion rates, iron oxide deposits, and substantial amounts of sulfur, which are characteristic of MIC, were analyzed in detail. Bacterial and archaeal community structures were investigated by automated ribosomal intergenic spacer analysis, multigenic (16S rRNA and functional genes) high-throughput Illumina MiSeq sequencing, and quantitative PCR analysis. The microbial community analysis indicated that bacteria, particularly Desulfovibrio species, dominated the biofilm microbial communities. However, other bacteria, such as Pelobacter, Pseudomonas, and Geotoga, as well as various methanogenic archaea, previously detected in oil facilities were also detected. The microbial taxa and functional genes identified suggested that the biofilm communities harbored the potential for a number of different but complementary metabolic processes and that MIC in oil facilities likely involves a range of microbial metabolisms such as sulfate, iron, and elemental sulfur reduction. Furthermore, extreme corrosion leading to leakage and exposure of the biofilms to the external environment modify the microbial community structure by promoting the growth of aerobic hydrocarbon-degrading organisms.

Artificial light at night desynchronizes strictly seasonal reproduction in a wild mammal.

Change in day length is an important cue for reproductive activation in seasonally breeding animals to ensure that the timing of greatest maternal investment (e.g. lactation in mammals) coincides with favourable environmental conditions (e.g. peak productivity). However, artificial light at night has the potential to interfere with the perception of such natural cues. Following a 5-year study on two populations of wild marsupial mammals exposed to different night-time levels of anthropogenic light, we show that light pollution in urban environments masks seasonal changes in ambient light cues, suppressing melatonin levels and delaying births in the tammar wallaby. These results highlight a previously unappreciated relationship linking artificial light at night with induced changes in mammalian reproductive physiology, and the potential for larger-scale impacts at the population level.

Chronic cerebrospinal venous insufficiency is not more prevalent in patients with mild multiple sclerosis: a sonographer-blinded, case-control ultrasound study.

OBJECTIVES: We designed a prospective case-control study of patients with clinically isolated syndrome (CIS) and Relapsing-Remitting Multiple Sclerosis (RRMS) with an Expanded Disability Status Score (EDSS) of ≤2, compared with age-and-sex-matched healthy controls, to test the hypothesis that chronic cerebrospinal venous insufficiency (CCSVI) is more prevalent in patients with CIS or mild MS. METHODS: All subjects were examined using a Siemens Antares duplex ultrasound machine. The internal jugular, vertebral and intracranial veins were studied in subjects in both supine and sitting postures. The sonographer was blind to the subject's clinical status. Measures included the criteria proposed by Zamboni and volume flow. Presence of CCSVI was defined as ≥2 Zamboni criteria. RESULTS: Seventy patient-control pairs were recruited, with 11 males and 59 females in each group. Only one subject, a control, satisfied the Zamboni definition of CCSVI; however, 19 patients and 13 controls had abnormalities as defined by Zamboni, the difference largely caused by a higher prevalence in patients of internal jugular vein (IJV) stenosis, defined as a cross-sectional area ≤0.3cm(2). This difference disappeared with a more rigorous stenosis definition. Further analysis revealed there was IJV valve variation in seven patients and one control. CONCLUSIONS: Our findings indicate that CCSVI, as defined by the Zamboni ultrasound criteria, is not present in CIS and mild RRMS (EDSS ≤2), providing further evidence that CCSVI does not have a causal role in MS; however, we found an apparent increase in IJV variation in patients with CIS or mild MS that would warrant further investigation.

Microembolic signals in patients with systemic lupus erythematosus.

INTRODUCTION: Central nervous system (CNS) involvement is a common and less understood aspect of systemic lupus erythematosus (SLE). Microembolic signals (MES) have been reported in SLE. We conducted a prospective study to evaluate the frequency of MES among patients with CNS involvement and those without. The main aim of the study is to clarify the pathophysiology of the CNS involvement in SLE. METHODS AND MATERIALS: Sixty eight patients with a diagnosis of SLE (60 females, 8 males) participated in the study. Both middle cerebral arteries were monitored using transcranial Doppler for 60 min to detect MES. All cases underwent neurology and psychiatry assessments. RESULTS: MES were detected in 7/68 patients (10.3%) with the mean number of 3.5 per hour. MES were significantly higher in patients with CNS involvement (6/24, 25%) than those without (1/44, 2.2%) (P=0.006). SLE disease activity index, duration of disease, plaque formation, intima-media thickness, and antiphospholipid antibodies were not associated with MES. MES were more frequent in patients receiving Aspirin and/or Warfarin (p=0.02). CONCLUSIONS: MES may be a predictor for CNS involvement in SLE patients at risk for neuropsychiatric syndromes. Cerebral embolism may be implicated in the pathophysiology of neuropsychiatric SLE.

Cerebral haemodynamics with head position changes post-ischaemic stroke: A systematic review and meta-analysis.

The effects of upright postures on the cerebral circulation early post-ischaemic stroke are not fully understood. We conducted a systematic review and meta-analysis to investigate the effects of head positioning on cerebral haemodynamics assessed by imaging methods post-ischaemic stroke. Of the 21 studies included (n = 529), 15 used transcranial Doppler. Others used near-infrared, diffuse correlation spectroscopy and nuclear medicine modalities. Most tested head positions between 0° and 45°. Seventeen studies reported changes in CBF parameters (increase at lying-flat or decrease at more upright) in the ischaemic hemisphere with position change. However, great variability was found and risk of bias was high in many studies. Pooled data of two studies ≤24 h (n = 28) showed a mean increase in cerebral blood flow (CBF) velocity of 8.5 cm/s in the ischaemic middle cerebral artery (95%CI,-2.2-19.3) from 30° to 0°. The increase found ≤48 h (n = 50) was of 2.3 cm/s (95%CI,-4.6-9.2), while ≤7 days (n = 38) was of 8.4 cm/s (95%CI, 1.8-15). Few very early studies (≤2 days) tested head positions greater than 30° and were unable to provide information about the response of acute stroke patients to upright postures (sitting, standing). These postures are part of current clinical practice and knowledge on their effects on cerebral haemodynamics is required.

Effects of the end point adjudication process on the results of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

BACKGROUND AND PURPOSE: End point adjudication committees (EPAC) are widely used in large-scale clinical trials to ensure the robustness of diagnosis for end points. METHODS: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a double-blind randomized trial of blood pressure lowering in 6105 participants with pre-existing cerebrovascular disease. Separate estimates of the effects of randomized treatment were determined using Cox regression models that were based on the unadjudicated events initially reported by the investigator and on the final events assigned by the EPAC. RESULTS: There were 992 strokes initially reported by the investigators and 894 (90%) retained these diagnoses after adjudication by the EPAC. The hazard ratios (95% CIs) for the effect of randomized treatment on stroke were 0.74 (0.64 to 0.85) based on the investigator diagnoses and 0.72 (0.62 to 0.83) based on the EPAC diagnoses (P homogeneity=0.7). For each stroke subtype reported, the corresponding numbers of diagnoses (investigators/EPAC) were ischemic (593/565), hemorrhagic (124/111), and unknown (124/93) with no impact of the EPAC review on the estimates of treatment effects (all P homogeneity >0.3). There was likewise no detectable effect of reclassification of diagnoses for the effect estimates calculated for myocardial infarction or the main causes of death (all P homogeneity >0.5). CONCLUSIONS: The EPAC process had no discernible impact on the trial conclusions. Very large trials powered to detect effects on stroke subtypes might obtain real scientific gain from an EPAC, but in the case of PROGRESS, the value of the EPAC was in the reassurance it provided.

Doppler ultrasound detection of side-vessel occlusion: an in vitro study.

BACKGROUND AND PURPOSE: Small-vessel knock is a recently reported Doppler ultrasound finding that has been identified in patients with cerebral ischemia. It has been hypothesized that knock-type signals are linked to the presence of either small-vessel occlusion or wall motion. The aim of this study was to investigate the origins of "knock-type" signals by reproducing occlusion of a peripheral artery model in vitro. METHODS: Synthetic bifurcations were fabricated from glass and latex and placed in a flow-rig mimicking physiological blood-flow conditions. The glass model permitted study of fluid flow in the absence of wall motion, whereas the latex model also produced wall motion effects. Vessels were artificially obstructed to examine Doppler signal characteristics associated with blood flow and wall motion. RESULTS: Complete obstruction of the peripheral branch of the glass model revealed discrete (<100 ms) knock-type signals caused by local fluid flow in the occluded branch. Imaging of the obstructed vessel using color Doppler revealed forward and reflected flow. The walls produced periodic bidirectional knock-type signals, which occurred during systole and were not related to the presence of an obstruction. CONCLUSIONS: In our laboratory model, transcranial Doppler ultrasound was found to be capable of detecting knock signals produced by circulating fluid within an occluded branch. However, because similar signals are also generated by nonpathological wall motion, these results cannot be directly translated to a clinical setting. Clinicians should be careful to avoid casual overinterpretation of transcranial Doppler ultrasound data.

Paracentral strip infarcts of the middle cerebral artery: borderzone ischaemia or cortical artery occlusion?

BACKGROUND AND PURPOSE: We have noted the presence of small strip-like infarcts involving the cortex within the interdivisional territory of the middle cerebral artery (MCA) and sometimes extending to the periventricular region. The incidence in a stroke unit population, mechanisms, clinical expression and prognosis of patients with these cortical infarcts are unknown. To clarify these issues we retrospectively and prospectively identified these patients in our own stroke unit population. METHODS: Patients were identified retrospectively and prospectively from the Austin Hospital Stroke Unit from March 2001 to May 2007. All were selected on the basis of the recent onset of an acute neurological deficit with imaging showing strip infarction within the MCA territory. Clinical features were recorded and the mechanism of infarction was classified based on the TOAST criteria from standard investigations. RESULTS: From 4,274 acute stroke admissions, there were 24 patients (0.6%), 12 males and 12 females (mean age 75 years; range 44-92 years) with CT or MRI showing characteristic linear infarction in the middle cerebral territory. In most cases, infarction was adjacent to the central sulcus. Common clinical features included mild-to-moderate hemiparesis with cortical signs. The most common TOAST criterion mechanism categories were artery-to-artery or cardiac embolism. It is postulated that this resulted in either isolated small cortical artery branch occlusion or borderzone infarction between superior and inferior divisions of the MCA due to more proximal large-artery vessel occlusion. Prognosis was good. CONCLUSIONS: We describe the phenotypic expression, postulated mechanisms and prognosis of strip-like infarcts between the superior and inferior MCA divisions. The likely artery-artery or cardio-embolic mechanisms should prompt clinicians to search for an embolic source. While the prognosis of the syndrome is generally good, its recognition may allow specific therapies to be developed to improve clinical outcomes further.

Microembolic signals in subarachnoid hemorrhage.

Microembolic signals (MES) detected by transcranial Doppler (TCD) have been reported in subarachnoid hemorrhage (SAH), although their origin and contribution to brain ischemia remain uncertain. We conducted a prospective study to evaluate the frequency of MES among patients with SAH and to determine their origin. Twenty-seven patients with SAH, comprising 15 aneurysmal and 12 non-aneurysmal patients, participated in the study. TCD evaluation was performed using a 2 MHz probe. Patients were studied three times per week during their in-patient stay to detect vasospasm, and then each middle cerebral artery (MCA) was monitored for 30 min using the Monolateral Multigate mode to detect MES. Using this method, MES were detected in 7 out of 15 patients (47%) with aneurysmal SAH and were not seen in non-aneurysmal patients (p=0.007). Vasospasm occurred in 52% (14/27) of cases. However, clinical signs and symptoms of vasospasm were identified in only 18.5% (5/27). There was no significant relationship between MES and vasospasm (p=0.224). Also, no relationship was found between MES and the location of the aneurysm (p=0.685). Thus, in this study MES were only detected in aneurysmal SAH. However, we did not find a relationship between the location of the aneurysm and MES, or the presence of vasospasm and MES. Therefore, MES in patients with SAH may also originate from vascular pathology other than the aneurysm sac or vascular spasm.

Asymptomatic Carotid Stenosis Is Associated With Circadian and Other Variability in Embolus Detection.

Background and Purpose: Variability in transcranial Doppler (TCD) detection of embolic signals (ES) is important for risk stratification. We tested the effect of time of day on ES associated with 60-99% asymptomatic carotid stenosis. Materials and Methods: Subjects were from the Asymptomatic Carotid Stenosis Embolus Detection (ASED) Study such that half were previously ES-positive and half ES-negative with 6-monthly 60-min TCD monitoring. All underwent bilateral TCD monitoring for two 12-h sessions separated by 24 h. ES detection rates were calculated using 6 and 4-h intervals from midnight and effective TCD monitoring time. Results: Ten subjects (8 male, mean age 79.5 years) were monitored. Over 24 h, 5/10 study arteries with 60-99% asymptomatic carotid stenosis were ES-positive (range 1-28 ES/artery, 56 total ES from 177.9 total effective monitoring hours). The remaining five study arteries and all eight successfully monitored contralateral arteries were ES-negative. Using 6-h intervals the mean ES detection rate peaked at 0600-midday (0.64/h) and was lowest 1800-midnight (0.09/h) with an incidence rate ratio of 7.26 (95% CI 2.52-28.64, P ≤ 0.001). Using 4-h intervals the mean ES detection rate peaked at 0800-midday (0.64/h) and was lowest midnight-0400 (0.12/h) with an incidence rate ratio of 5.51 (95% CI 1.78-22.67, P = 0.001). Conclusions: Embolism associated with asymptomatic carotid stenosis shows circadian variation with highest rates 4-6 h before midday. This corresponds with peak circadian incidence of stroke and other vascular complications. These and ASED Study results show that monitoring frequency, duration, and time of day are important in ES detection.

Risk assessments for quality-assured, source-segregated composts and anaerobic digestates for a circular bioeconomy in the UK.

A circular economy relies on demonstrating the quality and environmental safety of wastes that are recovered and reused as products. Policy-level risk assessments, using generalised exposure scenarios, and informed by stakeholder communities have been used to appraise the acceptability of necessary changes to legislation, allowing wastes to be valued, reused and marketed. Through an extensive risk assessment exercise, summarised in this paper, we explore the burden of proof required to offer safety assurance to consumer and brand-sensitive food sectors in light of attempts to declassify, as wastes, quality-assured, source-segregated compost and anaerobic digestate products in the United Kingdom. We report the residual microbiological and chemical risks estimated for both products in land application scenarios and discuss these in the context of an emerging UK bioeconomy worth £52bn per annum. Using plausible worst case assumptions, as demanded by the quality food sector, risk estimates and hazard quotients were estimated to be low or negligible. For example, the human health risk of E. coli 0157 illness from exposure to microbial residuals in quality-assured composts, through a ready-to-eat vegetable consumption exposure route, was estimated at ~10-8 per person per annum. For anaerobic digestion residues, 7 × 10-3cases of E. coli 0157 were estimated per annum, a potential contribution of 0.0007% of total UK cases. Hazard quotients for potential chemical contaminants in both products were insufficient in magnitude to merit detailed quantitative risk assessments. Stakeholder engagement and expert review was also a substantive feature of this study. We conclude that quality-assured, source-segregated products applied to land, under UK quality protocols and waste processing standards, pose negligible risks to human, animal, environmental and crop receptors, providing that risk management controls set within the standards and protocols are adhered to.

Demographic and genetic viability of a medium-sized ground-dwelling mammal in a fire prone, rapidly urbanizing landscape.

The rapid and large-scale urbanization of peri-urban areas poses major and complex challenges for wildlife conservation. We used population viability analysis (PVA) to evaluate the influence of urban encroachment, fire, and fauna crossing structures, with and without accounting for inbreeding effects, on the metapopulation viability of a medium-sized ground-dwelling mammal, the southern brown bandicoot (Isoodon obesulus), in the rapidly expanding city of Perth, Australia. We surveyed two metapopulations over one and a half years, and parameterized the PVA models using largely field-collected data. The models revealed that spatial isolation imposed by housing and road encroachment has major impacts on I. obesulus. Although the species is known to persist in small metapopulations at moderate levels of habitat fragmentation, the models indicate that these populations become highly vulnerable to demographic decline, genetic deterioration, and local extinction under increasing habitat connectivity loss. Isolated metapopulations were also predicted to be highly sensitive to fire, with large-scale fires having greater negative impacts on population abundance than small-scale ones. To reduce the risk of decline and local extirpation of I. obesulus and other small- to medium-sized ground-dwelling mammals in urbanizing, fire prone landscapes, we recommend that remnant vegetation and vegetated, structurally-complex corridors between habitat patches be retained. Well-designed road underpasses can be effective to connect habitat patches and reduce the probability of inbreeding and genetic differentiation; however, adjustment of fire management practices to limit the size of unplanned fires and ensure the retention of long unburnt vegetation will also be required to ensure persistence. Our study supports the evidence that in rapidly urbanizing landscapes, a pro-active conservation approach is required that manages species at the metapopulation level and that prioritizes metapopulations and habitat with greater long-term probability of persistence and conservation capacity, respectively. This strategy may help us prevent future declines and local extirpations, and currently relatively common species from becoming rare.

Cadmium availability to wheat grain in soils treated with sewage sludge or metal salts.

Grain Cd concentrations were determined in wheat (Triticum aestivum L.) grown in 1999, 2001 and 2003, at six sludge cake field experiments. Three of these sites also had comparisons with Cd availability from metal amended liquid sludge and metal salts. Grain Cd concentrations in all years and at all sites were significantly linearly correlated with NH4NO3 extractable Cd and soil total Cd (P<0.001). Soil extractability was greater in the liquid sludge and metal salt experiments than in the cake experiments, as were grain Cd concentrations. Across all the sites, NH4NO3 extractable soil Cd was no better at predicting grain Cd than soil total Cd. Stepwise multiple linear regression analysis showed that soil total Cd, pH and organic carbon were the only significant (P<0.001) variables influencing wheat grain Cd concentrations, explaining 78% of the variance across all field experiments (1408 plots). This regression predicted that the current UK soil total Cd limit of 3 mg kg(-1) was not sufficiently protective against producing grain above the European Union (EU) grain Cd Maximum Permissible Concentration (MPC) of 0.235 mg Cd kg(-1) dry weight, unless the soil pH was > 6.8. Our predictions show that grain would be below the MPC with > 95% confidence with the proposed new EU draft regulations permitting maximum total Cd concentrations in soils receiving sludge of 0.5 mg kg(-1) for soils of pH 5-6, 1 mg kg(-1) for soils of pH 6-7, and 1.5 mg kg(-1) for soils of pH > or = 7.

Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study.

BACKGROUND AND PURPOSE: We tested the hypothesis that transcranial Doppler embolic signal (ES) detection identifies an increased risk of ipsilateral carotid stroke or transient ischemic attack (TIA) in subjects with asymptomatic severe carotid stenosis. METHODS: Subjects with duplex-determined 60% to 99% carotid stenosis, without other apparent cerebroembolic sources, underwent 6-monthly neurological assessment and 60-minute ES monitoring. ES positivity was defined as > or =1 ES detected in > or =1 study, ES negativity as no ES in any study, and consistent ES negativity as no ES in any study where > or =6 studies were performed. Rates of ipsilateral carotid stroke/TIA were calculated using Kaplan-Meier analysis and correlated with ES status using odds ratios (ORs) and Cox proportional hazards regression analysis. RESULTS: A total of 202 subjects (138 male; mean age 74 years; mean follow-up 34 months) were recruited. The average annual rate of ipsilateral carotid stroke/TIA was 3.1%. A total of 231 arteries were monitored at least once (mean 4.3 studies/artery). Six of 60 (10.0%) ES-positive arteries had an ipsilateral carotid stroke/TIA compared with 12 of 171 (7.0%) ES-negative arteries (OR, 1.47; 95% CI, 0.43, 4.48; P=0.624) and 2 of 41 (4.9%) consistently ES-negative arteries (OR, 2.17; 95% CI, 0.36, 22.90; P=0.59). Differences in survival free of ipsilateral carotid stroke/TIA according to ES status were not statistically significant. CONCLUSIONS: Although there were more ipsilateral carotid cerebrovascular events among ES-positive arteries, this was not statistically significant. Less labor-intensive techniques are required to make further study and clinical application practical.

Pathogen survival during livestock manure storage and following land application.

This paper reports the first year results of field experiments to determine the survival times of pathogens in livestock manures during storage and following land application, using viable count methods. E. coli O157, Salmonella and Campylobacter survived in stored slurries and dirty water for up to three months, with Listeria surviving for up to three months. In contrast, all these pathogens survived for less than one month in solid manure heaps where temperatures greater than 55 degrees C were obtained. Following manure spreading to land, E. coli O157, Salmonella and Campylobacter generally survived in the soil for up to one month after application to both the sandy arable and clay loam grassland soils, whereas Listeria commonly survived for more than one month. These data are being used to develop guidelines on the management of manures to minimize the risks of pathogen transfer from animal manures to the human food chain.

Possible determinants of early microembolism after carotid endarterectomy.

BACKGROUND AND PURPOSE: High numbers of microembolic signals (MES) have been associated with increased risk of postoperative stroke after carotid endarterectomy (CEA). We sought to identify factors predictive of postoperative MES. METHODS: Transcranial Doppler monitoring of the ipsilateral middle cerebral artery for MES was performed for 30 minutes during the first postoperative hour in sequential patients undergoing CEA. Stepwise binomial logistic regression analysis was performed to identify preoperative and intraoperative variables that predicted the occurrence of postoperative MES. RESULTS: We studied 141 patients (mean age, 69 years); 102 (72%) were male, and 69 (49%) had at least 1 MES (range, 1 to 118) detected in the first postoperative hour. The risk of postoperative MES was greater in women (P=0.027), patients not receiving antiplatelet therapy (P=0.033), and patients undergoing left-sided CEA (P=0.049). Other variables such as residual stenosis seen on completion angiography and operative technique were not associated with postoperative MES. CONCLUSIONS: Postoperative MES were most likely in women, patients not receiving preoperative antiplatelet therapy, and patients who had a left CEA. Microembolism might explain why these same factors are associated with higher rates of perioperative stroke.

Trial application of a Model of Resource Utilization, Costs, and Outcomes for Stroke (MORUCOS) to assist priority setting in stroke.

BACKGROUND AND PURPOSE: Cost-effectiveness data for stroke interventions are limited, and comparisons between studies are confounded by methodological inconsistencies. The aim of this study was to trial the use of the intervention module of the economic model, a Model of Resource Utilization, Costs, and Outcomes for Stroke (MORUCOS) to facilitate evaluation and ranking of the options. METHODS: The approach involves using an economic model together with added secondary considerations. A consistent approach was taken using standard economic evaluation methods. Data from the North East Melbourne Stroke Incidence Study (NEMESIS) were used to model "current practice" (base case), against which 2 interventions were compared. A 2-stage process was used to measure benefit: health gains (expressed in disability-adjusted life years [DALYs]) and filter analysis. Incremental cost-effectiveness ratios (ICERs) were calculated, and probabilistic uncertainty analysis was undertaken. RESULTS: Aspirin, a low-cost intervention applicable to a large number of stroke patients (9153 first-ever cases), resulted in modest health benefits (946 DALYs saved) and a mean ICER (based on incidence costs) of US 1421 dollars per DALY saved. Although the health gains from recombinant tissue-type plasminogen activator (rtPA) were less (155 DALYs saved), these results were impressive given the small number of persons (256) eligible for treatment. rtPA dominates current practice because it is more effective and cost-saving. CONCLUSIONS: If used to assess interventions across the stroke care continuum, MORUCOS offers enormous capacity to support decision-making in the prioritising of stroke services.