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Docetaxel, cisplatin plus 5-fluorouracil is an efficacious induction regimen but is more toxic than cisplatin plus 5-fluorouracil. This study aimed to determine whether docetaxel and cisplatin without 5-fluorouracil maintains efficacy while decreasing toxicity.
A multicenter non-comparative pilot study of locally advanced squamous cell carcinoma of the head and neck was performed. Patients received primary therapy comprising three cycles of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin followed by concurrent chemoradiotherapy. The primary endpoint was the response rate to the docetaxel and cisplatin induction regimen.
A total of 26 patients were enrolled: of these, 23 (88.5 per cent) received all three docetaxel and cisplatin cycles. Common grade 3–4 adverse events were febrile neutropenia (19.2 per cent of patients), diarrhoea (19.2 per cent) and non-neutropenic infection (15.4 per cent). The overall response rate to docetaxel and cisplatin induction chemotherapy was 65.4 per cent. A total of 23 patients (88.5 per cent) subsequently received chemoradiotherapy with a median radiotherapy dose of 70 Gy. The response rate to chemoradiotherapy was 73 per cent. At a median follow up of 44 months, the 3-year progression-free survival and overall survival rates were 62 per cent and 69 per cent, respectively.
Docetaxel and cisplatin induction chemotherapy is a feasible induction regimen with comparable efficacy to docetaxel, cisplatin and 5-fluorouracil induction chemotherapy.
The analysis of axial dispersion of solute is presented in a pulsatile flow of Casson fluid through a tube in the presence of interfacial mass transport due to irreversible first-order reaction catalysed by the tube wall. The theory of dispersion is studied by employing the generalized dispersion model proposed by Sankarasubramanian & Gill (Proc. R. Soc. Lond. A, vol. 333 (1592), 1973, pp. 115–132). This dispersion model describes the whole dispersion process in terms of three effective transport coefficients, i.e. exchange, convection and dispersion coefficients. In the present study, the effects of yield stress of Casson fluid
, wall absorption parameter
, amplitude of fluctuating pressure component
and Womersley frequency parameter
on the dispersion process are discussed under the influence of pulsatile pressure gradient. In a pulsatile flow, the plug flow radius changes during the period of oscillation and it has an effect on the dispersion process. Even with the Casson fluid model also, in an oscillatory flow, for small values of
, the dispersion coefficient
is positive, but when the value of
is as large as 3,
takes both positive and negative values due to the fluctuations in the velocity profiles. This nature becomes more predominant for
. It is observed that initially, for small time, the amplitude and magnitude of fluctuations of
becomes more rapid and increases with time but it decreases after certain time and reaches a non-transient state for large time. Like in the case of Newtonian model, double frequency period for
is observed at small time for large values of
with the Casson model for blood. It is seen that critical time for which
reaches a non-transient state is independent of
but is dependent on
. It is also observed that the axial distribution of mean concentration
of solute depends on
. But the effect of
is not very significant. This dispersion model in non-Newtonian pulsatile flow can be applied to study the dispersion process in the cardiovascular system and blood oxygenators.
Global patterns of copy number variations (CNVs) in chromosomes are required to understand the dynamics of genome organization and complexity. For this study, analysis was performed using the Affymetrix Genome-Wide Human SNP Array 6.0 chip and CytoScan High-Density arrays. We identified a total of 44 109 CNVs from 1715 genomes with a mean of 25 CNVs in an individual, which established the first drafts of population-specific CNV maps providing a rationale for prioritizing chromosomal regions. About 19 905 ancient CNVs were identified across all chromosomes and populations at varying frequencies. CNV count, and sometimes CNV size, contributed to the bulk CNV size of the chromosome. Population specific lengthening and shortening of chromosomal length was observed. Sex bias for CNV presence was largely dependent on ethnicity. Lower CNV inheritance rate was observed for India, compared to YRI and CEU. A total of 33 candidate CNV hotspots from 5382 copy number (CN) variable region (CNVR) clusters were identified. Population specific CNV distribution patterns in p and q arms disturbed the assumption that CNV counts in the p arm are less common compared to long arms, and the CNV occurrence and distribution in chromosomes is length independent. This study unraveled the force of independent evolutionary dynamics on genome organization and complexity across chromosomes and populations.
We present here the results from observations of pulsed gamma ray emission from the Crab and Vela pulsars for energies above 100 GeV using the atmospheric Cerenkov technique. The results suggest a very steep energy spectrum for gamma rays emitted from pulsars at high energies. Our observations over the last 4 years suggest also that the flux is highly variable with time.
Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing.
To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals.
A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE.
Hospital epidemiologists and infection prevention experts.
No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE.
Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.
Infect Control Hosp Epidemiol 2015;36(10):1163–1172
Copy number variations (CNVs) alter the transcriptional and translational levels of genes by disrupting the coding structure and this burden of CNVs seems to be a significant contributor to phenotypic variations. Therefore it was necessary to assess the complexities of CNV burden on the coding genome. A total of 1715 individuals from 12 populations were used for CNV analysis in the present investigation. Analysis was performed using Affymetrix Genome-Wide Human SNP Array 6·0 chip and CytoScan High-Density arrays. CNVs were more frequently observed in the coding region than in the non-coding region. CNVs were observed vastly more frequently in the coding region than the non-coding region. CNVs were found to be enriched in the regions containing functional genes (83–96%) compared with the regions containing pseudogenes (4–17%). CNVs across the genome of an individual showed multiple hits across many genes, whose proteins interact physically and function under the same pathway. We identified varying numbers of proteins and degrees of interactions within protein complexes of single individual genomes. This study represents the first draft of a population-specific CNV genes map as well as a cross-populational map. The complex relationship of CNVs on genes and their physically interacting partners unravels many complexities involved in phenotype expression. This study identifies four mechanisms contributing to the complexities caused by the presence of multiple CNVs across many genes in the coding part of the genome.
In our earlier work  we had reported first theoretical observations of the spontaneous formation of 60° and 90° misfit dislocations in Au/Ni (15.9% mismatch) systems for the (111) and (001) interfaces respectively. Here, we present the analysis of the evolution of the dislocation configuration as it evolves from a highly strained coherent Au film. The driving force for the formation of these misfit dislocations was the reduction in the config-urational energy during the iterative relaxation of the atoms. A finely stepped energy minimization technique was developed to relax the high energy configuration. Misfit dislocations were also obtained for low misfit systems (Pd/Ni - 10% and Pd/Cu - 7.76%), but a modified approach, which is described here, was used for these systems which shows an energy barrier to the formation of dislocations in the low misfit systems.
Fe-O and Co-O films were prepared by DC magnetron sputtering in a mixture of Ar and O2 gases. By varying the oxygen to argon ratio, oxide films with stoichiometry FeO, Fe3O4, α-Fe2O3, CoO and Co3O4 were produced. TEM studies showed that the Fe – oxide films were polycrystalline consisting of small almost spherical grains, about 10 nm in size. Co-O films had different microstructure with grain size and shape dependent on the amount of oxygen. X-ray diffraction studies showed that the grains in Fe-O films were randomly oriented in contrast to Co-O films in which a <111> texture was observed. Pure FeO and α-Fe2O3 films were found to be superparamagnetic at room temperature but strongly ferromagnetic at low temperatures in contrast to the antiferromagnetic nature of bulk samples. A very large shift in the hysteresis loop, about 3800 Oe, was observed in field cooled Co-CoO films indicating the presence of a large unidirectional exchange anisotropy.
As the MOSFET gate lengths are scaled down to 50 nm or below, the expected increase in gate leakage will be countered by the use of a high dielectric constant (high K) material. The series capacitance from polysilicon gate electrode depletion significantly reduces the gate capacitance as the dielectric thickness is scaled down to 10 Å equivalent oxide thickness (EOT) or below. Metal gates promise to solve this problem and address other problems like boron penetration and enhanced gate resistance that will have increased focus as the polysilicon gate thickness is reduced. Extensive simulations have shown that the optimal gate work-functions for the sub-50 nm channel lengths should be 0.2 eV below (above) the conduction (valence) band edge of silicon for n-MOSFETs (p-MOSFETs). This study summarizes the evaluations of TiN, TaSiN, WN, TaN, TaSi, Ir and IrO2 as candidate metals for dual-metal gate CMOS using HfO2 as the gate dielectric. The gate work-function was determined by fabricating MOS capacitors with varying dielectric thicknesses and different post-gate anneals. The metal-dielectric compatibility and thermal stability was studied by annealing the stacks at different temperatures. The gate stacks were characterized using TEM, SIMS and X-ray diffraction. Based on workfunctions and thermal stability, TaSiN and TaN show most promise as metal electrodes for HfO2 n-MOSFETs.
Anodic aluminum oxide (AAO) template was prepared by using anodizing voltage step-decreasing method after two-step oxide method. Based on AAO template, Fe nanowires arrays were electrochemically deposited. Fe nanowires were coated by chitosan. Fe nanowires/chitosan was synthesized by glutaraldehyde as cross-linking reagent. By crosslinking α-human chorionic gonadotropin (α-HCG), biological probes with Fe nanowires/chitosan/antibody were prepared. An easy operating, easy taking and rapid reacting magnetic detecting system was developed after optimizing the geometry parameters of detect coil. Different concentration samples with 1, 2 and 5 g(Fe)/L were detected. The results show that the sensitivity of system is 0.2 g(Fe)/L and can be improve better.
Immunoassays are currently the main analytical technique for quantification of a wide range of analytes of clinical, medical, biotechnological, and environmental significance with high sensitivity and specificity. Miniaturization of immunoassays is achieved using microfluidics coupled with integrated optical detection of the antibody-antigen molecular recognition reaction using thin-film amorphous silicon (a-Si:H) photodiodes. The detection system used consists of an a-Si:H photodiode aligned with a polydimethylsiloxane (PDMS) microchannel. An enzymatic reaction taking place in the microchannel yields a product which is a light-absorbent molecule and hence can be optically detected by the integrated photodiode. Specific antigen-antibody reaction was detected and distinguished from the non-specific reaction.
Drop on demand inkjet printing is a potential method for depositing enzymes onto electrodes for sensor applications. This technology offers drop sizes in the region of picolitres and allows a production rate up to 200 mm/s. This enables not only a more rapid method of device prototyping but also a method for possible miniaturization of the sensors themselves. However, previous work  has indicated that inkjet printing may cause a drop in the retained activity of the enzyme.
Here we assess the criticality of this drop in activity and how it may have been influenced by changes to the protein structure during printing. The enzyme used is glucose oxidase and the test methods include; protein analysis, in the form of analytical ultra-centrifugation and circular dichroism, scanning electron microscopy, atomic force microscopy and phase contrast microscopy, to analyse the surface topology of the electrodes and contact angle analysis, to assess the degree of spreading and the interactions between the drops and the electrode surface.
With glucose oxidase there is no change in the conformation, structure or hydrodynamic radius of the protein after printing. The analysis of the electrode surface shows a relatively smooth surface that is made up of individual graphite flakes laid down by a screen printing method. When contact angle and spreading analysis is carried out it demonstrates reliability in the printing process as well as a drop in the sessile volume of the drop in conjunction with a growth in the base diameter of the drop as expected. It also demonstrates a fairly quick rate of evaporation of the drop. Upon the addition of surfactants to the solution the spreading is seen to be more extensive in relation to the surfactant concentration, although some initial reduction in experienced at low concentrations which may be due to the absorption into the carbon surface.
We report the synthesis and surface modification of bio-friendly ZnO based colloids, which have been used for cancer cell detection providing significant advantages on quantum confinement effects, high emission brightness in UV to blue-violate range, non-toxicity and a unique dual color imaging feature. The ZnO nanoparticles were single crystal nanoparticles having spherical shape in size of 1-2 or 4-5 nm depending on the surface capping agents. All the colloidal solutions were stable for 30-45 days. The surface capping is a more effective technique in controlling the nanoparticle size, while dopants are effective in modifying the bandgap and optical properties. Unique dual colour images with blue colour in nucleus and turquoise colour in cytoplasm were obtained using either pure ZnO or Co doped ZnO colloids on human osteosarcoma (Mg-63) cells. The dual colour function is the combined effects of quantum confinement and the bio-compatible surface capping groups. The cytotoxicity study proved no cell proliferation by the nanoparticles up to the concentration of 1000 μg/mL, which is the highest concentration reported so far. Since a dosage of only 50-100μM is enough for the in vivo detection on rate, these ZnO colloids have high potential for use as the detection media for Lab-on-a-Chip devices.
Incorporation of biophotonic components in artificial devices is an emerging trend in exploring biomimetic approaches for green technologies. In this study, highly efficient, nanoscaled light antenna structures from green photosynthetic bacteria, known as chlorosomes, comprised of bacteriochlorophyll-c pigment arrays that are stable in aqueous environments are studied in an electrochemical environment for their photoelectrogenic capacity. Biohybrid electrochemical cells containing chlorosomes coupled to the native bacterial photosynthetic apparatus have a higher dark charge storage density (at least 10-fold) than electrochemical cells with decoupled chlorosomes. Nevertheless, upon light stimulation, the charge storage density, also known as charge injection capacity, for both electrochemical systems increased the charge stored near the electrode. Decoupled chlorosome-based systems showed a light-intensity dose-dependent response reaching a maximum change of ˜300 nC/cm2 at near sunlight intensities (˜80-100mW/cm2). Chronoamperometric studies under light stimulation conditions confirmed the photo-induced effect. Current studies are focused on optimization of the electrode/chlorosome interfacial properties across various heterogeneous interfaces. Successful implementation of harvesting photo-energy using the chlorosome or its derivatives may lead to substantial innovations in current biophotonic technologies, such as biofuel cells and retinal prosthetics.
Dry film resist has been used in the fabrication of Masters in microfluidic devices for droplet generation. The minimum feature size in the resist was controlled by the type of mask (transparency or electron beam Cr mask), the resolution of the pattern in transparency masks (2400 or 5080 dpi) and thickness of resist in the range from 35 to 140 μm. The Master patterns formed in dry resist were replicated as a Ni shim and then hot embossed into Plexiglas 99524. These devices were used to generate water-in-oil droplets with a well defined dependence of diameter and frequency on flow parameters. The application of dry laminar resist and transparency masks has allowed the rapid fabrication of prototype devices.
The strength of adhesion at the cell-substrate interface is an important parameter in the design of many prosthetic implant material surfaces, due to the desire to create and maintain a strong implant-tissue bond. This study focuses on the mechanical strength of the interface and the ease of cell removal from ceramic coatings using normal and shear forces, but also looks at cell proliferation rates on the same series of surfaces.
This systematic study of cell proliferation and adhesion has been carried out on a series of oxide coated Ti6Al4V based substrates with a range of surface morphologies and chemistries. Oxide coatings were formed using Plasma Electrolytic Oxidation (the PEO process).
Cells were seeded at a low concentration onto substrates and proliferation monitored for up to three weeks. The same cell concentrations were seeded on samples for adhesion testing. These were cultured for a few days to ensure well established adhesion of viable cells. The normal and shear strength of osteoblasts (bone cells) and chondrocytes (cartilage cells) adhered to these substrates was measured using accelerated negative buoyancy within an ultracentrifuge.
The variation in proliferation rates on, and adhesive strengths to, the range of coatings, is discussed and related to morphological and chemical differences in the coatings. A comparison is made between the normal and shear strengths of the cell-coating bonds and the differences between the behaviour of the two cell types discussed.
Here we propose to detail an innovative FIB instrumental approach and processing methodologies we have developed for sub-10 nm nanopore fabrication. The main advantage of our method is first to allow direct fabrication of nanopores in relatively large quantities with an excellent reproducibility. Second our approach offers the possibility to further process or functionalize the vicinity of each pore on the same scale keeping the required deep sub-10 nm scale positioning and patterning accuracy.
We will summarise the optimisation efforts we have conducted aiming at fabricating thin (10-100 nm thick) and high quality dielectric films to be used as a template for the nanopore fabrication, and at performing efficient and controlled FIB nanoengraving of such a delicate media.
Finally, we will describe the method we have developed for integrating these “single nanopore devices” in electrophoresis experiments and our preliminary measurements.
The hot embossing properties of Cyclic Olefin Copolymer (COC) have been examined as a function of comonomer content. Six standard grades of COC with varying norbornene content (61-82 wt%) were used in these experiments in order to provide a range of glass transition temperatures, Tg. All grades of COC exhibited sharp increases in embossed depth over a critical range of temperature. The transition temperature in embossed depth increased linearly with norbornene content for both 35 and 70 μm deep structures. At temperatures above this transition, the dimensions of the embossed patterns were essentially independent of COC grade, the applied pressure and duration of loading. Channels formed above the transition in a regime of viscous liquid flow were extremely smooth in morphology for all grades. The average surface roughness, Ra, measured at the base of the channels decreased sharply at the transition temperature, with a levelling off at higher temperatures. Grades of COC with higher norbornene content exhibited extensive micro-cracking during embossing at temperatures close to the transition temperature.
Hafnium(IV) oxide (HfO2) has replaced silicon oxide as a gate dielectric material in leading edge CMOS technology, providing significant improvement in gate performance for field effect transistors (FETs). We are currently exploring this high-k dielectric for its use in nucleic acid-based FET biosensors. Due to its intrinsic negative charge, label-free detection of DNA can be achieved in the gate region of high-sensitivity FET devices. Previous work has shown that phosphates and phosphonates coordinate specifically onto metal oxide substrates including aluminum and titanium oxides. This property can therefore be exploited for direct immobilization of biomolecules such as nucleic acids. Our work demonstrates that 5’ phosphate-terminated single stranded DNA (ssDNA) can be directly immobilized onto HfO2 surfaces, without the need for additional chemical modification or crosslinking. Non-phosphorylated ssDNA does not form stable surface interactions with HfO2, indicating that immobilization is dependent upon the 5’ terminal phosphate. Further work has shown that surface immobilized ssDNA can be hybridized to complementary target DNA and that sequence-based hybridization specificity is preserved. These results suggest that the direct DNA-HfO2 immobilization strategy can enable nucleic acid-based biosensing assays on HfO2 terminated surfaces. This work will further enable high sensitivity electrical detection of biological targets utilizing transistor-based technologies.