210 research outputs found
Prediction of martensite start temperature by neural network analysis
Commercial steels are nowadays sophisticated alloys formed by a large number of alloying elements. The martensite start ( Ms) temperature of such steels is of vital engineering importance, and its prediction through models allows us to enhance the design and development of industrial products. In the present work, Ms temperature dependence on chemical composition has been examined by neural network analysis. Neural networks represent powerful methods of non-linear regression modelling. The network is a mathematical function which is fitted to experimental data. The influence of alloying elements such as C, Mn, Si, Cr, Ni, Mo, V, Co, W, Al, Nb, Cu, B and N on Ms temperature was analysed. Finally, a new empirical equation for Ms temperature was derived based on the neural network results.Peer Reviewe
A systematic review of naturalistic interventions in refugee populations
Naturalistic interventions with refugee populations examine outcomes following mental health interventions in existing refugee service organisations. The current review aimed to examine outcomes of naturalistic interventions and quality of the naturalistic intervention literature in refugee populations with the view to highlight the strengths and limitations of naturalistic intervention studies. Database search was conducted using the search terms ‘refugee’, ‘asylum seeker’, ‘treatment’, ‘therapy’ and ‘intervention. No date limitations were applied, but searches were limited to articles written in English. Seven studies were identified that assessed the outcome of naturalistic interventions on adult refugees or asylum seekers in a country of resettlement using quantitative outcome measures. Results showed significant variation in the outcomes of naturalistic intervention studies, with a trend towards showing decreased symptomatology at post-intervention. However, conclusions are limited by methodological problems of the studies reviewed, particularly poor documentation of intervention methods and lack of control in the design of naturalistic intervention studies. Further examination of outcomes following naturalistic interventions is needed with studies which focus on increasing the rigour of the outcome assessment process
Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil
Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated
cytotoxicity towards tumor cells.
Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was
determined using an angiogenic protein array. As positive control, the same experiments were conducted
with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM.
Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells.
Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors
Micro-Environmental Mechanical Stress Controls Tumor Spheroid Size and Morphology by Suppressing Proliferation and Inducing Apoptosis in Cancer Cells
Compressive mechanical stress produced during growth in a confining matrix limits the size of tumor spheroids, but little is known about the dynamics of stress accumulation, how the stress affects cancer cell phenotype, or the molecular pathways involved.We co-embedded single cancer cells with fluorescent micro-beads in agarose gels and, using confocal microscopy, recorded the 3D distribution of micro-beads surrounding growing spheroids. The change in micro-bead density was then converted to strain in the gel, from which we estimated the spatial distribution of compressive stress around the spheroids. We found a strong correlation between the peri-spheroid solid stress distribution and spheroid shape, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress. By compressing spheroids consisting of cancer cells overexpressing anti-apoptotic genes, we demonstrate that mechanical stress-induced apoptosis occurs via the mitochondrial pathway.Our results provide detailed, quantitative insight into the role of micro-environmental mechanical stress in tumor spheroid growth dynamics, and suggest how tumors grow in confined locations where the level of solid stress becomes high. An important implication is that apoptosis via the mitochondrial pathway, induced by compressive stress, may be involved in tumor dormancy, in which tumor growth is held in check by a balance of apoptosis and proliferation
Emotional problems in preadolescents in Norway: the role of gender, ethnic minority status, and home- and school-related hassles
<p>Abstract</p> <p>Background</p> <p>"The gender gap" refers to a lifelong higher rate of emotional problems in girls, as compared to boys, that appears during adolescence. The gender gap is a well-replicated finding among older adolescents and is assumed to be a cross-cultural phenomenon. However, these cross-cultural studies have not investigated the gender gap in ethnic minorities but sampled ethnic majority adolescents in different countries. Some studies that investigated the gender gap across ethnic groups indirectly (by presenting emotional problem scores stratified by gender and ethnic group) indicate that the gender gap is less prominent or even absent among minorities. The aims of this study were to assess whether the gender gap is found in both majority and minority preadolescents, and to investigate whether a possible (gender and ethnic) group difference can be accounted for by differences in home or school hassles.</p> <p>Methods</p> <p>Participants were 902 preadolescent students (aged 10 to 12) from two cities in Norway. We collected self-report measures of emotional problems and home and school hassles. Using mediated moderation analysis we tested whether the interaction effect between gender and ethnic minority background on emotional problems was mediated by home or school hassles.</p> <p>Results</p> <p>The gender gap in emotional problems was restricted to ethnic majority preadolescents. School hassles but not home hassles accounted in part for this effect.</p> <p>Conclusions</p> <p>The absence of the gender gap among minority as opposed to majority preadolescents may indicate that social circumstances may postpone or hamper the emergence and magnitude of the gender gap in ethnic minority preadolescents. In this study, school hassles partly accounted for the combined gender and ethnic group differences on emotional problems. This indicates that school hassles may play a role in the higher levels of emotional problems in preadolescent minority boys and consequently the absence of a gender gap found in our minority sample.</p
Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy
Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies
Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyxâ„¢) in human osteosarcoma xenografts
Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome
Better mental health in children of Vietnamese refugees compared with their Norwegian peers - a matter of cultural difference?
<p>Abstract</p> <p>Background</p> <p>There are conflicting results on whether immigrant children are at a heightened risk of mental health problems compared with native youth in the resettlement country.</p> <p>The objective of the study</p> <p>To compare the mental health of 94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4 - 18 years, with that of a Norwegian community sample.</p> <p>Methods</p> <p>The SDQ was completed by two types of informants; the children's self-reports, and the parents' reports, for comparison with Norwegian data from the Health Profiles for Children and Youth in the Akershus study.</p> <p>Results</p> <p>The self-perceived mental health of second-generation Vietnamese in Norway was better than that of their Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group, both children and parents reported a higher level of functioning.</p> <p>Conclusion</p> <p>This surprising finding may result from the lower prevalence of mental distress in Norwegian-Vietnamese children compared with their Norwegian peers, or from biased reports and cultural differences in reporting emotional and behavioural problems. These findings may represent the positive results of the children's bi-cultural competencies.</p
Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells
We have investigated the antiproliferative action towards CC531 colon adenocarcinoma cells of target cell-specific immunoliposomes containing the amphiphilic dipalmitoyl derivative of 5-fluorodeoxyuridine (FUdR-dP). FUdR-dP incorporated in immunoliposomes caused a 13-fold stronger inhibition of CC531 cell growth in vitro, during a 72-h treatment, than FUdR-dP in liposomes without antibody, demonstrating that the prodrug is efficiently hydrolysed to yield the active drug, FUdR, intracellularly. The intracellular release of active FUdR was confirmed by determining the fate of H-3-labelled immunoliposomal FUdR-dP. Treatments shorter than 72 h with FUdR-dP in immunoliposomes resulted in anti-tumour activities comparable to, or even higher than, that of free FUdR. The shorter treatments reflect more closely the in vivo situation and illustrate the potential advantage of the use of immunoliposomes over non-targeted liposomal FUdR-dP or free FUdR. Association of tumour cell-specific immunoliposomes with CC531 cells was up to tenfold higher than that of liposomes without antibody or with irrelevant IgG coupled, demonstrating a specific interaction between liposomes and target cells which causes an efficient intracellular delivery of the drug. Since biochemical evidence indicates a lack of internalization or degradation of the liposomes as such; we postulate that entry of the drug most likely involves the direct transfer of the prodrug from the immunoliposome to the cell membrane during its antigen-specific interaction with the cells. followed by hydrolysis of FUdR-dP leading to relatively high intracellular FUdR-levels. In conclusion, we describe a targeted liposomal formulation for the anticancer drug FUdR, which is able to deliver the active drug to colon carcinoma cells with high efficiency, without the need for the cells to internalize the liposomes as such
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