The case against a positivist philosophy of requirements engineering

Requirements engineering is a field with a heavy practical emphasis and for the most part is quite rightly unconcerned with philosophical reflection. However, there have been exceptions. Philosophical arguments are important because they can be used to powerful effect, facilitating explicit debate on views that may previously have been implicit, and shaping the direction of thought and research within the field. Several cases from both requirements engineering and software engineering have given prominence to the philosophy of positivism. This paper will outline arguments against such a view.

IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

Cerebral arteriovenous malformations in children: neuroimaging findings

Cerebral arteriovenous malformations (CAVMs) are uncommon in children. CAVMs represent the most frequent intracranial vascular pathology at pediatric ages. This report concerns 13 children below the age of 16; all were identified between September 1995 and December 1996 with 14 CAVMs among them. All were proved by conventional cerebral angiography (CCA). Thirteen computed tomography (CT), 7 magnetic resonance images (MRI), 2 magnetic resonance angiography (MRA) and 13 conventional cerebral angiography (CCA) were analyzed. Most CAVMs nidus were located in cerebral hemispheres. Four in the temporal lobe, two in the parietal lobe, three in the frontal lobe, two in the occipital lobe, and three in the corpus callosum. One of them was of a mixed type with two nidi. The major clinical features of CAVMs were intracranial hemorrhage and seizures. Experience here was that MRI is superior to CT in showing the exact anatomic relationships of the nidus and in demonstrating the extent of CAVMs nidus obliteration after treatment. MRA provided a noninvasive means of studying blood vessels and vascular pathology in relationship to the CAVMs nidus. Standard angiography is still necessary to characterize in-flow and out-flow of vessels in CAVMs when definitive treatment is considered.     

Molecular evolution of RNA in vitro

Experimental studies of RNA evolution in vitro are reviewed in the context of Eigen's 1971 theory and its subsequent extensions. Current research activity and future prospects for using automated molecular biology techniques for in vitro evolution experiments are surveyed.