Using millimeter-sized carbon-deuterium foils for high-precision deuterium-tritium neutron spectrum measurements in direct-drive inertial confinement fusion at the OMEGA laser facility.

Millimeter-sized CD foils fielded close (order mm) to inertial confinement fusion (ICF) implosions have been proposed as a game-changer for improving energy resolution and allowing time-resolution in neutron spectrum measurements using the magnetic recoil technique. This paper presents results from initial experiments testing this concept for direct drive ICF at the OMEGA Laser Facility. While the foils are shown to produce reasonable signals, inferred spectral broadening is seen to be high (∼5 keV) and signal levels are low (by ∼20%) compared to expectation. Before this type of foil is used for precision experiments, the foil mount must be improved, oxygen uptake in the foils must be better characterized, and impact of uncontrolled foil motion prior to detection must be investigated.

Systematic Fuel Cavity Asymmetries in Directly Driven Inertial Confinement Fusion Implosions.

We present narrow-band self-emission x-ray images from a titanium tracer layer placed at the fuel-shell interface in 60-laser-beam implosion experiments at the OMEGA facility. The images are acquired during deceleration with inferred convergences of ∼9-14. Novel here is that a systematically observed asymmetry of the emission is linked, using full sphere 3D implosion modeling, to performance-limiting low mode asymmetry of the drive.

Four key questions that identify severe disability.

BACKGROUND: Six hundred and four surviving children aged 2 years, who had been entered into a neonatal trial of fresh frozen plasma on the incidence of intraventricular haemorrhage, were grouped into four categories of disability based on a review by a full paediatric assessment. A 29 item questionnaire completed by the children's health visitors was used to group the children into the same categories. AIMS: To explore whether severe disability could be identified by using only a few of the 29 questions. METHOD: The sensitivity and specificity of individual questions were used first to find the subset of questions that best identified children with severe disability. The efficacy of the four most useful questions was tested in a separate cohort of 105 children for whom health visitors had completed questionnaires at the age of 2 years, and who had similarly been assessed by a paediatrician. RESULTS: In the original trial cohort, the four questions correctly identified 56 of the 61 children with the most severe disabilities as assessed by the paediatrician, and seven children were falsely identified as being severely disabled. In the second cohort, the four questions correctly identified six of the seven children classified as severely disabled by the paediatrician, with no false positives. CONCLUSION: If four such questions were included in routine child information systems at age 2 years, it might be possible to obtain useful data on the prevalence of severe disability in children.

A comparison of two methods of follow-up in a trial of prophylactic volume expansion in preterm babies.

The outcome at age 2 years of preterm babies recruited into a three-arm randomised controlled trial of prophylactic volume expansion was ascertained in two ways: from a neurodevelopmental assessment performed by a paediatrician and from responses on a brief questionnaire completed by the child's personal health visitor. Of 776 babies recruited into the trial, 604 survived to the age of 2 years and the findings of a paediatric assessment were available for all survivors. Questionnaires were sent to the health visitors of 601 of the survivors; 513 (85.4%) were returned. There was sufficient information on the returned questionnaires to categorise 449 of the children as normal, impaired, moderately disabled or severely disabled. We were unable to detect a response bias by severity of disability. Agreement on individual questions ranged between 86.3% and 98.4%. There was some mismatch in the reporting of vision (weighted kappa = 0.71) and hearing (weighted kappa = 0.73), with differences in perception of level of severity of sensory loss. Health visitors tended to underestimate the child's functional level compared with the paediatrician. However, of 56 children classified as severely disabled by the paediatrician, 48 were classified similarly and eight as moderately disabled on the basis of the questionnaire. The end point of the trial was death or severe disability at 2 years of age. There was close similarity in the trial results whether based on the paediatric assessment or on the questionnaire. Further refinement of the questionnaire is needed, but this methodology may be useful in ascertaining the frequency of severe disability in large cohorts of babies.

Comparing two methods of follow up in a multicentre randomised trial.

AIMS: To evaluate a parental questionnaire as a means of providing outcome measures for a multicentre randomised controlled trial of treatment for post-haemorrhagic ventricular dilatation. METHODS: The parents of 88 survivors were sent a questionnaire before a paediatric assessment at the age of 30 months. The parents' responses to individual questions taken mainly from the Griffiths' mental development scales and their perception of the child's ability to see and hear were compared with the paediatric findings. A model, based on the parents' responses to particular questions, allowed the categorisation of the children as normal, impaired, moderately or severely disabled; this was compared with similar categorisation based on the full paediatric assessment. RESULTS: Agreement on items concerning gross motor function ranged between 81 and 99%, concerning dressing between 77 and 80%, concerning feeding between 91 and 99%, and concerning language between 85 and 93%. Similar proportions of children were identified as disabled by the parents (60%) and by the paediatrician (66%). Of 29 children who had developmental quotients less than 70, parents identified 28 as disabled, 18 of them as severely disabled. They were not so good at identifying children with impairments without functional loss. CONCLUSIONS: Further work is required but there is sufficient encouragement from the results to pursue this methodology further for use in comparing groups in randomised trials.

Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine.

Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.

CLL Trials in the United Kingdom the Medical Research Council CLL Trials 1, 2 and 3.

The MRC has conducted randomised trials in CLL sine 1978: CLL 1 (1978-84), 660 patients; CLL 2 (1984-90), 640 patients; CLL 3 (from June 1990), 90 patients. Centralised morphological diagnosis and membrane marker studies have allowed the exclusion of non-CLL disorders. Some of the treatment questions were repeated in more than one trial. Chlorambucil (chl) given intermittently was compared with the combination COP in CLL 1: no differences in survival or response were observed although the response rate (CR + PR) of COP rose from 53% to 73% when the dose of cyclophosphamide was doubled; CR + PR with chl was 62%. Chlorambucil was used with or without prednisolone (pred) in CLL 2 (stages B and C) and no differences were observed in either response rate (chl 74%; chl + pred 80%) or survival. Comparing all cases which in both trials were allocated to receive a combination including pred (241) or chl alone (248), no advantage in survival could be detected with the addition of pred to alkylating agents. Splenic irradiation (SI) (116 patients) was compared to Chlorambucil (136 patients) in both trials. Although a survival advantage for SI was suggested in CLL 1, this was not confirmed in CLL 2. A new trial, CLL 3, will be testing the addition of an anthracycline, epirubicin, to chl in stages B and C. The effect of early therapy with chl was compared with deferred (or no) treatment in CLL 1 (stages I and II static) and CLL 2 (Stage A). The combined results in 306 patients show a survival advantage for the deferred treatment group (2p = 0.05) when allowance was made for age, stage and sex. Analysis of causes of death indicates that the main difference between the randomised groups is the number of deaths attributed to CLL itself. There was no significant difference in the incidence of cancer between the two groups.

Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults.

We report the analysis of prognostic factors in a cohort of 660 patients entered in the first Medical Research Council trial in chronic lymphocytic leukaemia (CLL) between 1978 and 1984. The majority (94%) of patients were aged 50 or over and the number of men (M) was almost twice that of women (F) with an M:F ratio of 1.8:1. The M:F ratio was lower, 1.5:1, in patients aged 70 or over. Stage A CLL was the most common, and stage C the least common, among women of all ages, in contrast to men for whom stage A only predominated in the older age group. As the majority of CLL patients are elderly we have examined the causes of death in great detail. 29% of deaths were unrelated to CLL, mainly other cancers (12%) and cardiovascular complications (16%). The majority of deaths in patients presenting with stages B and C were from CLL-related causes, whilst almost half of the deaths in patients presenting with stage A were not obviously related to CLL. Univariate analysis disclosed that the A, B, C staging system was the most important factor considered; stratified and multivariate analysis showed that age and response to treatment were the main prognostic factors after stage. Women always fared better than men and this was independent of stage and age. This and other features documented in the trial suggest a major biological difference between the sexes which has not been widely recognized. The significant influence of treatment response on patients' survival suggests that the search for better treatments in CLL may be rewarding. The improved median survival of stage C patients recorded in this trial, 41 months, compares favourably with previous reports and may have resulted from better treatment.

The UK Medical Research Council CLL trials 1 and 2.

The Medical Research Council (MRC) Working Party on Leukaemia in Adults has conducted two randomised trials in CLL since 1978. CLL 1 ran from 1978 to 1984 and recruited 660 eligible patients. The number of males was twice the number of females and the distribution of cases by stage was different in the sexes: 58% of females were stage A, 25% stage B and 17% stage C; in males the proportions for stages A, B and C were 40%, 30% and 30% respectively. The most important prognostic factor was stage (A, B, C), followed by age, sex and response to treatment, which were confirmed as independent variables by stratified log-rank and Cox multivariate analyses. Causes unrelated to CLL accounted for 28% of all deaths and were more common in older patients and in stage A disease. No significant difference was observed between the CLL 1 treatment schedules: chlorambucil, penta Cop and splenic irradiation (SI), although a somewhat better survival was seen for patients treated by SI. (When CLL deaths only were considered SI appeared superior to chlorambucil (p less than 0.05]. CLL 2 started in 1984 and is still accruing patients; 556 had been entered by July 1988. This trial compares early versus delayed therapy for stage A, chlorambucil with and without prednisolone for stages B and C in patients with a small or nonpalpable spleen, and SI vs chlorambucil with or without prednisolone for stages B and C in patients with a larger spleen (greater than or equal to 5 cm).(ABSTRACT TRUNCATED AT 250 WORDS)