Introduction: Currently available antigen tests for norovirus (NoV) have excellent specificity but negative results do not always rule out infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) is a useful method for detecting and genotyping NoV in humans and oysters. An outbreak of NoV associated with oyster consumption in northern New South Wales confirmed the value of real-time RT-PCR where immunochromatography (ICT) tests were negative. Methods: Eight cases of gastrointestinal illness in northern NSW, clinically suggestive of NoV infection, were associated with consumption of oysters. A joint environmental investigation was conducted by the New South Wales Food Authority and local council. One human sample was collected and tested for NoV using ICT and real-time RT-PCR. Oyster samples were tested for NoV utilising real-time RT-PCR. Results: The patient with a stool sample had NoV genogroup II (GII) confirmed by real-time RT-PCR after testing negative by ICT. Illness in all cases was consistent with NoV with median incubation and duration of 36 and 50.5 hours respectively. All cases consumed oysters that were harvested from the same area. Three oyster samples from the harvest area were also positive for NoV GII. A nearby leaking sewer line was identified as the likely source of the contamination with hydrological studies confirming its potential to contaminate implicated oyster leases. Conclusion: This investigation confirmed the value of real-time RT-PCR testing of human specimens where ICT tests are negative and clinical illness is suggestive of NoV infection. NoV real-time RT-PCR and epidemiological evidence effectively linked human infection with oyster contamination to motivate a thorough environmental investigation and appropriate action to mitigate further public health risk. Commun Dis Intell 2014;38(1):E9-E15.
Uptake of neoadjuvant chemotherapy (NC) for muscle invasive bladder cancer (MIBC) has been low despite evidence of a survival benefit. The primary aim of this study was to better understand why the rates are low and determine what factors specifically influence the decision to recommend NC for MIBC.
Eliciting a cellular response to a changing chemical microenvironment is central to many biological processes including gene expression, cell migration, differentiation, apoptosis, and intercellular signaling. The nature and scope of the response is highly dependent upon the spatiotemporal characteristics of the stimulus. To date, studies that investigate this phenomenon have been limited to digital (or step) chemical stimulation with little control over the temporal counterparts. Here, we demonstrate an acoustofluidic (i.e., fusion of acoustics and microfluidics) approach for generating programmable chemical waveforms that permits continuous modulation of the signal characteristics including the amplitude (i.e., sample concentration), shape, frequency, and duty cycle, with frequencies reaching up to 30 Hz. Furthermore, we show fast switching between multiple distinct stimuli, wherein the waveform of each stimulus is independently controlled. Using our device, we characterized the frequency-dependent activation and internalization of the ?2-adrenergic receptor (?2-AR), a prototypic G-protein coupled receptor (GPCR), using epinephrine. The acoustofluidic-based programmable chemical waveform generation and switching method presented herein is expected to be a powerful tool for the investigation and characterization of the kinetics and other dynamic properties of many biological and biochemical processes.
In this work, we develop an in situ method to grow highly controllable, sensitive, three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates via an optothermal effect within microfluidic devices. Implementing this approach, we fabricate SERS substrates composed of Ag@ZnO structures at prescribed locations inside microfluidic channels, sites within which current fabrication of SERS structures has been arduous. Conveniently, properties of the 3D Ag@ZnO nanostructures such as length, packing density, and coverage can also be adjusted by tuning laser irradiation parameters. After exploring the fabrication of the 3D nanostructures, we demonstrate a SERS enhancement factor of up to ?2 × 10(6) and investigate the optical properties of the 3D Ag@ZnO structures through finite-difference time-domain simulations. To illustrate the potential value of our technique, low concentrations of biomolecules in the liquid state are detected. Moreover, an integrated cell-trapping function of the 3D Ag@ZnO structures records the surface chemical fingerprint of a living cell. Overall, our optothermal-effect-based fabrication technique offers an effective combination of microfluidics with SERS, resolving problems associated with the fabrication of SERS substrates in microfluidic channels. With its advantages in functionality, simplicity, and sensitivity, the microfluidic-SERS platform presented should be valuable in many biological, biochemical, and biomedical applications.
Highly surface-roughened Ag nanoplate arrays are fabricated using a simple electrodeposition and in situ electrocorrosion method with inorganic borate ions as capping agent. The electrocorrosion process is induced by a change in the local pH value during the electrochemical growth, which is used to intentionally carve the electrodeposited structures. The three dimensionally arranged Ag nanoplates are integrated with substantial surface-enhanced Raman scattering (SERS) hot spots and are free of organic contaminations widely used as shaping agents in previous works, making them excellent candidate substrates for SERS biosensing applications. The SERS enhancement factor of the rough Ag nanoplates is estimated to be > 10(9). These Ag nanoplate arrays are used for SERS-based analysis of DNA hybridization monitoring, protein detection, and virus differentiation without any additional surface modifications or labelling. They all exhibit an extremely high detection sensitivity, reliability, and reproducibility.
Cell/bead washing is an indispensable sample preparation procedure used in various cell studies and analytical processes. In this article, we report a standing surface acoustic wave (SSAW)-based microfluidic device for cell and bead washing in a continuous flow. In our approach, the acoustic radiation force generated in a SSAW field is utilized to actively extract cells or beads from their original medium. A unique configuration of tilted-angle standing surface acoustic wave (taSSAW) is employed in our device, enabling us to wash beads with >98% recovery rate and >97% washing efficiency. We also demonstrate the functionality of our device by preparing high-purity (>97%) white blood cells from lysed blood samples through cell washing. Our SSAW-based cell/bead washing device has the advantages of label-free manipulation, simplicity, high biocompatibility, high recovery rate, and high washing efficiency. It can be useful for many lab-on-a-chip applications.
Shape-controlled synthesis of nanomaterials through a simple, continuous, and low-cost method is essential to nanomaterials research toward practical applications. Hydrodynamic focusing, with its advantages of simplicity, low-cost, and precise control over reaction conditions, has been used for nanomaterial synthesis. While most studies have focused on improving the uniformity and size control, few have addressed the potential of tuning the shape of the synthesized nanomaterials. Here we demonstrate a facile method to synthesize hybrid materials by three-dimensional hydrodynamic focusing (3D-HF). While keeping the flow rates of the reagents constant and changing only the flow rate of the buffer solution, the molar ratio of two reactants (i.e., tetrathiafulvalene (TTF) and HAuCl4) within the reaction zone varies. The synthesized TTF-Au hybrid materials possess very different and predictable morphologies. The reaction conditions at different buffer flow rates are studied through computational simulation, and the formation mechanisms of different structures are discussed. This simple one-step method to achieve continuous shape-tunable synthesis highlights the potential of 3D-HF in nanomaterials research.
Label-free measurements of the reaction kinetics of a small sample volume are essential for efficient drug discovery, requiring methods and systems that are rapid, accurate, and cost-effective. Herein, we present an integrated optofluidic system for label-free characterization of reactions in a nanoliter reagent volume. This system contains a droplet-based microfluidic sampling section and an optical fiber-based spectroscopy detection section. By manipulating droplets containing reagents at certain concentrations at different times, quantifiable measurements via absorption spectroscopy can be made in a simple, sensitive, and high-throughput manner. We have demonstrated our system's capability by performing potency (IC50) assays of an inhibitor in a TEM-1 ?-lactamase (enzyme) and nitrocefin (substrate) system. This integrated platform can potentially provide an automated, label-free, and low-cost method for many other assays of reaction kinetics.
Precise reconstruction of heterotypic cell-cell interactions in vitro requires the coculture of different cell types in a highly controlled manner. In this article, we report a standing surface acoustic wave (SSAW)-based cell coculture platform. In our approach, different types of cells are patterned sequentially in the SSAW field to form an organized cell coculture. To validate our platform, we demonstrate a coculture of epithelial cancer cells and endothelial cells. Real-time monitoring of cell migration dynamics reveals increased cancer cell mobility when cancer cells are cocultured with endothelial cells. Our SSAW-based cell coculture platform has the advantages of contactless cell manipulation, high biocompatibility, high controllability, simplicity, and minimal interference of the cellular microenvironment. The SSAW technique demonstrated here can be a valuable analytical tool for various biological studies involving heterotypic cell-cell interactions.
We present a programmable acoustofluidic pump that utilizes the acoustic streaming effects generated by the oscillation of tilted sharp-edge structures. This sharp-edge-based acoustofluidic pump is capable of generating stable flow rates as high as 8 ?L min(-1) (~76 Pa of pumping pressure), and it can tune flow rates across a wide range (nanoliters to microliters per minute). Along with its ability to reliably produce stable and tunable flow rates, the acoustofluidic pump is easy to operate and requires minimum hardware, showing great potential for a variety of applications.
Separation of cells is a critical process for studying cell properties, disease diagnostics, and therapeutics. Cell sorting by acoustic waves offers a means to separate cells on the basis of their size and physical properties in a label-free, contactless, and biocompatible manner. The separation sensitivity and efficiency of currently available acoustic-based approaches, however, are limited, thereby restricting their widespread application in research and health diagnostics. In this work, we introduce a unique configuration of tilted-angle standing surface acoustic waves (taSSAW), which are oriented at an optimally designed inclination to the flow direction in the microfluidic channel. We demonstrate that this design significantly improves the efficiency and sensitivity of acoustic separation techniques. To optimize our device design, we carried out systematic simulations of cell trajectories, matching closely with experimental results. Using numerically optimized design of taSSAW, we successfully separated 2- and 10-µm-diameter polystyrene beads with a separation efficiency of ? 99%, and separated 7.3- and 9.9-µm-polystyrene beads with an efficiency of ? 97%. We illustrate that taSSAW is capable of effectively separating particles-cells of approximately the same size and density but different compressibility. Finally, we demonstrate the effectiveness of the present technique for biological-biomedical applications by sorting MCF-7 human breast cancer cells from nonmalignant leukocytes, while preserving the integrity of the separated cells. The method introduced here thus offers a unique route for separating circulating tumor cells, and for label-free cell separation with potential applications in biological research, disease diagnostics, and clinical practice.
Sequencing of plant genomes often identified the hAT superfamily as the largest group of DNA transposons. Nevertheless, detailed information on the diversity, abundance and chromosomal localization of plant hAT families are rare. By in silico analyses of the reference genome assembly and bacterial artificial chromosome (BAC) sequences, respectively, we performed the classification and molecular characterization of hAT transposon families in Musa acuminata. Musa hAT transposons are organized in three families designated MuhAT I, MuhAT II and MuhAT III. In total, 70 complete autonomous elements of the MuhAT I and MuhAT II families were detected, while no autonomous MuhAT III transposons were found. Based on the terminal inverted repeat (TIR)-specific sequence information of the autonomous transposons, 1722 MuhAT I- and MuhAT II-specific miniature inverted-repeat transposable elements (MuhMITEs) were identified. Autonomous MuhAT I and MuhAT II elements are only moderately abundant in the sections of the genus Musa, while the corresponding MITEs exhibit an amplification in Musa genomes. By fluorescent in situ hybridization (FISH), autonomous MuhAT transposons as well as MuhMITEs were localized in subtelomeric, most likely gene-rich regions of M. acuminata chromosomes. A comparison of homoeologous regions of M. acuminata and Musa balbisiana BACs revealed the species-specific mobility of MuhMITEs. In particular, the activity of MuhMITEs II showing transduplications of genomic sequences might indicate the presence of active MuhAT transposons, thus suggesting a potential role of MuhMITEs as modulators of genome evolution of Musa.
The aim of this paper was to see whether all-cause and cause-specific mortality rates vary between Asian ethnic subgroups, and whether overseas born Asian subgroup mortality rate ratios varied by nativity and duration of residence. We used hierarchical Bayesian methods to allow for sparse data in the analysis of linked census-mortality data for 25-75 year old New Zealanders. We found directly standardised posterior all-cause and cardiovascular mortality rates were highest for the Indian ethnic group, significantly so when compared with those of Chinese ethnicity. In contrast, cancer mortality rates were lowest for ethnic Indians. Asian overseas born subgroups have about 70% of the mortality rate of their New Zealand born Asian counterparts, a result that showed little variation by Asian subgroup or cause of death. Within the overseas born population, all-cause mortality rates for migrants living 0-9 years in New Zealand were about 60% of the mortality rate of those living more than 25 years in New Zealand regardless of ethnicity. The corresponding figure for cardiovascular mortality rates was 50%. However, while Chinese cancer mortality rates increased with duration of residence, Indian and Other Asian cancer mortality rates did not. Future research on the mechanisms of worsening of health with increased time spent in the host country is required to improve the understanding of the process, and would assist the policy-makers and health planners.
A self-powered polymeric micropump based on boronate chemistry is described. The pump is triggered by the presence of glucose in ambient conditions and induces convective fluid flows, with pumping velocity proportional to the glucose concentration. The pumping is due to buoyancy convection that originates from reaction-associated heat flux, as verified from experiments and finite difference modeling. As predicted, the fluid flow increases with increasing height of the chamber. In addition, pumping velocity is enhanced on replacing glucose with mannitol because of the enhanced exothermicity associated with the reaction of the latter.
To inform endgame strategies in tobacco control, this study aimed to estimate the impact of interventions that markedly reduced availability of tobacco retail outlets. The setting was New Zealand, a developed nation where the government has a smoke-free nation goal in 2025.
BackgroundTransposable elements (TEs) are DNA sequences that are able to move from their location in the genome by cutting or copying themselves to another locus. As such, they are increasingly recognized as impacting all aspects of genome function. With the dramatic reduction in cost of DNA sequencing, it is now possible to resequence whole genomes in order to systematically characterize novel TE mobilization in a particular individual. However, this task is made difficult by the inherently repetitive nature of TE sequences, which in some eukaryotes compose over half of the genome sequence. Currently, only a few software tools dedicated to the detection of TE mobilization using next-generation-sequencing are described in the literature. They often target specific TEs for which annotation is available, and are only able to identify families of closely related TEs, rather than individual elements.ResultsWe present TE-Tracker, a general and accurate computational method for the de-novo detection of germ line TE mobilization from re-sequenced genomes, as well as the identification of both their source and destination sequences. We compare our method with the two classes of existing software: specialized TE-detection tools and generic structural variant (SV) detection tools. We show that TE-Tracker, while working independently of any prior annotation, bridges the gap between these two approaches in terms of detection power. Indeed, its positive predictive value (PPV) is comparable to that of dedicated TE software while its sensitivity is typical of a generic SV detection tool. TE-Tracker demonstrates the benefit of adopting an annotation-independent, de novo approach for the detection of TE mobilization events. We use TE-Tracker to provide a comprehensive view of transposition events induced by loss of DNA methylation in Arabidopsis. TE-Tracker is freely available at http://www.genoscope.cns.fr/TE-Tracker.ConclusionsWe show that TE-Tracker accurately detects both the source and destination of novel transposition events in re-sequenced genomes. Moreover, TE-Tracker is able to detect all potential donor sequences for a given insertion, and can identify the correct one among them. Furthermore, TE-Tracker produces significantly fewer false positives than common SV detection programs, thus greatly facilitating the detection and analysis of TE mobilization events.
In this article, we present a simple, rapid prototyped polystyrene-based microfluidic device with three-dimensional (3D) interconnected microporous walls for long term perfusion cell culture. Patterned 3D interconnected microporous structures were created by a chemical treatment together with a protective mask and the native hydrophobic nature of the microporous structures were selectively made hydrophilic using oxygen plasma treatment together with a protective mask. Using this polystyrene-based cell culture microfluidic device, we successfully demonstrated the support of four days perfusion cell culture of hepatocytes (C3A cells).
Salmonella Typhimurium is the most common bacterial cause of gastrointestinal disease in NSW. Regular review of surveillance procedures ensures system objectives are met and informs improvements in system utility and efficiency. This paper assesses the timeliness and data completeness of NSW Salmonella Typhimurium surveillance after the routine introduction of multilocus variable repeat analysis (MLVA), a rapid sub-typing technique. MLVA results were available significantly earlier than alternate sub-typing techniques over the 2 years of this review. Accordingly, from a timeliness perspective, MLVA offers a favourable Salmonella Typhimurium sub-typing option in NSW. Further opportunities to improve timeliness and data completeness are identified. This paper was produced as part of a review of Salmonella Typhimurium surveillance in NSW for the period 2008-2009 by members of OzFoodNet based at Hunter New England Population Health. OzFoodNet is a national network established by the then Commonwealth Department of Health and Ageing in 2000 to enhance foodborne disease surveillance in Australia.
Similar to many developed countries, vaccination against human papillomavirus (HPV) is provided only to girls in New Zealand and coverage is relatively low (47% in school-aged girls for dose 3). Some jurisdictions have already extended HPV vaccination to school-aged boys. Thus, exploration of the cost-utility of adding boys' vaccination is relevant. We modeled the incremental health gain and costs for extending the current girls-only program to boys, intensifying the current girls-only program to achieve 73% coverage, and extension of the intensive program to boys.
Oscillating sharp edges have been employed to achieve rapid and homogeneous mixing in microchannels using acoustic streaming. Here, we used a perturbation approach to study the flow around oscillating sharp edges in a microchannel. This work extends prior experimental studies to numerically characterize the effect of various parameters on the acoustically induced flow. Our numerical results match well with the experimental results. We investigated multiple device parameters such as the tip angle, oscillation amplitude, and channel dimensions. Our results indicate that, due to the inherent nonlinearity of acoustic streaming, the channel dimensions could significantly impact the flow patterns and device performance.
There have been recent important changes to adjuvant regimens and costs of taxanes for the treatment of early breast cancer, requiring a re-evaluation of comparative cost effectiveness. In particular, weekly paclitaxel is now commonly used but has not been subjected to cost-effectiveness analysis.
A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1-10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ?3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making.
Social and economic measures in early childhood or adolescence appear to be associated with drinking behavior in young adulthood. Yet, there has been little investigation to what extent drinking behavior of young adults changes within young adulthood when they experience changes in social and economic measures in this significant period of their life.
Health expenditure increases with age, but some of this increase is due to costs proximal to death. We used linked health datasets (HealthTracker) to determine health expenditure by proximity to death. We then determined the impact on future health expenditure projections of accounting for proximity to death in costs.
During the deep reactive ion etching process, the sidewalls of a silicon mold feature rough wavy structures, which can be transferred onto a polydimethylsiloxane (PDMS) microchannel through the soft lithography technique. In this article, we utilized the wavy structures of PDMS microchannel sidewalls to initiate and cavitate bubbles in the presence of acoustic waves. Through bubble cavitation, this acoustofluidic approach demonstrates fast, effective mixing in microfluidics. We characterized its performance by using viscous fluids such as poly(ethylene glycol) (PEG). When two PEG solutions with a resultant viscosity 54.9 times higher than that of water were used, the mixing efficiency was found to be 0.92, indicating excellent, homogeneous mixing. The acoustofluidic micromixer presented here has the advantages of simple fabrication, easy integration, and capability to mix high-viscosity fluids (Reynolds number: ~0.01) in less than 100 ms.
Site-specific electrochemical deposition is used to prepare polystyrene (PS)-Ag Janus particle arrays with superhydrophobic properties. The analyte molecules can be significantly enriched using the superhydrophobic property of the PS-Ag Janus particle array before SERS detections, enabling an extremely sensitive detection of molecules in a highly diluted solution (e.g., femtomolar level). This superhydrophobic surface enhanced Raman scattering sensing concept described here is of critical significance in biosensing and bioanalysis. Most importantly, the site-specific electrochemical growth method we developed here is a versatile approach that can be used to prepare Janus particle arrays with different properties for various applications.
The role of allogeneic (allo-) and autologous stem cell transplantation (auto-SCT) in the management of patients with transformed indolent nonfollicular non-Hodgkin lymphoma is unknown. This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B cell nonfollicular non-Hodgkin lymphoma and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with allo-SCT or auto-SCT between 1996 and 2013. All patients received myeloablative conditioning regimens. Outcomes were compared with a cohort of 246 patients with transformed follicular lymphoma who also underwent allo-SCT (n = 47) or auto-SCT (n = 199) across the same institutions and time frame. Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent allo-SCT, whereas 33 (65%) underwent auto-SCT. The 3-year overall survival rate after transplantation was 67% (allo-SCT 54%, auto-SCT 74%), and 3-year progression-free survival rate was 49% (allo-SCT 40%, auto-SCT 54%). The 3-year nonrelapse mortality rate was 14% (allo-SCT 15%, auto-SCT 7%). Transplant-related mortality at 100 days was 17% for allo-SCT and 0% for auto-SCT. Adjusted for type of stem cell transplantation, 3-year overall survival, progression-free survival, and nonrelapse mortality rates were similar to those of patients with transformed follicular lymphoma receiving allo-SCT and auto-SCT (P = .38, P = .69, and P = .54, respectively). Allo-SCT and auto-SCT may be reasonable treatments for selected patients with transformed nonfollicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with auto-SCT.
The ultrasonic propulsion of rod-shaped nanomotors inside living HeLa cells is demonstrated. These nanomotors (gold rods about 300 nm in diameter and about 3 mm long) attach strongly to the external surface of the cells, and are readily internalized by incubation with the cells for periods longer than 24 h. Once inside the cells, the nanorod motors can be activated by resonant ultrasound operating at 4 MHz, and show axial propulsion as well as spinning. The intracellular propulsion does not involve chemical fuels or high-power ultrasound and the HeLa cells remain viable. Ultrasonic propulsion of nanomotors may thus provide a new tool for probing the response of living cells to internal mechanical excitation, for controllably manipulating intracellular organelles, and for biomedical applications.
A large fraction of eukaryotic genomes is made up of long interspersed nuclear elements (LINEs). Due to their capability to create novel copies via error-prone reverse transcription, they generate multiple families and reach high copy numbers. Although mammalian LINEs have been well described, plant LINEs have been only poorly investigated. Here, we present a systematic cross-species survey of LINEs in higher plant genomes shedding light on plant LINE evolution as well as diversity, and facilitating their annotation in genome projects. Applying a Hidden Markov Model (HMM)-based analysis, 59 390 intact LINE reverse transcriptases (RTs) were extracted from 23 plant genomes. These fall in only two out of 28 LINE clades (L1 and RTE) known in eukaryotes. While plant RTE LINEs are highly homogenous and mostly constitute only a single family per genome, plant L1 LINEs are extremely diverse and form numerous families. Despite their heterogeneity, all members across the 23 species fall into only seven L1 subclades, some of them defined here. Exemplarily focusing on the L1 LINEs of a basal reference plant genome (Beta vulgaris), we show that the subclade classification level does not only reflect RT sequence similarity, but also mirrors structural aspects of complete LINE retrotransposons, like element size, position and type of encoded enzymatic domains. Our comprehensive catalogue of plant LINE RTs serves the classification of highly diverse plant LINEs, while the provided subclade-specific HMMs facilitate their annotation.
The ability of zero-mode waveguides (ZMWs) to guide light energy into subwavelength-diameter cylindrical nanoapertures has been exploited for single-molecule fluorescence studies of biomolecules at micromolar concentrations, the typical dissociation constants for biomolecular interactions. Although epi-fluorescence microscopy is now adopted for ZMW-based imaging as an alternative to the commercialized ZMW imaging platform, its suitability and performance awaits rigorous examination. Here, we present conical lens-based dark-field fluorescence microscopy in combination with a ZMW/microfluidic chip for single-molecule fluorescence imaging. We demonstrate that compared to epi-illumination, the dark-field configuration displayed diminished background and noise and enhanced signal-to-noise ratios. This signal-to-noise ratio for imaging using the dark-field setup remains essentially unperturbed by the presence of background fluorescent molecules at micromolar concentration. Our design allowed single-molecule FRET studies that revealed weak DNA-protein and protein-protein interactions found with T4 replisomal proteins.
Cost-effective, high-performance diagnostic instruments are vital to providing the society with accessible, affordable, and high-quality healthcare. Here we present an integrated, "microfluidic drifting" based flow cytometry chip as a potential inexpensive, fast, and reliable diagnostic tool. It is capable of analyzing human blood for cell counting and diagnosis of diseases. Our device achieves a throughput of ~3754 events/s. Calibration with Flow-Check calibration beads indicated good congruency with a commercially available benchtop flow cytometer. Moreover, subjection to a stringent 8-peak rainbow calibration particle test demonstrated its ability to perform high-resolution immunological studies with separation resolution of 4.28 between the two dimmest fluorescent populations. Counting accuracy at different polystyrene bead concentrations showed strong correlation (r = 0.9991) with hemocytometer results. Finally, reliable quantification of CD4+ cells in healthy human blood via staining with monoclonal antibodies was demonstrated. These results demonstrate the potential of our microfluidic flow cytometry chip as an inexpensive yet high-performance point-of-care device for mobile medicine.
As with many high-income countries, vaccination coverage against human papilloma virus (HPV) infection is not high in New Zealand (NZ) at 47% in school-aged girls for three doses. We estimate the health gains, net-cost and cost-effectiveness of the currently implemented HPV national vaccination programme of vaccination dispersed across schools and primary care, and two alternatives: school-based only (assumed coverage as per Australia: 73%), and mandatory school-based vaccination but with opt-out permitted (coverage 93%). We also generate estimates by social group (sex, ethnic and deprivation group).
It is hypothesized that unconditional (given without obligation) publicly funded financial credits more effectively improve health than conditional financial credits in high-income countries. We previously reported no discernible short-term impact of an employment-conditional tax credit for families on self-rated health (SRH) in adults in New Zealand. This study estimates the effect of an unconditional tax credit for families, called Family Tax Credit (FTC), on SRH in the same study population and setting. A balanced panel of 6900 adults in families was extracted from seven waves (2002-2009) of the Survey of Family, Income and Employment. The exposures, eligibility for and amount of FTC, were derived by applying government eligibility and entitlement criteria. The outcome, SRH, was collected annually. Fixed effects regression analyses eliminated all time-invariant confounding and adjusted for measured time-varying confounders. Becoming eligible for FTC was associated with a small and statistically insignificant change in SRH over the past year [effect estimate: 0.013; 95% confidence interval (CI) -0.011 to 0.037], as was an increase in the estimated amount of FTC by $1000 (effect estimate: -0.001; 95% CI -0.006 to 0.004). The unconditional tax credit for families had no discernible short-term impact on SRH in adults in New Zealand. It did not more effectively improve health status than an employment-conditional tax credit for families.
Cell enrichment is a powerful tool in a variety of cellular studies, especially in applications with low-abundance cell types. In this work, we developed a standing surface acoustic wave (SSAW) based microfluidic device for non-contact, continuous cell enrichment. With a pair of parallel interdigital transducers (IDT) deposited on a piezoelectric substrate, a one-dimensional SSAW field was established along disposable micro-tubing channels, generating numerous pressure nodes (and thus numerous cell-enrichment regions). Our method is able to concentrate highly diluted blood cells by more than 100 fold with a recovery efficiency of up to 99%. Such highly effective cell enrichment was achieved without using sheath flow. The SSAW-based technique presented here is simple, bio-compatible, label-free, and sheath-flow-free. With these advantages, it could be valuable for many biomedical applications.
Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed.
The development of microfluidic chip-based cytometers has become an important area due to their advantages of compact size and low cost. Herein, we demonstrate a sheathless microfluidic cytometer which integrates a standing surface acoustic wave (SSAW)-based microdevice capable of 3D particle/cell focusing with a laser-induced fluorescence (LIF) detection system. Using SSAW, our microfluidic cytometer was able to continuously focus microparticles/cells at the pressure node inside a microchannel. Flow cytometry was successfully demonstrated using this system with a coefficient of variation (CV) of less than 10% at a throughput of ~1000 events s(-1) when calibration beads were used. We also demonstrated that fluorescently labeled human promyelocytic leukemia cells (HL-60) could be effectively focused and detected with our SSAW-based system. This SSAW-based microfluidic cytometer did not require any sheath flows or complex structures, and it allowed for simple operation over a wide range of sample flow rates. Moreover, with the gentle, bio-compatible nature of low-power surface acoustic waves, this technique is expected to be able to preserve the integrity of cells and other bioparticles.
Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre-induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 10(9) /l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre-induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998-2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 10(9) /l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 10(9) /l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre-induction leucoreduction.
A critical first step toward incorporating equity into cost-effectiveness analyses is to appropriately model interventions by population subgroups. In this paper we use a standardized treatment intervention to examine the impact of using ethnic-specific (M?ori and non-M?ori) data in cost-utility analyses for three cancers.
The analysis of repeated measures or panel data allows control of some of the biases which plague other observational studies, particularly unmeasured confounding. When this bias is suspected, and the research question is: Does a change in an exposure cause a change in the outcome?, a fixed effects approach can reduce the impact of confounding by time-invariant factors, such as the unmeasured characteristics of individuals. Epidemiologists familiar with using mixed models may initially presume that specifying a random effect (intercept) for every individual in the study is an appropriate method. However, this method uses information from both the within-individual/unit exposure-outcome association and the between-individual/unit exposure-outcome association. Variation between individuals may introduce confounding bias into mixed model estimates, if unmeasured time-invariant factors are associated with both the exposure and the outcome. Fixed effects estimators rely only on variation within individuals and hence are not affected by confounding from unmeasured time-invariant factors. The reduction in bias using a fixed effects model may come at the expense of precision, particularly if there is little change in exposures over time. Neither fixed effects nor mixed models control for unmeasured time-varying confounding or reverse causation.
The recent discovery of fuel-free propulsion of nanomotors using acoustic energy has provided a new avenue for using nanomotors in biocompatible media. Crucial to the application of nanomotors in biosensing and biomedical applications is the ability to remotely control and steer them toward targets of interest, such as specific cells and tissues. We demonstrate in vitro magnetic steering of acoustically powered nanorod motors in a biologically compatible environment. Steering was accomplished by incorporating (40 ± 5) nm thick nickel stripes into the electrochemically grown nanowires. An external magnetic field of 40-45 mT was used to orient the motors, which were acoustically propelled along their long axes. In the absence of a magnetic field, (300 ± 30) nm diameter, (4.3 ± 0.2) ?m long nanowires with (40 ± 5) nm thick magnetic stripes exhibit the same self-acoustophoretic behavior, including pattern formation into concentric nanowire circles, aligned spinning chains, and autonomous axial motion, as their non-magnetic counterparts. In a magnetic field, these wires and their paths are oriented as evidenced by their relatively linear trajectories. Coordinated motion of multiple motors and targeting of individual motors toward HeLa cells with micrometer-level precision was demonstrated.
In this article, we demonstrate single-layered, "microfluidic drifting" based three-dimensional (3D) hydrodynamic focusing devices with particle/cell focal positioning approaching submicron precision along both lateral and vertical directions. By systematically optimizing channel geometries and sample/sheath flow rates, a series of "microfluidic drifting" based 3D hydrodynamic focusing devices with different curvature angles are designed and fabricated. Their performances are then evaluated using confocal microscopy, fast camera imaging, and side-view imaging techniques. Using a device with a curvature angle of 180°, we have achieved a standard deviation of ±0.45 ?m in particle focal position and a coefficient of variation (CV) of 2.37% in flow cytometric measurements. To the best of our knowledge, this is the best CV that has been achieved using a microfluidic flow cytometry device. Moreover, the device showed the capability to distinguish 8 peaks when subjected to a stringent 8-peak rainbow calibration test, signifying the ability to perform sensitive, accurate tests similar to commercial flow cytometers. We have further tested and validated our device by detection of HEK-293 cells. With its advantages in simple fabrication (i.e., single-layered device), precise 3D hydrodynamic focusing (i.e., submicrometer precision along both lateral and vertical directions), and high detection resolution (i.e., low CV), our method could serve as an important basis for high-performance, mass-producible microfluidic flow cytometry.
We present a theoretical analysis and experimental demonstration of particle trapping and manipulation around optothermally generated bubbles. We show that a particle located within 500 ?m of a surface bubble can be attracted towards a bubble by drag force resulting from a convective flow. Once the particle comes in contact with the bubbles surface, a balance between surface tension forces and pressure forces traps the particle on the bubble surface, allowing the particle to move with the bubble without detaching. The proposed mechanism is confirmed by computational fluid dynamics simulations, force calculations, and experiments. Based on this mechanism, we experimentally demonstrated a novel approach for manipulating microparticles via optothermally generated bubbles. Using this approach, randomly distributed microparticles were effectively collected and carried to predefined locations. Single particles were also manipulated along prescribed trajectories. This bubble-based particle trapping and manipulation technique can be useful in applications such as micro assembly, particle concentration, and high-precision particle separation.
An analysis of general practice data for rural communities in close proximity to coal mining and coal-fired power generation in the Hunter Valley region of NSW was conducted to identify unusual patterns of illness.
Considerable advances have been made in the development of micro-physiological systems that seek to faithfully replicate the complexity and functionality of animal and human physiology in research laboratories. Sometimes referred to as "organs-on-chips", these systems provide key insights into physiological or pathological processes associated with health maintenance and disease control, and serve as powerful platforms for new drug development and toxicity screening. In this Focus article, we review the state-of-the-art designs and examples for developing multiple "organs-on-chips", and discuss the potential of this emerging technology to enhance our understanding of human physiology, and to transform and accelerate the drug discovery and preclinical testing process. This Focus article highlights some of the recent technological advances in this field, along with the challenges that must be addressed for these technologies to fully realize their potential.
Health care resources are scarce, and future funding increases are less likely than in the past; reorientation of health services to more efficient and effective delivery is as timely as ever. In this light, we consider the recent funding decision by the Government to provide $16 million over the next 4 years for cancer coordination nurses. While the intricacies of the role are still being defined, it is likely that cancer care coordinators could benefit patients in terms of access to and timeliness of care, and patient satisfaction. Our research into the role shows that many coordinating activities for cancer patients are already being done, but often in an ad hoc manner by a number of different personnel. Thus, we estimate that the likely true incremental cost of cancer care coordinators is in fact relatively low when considered in opportunity cost terms because the cancer care coordinator will be able to free up time for other staff enabling them to provide care elsewhere in the health system and reduce tasks being unnecessarily repeated. The funding of cancer care coordinators is a great opportunity to improve the timeliness of care and improve the experience of patients through their cancer journey, but the success of these roles depends on the leadership provided, peer support, continual appraisal and the resources available.
Recruitment rates into cancer treatment trials are generally very low, both in New Zealand and internationally. This viewpoint article suggests that recruitment rates could be substantially increased by considering all patients newly diagnosed with cancer to be automatically eligible for randomisation if experimental treatments were available under study protocols for patients with their type of cancer. Patients randomised to be offered the experimental treatment would be approached for consent to receive it, whereas patients randomised not to be offered this treatment would continue to receive standard treatment (thus serving as the control group) and not be approached for consent. Routine adoption of this approach, known as "post-randomisation consent" or "pre-randomisation", would require public consultation and "societal consent". While this proposal is not without significant challenges and potential disadvantages, an informed public discussion on the subject would seem worthwhile given the potential for increasing patient access to new cancer treatments and advancing medical science.
New Zealand has a goal of becoming a smokefree nation by the year 2025. Smoking prevalence in 2012 was 17%, but is over 40% for M?ori (indigenous New Zealanders). We forecast the prevalence in 2025 under a business-as-usual (BAU) scenario, and determined what the initiation and cessation rates would have to be to achieve a <5% prevalence.
Nutrition has always been closely related to human health, which is a constant motivational force driving research in a variety of disciplines. Over the years, the rapidly emerging field of microfluidics has been pushing forward the healthcare industry with the development of microfluidic-based, point-of-care (POC) diagnostic devices. Though a great deal of work has been done in developing microfluidic platforms for disease diagnoses, potential microfluidic applications in the field of nutrition remain largely unexplored. In this Focus article, we would like to investigate the potential chances for microfluidics in the field of nutrition. We will first highlight some of the recent advances in microfluidic blood analysis systems that have the capacity to detect biomarkers of nutrition. Then we will examine existing examples of microfluidic devices for the detection of specific biomarkers of nutrition or nutrient content in food. Finally, we will discuss the challenges in this field and provide some insight into the future of applied microfluidics in nutrition.
Pricing policies such as taxes and subsidies are important tools in preventing and controlling a range of threats to public health. This is particularly so in tobacco and alcohol control efforts and efforts to change dietary patterns and physical activity levels as a means of addressing increases in noncommunicable diseases. To understand the potential impact of pricing policies, it is critical to understand the nature of price elasticities for consumer products. For example, price elasticities are key parameters in models of any food tax or subsidy that aims to quantify health impacts and cost-effectiveness. We detail relevant terms and discuss key issues surrounding price elasticities to inform public health research and intervention studies.
Improving social circumstances (eg, an increase in income, finding a job or moving into a good neighbourhood) may reduce tobacco use, but robust evidence on the effects of such improvements is scarce. Accordingly we investigated the link between changing social circumstances and changing tobacco smoking using repeated measures data.
By improving two social determinants of health (poverty and unemployment) in low- and middle-income families on or at risk of welfare, in-work tax credit for families (IWTC) interventions could impact health status and outcomes in adults.
Pacific people living in New Zealand have higher mortality rates than New Zealand residents of European/Other ethnicity. The aim of this paper is to see whether Pacific mortality rates vary by natality and duration of residence. We used linked census-mortality information for 25- to 74-year-olds in the 2001 census followed for up to three years. Hierarchical Bayesian modeling provided a means of handling sparse data. Posterior mortality rates were directly age-standardized. We found little evidence of mortality differences between the overseas-born and the New Zealand-born for all-cause, cancer, and cardiovascular disease (CVD) mortality. However, we found evidence for lower all-cause (and possibly cancer and CVD) mortality rates for Pacific migrants resident in New Zealand for less than 25 years relative to those resident for more than 25 years. This result may arise from a combination of processes operating over time, including health selection effects from variations in New Zealands immigration policy, the location of Pacific migrants within the social, political, and cultural environment of the host community, and health impacts of the host culture. We could not determine the relative importance of these processes, but identifying the (modifiable) drivers of the inferred long-term decline in health of the overseas-born Pacific population relative to more-recent Pacific migrants is important to Pacific communities and from a national health and policy perspective.
The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next.
Rapid and homogeneous mixing inside a microfluidic channel is demonstrated via the acoustic streaming phenomenon induced by the oscillation of sidewall sharp-edges. By optimizing the design of the sharp-edges, excellent mixing performance and fast mixing speed can be achieved in a simple device, making our sharp-edge-based acoustic micromixer a promising candidate for a wide variety of applications.
Intercellular communication is a mechanism that regulates critical events during embryogenesis and coordinates signalling within differentiated tissues, such as the nervous and cardiovascular systems. To perform specialized activities, these tissues utilize the rapid exchange of signals among networks that, while are composed of different cell types, are nevertheless functionally coupled. Errors in cellular communication can lead to varied deleterious effects such as degenerative and autoimmune diseases. However, the intercellular communication network is extremely complex in multicellular organisms making isolation of the functional unit and study of basic mechanisms technically challenging. New experimental methods to examine mechanisms of intercellular communication among cultured cells could provide insight into physiological and pathological processes alike. Recent developments in microfluidic technology allow miniaturized and integrated devices to perform intercellular communication experiments on-chip. Microfluidics have many advantages, including the ability to replicate in vitro the chemical, mechanical, and physical cellular microenvironment of tissues with precise spatial and temporal control combined with dynamic characterization, high throughput, scalability and reproducibility. In this Focus article, we highlight some of the recent work and advances in the application of microfluidics to the study of mammalian intercellular communication with particular emphasis on cell contact and soluble factor mediated communication. In addition, we provide some insights into likely direction of the future developments in this field.
We present a novel concept of generating both static and pulsatile chemical gradients using acoustically activated bubbles designed in a ladder-like arrangement. Furthermore, by regulating the amplitude of the bubble oscillation, we demonstrate that the chemical gradient profiles can be effectively tuned.
There is increasing evidence of a direct association between unaffordable housing and poor mental health, over and above the effects of general financial hardship. Type of housing tenure may be an important factor in determining how individuals experience and respond to housing affordability problems. This study investigated whether a relationship exists between unaffordable housing and mental health that differs for home purchasers and private renters among low-income households. Data from 2001 to 2010 of the longitudinal Household, Income and Labour Dynamics in Australia (HILDA) survey were analysed using fixed-effects linear regression to examine change in the SF-36 Mental Component Summary (MCS) score of individuals aged 25-64 years, associated with changes in housing affordability, testing for an interaction with housing tenure type. After adjusting for age, survey year and household income, among individuals living in households in the lower 40% of the national income distribution, private renters in unaffordable housing experienced somewhat poorer in mental health than when their housing was affordable (difference in MCS = -1.18 or about 20% of one S.D. of the MCS score; 95% CI: -1.95,-0.41; p = 0.003) while home purchasers experienced no difference on average. The statistical evidence for housing tenure modifying the association between unaffordable housing and mental health was moderate (p = 0.058). When alternatives to 40% were considered as income cut-offs for inclusion in the sample, evidence of a difference between renters and home purchasers was stronger amongst households in the lowest 50% of the income distribution (p = 0.020), and between the 30th and 50th percentile (p = 0.045), with renters consistently experiencing a decline in mental health while mean MCS scores of home purchasers did not change. In this study, private renters appeared to be more vulnerable than home purchasers to mental health effects of unaffordable housing. Such a modified effect suggests that tenure-differentiated policy responses to poor housing affordability may be appropriate.
It is well understood that health affects labour force participation (LFP). However, much of the published research has been on older (retiring age) populations and using subjective health measures. This paper aims to assess the impact of an objective measure of health shock (cancer registration or hospitalisation) on LFP in a working age population using longitudinal panel study data and fixed effect regression analyses.
AIM : Cancer burden measured in disability adjusted life years (DALYs) captures survival and disability impacts of incident cancers. In this paper, we estimate the prospective burden of disease arising from 27 cancer sites diagnosed in 2006, by sex and ethnicity; and determine how its distribution differs from that for incidence rates alone. METHODS : Using a prospective approach, Markov and cancer disease models were used to estimate DALYs with inputs of population counts, incidence and excess mortality rates, disability weights, and background mortality. DALYs were discounted at 3.5% per year. RESULTS : The age standardised M?ori:non-M?ori incidence rate ratios were 1.00 for males and 1.19 for females, whereas for DALYs they were greater at 1.42 for males and 1.68 for females. The total burden of cancer for 2006 incident cases (i.e. not age standardised) was estimated to be approximately 127,000 DALYs. Breast (27%), lung (14%) and colorectal (13%) cancers for females and lung (16%), colorectal (14%), and prostate (16%) cancers for males were the top contributors. By ethnicity, M?ori experienced a substantially higher burden from lung cancer (around 25% for both sexes).
We have fabricated porous silicon nanopillar arrays over large areas with a rapid, simple, and low-cost technique. The porous silicon nanopillars show unique longitudinal features along their entire length and have porosity with dimensions on the single-nanometer scale. Both Raman spectroscopy and photoluminescence data were used to determine the nanocrystallite size to be <3 nm. The porous silicon nanopillar arrays also maintained excellent ensemble properties, reducing reflection nearly fivefold from planar silicon in the visible range without any optimization, and approaching superhydrophobic behavior with increasing aspect ratio, demonstrating contact angles up to 138°. Finally, the porous silicon nanopillar arrays were made into sensitive surface-enhanced Raman scattering (SERS) substrates by depositing metal onto the pillars. The SERS performance of the substrates was demonstrated using a chemical dye Rhodamine 6G. With their multitude of properties (i.e., antireflection, superhydrophobicity, photoluminescence, and sensitive SERS), the porous silicon nanopillar arrays described here can be valuable in applications such as solar harvesting, electrochemical cells, self-cleaning devices, and dynamic biological monitoring.
The emerging field of droplet microfluidics requires effective on-chip handling and sorting of droplets. In this work, we demonstrate a microfluidic device that is capable of sorting picoliter water-in-oil droplets into multiple outputs using standing surface acoustic waves (SSAW). This device integrates a single-layer microfluidic channel with interdigital transducers (IDTs) to achieve on-chip droplet generation and sorting. Within the SSAW field, water-in-oil droplets experience an acoustic radiation force and are pushed toward the acoustic pressure node. As a result, by tuning the frequency of the SSAW excitation, the position of the pressure nodes can be changed and droplets can be sorted to different outlets at rates up to 222 droplets s(-1). With its advantages in simplicity, controllability, versatility, noninvasiveness, and capability to be integrated with other on-chip components such as droplet manipulation and optical detection units, the technique presented here could be valuable for the development of droplet-based micro total analysis systems (?TAS).
We demonstrate reflection-mode plasmonic color filters based on lithographically patterned silver nanorods with ultrasmall inter-rod gaps. Fine and effective tuning of the plasmon resonance is shown by varying array periodicities. We determine the dependence of reflected intensity on diameter/periodicity ratio and then develop reflective plasmonic color filters using dense nanorod arrays. Experimental results agree well with theoretical calculations. Our approach is potentially useful for plasmon-assisted sensing, imaging and displays.
Recent developments on various lab-on-a-chip techniques allow miniaturized and integrated devices to perform on-chip single-molecule studies. Fluidic-based platforms that utilize unique microscale fluidic behavior are capable of conducting single-molecule experiments with high sensitivities and throughputs, while biomolecular systems can be studied on-chip using techniques such as DNA curtains, magnetic tweezers, and solid-state nanopores. The advances of these on-chip single-molecule techniques lead to next-generation lab-on-a-chip devices, such as DNA transistors, and single-molecule real-time (SMRT) technology for rapid and low-cost whole genome DNA sequencing. In this Focus article, we will discuss some recent successes in the development of lab-on-a-chip techniques for single-molecule studies and expound our thoughts on the near future of on-chip single-molecule studies.
The two-stage tissue expander/implant (TE/I) reconstruction is currently the gold standard method of implant-based immediate breast reconstruction in North America. Recently, however, there have been numerous case series describing the use of one-stage direct to implant reconstruction with the aid of acellular dermal matrix (ADM). In order to rigorously investigate the novel application of ADM in one-stage implant reconstruction, we are currently conducting a multicentre randomized controlled trial (RCT) designed to evaluate the impact on patient satisfaction and quality of life (QOL) compared to the two-stage TE/I technique.Methods/designsThe MCCAT study is a multicenter Canadian ADM trial designed as a two-arm parallel superiority trial that will compare ADM-facilitated one-stage implant reconstruction compared to two-stage TE/I reconstruction following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) at 2 weeks, 6 months, and 12 months. The source population will be members of the mastectomy cohort with stage T0 to TII disease, proficient in English, over the age of 18 years, and planning to undergo SSM or NSM with immediate implant breast reconstruction. Stratified randomization will maintain a balanced distribution of important prognostic factors (study site and unilateral versus bilateral procedures). The primary outcome is patient satisfaction and QOL as measured by the validated and procedure-specific BREAST-Q. Secondary outcomes include short- and long-term complications, long-term aesthetic outcomes using five standardized photographs graded by three independent blinded observers, and a cost effectiveness analysis.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is now the standard management for mucinous tumors of appendiceal origin at many centers. We examined the role of expectant observation (EO) in patients who had undergone an initial resection at the time of referral to our center and who had limited residual disease.
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