Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

High efficiency quantum dot-sensitised solar cells by material science and device architecture

This thesis studied cadmium sulfide and cadmium selenide quantum dots and their performance as light absorbers in quantum dot-sensitised solar cells. This research has made contributions to the understanding of size dependent photodegradation, passivation and particle growth mechanism of cadmium sulfide quantum dots using SILAR method and the role of ZnSe shell coatings on solar cell performance improvement.

One step closer into the design of fall protective device for individuals fitted with a bone-anchored prosthesis

The consequences of falls are often dreadful for individuals with lower limb amputation using bone-anchored prosthesis.[1-5] Typically, the impact on the fixation is responsible for bending the intercutaneous piece that could lead to a complete breakage over time. .[3, 5-8] The surgical replacement of this piece is possible but complex and expensive. Clearly, there is a need for solid data enabling an evidence-based design of protective devices limiting impact forces and torsion applied during a fall. The impact on the fixation during an actual fall is obviously difficult to record during a scientific experiment.[6, 8-13] Consequently, Schwartze and colleagues opted for one of the next best options science has to offer: simulation with an able-bodied participant. They recorded body movements and knee impacts on the floor while mimicking several plausible falling scenarios. Then, they calculated the forces and moments that would be applied at four levels along the femur corresponding to amputation heights.[6, 8-11, 14-25] The overall forces applied during the falls were similar regardless of the amputation height indicating that the impact forces were simply translated along the femur. As expected, they showed that overall moments generally increased with amputation height due to changes in lever arm. This work demonstrates that devices preventing only against force overload do not require considering amputation height while those protecting against bending moments should. Another significant contribution is to provide, for the time, the magnitude of the impact load during different falls. This loading range is crucial to the overall design and, more precisely, the triggering threshold of protective devices. Unfortunately, the analysis of only a single able-bodied participant replicating falls limits greatly the generalisation of the findings. Nonetheless, this case study is an important milestone contributing to a better understanding of load impact during a fall. This new knowledge will improve the treatment, the safe ambulation and, ultimately, the quality of life of individuals fitted with bone-anchored prosthesis.

Initial design and physical characterization of a polymeric device for osmosis-driven delayed burst delivery of vaccines

Achieving the combination of delayed and immediate release of a vaccine from a delivery device without applying external triggers remains elusive in implementing single administration vaccination strategies. Here a means of vaccine delivery is presented, which exploits osmosis to trigger delayed burst release of an active compound. Poly(-caprolactone) capsules of 2 mm diameter were prepared by dip-coating, and their burst pressure and release characteristics were evaluated. Burst pressures (in bar) increased with wall thickness (t in mm) following Pburst = 131.t + 3.4 (R2 = 0.93). Upon immersion in PBS, glucose solution-filled capsules burst after 8.7 ± 2.9 days. Copolymers of hydrophobic  -caprolactone and hydrophilic polyethylene glycol were synthesized and their physico-chemical properties were assessed. With increasing hydrophilic content, the copolymer capsules showed increased water uptake rates and maximum weight increase, while the burst release was earlier: 5.6 ± 2.0 days and 1.9 ± 0.2 days for 5 and 10 wt% polyethylene glycol, respectively. The presented approach enables the reproducible preparation of capsules with high versatility in materials and properties, while these vaccine delivery vehicles can be prepared separately from, and independently of the active compound.

Turbulence and Mixing in the Environment: Multi-Device Study in a Sub-tropical Estuary

In an estuary, mixing and dispersion result from a combination of large-scale advection and smallscale turbulence, which are complex to estimate. The predictions of scalar transport and mixing are often inferred and rarely accurate, due to inadequate understanding of the contributions of these difference scales to estuarine recirculation. A multi-device field study was conducted in a small sub-tropical estuary under neap tide conditions with near-zero fresh water discharge for about 48 hours. During the study, acoustic Doppler velocimeters (ADV) were sampled at high frequency (50 Hz), while an acoustic Doppler current profiler (ADCP) and global positioning system (GPS) tracked drifters were used to obtain some lower frequency spatial distribution of the flow parameters within the estuary. The velocity measurements were complemented with some continuous measurement of water depth, conductivity, temperature and some other physiochemical parameters. Thorough quality control was carried out by implementation of relevant error removal filters on the individual data set to intercept spurious data. A triple decomposition (TD) technique was introduced to access the contributions of tides, resonance and ‘true’ turbulence in the flow field. The time series of mean flow measurements for both the ADCP and drifter were consistent with those of the mean ADV data when sampled within a similar spatial domain. The tidal scale fluctuation of velocity and water level were used to examine the response of the estuary to tidal inertial current. The channel exhibited a mixed type wave with a typical phase-lag between 0.035π– 0.116π. A striking feature of the ADV velocity data was the slow fluctuations, which exhibited large amplitudes of up to 50% of the tidal amplitude, particularly in slack waters. Such slow fluctuations were simultaneously observed in a number of physiochemical properties of the channel. The ensuing turbulence field showed some degree of anisotropy. For all ADV units, the horizontal turbulence ratio ranged between 0.4 and 0.9, and decreased towards the bed, while the vertical turbulence ratio was on average unity at z = 0.32 m and approximately 0.5 for the upper ADV (z = 0.55 m). The result of the statistical analysis suggested that the ebb phase turbulence field was dominated by eddies that evolved from ejection type process, while that of the flood phase contained mixed eddies with significant amount related to sweep type process. Over 65% of the skewness values fell within the range expected of a finite Gaussian distribution and the bulk of the excess kurtosis values (over 70%) fell within the range of -0.5 and +2. The TD technique described herein allowed the characterisation of a broader temporal scale of fluctuations of the high frequency data sampled within the durations of a few tidal cycles. The study provides characterisation of the ranges of fluctuation required for an accurate modelling of shallow water dispersion and mixing in a sub-tropical estuary.

Spine curvature analysis between participants with obesity and normal weight participants: A biplanar electromagnetic device measurement

To analyse and compare standing thoracolumbar curves in normal weight participants and participants with obesity, using an electromagnetic device, and to analyse the measurement reliability. Material and Methods. Cross-sectional study was carried out. 36 individuals were divided into two groups (normal-weight and participants with obesity) according to their waist circumference. The reference points (T1–T8–L1–L5 and both posterior superior iliac spines) were used to perform a description of thoracolumbar curvature in the sagittal and coronal planes. A transformation from the global coordinate system was performed and thoracolumbar curves were adjusted by fifth-order polynomial equations. The tangents of the first and fifth lumbar vertebrae and the first thoracic vertebra were determined from their derivatives. The reliability of the measurement was assessed according to the internal consistency of the measure and the thoracolumbar curvature angles were compared between groups. Results. Cronbach’s alpha values ranged between 0.824 (95% CI: 0.776–0.847) and 0.918 (95% CI: 0.903–0.949). In the coronal plane, no significant differences were found between groups; however, in sagittal plane, significant differences were observed for thoracic kyphosis. Conclusion. There were significant differences in thoracic kyphosis in the sagittal plane between two groups of young adults grouped according to their waist circumference.

The microwell-mesh: A novel device and protocol for the high throughput manufacturing of cartilage microtissues

Microwell platforms are frequently described for the efficient and uniform manufacture of 3-dimensional (3D) multicellular microtissues. Multiple partial or complete medium exchanges can displace microtissues from discrete microwells, and this can result in either the loss of microtissues from culture, or microtissue amalgamation when displaced microtissues fall into common microwells. Herein we describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells; the microwell-mesh. We show that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells. To demonstrate the utility of this platform, we used the microwell-mesh to manufacture hundreds of cartilage microtissues, each formed from 5 × 10(3) bone marrow-derived mesenchymal stem/stromal cells (MSC). The microwell-mesh enabled reliable microtissue retention over 21-day cultures that included multiple full medium exchanges. Cartilage-like matrix formation was more rapid and homogeneous in microtissues than in conventional large diameter control cartilage pellets formed from 2 × 10(5) MSC each. The microwell-mesh platform offers an elegant mechanism to retain microtissues in microwells, and we believe that this improvement will make this platform useful in 3D culture protocols that require multiple medium exchanges, such as those that mimic specific developmental processes or complex sequential drug exposures.

Intravascular device administration sets: Replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)

Introduction Vascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload. Methods and analysis This is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.

The fossil calibration database - A new resource for divergence dating

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important, and often least appreciated, step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for non-specialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open-access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as one key pipeline for peer-reviewed calibrations to enter the database.

Towards the development of a low cost airborne sensing system to monitor dust particles after blasting at open-pit mine sites

Blasting is an integral part of large-scale open cut mining that often occurs in close proximity to population centers and often results in the emission of particulate material and gases potentially hazardous to health. Current air quality monitoring methods rely on limited numbers of fixed sampling locations to validate a complex fluid environment and collect sufficient data to confirm model effectiveness. This paper describes the development of a methodology to address the need of a more precise approach that is capable of characterizing blasting plumes in near-real time. The integration of the system required the modification and integration of an opto-electrical dust sensor, SHARP GP2Y10, into a small fixed-wing and multi-rotor copter, resulting in the collection of data streamed during flight. The paper also describes the calibration of the optical sensor with an industry grade dust-monitoring device, Dusttrak 8520, demonstrating a high correlation between them, with correlation coefficients (R2) greater than 0.9. The laboratory and field tests demonstrate the feasibility of coupling the sensor with the UAVs. However, further work must be done in the areas of sensor selection and calibration as well as flight planning.

Calibration, estimation, and sampling issues of car-following parameters

Drivers behave in different ways, and these different behaviors are a cause of traffic disturbances. A key objective for simulation tools is to correctly reproduce this variability, in particular for car-following models. From data collection to the sampling of realistic behaviors, a chain of key issues must be addressed. This paper discusses data filtering, robustness of calibration, correlation between parameters, and sampling techniques of acceleration-time continuous car-following models. The robustness of calibration is systematically investigated with an objective function that allows confidence regions around the minimum to be obtained. Then, the correlation between sets of calibrated parameters and the validity of the joint distributions sampling techniques are discussed. This paper confirms the need for adapted calibration and sampling techniques to obtain realistic sets of car-following parameters, which can be used later for simulation purposes.

Microscopic cooperative traffic flow: Calibration and simulation based on a next generation simulation dataset

The deployment of new emerging technologies, such as cooperative systems, allows the traffic community to foresee relevant improvements in terms of traffic safety and efficiency. Autonomous vehicles are able to share information about the local traffic state in real time, which could result in a better reaction to the mechanism of traffic jam formation. An upstream single-hop radio broadcast network can improve the perception of each cooperative driver within a specific radio range and hence the traffic stability. The impact of vehicle to vehicle cooperation on the onset of traffic congestion is investigated analytically and through simulation. A next generation simulation field dataset is used to calibrate the full velocity difference car-following model, and the MOBIL lane-changing model is implemented. The robustness of the calibration as well as the heterogeneity of the drivers is discussed. Assuming that congestion can be triggered either by the heterogeneity of drivers' behaviours or abnormal lane-changing behaviours, the calibrated car-following model is used to assess the impact of a microscopic cooperative law on egoistic lane-changing behaviours. The cooperative law can help reduce and delay traffic congestion and can have a positive effect on safety indicators.

Multifunctional three-dimensional T-junction graphene micro-wells: Energy-efficient, plasma-enabled growth and instant water-based transfer for flexible device applications

The “third-generation” 3D graphene structures, T-junction graphene micro-wells (T-GMWs) are produced on cheap polycrystalline Cu foils in a single-step, low-temperature (270 °C), energy-efficient, and environment-friendly dry plasma-enabled process. T-GMWs comprise vertical graphene (VG) petal-like sheets that seemlessly integrate with each other and the underlying horizontal graphene sheets by forming T-junctions. The microwells have the pico-to-femto-liter storage capacity and precipitate compartmentalized PBS crystals. The T-GMW films are transferred from the Cu substrates, without damage to the both, in de-ionized or tap water, at room temperature, and without commonly used sacrificial materials or hazardous chemicals. The Cu substrates are then re-used to produce similar-quality T-GMWs after a simple plasma conditioning. The isolated T-GMW films are transferred to diverse substrates and devices and show remarkable recovery of their electrical, optical, and hazardous NO2 gas sensing properties upon repeated bending (down to 1 mm radius) and release of flexible trasparent display plastic substrates. The plasma-enabled mechanism of T-GMW isolation in water is proposed and supported by the Cu plasma surface modification analysis. Our GMWs are suitable for various optoelectronic, sesning, energy, and biomedical applications while the growth approach is potentially scalable for future pilot-scale industrial production.