Audit in the management of T3 fixed-cord laryngeal cancer

EPIDEMIOLOGY: Disseminated MAC-infection is one of the most frequent opportunistic infections occurring in HIV-infected patients. Severely immunocompromised patients with CD4-counts < 50/microliter are at greatest risk for the disease. Survival of untreated infection is very poor (5 to 6 months). With therapy survival is prolonged by about 4 months. CLINICAL PRESENTATION AND DIAGNOSTIC PROCEDURES: The leading symptom of MAC-infection is fever eventually accompanied by weight lost, night sweats, enlarged lymph nodes, hepatosplenomegaly, abdominal pain and anemia. Blood cultures are very sensitive and the most appropriate examination. Other diagnostic procedures include bone marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the liver. Detection of MAC in sputum and stool samples only proves colonisation but not dissemination. However, colonisation of the gastrointestinal tract frequently precedes disseminated disease. THERAPY: Combination of clarithromycin, rifabutin and ethambutol has proven to be the most efficacious therapy and therefore has to be considered as standard therapy for disseminted MAC-infection. Problems most frequently encountered with this medication include uveitis (rifabutin) gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well as drug interactions with protease-inhibitors (rifabutin). PROPHYLAXIS: Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can diminish the risk of disseminated MAC-infection. Although a survival benefit has been seen with clarithromycin, primary prophylaxis of MAC-infection is not standard care in many centers. Reasons to withhold MAC-prophylaxis include lower incidence rates in some countries as well as possible side effects and drug interactions. CONCLUSION: Disseminated MAC-infection is a frequent opportunistic disease in HIV-infected persons who are severely immunocompromised. Antibiotic combination therapy with clarithromycin, rifabutin and ethambutol improves clinical symptoms and survival. Primary prophylaxis with different regimens is efficacious but the specific epidemiologic situation in each country has to be considered.     

Methotrexate-resistant form of dihydrofolate reductase protects transgenic murine embryos from teratogenic effects of methotrexate

Methotrexate, a potent inhibitor of the ubiquitously expressed enzyme dihydrofolate reductase, induces limb and facial anomalies that resemble vascular disruptions in their evolution and final outcome. Previous studies suggest that inhibition of dihydrofolate reductase is responsible for methotrexate-induced embryopathy, although specific sites of methotrexate activity have not been well defined. In this report, we show that constitutive expression of a methotrexate-resistant form of dihydrofolate reductase in transgenic embryos and their placentas ameliorates methotrexate teratogenicity. However, expression of the transgene in maternal tissues had no significant protective effect. The results confirm the role of dihydrofolate reductase inhibition in the pathogenesis of methotrexate-induced birth defects and provide a foundation for future studies of targeted transgene expression in select embryonic or placental cell populations.     

New techniques for guiding catheter management during directional coronary atherectomy

In an uncontrolled retrospective recall study of 57 patients treated with conical crown retained dentures, 60 restorations (37 in the maxillae and 23 in the mandible jaw) with a mean wearing time of 30.1 months (range 4 to 76) were evaluated. Of the 248 abutments, eight (3.2%) had been lost. Clinically healthy mucosa was seen in 35 jaws. The marginal fit of the copings was judged to be good. No caries or new restorations were observed in 44 patients. Thirteen patients had 19 surfaces with new restorations and 20 surfaces with caries lesions. Of these 39 surfaces, 38 were located subgingivally.     

A fast single pass edgel extraction routine

An edgel extraction algorithm is presented that requires only a single pass of the image. This algorithm determines the connectivity of all edgels found and also finds all junctions. Thresholding with hysteresis is used within the routine to improve the connectivity of the found edges.     

Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo

Chronic myelogenous leukemia (CML) is a malignant disease of the human hematopoietic stem cell caused by the BCR/ABL gene rearrangement. The only curative therapy is allogeneic transplantation. Although autologous transplants may prolong survival, most patients relapse because of disease persisting in the host and in the graft. Continued administration of chemotherapy after transplant could reduce the incidence of relapse provided that the autograft can be protected by transfer of a drug-resistance gene. However, CML autografts will almost certainly contain malignant stem cells that will also be rendered drug-resistant. The presence of the BCR/ABL oncoprotein is necessary and sufficient for malignant transformation seen in CML. We thus hypothesized that transfer of a vector that combines a drug-resistance gene with anti-BCR/ABL antisense (AS) sequences may allow for posttransplant chemotherapy to decrease persistent disease while rendering inadvertently transduced CML stem and progenitor cells functionally normal. We constructed a retroviral vector, LasBD, that combines the methotrexate (MTX)-resistant tyrosine-22 dihydrofolate-reductase (tyr22-DHFR) gene and AS sequences directed at the b3a2 BCR/ABL breakpoint. b3a2 BCR/ABL containing 32D and MO7e cells were transduced with LasBD and selected in MTX for 14 days. Expression of the AS sequences reduced BCR/ABL mRNA and p210(BCR/ABL) protein levels by 6- to 10-fold in most cells. This subsequently led to the restoration of normal function of BCR/ABL cDNA+ cells: they grew significantly slower in the presence of interleukin-3 (IL-3); they underwent apoptotic cell death when cultured without IL-3; and they had restored expression and function of adhesion receptors. These effects were specific, because LasBD-containing AS sequences directed at the b3a2 BCR/ABL breakpoint did not affect p190(BCR/ABL)-containing cells. LasBD also rendered 20% to 30% of primary Ph- and Ph+ CD34(+) cells MTX-resistant and decreased BCR/ABL mRNA levels in MTX resistant Ph+ CD34(+) cells by 10-fold. Expression of the MTX-resistant DHFR gene and the AS sequences has been stable for at least 1 year in vitro and for more than 70 days in vivo. Finally, LasBD decreased tumorigenicity of 32DBCR/ABL cells in vivo by 3 to 4 logs. In conclusion, the tyr22-DHFR gene in the LasBD vector can protect normal hematopoietic cells from MTX-mediated toxicity, whereas the AS sequences in LasBD can suppress expression of the BCR/ABL gene and restore normal function of BCR/ABL cDNA-containing cells. The LasBD vector may therefore prove to be an extremely useful adjunct in autologous transplantation for CML.     

High-speed & Low Area Hardware Architectures of the Whirlpool Hash Function

High-speed and low area hardware architectures of the Whirlpool hash function are presented in this paper. A full Look-up Table (LUT) based design is shown to be the fastest method by which to implement the non-linear layer of the algorithm in terms of logic. An unrolled Whirlpool architecture implemented on the Virtex XC4VLX100 device achieves a throughput of 4.9 Gbps. This is faster than a SHA-512 design implemented on the same device and other previously reported hash function architectures. A low area iterative architecture, which utilises 64-bit operations as opposed to full 512-bit operations, is also described. It runs at 430 Mbps and occupies 709 slices on a Virtex X4VLX15. This proves to be one of the smallest 512-bit hash function architectures currently available.

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.     

A comparison of local surface geometry estimation methods

The performance of several methods for estimating local surface geometry (the principal frame plus the principal quadric) are examined by applying them to a suite of synthetic and real test data which have been corrupted by various amounts of additive Gaussian noise. Methods considered include finite differences, a facet based approach, and quadric surface fitting. The nonlinear quadric fitting method considered was found to perform the best but has the greatest computational cost. The facet based approach works as well as the other quadric fitting methods and has a much smaller computational cost. Hence it is the recommended method to use in practice.     

Minimizing the bullwhip effect in a supply chain using genetic algorithms

This paper presents a computational intelligence approach, which addresses the bullwhip effect in supply chains (SCs). A genetic algorithm (GA) is employed to reduce the bullwhip effect and cost in the MIT beer distribution game. The GA is used to determine the optimal ordering policy for members of the SC. The paper shows that the GA can reduce the bullwhip effect when facing deterministic and random customer demand combined with deterministic and random lead times. The paper then examines the effect of sales promotion on the ordering policies and shows that the bullwhip effect can be reduced, even when sales promotions occur in the SC.     

Employing dynamic fuzzy membership functions to assess environmental performance in the supplier selection process

The proposed system illustrates that logic fuzzy can be used to aid management in assessing a supplier's environmental performance in the supplier selection process. A user-centred hierarchical system employing scalable fuzzy membership functions implement human priorities in the supplier selection process, with particular focus on a supplier's environmental performance. Traditionally, when evaluating supplier performance, companies have considered criteria such as price, quality, flexibility, etc. These criteria are of varying importance to individual companies pertaining to their own specific objectives. However, with environmental pressures increasing, many companies have begun to give more attention to environmental issues and, in particular, to their suppliers’ environmental performance. The framework presented here was developed to introduce efficiently environmental criteria into the existing supplier selection process and to reflect on its relevant importance to individual companies. The system presented attempts to simulate the human preference given to particular supplier selection criteria with particular focus on environmental issues when considering supplier selection. The system considers environmental data from multiple aspects of a suppliers business, and based on the relevant impact this will have on a Buying Organization, a decision is reached on the suitability of the supplier. This enables a particular supplier's strengths and weaknesses to be considered as well as considering their significance and relevance to the Buying Organization.