The road to maturity: navigating between craft and science

C. Ebert presents his views on the state of software engineering as a field, its roots and inherent conflicts, its relationship to other engineering disciplines, where it is headed, and what we can do to influence that direction. T. Matsubara, T. Webb, M. Pezze, and O.W. Bertelsen offer a spectrum of further insights     

Direct evidence of high DNA binding activity of transcription factor AP-1 in rheumatoid arthritis synovium

Green fluorescent protein (GFP) is increasingly being used in plant biology from the cellular level to whole plant level. At the cellular level, GFP is being used as an in vivo reporter to assess frequency of transient and stable transformation. GFP has also proven to be an invaluable tool in monitoring trafficking and subcellular localization of protein. At the organ level and up, many exciting applications are rapidly emerging. The development of brighter GFP mutants with more robust folding properties has enabled better macroscopic visualization of GFP in whole leaves and plants. One interesting example has been the use of GFP to monitor virus movement in and among whole plants. GFP is also emerging as a powerful tool to monitor transgene movement and transgenic plants in the field. In a proof-of-concept study, tobacco was transformed with a modified version of the GFP gene controlled by a constitutive (35S) promoter. GFP expression in progeny plants ranged from 0% to 0.5%, and approximately 0.1% GFP was the minimal amount needed for unambiguous macroscopic detection. GFP is the first truly in vivo reporter system useful in whole plants, and we project its usefulness will increase even further as better forms of GFP genes become available.     

Effect of hygiene measures, water sanitation and oral rehydration therapy on diarrhea in children less than five years old in the south of Ivory Coast

BACKGROUND: Gastric sucrose permeability is a noninvasive marker that reliably increases in association with gastrointestinal injury due to use of nonsteroidal antiinflammatory drugs. Despite the effect of Helicobacter pylori infection on the gastric mucosa, in a previous study we were unable to demonstrate that H. pylori infection was associated with abnormal gastric sucrose permeability. Our goal in this study was to explore further whether H. pylori infection changed gastric permeability; therefore, we evaluated the effect of treatment of H. pylori infection on gastric permeability to sucrose and the relation of sucrose permeability to density of polymorphonuclear leukocytes. MATERIALS AND METHODS: Five hundred milliliters of a solution containing 100 gm of sucrose was ingested by the subject at bedtime. Overnight urine was collected and assayed for sucrose by high-performance liquid chromatography. Sucrose permeability was assessed both before and approximately 4 weeks after anti-H. pylori therapy. RESULTS: Seventeen asymptomatic H. pylori-infected volunteers participated; 8 were cured. Sucrose permeability was in the range commonly found in normal controls both before and after anti-H. pylori therapy (mean excretion, 76.3 mg; range, 13-171 mg). Gastric sucrose permeability correlated with the density of polymorphonulcear cell infiltration of the mucosa. Cure of the H. pylori infection was associated with a small but significant decrease in sucrose permeability (98.8 +/- 18 mg to 51.7 +/- 9.8 mg (p = .01). Sucrose permeability was greater in those with a high density of mucosal polymorphonuclear cells compared to those with lower scores (119.5 +/- 4 vs 71.4 +/- 13 for those with scores > or = 5 compared to scores < or = 4; p = .023). Failed therapy resulted in an increase in the mucosal density of polymorphonuclear infiltration and sucrose permeability (56.4 +/- 13 mg-99.7 +/- 19 mg pretreatment vs posttreatment, respectively; p = .031). CONCLUSION: H. pylori gastritis causes a small but measurable increase in gastric permeability to sucrose that may reflect epithelial transmigration of neutrophils.     

Regression of severe atherosclerotic plaque in patients with mild elevation of LDL cholesterol

BACKGROUND: Intensive risk factor reduction in patients with dyslipidemias and coronary atherosclerosis has been shown to result in alterations in coronary artery morphology and reduced clinical events. However, the impact of such interventions in populations with relatively normal levels of low-density lipoproteins (LDL) is unclear. METHODS: To test the hypothesis that intensive risk factor reduction results in angiographic regression in patients with only mildly elevated levels of LDL, 14 patients with angiographically proven coronary atherosclerosis were entered into the University of California Davis Coronary Artery Disease Regression Program and intensively treated with pharmacologic and nonpharmacologic interventions for 2 years. Quantitative angiography was performed prior to and after 2 years of therapy to determine changes in coronary artery diameter. RESULTS: As a result of this program, dietary fat intake was reduced by 58% and LDL fell from 120 +/- 7 mg/dL to 104 +/- 6 mg/dL (p = 0.05). The average diameter of the measured arterial locations (including all 53 stenoses and 292 nondiscrete regions) on study entry was 2.74 +/- 0.05 mm. After 24 months, there was a net increase in arterial diameter (regression) of +0.05 +/- 0.04 mm to 2.81 +/- 0.05 mm (p = 0.01). While there was no significant change in the average diameter of discrete stenoses, all 8 lesions > or = 50% initial diameter narrowing regressed, with a mean diameter change of + 0.2 mm. Conversely, only 1 of 8 mild lesions < or = 20% regressed, while 4 progressed. Intermediate lesions (20% to 50%, n = 37) had balanced progression and regression. CONCLUSIONS: When examined as a continuous variable, there was a significant linear correlation between initial lesion severity (% stenosis) and the extent of regression (mm). Therefore, risk factor reduction (dietary therapy, exercise, psycho-social counseling, and lipid lowering therapy) in patients with only mild dyslipidemia results in angiographic regression of more severe lesions (> 50% initial stenosis), but does not prevent progression of mild lesions (< 20%). These findings demonstrate that intensive risk factor reduction in patients with only mild elevation of lipids beneficially influences the morphology of the most severe lesions.     

Study of the heart rate and energy expenditure of ponies during transport

The energy expenditure and heart rate of five Shetland ponies were measured during transport and compared with the values recorded while they were at rest and walking. Secondary aims of the study were to investigate whether there was any correlation between heart rate and energy expenditure and whether different orientations affected the values to different degrees. The measurements were recorded at one-minute intervals while the ponies were at rest, walking and being transported in four different orientations, on journeys lasting 30 minutes. There were significant increases (P < 0.001) in both heart rate and energy expenditure during transport which were similar to those associated with walking, and there was a strong correlation between the two measurements. There was no conclusive evidence that orientation affected the measurements, but it appeared that rear facing transport might have had the least effect.     

Peer evaluation. A visual picture

To meet the criteria of role accountability, nursing competence and ongoing staff development, an improved peer-evaluation system was designed to continuously monitor these new roles. This peer-evaluation process converts evaluation input into data, giving staff a visual picture of how their performance compares within their peer group. This peer-evaluation process was designed as a tool to assist in staff growth and development, not as a punitive system.     

Experimental methods in hepatology. Guidelines of the German Association for the Study of the Liver (GASL). Liver perfusion--technique and applications

Purified cell-envelope polyphosphatase as well as polyphoshatase activities of cytosol and isolated vacuoles, of nuclei and mitochondria of the yeast Saccharomyces cerevisiae were compared. The polyphosphatases of cell envelope and cytosol are similar, the polyphosphatases of nuclei, vacuoles and mitochondria differ in their kinetic properties, substrate specificity, requirements in divalent cations and in some effector actions both from these and from each other.     

Magnetic resonance of the encephalon in 17 patients with ocular Beh?et''s disease

OBJECTIVE: To evaluate the relationships between patient and physician pretreatment expectations of pain relief and subsequent pain relief reported by chronic pain patients immediately after treatment. DESIGN: Prospective study of consecutive patients undergoing a procedure in a pain clinic for treatment of chronic pain. Patients rated their current pain level and their expectation of pain relief immediately prior to undergoing a procedure (e.g., intravenous drug infusion, nerve block) for the treatment of chronic pain. Simultaneously and independently, the treating physician completed a similar questionnaire. At completion of the procedure, patients rated their current pain level and degree of pain relief. SETTING: University of Washington Multidisciplinary Pain Center procedure suite. PATIENTS: Forty-six consecutive chronic pain patients. INTERVENTION: Intravenous drug infusions and nerve blocks. OUTCOME MEASURES: Current pain and pain relief ratings. RESULTS: Patients' pain relief expectation ratings were not correlated significantly with their postprocedure pain relief ratings or pre-post procedure changes in pain ratings. However, a statistically significant correlation was found between physician expectations of pain relief and patient pain relief ratings and patient pre-post procedure changes in pain. CONCLUSIONS: The results of this study suggest that physicians are better predictors than are patients of patients responses to these procedures and/or that physicians may somehow subtly communicate their expectations to patients during the procedure, and these expectations then influence patient response. Patient pretreatment expectations may not always play a significant role in nonspecific treatment effects.     

An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.     

Certain nonlinear partially observable stochastic optimal controlproblems with explicit control laws equivalent to LEQG/LQG problems

This paper is concerned with partially observed stochastic optimal control problems when nonlinearities enter the dynamics of the unobservable state and the observations as gradients of potential functions. Explicit representations for the information state are derived in terms of a finite number of sufficient statistics. Consequently, the partially observed problem is recast as one of complete information with a new state generated by a modified version of the Kalman filter. When the terminal cost is quadratic in the unobservable state and includes the integral of the nonlinearities, the optimal control laws are explicitly computed, similar to linear-exponential-quadratic-Gaussian (LEQG) and linear-quadratic-Gaussian (LQG) tracking problems. The results are applicable to filtering and control of Hamiltonian systems