A phase IIa, randomized, double-blind, safety, immunogenicity and efficacy trial of Plasmodium falciparum vaccine antigens merozoite surface protein 1 and RTS,S formulated with AS02 adjuvant in healthy, malaria-naïve adults.

BACKGROUND: To improve the efficacy of Plasmodium falciparum malaria vaccine RTS,S/AS02, we conducted a study in 2001 in healthy, malaria-naïve adults administered RTS,S/AS02 in combination with FMP1, a recombinant merozoite surface-protein-1, C-terminal 42kD fragment. METHODS: A double-blind Phase I/IIa study randomized N = 60 subjects 1:1:1:1 to one of four groups, N = 15/group, to evaluate safety, immunogenicity, and efficacy of intra-deltoid half-doses of RTS,S/AS02 and FMP1/AS02 administered in the contralateral (RTS,S + FMP1-separate) or same (RTS,S + FMP1-same) sites, or FMP1/AS02 alone (FMP1-alone), or RTS,S/AS02 alone (RTS,S-alone) on a 0-, 1-, 3-month schedule. Subjects receiving three doses of vaccine and non-immunized controls (N = 11) were infected with homologous P. falciparum 3D7 sporozoites by Controlled Human Malaria Infection (CHMI). RESULTS: Subjects in all vaccination groups experienced mostly mild or moderate local and general adverse events that resolved within eight days. Anti-circumsporozoite antibody levels were lower when FMP1 and RTS,S were co-administered at the same site (35.0 µg/mL: 95 % CI 20.3-63), versus separate arms (57.4 µg/mL: 95 % CI 32.3-102) or RTS,S alone (62.0 µg/mL: 95 % CI: 37.8-101.8). RTS,S-specific lymphoproliferative responses and ex vivo ELISpot CSP-specific interferon-gamma (IFN-γ) responses were indistinguishable among groups receiving RTS,S/AS02. There was no difference in antibody to FMP1 among groups receiving FMP1/AS02. After CHMI, groups immunized with a RTS,S-containing regimen had âˆ¼ 30 % sterile protection against parasitemia, and equivalent delays in time-to-parasitemia. The FMP1/AS02 alone group showed no sterile immunity or delay in parasitemia. CONCLUSION: Co-administration of RTS,S and FMP1/AS02 reduced anti-RTS,S antibody, but did not affect tolerability, cellular immunity, or efficacy in a stringent CHMI model. Absence of efficacy or delay of patency in the sporozoite challenge model in the FMP1/AS02 group did not rule out efficacy of FMP1/AS02 in an endemic population. However, a Phase IIb trial of FMP1/AS02 in children in malaria-endemic Kenya did not demonstrate efficacy against natural infection. CLINICALTRIALS: gov identifier: NCT01556945.

The validity of an experiment testing the influence of acceleration on time dilation using a rotating Mössbauer absorber and a Synchrotron Mössbauer Source.

Three experiments are reviewed, performed (in 2014-2016) at ID18 of ESRF to measure the influence of acceleration on time dilation by measuring the relative shift between the absorption lines of two states of the same rotating absorber with accelerations anti-parallel and parallel to the incident beam. Statistically significant data for rotation frequencies up to 510 Hz in both directions of rotation were collected. For each run with high rotation, a stable statistically significant `vibration-free' relative shift between the absorption lines of the two states was measured. This may indicate the influence of acceleration on time dilation. However, the measured relative shift was also affected by the use of a slit necessary to focus the beam to the axis of rotation to a focal spot of sub-micrometre size. The introduction of the slit broke the symmetry in the absorption lines due to the nuclear lighthouse effect and affected the measured relative shift, preventing to claim conclusively the influence of acceleration on time dilation. Assuming that this loss of symmetry is of first order, the zero value of the relative shift, corrected for this loss, falls always within the experimental error limits, as predicted by Einstein's clock hypothesis. The requirements and an indispensable plan for a conclusive experiment, once the improved technology becomes available, is presented. This will be useful to future experimentalists wishing to pursue this experiment or a related rotor experiment involving a Mössbauer absorber and a synchrotron Mössbauer source.

Advances in testing the effect of acceleration on time dilation using a synchrotron Mössbauer source.

New results, additional techniques and know-how acquired, developed and employed in a recent HC-1898 experiment at the Nuclear Resonance Beamline ID18 of ESRF are presented, in the quest to explore the acceleration effect on time dilation. Using the specially modified Synchrotron Mössbauer Source and KB-optics together with a rotating single-line semicircular Mössbauer absorber on the rim of a specially designed rotating disk, the aim was to measure the relative spectral shift between the spectra of two states when the acceleration of the absorber is anti-parallel and parallel to the source. A control system was used for the first time and a method to quantify the effects of non-random vibrations on the spectral shift was developed. For several runs where the effect of these vibrations was negligible, a stable statistically significant non-zero relative shift was observed. This suggests the influence of acceleration on time.

Synchrotron radiation Mössbauer spectra of a rotating absorber with implications for testing velocity and acceleration time dilation.

Many Mössbauer spectroscopy (MS) experiments have used a rotating absorber in order to measure the second-order transverse Doppler (TD) shift, and to test the validity of the Einstein time dilation theory. From these experiments, one may also test the clock hypothesis (CH) and the time dilation caused by acceleration. In such experiments the absorption curves must be obtained, since it cannot be assumed that there is no broadening of the curve during the rotation. For technical reasons, it is very complicated to keep the balance of a fast rotating disk if there are moving parts on it. Thus, the Mössbauer source on a transducer should be outside the disk. Friedman and Nowik have already predicted that the X-ray beam finite size dramatically affects the MS absorption line and causes its broadening. We provide here explicit formulas to evaluate this broadening for a synchrotron Mössbauer source (SMS) beam. The broadening is linearly proportional to the rotation frequency and to the SMS beam width at the rotation axis. In addition, it is shown that the TD shift and the MS line broadening are affected by an additional factor assigned as the alignment shift which is proportional to the frequency of rotation and to the distance between the X-ray beam center and the rotation axis. This new shift helps to align the disk's axis of rotation to the X-ray beam's center. To minimize the broadening, one must focus the X-ray on the axis of the rotating disk and/or to add a slit positioned at the center, to block the rays distant from the rotation axis of the disk. Our experiment, using the (57)Fe SMS, currently available at the Nuclear Resonance beamline (ID18) at the ESRF, with a rotating stainless steel foil, confirmed our predictions. With a slit installed at the rotation axis (reducing the effective beam width from 15.6 µm to 5.4 µm), one can measure a statistically meaningful absorption spectrum up to 300 Hz, while, without a slit, such spectra could be obtained up to 100 Hz only. Thus, both the broadening and the alignment shift are very significant and must be taken into consideration in any rotating absorber experiment. Here a method is offered to measure accurately the TD shift and to test the CH.

Structure and electrical resistivity of mixed-valent EuNi2P2 at high pressure.

The structural properties and electrical resistivity of homogeneous mixed-valent EuNi2P2 are studied at pressures up to 45 GPa. No structural phase transition is observed in the whole pressure range and the overall pressure behavior of the structural parameters is similar to that of related compounds in the collapsed tetragonal ThCr2Si2-type structure. Electrical resistivity measured up to 31 GPa at temperatures between 4 and 300 K exhibits continuous changes from the behavior typical for a mixed-valent Eu system to that of a normal metallic system at pressures above 20 GPa, indicating a transition of the strongly mixed-valent Eu atoms with a valence ~2.5 towards a pure trivalent state. No superconductivity was observed in the whole studied pressure-temperature range.

Equivalence of the boson peak in glasses to the transverse acoustic van Hove singularity in crystals.

We compare the atomic dynamics of the glass to that of the relevant crystal. In the spectra of inelastic scattering, the boson peak of the glass appears higher than the transverse acoustic (TA) singularity of the crystal. However, the density of states shows that they have the same number of states. Increasing pressure causes the transformation of the boson peak of the glass towards the TA singularity of the crystal. Once corrected for the difference in the elastic medium, the boson peak matches the TA singularity in energy and height. This suggests the identical nature of the two features.

Role of the local structure and the energy trap centers in the quenching of luminescence of the Tb3+ ions in fluoroborate glasses: a high pressure study.

The concentration and pressure dependent luminescence properties of the Tb(3+) ions in a lithium fluoroborate glasses have been studied by analyzing the deexcitation processes of the (5)D(4) level at ambient conditions as well as a function of pressure up to 35 GPa at room temperature. The luminescence spectra of Tb(3+) ions have been measured as a function of pressure and observed a continuous redshift as well as a progressive increase in the magnitude of the crystal-field splittings for the (5)D(4)-->(7)F(3,4,5) transitions. Monitoring the (5)D(4)-->(7)F(5) transition, the luminescence decay curves have been measured and analyzed in order to understand the dynamics of the deexcitation of the Tb(3+) ions in these glasses. At ambient conditions a nonexponential behavior has been found for doping concentrations as low as 0.1 mol % of Tb(4)O(7), although no cross-relaxation channels exist to explain this behavior. The modelization of the energy transfer processes surprisingly shows that the nonexponential character of the decay curves of the (5)D(4) level with concentration or with pressure has to be ascribed to energy transfer to traps without migration of energy between Tb(3+) ions. For all the experimental situations the nonexponential character of the decay curves is well described by the generalized Yokota-Tanimoto model with a dipole-dipole interaction between the Tb(3+) ions and the nearby luminescence quenching traps. The luminescence properties observed with releasing pressure are slightly different to those obtained while increasing pressure suggesting a local structural hysteresis in the lithium fluoroborate glass matrix giving rise to the generation of a new distribution of environments for the Tb(3+) ions.

Syphilis co-infection does not affect HIV disease progression.

HIV and syphilis are often seen as co-infections since they share a common mode of transmission. During episodes of syphilis, CD4 counts transiently decrease and HIV viral loads increase; however, the effect of syphilis co-infection on HIV disease progression (time to AIDS or death) is unclear. We analysed prospectively collected information on 2239 persons with estimated dates of HIV seroconversion (205 [9.2%] with confirmed syphilis and 66 [2.9%] with probable syphilis) in order to determine the effect of syphilis co-infection on HIV disease progression. In multivariate models censored at highly active antiretroviral therapy (HAART) initiation or last visit, adjusting for CD4 count, age, race, gender, and hepatitis B and C status, syphilis (confirmed + probable) was not associated with increased hazard of AIDS or death (hazard ratio 0.99, 95% CI 0.73-1.33). Treating HAART as a time-varying covariate or limiting the analysis to only confirmed syphilis cases did not significantly alter the results. Despite transient changes in CD4 counts and viral loads, syphilis does not appear to affect HIV disease progression.

Electronic and magnetic phase diagram of beta-Fe(1.01)Se with superconductivity at 36.7 K under pressure.

The discovery of new high-temperature superconductors based on FeAs has led to a new 'gold rush' in high-T(C) superconductivity. All of the new superconductors share the same common structural motif of FeAs layers and reach T(C) values up to 55 K (ref. 2). Recently, superconductivity has been reported in FeSe (ref. 3), which has the same iron pnictide layer structure, but without separating layers. Here, we report the magnetic and electronic phase diagram of beta-Fe(1.01)Se as a function of temperature and pressure. The superconducting transition temperature increases from 8.5 to 36.7 K under an applied pressure of 8.9 GPa. It then decreases at higher pressures. A marked change in volume is observed at the same time as T(C) rises, owing to a collapse of the separation between the Fe(2)Se(2) layers. No static magnetic ordering is observed for the whole p-T phase diagram. We also report that at higher pressures (starting around 7 GPa and completed at 38 GPa), Fe(1.01)Se transforms to a hexagonal NiAs-type structure and exhibits non-magnetic behaviour.

Luminescence properties of Sm(3+)-doped P(2)O(5)-PbO-Nb(2)O(5) glass under high pressure.

Samarium doped lead phosphate glass modified with niobium having a composition (in mol%) of 55P(2)O(5)+39.5PbO+5Nb(2)O(5)+0.5Sm(2)O(3) has been prepared by the conventional melt quenching technique. The emission spectra and the decay curves for the (4)G(5/2) level of Sm(3+) ions have been measured as a function of pressure up to 23.6 GPa at room temperature. A discontinuity in the observed shifts and crystal-field splittings as a function of pressure around 9-10 GPa suggests that a phase transition is taking place in the glass matrix. The [Formula: see text], (6)H(7/2) and (6)H(9/2) transitions are shifted towards the lower energy side with magnitudes of -7.1, -7.6 and -5.5 cm(-1) GPa(-1) up to 8.9 GPa (phase 1) and -5.6, -4.9 and -4.4 cm(-1) GPa(-1) beyond 10.3 GPa (phase 2), respectively. A much stronger increase in the splitting of the [Formula: see text] and [Formula: see text] Stark levels with pressure is observed in phase 1 than in phase 2. The lifetime of the (4)G(5/2) level decreases from 2.29 ms (0 GPa) to 0.64 ms (23.6 GPa) with pressure. The decay curves of the (4)G(5/2) level exhibit non-exponential behavior for all the pressures and were fitted by the generalized Yokota-Tanimoto model to probe the nature of the energy transfer process. The best fits with S = 6 indicate that the energy transfer between donor and acceptor is of dipole-dipole type. The crystal-field splitting experienced by the Sm(3+) ions in the title glass are found to be larger than those found in borate, K-Ba-Al phosphate and tellurite glasses.

Paramagnetic hyperfine splitting in the Eu Mössbauer spectra of CaF(2):Eu.

(151)Eu Mössbauer spectra in zero magnetic field of highly dilute (0.1 mol%) Eu(2+) ions in CaF(2) showed an almost temperature-independent asymmetrically split pattern, arising from the paramagnetic hyperfine interaction AS. I in a cubic crystal field with slow electron spin relaxation; in a small external magnetic field B of 0.2 T such that gµ(B)B>A an almost symmetrical pattern was observed. Both the spectra with and without external field are well described using the spin Hamiltonian and previous electron paramagnetic resonance data. A more concentrated (2 mol% Eu(2+)) sample exhibited a strongly broadened symmetrical resonance line due to an increased Eu-Eu spin relaxation rate; in an external magnetic field of 0.2 T the Mössbauer spectra exhibited further broadening and additional magnetic structures due to the reduced relaxation rate. When a large field of 6 T was applied such that gµ(B)B is much larger than the crystal field splitting, a fully resolved hyperfine pattern was observed at 2.5 K, with an effective field at the Eu nuclei of -33.7 T; at higher temperatures superimposed patterns originating from excited electronic states were observed in the spectra. The present results on the highly dilute CaF(2) : 0.1%Eu(2+) sample deliver a straightforward explanation for previous observations of a seemingly large dependence of the Eu(2+) isomer shift on europium concentration.

Photoluminescence from the (5)D(0) level of Eu(3+) ions in a phosphate glass under pressure.

The pressure dependence of the luminescence from [Formula: see text] transitions of Eu(3+) ions in 58.5P(2)O(5)-9Al(2)O(3)-14.5BaO-17K(2)O-1Eu(2)O(3) glass has been investigated up to 38.3 GPa at room temperature. The relative luminescence intensity ratio of [Formula: see text] to [Formula: see text] transitions of the Eu(3+) ions is found to decrease with increasing pressure, indicating a lowering of the asymmetry around the Eu(3+) ions with pressure. The [Formula: see text] transitions exhibit pressure-induced red shifts of different magnitude, which suggests a decrease in Slater parameters (F(k)) and in the spin-orbit coupling parameters (ζ) for the Eu(3+) ions. Stark components of the (7)F(1) level have been used to evaluate the crystal-field (CF) parameters B(20) and B(22), which are in turn used to estimate the CF strength experienced by the Eu(3+) ions in the glass. The observed increase in the CF strength parameter is found to have an almost cubic dependence on pressure. Luminescence decay curves for the [Formula: see text] transition are found to be single exponential over the entire pressure range studied. The lifetime did not change under pressure up to 5 GPa, although a significant change in the CF strength is noticed in this pressure range. The reduction of lifetime observed at pressures above 5 GPa could be partially due to an increase of pressure-induced defect centres. Such a process can then explain the hysteresis observed in the variation of lifetime and crystal-field strength on the release of pressure.

Multiple myeloma-associated amyloidosis manifesting as fulminant hepatic failure.

We report a case of amyloidosis associated with K light chain multiple myeloma in a 42-year-old African American man. The patient initially had mild dyspepsia, which rapidly progressed to include anorexia, fulminant hepatic failure, and death within 9 weeks. This is only the fourth reported case of hepatic failure from myeloma-associated amyloidosis and the second reported case of light chain myeloma with amyloidosis resulting in a progressive clinical course of hepatic failure. Our patient was unique in that, despite severe disease, he had mild symptoms without laboratory abnormalities until 2 weeks prior to death.

Rapid diagnosis of leishmaniasis by fluorogenic polymerase chain reaction.

A fluorescent DNA probe (LEIS.P1) specific for a conserved region of the small-subunit ribosomal RNA gene of Leishmania and a pair of flanking primers (LEIS.U1 and LEIS.L1) were designed for use in a fluorogenic polymerase chain reaction. Optimal assay conditions with zero background were established to detect low levels of Leishmania from clinical samples. By use of this assay, we amplified DNA from 27 strains of cultured Leishmania (both Old and New World strains) and selectively amplified Leishmania DNA from 12 paraffin-embedded human biopsy samples and 3 fresh human skin biopsy specimens. For the fresh human tissue biopsies, the turnaround time from biopsy to test result was < 24 hr. No amplification was detected in negative control samples (including the kinetoplastid protozoa Trypanosoma rangelli and Crithidia fasiculata). This assay provides a specific and rapid diagnostic modality to detect infection with Leishmania.

Phonon density of states of iron up to 153 gigapascals.

We report phonon densities of states (DOS) of iron measured by nuclear resonant inelastic x-ray scattering to 153 gigapascals and calculated from ab initio theory. Qualitatively, they are in agreement, but the theory predicts density at higher energies. From the DOS, we derive elastic and thermodynamic parameters of iron, including shear modulus, compressional and shear velocities, heat capacity, entropy, kinetic energy, zero-point energy, and Debye temperature. In comparison to the compressional and shear velocities from the preliminary reference Earth model (PREM) seismic model, our results suggest that Earth's inner core has a mean atomic number equal to or higher than pure iron, which is consistent with an iron-nickel alloy.

Cutaneous leishmaniasis following local trauma: a clinical pearl.

Cutaneous leishmaniasis is acquired from the bite of an infected sand fly and can result in chronic skin lesions that develop within weeks to months after a bite. Local trauma has been implicated as a precipitating event in the development of skin lesions in patients who have been infected with Leishmania species. Here we report a case series and review the literature on patients who developed cutaneous leishmaniasis after local trauma, which may familiarize clinicians with this presentation.

Trovafloxacin-induced weakness due to a demyelinating polyneuropathy.

Fluoroquinolones have been associated with peripheral sensory disorders and weakness, especially in patients with underlying myasthenia gravis or myasthenia-like Eaton-Lambert syndrome. Trovafloxacin is a relatively new quinolone for which these side effects have not been described. We report a case of diffuse weakness due to a demyelinating polyneuropathy that began after initiation of trovafloxacin in a patient without an underlying neurologic disorder.

Density of phonon states in iron at high pressure

The lattice dynamics of the hexagonal close-packed (hcp) phase of iron was studied with nuclear inelastic absorption of synchrotron radiation at pressures from 20 to 42 gigapascals. A variety of thermodynamic parameters were derived from the measured density of phonon states for hcp iron, such as Debye temperatures, Gruneisen parameter, mean sound velocities, and the lattice contribution to entropy and specific heat. The results are of geophysical interest, because hcp iron is considered to be a major component of Earth's inner core.