Publications
286 results found
Singh M, Nabavi E, Zhou Y, et al., 2019, Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment, Nanotheranostics, Vol: 3, Pages: 89-102, ISSN: 2206-7418
Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.
Grell M, Dincer C, Le T, et al., 2019, Autocatalytic metallization of fabrics using Si ink, for biosensors, batteries and energy harvesting, Advanced Functional Materials, Vol: 29, Pages: 1-11, ISSN: 1616-301X
Commercially available metal inks are mainly designed for planar substrates (for example, polyethylene terephthalate foils or ceramics), and they contain hydrophobic polymer binders that fill the pores in fabrics when printed, thus resulting in hydrophobic electrodes. Here, a low‐cost binder‐free method for the metallization of woven and nonwoven fabrics is presented that preserves the 3D structure and hydrophilicity of the substrate. Metals such as Au, Ag, and Pt are grown autocatalytically, using metal salts, inside the fibrous network of fabrics at room temperature in a two‐step process, with a water‐based silicon particle ink acting as precursor. Using this method, (patterned) metallized fabrics are being enabled to be produced with low electrical resistance (less than 3.5 Ω sq−1). In addition to fabrics, the method is also compatible with other 3D hydrophilic substrates such as nitrocellulose membranes. The versatility of this method is demonstrated by producing coil antennas for wireless energy harvesting, Ag–Zn batteries for energy storage, electrochemical biosensors for the detection of DNA/proteins, and as a substrate for optical sensing by surface enhanced Raman spectroscopy. In the future, this method of metallization may pave the way for new classes of high‐performance devices using low‐cost fabrics.
Bollella P, Sharma S, Cass AEG, et al., 2019, Microneedle-based biosensor for minimally-invasive lactate detection, BIOSENSORS & BIOELECTRONICS, Vol: 123, Pages: 152-159, ISSN: 0956-5663
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- Citations: 120
Rawson T, Ming D, Gowers S, et al., 2019, Public acceptability of computer-controlled antibiotic management: an exploration of automated dosing and opportunities for implementation, Journal of Infection, Vol: 78, Pages: 75-86, ISSN: 0163-4453
Maniyam MN, Ibrahim AL, Cass AEG, 2019, Enhanced cyanide biodegradation by immobilized crude extract of Rhodococcus UKMP-5M, ENVIRONMENTAL TECHNOLOGY, Vol: 40, Pages: 386-398, ISSN: 0959-3330
Loh AYY, Burgess CH, Tanase DA, et al., 2018, Electric single-molecule hybridization detector for short DNA fragments, Analytical Chemistry, Vol: 90, Pages: 14063-14071, ISSN: 0003-2700
By combining DNA nanotechnology and high-bandwidth single-molecule detection in nanopipets, we demonstrate an electric, label-free hybridization sensor for short DNA sequences (<100 nucleotides). Such short fragments are known to occur as circulating cell-free DNA in various bodily fluids, such as blood plasma and saliva, and have been identified as disease markers for cancer and infectious diseases. To this end, we use as a model system an 88-mer target from the RV1910c gene in Mycobacterium tuberculosis, which is associated with antibiotic (isoniazid) resistance in TB. Upon binding to short probes attached to long carrier DNA, we show that resistive-pulse sensing in nanopipets is capable of identifying rather subtle structural differences, such as the hybridization state of the probes, in a statistically robust manner. With significant potential toward multiplexing and high-throughput analysis, our study points toward a new, single-molecule DNA-assay technology that is fast, easy to use, and compatible with point-of-care environments.
Piletsky SS, Cass AEG, Piletska EV, et al., 2018, A novel assay format as an alternative to ELISA: MINA test for biotin, ChemNanoMat, Vol: 4, Pages: 1214-1222, ISSN: 2199-692X
A novel abiotic assay based on biotin‐specific fluorescent molecularly imprinted polymer nanoparticles (nanoMIPs) which acted as both reporter probes and binding agents, was developed. This is a first report of an assay which, unlike ELISA, required no washing steps or addition of enzyme substrates, making it more user‐friendly. The components of the molecularly imprinted polymer nanoparticles assay (MINA) were assembled in microtiter plates fitted with magnetic inserts. The fluorescent nanoMIPs were bound to biotin‐conjugated magnetic particles, which were attracted to the inserts. The addition of free biotin caused a displacement of the fluorescent nanoMIPs into solution, generating a signal proportional to the concentration of biotin. The nanoMIPs had a dissociation constant (Kd) of 14 nM, allowing the assay to detect biotin at nano‐molar concentrations. The pre‐assembled assay only required the addition of the sample and measurement of the fluorescence, and it functioned well after six weeks of storage without refrigeration. The assay did not show the susceptibility to several compounds which are known to interfere with avidin and streptavidin‐based assays, such as mercaptoethanol and sugars. The protocols optimized in this work could be used to develop the abiotic assays for any other compound of interest.
Panagiotopoulos A, Gkouma A, Vassi A, et al., 2018, Hemin Modified SnO2 Films on ITO-PET with Enhanced Activity for Electrochemical Sensing, ELECTROANALYSIS, Vol: 30, Pages: 1956-1964, ISSN: 1040-0397
Rawson TM, Gowers S, Rogers M, et al., 2018, Towards a minimally invasive device for continuous monitoring of beta-lactam antibiotics, Publisher: ELSEVIER SCI LTD, Pages: 109-109, ISSN: 1201-9712
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Maniyam MN, Ibrahim AL, Cass AEG, 2018, Decolourization and biodegradation of azo dye methyl red by Rhodococcus strain UCC 0016., Environ Technol, Pages: 1-15
In the present study, locally isolated Rhodococcus strains were attempted as biological tools for methyl red removal, a mutagenic azo dye posing threat to the environment if left untreated. Rhodococcus strain UCC 0016 demonstrated superior methyl red-decolourizing activity of 100% after 24 h at static condition in comparison to Rhodococcus strain UCC 0008 which recorded 65% decolourization after 72 h. Optimization of physicochemical parameters at 30°C, pH 7 and supplementing glucose as the carbon source resulted in improved methyl red-decolourizing activity at static condition and reduced the time taken to achieve complete decolourization by 80%. Higher concentration of methyl red (5 g/L) was able to be decolourized completely within 10 h by adopting the technology of immobilization. The encapsulated cells of Rhodococcus strain UCC 0016 demonstrated higher substrate affinity (Km = 0.6995 g/L) and an accelerated rate of disappearance of methyl red (Vmax = 0.3203 g/L/h) compared to the free cells. Furthermore, the gellan gum beads could be reused up to nine batches without substantial loss in the catalytic activity indicating the economic importance of this protocol. Analysis of methyl red degradation products revealed no germination inhibition on Triticum aestivum and Vigna radiata demonstrating complete toxicity removal of the parent dye after biological treatment. The occurrence of new and altered peaks (UV-Vis and FTIR) further supported the notion that the removal of methyl red by Rhodococcus strain UCC 0016 was indeed through biodegradation. Therefore, this strain has a huge potential as a candidate for efficient bioremediation of wastewater containing methyl red.
Sharma S, El-Laboudi A, Reddy M, et al., 2018, A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring, Analytical Methods, Vol: 10, Pages: 2088-2095, ISSN: 1759-9660
Although subcutaneously implanted continuous glucose monitoring (CGM) devices have been shown to support diabetes self-management, their uptake remains low due to a combination of high manufacturing cost and limited accuracy and precision arising from their invasiveness. To address these points, minimally invasive, a solid microneedle array-based sensor for continuous glucose monitoring is reported here. These intradermal solid microneedle CGM sensors are designed for low cost manufacturing. The tolerability and performance of these devices is demonstrated through clinical studies, both in healthy volunteers and participants with type 1 diabetes (T1D). The geometry of these solid microneedles allows them to penetrate dermal tissue without the need for an applicator. The outer surface of these solid microneedles are modified as glucose biosensors. The microneedles sit in the interstitial fluid of the skin compartment and monitor real-time changes in glucose concentration. Optical coherence tomography measurements revealed no major axial movement of the microneedles in the tissue. No significant adverse events were observed and low pain scores were reported when compared to catheter insertion, deeming it safe for clinical studies in T1D. These amperometric sensors also yielded currents that tracked venous blood glucose concentrations, showing a clinically acceptable correlation. Studies in people with T1D gave a mean absolute relative difference (MARD) of 9% (with respect to venous blood glucose) with over 94% of the data points in the A and B zones of the Clarke error grid. These findings provide baseline data for further device development and a larger clinical efficacy and acceptability study of this microneedle intradermal glucose sensor in T1D.
Rawson T, o'hare D, Herrero P, et al., 2018, Delivering precision antimicrobial therapy through closed-loop control systems, Journal of Antimicrobial Chemotherapy, Vol: 73, Pages: 835-843, ISSN: 0305-7453
Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.
Singh M, Nabavi E, Zhou Y, et al., 2018, Fluorescence image-guided photothermal therapy: Diagnosis and treatment of upper gastrointestinal cancer and beyond (prize winner), Global Surgery
Cass AEG, Hill HAO, 2018, Nuclear magnetic resonance spectroscopy of copper proteins, Copper Proteins and Copper Enzymes, Pages: 63-91, ISBN: 9781315891804
Of all the techniques currently used to study macromolecules in solution, only nuclear magnetic resonance (NMR) spectroscopy has the power to reveal details of molecular structure and motion at atomic resolution.1–5Though the complexity of the spectra of most molecules of interest makes it difficult to express this power and capitalize on the information provided, recent advances in spectrometer design and data manipulation have considerably extended its range of fruitful applications. Compare, e.g., an early (about 1975) 1H NMR spectrum of azurin with one obtained recently (Figure 1) in which the increased resolution and signal-to-noise ratio are only two of the improved features apparent. Many other advances will be revealed in examples considered in detail later in this chapter. First, we provide a brief description of the object of our spectroscopic attentions and the salient features of the technique for those unfortunate to have not yet made its acquaintance.
Sze JYY, Ivanov AP, Cass AEG, et al., 2017, Single molecule multiplexed nanopore protein screening in human serum using aptamer modified DNA carriers, Nature Communications, Vol: 8, Pages: 1-10, ISSN: 2041-1723
The capability to screen a range of proteins at the single-molecule level with enhanced selectivity in biological fluids has been in part a driving force in developing future diagnostic and therapeutic strategies. The combination of nanopore sensing and nucleic acid aptamer recognition comes close to this ideal due to the ease of multiplexing, without the need for expensive labelling methods or extensive sample pre-treatment. Here, we demonstrate a fully flexible, scalable and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific sequences along the backbone of a double-stranded DNA carrier. Protein bound to the aptamer produces unique ionic current signatures which facilitates accurate target recognition. This powerful approach allows us to differentiate individual protein sizes via characteristic changes in the sub-peak current. Furthermore, we show that by using DNA carriers it is possible to perform single-molecule screening in human serum at ultra-low protein concentrations.
Harris-Birtill D, Singh M, Zhou Y, et al., 2017, Gold nanorod reshaping in vitro and in vivo using a continuous wave laser., PLoS ONE, Vol: 12, ISSN: 1932-6203
Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorpt
Rawson TM, Sharma S, Georgiou P, et al., 2017, Towards a minimally invasive device for beta-lactam monitoring in humans, Electrochemistry Communications, Vol: 82, Pages: 1-5, ISSN: 1388-2481
Antimicrobial resistance is a leading patient safety issue. There is a need to develop novel mechanisms for monitoring and subsequently improving the precision of how we use antibiotics. A surface modified microneedle array was developed for monitoring beta-lactam antibiotic levels in human interstitial fluid. The sensor was fabricated by anodically electrodepositing iridium oxide (AEIROF) onto a platinum surface on the microneedle followed by fixation of beta-lactamase enzyme within a hydrogel. Calibration of the sensor was performed to penicillin-G in buffer solution (PBS) and artificial interstitial fluid (ISF). Further calibration of a platinum disc electrode was undertaken using amoxicillin and ceftriaxone. Open-circuit potentials were performed and data analysed using the Hill equation and log(concentration [M]) plots. The microneedle sensor demonstrated high reproducibility between penicillin-G runs in PBS with mean Km (± 1SD) = 0.0044 ± 0.0013 M and mean slope function of log(concentration plots) 29 ± 1.80 mV/decade (r2 = 0.933). Response was reproducible after 28 days storage at 4 °C. In artificial ISF, the sensors response was Km (± 1SD) = 0.0077 ± 0.0187 M and a slope function of 34 ± 1.85 mv/decade (r2 = 0.995). Our results suggest that microneedle array based beta-lactam sensing may be a future application of this AEIROF based enzymatic sensor.
Sharma S, Takagi E, Cass T, et al., 2017, Minimally invasive microneedle array electrodes employing direct electron transfer type glucose dehydrogenase for the development of continuous glucose monitoring sensors, BIOSENSORS 2016, Vol: 27, Pages: 208-209, ISSN: 2212-0173
Le T, Chang P, Benton DJ, et al., 2017, Dual recognition element lateral flow assay (DRELFA) towards multiplex strain-specific influenza virus detection, Analytical Chemistry, Vol: 89, Pages: 6781-6786, ISSN: 1520-6882
Different influenza virus strains have caused a number of recent outbreaks killing scores of people and causing significant losses in animal farming. Simple, rapid, sensitive, and specific detection of particular strains, such as a pandemic strain versus a previous seasonal influenza, plays a crucial role in the monitoring, controlling, and management of outbreaks. In this paper we describe a dual recognition element lateral flow assay (DRELFA) which pairs a nucleic acid aptamer with an antibody for use as a point-of-care platform which can detect particular strains of interest. The combination is used to overcome the individual limitations of antibodies’ cross-reactivity and aptamers’ slow binding kinetics. In the detection of influenza viruses, we show that DRELFA can discriminate a particular virus strain against others of the same subtype or common respiratory diseases while still exhibiting fast binding kinetic of the antibody-based lateral flow assay (LFA). The improvement in specificity that DRELFA exhibits is an advantage over the currently available antibody-based LFA systems for influenza viruses, which offer discrimination between influenza virus types and subtypes. Using quantitative real-time PCR (qRT-PCR), it showed that the DRELFA is very effective in localizing the analyte to the test line (consistently over 90%) and this is crucial for the sensitivity of the device. In addition, color intensities of the test lines showed a good correlation between the DRELFA and the qRT-PCR over a 50-fold concentration range. Finally, lateral flow strips with a streptavidin capture test line and an anti-antibody control line are universally applicable to specific detection of a wide range of different analytes.
Sharma S, Cass AEG, 2017, Microneedle Enzyme Sensor Arrays for Continuous In Vivo Monitoring, Methods in Enzymology, Pages: 414-426, ISSN: 0076-6879
Microneedle enzyme sensors by virtue of their minimally invasive and hence pain-free penetration of skin allow for the measurement of metabolites, biomarkers, and drugs in the interstitial fluid that bathes the dermal tissue. Such devices if they are to be adopted widely into clinical practice need to be capable of delivering reliable measurements over extended periods of time (days) and to be fabricated by low-cost, scalable methods. Using injection molding of the base structures in polycarbonate, metal film deposition by sputtering and enzyme immobilization by electrodeposition can meet these requirements. The workflow to produce devices for clinical evaluation is then completed by sterilization and packaging. In vitro evaluation of the sensors' response to varying analyte concentrations and their mechanical testing establish performance and safety characteristics. While most of the work is focused on glucose sensing, reflecting the significance of the global diabetes "epidemic," the microneedles can also be used to measure lactate (another metabolite) and theophylline (a therapeutic drug).
Sharma S, Huang Z, Rogers M, et al., 2016, Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring, Analytical and Bioanalytical Chemistry, Vol: 408, Pages: 8427-8435, ISSN: 1618-2650
We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T90) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3–6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these.
Sharma S, Saeed A, Johnson C, et al., 2016, Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring, Sensing and Bio-Sensing Research, Vol: 13, Pages: 104-108, ISSN: 2214-1804
The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective.We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases.
Badve SV, Palmer SC, Strippoli GFM, et al., 2016, The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and Meta-analysis., Am J Kidney Dis, Vol: 68, Pages: 554-563
BACKGROUND: Left ventricular mass (LVM) is a widely used surrogate end point in randomized trials involving people with chronic kidney disease (CKD) because treatment-induced LVM reductions are assumed to lower cardiovascular risk. The aim of this study was to assess the validity of LVM as a surrogate end point for all-cause and cardiovascular mortality in CKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Participants with any stages of CKD. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials with 3 or more months' follow-up that reported LVM data. INTERVENTION: Any pharmacologic or nonpharmacologic intervention. OUTCOMES: The surrogate outcome of interest was LVM change from baseline to last measurement, and clinical outcomes of interest were all-cause and cardiovascular mortality. Standardized mean differences (SMDs) of LVM change and relative risk for mortality were estimated using pairwise random-effects meta-analysis. Correlations between surrogate and clinical outcomes were summarized across all interventions combined using bivariate random-effects Bayesian models, and 95% credible intervals were computed. RESULTS: 73 trials (6,732 participants) covering 25 intervention classes were included in the meta-analysis. Overall, risk of bias was uncertain or high. Only 3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials; SMD, -0.13; 95% CI, -0.23 to -0.03), renin-angiotensin-aldosterone system inhibitors (13 trials; SMD, -0.28; 95% CI, -0.45 to -0.12), and isosorbide mononitrate (2 trials; SMD, -0.43; 95% CI, -0.72 to -0.14). All interventions had uncertain effects on all-cause and cardiovascular mortality. There were weak and imprecise associations between the effects of interventions on LVM change and all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95% credible interval, -0.13 to 0.59) and cardiovascular mortality (13 trials; 2,32
Maple-Brown LJ, Hughes JT, Ritte R, et al., 2016, Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study., Clin J Am Soc Nephrol, Vol: 11, Pages: 993-1004
BACKGROUND AND OBJECTIVES: Indigenous Australians experience a heavy burden of CKD. To address this burden, the eGFR Follow-Up Study recruited and followed an Indigenous Australian cohort from regions of Australia with the greatest ESRD burden. We sought to better understand factors contributing to the progression of kidney disease. Specific objectives were to assess rates of progression of eGFR in Indigenous Australians with and without CKD and identify factors associated with a decline in eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational longitudinal study of Indigenous Australian adults was conducted in >20 sites. The baseline cohort was recruited from community and primary care clinic sites across five strata of health, diabetes status, and kidney function. Participants were then invited to follow up at 2-4 years; if unavailable, vital status, progression to RRT, and serum creatinine were obtained from medical records. Primary outcomes were annual eGFR change and combined renal outcome (first of ≥30% eGFR decline with follow-up eGFR<60 ml/min per 1.73 m(2), progression to RRT, or renal death). RESULTS: Participants (n=550) were followed for a median of 3.0 years. Baseline and follow-up eGFR (geometric mean [95% confidence interval], 83.9 (80.7 to 87.3) and 70.1 (65.9 to 74.5) ml/min per 1.73 m(2), respectively. Overall mean annual eGFR change was -3.1 (-3.6 to -2.5) ml/min per 1.73 m(2). Stratified by baseline eGFR (≥90, 60-89, <60 ml/min per 1.73 m(2)), annual eGFR changes were -3.0 (-3.6 to -2.4), -1.9 (-3.3 to -0.5), and -5.0 (-6.5 to -3.6) ml/min per 1.73 m(2). Across baseline eGFR categories, annual eGFR decline was greatest among adults with baseline albumin-to-creatinine ratio (ACR) >265 mg/g (30 mg/mmol). Baseline determinants of the combined renal outcome (experienced by 66 participants) were higher urine ACR, diabetes, lower measured GFR, and higher C-reactive protein. CONCLUSIONS: The observed eGFR decline w
Roberts MA, Pilmore HL, Ierino FL, et al., 2016, The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) Feasibility Study: A Randomized Controlled Trial., Am J Kidney Dis, Vol: 67, Pages: 902-911
BACKGROUND: β-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT). STUDY DESIGN: Pilot RCT. SETTING & PARTICIPANTS: Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants. INTERVENTION: After a 6-week run-in with the β-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months. OUTCOMES & MEASUREMENTS: The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH). RESULTS: Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P=0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P=0.7). LIMITATIONS: Unable to recruit planned sample size. CONCLUSIONS: Recruiting patients receiving dialysis to an RCT of β-blocker versus placebo will prove challenging. Possible solutions include international collaboratio
Singh M, Nabavi E, Zhou Y, et al., 2016, Application of Gold Nanorods in Cancer Theranostics (plenary presentation winner), Society for Surgery of the Alimentary Tract Annual Meeting, 31st Annual SSAT Residents and Fellows Research Conference
Elson DS, Singh M, Nabavi E, et al., 2016, Application of Gold Nanorods in Cancer Theranostics, Association of Surgeons in Training
Singh M, Harris-Birtill DCC, Zhou Y, et al., 2016, Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma, Journal of Biomedical Nanotechnology, Vol: 12, Pages: 481-490, ISSN: 1550-7041
Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 × 1010 GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 °C was observed in tissues incubated with GNRs, whereas only a modest 2 °C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs.
Nabavi E, Singh M, Zhou Y, et al., 2016, Preliminary studies of fluorescence image-guided photothermal therapy of human oesophageal adenocarcinoma in vivo using multifunctional gold nanorods, Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXV, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
We present a preliminary in vivo study of fluorescence imaging and photothermal therapy (PTT) of human oesophageal adenocarcinoma using multi-functionalised gold nanorods (GNRs). After establishing tumour xenograft in mouse functionalised GNRs were administrated intravenously (IV). Fluorescence imaging was performed to detect the tumour area. The intensity of the fluorescence signal varied significantly across the tumour site and surrounding tissues. PTT was then performed using a 808 nm continuous wave diode laser to irradiate the tumour for 3 minutes, inducing a temperature rise of ~44°C, which photothermally ablated the tumour.
Sharma S, El-Laboudi A, Oliver N, et al., 2016, Chemical cross talk studies on a microprobe array based continuous glucose monitoring sensor, ATTD 2016, Publisher: Mary Ann Liebert, ISSN: 1557-8593
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