Interface of chip-based capillary electrophoresis-inductively coupled plasma-atomic emission spectrometry (CE-ICP-AES)

An interface of chip-based capillary electrophoresis (CE)-inductively coupled plasma-atomic emission spectrometry (ICP-AES) that is based on cross-flow nebulization has been developed. A polydimethylsiloxane (PDMS) CE-chip with conventional cross channel layout was used. A stainless steel tube was placed orthogonal to the exit of the CE separation channel for cross flow nebulization. A supplementary flow of buffer solution at the channel exit was used to improve nebulization efficiency. Two capillaries were inserted into the CE chip near the inlet of the separation channel for sample and buffer solution injection. Syringe pumps were used to manipulate the flow rate and flow direction of the sample, buffer, and supplementary buffer solution. Peak broadening due to the shape (bulb and tube-shaped) and size of the spray chambers was studied. The smaller tube-shaped spray chamber was used because of smaller peak broadening effect due to aerosol transport. The nebulization and transport efficiency of the CE-ICP interface was approximately 10%. Ba2+ and Mg2+ ions were eluted from the CE-chip within 30 s. Resolution of the Ba2+ and Mg2+ peaks was 0.7 using the chip-based CE-ICP-AES system.

Computer technology in detection and staging of prostate carcinoma: a review

Y. Zhu, S. Williams and R. Zwiggelaar, 'Computer technology in detection and staging of prostate carcinoma: a review', Medical Image Analysis 10 (2), 178-199 (2006)

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

PURPOSE: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. PATIENTS AND METHODS: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. RESULTS: Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative. CONCLUSION: No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

PURPOSE: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. PATIENTS AND METHODS: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. RESULTS: Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. CONCLUSION: Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

Cross-cultural dimensions of meaning in the evaluation of events in world history? Perceptions of historical calamities and progress in cross-cultural data from 30 societies

The universality versus culture specificity of quantitative evaluations (negative-positive) of 40 events in world history was addressed using World History Survey data collected from 5,800 university students in 30 countries/societies. Multidimensional scaling using generalized procrustean analysis indicated poor fit of data from the 30 countries to an overall mean configuration, indicating lack of universal agreement as to the associational meaning of events in world history. Hierarchical cluster analysis identified one Western and two non-Western country clusters for which adequate multidimensional fit was obtained after item deletions. A two-dimensional solution for the three country clusters was identified, where the primary dimension was historical calamities versus progress and a weak second dimension was modernity versus resistance to modernity. Factor analysis further reduced the item inventory to identify a single concept with structural equivalence across cultures, Historical Calamities, which included man-made and natural, intentional and unintentional, predominantly violent but also nonviolent calamities. Less robust factors were tentatively named as Historical Progress and Historical Resistance to Oppression. Historical Calamities and Historical Progress were at the individual level both significant and independent predictors of willingness to fight for one’s country in a hierarchical linear model that also identified significant country-level variation in these relationships. Consensus around calamity but disagreement as to what constitutes historical progress is discussed in relation to the political culture of nations and lay perceptions of history as catastrophe.

Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

BACKGROUND: To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. METHODS: Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. RESULTS: Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). CONCLUSION: Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.

Understanding GPU programming for statistical computation: Studies in massively parallel massive mixtures

This article describes advances in statistical computation for large-scale data analysis in structured Bayesian mixture models via graphics processing unit (GPU) programming. The developments are partly motivated by computational challenges arising in fitting models of increasing heterogeneity to increasingly large datasets. An example context concerns common biological studies using high-throughput technologies generating many, very large datasets and requiring increasingly high-dimensional mixture models with large numbers of mixture components.We outline important strategies and processes for GPU computation in Bayesian simulation and optimization approaches, give examples of the benefits of GPU implementations in terms of processing speed and scale-up in ability to analyze large datasets, and provide a detailed, tutorial-style exposition that will benefit readers interested in developing GPU-based approaches in other statistical models. Novel, GPU-oriented approaches to modifying existing algorithms software design can lead to vast speed-up and, critically, enable statistical analyses that presently will not be performed due to compute time limitations in traditional computational environments. Supplementalmaterials are provided with all source code, example data, and details that will enable readers to implement and explore the GPU approach in this mixture modeling context. © 2010 American Statistical Association, Institute of Mathematical Statistics, and Interface Foundation of North America.

Where are cultural and social in ecosystem services? A framework for constructive engagement

A focus on ecosystem services (ES) is seen as a means for improving decisionmaking. In the research to date, the valuation of the material contributions of ecosystems to human well-being has been emphasized, with less attention to important cultural ES and nonmaterial values. This gap persists because there is no commonly accepted framework for eliciting less tangible values, characterizing their changes, and including them alongside other services in decisionmaking. Here, we develop such a framework for ES research and practice, addressing three challenges: (1) Nonmaterial values are ill suited to characterization using monetary methods; (2) it is difficult to unequivocally link particular changes in socioecological systems to particular changes in cultural benefits; and (3) cultural benefits are associated with many services, not just cultural ES. There is no magic bullet, but our framework may facilitate fuller and more socially acceptable integrations of ES information into planning and management. © 2012 by American Institute of Biological Sciences. All rights reserved.

The Multiscale Systems Immunology project: software for cell-based immunological simulation.

BACKGROUND: Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent based immune response simulation that incorporates realistic biophysics and intracellular dynamics, and which is sufficiently flexible to accurately model the multi-scale nature and complexity of the immune system, while maintaining the high performance critical to scientific computing. RESULTS: The Multiscale Systems Immunology (MSI) simulation framework is an object-oriented, modular simulation framework written in C++ and Python. The software implements a modular design that allows for flexible configuration of components and initialization of parameters, thus allowing simulations to be run that model processes occurring over different temporal and spatial scales. CONCLUSION: MSI addresses the need for a flexible and high-performing agent based model of the immune system.

Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. © 2014 Elsevier Ltd.

The effect of reflow process on the contact resistance and reliability of anisotropic conductive film interconnection for flip chip on flex applications

The work presented in this paper focuses on the effect of reflow process on the contact resistance and reliability of anisotropic conductive film (ACF) interconnection. The contact resistance of ACF interconnection increases after reflow process due to the decrease in contact area of the conducting particles between the mating I/O pads. However, the relationship between the contact resistance and bonding parameters of the ACF interconnection with reflow treatment follows the similar trend to that of the as-bonded (i.e. without reflow) ACF interconnection. The contact resistance increases as the peak temperature of reflow profile increases. Nearly 40% of the joints were found to be open after reflow with 260 °C peak temperature. During the reflow process, the entrapped (between the chip and substrate) adhesive matrix tries to expand much more than the tiny conductive particles because of the higher coefficient of thermal expansion, the induced thermal stress will try to lift the bump from the pad and decrease the contact area of the conductive path and eventually, leading to a complete loss of electrical contact. In addition, the environmental effect on contact resistance such as high temperature/humidity aging test was also investigated. Compared with the ACF interconnections with Ni/Au bump, higher thermal stress in the Z-direction is accumulated in the ACF interconnections with Au bump during the reflow process owing to the higher bump height, thus greater loss of contact area between the particles and I/O pads leads to an increase of contact resistance and poorer reliability after reflow.

Experimental and modeling analysis of the reliability of the anisotropic conductive films

Experiments as well as computer modeling methods have been used to investigate the effect of the solder reflow process on the electrical characteristics and reliability of anisotropic conductive film (ACF) interconnections. In the experiments, the contact resistance of the ACF interconnections was found to increase after a subsequent reflow and the magnitude of this increase was strongly correlated to the peak temperature of the reflow profile. In fact, nearly 40 percent of the joints were opened (i.e. lifted away from the pad) after the reflow with a peak temperature of 260 OC while no openings was observed when the peak temperature was 210 "C. It is believed that the CTE mismatch between the polymer particle and the adhesive matrix is the main cause of this contact degradation. To understand this phenomenon better, a 3-D model of an ACF joint structure was built and Finite Element Analysis was used to predict the stress distrihution in the conductive particles, adhesive matrix and metal pads during the reflow process. The effects of the peak temperature, the CTE of the adhesive matrix and the bump height on the reliability of the ACF interconnections were discussed.

Domain decomposition methods for welding problems

This paper, a 2-D non-linear electric arc-welding problem is considered. It is assumed that the moving arc generates an unknown quantity of energy which makes the problem an inverse problem with an unknown source. Robust algorithms to solve such problems e#ciently, and in certain circumstances in real-time, are of great technological and industrial interest. There are other types of inverse problems which involve inverse determination of heat conductivity or material properties [CDJ63][TE98], inverse problems in material cutting [ILPP98], and retrieval of parameters containing discontinuities [IK90]. As in the metal cutting problem, the temperature of a very hot surface is required and it relies on the use of thermocouples. Here, the solution scheme requires temperature measurements lied in the neighbourhood of the weld line in order to retrieve the unknown heat source. The size of this neighbourhood is not considered in this paper, but rather a domain decomposition concept is presented and an examination of the accuracy of the retrieved source are presented. This paper is organised as follows. The inverse problem is formulated and a method for the source retrieval is presented in the second section. The source retrieval method is based on an extension of the 1-D source retrieval method as proposed in [ILP].

No-flow underfill flip chip assembly–an experimental and modeling analysis

In the flip-chip assembly process, no-flow underfill materials have a particular advantage over traditional underfill: the application and curing of the former can be undertaken before and during the reflow process. This advantage can be exploited to increase the flip-chip manufacturing throughput. However, adopting a no-flow underfill process may introduce reliability issues such as underfill entrapment, delamination at interfaces between underfill and other materials, and lower solder joint fatigue life. This paper presents an analysis on the assembly and the reliability of flip-chips with no-flow underfill. The methodology adopted in the work is a combination of experimental and computer-modeling methods. Two types of no-flow underfill materials have been used for the flip chips. The samples have been inspected with X-ray and scanning acoustic microscope inspection systems to find voids and other defects. Eleven samples for each type of underfill material have been subjected to thermal shock test and the number of cycles to failure for these flip chips have been found. In the computer modeling part of the work, a comprehensive parametric study has provided details on the relationship between the material properties and reliability, and on how underfill entrapment may affect the thermal–mechanical fatigue life of flip chips with no-flow underfill.