Determining the composition of the vacuum-liquid interface in ionic-liquid mixtures.

The vacuum-liquid interfaces of a number of ionic-liquid mixtures have been investigated using the combination of reactive-atom scattering with laser-induced fluorescence detection (RAS-LIF), selected surface tension measurements, and molecular dynamics (MD) simulations. The mixtures are based on the widespread 1-alkyl-3-methylimidazolium ([Cnmim]+) cation, including mixed cations which differ in chain length or chemical functionality with a common anion; and different anions for a common cation. RAS-LIF results imply that the surface compositions exhibit a general form of non-stoichiometric behaviour that mimics the well-known Henry's and Raoult's laws at low and high mole fraction, respectively. The extended Langmuir model provides a moderately good single-parameter fit, but higher-order terms are required for an accurate description. The quantitative relationship between RAS-LIF and surface tension, which probes the surface composition only indirectly, is explored for mixtures of [C2mim]+ and [C12mim]+ with a common bis(trifluoromethylsulfonyl)imide ([NTf2]-) anion. Extended Langmuir model fits to surface tension data are broadly consistent with those to RAS-LIF; however, several other common approaches to extracting surface compositions from measured surface tensions result in much larger discrepancies. MD simulations suggest that RAS-LIF faithfully reports on the alkyl-chain exposure at the surface, which is only subtly modified by composition-dependent structural reorganisation.

The prognosis of adult-onset motor neuron disease: a prospective study based on the Scottish Motor Neuron Disease Register.

The Scottish Motor Neuron Disease Register (SMNDR) is a prospective, collaborative, population-based project which has been collecting data on incident patients since 1989. In this report we present the clinical features of 229 patients with motor neuron disease (218 sporadic and 11 familial) diagnosed in 1989 and 1990 and compare their prognosis with previous studies of survival. The overall 50% survival from symptom onset was 2.5 years (95% CI, 2.2-3.0) and 5-year survival 28% (95% CI, 20-36%). The presence of progressive bulbar palsy (PBP), either at presentation or developing during the course of the illness, significantly reduced survival and was the most important prognostic indicator. Patients who survived longer than 5 years from symptom onset did not have PBP as part of their presenting illness. The prognosis was worse for women, and this was in part related to the higher frequency of PBP in older women, but age was also an independent adverse risk factor. Differences in survival between this and previous series can probably be explained on the basis of variation in case definition and ascertainment methods.

Risk of death from cardiovascular disease and chronic bronchitis determined by place of birth in England and Wales.

STUDY OBJECTIVE: The aim of the study was to examine the relation between place of birth within England and Wales and cause of death. DESIGN: The study was a population survey using data provided by the Office of Population Censuses and Surveys which, for a trial period between 1969 and 1972, coded place of birth on death certificates. SETTING: The survey involved almost 2 million people who died in England and Wales between April 1969 and December 1972. MAIN RESULTS: Persons born in northern counties and industrial towns, and in Wales, had increased risk of ischaemic heart disease and stroke, which persisted whether or not they had moved to other parts of the country. A low risk of cardiovascular disease among people born in and around London went with them when they moved. People born in cities and large towns had an increased and persisting risk of chronic bronchitis. CONCLUSIONS: These findings are evidence that past geographical differences in fetal and infant growth, and in exposure to respiratory infection in early childhood, partly determine today's differences in adult death rates.

Why we need a clinical trial for vitamin K.

Vitamin K is given to many babies born in the United Kingdom, but we still do not know if it has substantial hazards. Because the population exposed to vitamin K is very large even quite small hazards would involve many adverse events. It is therefore important to be able to put reasonably close bounds on the potential damage that vitamin K prophylaxis could cause. Past research has not allowed us to do this but a large randomised controlled clinical trial of vitamin K against no vitamin K, enrolling only infants at low risk of haemorrhagic disease, would do so. There is no question that vitamin K is a useful treatment in babies at highest risk of haemorrhagic disease: the question is whether the trend towards use of vitamin K in lower risk babies should be encouraged.

Prognosis and prognostic factors of retinal infarction: a prospective cohort study.

OBJECTIVE: To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. DESIGN: Prospective cohort study. SETTING: University hospital departments of clinical neurology. PATIENTS: 99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). INTERVENTIONS: Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). MAIN OUTCOME MEASURES: Death, stroke, coronary events, contralateral retinal infarction; survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. RESULTS: During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year; of stroke 2.5% per year (7.4% in the first year); of coronary events 5.3% per year, exceeding that of stroke; and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid bruit both for coronary events and for stroke, myocardial infarction, or vascular death. CONCLUSIONS: Patients who present with retinal infarction due to presumed atherothromboembolism or cardiogenic embolism are at considerable risk of a coronary event. The risk of stroke, although high, is not so great. Not all strokes occurring after retinal infarction relate directly to disease of the ipsilateral carotid system, although this is probably the most common cause. Few patients experience contralateral retinal infarction. Non-arteritic retinal infarction should be diagnosed or confirmed by an ophthalmologist, and the long term care of patients with the condition should involve a physician who has an active interest in managing vascular disease.

Why is the outcome of transient ischaemic attacks different in different groups of patients?

The outcomes of each of three large cohorts of patients with transient ischaemic attacks, which were studied in the same country at much the same time with the same methods, were compared and found to be quite different from each other. The differences in outcome were related not only to different strategies of treatment but also to differences in the prevalence and level of important prognostic factors (for example, case mix) and other factors such a the time delay from transient ischaemic attack to entry into the study and the play of chance. The implications for purchasers of health care are that they cannot rely solely on non-randomised comparisons of outcome of patients treated in competing units as a measure of the quality of care (which has only rather modest effects) without accounting for other factors that may influence outcome such as the nature of the illness, the case mix, observer bias, and the play of chance.

Hyperphagia: a necessary precondition to obesity?

Weight-gain is generally attributed to a caloric imbalance resulting from hyperphagia. However, this attribution is often made without observing caloric intakes during the initial accumulation of fat stores. Instead, this conclusion is drawn because many obese organisms overeat, and overconsumption is sufficient to cause weight-gain. The literature is reviewed, specifically those studies on the onset of caloric overconsumption relative to weight-gain and the accumulation of fat during food restriction, which suggests that hyperphagia is not necessary for animals prone to obesity to become fatter and heavier. It is observed that animals with genetically- and surgically-induced obesity often become fat prior to hyperphagia and continue to gain even if food restricted to subnormal levels. Overconsumption does speed this gain.

The prognosis of hospital-referred transient ischaemic attacks.

A cohort of 469 hospital-referred patients with transient ischaemic attacks (TIA) of the brain (66%) or eye (34%) due to presumed atheromatous thromboembolism, lipohyalinosis or cardiogenic embolism, without prior stroke, was assembled between 1976-86. Follow up was prospective and complete until the patients death or the end of 1986. During a mean period of follow up of 4.1 years there were 82 deaths (58 vascular, 24 non-vascular), 63 first-ever strokes and 58 patients with coronary events. A coronary event accounted for 51% of deaths whilst stroke was the cause in 12%. The average risk of death over the first five years after TIA was 4.5% per year. The risk of stroke was 6.6% in the first year and 3.4% per year on average over the first five years. Stroke occurred in the same vascular territory as the initial TIA in about two-thirds of cases, and was of lacunar type in one fifth of these strokes. The average risk of a coronary event over the first five years after TIA was 3.1% per year, similar to that of stroke. However, the risk of a coronary event, and also death, was fairly constant each year after a TIA, in contrast to the risk of stroke which was highest in the first year. The average risk of stroke, myocardial infarction or vascular death over the first five years after TIA was 6.5% per year and the average risk of stroke, myocardial infarction or death from any cause was 7.5% per year. The prognosis of this cohort of hospital-referred TIA patients was better than that of TIA patients in the same community who presented to the Oxfordshire Community Stroke Project (OCSP), and reflected the impact of referral bias. The hospital-referred patients were younger, assessed at a later date after their last TIA, and comprised a greater proportion of patients who had had a TIA of the eye (amaurosis fugax), which had a better prognosis than TIA of the brain. Knowledge of the prognosis of different populations of TIA patients not only enhances understanding and interpretation of previous studies but is also required for optimal patient management and the planning of treatment trials.

Can the long term outcome of individual patients with transient ischaemic attacks be predicted accurately?

The prognosis of individual patients with transient ischaemic attacks (TIAs) is extremely variable; some patients are at high risk and others at low risk of a serious vascular event. Prediction equations of outcome were developed, based on eight clinical prognostic factors, from a cohort of 469 hospital-referred TIA patients ("training" data set), that enable high (and low) risk patients to be identified and for whom costly and risky treatments may (or may not) be targeted. The study aimed to determine whether these equations are externally valid and can predict outcome, with reliability and discrimination, in two independent cohorts of TIA patients ("test" data sets): 1653 TIA patients in the UK-TIA aspirin trial and 107 TIA patients in the Oxfordshire Community Stroke Project. Predicted outcomes agreed closely with the observed outcomes in the "test" data sets (reliability) for all outcome events at low five year risk (< 30%) but the estimates of risk were less precise in groups predicted to have a high five year risk (> 40%). The prediction equations were fairly accurate in discriminating between patients who subsequently suffered the outcome event of interest and those who survived free of the event at five years after the TIA, particularly at lower cut-off levels distinguishing high and low risk (for example, < 30% vs > 30% at five years). It is very difficult to achieve perfect discrimination because there is no single important prognostic factor for TIA patients that indicates whether a patient is going to suffer an event or not. These equations can be used to provide a reliable estimate of the absolute five year risk of a serious vascular event in hospital-referred TIA patients but they cannot, as yet, be used with confidence to distinguish patients at high risk from patients at low risk.

Transient ischaemic attacks: which patients are at high (and low) risk of serious vascular events?

The aims of this study were to determine the important prognostic factors at presentation which identify patients with transient ischaemic attacks (TIA) who are at high risk (and low risk) of serious vascular events and to derive a prediction model (equation) for each of the major vascular outcome events. A cohort of 469 TIA patients referred to a University hospital, without prior stroke, were evaluated prospectively and followed up over a mean period of 4.1 years (range 1-10 years). The major outcome events of interest were 1) stroke 2) coronary event and 3) stroke, myocardial infarction or vascular death (whichever occurred first). Prognostic factors and their hazard ratios were identified by means of the Cox proportional hazards multiple regression analysis. The significant adverse prognostic factors (in order of strength of association) for stroke were an increasing number of TIAs in the three months before presentation, increasing age, peripheral vascular disease, left ventricular hypertrophy and TIAs of the brain (compared with the eye); the prognostic factors for coronary event were increasing age, ischaemic heart disease, male sex, and a combination of carotid and vertebrobasilar TIAs at presentation; and for stroke, myocardial infarction or vascular death they were increasing age, peripheral vascular disease, increasing number of TIAs in the three months before presentation, male sex, a combination of carotid and vertebrobasilar TIAs at presentation, TIAs of the brain (compared with the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the presence of residual neurological signs after the TIA. Prediction models (equations) of both the relative risk and absolute risk of each of the major outcome events were produced, based on the presence or level of the significant prognostic factors and their hazard. Before it can be concluded that our equations accurately predict prognosis and can be generalised to other populations, their predictive power needs to be validated in other, independent samples of TIA patients (which we are currently doing).

Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register.

In order to identify risk factors for the subsequent development of motor neuron disease (MND) we have carried out a case-control study of incident patients in Scotland, identified using the Scottish Motor Neuron Disease Register. A standard questionnaire was given to 103 patients and the same number of community controls matched on a one to one basis using the general practitioner's (GP) age and sex register. Recall bias was minimised by using GP records to verify the subject's report. There was an overall lifetime excess of fractures in patients, odds ratio (OR) = 1.3 (95% confidence interval (CI), 0.7-2.5) and this was highest in the 5 years before symptom onset (OR = 15, 95% CI, 3.3-654). There was no association with non-fracture trauma but the OR for a manual occupation in patients was 2.6 (95% CI, 1.1-6.3). Both occupational exposure to lead (OR = 5.7, 95% CI, 1.6-30) and solvents/chemicals (OR = 3.3, 95% CI 1.3-10) were significantly more common in patients. No consistent association was found between MND and factors reflecting socioeconomic deprivation in childhood; childhood infections or social class. Our results identify a number of different factors which may contribute to the aetiology of MND.

Parametric imaging of cerebral vascular reserve. 2. Reproducibility, response to CO2 and correlation with middle cerebral artery velocities.

We report the reproducibility and response to change in end-tidal CO2 of a new method of quantifying regional mean cerebral transit time (MCTT) compared with the reproducibility and CO2 reactivity of middle cerebral artery (MCA) blood flow velocities measured using transcranial Doppler ultrasound. Within the range of end-tidal CO2 which could be achieved in conscious subjects breathing spontaneously, hemispheric MCTT, peak MCA velocity and mean MCA velocity showed a linear relationship with end-tidal CO2. After correction to a standardised end-tidal CO2, the coefficients of variation were 5.7% for hemispheric MCTT, 6.3% for peak MCA velocity and 6.8% for mean MCA velocity. Under the conditions of this study, MCA blood flow velocity was proportional to the reciprocal of MCTT, which in turn represents the ratio of blood flow to blood volume. Although the two methods appear to provide similar information, measurement of MCTT is quicker to perform, is less observer-dependent, provides regional information, uses conventional equipment present in most nuclear medicine departments and is less subject to problems associated with patient movement.

Creutzfeldt-Jakob disease and blood transfusion.

Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) in the UK identified 21 patients who had received a blood transfusion and 29 who had donated blood, out of a total of 202 definite and probable cases. This frequency of blood transfusion or donation did not differ from that in age and sex matched controls, and the clinical features in patients with a history of blood transfusion were similar to those of classical CJD and clearly distinct from CJD in recipients of human growth hormone. This evidence does not suggest that blood transfusion is a major risk factor for CJD.