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Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.

The peculiar characteristics of the italian neoplastic patients, as far as their knowledge concerning the disease (information, prognosis, therapeutic options, etc) and the different cultural, environmental and health realities, place different problems on the routine application of the quality of life questionnaires wich were constructed and edited in North European or North American Countries, even if correctly translated and validated in Italy. The QVonc (Quality of Life in Oncology) Project started five years ago from the common interest of medical oncologists who felt the need to make a careful study on some aspects regarding the evaluation of italian patient's quality of life. A multidisciplinary working group, comprehensive of statisticians, epidemiologists, psychologists, nurses and methodologists, was then put together. During the last three years the Group produced a deep analysis of the different aspects and determinants of the italian patient's quality of life, mainly about their disease and medical environment perception. A prospective research was started in 1995 with the aims of identifying the contents of quality of life, using a sample of cancer patients as “experts” and of measuring the relevance of selected contents in different subgroups of patients. In the first study the quality of life dimensions were analysed as perceived from 248 neoplastic patients, uniformely and randomly distributed for pathology and place of residence in Italy, through an open questionnaire and interviews conducted by our psychologists. Some peculiar aspects of the quality of life perception in italian patients were evidenced: relationship with the family, with the medical team and health facilities, economic problems and occupational difficulties. The study confirmed that the information on the contents of quality of life can be derived only studying people suffering the specific disease and cast a doubt on the available QL instruments currently used. The second study evaluated the quality of life perception in 6939 consecutive cancer patients referred in the second week of July 1996 to 79 Italian medical oncology/radiotherapy Institutions. Patients were asked to fill out a questionnaire concerning the importance of 46 domains of QL, each one scored on 4 levels (not at all, a little, much and very much). Domains were derived from a previous content analysis of 268 pts answers to 4 questions related to their own QL: “in your experience, what is QL?”, “what is a bad QL?”, “what is a good QL?”, “Did the diagnosis and treatment received modify your QL?”. 6939 patients entered the study; of these, 820 (11.8%) did not fill out the questionnaire due to various reasons. Among the 6,119 evaluable pts, the most frequent cancers were: breast (2,328), colo-rectal (968), lung (517), lymphoma (351), gastric (225). The most frequently chosen domains (much or very much) were related to health facilities or communication between patient-physician/nurse. Family relationship and general well being were also found important, while from the negative perspective the presence of the disease and the related anxiety were the most relevant problems. In conclusion, when choosing or constructing QL instruments, at least for Italian cancer pts, factors such as health facilities and pt ‘- physician/nurse relationship should be more adequately considered. Most currently used QL questionnaires are probably lacking in this regard.

We have studied two temperature-related effects in the fabrication of high quality SIMOX materials: 1) the large ion beam induced rise in sample temperature during oxygen implantation, and 2) the time dependence of the high temperature annealing required after implantation. Oxygen ions were implanted at 160 keV into (100) Si wafers to a total dose of 4 × 10 17 O + cm 2 with current densities from 10 to 60 μA/cm2. The samples were annealed at 1300°C for 0 to 6 h. The microstructures were examined using cross-sectional transmission electron microscopy. With a current density of 60 μA/cm2, permanent damage occurred in the top Si layer. No effects were observed after post-implantation annealing for samples implanted with 10–50 μA/cm2 current densities. Oxygen precipitates were found to grow and coarsen with increasing anneal time, finally becoming a non-uniform buried oxide layer. Oxide layer formation is an oxygen diffusion controlled process.

Although the subjective nature of quality of life perception is generally accepted, less attention has been paid to the procedure of selecting domains to be explored with questionnaires. In most cases domains are selected by panel of experts. It is not known whether these domains are relevant for the patients. Moreover, questionnaires developed in 'foreign' countries may not be culturally sound or relevant for patients living in different cultural background. In order to explore what really contributes to quality of life of Italian patients, a survey was conducted with the aim of identifying any dimension of quality of life, positively or negatively impacted on from the illness and therapies. A sample of two hundred and eighty eight cancer patients with previously specified characteristics (primary tumor, stage of disease and place of residence) were identified. After consenting to partecipate to the study, a staff member (a physician, a nurse or a psychologist) asked the patient to complete an open-ended questionnaire in the out-patient clinic or at home. This questionnaire, partially derived from a study by Padilla et al. made up of 5 questions: 'What does the term quality of life mean to you?', 'What contributes to a good quality of life?', 'What contributes to a poor or bad quality of life?', 'Which either physical or psychological symptom interferes with your quality of life?', 'State any positive or negative change in your quality of life, due to illness or treatments'. The first question was asked to explore the meaning of quality of life for the patient; the second and third question were asked to determine the contents of quality of life not health related; the fourth question and the diary provided information about quality of life contents related to his own experience of disease. Two hundred and forty eight questionnaires (86.1%) were obtained from 7 Cancer Centres participating to the study (Genova, Milano, Roma, Perugia, Napoli, Cagliari, Palermo). All the questionnaires were transcribed and subsequently broken down in phrases on a form that allowed coding. Three raters (a research nurse, an oncologist and a clinical psychologist) made the content analysis using as conceptual framework the list of domains identified by the Italian Society of Psycho-Oncology. The present study shows the possibility to define the content domain of quality of life attributes for cancer patients, using patients as experts.

The poor vaccination coverage among health-care workers in a hospital, resulted from a self-administered questionnaire, showed the necessity to improve educational efforts and to promote vaccination campaign.

Results and mechanisms involved in producing high-quality separation by implantation of oxygen (SIMOX) material at low energy (30-80 keV) are presented and discussed in detail. The theoretical advantages of using low-energy implantation are derived and verified. Some of these advantages are: (1) a continuous oxide layer can be formed with a smaller dose, resulting in a faster and more economical SIMOX process; (2) introduction of contaminants is reduced because of reduced implantation time; and (3) the process is viable over a much wider range of implantation facilities. This process should have a great impact on production of SOI for military and commercial purposes not only because of reduced cost due to reducing implantation time by an order of magnitude, but also because it provides a means to produce SIMOX structures with an ultrathin SiO/sub 2/ layer. >

Summary form only given. The authors discuss optical waveguiding at a wavelength of 1.3 microns in a separation by implantation of oxygen (SIMOX) sample with a silicon top layer about two microns thick on a buried SiO/sub 2/ layer about 4000 AA thick. The sample was formed using the standard SIMOX process with subsequent growth of epitaxial Si by chemical vapor deposition (CVD). The waveguide length was 1.1 cm. Very thin, very thick, and double-layer buried oxide structures have also been obtained with a multiple implantation process and growth of epitaxial Si by CVD. Optical waveguiding can be obtained in both silicon layers of a double-buried-layer SIMOX wafer. In addition, when the SiO/sub 2/ layer between 1 and 2 has a thickness of one micron, the guided optical signals in 1 will be independent of those in 2 because the guides are not coupled. Alternatively, optical signals can be transferred from one level to another at certain locations. For example, if the thickness of the 1-2 SiO/sub 2/ layer is reduced locally to 1000 AA, waveguide theory predicts that the waveguides in 1 will couple strongly to waveguides in 2 at that location. >

The threading dislocation densities of 10/sup 8//cm/sup 2/ to 10/sup 10//cm/sup 2/ that are typical of SIMOX material are detrimental for bipolar structures and orders-of-magnitude reduction of defect density is still required to permit SIMOX (separation by implanted oxygen) material to be acceptable for high-performance bipolar and analog devices. Two methods have been developed to produce low-defect SIMOX wafers. In the first method, threading dislocation defects are reduced by low-dose Ge implantation and subsequent solid-phase epitaxial (SPE) regrowth. Ge implantation produces a strained and amorphized layer that during the subsequent SPE acts as an artificial interface and deflects or stops the propagation of threading dislocations. In the second method, threading dislocations are prevented by a multiple low-dose implantation and high-temperature annealing process. No defects were observed for implantation with doses up to 8*10/sup 17/ O/sup +//cm/sup 2/, and threading dislocation density has been reduced by three to four orders of magnitude. Continuous and uniform buried layers are formed with about 65% of the dose required by the standard SIMOX process. Preliminary results have shown that by use of these methods low defect, superior quality, SIMOX wafers for submicron CMOS and bipolar device applications can be produced. >

A systematic study to determine the effect of dose and dose rate on implanting oxygen at 80 and 160 keV is reported. Samples were produced by implanting oxygen into p-type Si

The authors report on an extensive study of a Secco etch process for determining dislocation densities that was performed by three different groups using nine SIMOX (separation by implanted oxygen) wafers from the same lot. The average dislocation density across the entire current data set (except transmission electron microscopy, TEM) is 2.2*10/sup 6//cm/sup 2/ with a standard deviation of 1.0*10/sup 6//cm/sup 2/. Most of the data points are in the low 10/sup 6/ dislocations/cm/sup 2/ range, in agreement with the TEM results, and indicate good consistency of results from facility to facility. >

Improvement of the crystalline quality of epitaxial silicon grown on separation by implantation of oxygen (SIMOX) material was investigated by confining the threading dislocations in the silicon top layer with a GeSi strained layer. The standard SIMOX used was produced by implantation of 1.6*10/sup 18/ O+/cm/sup 2/ at 160 keV, followed by annealing for 6 h at 1300 degrees C in N/sub 2/. Thin Si/GeSi/Si epitaxial structures were grown on the SIMOX and on Si substrates by chemical vapor deposition (CVD). The material was evaluated using a variety of methods, including cross-sectional transmission electron microscopy (XTEM), plane view TEM, and Rutherford backscattering spectroscopy (RBS)/channeling. The GeSi strained layer grown by CVD appears to be high quality, and no misfit dislocations were observed for Si/GeSi/Si structures grown at the same time on bulk silicon. CVD may also be a simple and economical method for growing Si/GeSi/Si structures for device applications such as heterojunction bipolar transistors. >

Formation of ultra-thin SOI material using the SIMOX process is addressed. Research has been carried out to determine the effect of total dose, dose step, dose rate, implantation temperature, and energy on the formation of ultra-thin SIMOX material. Attempts were made to determine the lowest energy possible for the implantation of oxygen which results in the formation of high quality, thin SIMOX material. All samples were annealed at 1300 degrees C for 6 h in N/sub 2/ and analyzed using a variety of techniques, including TEM. The electrical properties of the LES samples were characterized and compared with those of standard SIMOX samples. An empirical curve of voltage breakdown versus oxide thickness for both LES and standard SIMOX samples was developed. The results show the formation of high quality SOI structures by oxygen implantation at 20-80 keV. >

In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC).Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis.The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed.Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may kill cells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients.Two hundred fourteen patients from nineteen Italian centers were randomized to the control arm consisting of biweekly cycles of MTX, 200 mg/m2 on day 1, followed by bolus 5-FU 600 mg/m2 on day 2 and 6-S-leucovorin rescue, or to the experimental arm consisting of two biweekly cycles of the same regimen as in the control arm alternated to three weeks of continuous infusion 5-FU (200 mg/m2 day) + weekly bolus 6-S-leucovorin, 20 mg/m2.Nine CR and twenty-seven PR were obtained on one hundred eleven evaluable patients treated in experimental arm (RR = 32%, 95% confidence interval (95% CI): 24%-42%), while two CR and eleven PR were observed among one hundred three evaluable patients in control arm (RR = 13%, 95% CI: 7%-21%). WHO grade 3-4 toxicity occurred in 13% of cycles of experimental arm and in 8% of cycles in control arm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months, odds ratio 0.66, P = 0.003), while the overall survival was similar in both arms (14.8 months in experimental arm vs. 14.1 months in control arm); quality of life was similar as well. Eighty percent of patients receiving second-line chemotherapy in control arm were treated with continuous infusion 5-FU.Alternating, schedule-specific biochemical modulation of FU is more active than MTX --5-FU as first-line treatment of advanced colorectal cancer. However, the overall survival was similar suggesting that alternating bolus and infusional 5-FU upfront may be as effective as giving them in sequence as first- and second-line treatment.

A SiO/sub 2/-Si-SiO/sub 2/-Si-SiO/sub 2/-Si structure produced by the separation by implantation of oxygen (SIMOX) process used for dual vertically integrated waveguiding in silicon at lambda =1.3 mu m is discussed. Independent waveguiding is observed when 2- mu m-thick Si cores are separated by 0.36- mu m-thick SiO/sub 2/. Coupled waveguiding is found for an 0.12- mu m intercore oxide thickness. >

We report a clinical case of a patient with NSCLC who experienced an atrial fibrillation during paclitaxel infusion. Before chemotherapy, his cardiological function was normal. No cardiovascular and/or thyroid associated disease were previously reported. The patient did not receive any drugs with pro-arrhythmic effects. Incidence of cardiovascular toxicity in patients treated with paclitaxel is low, and does not justify strict cardiological monitoring otherwise deserved to patients with preexistent risk factors.

The peculiar characteristics of the Italian neoplastic patients, as far as their knowledge concerning the disease (information, prognosis, therapeutic options, etc) and the different cultural, environmental and health realities, place different problems on the routine application of the quality of life questionnaires which were constructed and edited in North European or North American Countries, even if correctly translated and validated in Italy. The QVonc (Quality of Life in Oncology) Project started five years ago from the common interest of medical oncologists who felt the need to make a careful study on some aspects regarding the evaluation of Italian patient's quality of life. A multidisciplinary working group, comprehensive of statisticians, epidemiologists, psychologists, nurses and methodologists, was then put together. During the last three years the Group produced a deep analysis of the different aspects and determinants of the italian patient's quality of life, mainly about their disease and medical environment perception. A prospective research was started in 1995 with the aims of identifying the contents of quality of life, using a sample of cancer patients as "experts" and of measuring the relevance of selected contents in different subgroups of patients. In the first study the quality of life dimensions were analysed as perceived from 248 neoplastic patients, uniformely and randomly distributed for pathology and place of residence in Italy, through an open questionnaire and interviews conducted by our psychologists. Some peculiar aspects of the quality of life perception in italian patients were evidenced: relationship with the family, with the medical team and health facilities, economic problems and occupational difficulties. The study confirmed that the information on the contents of quality of life can be derived only studying people suffering the specific disease and cast a doubt on the available QL instruments currently used. The second study evaluated the quality of life perception in 6939 consecutive cancer patients referred in the second week of July 1996 to 79 Italian medical oncology/radiotherapy institutions. Patients were asked to fill out a questionnaire concerning the importance of 46 domains of QL, each one scored on 4 levels (not at all, a little, much and very much). Domains were derived from a previous content analysis of 268 pts answers to 4 questions related to their own QL: "in your experience, what is QL?", "what is a bad QL?", "what is a good QL?", "Did the diagnosis and treatment received modify your QL?". 6939 patients entered the study; of these, 820 (11.8%) did not fill out the questionnaire due to various reasons. Among the 6,119 evaluable pts, the most frequent cancers were: breast (2,328), colo-rectal (968), lung (517), lymphoma (351), gastric (225). The most frequently chosen domains (much or very much) were related to health facilities or communication between patient-physician/nurse. Family relationship and general well being were also found important, while from the negative perspective the presence of the disease and the related anxiety were the most relevant problems. In conclusion, when choosing or constructing QL instruments, at least for Italian cancer pts, factors such as health facilities and pt--physician/nurse relationship should be more adequately considered. Most currently used QL questionnaires are probably lacking in this regard.

SCLC relapsing or refractory after induction chemotherapy is a chemoresistant tumor. The outcome of salvage chemotherapy is poor, with low response rates (30%) and short survival times (3-4 months). The development of drug resistance is considered the major cause of failure of treatment. VM-26 is one of the most active drugs in SCLC. Lonidamine has shown to enhance in both vivo and vitro antitumor activity of several cytotoxic drugs acting on drug resistance mechanisms.VM-26 and lonidamine were employed as salvage chemotherapy in 30 small cell lung cancer patients. The doses of chemotherapy used were: VM-26 100 mg/m2, i.v., days 1 to 3; lonidamine 600 mg, p.o., days 1 to 5, recycled every 3 weeks.We observed 13.3% of objective response and a median survival of 4 months. All the responses were obtained in patients relapsing after a response to induction chemotherapy. Toxicity was moderate with no toxic death.Our study shows that Lonidamine failed to increase the VM-26 activity in pretreated small cell lung cancer patients.

The role of Neo-Adjuvant chemotherapy in locally advanced bladder urothelial tumors is not yet established: a number of prospective studies are evaluating the role of chemotherapy in DFS, OS and bladder preservation in selected patients.

Circulating immune complexes (CIC) have been detected in several autoimmune diseases, and studies have also suggested that CIC provide a useful tool as tumor markers. In order to identify differences or similarities in antigenic composition, CIC from 23 patients with gastrointestinal (GI) tumors, from 20 patients with stage III and IV melanoma and from 6 patients with inflammatory bowel disease (IBD) were studied. Serum from all GI, melanoma and IBD patients showed higher levels of CIC than controls. SDS/PAGE electrophoresis under reducing conditions revealed some differences between cancer and IBD patients as far as the CIC protein composition was concerned. In melanoma patients, two fast-migrating bands, in the regions of 71-74 and 30-49 kD, were found, consistent with previously isolated and characterized antigens described in the literature.

Although silicon-on-insulator (SOI) materials made by standard energy (150–200 keV) SIMOX processes have shown great promise for meeting the needs of radiation hard microelectronics, there are still problems relating to the radiation hardness and economic viability of standard SIMOX. A low energy SIMOX (LES) process reduces cost and improves radiation hardness and increased throughput of any implanter because much smaller doses are required. In addition, the process is uniquely able to produce high quality thin SIMOX structures that are of particular interest for fully depleted device structures. In this paper, we address the formation of high quality ultrathin SIMOX structures by low energy implantation.

We have studied the formation of platinum silicide layers by ion implantation and annealing, and have determined the dependence of platinum silicide phase formation on ion implantation conditions and substrate orientation. The results indicate that in most cases, the ion implanted layer consists of PtSi phase. However, depending on the implantation and annealing conditions and substrate orientation, other phases, including Pt2Si, Pt3Si, and Pt12Si5, as well as Si and Pt microcrystals, also form.

Results are presented for the propagation loss of planar optical waveguides fabricated in SIMOX structures with Si overlayers whose thickness varies from 0.57 μm to 6.0 μm. The results demonstrate that thick Si overlayers are required to produce propagation losses below 1 dB/cm. In addition, the results of the coupling between two vertically integrated waveguides formed using two buried SiO2 layers are also reported.

We have studied Separation by IMplantation of OXygen (SIMOX) processes using very high dose rates (40–60 μA/cm2). For a dose of 4 × 1017 O+/cm2 at 160 keV, the structure formed by implantation at 50 μA/cm2 is very similar to that associated with lower dose rates. The same dose implanted at a dose rate of 60 μA/cm2, however, results in the formation of pits in the silicon surface as well as a somewhat different oxide structure. Implantation through a surface oxide layer appears to result in a structure similar to that associated with lower dose rate implantation. These and higher dose samples suggest that the threshold for pit formation is related to both dose rate and dose.

We have investigated improving the crystalline quality of epitaxial silicon grown on SIMOX by confining threading dislocations in the original Si top layer using a GeSi strained layer. Epitaxial Si/GeSi/Si structures were grown by CVD on SIMOX and Si substrates with a GeSi alloy layer about 1000 − 1500 angstroms thick with Ge concentrations of about 0−20%. A Ge concentration in the alloy layer of about 5.5% or higher appears to be necessary in order to bend any of the threading dislocations from the original SIMOX top layer. For a higher Ge concentration of about 16%, most of the threading dislocations appear to be bent and confined by the GeSi layer. In addition, the GeSi strained layers grown by CVD (at about 1000°C) appear to be high quality and no misfit dislocations were observed in the regions studied by XTEM and plane view TEM.

Substantial reduction of defect density in silicon-on-sapphire (SOS) material is required to broaden its range of applications to include CMOS and bipolar devices. In recent years, solid phase epitaxy and regrowth (SPEAR) and double solid phase epitaxy (DSPE) processes were applied to SOS to reduce the density of defects in the silicon. These methods result in improved carrier mobilities, but also in increased leakage current, even before irradiation. In a radiation environment, this material has a large increase in radiation induced back channel leakage current as compared to standard wafers. In other words, the radiation hardness quality of the SOS declines when the crystalline quality of the Si near the sapphire interface is improved.In this paper, we will demonstrate that Ge implantation, rather than Si implantation normally employed in DSPE and SPEAR processes, is an efficient and more effective way to reduce the density of defects near the surface silicon region without improving the Si/sapphire interface region. Ge implantation may be used to engineer defects in the Si/sapphire interface region to eliminate back channel leakage problems.

Azelaic acid (C9- -dicarboxylic acid) is a competitive inhibitor of tyrosinase and some oxido-reductase in vitro , and in vivo has a beneficial effect of lentigo maligna and malignant melanoma. A definite cytotoxic effect in cultures of malignant melanocytes was also reported. In order to establish if the cytotoxic effect of the diacid is exerted equally in the absence of tyrosinase, lymphoma- and leukemia-derived cell lines were cultured for 72 hr with 10 −3 M, 10 −2 M and 5 × 10 −2 M C9 dosodium salt. Normal resting lymphocytes, lymphocytes activated by phytohemoagglutinin, and mouse Balb/c 3T3 fibroblasts were also tested to study a possible effect of azelaic acid on DNA synthesis and cell duplication. At 10 −3 M C9 had no effect on the viability of all the cells tested: at 10 −2 M and 5 × 10 −2 M, C9 2Na had a 50–80% cytotoxic effect on lymphoma- and leukemia-derived cell lines, while at the same concentrations it was not toxic to normal lymphocytes, either resting or stimulated, or to 3T3 fibroblasts. The experiments on cellular incorporation of (1–9 14 C) azelaic acid showed that the radiocarbon uptake was two to three times higher for lymphoma- and leukemia-derived cell lines than for lymphocytes, either resting or stimulated, or 3T3 fibroblasts. Biochemical analysis revealed that the diacid underwent beta-oxidation in all the cell cultures. Fractionated centrifugations of 3T3 fibroblasts cultured in the presence of radiolabelled azelaic acid (2 × 10 −4 M) plus cold C9 2Na (10 −2 M), showed that the radioactivity was mainly concentrated in the cytoplasm. The results, being similar to those obtained by adding azelaic acid to cultures of melanoma cells, suggest that the cytotoxic effect of azelaic acid may be due to interference with mitochondrial oxido-reductase enzymes, rather than with tyrosinase. The difference in reaction between lymphoma- and leukemia-derived cell lines and normal or stimulated lymphocytes, and 3T3 fibroblasts, could be explained on the basis of a different degree of permeability of the cell membrane, and/or to a possible different sensitivity of reaction of mitochondrial functions. A similar argument could be used to explain the absence of an effect of dicarboxylic acids upon normal as compared with hyperactive or malignant melanocytes in vivo .

Because of potential “back channel” leakage problems in silicon-oninsulator (SOI) metal-oxide-semiconductor (MOS) devices, especially n-channel MOS devices which must operate in an ionizing radiation environment, it is desirable to produce Separation by IMplantation of OXygen (SIMOX) wafers which have a layer of poor quality silicon near the Si/buried SiO2 interface. At the same time, these wafers must have low defect, high quality silicon near the wafer surface for device fabrication.We have demonstrated that with Ge ion implantation and solid phase epitaxy regrowth, the surface region of the silicon top layer of the SIMOX wafer is improved and the region adjacent to the buried SiO2 is degraded. These results have been observed by RBS/channeling, XTEM, and plane view TEM.

This paper will address the formation of SIMOX structures with thick and multiple buried SiO2 layers by multiple oxygen implantation and growth of epitaxial Si by chemical vapor deposition (CVD). Our results indicate that SIMOX material can be produced with a buried layer of any thickness or with any number of distinct buried oxide layers and distinct silicon layers. Thick and double buried SiO2 layer material may be useful for high voltage isolation and electric field shielding.In addition, we have demonstrated optical waveguide action in SIMOX wafers. This suggests that in a double buried SiO2 layer system, three dimensional stacked integration of silicon waveguides is possible, including two level optical interconnects.

We have studied the effect of implantation temperature, dose step, and total dose on the buried Si02 layer formed with a multiple low dose oxygen implantation process. Furthermore, we have produced a continuous, high quality buried SiO2 layer about 1500 Å thick with a dose of only 7 × 1017 0+/cm2 at 160 keV. The thin SiO2 layer is important not only because of the possible economic advantages of reduced dose, but also because a thinner oxide layer is more radiation hard.

This work addresses the formation of Separation by IMplantation of OXygen (SIMOX) structures by multiple oxygen implantation into silicon and high temperature annealing. We observed no threading dislocation defects in the several plane view TEM and XTEM micro graphs of each of the samples implanted with a single dose of up to 8 × 1017 0+/cm2. We also demonstrated that with a multiple low-dose (3 to 4 × 1017 0+/cm2) oxygen implantation and high temperature annealing process, we are able to produce continuous and uniform buried SiO2 layers with a total dose of 1.1 × 1018 0+/cm2 (about 60% of the total dose for standard SIMOX). The density of defects is about 105/cm2. There are no silicon islands in the buried layer, no SiO2 precipitates in the silicon top layer, and the Si-SiO2 interfaces are sharp and smooth. SIMOX material with a high-quality Si top layer and a continuous buried layer has been produced with a total dose of 7 × 1017 0+/cm2 (40% of the total dose for standard SIMOX) and a two-step process. However, in this case there are a few Si islands present in the buried SiO2 layer.

We have prepared GexSi1-x/Si structures by implanting germanium into silicon surfaces and thermally annealing. Implant energies were 100 and 150 keV and the total ion doses were between 1 and 10 × 1015 ions/cm2. Ion channeling studies of these structures indicates that after annealing, the germanium atoms substitute into the silicon lattice and create a pseu-domorphic strained layer. In addition, channeling results suggest a residual band of dislocations at or beyond the ion range in the as-annealed samples.

The Far-infrared-Outgoing-Radiation Understanding and Monitoring (FORUM) mission concept, selected by ESA for the feasibility study of the Earth Explorer 9 (EE9) will have to evaluate of water vapor and temperature profile precision and accuracy from FORUM observations in the wavelength range of 7 - 100 micrometers. These observations are important because Earth's infrared emission to space is affected by water vapor and cirrus clouds, which, in turn, play key roles in Earth's temperature. The characterization of the radiative effects of the main atmospheric components in this spectral range is a new measure from space, as it fills the observational gap in the far-infrared (FIR) region from space. In the framework of the FORUM mission, the Kyoto protocoL Informed Management of the Adaptation (KLIMA) algorithm has been used to simulate the FORUM wide-band spectral radiance measurements, with the aim to assess the water vapor and temperature profile precision and accuracy obtained using the Fourier Transform Spectrometer (FTS) observations and to evaluate the quality of the retrieval. The algorithm consists of two distinct modules, the Forward Model (FM) and the Retrieval Model (RM). The FM is a line-by-line radiative transfer model, with capability to simulate wide-band spectral radiances from 100 to 1600 cm-1 (i.e. the FORUM spectral range requirement); the RM uses a constrained Nonlinear Least Square Fit (NLSF) approach and the cost function to be minimized takes into account the a priori information (optimal estimation method) and the Marquardt parameter. We performed several tests to retrieve temperature and water vapor profile, using different quantifiers to assess the quality of the retrieval. In this work, we describe the strategy adopted for the analysis and we show first results of these evaluation activities.

Purpose In a previous cohort study, we proposed that responsiveness of metastatic colorectal cancer (mCRC) to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies has a genetic basis, being associated with increased EGFR gene copy number (GCN) as measured by fluorescence in situ hybridization (FISH) in individual tumors. The present study was aimed at assessing the predictive role of EGFR GCN, in terms of clinical outcome, in patients treated with panitumumab. Patients and Methods Patients with mCRC refractory to standard therapies were a subset of patients from a phase III trial of panitumumab plus best supportive care (BSC; n = 58) versus BSC alone (n = 34) who were selected on the basis of availability of tumor samples adequate for FISH. Results In patients treated with panitumumab, a mean EGFR GCN of less than 2.5/nucleus or less than 40% of tumor cells displaying chromosome 7 polysomy within the tumor predicted for shorter progression-free survival (PFS; P = .039 and P = .029, respectively) and overall survival (P = .015 and P = .014, respectively). None of the treated patients with mean EGFR GCN of less than 2.47/nucleus or less than 43% of tumor cells displaying chromosome 7 polysomy obtained objective response compared with six of 20 and six of 19 patients with values greater than these cutoff limits, respectively (P = .0009 and P = .0007, respectively). Evaluation of BSC-treated patients showed no correlation between EGFR GCN or chromosome 7 polysomy status and PFS. Conclusion In a larger and more homogeneous series than in previous studies, present exploratory data suggest that mCRC patients with tumors distinguishable by FISH analysis of EGFR as homogenously disomic or with low chromosome 7 polysomy have a reduced likelihood of response to panitumumab.