Spatial-temporal analysis of HIV-1 PR and RT resistance-associated mutations of nucleotide sequences from Western Europe, using vircoTYPE™ HIV-1 assay

Highly effective regimens have drastically improved HIV morbidity and mortality although anti-retro viral resistance remains a limiting factor in disease management. Therefore, analysis of large sequence datasets may provide better insight into drug resistance & assist policy makers to select optimized treatment strategies. Using a secure, web-based sequence submission tool (vircoNETTM, Janssen Diagnostics BVBA), centers within EU have been able to retrieve the CE-marked vircoTYPETM HIV-1 (VTY) genotyping reports for their patients. The purpose of this study is to perform a descriptive analysis of the prevalence of HIV-1 PR & RT resistance-associated mutations (RAMs) from submitted nucleotide sequences, collected during an 8 year period, from 5 West-European countries & Switzerland. From January 2005-June 2012, 27,262 sequences were submitted via vircoNETTM & analyzed using VTY. Approximately 50% of the sequences were submitted from Spain (n=14120) & 24% from Italy (n=6415). The remaining sequences were from UK (n=2097), France (n=1508), Germany (n=1041) & Switzerland (n=2081). The majority (80%, 21,647/27,262) of the sequences were Clade B. For NRTI RAMs, M184V was the most prevalent mutation (36%, n=9944) followed by M41L (25%, n=6701). For NNRTI RAMs, K103N mutation was most prevalent (24%, n=6481) followed by Y181C (10% n=2704). For PIs, L90M (16%, n=4453) and M46I (12%, n=3397) were the most prevalent. The overall RAM prevalence has declined over the 8 year period. 7602 (28%) sequences had no major RAMs and were sensitive to all 18 FDA & EMA-approved drugs present on VTY. In the PI class, VTY predicted 95% (20097/21243) of the sequences as sensitive & 5% (1146/21243) resistant to darunavir, followed by tipranavir, lopinavir & saquinavir with equal sensitivity rate (SR) of 81% & a resistance rate (RR) of 13%, 18% & 19% respectively. In the NNRTI class, etravirine had a better SR (81%, 8628/10683) & RR (19%, 2055/10683) when compared to nevirapine and efavirenz, with a SR of 59% & RR of 41% for both drugs. For NRTIs, the highest SR was found for stavudine (77%, 20889/27262) followed by tenofovir (67%, 18249/27262) with 23% (6499/27262) resistant sequences observed for stavudine & 33% (9114/27262) for tenofovir. The current analysis provides some preliminary insight into HIV mutation pattern prevalence and resistance within Western Europe, suggesting good therapeutic opportunities for regimens containing new generation PIs & NNRTIs

Low-energy dipole excitations towards the proton drip-line: doubly magic 48Ni

The properties of the low-energy dipole response are investigated for the proton-rich doubly magic nucleus $^{48}$Ni, in a comparative study of two microscopic models: fully self-consistent Relativistic Random-Phase Approximation(RRPA) based on the novel density-dependent meson-exchange interactions, and Continuum Random-Phase Approximation(CRPA) using Skyrme-type interactions with the continuum properly included. Both models predict the existence of the low-energy soft mode, i.e. the proton pygmy dipole resonance (PDR), for which the transition densities and RPA amplitudes indicate the dynamics of loosely bound protons vibrating against the rest of the nucleons. The CRPA analysis indicates that the escape width for the proton PDR is rather large, as a result of the coupling to the continuum.Comment: 12 pages, 3 figures, accepted for publication in Phys. Lett.

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain

Concentration of electric dipole strength below the neutron separation energy in N = 82 nuclei

The semi-magic nuclei Ba-138, Ce-140, and Sm-144 have been investigated in photon scattering experiments up to an excitation energy of about 10 MeV. The distribution of the electric dipole strength shows a resonance like structure at energies between 5.5 and 8 MeV exhausting up to 1% of the isovector E1 Energy Weighted Sum Rule.Comment: 10 pages, 3 figure

Direct determination of photodisintegration cross sections and the p-process

Photon-induced reactions play a key role in the nucleosynthesis of heavy neutron-deficient nuclei, the so-called p-nuclei. In this paper we review the present status of experiments on photon-induced reactions at energies of astrophysical importance and their relevance to p-process modeling.Comment: Nucl. Phys. A, in pres

Search for the electric dipole excitations to the 3s1/2⊗[21+⊗31−]3s_{1/2} \otimes [2^{+}_{1} \otimes 3^{-}_{1}] multiplet in 117^{117}Sn

The odd-mass $^{117}$Sn nucleus was investigated in nuclear resonance fluorescence experiments up to an endpoint energy of the incident photon spectrum of 4.1 MeV at the bremsstrahlung facility of the Stuttgart University. More than 50 mainly hitherto unknown levels were found. From the measurement of the scattering cross sections model independent absolute electric dipole excitation strengths were extracted. The measured angular distributions suggested the spins of 11 excited levels. Quasi-particle phonon model calculations including a complete configuration space were performed for the first time for a heavy odd-mass spherical nucleus. These calculations give a clear insight in the fragmentation and distribution of the $E1$, $M1$, and $E2$ excitation strength in the low energy region. It is proven that the $1^{-}$ component of the two-phonon $[2^{+}_{1} \otimes 3^{-}_{1}]$ quintuplet built on top of the $1/2^{+}$ ground state is strongly fragmented. The theoretical calculations are consistent with the experimental data.Comment: 10 pages, 5 figure

Changes in globus pallidus with (pre)term kernicterus

OBJECTIVE: We report serial magnetic resonance (MR) and sonographic behavior of globus pallidus in 5 preterm and 3 term infants with kernicterus and describe the clinical context in very low birth weight preterm infants. On the basis of this information, we suggest means of diagnosis and prevention. METHODS: Charts and MR and ultrasound images of 5 preterm infants and 3 term infants with suspected bilirubin-associated brain damage were reviewed. Included were preterm infants with severe hearing loss, quadriplegic hypertonia, and abnormal hypersignal of globus pallidus on T2-weighted MR imaging (MRI). In 1 infant who died on day 150, the diagnosis was confirmed during the neonatal period. The others were picked up as outpatients and scanned at 12 or 22 months' corrected age. Three instances of term kernicterus were included for comparison of serial MRI in the neonatal period and early infancy: they were caused by glucose-6-phosphate dehydrogenase deficiency, urosepsis, and dehydration plus fructose 1-6 biphosphatase deficiency. RESULTS: Five preterm infants of 25 to 29 weeks' gestational age presented with total serum bilirubin (TSB) levels below exchange transfusion thresholds commonly advised. Mixed acidosis was present in 3 infants around the TSB peak. The bilirubin/albumin molar ratio was >0.5 in all, in the absence of displacing drugs. All failed to pass bedside hearing screen tests and had severe hearing loss on auditory brain response testing. Symmetrical homogeneous hyperechogenicity of globus pallidus was the alerting feature in 1 infant. Globus pallidus was hyperintense on T1-weighted MR images in this child. The other infants presented with severe developmental delay as a result of dyskinetic quadriplegia and hearing loss. Globus pallidus was normal on T1- but hyperintense on T2-weighted MR images at 12

Orientation of dichroic dyes in ultra-drawn polyethylenes

The excellent solid-state drawing characteristics of linear polyethylenes were exploited for the orientation of dichroic dyes. Polarizers with high transparency and high level of optical anisotropy were produced from the drawn films contg. anthraquinone or azo dyes. [on SciFinder (R)