Spin-enhanced nanodiamond biosensing for ultrasensitive diagnostics.

The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.

Probabilistic modelling of prospective environmental concentrations of gold nanoparticles from medical applications as a basis for risk assessment.

BACKGROUND: The use of gold nanoparticles (Au-NP) based medical applications is rising due to their unique physical and chemical properties. Diagnostic devices based on Au-NP are already available in the market or are in clinical trials and Au-NP based therapeutics and theranostics (combined diagnostic and treatment modality) are in the research and development phase. Currently, no information on Au-NP consumption, material flows to and concentrations in the environment are available. Therefore, we estimated prospective maximal consumption of Au-NP from medical applications in the UK and US. We then modelled the Au-NP flows post-use and predicted their environmental concentrations. Furthermore, we assessed the environment risks of Au-NP by comparing the predicted environmental concentrations (PECs) with ecological threshold (PNEC) values. RESULTS: The mean annual estimated consumption of Au-NP from medical applications is 540 kg for the UK and 2700 kg for the US. Among the modelled concentrations of Au-NP in environmental compartments, the mean annual PEC of Au-NP in sludge for both the UK and US was estimated at 124 and 145 µg kg(-1), respectively. The mean PEC in surface water was estimated at 468 and 4.7 pg L(-1), respectively for the UK and US. The NOEC value for the water compartment ranged from 0.12 up to 26,800 µg L(-1), with most values in the range of 1000 µg L(-1). CONCLUSION: The results using the current set of data indicate that the environmental risk from Au-NP used in nanomedicine in surface waters and from agricultural use of biosolids is minimal in the near future, especially because we have used a worst-case use assessment. More Au-NP toxicity studies are needed for the soil compartment.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Nanoparticle augmented radiation treatment decreases cancer cell proliferation.

We report significant and controlled cell death using novel x-ray-activatable titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of such materials into tumor tissue can enhance the effect of radiation therapy. Herein, the incorporation of gadolinium into the NPs is designed to optimize localized energy absorption from a conventional medical x-ray. This result is further optimized by the addition of other rare earth elements. Upon irradiation, energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species (ROS). FROM THE CLINICAL EDITOR: The authors report significant and controlled cell death using x-ray-activated titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species.

Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis.

Cellular microvesicles and nanovesicles (exosomes) are involved in many disease processes and have major potential as biomarkers. However, developments in this area are constrained by limitations in the technology available for their measurement. Here we report on the use of fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles. In this system vesicles are visualized by light scattering using a light microscope. A video is taken, and the NTA software tracks the brownian motion of individual vesicles and calculates their size and total concentration. Using human placental vesicles and plasma, we have demonstrated that NTA can measure cellular vesicles as small as ≈ 50 nm and is far more sensitive than conventional flow cytometry (lower limit ≈ 300 nm). By combining NTA with fluorescence measurement we have demonstrated that vesicles can be labeled with specific antibody-conjugated quantum dots, allowing their phenotype to be determined. FROM THE CLINICAL EDITOR: The authors of this study utilized fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles, demonstrating that NTA is far more sensitive than conventional flow cytometry.

Development of an in-line magnetometer for flow chemistry and its demonstration for magnetic nanoparticle synthesis.

Despite the wide usage of magnetic nanoparticles, it remains challenging to synthesise particles with properties that exploit each application's full potential. Time consuming experimental procedures and particle analysis hinder process development, which is commonly constrained to a handful of experiments without considering particle formation kinetics, reproducibility and scalability. Flow reactors are known for their potential of large-scale production and high-throughput screening of process parameters. These advantages, however, have not been utilised for magnetic nanoparticle synthesis where particle characterisation is performed, with a few exceptions, post-synthesis. To overcome this bottleneck, we developed a highly sensitive magnetometer for flow reactors to characterise magnetic nanoparticles in solution in-line and in real-time using alternating current susceptometry. This flow magnetometer enriches the flow-chemistry toolbox by facilitating continuous quality control and high-throughput screening of magnetic nanoparticle syntheses. The sensitivity required to monitor magnetic nanoparticle syntheses at the typically low concentrations (<100 mM of Fe) was achieved by comparing the signals induced in the sample and reference cell, each of which contained near-identical pairs of induction and pick-up coils. The reference cell was filled only with air, whereas the sample cell was a flow cell allowing sample solution to pass through. Balancing the flow and reference cell impedance with a newly developed electronic circuit was pivotal for the magnetometer's sensitivity. To showcase its potential, the flow magnetometer was used to monitor two iron oxide nanoparticle syntheses with well-known particle formation kinetics, i.e., co-precipitation syntheses with sodium carbonate and sodium hydroxide as base, which have been previously studied via synchrotron X-ray diffraction. The flow magnetometer facilitated batch (on-line) and flow (in-line) synthesis monitoring, providing new insights into the particle formation kinetics as well as, effect of temperature and pH. The compact lab-scale flow device presented here, opens up new possibilities for magnetic nanoparticle synthesis and manufacturing, including 1) early stage reaction characterisation 2) process monitoring and control and 3) high-throughput screening in combination with flow reactors.

Reintervention after mobile-bearing Oxford unicompartmental knee arthroplasty.

BACKGROUND: Medial compartment osteoarthritis is a common disorder that often is treated by unicompartmental knee arthroplasty (UKA). Although the Oxford 3 prosthesis is commonly used based on revision rate and cumulative survival, our experience suggests that although there may be adequate implant survival rates, we observed a worrisome and undisclosed reintervention rate of nonrevision procedures. PURPOSE: We describe the frequency and cause of repeat intervention subsequent to implanting this device. METHODS: Between 1998 and 2005, 398 patients underwent UKA using the Oxford 3 prosthesis. The minimum followup was 12 months (mean, 43 months; range, 12-102 months). RESULTS: Forty of the 398 (10%) patients had 55 (13.8%) repeat anesthetics (reintervention). There were 38 nonrevision reinterventions. Revision was performed in 15 patients (3.8%), but two patients had a second revision (17 revisions or 4.3%). We revised the UKA to a second UKA in seven of the 15 cases but two subsequently were rerevised to a TKA; eight were revised directly to a TKA. CONCLUSIONS: Although our data confirm the reported revision rates for this prosthesis, we observed a substantial reintervention rate. Most of the reinterventions are minor and are diagnosed frequently and treated arthroscopically. If revision is required, a second UKA may be considered and performed successfully in patients with isolated loosening of one component. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Tibial interference screw fixation in anterior cruciate ligament reconstruction with and without autograft bone augmentation.

PURPOSE: Because tibial fixation of soft-tissue grafts in anterior cruciate ligament (ACL) reconstruction is problematic, this study aimed to develop a means of delivering bone graft evenly around tendon autograft and define any mechanical, radiologic, or histologic benefit using an ovine model. METHODS: A device to deliver bone graft evenly throughout the tibial tunnel was developed. Forty mature sheep underwent simulated quadruple hamstring tendon-ACL reconstruction by use of a bioresorbable interference screw, either with or without bone graft augmentation of the tibial tunnel. Endpoint data were derived at time 0 and after 6 weeks in vivo. Radiostereometric analysis provided quantitation of the translational characteristics; computed tomography evaluated tunnel volume, and measures of yield strength and stiffness were obtained. Sequential fluorochrome administration assessed bone formation, and light microscopy surveyed the biological response. RESULTS: Radiostereometric analysis highlighted differences in the translational characteristics of ACL-deficient knees when compared with intact knees. Reconstructed knees (with or without autograft) showed significantly greater translation when compared with unoperated knees at 6 weeks; autograft bone augmentation provided no benefit. Neither tunnel volume nor yield strength nor stiffness was improved with the addition of autograft bone. No untoward histologic responses were observed. Bone apposition rates were similar between treatment groups. An even distribution of bone graft throughout the tunnels was observed. CONCLUSIONS: This model has confirmed the ability of the bone graft-delivery system to evenly distribute bone graft throughout the tunnels. However, the study has failed to show improvement in stability or fixation strength after augmentation with autograft bone. CLINICAL RELEVANCE: The autograft bone-delivery system may provide a means of establishing an osteoconductive/inductive environment. At this early juncture (6 weeks), no benefit could be defined. Its use in combination with bone morphogenetic proteins or stem cells may provide more rapid fixation, rehabilitation, and reconstitution of bone volume within the tunnel.

Decarbonising energy: The developing international activity in hydrogen technologies and fuel cells.

Hydrogen technologies and fuel cells offer an alternative and improved solution for a decarbonised energy future. Fuel cells are electrochemical converters; transforming hydrogen (or energy sources containing hydrogen) and oxygen directly into electricity. The hydrogen fuel cell, invented in 1839, permits the generation of electrical energy with high efficiency through a non-combustion, electrochemical process and, importantly, without the emission of CO2 at its point of use. Hitherto, despite numerous efforts to exploit the obvious attractions of hydrogen technologies and hydrogen fuel cells, various challenges have been encountered, some of which are reviewed here. Now, however, given the exigent need to urgently seek low-carbon paths for humankind's energy future, numerous countries are advancing the deployment of hydrogen technologies and hydrogen fuel cells not only for transport, but also as a means of the storage of excess renewable energy from, for example, wind and solar farms. Furthermore, hydrogen is also being blended into the natural gas supplies used in domestic heating and targeted in the decarbonisation of critical, large-scale industrial processes such as steel making. We briefly review specific examples in countries such as Japan, South Korea and the People's Republic of China, as well as selected examples from Europe and North America in the utilization of hydrogen technologies and hydrogen fuel cells.

Transforming carbon dioxide into jet fuel using an organic combustion-synthesized Fe-Mn-K catalyst.

With mounting concerns over climate change, the utilisation or conversion of carbon dioxide into sustainable, synthetic hydrocarbons fuels, most notably for transportation purposes, continues to attract worldwide interest. This is particularly true in the search for sustainable or renewable aviation fuels. These offer considerable potential since, instead of consuming fossil crude oil, the fuels are produced from carbon dioxide using sustainable renewable hydrogen and energy. We report here a synthetic protocol to the fixation of carbon dioxide by converting it directly into aviation jet fuel using novel, inexpensive iron-based catalysts. We prepare the Fe-Mn-K catalyst by the so-called Organic Combustion Method, and the catalyst shows a carbon dioxide conversion through hydrogenation to hydrocarbons in the aviation jet fuel range of 38.2%, with a yield of 17.2%, and a selectivity of 47.8%, and with an attendant low carbon monoxide (5.6%) and methane selectivity (10.4%). The conversion reaction also produces light olefins ethylene, propylene, and butenes, totalling a yield of 8.7%, which are important raw materials for the petrochemical industry and are presently also only obtained from fossil crude oil. As this carbon dioxide is extracted from air, and re-emitted from jet fuels when combusted in flight, the overall effect is a carbon-neutral fuel. This contrasts with jet fuels produced from hydrocarbon fossil sources where the combustion process unlocks the fossil carbon and places it into the atmosphere, in longevity, as aerial carbon - carbon dioxide.

A one-step aqueous synthetic route to extremely small CdSe nanoparticles.

By employing Na2Se as a selenium source, we demonstrate that extremely small ( approximately 1 nm) mercapto acid-stabilized CdSe nanoparticles can be conveniently prepared in water. The as-prepared nanoparticles start to show dominant near band-gap photoluminescence in the blue spectral range and show high photoluminescence in the green spectral range.

Internet-based knowledge management database for children and adults with epilepsy: a possible model project for evidence-based medicine in the future.

With an incidence of nearly 1%, epilepsy represents one of the most frequent diseases in the population. Nevertheless substantial information gaps exist as to the exact incidence, prevalence, therapy and particularly to associated therapeutic success. Adequate studies are not performed on many of these issues which are primarily beyond the current interests of the pharmaceutical industry. An Internet-based knowledge management database is presented to illustrate initial results of the online system with a focus on medication and side effects (http://www.ligaepilepsie.org/KnowledgeDB/index.htm). Further, it is worth noting that this database was designed as a potential model for similar projects in other medical fields.

Patient-perceived outcomes and return to sport and work: TKA versus mini-incision unicompartmental knee arthroplasty.

Few reports have been published about patient-perceived outcomes and return to sport following total knee arthroplasty (TKA) compared with unicompartmental knee arthroplasty (UKA). This article compares the two procedures using self-assessment questionnaires to determine whether there was a difference in patient-perceived Oxford scores, return to sport, and return to work. Patient-perceived outcomes of mini-incision UKA (Oxford; Biomet Inc, Warsaw, Ind) and TKA were retrospectively reviewed at a minimum of 12 months after surgery. A total of 150 patients underwent 183 UKAs (mean age: 71.5 years; standard deviation [SD]: 9.85) and 120 patients underwent 142 TKAs (mean age: 71.53 years; SD: 9.87). Oxford knee questionnaires were used assessing modified Grimby score, sports, and work activities. Mean Oxford knee score (22.17; SD: 9.03) for UKA was superior to TKA (24.5; SD: 9.68) (P=.04) scores. Mean modified Grimby score for UKA (3.89; SD:1.27) was superior to TKA (2.76; SD:1.12) (P<.0001). More patients returned to or increased sports following UKA (P=.0003), but no sooner than TKA patients. Patient-perceived Oxford and modified Grimby scores were better and sporting activity was greater following mini-incision UKA compared to TKA.

Hydrophobin-Encapsulated Quantum Dots.

The phase transfer of quantum dots to water is an important aspect of preparing nanomaterials that are suitable for biological applications, and although numerous reports describe ligand exchange, very few describe efficient ligand encapsulation techniques. In this report, we not only report a new method of phase transferring quantum dots (QDs) using an amphiphilic protein (hydrophobin) but also describe the advantages of using a biological molecule with available functional groups and their use in imaging cancer cells in vivo and other imaging applications.

Effect of total knee arthroplasty on recreational and sporting activity.

BACKGROUND: Common concerns of patients undergoing total knee arthroplasty (TKA) are whether they can continue with certain recreational and sporting activities or even commence new ones after the procedure. The present study was designed to determine preoperative and postoperative activities, the numbers participating and the time to resume these activities. METHODS: Between 1 and 2 years after TKA, patients who had undergone 144 arthroplasties, were surveyed by postal questionnaire to ascertain how the arthroplasty had affected their recreational and sporting ability. Their preoperative and postoperative activity along with the time to resume was recorded. The Oxford knee score and estimate of physical activity was also collected. RESULTS: Out of the 144 TKA performed, 122 participated in sport and recreational activity preoperatively and 108 participated postoperatively. Patients stated that the surgery had a beneficial effect on their performance of sporting and recreational activities although the number of sporting events decreased. By multiplying individuals by the number of activities they participated in, there were 254 occurrences of sport and recreational activities preoperatively giving a mean for the group of 1.76 sports/patient. Postoperatively this had reduced to 204, giving a mean of 1.41. Three activities showed a significant change for individual patients from pre- to postoperation. Those which showed an increase were exercise walking, where 19 patients (13.2%) who did not walk before surgery took up walking afterwards (P < 0.006) and aqua aerobics, where five took up aqua aerobics postoperatively for the first time (P < 0.025). Golf was the only sport which had a significant fall in participation from pre- to postoperation, with 10 out of 19 golfers giving up (P < 0.025). CONCLUSION: The present study has shown that patients are adopting lower impact activities to participate in after TKA. The total number of patients performing a sport decreases postoperatively and the total amount of sport played decreases. These data will help to counsel patients.

The effect of screw taper on interference fit during load to failure at the soft tissue/bone interface.

The effect of screw geometry on the pullout strength of an anterior cruciate ligament reconstruction is well documented. The effect of a truly tapered screw has not been previously investigated. Thirty bovine knees in right and left knee pairs were collected. Superficial digital flexors from the hind legs of sheep were harvested to form a quadruple tendon graft. For each knee pair, one tendon graft was fixed using a tapered screw (n=15) and the other with a non-tapered screw (n=15). Interference screws were manufactured from stainless steel, and apart from the tapered or non-tapered profile were identical. The screws were inserted into a tibial tunnel already containing the tendon graft. The interference fit was tested by extensile load to failure tests. The insertion torque of the screws and first sign of load to failure (by pullout) of the interference fit were recorded. Results were analysed using paired t-tests. The results indicated that tapered screws have significantly higher resistance to interference failure (p=0.007) and insertion torque (p<0.001) than non-tapered screws. The improved biomechanical performance of tapered screws demonstrated in this study may translate into superior clinical results, particularly at the tibial attachment of hamstring anterior cruciate ligament reconstruction, and also of hamstring fixation to the medial femoral condyle for patella instability.

Effect of total hip arthroplasty on recreational and sporting activity.

BACKGROUND: Common concerns of patients undergoing total hip arthroplasty are whether they can continue with certain recreational and sporting activities or even commence new ones after the procedure. The present paper describes preoperative and postoperative activities, the numbers participating and the time to resume these activities. METHODS: Between 1 and 2 years after total hip arthroplasty, 216 patients, who had undergone a total of 235 arthroplasties, were surveyed by postal questionnaire to ascertain how the arthroplasty had affected their recreational and sporting ability. Their preoperative and postoperative activity along with the time to resume was recorded. A general hip score and estimate of physical activity was also collected. RESULTS: The number of patients participating in sport increased from 188 preoperatively to 196 postoperatively. Patients stated that the surgery had a beneficial effect on their performance of sporting activities although the number of sporting events decreased. By multiplying individuals by the number of sports they participated in, there were 434 occurrences of sport preoperatively giving a mean for the group of 1.9 sports per patient. Postoperatively this had reduced to 382, giving a mean of 1.7. Five sports showed a significant change for individual patients from pre to postoperation. Those which showed an increase were exercise walking, where 38 patients (16.8%) who did not walk before surgery took up walking afterwards (P < 0.0001) and aqua aerobics, where 15 took up this activity postoperatively for the first time (P = 0.002). There were three sports which decreased significantly from pre to postoperation. They were, golf where 13 out of 39 (P = 0.005), tennis 13 out of 14 (P = 0.01) and jogging where six out of seven (P = 0.01) patients stopped participating. CONCLUSION: This study has shown that patients are adopting lower impact activities to participate in after total hip arthroplasty. The total number of patients performing a sport increases postoperatively but the total amount of sport played decreases. These data will help to counsel patients.

Potential environmental implications of nano-enabled medical applications: critical review.

The application of nanotechnology and nanoscience for medical purposes is anticipated to make significant contributions to enhance human health in the coming decades. However, the possible future mass production and use of these medical innovations exhibiting novel and multifunctional properties will very likely lead to discharges into the environment giving rise to potentially new environmental hazards and risks. To date, the sources, the release form and environmental fate and exposure of nano-enabled medical products have not been investigated and little or no data exists, although there are a small number of currently approved medical applications and a number in clinical trials. This paper discusses the current technological and regulatory landscape and potential hazards and risks to the environment of nano-enabled medical products, data gaps and gives tentative suggestions relating to possible environmental hotspots.

Synthesis of semiconductor nanoparticles.

Here, we describe typical methods and provide detailed experimental protocols for synthesizing and processing various semiconductor nanoparticles which have potential application in biology and medicine. These include synthesis of binary semiconductor nanoparticles; core@shell nanoparticles and alloyed nanoparticles; size-selective precipitation to obtain monodisperse nanoparticles; and strategies for phase transfer of nanoparticles from organic solution to aqueous media.