The pickup and delivery problem: Faces and branch-and-cut algorithm

This paper formulates the pickup and delivery problem, also known as the dial-a-ride problem, as an integer program. Its polyhedral structure is explored and four classes of valid inequalities developed. The results of a branch-and-cut algorithm based on these constraints are presented.     

Giuseppe Gradenigo and his contributions to audiology

Giuseppe Gradenigo (1859-1926) was an important figure in the development of Otology. Within this paper the authors consider his background and his particular contributions to the development of various aspects of audiology.     

Procedural memory stimulation in Alzheimer''s disease: impact of a training programme

The operative results of 23 patients with a specific or unspecific spondylodiscitis were documented over 2 years after the focus of the inflammation had been eradicated, bone chip had been interposed and a CDH instrumentation had been performed by an anterior approach only. These outcomes were compared with the results of 32 patients in whom the focus had been removed and the defect had been filled with bone graft from an anterior approach, followed by stabilisation with CD instrumentation through an additional dorsal approach. In the cases where CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This was clearly less extensive than in dorsoventral stabilisation, in which on average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved without orthesis. Eight months after the operations bony fusion could be observed radiologically in all patients. The mean preoperative kyphotic angle of the affected segments was 14.4 degrees, compared to 4 degrees after the operation. The mean loss of reposition was measured to be about 2.7 degrees in both groups. Average operation time and blood loss were about 50% higher in the patients treated dorsoventrally. We conclude that even in the case of florid spondylodiscitis, a short-range anterior fusion of the affected spinal segment may be performed by use of a stable-angle implant without an increased risk of infection-related loosening.     

Growth factor receptor expression during in vitro differentiation of partially purified populations containing murine stem cells

The Word Accentuation Test assesses the accentuation of 30 infrequent Spanish words written without the accentuation mark and is an easy-to-use tool for estimating premorbid intelligence of Spanish-speaking people. Its intraobserver (0.97) and interobserver (0.93) reliabilities and its correlation with the Wechsler Adult Intelligence Scale (.837) and Raven's Progressive Matrices (.655) are high, offering a good prediction of general intelligence. It is resistant to mental deterioration; 20 demented and 40 controls matched by sex, age, and education obtained similar scores. The discrepancies between current and predicted scores in Raven's scale can diagnose mild-moderate dementia with 0.79 accuracy (sensitivity, 0.78; specificity, 0.82).     

AHMED experiments on hygroscopic and inert aerosol behaviour in LWR containment conditions: experimental results

Hygroscopic NaOH, CsI, CsOH and inert Ag aerosol behaviour at different temperatures and relative humidities (RH) has been studied in a well instrumented and controlled vessel of 1.81 m³ total free volume. Homogeneous thermal-hydraulic conditions for aerosol measurement in the vessel were achieved. The aerosol number and mass concentration were measured continuously during the experiments using a Condensation Nucleus Counter and a Tapered Element Oscillating Microbalance. The particle size distribution and chemical composition in the test conditions were measured by Berner low pressure impactors. In the case of NaOH the half life of the aerosol mass concentration was more than four times longer at low RH (22%) as compared to high RH (96%). The half lives of the CsOH and CsI aerosols were only twice as long at low RH as compared to high RH. Thus at high RH (96–97%) the half lives of CsOH and CsI were twice as long as the half life for the NaOH aerosol. The faster decay of the NaOH aerosol is due to the smaller density decrease of NaOH during water condensation. CsOH particles grew rapidly to their equilibrium size at all humidities. The measured equilibrium size for CsOH aerosol agree well with the calculated particle size at different RHs. Experimental results were also compared with calculations obtained by severe accident computer codes. These calculated results will be presented in a later paper.     

Influence of structure on the antioxidant activity of indolinic nitroxide radicals

An in vitro study was carried out to verify whether the chain length of a substituent on an indolinic nitroxide could influence its antioxidant activity in different biological environments subjected to oxidative stress. Three distinct indolinic nitroxides were synthesized and compared with vitamin E and Trolox (a hydrophilic analogue of vitamin E), where the only difference between the nitroxides was the length of the hydrocarbon chain in the 2-position of indole, namely 2 (C2), 10 (C10), and 18 (C18) carbons. All the nitroxides were effective in preventing oxidation of bovine serum albumin, but to different extents, with the longer chain derivatives being more efficient. However, the C2 compound was the most efficient in preventing lipid peroxidation in microsomal membranes. The C2 and C18 compounds, Trolox, and vitamin E protected microsomal protein oxidation to the same extent at the highest concentration used (13 microM). The nitroxide with a C10 chain was less effective in this system. The influence of these compounds on the enzymatic activity of two mitochondrial proteins subjected to oxidative stress was also studied by means of oxygraph measurements. Mitochondrial rotenone-sensitive NADH oxidase and succinate oxidase responded differently to BuOOH-induced radical chemistry, and the compounds under study also protected the activity of the two enzymes but to different extents. The results clearly demonstrate that indolinic nitroxides are very efficient antioxidants, protecting both lipids and proteins from peroxidation. The indole structure influences the antioxidant efficacy in biological systems.     

Anatomically constrained electrical impedance tomography forthree-dimensional anisotropic bodies

As shown previously for two-dimensional geometries, anisotropy effects should not be ignored in electrical impedance tomography (EIT) and structural information is important for the reconstruction of anisotropic conductivities. Here, we describe the static reconstruction of an anisotropic conductivity distribution for the more realistic three-dimensional (3-D) case. Boundaries between different conductivity regions are anatomically constrained using magnetic resonance imaging (MRI) data. The values of the conductivities are then determined using gradient-type-algorithms in a nonlinear-indirect approach. At each iteration, the forward problem is solved by the finite element method. The approach is used to reconstruct the 3-D conductivity profile of a canine torso. Both computational performance and simulated reconstruction results are presented together with a detailed study on the sensitivity of the prediction error with respect to different parameters. In particular, the use of an intracavity catheter to better extract interior conductivities is demonstrated     

Comorbidity of drug dependence and other mental disorders: a two-phase study of prevalence at outpatient treatment centres in Italy

The proposed mechanism of action of the antineoplastic drug 3-nitrobenzothiazolo[3,2-alpha]quinolinium chloride (NBQ-2) involves its interaction with DNA by intercalation and inhibition of topoisomerase II activity by arresting the enzyme in a covalent cleavage complex. In an attempt to identify some structural determinants for activity and develop a molecular structure/cytotoxicity correlation, four new structural analogs of the antitumor NBQ-2 were prepared and their cytotoxic activity and DNA binding properties were investigated. The cytotoxic activity was evaluated against six different human tumor cell lines: U937, K-562, HL-60, HT-29, HeLa, and A431. The results showed that these new drugs elicit pronounced cytotoxic effects against U937, K-562, HL-60 and A431 while HeLa and HT-29 were less sensitive to the new drugs. This apparent selectivity was different to that of m-AMSA, a drug currently used for cancer treatment. Since the interaction of NBQ-2 to DNA by intercalation has been proposed as the initial step leading to its antineoplastic activity, DNA binding and changes in DNA contour length induced by the new NBQ-2 structural analogs were also investigated using calf thymus and human DNA. The drug, 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-alpha]quinolinium chloride (NBQ-59) was the most cytotoxic agent of the analog series (IC50 = 16 microM for HL-60 cells), however, it demonstrated the weakest binding to DNA (Kint = 0.9 x 10[5] M-1 for calf thymus DNA). NBQ-59 was also found to be a poor intercalator into the DNA double helix. Therefore, our results suggest that DNA binding is not the primary mechanism of drug action for this family of compounds. In addition structural determinants important for cytotoxicity of the benzazolo quinolinium chlorides were suggested by our results. In particular, the nitro group in the 3 position does not seem to be necessary for bioactivity, while substitutions in the benzazolo moiety have striking effects on the biological activity of the drugs.     

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.     

Computerized determination of proliferating cell nuclear antigen expression in meningiomas. A comparison with non-automated method

Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas.