Multiple-time signature schemes against adaptive chosen message attacks

Multiple-time signatures are digital signature schemes where the signer is able to sign a predetermined number of messages. They are interesting cryptographic primitives because they allow to solve many important cryptographic problems, and at the same time offer substantial efficiency advantage over ordinary digital signature schemes like RSA. Multiple-time signature schemes have found numerous applications, in ordinary, on-line/off-line, forward-secure signatures, and multicast/stream authentication. We propose a multiple-time signature scheme with very efficient signing and verifying. Our construction is based on a combination of one-way functions and cover-free families, and it is secure against the adaptive chosen-message attack.

Novel sequential methods in dose-finding designs : extensions of the continual reassessment method

Dose-finding trials are a form of clinical data collection process in which the primary objective is to estimate an optimum dose of an investigational new drug when given to a patient. This thesis develops and explores three novel dose-finding design methodologies. All design methodologies presented in this thesis are pragmatic. They use statistical models, incorporate clinicians' prior knowledge efficiently, and prematurely stop a trial for safety or futility reasons. Designing actual dose-finding trials using these methodologies will minimize practical difficulties, improve efficiency of dose estimation, be flexible to stop early and reduce possible patient discomfort or harm.

Damage evaluation based on a wave energy flow map using multiple PZT sensors

A new wave energy flow (WEF) map concept was proposed in this work. Based on it, an improved technique incorporating the laser scanning method and Betti’s reciprocal theorem was developed to evaluate the shape and size of damage as well as to realize visualization of wave propagation. In this technique, a simple signal processing algorithm was proposed to construct the WEF map when waves propagate through an inspection region, and multiple lead zirconate titanate (PZT) sensors were employed to improve inspection reliability. Various damages in aluminum and carbon fiber reinforced plastic laminated plates were experimentally and numerically evaluated to validate this technique. The results show that it can effectively evaluate the shape and size of damage from wave field variations around the damage in the WEF map.

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial

Background Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. Methods/Design In a double–blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Discussion Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. Trial registration

Factors affecting the extraction of absorbed dose information in a 3D polymer gel dosimeter by X ray computed tomography (IAEA-CN-96/122P)

Two sources of uncertainty in the X ray computed tomography imaging of polymer gel dosimeters are investigated in the paper.The first cause is a change in postirradiation density, which is proportional to the computed tomography signal and is associated with a volume change. The second cause of uncertainty is reconstruction noise.A simple technique that increases the residual signal to noise ratio by almost two orders of magnitude is examined.

Verifiable multi-secret sharing schemes for multiple threshold access structures

A multi-secret sharing scheme allows several secrets to be shared amongst a group of participants. In 2005, Shao and Cao developed a verifiable multi-secret sharing scheme where each participant’s share can be used several times which reduces the number of interactions between the dealer and the group members. In addition some secrets may require a higher security level than others involving the need for different threshold values. Recently Chan and Chang designed such a scheme but their construction only allows a single secret to be shared per threshold value. In this article we combine the previous two approaches to design a multiple time verifiable multi-secret sharing scheme where several secrets can be shared for each threshold value. Since the running time is an important factor for practical applications, we will provide a complexity comparison of our combined approach with respect to the previous schemes.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

Incorporating adverse event relatedness into dose-finding clinical trial designs

Dose-finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose-level estimation. We incorporate adverse event relatedness into the so-called continual reassessment method. Adverse events that have ‘doubtful’ or ‘possible’ relationships to the drug are modelled using a two-parameter logistic model with an additive probability mass. Adverse events ‘probably’ or ‘definitely’ related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies.

Management of multiple heterogeneous UAVs using capability and autonomy visualisation: theory, experiment and result

The interest in utilising multiple heterogeneous Unmanned Aerial Vehicles (UAVs) in close proximity is growing rapidly. As such, many challenges are presented in the effective coordination and management of these UAVs; converting the current n-to-1 paradigm (n operators operating a single UAV) to the 1-to-n paradigm (one operator managing n UAVs). This paper introduces an Information Abstraction methodology used to produce the functional capability framework initially proposed by Chen et al. and its Level Of Detail (LOD) indexing scale. This framework was validated through comparing the operator workload and Situation Awareness (SA) of three experiment scenarios involving multiple autonomously heterogeneous UAVs. The first scenario was set in a high LOD configuration with highly abstracted UAV functional information; the second scenario was set in a mixed LOD configuration; and the final scenario was set in a low LOD configuration with maximal UAV functional information. Results show that there is a significant statistical decrease in operator workload when a UAV’s functional information is displayed at its physical form (low LOD - maximal information) when comparing to the mixed LOD configuration.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough

Background Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. Methods 50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was ‘cough resolution’ defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Results Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. Conclusion A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children.

Effects of small field output factors on IMRT optimisation and dose calculation

Introduction Given the known challenges of obtaining accurate measurements of small radiation fields, and the increasing use of small field segments in IMRT beams, this study examined the possible effects of referencing inaccurate field output factors in the planning of IMRT treatments. Methods This study used the Brainlab iPlan treatment planning system to devise IMRT treatment plans for delivery using the Brainlab m3 microMLC (Brainlab, Feldkirchen, Germany). Four pairs of sample IMRT treatments were planned using volumes, beams and prescriptions that were based on a set of test plans described in AAPM TG 119’s recommendations for the commissioning of IMRT treatment planning systems [1]: • C1, a set of three 4 cm volumes with different prescription doses, was modified to reduce the size of the PTV to 2 cm across and to include an OAR dose constraint for one of the other volumes. • C2, a prostate treatment, was planned as described by the TG 119 report [1]. • C3, a head-and-neck treatment with a PTV larger than 10 cm across, was excluded from the study. • C4, an 8 cm long C-shaped PTV surrounding a cylindrical OAR, was planned as described in the TG 119 report [1] and then replanned with the length of the PTV reduced to 4 cm. Both plans in each pair used the same beam angles, collimator angles, dose reference points, prescriptions and constraints. However, one of each pair of plans had its beam modulation optimisation and dose calculation completed with reference to existing iPlan beam data and the other had its beam modulation optimisation and dose calculation completed with reference to revised beam data. The beam data revisions consisted of increasing the field output factor for a 0.6 9 0.6 cm2 field by 17 % and increasing the field output factor for a 1.2 9 1.2 cm2 field by 3 %. Results The use of different beam data resulted in different optimisation results with different microMLC apertures and segment weightings between the two plans for each treatment, which led to large differences (up to 30 % with an average of 5 %) between reference point doses in each pair of plans. These point dose differences are more indicative of the modulation of the plans than of any clinically relevant changes to the overall PTV or OAR doses. By contrast, the maximum, minimum and mean doses to the PTVs and OARs were smaller (less than 1 %, for all beams in three out of four pairs of treatment plans) but are more clinically important. Of the four test cases, only the shortened (4 cm) version of TG 119’s C4 plan showed substantial differences between the overall doses calculated in the volumes of interest using the different sets of beam data and thereby suggested that treatment doses could be affected by changes to small field output factors. An analysis of the complexity of this pair of plans, using Crowe et al.’s TADA code [2], indicated that iPlan’s optimiser had produced IMRT segments comprised of larger numbers of small microMLC leaf separations than in the other three test cases. Conclusion: The use of altered small field output factors can result in substantially altered doses when large numbers of small leaf apertures are used to modulate the beams, even when treating relatively large volumes.

Development of a dose assessment tool for the auditing of radiotherapy treatment dosimetric quality

The reporting and auditing of patient dose is an important component of radiotherapy quality assurance. The manual extraction of dose-volume metrics is time consuming and undesirable when auditing the dosimetric quality of a large cohort of patient plans. A dose assessment application was written to overcome this, allowing the calculation of various dose-volume metrics for large numbers of plans exported from treatment planning systems. This application expanded on the DICOM-handling functionality of the MCDTK software suite. The software extracts dose values in the volume of interest by using a ray casting point-in-polygon algorithm, where the polygons have been defined by the contours in the RTSTRUCT file...

Origins of the observed asymmetry in out-of-field dose from a linac fitted with an external micro-MLC

Objective Recently, Taylor et al. reported that use of the BrainLAB m3 microMLC, for stereotactic radiosurgery, results in a decreased out-of-field dose in the direction of leaf-motion compared to the outof- field dose measured in the direction orthogonal to leaf-motion [1]. It was recommended that, where possible, patients should be treated with their superior–inferior axes aligned with the microMLCs leafmotion direction, to minimise out-of-field doses [1]. This study aimed, therefore, to examine the causes of this asymmetry in outof- field dose and, in particular, to establish that a similar recommendation need not be made for radiotherapy treatments delivered by linear accelerators without external micro-collimation systems. Methods Monte Carlo simulations were used to study out-of-field dose from different linear accelerators (the Varian Clinacs 21iX and 600C and the Elekta Precise) with and without internal MLCs and external microMLCs [2]. Results Simulation results for the Varian Clinac 600C linear accelerator with BrainLAB m3 microMLC confirm Taylor et als [1] published experimental data. The out-of-field dose in the leaf motion direction is deposited by lower energy (more obliquely scattered) photons than the out-of-field dose in the orthogonal direction. Linear accelerators without microMLCs produce no asymmetry in out-offield dose. Conclusions The asymmetry in out-of-field dose previously measured by Taylor et al. [1] results from the shielding characteristics of the BrainLAB m3 microMLC device and is not produced by the linear accelerator to which it is attached.

Three-dimensional dose verification for clinical treatments of small intracranial tumours

Cancers of the brain and central nervous system account for 1.6% of new cancers and 1.8% of cancer deaths globally. The highest rates of all developed nations are observed in Australia and New Zealand. There are known complexities associated with dose measurement of very small radiation fields. Here, 3D dosimetric verification of treatments for small intracranial tumours using gel dosimetry was investigated.

Multiple repeats of a promoter segment causes transcription factor autoregulation in red apples

Mutations in the genes encoding for either the biosynthetic or transcriptional regulation of the anthocyanin pathway have been linked to color phenotypes. Generally, this is a loss of function resulting in a reduction or a change in the distribution of anthocyanin. Here, we describe a rearrangement in the upstream regulatory region of the gene encoding an apple (Malus x domestica) anthocyanin-regulating transcription factor, MYB10. We show that this modification is responsible for increasing the level of anthocyanin throughout the plant to produce a striking phenotype that includes red foliage and red fruit flesh. This rearrangement is a series of multiple repeats, forming a minisatellite-like structure that comprises five direct tandem repeats of a 23-bp sequence. This MYB10 rearrangement is present in all the red foliage apple varieties and species tested but in none of the white fleshed varieties. Transient assays demonstrated that the 23-bp sequence motif is a target of the MYB10 protein itself, and the number of repeat units correlates with an increase in transactivation by MYB10 protein. We show that the repeat motif is capable of binding MYB10 protein in electrophoretic mobility shift assays. Taken together, these results indicate that an allelic rearrangement in the promoter of MYB10 has generated an autoregulatory locus, and this autoregulation is sufficient to account for the increase in MYB10 transcript levels and subsequent ectopic accumulation of anthocyanins throughout the plant.