Computer system for assisting with clinical interpretation of tumour marker data.

OBJECTIVE--To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN--A comparison of clinicians'' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING--Department of medical oncology. PATIENTS--Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES--The system''s accuracy in predicting need to change treatment compared with clinicians'' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS--On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS--The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.     

Preregistration house officers in eight English regions: survey of quality of training.

OBJECTIVE--To assess the quality of preregistration house officer training in eight English regions. DESIGN--Postal questionnaire. SETTING--Thames, East Anglian, Mersey, Northern, and Wessex regions. PARTICIPANTS--1670 preregistration house officers. MAIN OUTCOME MEASURES--Education, hours of work, workload, conditions of work, and attitudes to job and medicine as a career. RESULTS--Response rate was 69% (1146 replies). Most house officers had attended induction courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The proportions who had never received adequate guidance on how to break bad news and how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There was much variation between regions. Overall, 65% (736/1138) reported confidence in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142)) worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift; 19% (202) were on duty for average weekly hours that exceeded the targets for 1 April 1993. House officers had a median of 20 patients under their care and clerked a median of 10 emergency cases, six routine cases, and two day cases a week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20% (223/1095) did not always have clean sheets available in their on call room, and 45% (462/1036) did not consider the protection of staff against violence to be adequate at their hospital. The most important problems with the preregistration year were inappropriate or non-medical tasks (ranked first by 360 respondents), hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125) would encourage a friend to apply for their post, but only 24% (266/1112) would encourage a friend to take up medicine and 44% (494/1112) would discourage the idea. CONCLUSIONS--House officers'' training is deficient in important respects, with inappropriate tasks and heavy clinical workloads impeding the provision of proper education.     

Flux Analysis of Glucose Metabolism in Rhizopus oryzae for the Purpose of Increasing Lactate Yields

A flux analysis of glucose metabolism in the filamentous fungus Rhizopus oryzae was achieved using a specific radioactivity curve-matching program, TFLUX. Glycolytic and tricarboxylic acid cycle intermediates labeled through the addition of extracellular [U-14C]glucose were isolated and purified for specific radioactivity determinations. This information, together with pool sizes and the rates of glucose utilization and end product production, provided input for flux maps of the metabolic network under two different experimental conditions. Based upon the flux analysis of this system, a mutant of R. oryzae with higher lactate and lower ethanol yields than the parent was sought for and found.     

Cortical neurite outgrowth and growth cone behaviors reveal developmentally regulated cues in spinal cord membranes.

Corticospinal axon outgrowth in vivo and the ability to sprout or regenerate after injury decline with age. This developmental decline in growth potential has been correlated with an increase in inhibitory myelin-associated proteins in older spinal cord. However, previous results have shown that sprouting of corticospinal fibers after contralateral lesions begins to diminish prior to myelination, suggesting that a decrease in growth promoting and/or an increase in inhibitory molecules in spinal gray matter may also regulate corticospinal axon outgrowth. To address this possibility, we carried out in vitro experiments to measure neurite outgrowth from explants of 1-day-old hamster forelimb sensorimotor cortex that were plated onto membrane carpets or membrane stripe assays prepared from white or gray matter of 1-to 22-day-old cervical spinal cord. On uniform carpets and in the stripe assays cortical neurites grew robustly on young but not older membranes from both white and gray matter. Mixtures of membranes from 1- and 15-day spinal cord inhibited neurite outgrowth, suggesting that the presence of inhibitory molecules in the 15-day cord overwhelmed permissive or growth promoting molecules in membranes from 1-day cord. Video microscopic observations of growth cone behaviors on membrane stripe assays transferred to glass coverslips supported this view. Cortical growth cones repeatedly collapsed at borders between permissive substrates (laminin or young membrane stripes) and nonpermissive substrates (older membrane stripes). Growth cones either turned away from the older membranes or reduced their growth rates. These results suggest that molecules in both the gray and white matter of the developing spinal cord can inhibit cortical neurite outgrowth.     

Behaviorally measured audiograms and gap detection thresholds in CBA/CaJ mice

Tone detection and temporal gap detection thresholds were determined in CBA/CaJ mice using a Go/No-go procedure and the psychophysical method of constant stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ mice. Thresholds were obtained for eight pure tones ranging in frequency from 1 to 42 kHz. Audiograms showed peak sensitivity between 8 and 24 kHz, with higher thresholds at lower and higher frequencies. In the second experiment, thresholds for gap detection in broadband and narrowband noise bursts were measured at several sensation levels. For broadband noise, gap thresholds were between 1 and 2 ms, except at very low sensation levels, where thresholds increased significantly. Gap thresholds also increased significantly for low pass-filtered noise bursts with a cutoff frequency below 18 kHz. Our experiments revised absolute auditory thresholds in the CBA/CaJ mouse strain and demonstrated excellent gap detection ability in the mouse. These results add to the baseline behavioral data from normal-hearing mice which have become increasingly important for assessing auditory abilities in genetically altered mice.