Optimal Use of Treatment Modalities and Treatment Results of Osteosarcoma and Soft Tissue Sarcomas

Soft tissue sarcomas are malignant tumours of mesenchymal origin. Because of infiltrative growth pattern, simple enucleation of the tumour causes a high rate of local recurrence. Instead, these tumours should be resected with a rim of normal tissue around the tumour. Data on the adequate margin width are scarce. At Helsinki University Central Hospital (HUCH) a multidisciplinary treatment group started in 1987. Surgical resection with a wide margin (2.5 cm) is the primary aim. In case of narrower margin radiation therapy is necessary. The role of adjuvant chemotherapy remains unclear. Our aims were to study local control by the surgical margin and to develop a new prognostic tool to aid decision-making on which patients should receive adjuvant chemotherapy. Patients with soft tissue sarcoma of the extremity or the trunk wall referred to HUCH during 1987-2002 form material in Studies I and II. External validation material comes from the Lund university sarcoma registry. The smallest surgical margin of at least 2.5 centimetres yielded local control of 89 per cent at five years. Amputation rate was 9 per cent. The proposed prognostic model with necrosis, vascular invasion, size on a continuous scale, depth, location and grade worked well both in Helsinki material and in the validation material, and it also showed good calibration. Based on the present study, we recommend the smallest surgical margin of 2-3 centimetres in soft tissue sarcoma irrespective of grade. Improvement in local control was present but modest in margins wider than 1 centimetre. In cases where gaining a wider margin would lead to a considerable loss of function, smaller margin is to be considered combined to radiation therapy. Patients treated with inadequate margins should be offered radiation therapy irrespective of tumour grade. Our new prognostic model to estimate 10-year survival probability in patients with soft tissue sarcoma of the extremities or trunk wall showed good dicscrimination and calibration. For time being the prognostic model is available for scientific use and further validations. In the future, the model may aid in clinical decision-making. For operable osteosarcoma, neoadjuvant multidrug chemotherapy followed by delayed surgery and multidrug adjuvant chemotherapy is the treatment of choice. Overall survival rates at five years are approximately 75 per cent in modern trials with classical osteosarcoma. All patients diagnosed and reported to the Finnish Cancer Registry with osteosarcoma in Finland during 1971-2005 form the material in Studies III and IV. Limb-salvage rate increased from 23 per cent to 78 per cent during 1971-2005. The 10-year sarcoma-specific survival for the whole study population improved from 32 per cent to 62 per cent. It was 75 per cent for patients with a local high-grade osteosarcoma of the extremity diagnosed during 1991-2005. This study outlines the improved prognosis of osteosarcoma patients in Finland with modern chemotherapy. The 10-year survival rates are good also in an international scale. Nonetheless, their limb-salvage rate remains inferior to those seen for highly selected patient series. Overall, the centralisation of osteosarcoma treatment would most likely improve both survival and limb-salvage rates even further.

Myoblast Sheet Transplantation for Treatment of Heart Failure after Myocardial Infarction

Heart failure is a common, severe, and progressive condition associated with high mortality and morbidity. Because of population-aging in the coming decades, heart failure is estimated to reach epidemic proportions. Current medical and surgical treatments have reduced mortality, but the prognosis for patients has remained poor. Transplantation of skeletal myoblasts has raised hope of regenerating the failing heart and compensating for lost cardiac contractile tissue. In the present work, we studied epicardial transplantation of tissue-engineered myoblast sheets for treatment of heart failure. We employed a rat model of myocardial infarction-induced acute and chronic heart failure by left anterior descending coronary artery ligation. We then transplanted myoblast sheets genetically modified to resist cell death after transplantation by expressing antiapoptotic gene bcl2. In addition, we evaluated the regenerative capacity of myoblast sheets expressing the cardioprotective cytokine hepatocyte growth factor in a rat chronic heart failure model. Furthermore, we utilized in vitro cardiomyocyte and endothelial cell culture models as well as microarray gene expression analysis to elucidate molecular mechanisms mediating the therapeutic effects of myoblast sheet transplantation. Our results demonstrate that Bcl2-expression prolonged myoblast sheet survival in rat hearts after transplantation and induced secretion of cardioprotective, proangiogenic cytokines. After acute myocardial infarction, these sheets attenuated left ventricular dysfunction and myocardial damage, and they induced therapeutic angiogenesis. In the chronic heart failure model, inhibition of graft apoptosis by Bcl-2 improved cardiac function, supported survival of cardiomyocytes in the infarcted area, and induced angiogenesis in a vascular endothelial growth factor receptor 1- and 2-dependent mechanism. Hepatocyte growth factor-secreting myoblast sheets further enhanced the angiogenic efficacy of myoblast sheet therapy. Moreover, myoblast-secreted paracrine factors protected cardiomyocytes against oxidative stress in an epidermal growth factor receptor- and c-Met dependent manner. This protection was associated with induction of antioxidative genes and activation of the unfolded protein response. Our results provide evidence that inhibiting myoblast sheet apoptosis can enhance the sheets efficacy for treating heart failure after acute and chronic myocardial infarction. Furthermore, we show that myoblast sheets can serve as vehicles for delivery of growth factors, and induce therapeutic angiogenesis in the chronically ischemic heart. Finally, myoblasts induce, in a paracine manner, a cardiomyocyte-protective response against oxidative stress. Our study elucidates novel mechanisms of myoblast transplantation therapy, and suggests effective means to improve this therapy for the benefit of the heart failure patient.

Casting and heat treatment variables of Al–7Si–Mg alloy

A review of the research work that has been carried out thus far relating the casting and heat treatment variables to the structure and mechanical properties of Al–7Si–Mg (wt-%) is presented here. Although specifications recommend a wide range of magnesium contents and a fairly high content of iron, a narrow range of magnesium contents, closer to either the upper or lower specified limits depending on the properties desired, and a low iron content will have to be maintained to obtain optimum and consistent mechanical properties. A few studies have revealed that the modification of eutectic silicon slightly increases ductility and fracture toughness and also that the effect of modification is predominant at low iron content. Generally, higher solidification rates give superior mechanical properties. Delayed aging (the time elapsed between quenching and artificial aging during precipitation hardening) severely affects the strength of the alloy. The mechanism of delayed aging can be explained on the basis of Pashley's kinetic model. It has been reported that certain trace additions (cadmium, indium, tin, etc.) neutralise the detrimental effect of delayed aging. In particular, it should be noted that delayed aging is not mentioned in any of the specifications. With reference to the mechanism by which trace additions neutralise the detrimental effect of delayed aging, various hypotheses have been postulated, of which impurity–vacancy interaction appears to be the most widely accepted.

Optimal scheduling of a processor executing a communication protocol stack

We consider the problem of optimally scheduling a processor executing a multilayer protocol in an intelligent Network Interface Controller (NIC). In particular, we assume a typical LAN environment with class 4 transport service, a connectionless network service, and a class 1 link level protocol. We develop a queuing model for the problem. In the most general case this becomes a cyclic queuing network in which some queues have dedicated servers, and the others have a common schedulable server. We use sample path arguments and Markov decision theory to determine optimal service schedules. The optimal throughputs are compared with those obtained with simple policies. The optimal policy yields upto 25% improvement in some cases. In some other cases, the optimal policy does only slightly better than much simpler policies.

Role of lipid peroxidation in impairment of mitochondrial function at complex I by methyl isocyanate treatment of rats in vivo

The subcutaneous administration of methyl isocyanate (MIC) in 1.0 LD50 dose in rats caused a significant effect on hepatic mitochondrial function only at complex I region of the respiratory chain. MIC administration at 1.0 LD50 dose also resulted in significant increases in malondialdehyde and ferrous ion concentration in liver mitochondria. It is suggested that the augmented lipid peroxidation in hepatic mitochondria, catalyzed by iron, possibly mobilized from intracellular stores leads to the inhibition of enzymes of mitochondrial respiration at complex I region, in vivo, in rats receiving a lethal dose of MIC subcutaneously.

Algorithms for Routing and Centralized Scheduling in IEEE 802.16 Mesh Networks

IEEE 802.16 standards for Wireless Metropolitan Area Networks (WMANs) include a mesh mode of operation for improving the coverage and throughput of the network. In this paper, we consider the problem of routing and centralized scheduling for such networks. We first fix the routing, which reduces the network to a tree. We then present a finite horizon dynamic programming framework. Using it we obtain various scheduling algorithms depending upon the cost function. Next we consider simpler suboptimal algorithms and compare their performances.

Efficient and Fair Scheduling of Uplink and Downlink in IEEE 802.16 OFDMA Networks

We develop new scheduling algorithms for the IEEE 802.16d OFDMA/TDD based broadband wireless access system, in which radio resources of both time and frequency slots are dynamically shared by all users. Our objective is to provide a fair and efficient allocation to all the users to satisfy their quality of service.

Studies on Compact Discharge Plasma Source for NOX Treatment in Engine Exhaust

This paper proposes a compact electric discharge plasma source for controlling NOX emission in diesel engine exhaust. An automobile ignition coil was used to generate the high voltage pulse using flyback topology. This design is aimed at retrofitting the existing catalytic converters with pulse assisted cleaning technique. In this paper we bring out a relative comparison of discharge plasma and plasma-adsorbent process at different gas flow rates. Activated alumina was used as adsorbent. The main emphasis is laid on the development of a compact pulse source from a DC supply for the removal of NOX from the filtered diesel engine exhaust.

Past Queue Length Based Low-Overhead Link Scheduling in Multi-beam Wireless Mesh Networks

Wireless mesh networks with multi-beam capability at each node through the use of multi-antenna beamforming are becoming practical and attracting increased research attention. Increased capacity due to spatial reuse and increased transmission range are potential benefits in using multiple directional beams in each node. In this paper, we are interested in low-complexity scheduling algorithms in such multi-beam wireless networks. In particular, we present a scheduling algorithm based on queue length information of the past slots in multi-beam networks, and prove its stability. We present a distributed implementation of this proposed algorithm. Numerical results show that significant improvement in delay performance is achieved using the proposed multi-beam scheduling compared to omni-beam scheduling. In addition, the proposed algorithm is shown to achieve a significant reduction in the signaling overhead compared to a current slot queue length approach.

Dynamic scheduling in manufacturing systems using brownian approximations

Recently, Brownian networks have emerged as an effective stochastic model to approximate multiclass queueing networks with dynamic scheduling capability, under conditions of balanced heavy loading. This paper is a tutorial introduction to dynamic scheduling in manufacturing systems using Brownian networks. The article starts with motivational examples. It then provides a review of relevant weak convergence concepts, followed by a description of the limiting behaviour of queueing systems under heavy traffic. The Brownian approximation procedure is discussed in detail and generic case studies are provided to illustrate the procedure and demonstrate its effectiveness. This paper places emphasis only on the results and aspires to provide the reader with an up-to-date understanding of dynamic scheduling based on Brownian approximations.

Effect of heat-treatment on strength of clays

The main objective of this investigation was to understand the strength development of clays below fusion or vitrification temperatures of 900°C. The other objective was to establish threshold temperatures to produce a satisfactory construction material from clayey sediments from the Western Beaufort Sea for shore protection of artificial islands with minimum expense of thermal energy. Studies were, therefore, conducted using kaolinite, bentonite, and a clayey sediment from the Beaufort Sea. Unconfined-compressive-strength tests were conducted on clay samples heat treated from 110 to 700°C. Furthermore, to understand the factors responsible for strength-development-thermogravimetric studies and pore-size analysis, using mercury porosimetry, were also conducted. A gradual increase in strength was obtained with an increase in firing temperature. However, substantial and permanent increase in strength occurred only after dehydroxylation of all the clays studied; Clay samples heated to temperatures above dehydroxylation became resistant to disintegration upon immersion in water. Results indicate that the clayey sediments from Western Beaufort Sea have to be heat treated to about 600°C to produce granular material for use as a fill or shore-protection material for artificial islands.

An Efficient Simulated Annealing With a Valid Solution Mechanism For TDMA Brodcast Scheduling problem

This paper presents an efficient Simulated Annealing with valid solution mechanism for finding an optimum conflict-free transmission schedule for a broadcast radio network. This is known as a Broadcast Scheduling Problem (BSP) and shown as an NP-complete problem, in earlier studies. Because of this NP-complete nature, earlier studies used genetic algorithms, mean field annealing, neural networks, factor graph and sum product algorithm, and sequential vertex coloring algorithm to obtain the solution. In our study, a valid solution mechanism is included in simulated annealing. Because of this inclusion, we are able to achieve better results even for networks with 100 nodes and 300 links. The results obtained using our methodology is compared with all the other earlier solution methods.

Effective drug dosage design for treatment of infectious diseases using dynamic inversion

A generic nonlinear mathematical model describing the human immunological dynamics is used to design an effective automatic drug administration scheme. Even though the model describes the effects of various drugs on the dynamic system, this work is confined to the drugs that kill the invading pathogen and heal the affected organ. From a system theoretic point of view, the drug inputs can be interpreted as control inputs, which can be designed based on control theoretic concepts. The controller is designed based on the principle of dynamic inversion and is found to be effective in curing the �nominal model patient� by killing the invading microbes and healing the damaged organ. A major advantage of this technique is that it leads to a closed-form state feedback form of control. It is also proved from a rigorous mathematical analysis that the internal dynamics of the system remains stable when the proposed controller is applied. A robustness study is also carried out for testing the effectiveness of the drug administration scheme for parameter uncertainties. It is observed from simulation studies that the technique has adequate robustness for many �realistic model patients� having off-nominal parameter values as well.

Integral treatment for the representation of thermodynamic properties in multicomponent systems using interaction parameters

The partial thermodynamic functions of the solvent component of a ternary system have been deduced in terms of the interaction parameters by integration of several series which emerge from the Maclaurin infinite series based on the integral property of the system and subjected to appropriate boundary conditions. The series integration shows that the resulting partial functions are suitable for interpreting the thermodynamic properties of the system and are independent of compositional paths. In the present analysis, the higher order terms of these series are found to make insignificant contributions.

Passivation of surface and bulk defects in p-GaSb by hydrogenated amorphous silicon treatment

Passivation of point and extended defects in GaSb has been observed as a result of hydrogenated amorphous silicon (a-Si:H) treatment by the glow discharge technique. Cathodoluminescence (CL) images recorded at various depths in the samples clearly show passivation of defects on the surface as well as in the bulk region. The passivation of various recombination centers in the bulk is attributed to the formation of hydrogen-impurity complexes by diffusion of hydrogen ions from the plasma a-Si:H acts as a protective cap layer and prevents surface degradation which is usually encountered by bare exposure to hydrogen plasma. An enhancement in luminescence intensity up to 20 times is seen due to the passivation of nonradiative recombination centers. The passivation efficiency is found to improve with an increase in a-Si:H deposition temperature. The relative passivation efficiency of donors and acceptors by hydrogen in undoped and Te-compensated p-GaSb has been evaluated by CL and by the temperature dependence of photoluminescence intensities. Most notably, effective passivation of minority dopants in tellurium compensated p-GaSb is evidenced for the first time. (C) 1996 American Institute of Physics.