Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine : randomized, double-blind, 5-year phase II study in healthy adults.

In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity, and persistence of antibodies to month 60 were evaluated. There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine : randomized double-blind phase II evaluation of safety and immunogenicity

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

Computed success rates of various carrier phase integer estimation solutions and their comparison with statistical success rates

The success rate of carrier phase ambiguity resolution (AR) is the probability that the ambiguities are successfully fixed to their correct integer values. In existing works, an exact success rate formula for integer bootstrapping estimator has been used as a sharp lower bound for the integer least squares (ILS) success rate. Rigorous computation of success rate for the more general ILS solutions has been considered difficult, because of complexity of the ILS ambiguity pull-in region and computational load of the integration of the multivariate probability density function. Contributions of this work are twofold. First, the pull-in region mathematically expressed as the vertices of a polyhedron is represented by a multi-dimensional grid, at which the cumulative probability can be integrated with the multivariate normal cumulative density function (mvncdf) available in Matlab. The bivariate case is studied where the pull-region is usually defined as a hexagon and the probability is easily obtained using mvncdf at all the grid points within the convex polygon. Second, the paper compares the computed integer rounding and integer bootstrapping success rates, lower and upper bounds of the ILS success rates to the actual ILS AR success rates obtained from a 24 h GPS data set for a 21 km baseline. The results demonstrate that the upper bound probability of the ILS AR probability given in the existing literatures agrees with the actual ILS success rate well, although the success rate computed with integer bootstrapping method is a quite sharp approximation to the actual ILS success rate. The results also show that variations or uncertainty of the unit–weight variance estimates from epoch to epoch will affect the computed success rates from different methods significantly, thus deserving more attentions in order to obtain useful success probability predictions.

Mechanical conditions in the initial phase of bone healing

Background: Bone healing is sensitive to the initial mechanical conditions with tissue differentiation being determined within days of trauma. Whilst axial compression is regarded as stimulatory, the role of interfragmentary shear is controversial. The purpose of this study was to determine how the initial mechanical conditions produced by interfragmentary shear and torsion differ from those produced by axial compressive movements. ----- ----- Methods: The finite element method was used to estimate the strain, pressure and fluid flow in the early callus tissue produced by the different modes of interfragmentary movement found in vivo. Additionally, tissue formation was predicted according to three principally different mechanobiological theories. ----- ----- Findings: Large interfragmentary shear movements produced comparable strains and less fluid flow and pressure than moderate axial interfragmentary movements. Additionally, combined axial and shear movements did not result in overall increases in the strains and the strain magnitudes were similar to those produced by axial movements alone. Only when axial movements where applied did the non-distortional component of the pressure–deformation theory influence the initial tissue predictions. ----- ----- Interpretation: This study found that the mechanical stimuli generated by interfragmentary shear and torsion differed from those produced by axial interfragmentary movements. The initial tissue formation as predicted by the mechanobiological theories was dominated by the deformation stimulus.

Pressure, oxygen tension and temperature in the periosteal callus during bone healing - An in vivo study in sheep

Adequate blood supply and sufficient mechanical stability are necessary for timely fracture healing. Damage to vessels impairs blood supply; hindering the transport of oxygen which is an essential metabolite for cells involved in repair. The degree of mechanical stability determines the mechanical conditions in the healing tissues. The mechanical conditions can influence tissue differentiation and may also inhibit revascularization. Knowledge of the actual conditions in a healing fracture in vivo is extremely limited. This study aimed to quantify the pressure, oxygen tension and temperature in the external callus during the early phase of bone healing. Six Merino-mix sheep underwent a tibial osteotomy. The tibia was stabilized with a standard mono-lateral external fixator. A multi-parameter catheter was placed adjacent to the osteotomy gap on the medial aspect of the tibia. Measurements of oxygen tension and temperature were performed for ten days post-op. Measurements of pressure were performed during gait on days three and seven. The ground reaction force and the interfragmentary movements were measured simultaneously. The maximum pressure during gait increased (p=0.028) from three (41.3 [29.2-44.1] mm Hg) to seven days (71.8 [61.8-84.8] mm Hg). During the same interval, there was no change (p=0.92) in the peak ground reaction force or in the interfragmentary movement (compression: p=0.59 and axial rotation: p=0.11). Oxygen tension in the haematoma (74.1 mm Hg [68.6-78.5]) was initially high post-op and decreased steadily over the first five days. The temperature increased over the first four days before reaching a plateau at approximately 38.5 degrees C on day four. This study is the first to report pressure, oxygen tension and temperature in the early callus tissues. The magnitude of pressure increased even though weight bearing and IFM remained unchanged. Oxygen tensions were initially high in the haematoma and fell gradually with a low oxygen environment first established after four to five days. This study illustrates that in bone healing the local environment for cells may not be considered constant with regard to oxygen tension, pressure and temperature.

Re-engineering project planning processes : a best practice model for managing project phase integration issues

Competitive markets are increasingly driving new initiatives for shorter cycle times resulting in increased overlapping of project phases. This, in turn, necessitates improving the interfaces between the different phases to be overlapped (integrated), thus allowing transfer of processes, information and knowledge from one individual or team to another. This transfer between phases, within and between projects, is one of the basic challenges to the philosophy of project management. To make the process transfer more transparent with minimal loss of momentum and project knowledge, this paper draws upon Total Quality Management (TQM) and Business Process Re-engineering (BPR) philosophies to develop a Best Practice Model for managing project phase integration. The paper presents the rationale behind the model development and outlines its two key parts; (1) Strategic Framework and (2) Implementation Plan. Key components of both the Strategic Framework and the Implementation Plan are presented and discussed.

Stability boundary analysis of the dynamic voltage restorer in weak systems with dynamic loads

In this contribution, a stability analysis for a dynamic voltage restorer (DVR) connected to a weak ac system containing a dynamic load is presented using continuation techniques and bifurcation theory. The system dynamics are explored through the continuation of periodic solutions of the associated dynamic equations. The switching process in the DVR converter is taken into account to trace the stability regions through a suitable mathematical representation of the DVR converter. The stability regions in the Thevenin equivalent plane are computed. In addition, the stability regions in the control gains space, as well as the contour lines for different Floquet multipliers, are computed. Besides, the DVR converter model employed in this contribution avoids the necessity of developing very complicated iterative map approaches as in the conventional bifurcation analysis of converters. The continuation method and the DVR model can take into account dynamics and nonlinear loads and any network topology since the analysis is carried out directly from the state space equations. The bifurcation approach is shown to be both computationally efficient and robust, since it eliminates the need for numerically critical and long-lasting transient simulations.

A new unequal DC link voltage configuration for a single phase multilevel converter to reduce low order harmonics

Multilevel converters are used in high power and high voltage applications due to their attractive benefits in generating high quality output voltage. Increasing the number of voltage levels can lead to a reduction in lower order harmonics. Various modulation and control techniques are introduced for multilevel converters like Space Vector Modulation (SVM), Sinusoidal Pulse Width Modulation (SPWM) and Harmonic Elimination (HE) methods. Multilevel converters may have a DC link with equal or unequal DC voltages. In this paper a new modulation technique based on harmonic elimination method is proposed for those multilevel converters that have unequal DC link voltages. This new technique has better effect on output voltage quality and less Total Harmonic Distortion (THD) than other modulation techniques. In order to verify the proposed modulation technique, MATLAB simulations are carried out for a single-phase diode-clamped inverter.

Thermal stability of the soil minerals destinezite and diadochite Fe3+2(PO4)(SO4)(OH)·6H2O - implications for soils in bush fires

Thermogravimetry combined with evolved gas mass spectrometry has been used to ascertain the stability of the soil minerals destinezite and diadochite. These two minerals are identical except for their morphology. Diadochite is amorphous whereas destinezite is crystalline. Both minerals are found in soils. It is important to understand the stability of these minerals because soils are subject to bush fires especially in Australia. The thermal analysis patterns of the two minerals are similar but not identical. Subtle differences are observed in the DTG patterns. For destinezite, two DTG peaks are observed at 129 and 182°C attributed to the loss of hydration water, whereas only a broad peak with maximum at 84°C is observed for diadochite. Higher temperature mass losses at 685°C for destinezite and 655°C for diadochite, based upon the ion current curves, are due to sulphate decomposition. This research has shown that at low temperatures the minerals are stable but at high temperatures, as might be experienced in a bush fire, the minerals decompose.

Thermal stability of the ‘cave’ mineral brushite CaHPO4•2H2O -mechanism of formation and decomposition

Thermogravimetry combined with evolved gas mass spectrometry has been used to ascertain the stability of the ‘cave’ mineral brushite. X-ray diffraction shows that brushite from the Jenolan Caves is very pure. Thermogravimetric analysis coupled with ion current mass spectrometry shows a mass loss at 111°C due to loss of water of hydration. A further decomposition step occurs at 190°C with the conversion of hydrogen phosphate to a mixture of calcium ortho-phosphate and calcium pyrophosphate. TG-DTG shows the mineral is not stable above 111°C. A mechanism for the formation of brushite on calcite surfaces is proposed, and this mechanism has relevance to the formation of brushite in urinary tracts.

Numerical study of two ill-posed one-phase Stefan problems

We treat two related moving boundary problems. The first is the ill-posed Stefan problem for melting a superheated solid in one Cartesian coordinate. Mathematically, this is the same problem as that for freezing a supercooled liquid, with applications to crystal growth. By applying a front-fixing technique with finite differences, we reproduce existing numerical results in the literature, concentrating on solutions that break down in finite time. This sort of finite-time blow-up is characterised by the speed of the moving boundary becoming unbounded in the blow-up limit. The second problem, which is an extension of the first, is proposed to simulate aspects of a particular two-phase Stefan problem with surface tension. We study this novel moving boundary problem numerically, and provide results that support the hypothesis that it exhibits a similar type of finite-time blow-up as the more complicated two-phase problem. The results are unusual in the sense that it appears the addition of surface tension transforms a well-posed problem into an ill-posed one.

A Raman spectroscopic study of bukovskýite Fe2(AsO4)(SO4)(OH)•7H2O-a mineral phase with a significant role in arsenic migration

The Raman spectrum of bukovskýite, Fe3+2(OH)(SO4)(AsO4)•7H2O has been studied and compared with the Raman spectrum of an amorphous gel containing specifically Fe, As and S elements and is understood as an intermediate product in the formation of bukovskýite. Observed bands are assigned to the stretching and bending vibrations of (SO4)2- and (AsO4)3- units, stretching and bending vibrations and librational modes of hydrogen bonded water molecules, stretching and bending vibrations of hydrogen bonded (OH)- ions and Fe3+-(O,OH) units. Approximate range of O-H...O hydrogen bond lengths is inferred from the Raman spectra. Raman spectra of crystalline bukovskýite and of the amorphous gel differ in that the bukovskýite spectrum is more complex, observed bands are sharp, the degenerate bands of (SO4)2- and (AsO4)3- are split and more intense. Lower wavenumbers of  H2O bending vibration in the spectrum of the amorphous gel may indicate the presence of weaker hydrogen bonds compared with those in bukovskýite.