Single shot spatial and temporal coherence properties of the SLAC Linac Coherent Light Source in the hard x-ray regime.

We measured the transverse and longitudinal coherence properties of the Linac Coherent Light Source (LCLS) at SLAC in the hard x-ray regime at 9 keV photon energy on a single shot basis. Speckle patterns recorded in the forward direction from colloidal nanoparticles yielded the transverse coherence properties of the focused LCLS beam. Speckle patterns from a gold nanopowder recorded with atomic resolution allowed us to measure the shot-to-shot variations of the spectral properties of the x-ray beam. The focused beam is in the transverse direction fully coherent with a mode number close to 1. The average number of longitudinal modes behind the Si(111) monochromator is about 14.5 and the average coherence time τ(c)=(2.0±1.0) fc. The data suggest a mean x-ray pulse duration of (29±14) fs behind the monochromator for (100±14) fc electron pulses.

Once-daily tobramycin in the treatment of adult patients with cystic fibrosis.

The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis. Sixty adult patients with an acute respiratory exacerbation were randomized to receive either 10 mg x kg(-1) tobramycin once-daily or 3.3 mg x kg(-1) tobramycin thrice-daily. Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing. Both groups showed a significant increase in respiratory function without a clinically significant change in renal function. For changes in forced vital capacity % predicted and serum potassium and magnesium levels, equivalence was demonstrated. For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels, there was insufficient power to demonstrate equivalence. One patient in each group showed bilateral impairment in pure tone audiogram after treatment. This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing. Equivalence between the two regimens was shown for some, but not all primary endpoints. Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results.

Management of lymphoma patients in a cancer unit: an audit of 15 years' experience in a district general hospital.

The objectives were to analyse data obtained in a district general hospital medical oncology unit over a 15-year period, and to provide a comparator for standards of care for lymphoma patients in new cancer units. Prospectively collected data were analysed on 208 consecutive patients presenting with lymphoma, on an 'all-comers' basis, between 1981 and 1996. Treatment was with radiotherapy and/or chemotherapy, according to local protocols. The outcome measure was survival from the date of diagnosis. The 5-year actuarial survival was 72.7% for Hodgkin's disease and 55.7% for non-Hodgkin's lymphoma. Age and stage of disease were the only predictors of survival in a multivariate analysis. Histological classification was not a useful predictor of survival in this analysis. Survival figures comparable with those obtained nationally and across Europe are attainable in a cancer unit. Multiple pathways of referral of lymphoma patients operate in our region.

Determinants of social outcome measured by the Frenchay Activities Index at one year after stroke onset.

We report an investigation to identify patient factors which influence social outcome measured by the Frenchay Activities Index at 12 months after a disabling stroke. Using data from a previous randomised trial a logistic regression model identified gait speed, prestroke Frenchay Activities Index, the Abbreviated Mental Test score, sensory neglect, chronic obstructive airways disease and left hemiplegia as significantly associated with 12-month social outcome scores. The model correctly predicted the social outcome for 78% of the study population and, when tested on a second data set, correctly predicted 76% of cases. These patient factors provide insight into social activity recovery after stroke and could be considered as stratification factors in future community stroke randomised trials.

The effects on prescribing patterns and costs of having a special interest in asthma.

To define the characteristics of general practices with a special clinical interest in asthma and to estimate the resulting extra prescribing costs, we sent a postal questionnaire to all English practices containing members of the General Practitioners in Asthma Group. Item and cost comparisons for 24 PACT (prescribing analysis and cost) aggregates were made between practices who had operated an agreed, written management plan for asthma before 1 April 1990 and all other practices in their respective Family Health Services Authorities. One hundred and sixty-three practices with GPIAG members responded (70%), of which 26 filled the management plan requirement. These 26 practices showed evidence of significantly better asthma care provision than the remainder of the sample. Their prescribing costs were significantly higher for respiratory drugs (median 37% higher) but lower in other drug categories. For respiratory drugs, costs were significantly higher for inhaled adrenoceptor stimulants, steroid inhalers, large spacers, and peak flow meters, but lower for cough medicines and systemic nasal decongestants: the number of items prescribed showed similar patterns. The prescribing costs of practices claiming a special interest in asthma are likely to show higher respiratory drug costs, but overall prescribing costs showed no increase in the practices studied.

Serum albumin and CA125 are powerful predictors of survival in epithelial ovarian cancer.

OBJECTIVE: To assess the prognostic significance of presentation serum albumin, clinical stage and CA125 levels in ovarian cancer. DESIGN: Retrospective analysis of data using a Cox proportional hazards model. SETTING: A district general hospital oncology unit. SUBJECTS: One hundred and fourteen consecutive patients with epithelial ovarian cancer. INTERVENTIONS: Cytotoxic chemotherapy and surgery. MAIN OUTCOME MEASURE: Survival. RESULTS: A linear increase in risk was observed with high log CA125 (P < 0.0001) and with low albumin (P < 0.0001). In late stage patients (III and IV) albumin is the best predictor of survival (P = 0.0006). The presence of ascites, blood transfusion, type of surgery or chemotherapy did not improve the predictive model. CONCLUSIONS: CA125 and albumin can be used to identify prognostic subgroups independently of stage. Albumin alone can also be used as a predictor of survival. A simple classification of patients into three groups based on serum albumin of 41 g/l or more, 35 to 40 g/l and 34 g/l or less provides a clear separation of survival curves in the present group of patients.

Measuring prescribing: the shortcomings of the item.

OBJECTIVES: To assess the validity of the item as a measure of the volume of a drug prescribed; and to investigate the possibility that higher quantities per item are prescribed for patients who are not exempt from the prescription charge. DESIGN: Five substudies. For the first, a frequency distribution was derived of the different quantities per item of 10 commonly used drugs prescribed by 20 randomly selected practices in each of five family health service authority areas. For the second, the variation in average quantity per item for the same drugs in the same practices was calculated. For the third and fourth, variation in average quantity per item for 90 commonly used drugs was calculated for all 90 family health service authorities and for all 14 regional health authorities in England. For the fifth, the average quantity per item for each of the 90 drugs was regressed on the percentage of items exempt from the prescription charge, at family health service authority level, and the percentage of variation explained by the regression found. MAIN OUTCOME MEASURE: Distribution of quantity per item; variation in average quantity per item between the practices, between family health service authorities, and between regions; and percentage of variation between family health service authorities accounted for by exemption from the prescription charge. RESULTS: Wide variation was found in the quantities per item prescribed by the practices, and in the average quantity per item between practices and between family health service authorities. No family health service authority was consistently high or low in quantity per item across the 90 drugs. Variation in average quantity per item was less at regional than at family health service authority level, though still high for many of the drugs. The proportion of variation accounted for by exemption from prescription charges ranged from 0% to 49% across the 90 drugs. CONCLUSIONS: The item is unsuitable as a measure of prescribing volume, even at regional level: a new measure, based on standard daily dosages, is needed. The percentage of the variation in quantity per item accounted for by exemption is inconsistent, and in over half the 90 drugs it was below 20%--therefore it is not a useful predictor.

Ozone depletion: causes, potential effects and remedies.

The ozone layer functions as a protective screen, filtering out most of the sun's harmful ultraviolet (UV) rays. This protective layer is located in the stratosphere between 15km and 35km above the earth's surface. Ozone is actually a form of oxygen. In the lower atmosphere, oxygen atoms commonly bond with each other in pairs. This molecule, abbreviated as O2, is the form of oxygen we need to breathe. Ozone is a more unstable and uncommon molecule made up of 3 oxygen atoms and is abbreviated O3.

The Acute Infarction Ramipril Efficacy (AIRE) Study: rationale, design, organization, and outcome definitions.

The rationale, design, organization, and outcome definitions of the Acute Infarction Ramipril Efficacy (AIRE) Study are described prospectively. A total of 2,000 patients (1,000 per treatment group) will be recruited to this multicenter, multinational, double-blind, randomized, placebo-controlled study investigating the effect of oral treatment with ramipril (2.5 or 5 mg twice daily) on the total mortality of survivors of an acute myocardial infarction (AMI) with early clinical evidence of heart failure. Secondary outcomes of the study include progression to severe/resistant heart failure (at which time the patient will be withdrawn from the study treatment), reinfarction, and stroke. Treatment will be initiated in hospital between day 3 and day 10 following AMI, and follow-up continued for an average of 15 months and a minimum of 6 months. The study data will be analyzed on an intention-to-treat basis: a single formal interim analysis will be conducted after 175 deaths. An Independent Adjudicating Panel will act as the overall ethical supervisory body for the study and will retain the randomization code. An International Steering Committee will be responsible for the clinical definitions of the secondary study outcomes, and will regularly review progress of the study. We believe that early treatment with ramipril may reduce the total mortality of patients surviving an AMI with clinical evidence of heart failure.

Outcome in patients on continuous ambulatory peritoneal dialysis and haemodialysis: 4-year analysis of a prospective multicentre study.

In a study in seven large renal units in England, the morbidity and mortality of all patients starting continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis during 1983-85 were monitored prospectively over a 4-year period and related to reasons for choice of therapy and potential risk factors. 610 new patients (median age 52 years, range 3-80 years) started CAPD; 16% had diabetes mellitus and 21% cerebrovascular or cardiovascular disease. 329 patients (median age 48 years, range 5-77 years) started haemodialysis; 7% had diabetes mellitus and 17% cerebrovascular or cardiovascular disease. The Kaplan-Meier patient survival estimates at 4 years were 74% for haemodialysis and 62% for CAPD; technique survival figures for the same period were 91% for haemodialysis and 61% for CAPD. Cox's proportional hazards regression analysis showed that cerebrovascular/cardiovascular disease, age over 60 years, and diabetes mellitus were important predictors for survival in CAPD patients; there were no risk factors associated with permanent change to haemodialysis. In the haemodialysis group early change to CAPD was associated with presence of cerebrovascular or cardiovascular disease. The major cause of drop-out in both groups was transplantation. The mean length of hospital admission was 14.8 days per patient-year for CAPD and 12.4 days per patient-year for haemodialysis.

Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies.

231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha-tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion.

Multi-centre study on outcome of treatment in patients on continuous ambulatory peritoneal dialysis and haemodialysis.

In a multi-centre study by seven large renal units in the United Kingdom, the morbidity and mortality of all patients starting CAPD and haemodialysis during a 2-year period (1983-1984) has been monitored prospectively and related to reasons for choice of therapy and potential risk factors. Over this period 338 new patients (mean age 48; range 3-77 years) started CAPD; 17% had diabetes mellitus and 25% had cerebro/cardiovascular disease. One hundred and seventy-five patients (mean age 45; range 5-73 years) started haemodialysis; 6% had diabetes mellitus and 14% had cerebro/cardiovascular disease. The Kaplan-Meier actuarial patient survival estimates at 2 years were haemodialysis 84% and CAPD 83%, whilst technique survival figures for the same period were haemodialysis 92% and CAPD 80%. Cox's regression analysis showed that cerebro/cardiovascular disease and age greater than 60 years were most important predictors for survival in CAPD patients, in whom smoking appeared to be a significant risk factor, for permanent change of therapy to haemodialysis. The major cause of 'drop out' in both groups was transplantation, whilst hospitalisation was 14.9 days per patient year for CAPD and 12.8 for haemodialysis patients. Within the CAPD group a temporary change to haemodialysis (less than 2 months) occurred on 106 occasions (each of mean of 19 days duration), amounting to 10 days per patient year of therapy. CAPD was used twice as often as haemodialysis for managing new patients. After 2 years hospitalisation technique and patient survival were comparable in the two groups, with cerebro/cardiovascular disease, age, and smoking being significant predictors of outcome.

Estimating the composition of tissue gained or lost from measurements of elementary body composition.

Studies of relationships between changes in body constituents resulting from disease or treatment can, in principle, give information about the composition of the tissues gained or lost. Frequently, however, the random errors of measurement are of similar magnitude to the changes measured, so that standard statistical methods such as linear regression analysis give biased estimates of the parameters in the relationships. Possible ways of obtaining better estimates are discussed and models suitable for two types of experiment are described. In the first, patients are measured before and after the changes; in the second, patients are measured only after the changes have occurred and their results compared with those for a group of control subjects assumed to be representative of the patients before they became ill. The models have been used to analyse losses of total body nitrogen and potassium as a result of surgery and of disease. The results suggest that patients who underwent surgical operation lost 1.7 mmol K per g N. Those who suffered from disease lost 2.0 mmol K per g N, but also lost, on average, 234 mmol K independently of N. Conventional linear regression analysis would have led to very different conclusions, emphasising the importance of applying appropriate models to the analysis of such data.

Statistics of response slopes.

Daubenspeck and Ogden in a recent paper recommended the use of directional statistics in the analysis of response slopes, and their advice has been followed by other workers. Their method is not valid, since it does not follow directly from their model. An efficient estimator of the slope (i.e., an estimator with minimum variance) is well known and is given here with a confidence interval for the true slope. They were also concerned with the two-sample problem to compare the slopes from two different samples. The method for this is more complicated but is summarized here. The likelihood ratio test and point and interval estimates are given. We discuss Daubenspeck and Ogden's example and the reason why, despite its invalidity, their method gave good results using their own data. Their data are also used to illustrate the methods described in this paper, and examples are given to highlight the practical differences between the two methods. Step-by-step procedures are included in the appendixes to enable readers to use these methods.