Optimal cue combination and landmark-stability learning in the head direction system.

Maintaining a sense of direction requires combining information from static environmental landmarks with dynamic information about self-motion. This is accomplished by the head direction system, whose neurons - head direction cells - encode specific head directions. When the brain integrates information in sensory domains, this process is almost always 'optimal' - that is, inputs are weighted according to their reliability. Evidence suggests cue combination by head direction cells may also be optimal. The simplicity of the head direction signal, together with the detailed knowledge we have about the anatomy and physiology of the underlying circuit, therefore makes this system a tractable model with which to discover how optimal cue combination occurs at a neural level. In the head direction system, cue interactions are thought to occur on an attractor network of interacting head direction neurons, but attractor dynamics predict a winner-take-all decision between cues, rather than optimal combination. However, optimal cue combination in an attractor could be achieved via plasticity in the feedforward connections from external sensory cues (i.e. the landmarks) onto the ring attractor. Short-term plasticity would allow rapid re-weighting that adjusts the final state of the network in accordance with cue reliability (reflected in the connection strengths), while longer term plasticity would allow long-term learning about this reliability. Although these principles were derived to model the head direction system, they could potentially serve to explain optimal cue combination in other sensory systems more generally

A Computational Model of the Development of Separate Representations of Facial Identity and Expression in the Primate Visual System

Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression

Relative Pitch Perception and the Detection of Deviant Tone Patterns.

Most people are able to recognise familiar tunes even when played in a different key. It is assumed that this depends on a general capacity for relative pitch perception; the ability to recognise the pattern of inter-note intervals that characterises the tune. However, when healthy adults are required to detect rare deviant melodic patterns in a sequence of randomly transposed standard patterns they perform close to chance. Musically experienced participants perform better than naïve participants, but even they find the task difficult, despite the fact that musical education includes training in interval recognition.To understand the source of this difficulty we designed an experiment to explore the relative influence of the size of within-pattern intervals and between-pattern transpositions on detecting deviant melodic patterns. We found that task difficulty increases when patterns contain large intervals (5-7 semitones) rather than small intervals (1-3 semitones). While task difficulty increases substantially when transpositions are introduced, the effect of transposition size (large vs small) is weaker. Increasing the range of permissible intervals to be used also makes the task more difficult. Furthermore, providing an initial exact repetition followed by subsequent transpositions does not improve performance. Although musical training correlates with task performance, we find no evidence that violations to musical intervals important in Western music (i.e. the perfect fifth or fourth) are more easily detected. In summary, relative pitch perception does not appear to be conducive to simple explanations based exclusively on invariant physical ratios

Metabonomics and Intensive Care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Effects of an exercise programme with people living with HIV: Research in a disadvantaged setting

This study aimed to analyse the physical health effects of a community based 10-week physical activity programme with people living with HIV. It was developed, implemented and evaluated in a disadvantaged community in South Africa. A pre-post research design was chosen. Major recruitment and adherence challenges resulted in a small sample. Among the 23 participants who took part in both baseline and final testing, compliant participants (n = 12) were compared to non-compliant participants (n = 11). Immunological (CD4, viral load), anthropometric (height, weight, skinfolds and waist to hip ratio), muscular strength (h1RM) and cardiopulmonary fitness (time on treadmill) parameters were measured. The compliant and non-compliant groups were not different at baseline. Muscular strength was the parameter most influenced by compliance with the physical activity programme (F = 4.516, p = 0.047). Weight loss and improvement in cardiopulmonary fitness were restricted by the duration of the programme, compliance and influencing factors (e.g. nutrition, medication). The increase in strength is significant and meaningful in the context, as the participants goals were to look healthy and strong to avoid HIV related stigma. The improvements in appearance were a motivational factor, especially since the changes were made visible in a short time. Practical implications for health promotion are described. More research contextualised in disadvantaged settings is needed.DHE

Accurate path integration in continuous attractor network models of grid cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10–100 meters and ~1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other

Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia- a case-control study

BACKGROUND: Pneumocystis jiroveci (formerly known as P. carinii f.sp. hominis) is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised individuals. Pneumocystis jiroveci can be detected by polymerase chain reaction (PCR). To investigate the clinical importance of a positive Pneumocystis-PCR among HIV-uninfected patients suspected of bacterial pneumonia, a retrospective matched case-control study was conducted. METHODS: Respiratory samples from 367 patients suspected of bacterial pneumonia were analysed by PCR amplification of Pneumocystis jiroveci. To compare clinical factors associated with carriage of P. jiroveci, a case-control study was done. For each PCR-positive case, four PCR-negative controls, randomly chosen from the PCR-negative patients, were matched on sex and date of birth. RESULTS: Pneumocystis-DNA was detected in 16 (4.4%) of patients. The median age for PCR-positive patients was higher than PCR-negative patients (74 vs. 62 years, p = 0.011). PCR-positive cases had a higher rate of chronic or severe concomitant illness (15 (94%)) than controls (32 (50%)) (p = 0.004). Twelve (75%) of the 16 PCR positive patients had received corticosteroids, compared to 8 (13%) of the 64 PCR-negative controls (p < 0.001). Detection of Pneumocystis-DNA was associated with a worse prognosis: seven (44%) of patients with positive PCR died within one month compared to nine (14%) of the controls (p = 0.01). None of the nine PCR-positive patients who survived had developed PCP at one year of follow-up. CONCLUSIONS: Our data suggest that carriage of Pneumocystis jiroveci is associated with old age, concurrent disease and steroid treatment. PCR detection of P. jiroveci has low specificity for diagnosing PCP among patients without established immunodeficiency. Whether overt infection is involved in the poorer prognosis or merely reflects sub-clinical carriage is not clear. Further studies of P. jiroveci in patients receiving systemic treatment with corticosteroids are warranted

Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant.

BACKGROUND: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. METHODS: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. RESULTS: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. CONCLUSIONS: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO