Learning auditory space: generalization and long-term effects

Background: Previous findings have shown that humans can learn to localize with altered auditory space cues. Here we analyze such learning processes and their effects up to one month on both localization accuracy and sound externalization. Subjects were trained and retested, focusing on the effects of stimulus type in learning, stimulus type in localization, stimulus position, previous experience, externalization levels, and time. Method: We trained listeners in azimuth and elevation discrimination in two experiments. Half participated in the azimuth experiment first and half in the elevation first. In each experiment, half were trained in speech sounds and half in white noise. Retests were performed at several time intervals: just after training and one hour, one day, one week and one month later. In a control condition, we tested the effect of systematic retesting over time with post-tests only after training and either one day, one week, or one month later. Results: With training all participants lowered their localization errors. This benefit was still present one month after training. Participants were more accurate in the second training phase, revealing an effect of previous experience on a different task. Training with white noise led to better results than training with speech sounds. Moreover, the training benefit generalized to untrained stimulus-position pairs. Throughout the post-tests externalization levels increased. In the control condition the long-term localization improvement was not lower without additional contact with the trained sounds, but externalization levels were lower. Conclusion: Our findings suggest that humans adapt easily to altered auditory space cues and that such adaptation spreads to untrained positions and sound types. We propose that such learning depends on all available cues, but each cue type might be learned and retrieved differently. The process of localization learning is global, not limited to stimulus-position pairs, and it differs from externalization processes.Foundation for Science and TechnologyFEDE

Bartonella quintana coinfection with Mycobacterium avium complex and CMV in an AIDS patient: case presentation

BACKGROUND: As a greater number of HIV-infected patients survive despite profound immunodepression due to medical progress, we face complex infection with multiple agents in AIDS-patients. CASE PRESENTATION: We report the case of an AIDS patient with a primary clinical presentation suggestive of bacillary angiomatosis. We also found in cutaneous lesions Mycobacterium avium complex and cytomegalovirus. CONCLUSION: This clinical case illustrates the possibility of multiple coinfections in AIDS patients and the need to be exhaustive in evaluating infectious diseases in severely immunocompromised patients

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Meta-Analysis of Genome-Wide Scans for Human Adult Stature Identifies Novel Loci and Associations with Measures of Skeletal Frame Size

Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1×10−8 and rs910316 in TMED10, P-value = 1.4×10−7) and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3×10−7 and rs849141 in JAZF1, P-value = 3.2×10−11). One locus (rs1182188 at GNA12) identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk) and lower-body (hip axis and femur) skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4×10−5 and rs6817306 in LCORL, P-value = 4×10−4), hip axis length (including rs6830062 at LCORL, P-value = 4.8×10−4 and rs4911494 at UQCC, P-value = 1.9×10−4), and femur length (including rs710841 at PRKG2, P-value = 2.4×10−5 and rs10946808 at HIST1H1D, P-value = 6.4×10−6). Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

On the Rotating and Oscillating strings in (AdS3×S3)ϰ(AdS_3\times S^3)_{\varkappa}

We study rigidly rotating strings in the $\varkappa$-deformed $AdS_3 \times S^3$ background. We find out two classes of solutions corresponding to the giant magnon and single spike solutions of the string rotating in two $S^2_{\varkappa}$ subspace of rotations reduced along two different isometries. We verify that the dispersion relations reduce to the well known relation in the $\varkappa\rightarrow 0$ limit. We further study some oscillating string solutions in the $S^3_{\varkappa}$ subspace.Comment: 20 pages, clarifications added, version to appear in JHE

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let