Invited review: A position on the Global Livestock Environmental Assessment Model (GLEAM).

The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.

Disappearance of the hyperdense MCA sign after stroke thrombolysis: implications for prognosis and early patient selection for clot retrieval.

Disappearance of the hyperdense middle cerebral artery sign (HMCAS) following intravenous thrombolysis for ischaemic stroke is associated with improved outcome. Debate exists over which radiological thrombus characteristics can predict disappearance of the HMCAS after thrombolysis such as vessel attenuation or extent of thrombus length. Methods Ischaemic stroke patients treated with intravenous thrombolysis from our hospital were entered into a European registry. Patient demographics, stroke severity pre- and 24 hours post-thrombolysis were recorded. Patients with HMCAS were identified from the registry using records from 2010-2013. Images from the pre and post-thrombolysis computed tomography scan were measured. Thrombus characteristics (length and attenuation), extent of ischaemic change and clinical outcome (stroke severity and 3 month survival) were compared between patients with and without HMCAS disappearance. Logistic regression analysis was performed to identify predictors of HMCAS disappearance. Results HMCAS was present in 88/315 (28%) of thrombolysed ischaemic stroke patients. 36/88 (41%) of patients had thrombus disappearance 24 hours after thrombolysis. HMCAS disappearance was associated with reduced stroke severity, less radiological ischaemic change, and higher 3 month survival (87% vs 56%). Median thrombus length was shorter in the HMCAS disappearance group (11 vs 17 mm, p = 0.0004), but no significant difference in vessel attenuation was observed (48 vs 51 Hounsfield Units, p = 0.25). HMCAS disappearance occurred in 73% of cases where HMCAS length was > 10 mm, 38% when length was 10-20 mm, and 21% if < 20 mm. Thrombus length was the only independent predictor of HMCAS disappearance (odds ratio 0.90 per mm; 95% CI 0.84-0.96, p = 0.01). Conclusion Disappearance of HMCAS is associated with better clinical and radiological outcomes. A shorter thrombus is more likely to disappear postthrombolysis. The data highlight the limitation of intravenous thrombolysis in patients with longer hyperattenuated vessels, and the potential role for clot retrieval in such patients.

Pre-hospital notification is associated with improved stroke thrombolysis timing.

Intravenous thrombolysis increases disability-free survival after acute ischaemic stroke in a time-dependent fashion. We aimed to determine whether pre-hospital notification, introduction of a CT scanner near to assessment site and introduction of out-of-hours thrombolysis services affect thrombolysis timing. Methods Timings related to thrombolysis were collected between May 2012 and June 2014 at a single hospital site; these included time to stroke physician assessment, time to cranial CT imaging and door to needle time. All thrombolysed ischaemic stroke patients admitted via the emergency department were included. Ambulance services were asked to pre-notify the emergency department of any suspected stroke patient during this period. Results We studied 182 patients (48% female; mean age 74 years; 59% pre-notified). Pre-hospital notification was associated with a significantly higher rate of CT scanning within 25 minutes (60% vs 24%, odds ratio [OR] 4.7, 95% confidence interval [CI] 2.4-9.0; p<0.001), earlier stroke physician assessment (median 6 vs 32 minutes; p<0.001) and receiving thrombolysis within 60 minutes (89% vs 49%, OR 8.0, 95% CI 3.8-16.9; p<0.001). Being treated outside normal working hours did not alter thrombolysis timing. Logistic regression identified the introduction of a near-site CT scanner (OR 4.6 [95% CI 1.7-12.5]) and pre-hospital notification (OR 4.7, [95% CI 2.3-9.6]) as independent predictors of door to CT time less than or equal to 25 minutes, and pre-hospital notification (OR 11.6, [95% CI 4.9-30.3]) and stroke severity (OR 1.15 per point of NIHSS scale, [95% CI 1.08-1.23]) as predictors of door to thrombolysis time less than or equal to 60 minutes. The most common perceived timing delays were radiology-related (33%), the need to acutely lower blood pressure (15%) and obtaining consent (12%). Conclusion Pre-hospital notification is associated with earlier stroke physician review, CT imaging and delivery of thrombolysis. Referral to an out of hours thrombolysis service was not associated with additional delay.

Comparison of predictive scores of symptomatic intracerebral haemorrhage after stroke thrombolysis in a single centre.

UNLABELLED: Symptomatic intracerebral haemorrhage following thrombolysis for ischaemic stroke causes significant morbidity and mortality. This study assessed which of four risk scores (SEDAN, HAT, GRASPS and SITS) best predicts symptomatic intracerebral haemorrhage. METHODS: Data from 431 patients treated at Aberdeen Royal Infirmary (2003-2013) were extracted from a thrombolysis database. Score performance was compared using area under the curve. RESULTS: Any intracerebral haemorrhage occurred in 12% of patients (53/413); 11% fulfilling the SITS-MOST symptomatic intracerebral haemorrhage definition (6/53), 34% the ECASS II definition (18/53), and 43% the National Institute of Neurological Disorder and Stroke definition (23/53). Stroke severity, as defined by the National Institutes of Health Stroke Scale, significantly improved after 24 hours in patients without intracerebral haemorrhage, but not in those with. Significant symptomatic intracerebral haemorrhage predictors were age, glucose, stroke severity, hyperdense middle cerebral artery on CT scan, ASPECTS score and anti-platelet therapy. The haemorrhage after thrombolysis score performed best at predicting symptomatic intracerebral haemorrhage (area under the curve 0.67-0.78, p < 0.001). CONCLUSION: The haemorrhage after thrombolysis score uses the least variables and has the best predictive value for symptomatic intracerebral haemorrhage. Using predictive scores for clinical decision making depends on estimation of overall benefits as well as risk.

The Causative Classification of Stroke system: an international reliability and optimization study.

BACKGROUND: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. METHODS: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. RESULTS: The κ value for causative classification was 0.80 (95% confidence interval [CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: κ = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The κ value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. CONCLUSIONS: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras.

Timing of aspirin and secondary preventative therapies in acute stroke: support for use of stroke units.

BACKGROUND: We aimed to study the timing of aspirin prescription in ischaemic stroke comparing patients admitted to an acute stroke unit (ASU) directly or via a general medical ward. We also analysed prescription of secondary preventive therapies in stroke patients in an ASU. METHODS: Retrospective analysis was made of medical notes and prescription records of 69 patients admitted to an ASU over a three month period to establish timing of aspirin prescription with respect to onset of stroke symptoms, CT brain scan and route of admission to the ASU. RESULTS: CT brain scans were obtained at a median of 2.1 days post stroke (IQ range 1.3-4.3). Patients directly admitted to the ASU received aspirin earlier post admission compared to those admitted via a medical ward (0.7 vs 2.2 days, p < 0.01) and were also more likely to receive aspirin prior to CT scan being performed (57% vs 19%, p = 0.02). 86% of stroke patients were discharged on an antiplatelet therapy, 79% on a statin, 37% on a thiazide diuretic and 32% on an ACE inhibitor or angiotensin II antagonist. CONCLUSION: Aspirin was given more promptly in acute stroke and more commonly prior to CT scanning in an ASU compared to a medical ward. Statin therapy is used extensively in stroke but there is a much lower rate of initiation of other secondary preventive therapies (e.g. anti-hypertensive therapy) in hospital. These findings demonstrate a hesitancy in early use of aspirin amongst general physicians and lends support for the use of stroke units.

Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population.

Cardiovascular diseases, including myocardial infarction (MI) and stroke, most often occur on the background of atherosclerosis, a condition attributed to the interactions between multiple genetic and environmental risk factors. We recently reported a linkage and association study of MI and stroke that yielded a genetic variant, HapA, in the gene encoding 5-lipoxygenase-activating protein (ALOX5AP), that associates with both diseases in Iceland. We also described another ALOX5AP variant, HapB, that associates with MI in England. To further assess the contribution of the ALOX5AP variants to cardiovascular diseases in a population outside Iceland, we genotyped seven single-nucleotide polymorphisms that define both HapA and HapB from 450 patients with ischemic stroke and 710 controls from Aberdeenshire, Scotland. The Icelandic at-risk haplotype, HapA, had significantly greater frequency in Scottish patients than in controls. The carrier frequency in patients and controls was 33.4% and 26.4%, respectively, which resulted in a relative risk of 1.36, under the assumption of a multiplicative model (P=.007). We did not detect association between HapB and ischemic stroke in the Scottish cohort. However, we observed that HapB was overrepresented in male patients. This replication of haplotype association with stroke in a population outside Iceland further supports a role for ALOX5AP in cardiovascular diseases.

Patient compliance in hypertension: role of illness perceptions and treatment beliefs.

Despite many years of study, questions remain about why patients do or do not take medicines and what can be done to change their behaviour. Hypertension is poorly controlled in the UK and poor compliance is one possible reason for this. Recent questionnaires based on the self-regulatory model have been successfully used to assess illness perceptions and beliefs about medicines. This study was designed to describe hypertensive patients' beliefs about their illness and medication using the self-regulatory model and investigate whether these beliefs influence compliance with antihypertensive medication. We recruited 514 patients from our secondary care population. These patients were asked to complete a questionnaire that included the Beliefs about Medicines and Illness Perception Questionnaires. A case note review was also undertaken. Analysis shows that patients who believe in the necessity of medication are more likely to be compliant (odds ratio (OR)) 3.06 (95% CI 1.74-5.38), P<0.001). Other important predictive factors in this population are age (OR 4.82 (2.85-8.15), P<0.001), emotional response to illness (OR 0.65 (0.47-0.90), P=0.01) and belief in personal ability to control illness (OR 0.59 (0.40-0.89), P=0.01). Beliefs about illness and about medicines are interconnected; aspects that are not directly related to compliance influence it indirectly. The self-regulatory model is useful in assessing patients health beliefs. Beliefs about specific medications and about hypertension are predictive of compliance. Information about health beliefs is important in achieving concordance and may be a target for intervention to improve compliance.

Effects of mailed dissemination of the Royal College of Radiologists' guidelines on general practitioner referrals for radiography: a time series analysis.

AIM: To evaluate the effect of postal dissemination of the third edition of the Royal College of Radiologists' (RCR) guidelines on general practitioner referrals for radiography. MATERIALS AND METHODS: An interrupted time series using monthly data for 34 months before and 14 months after dissemination of the guidelines was employed. Data were abstracted for the period April 1994 to March 1998 from the computerized administrative systems of open access radiological services provided by two teaching hospitals in one region of Scotland. The time series results are contrasted with those obtained by using a simple before and after design. RESULTS: A total of 117 747 imaging requests from general practice were received in the two departments. There were no significant effects of disseminating the guidelines on the total number of requests, or on requests for individual examinations. If a simple before and after study had been used, then we would have erroneously concluded that significant changes had occurred in referral practice for 11 of the 18 procedures concerned. CONCLUSION: Mailing of copies of the RCR guidelines had a small effect on general practitioners' use of X-ray investigations of uncertain clinical significance. Additional dissemination and implementation strategies appear necessary to promote the use of guidelines.

Lack of association between apolipoprotein E genoype and ischaemic stroke in a Scottish population.

BACKGROUND: Apolipoprotein E epsilon4 allele has been associated with increased risk of coronary heart disease, and is also a major genetic susceptibility locus for Alzheimer's disease. Some studies have shown an association between apoE genotype and ischaemic stroke or outcome following stroke, while other studies have failed to do so. Materials and methods Using PCR and the Taqman fluorescence system to detect polymorphisms we examined apoE genotype in 266 ischaemic stroke cases and in a control population. RESULTS: We found no association between apoeE epsilon 4 allele distribution and ischaemic stroke, or with outcome following stroke as measured using the Rankin score. Conclusion This study disagrees with a recent meta-analysis, and suggests that further studies are required to clarify the exact relationship between apoE genotype and ischaemic stroke.

Acute sensory neuropathy in an adolescent girl following BCG vaccination.

A 13-year-old girl developed a sensory neuropathy following bacille Calmette-Guérin (BCG) vaccination, consistent with acute inflammatory demyelinating polyradiculoneuropathy or acute sensory axonal neuropathy.

No association between Glu/Asp polymorphism of NOS3 gene and ischemic stroke.

Endothelial nitric oxide synthase (NOS3) gene has been shown to modulate the degree of cerebral ischemia following stroke in animal models and is thus a candidate genetic risk factor for stroke. We compared 265 ischemic stroke cases with 293 controls and found no difference in distribution of the common structural variant Glu/Asp in codon 298 of exon 7 in the NOS3 gene. Our data do not support the hypothesis that NOS3 is a genetic risk factor for stroke.

Prenatal onset spinal muscular atrophy.

Five patients with severe spinal muscular atrophy (SMA) type I, all of whom presented with reduced fetal movements in utero, severe weakness at birth, and short survival time were assessed to attempt to determine whether their phenotype could be explained by their genotype. The diagnosis was confirmed by clinical, electrophysiological and histopathological features. Polymerase chain reaction assays were used to define the molecular diagnosis. A gene-dosage assay was used to assess the quantity of centromeric survival motor neuron gene (SMNc) present. In all cases the telomeric survival motor neuron gene (SMNt) was absent. The SMNc gene was present but in reduced copy number compared with a control group of children with less severe type I SMA, so may be important in determining severity. In the differential diagnosis of reduced fetal movements, SMA should be considered. The clinical classification may in future be clarified by molecular genetic findings.

Drug treatment of hypertension complicating diabetes mellitus.

Hypertension and diabetes mellitus are both common conditions associated with a high morbidity and mortality. When the two conditions occur together, as they do in 50% of diabetic individuals, the result is a 7.2-fold increase in mortality. If hypertension occurs in association with diabetes mellitus and diabetic nephropathy, mortality rises to 37-fold above that of a healthy population. Despite the increase in incidence of nephropathy, cardiovascular disease remains the major cause of death in diabetic individuals. Therapy should therefore take into consideration the results of large, placebo-controlled trials which have shown reduction in cardiovascular morbidity and mortality as a result of active treatment. Although studies with the newer antihypertensive agents such as calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are ongoing, only diuretics and beta-adrenoceptor antagonists have been clearly shown to reduce cardiovascular risk. Despite concerns regarding adverse metabolic effects and loss of hypoglycaemic awareness, beta-blockers and diuretics do have a role in the management of diabetic patients. While it is clear that ACE inhibitors reduce the progression of diabetic nephropathy, evidence suggests that diuretics may be just as effective. However, unlike diuretics or beta-blockers, ACE inhibitors have no proven benefit in the prevention of stroke of myocardial infarction. Despite the claims of metabolic neutrality made for many antihypertensive agents there appears to be no advantage in their use in the majority of hypertensive diabetic patients, except where there exist specific contraindications to established therapies.

Identification of a common low density lipoprotein receptor mutation (C163Y) in the west of Scotland.

Familial hypercholesterolaemia (FH) is an autosomal codominant disorder characterised by high levels of LDL cholesterol and a high incidence of coronary artery disease. Our aims were to track the low density lipoprotein receptor (LDLR) gene in individual families with phenotypic FH and to identify and characterise any mutations of the LDLR gene that may be common in the west of Scotland FH population using single strand conformational polymorphism analysis (SSCP). Patient samples consisted of 80 heterozygous probands with FH, 200 subjects who were related to the probands, and a further 50 normal, unrelated control subjects. Tracking of the LDLR gene was accomplished by amplification of a 19 allele tetranucleotide microsatellite that is tightly linked to the LDLR gene locus. Primers specific for exon 4 of the LDLR gene were used to amplify genomic DNA and used for SSCP analysis. Any PCR products with different migration patterns as assessed by SSCP were then sequenced directly. In addition to identifying probands with a common mutation, family members were screened using a forced restriction site assay and analysed using microplate array diagonal gel electrophoresis (MADGE). Microsatellite D19S394 analysis was informative in 20 of 23 families studied. In these families there was no inconsistency with segregation of the FH phenotype with the LDLR locus. Of the FH probands, 15/80 had a mutant allele as assessed by SSCP using three pairs of primers covering the whole of exon 4 of the LDLR gene. Direct DNA sequencing showed that 7/15 of the probands had a C163Y mutation. Using a PCR induced restriction site assay for the enzyme RsaI and MADGE, it was determined that the C163Y mutation cosegregated with the FH phenotype in family members of the FH probands. This mutant allele was not present in any of the control subjects. Microsatellite analysis has proven useful in tracking the LDLR gene and could be used in conjunction with LDL cholesterol levels to diagnose FH, especially in children and young adults where phenotypic diagnosis can be difficult.

Renal artery stent placement in renal artery stenosis: technical and early clinical results.

We report the technical and early clinical results of renal artery stent placement in 29 consecutive patients treated at a single centre over a 30-month period, employing the Palmaz balloon-expandable stent. Of 32 arteries treated, 23 (72%) were atheromatous, ostial stenoses. Immediate technical success was achieved in all 29 patients. Follow-up angiography was performed on 25 patients at 6.7 months (mean) and demonstrated a patient restenosis rate of 16%. All surviving patients were followed up for a minimum of 6 months. Blood pressure control was improved in eight (50%) of hypertensive patients, and renal function improved in seven (33%) and stabilized in six (29%) patients with chronic renal impairment (serum creatinine > 150 mumols/l). Complications occurred in seven (24%) of patients, including one procedure-related death. Our experience indicates that stent placement has an initial high technical success rate in renal artery stenosis and that this patency is maintained at repeat angiography with a low restenosis rate. Renal artery stenting is likely to extend the role of percutaneous renal revascularization especially in atheromatous ostial lesions. A randomized trial will be required to evaluate its role compared with balloon angioplasty.

Effect of renal-artery stenting on progression of renovascular renal failure.

BACKGROUND: Placement of renal-artery stents has a high technical success rate in atherosclerotic renovascular disease, but little is known about the clinical benefits of the procedure. We monitored renal function serially before and after stent insertion in patients with renovascular renal failure. METHODS: Renal function was assessed before and after stent placement by means of serial serum creatinine values in 32 patients with atherosclerotic renal-artery stenosis. The effect on the progression of renal failure was analysed in 23 patients by comparison of the reciprocal slopes of serum creatinine versus time plots before and after stent placement. FINDINGS: 33 transluminal stents were placed in 32 patients with atherosclerotic renovascular disease. Immediate patency was achieved in all cases: the angiographic restenosis rate at 6 months was 12% (n = 24). One patient died after a procedure-related haemorrhage. Median diastolic blood pressure was significantly lower after stenting than before (95 [IQR 86-103] vs 87 [81-90] mm Hg; p > 0.01) but the requirement for antihypertensive drugs was unchanged. Renal function improved or stabilised in 22 (69%) of the 32 patients. Progression of renal failure was significantly slowed after the procedure; the mean (SE) of the slopes of reciprocal serum creatinine values was -4.34 (0.85) L mumol-1 day-1 before stent placement, and -0.55 (1.0) L mumol-1 day-1 after stent placement (p < 0.01, two-sample t test). INTERPRETATION: Renal-stent placement in selected patients slows the progression of renovascular renal failure and may delay the need for renal replacement therapy.

Sodium-lithium countertransport, sodium-hydrogen exchange and membrane microviscosity in patients with hyperlipidaemia.

1. We measured sodium-lithium countertransport, sodium-hydrogen exchange and membrane micro-viscosity in 48 individuals with familial hypercholesterolaemia, 33 subjects with hypertriglyceridaemia and 54 normolipaemic controls. Full lipid profile, blood pressure, body mass index, fasting glucose and insulin levels were also measured. 2. Subjects with hypertriglyceridaemia had higher blood pressure, body mass index, fasting glucose and insulin levels than normal controls. 3. Vmax of the sodium-lithium countertransport was elevated in the hypertriglyceridaemic group compared with controls. Across the whole group log(e) triacylglycerols correlated with Vmax of the sodium-lithium countertransport. There was no difference in sodium-lithium countertransport K(m) between the groups. 4. Sodium-hydrogen maximal proton efflux rate (Vmax) and K(m) were not different between the three groups. There were no correlations between sodium-hydrogen exchange and sodium-lithium countertransport parameters. 5. Microviscosity as measured by diphenylhexatriene was reduced at the core of the membrane in subjects with hypertriglyceridaemia compared with those with familial hypercholesterolaemia or normolipaemic controls, suggesting an alteration in membrane structure. 6. Changes in sodium transport in hyperlipidaemia may be mediated by changes in membrane structure resulting in altered protein conformation or turnover.