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In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p< 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a sub-population with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptor type 1 (HTR1) compared with healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. In vivoregeneration capacity of primary AML samples was disrupted upon inhibition of HTR1. The self-renewal capacity remaining in AML cells upon in vivotreatment was severely reduced as demonstrated by serial transplantation. Thus, treatment with HTR1 antagonists showed antileukemia effect, especially anti-LSC activity while sparing healthy blood cells. Our results highlight the importance of HTR1 in leukemogenesis and LSC survival and identify this receptor family as a new target for therapy in AML with prognostic value.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.

Despite their favorable prognosis, 10–20% of acute promyelocytic leukemia (APL) patients relapse. Reinduction therapy is often followed by autologous hematopoietic cell transplantation (auto-HCT). Arsenic trioxide (ATO) has become part of standard reinduction and is often followed by auto-HCT. Data on patients in CR2 were collected from two large transplant registries (Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplant (EBMT)) and two specialty referral centers. The outcome of patients in CR2 who received only ATO-based therapy as reinduction was retrospectively compared with those who got an auto-HCT, with or without ATO. Prognostic factors included age, disease risk, extramedullary disease and duration of CR1. Of 207 evaluable patients, the median age was 31.5 years, 15.3% had extramedullary disease and median WBC at diagnosis was 4.8 × 109/L. Sixty-seven patients received ATO alone and 140 underwent auto-HCT. The groups were comparable for age, gender, extramedullary disease, risk group and duration of CR1. At 5 years, overall survival (OS) was 42% and 78% for the ATO-only and auto-HCT groups, respectively (P<0.001). In addition, OS was associated with longer duration of CR1 (P=0.002), but not with disease risk at diagnosis. These data suggest that auto-HCT for APL patients in CR2 results in better OS than ATO-based therapy alone.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan–cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10−5and 10−4, respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34–0.86), P=0.01) and overall survival (HR=0.54 (0.34–0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

Ground hardmetals are exposed to high temperatures during both processing (e.g. coating deposition) and use (e.g. as a cutting tool). However, studies on thermally induced changes of surface integrity are limited. Here we address this by means of FIB/FESEM and EBSD investigation, with special focus on the binder phase characterization. Our findings indicate that thermal treatment causes two main surface modifications. First, an unexpected microporosity appears in the binder within the subsurface layer when ground surfaces are heated. Second, the metallic phase underneath the ground surface experiences metallurgical changes, in terms of grain and crystallographic phase structures. The mechanisms responsible for these modifications of the binder are discussed in terms of grinding-induced and thermally-reversed phase transformation as well as recrystallization phenomena. We also note that no additional heat treatment related changes such as microcracking and carbide fragmentation in the subsurface layer, are discerned.

Acute myeloid leukemia (AML) with 11q23/MLLrearrangement (MLL-r AML) is allocated to the intermediate- or high-risk cytogenetic prognostic category depending on the MLLfusion partner. A more favorable outcome has been reported in patients receiving an allogeneic hematopoietic stem-cell transplantation (alloHSCT), but this has not been confirmed in large series. We analyzed the outcome of alloHSCT among adult patients reported to the Acute Leukemia Working Party between 2000 and 2010. We identified 159 patients with 11q23/MLLrearranged AML allografted in first complete remission (CR1, n=138) or CR2, mostly corresponding to t(9;11), t(11;19), t(6;11) and t(10;11) translocations. Two-year overall survival (OS), leukemia-free survival (LFS), relapse incidence and non-relapse mortality were 56±4%, 51±4%, 31±3% and 17±4%, respectively. The outcome differed according to 11q23/MLLrearrangement, being more favorable in patients with t(9;11) and t(11;19) compared with t(10;11) and t(6;11) (2-year OS: 64±6% and 73±10% vs 40±13% and 24±11%, respectively; P<0.0001). Multivariate analysis for OS identified t(6;11), t(10;11), age>40 years and CR2 as unfavorable features, whereas t(6;11), t(10;11), CR2 and the use of reduced-intensity conditioning regimen affected poorly the LFS. This study confirms the potential role of alloHSCT for adult patients with 11q23/MLLrearranged AML in CR1.

Thin films obtained by plasma polymerization of pyrrole were deposited on different substrates. The polymer films were obtained in a R.F. plasma polymerization reactor from low-pressure vapor of the pyrrole monomer. The R.F. power and gas pressure were adjusted to obtain optimal deposition rate and film adhesion to substrates. The film composition was determined using InfraRed Transmission and X-ray Photoelectron Spectroscopy (XPS).

Ancient calcographic plates made of copper metal were restored by cleaning the residual dry ink by means of a surface plasma etching. The clean copper plates require some additional surface preservation in order to protect them against further atmospheric oxidation and corrosion. We studied the properties of polymer film coatings on the copper plates. The films were obtained by plasma polymerization of methane gas in a low pressure R.F. reactor. We then studied the surface free energy of the films and their resistance to ketone solvent. We evaluated thermal stability by thermogravimetric analysis and their aging behavior by accelerated climatic tests. The electrochemical behavior of the films was characterized by impedance spectroscopy and polarization curves.

For over a decade, special emphasis has been placed in the convergence of different fields of science and technology, in an effort to serve human needs by way of enhancing human capabilities. The convergence of the Nano-Bio-Info-Cogni (NBIC) quartet will provide unique solutions to specific needs. This is the case of, Nano-opto mechanical Systems (NOMS), presented as a solution to tactile perception, both for the visually-impaired and for the general public. NOMS, based on photoactive polymer actuators and devices, is a much sought-after technology. In this scheme, light sources promote mechanical actuation producing a variety of nano-opto mechanical systems such as nano-grippers. In this paper, we will provide a series of specifications that the NOMS team is targeting towards the development of a tactile display using optically-activated smart materials. Indeed, tactile displays remain mainly mechanical, compromising reload speeds and resolution which inhibit 3D tactile representation of web interfaces. We will also discuss how advantageous NOMS tactile displays could be for the general public. Tactile processing based on stimulation delivered through the NOMS tablet, will be tested using neuropsychology methods, in particular event-related brain potentials. Additionally, the NOMS tablet will be instrumental to the development of basic neuroscience research.

In the current information age, scientists and educators are urged to disseminate scientific findings in a prompt manner for increased public acceptance, later on, in the market place. Customer acceptance of highly novel technologies is an education-driven effort that requires attention early-on during the stage of technology development. Prompt attention is particularly needed in technologies where nanoparticles are employed, such as those being developed within the Nano- Optical Mechanical Systems (NOMS) project. Another driving force to disseminate photoactuation is to generate interest and curiosity amongst the K-12 population that could eventually lead to increased enrollment of students in the physical sciences. In this paper, we present a work plan for the dissemination of photoactuation to society at large; from K-12 to the general public. The work plan will be designed in accordance with the logic model, following indications of the National Academy of Sciences, and will include a proposal for evaluating translational research following a process marker model.

Electron microscopy was used to study previously sintered nanocomposites featuring dispersed carbon nanotubes by liquid crystal polymer dispersion and further cross-linking into liquid crystal elastomers, which resulted in a thermo-mechanical actuator. The suitability of conventional scanning electron microscopy techniques with varying coating conditions revealed the development of local charging effects, although enough latitude was granted for imaging at high vacuum modes, with differentiating contrast of the filler in the matrix. Carbon coating did contribute to charge management, although the composite might have been thermo-mechanically activated during deposition. Further, effects from focus ion beam thinning and contrast in transmission electron microscopy are discussed.

The development of the so-called “targeted therapies”, particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of neoplastic diseases. The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and trastuzumab, the humanized monoclonal antibody against the ERBB2 receptor tyrosine kinase, has proved to have a high efficacy in 25 of breast cancers. On the basis of treatment success it is expected that targeted therapies will spread its use in the future. Recent data has shown that some of these therapies are associated with certain cardiotoxicity ranging from asymptomatic mild left ventricular dysfunction to congestive heart failure through different mechanisms. However, rates of cardiotoxicity associated with TKI are not well known mainly because clinical trials usually do not include predefined cardiac endpoints or the assessment of left ventricular function before and during treatment. In addition, it is especially difficult to diagnose heart failure in patients with some kinds of cancer who have many reasons to develop dyspnoea. Here we summarize what is known up to date about the cardiotoxicity of drugs targeting the tyrosine kinases. Being aware of the risk of using these drugs is particularly important to early detect and institute the appropriate treatment to prevent irreversible myocardial injury, especially when some neoplastic diseases, as hematological or breast cancers, can affect young people with an estimated long-term survival.

New international regulation imposing double hull tankers, lead to turn over end of life tankers to FPSO (Floating production Storage Offloading). This raises a problem with the life extension of the units that must account for the new operational conditions. Bureau Veritas has introduced a method to assess the residual life of a tanker and to decide of the necessary modifications and improvements to reach the new contractual life time. The method is described with the support of an actual example.

A correlation between high plasma serotonin levels and total pulmonary resistance was reported in more than 80% of pulmonary hypertensive patients. When submitted to chronic hypoxia (10% O(2) for more than 3 weeks), wild-type mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, in contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-hydroxytryptamine (5-HT)(2B) receptor. In the present study, we asked whether 5-HT(2B) receptors could be involved in the control of plasma serotonin levels. Further investigating the chronic hypoxic mouse model of pulmonary hypertension, we first show that in wild-type mice, plasma serotonin levels and 5-HT(2B) receptors expression were significantly increased after chronic exposure to hypoxia. This increase appeared before significant changes in remodeling factors could be detected and persisted when the pathology was established. Conversely, in mice with either genetically or pharmacologically inactive 5-HT(2B) receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT(2B) receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT(2B) receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT(2B) receptor-selective antagonist or genetic ablation. Our data support the notion that a 5-HT(2B) receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels.

The oligothiophene derivative 4-(5‘ ‘‘ ‘-decyl-[2,2‘;5‘,2‘ ‘;5‘ ‘,2‘ ‘‘;5‘ ‘‘,2‘ ‘‘ ‘] pentathiophen-5-yl)-butyric acid (D5TBA) was synthesized by Stille cross-coupling methods using functionalized thiophene monomers. The structural and mechanical properties of D5TBA self-assembled monolayers on mica have been studied by atomic force microscopy (AFM). The self-assembled films were prepared by immersing the mica in dilute chloroform or tetrahydrofuran (THF) solutions. The films were predominantly of monolayer thickness with molecules packed in nearly upright orientations. In regions covered with multilayers, the molecules in each monolayer were oriented opposite to those in the neighboring ones, that is, with COOH−COOH and CH3−CH3 contact. The nature of the end group in contact with the substrate depended on the solvent used and the degree of hydration of the substrate, with hydrophobic chloroform solvent favoring the methyl end down and hydrophilic THF favoring the acid group end down. The orientation could also be controlled by dipping using the Langmuir−Blodgett technique.

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Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM. Semin Oncol 30:178-181. © 2003 Elsevier Inc. All rights reserved.

Nanometric CrN/Cr multilayers deposited by rf magnetron sputtering have been characterized in their mechanical behaviour by means of the nanoindentation technique. Mechanical and tribological properties have been studied as a function of the compositional period thickness of the multilayers. It has been found that the hardness of these CrN/Cr multilayers increases monotonically from 15 to 27 GPa with period thickness decreasing from 120 nm down to 11 nm, while the Young's modulus of the coatings shows less than 10{%} of variation with the bilayer period thickness. The hardness behaviour has been analysed in terms of the Chu and Barnett model and possible hardening mechanisms are discussed.

Notch signaling is involved in the regulation of many cell fate determination events in both embryonic development and adult tissue homeostasis. We previously demonstrated that Notch1 and Notch2 molecules inhibit myeloid differentiation in a cytokine-specific manner and that the Notch cytokine response domain is necessary for this functional specificity. We have now investigated the putative role of phosphorylation in the activity of Notch in response to cytokine signals. Our results show that the granulocyte colony-stimulating factor (G-CSF) stimulation of 32D cells expressing the intracellular Notch2 protein induces phosphorylation at specific sites of this molecule, rendering the molecule inactive and permitting differentiation of these cells. In contrast, when cells are stimulated with granulocyte macrophage colony-stimulating factor (GM-CSF), intracellular notch2 is not phosphorylated at these residues and differentiation is inhibited. We also show that deletion of the Ser/Thr-rich region between amino acids 2067 and 2099 abrogates G-CSF-induced phosphorylation and results in a molecule that inhibits differentiation in response to either G-CSF or GM-CSF. Our results further indicate that Ser(2078) is a critical residue for phosphorylation and modulation of Notch2 activity in the context of G-CSF-induced differentiation of 32D cells.

NiTi thin film alloys have been grown on Si (1 0 0) substrates by sequential multilayer deposition of Ni and Ti layers followed by metal interdiffusion via annealing. Short-time (5 min) annealing of the deposited layers at 500 °C leads to alloying of Ni and Ti, provided that preferential oxidation of Ti is avoided. This has been achieved by capping the layers with AlN, which constitutes a very efficient barrier preventing oxygen contamination of the film. For uncapped films, annealing has to be performed under high vacuum conditions. The structure of the processed films strongly depends on the temperature and time of the thermal process, obtaining Ni- and Ti-rich phases when the films are annealed at higher temperatures and/or during longer times. As-grown and processed films are analyzed by X-ray diffraction, in-depth Auger electron spectroscopy and X-ray photoelectron spectroscopy techniques. Finally, resistivity measurements show the existence of a phase transition in the films annealed at 600 °C without the capping layers (vacuum furnace). This contrasts with the behavior observed for AlN capped films, where cracking of the film occurs during cooling, which has been attributed to generation of stress in the buried film during the phase transition.

Abstract:: We show that nodal points of ground states of some quantum systems with magnetic interactions can be identified in simple geometric terms. We analyse in detail two different archetypical systems: i) the planar rotor with a non-trivial magnetic flux Φ and ii) the Hall effect on a torus. In the case of the planar rotor we show that the level repulsion generated by any reflection invariant potential V is encoded in the nodal structure of the unique vacuum for θ=π. In the second case we prove that the nodes of the first Landau level for unit magnetic charge appear at the crossing of the two non-contractible circles α−, β− with holonomies h α-(A)=h β-(A)=−1 for any reflection invariant potential V. This property illustrates the geometric origin of the quantum translation anomaly.

The fusion protein, promyelocytic leukemia-retinoic acid receptor (PML-RAR)alpha, generated by the t(15;17) translocation has an abnormal cellular distribution with colocalization of RARalpha and PML proteins. We analyzed the immunostaining pattern of PML protein using the PG-M3 monoclonal antibody directed against the amino terminal portion of PML (retained in wild-type PML and PML-RARalpha fusion protein) in the diagnosis of acute promyelocytic leukemia (APL). In addition, we compared this test with other methods for detecting the PML-RARalpha fusion gene. A normal immunostaining pattern was observed in nonmyeloid disorders and in 78 of 111 acute myeloid leukemias (AMLs). A microgranular pattern was observed in 25 AMLs, all corresponding to APL. These results were concordant with the reverse transcriptase-polymerase chain reaction results for PML-RARalpha fusion gene. Only 1 case positive for the PML-RARalpha transcript showed a normal protein pattern by immunocytochemistry. PML immunostaining was helpful to rapidly differentiate 7 cases with borderline characteristics and to obtain the diagnosis in 2 cases with scarce material. The effectiveness and low cost of this technique support its routine use as a first-line procedure in the differential diagnosis of AML.

Interferon-α (IFN-α) generally inhibits myeloma cell growth. However, a growth stimulatory effect for myeloma cells has also been reported. In patients with untreated multiple myeloma (MM) IFN-α, used as a single agent, produced an objective response rate ranging from 10 to 25%. In previously untreated patients: (1) the time to response is short, (2) the median duration of response is similar to the duration of response observed in patients given chemotherapy, and (3) the patients who are more likely to benefit are those with IgA myeloma type. Concerning the results of IFN-α given as a single agent in relapsing and resistant MM, they are poor, with a response rate ranging between 10–20%. The combination of high-dose glucocorticoids and IFN-α for relapsing/resistant patients produced controversial results. Some studies showed an increased response rate and/or longer survival with chemotherapy plus IFN-α versus chemotherapy alone in previously untreated patients. In contrast, most reports did not show a significant increase in response rate or survival benefit by adding IFN-α to the initial chemotherapy. Perhaps the most encouraging role for IFN in MM is as maintenance therapy in patients responding to first line treatment (ie conventional chemotherapy followed or not by high-dose intensification/autotransplantation). In spite of that, several reports failed to show longer response duration. The majority of studies have shown a modest but significant prolongation in response duration in favour of the IFN arm. However, most of these studies have failed to show a significant survival advantage with IFN maintenance. A meta-analysis, by the Myeloma Trialists' Collaborative Group in Oxford, based on the individual data from 4012 patients included in 24 randomized trials (induction and/or maintenance) has shown that IFN produced a moderate improvement in relapse-free survival and a minor improvement in overall survival. In summary, the only role of IFN in MM is as maintenance treatment after a response is achieved. However, looking at the published data, it seems that the vast majority of patients do not benefit from IFN maintenance, while a small proportion of them, in the range of 5–10%,

Materials with composition within the system B–C–N are very interesting because they are expected to combine some of the excellent properties of BN, B4C and C3N4. In this work our interest is focused on the region around B4C in the B–C–N composition diagram. Films were deposited by radio frequency magnetron sputtering using a target of sintered B4C. A mixture of Ar and N2was used as the plasma gas at a constant working pressure of 2×10−3mbar, and with variable N2/Ar composition. The substrate was heated to 500°C. Film composition, structure, and mechanical properties are presented. As the N2/Ar content in the plasma gas is varied from 0 to 10%, both secondary ion mass spectroscopy and X-ray photoelectron spectroscopy analyses show a continuous increase in the nitrogen incorporated into the film. From the Fourier transform IR spectra, a structure evolution from B4C towards h-BN can be deduced. Film growth rate increased from 0.5μm/h to 1μm/h, whereas film stress decreased from 5GPa to 2GPa, and film hardness also decreased from 26GPa to 12GPa. From these results, a suitable value of the N2/Ar plasma gas composition can be selected in order to deposit films with a satisfactory low stress while keeping a sufficiently high hardness, as required in hard coating applications.

Thin polymeric films have been obtained by plasma polymerisation of dimethylsiloxane (DMSO). Such films are widely used as protective coatings on optical reflective surfaces and decorative parts. Thin films of polydimethylsiloxane (PDMS) have been deposited by a DC glow discharge plasma from DMSO vapour on pre-treated and untreated polycarbonate (PC) substrates, with or without previous evaporation of an additional aluminium film. A subsequent process of mineralisation by immersion in an air plasma has been applied in order to improve the PDMS films wear resistance. Polycarbonate substrates have been treated in a similar way aiming at improved adhesion of Al films. The present paper is specially focused on the surface mechanical properties of these films. These have been measured by nanoindentation and microscratch techniques and the improvement of the surface hardness and scratch resistance of PDMS films and PC substrates has been assessed.