Can meaningful effective connectivities be obtained between auditory cortical regions?

Structural equation modelling (SEM) of neuroimaging data can be evaluated both for the goodness of fit of the model and for the strength of path coefficients (as an index of effective connectivity). SEM of auditory fMRI data is made difficult by the necessary sparse temporal sampling of the time series (to avoid contamination of auditory activation by the response to scanner noise), and by the paucity of well-defined anatomical information to constrain the functional model. We used SEM (i.e. a model incorporating latent variables) to investigate how well fMRI data in four adjacent cortical fields can be described as an auditory network. Seven out of 14 models (2 hemispheres x (6 subjects and 1 group)) produced a plausible description of the measured data. Since the auditory model to be tested is not fully validated by anatomical data, our approach requires that goodness of fit must be confirmed to assure generalisability of connectivity patterns. For good-fitting models, connectivity patterns varied significantly across subjects and were not replicable across stimulus conditions. SEM of central auditory function therefore appears to be highly sensitive to the voxel-selection procedure and/or the sampling of the time series

Spectral and temporal processing in human auditory cortex

Hierarchical processing suggests that spectrally and temporally complex stimuli will evoke more activation than do simple stimuli, particularly in non-primary auditory fields. This hypothesis was tested using two tones, a single frequency tone and a harmonic tone, that were either static or frequency modulated to create four stimuli. We interpret the location of differences in activation by drawing comparisons between fMRI and human cytoarchitectonic data, reported in the same brain space. Harmonic tones produced more activation than single tones in right Heschl's gyrus (HG) and bilaterally in the lateral supratemporal plane (STP). Activation was also greater to frequency-modulated tones than to static tones in these areas, plus in left HG and bilaterally in an anterolateral part of the STP and the superior temporal sulcus. An elevated response magnitude to both frequency-modulated tones was found in the lateral portion of the primary area, and putatively in three surrounding non-primary regions on the lateral STP (one anterior and two posterior to HG). A focal site on the posterolateral STP showed an especially high response to the frequency-modulated harmonic tone. Our data highlight the involvement of both primary and lateral non-primary auditory regions

Theory of Gaussian variational approximation for a Poisson mixed model

Likelihood-based inference for the parameters of generalized linear mixed models is hindered by the presence of intractable integrals. Gaussian variational approximation provides a fast and effective means of approximate inference. We provide some theory for this type of approximation for a simple Poisson mixed model. In particular, we establish consistency at rate m -1/2 +n-1, where m is the number of groups and n is the number of repeated measurements

Functional magnetic resonance imaging measurements of sound-level encoding in the absence of background scanner noise

Effects of sound level on auditory cortical activation are seen in neuroimaging data. However, factors such as the cortical response to the intense ambient scanner noise and to the bandwidth of the acoustic stimuli will both confound precise quantification and interpretation of such sound-level effects. The present study used temporally "sparse" imaging to reduce effects of scanner noise. To achieve control for stimulus bandwidth, three schemes were compared for sound-level matching across bandwidth: component level, root-mean-square power and loudness. The calculation of the loudness match was based on the model reported by Moore and Glasberg [Acta Acust. 82, 335–345 (1996)]. Ten normally hearing volunteers were scanned using functional magnetic resonance imaging (fMRI) while listening to a 300-Hz tone presented at six different sound levels between 66 and 91 dB SPL and a harmonic-complex tone (F0 = 186 Hz) presented at 65 and 85 dB SPL. This range of sound levels encompassed all three bases of sound-level matching. Activation in the superior temporal gyrus, induced by each of the eight tone conditions relative to a quiet baseline condition, was quantified as to extent and magnitude. Sound level had a small, but significant, effect on the extent of activation for the pure tone, but not for the harmonic-complex tone, while it had a significant effect on the response magnitude for both types of stimulus. Response magnitude increased linearly as a function of sound level for the full range of levels for the pure tone

Fretting of CoCrMo and Ti6Al4V Alloys in Modular Prostheses

Implantation of a total hip replacements (THR) is an effective intervention in the management of arthritis. Modularity at the taper junction of THR was introduced in order to improve the ease with which the surgeon could modify the length of the taper section and the overall length of the replacement. Cobalt chromium (Co–28Cr–6Mo) and titanium (Ti–6Al–4V) alloys are the most commonly used materials for the device. This study investigates the fretting behaviour of both CoCr–CoCr and CoCr–Ti couplings and analyses their damage mechanisms. A reciprocating tribometer ball on plate fretting contact was instrumented with in situ electrochemistry to characterise the damage inflicted by tribocorrosion on the two couplings. Fretting displacements amplitudes of 10, 25 and 50 mm at an initial contact pressure of 1 GPa were assessed. The results reveal larger metallic volume loss from the CoCr–CoCr alloy compared to the CoCr–Ti alloy, and the open circuit potential indicates a depassivation of the protective oxide layer at displacement amplitudes .25 mm. In conclusion, the damage mechanisms of CoCr–CoCr and CoCr–Ti fretting contacts were identified to be wear and fatigue dominated mechanisms respectively

Biobanking, consent, and commercialization in international genetics research: the Type 1 Diabetes Genetics Consortium

Background and Purpose This article describes several ethical, legal, and social issues typical of international genetics biobanking, as encountered in the Type 1 Diabetes Genetics Consortium (T1DGC)

The incidence and clinical burden of respiratory syncytial virus disease identified through hospital outpatient presentations in Kenyan children

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting. Methods We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence. Results Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively. Conclusion The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis

Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

The key role of nitric oxide in hypoxia: hypoxic vasodilation and energy supply-demand matching

Significance: a mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow - 'hypoxic vasodilation' - occur in an attempt to restore oxygen supply. Nitric oxide is a major signalling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways). Recent advances: this review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of nitric oxide, and mechanisms underlying the involvement of nitric oxide in hypoxic vasodilation. Recent insights into nitric oxide metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite reductases, and release of nitric oxide from storage pools. The processes through which nitric oxide levels are elevated during hypoxia are presented, namely (i) increased synthesis from nitric oxide synthases, increased reduction of nitrite to nitric oxide by heme- or pterin-based enzymes and increased release from nitric oxide stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase. Critical issues: several reviews covered modulation of energetic metabolism by nitric oxide, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression Future directions: we identify a key position for nitric oxide in the body's adaptation to an acute energy supply-demand mismatc

Phylogenetic position of an uncharacterized Brazilian strain of bovine papillomavirus in the genus Xipapillomavirus based on sequencing of the L1 open reading frame

The use of PCR assays with degenerate primers has suggested the existence of numerous as yet uncharacterized bovine papillomaviruses (BPV). Despite the endemic nature of BPV infections, the identification of BPV types in Brazilian cattle is still only sporadic. However, in a recent analysis of a partial segment of the L1 gene, we observed notable diversity among the BPV types detected. The aim of this study was to determine the phylogenetic position of the previously identified wild strain BPV/BR-UEL2 detected in the state of Paraná in Brazil. Since previous analysis of the partial L1 sequence had shown that this strain was most closely related to BPV type 4, genus-specific primers were designed. Phylogenetic analysis using complete L1 ORF sequences revealed that BPV/BR-UEL2 was related to BPV types classified in the genus Xipapillomavirus and shared the highest L1 nucleotide sequence similarity with BPV type 4 (78%). This finding suggests that BPV/BR-UEL2 should be classified as a potential new type of BPV in the genus Xipapillomavirus