Coherent mapping of position and head direction across auditory and visual cortex.

Neurons in primary visual cortex (V1) may not only signal current visual input but also relevant contextual information such as reward expectancy and the subject's spatial position. Such contextual representations need not be restricted to V1 but could participate in a coherent mapping throughout sensory cortices. Here, we show that spiking activity coherently represents a location-specific mapping across auditory cortex (AC) and lateral, secondary visual cortex (V2L) of freely moving rats engaged in a sensory detection task on a figure-8 maze. Single-unit activity of both areas showed extensive similarities in terms of spatial distribution, reliability, and position coding. Importantly, reconstructions of subject position based on spiking activity displayed decoding errors that were correlated between areas. Additionally, we found that head direction, but not locomotor speed or head angular velocity, was an important determinant of activity in AC and V2L. By contrast, variables related to the sensory task cues or to trial correctness and reward were not markedly encoded in AC and V2L. We conclude that sensory cortices participate in coherent, multimodal representations of the subject's sensory-specific location. These may provide a common reference frame for distributed cortical sensory and motor processes and may support crossmodal predictive processing.

Socioeconomic differences in caesarean section - are they explained by medical need? An analysis of patient record data of a large Kenyan hospital.

BACKGROUND: Caesarean section (C-section) rates are often low among the poor and very high among the better-off in low- and middle-income countries. We examined to what extent these differences are explained by medical need in an African context. METHODS: We analyzed electronic records of 12,209 women who gave birth in a teaching hospital in Kenya in 2014. C-section rates were calculated by socioeconomic position (SEP), using maternal occupation (professional, small business, housewife, student) as indicator. We assessed if women had documented clinical indications according to hospital guidelines and if socioeconomic differences in C-section rates were explained by indication. RESULTS: Indication for C-section according to hospital guidelines was more prevalent among professionals than housewives (16% vs. 9% of all births). The C-section rate was also higher among professionals than housewives (21.1% vs. 15.8% [OR 1.43; 95%CI 1.23-1.65]). This C-section rate difference was largely explained by indication (4.7 of the 5.3 percentage point difference between professionals and housewives concerned indicated C-sections, often with previous C-section as indication). Repeat C-sections were near-universal (99%). 43% of primary C-sections had no documented indication. Over-use was somewhat higher among professionals than housewives (C-section rate among women without indication: 6.6 and 5.5% respectively), which partly explained socioeconomic differences in primary C-section rate. CONCLUSIONS: Socioeconomic differences in C-section rates can be largely explained by unnecessary primary C-sections and higher supposed need due to previous C-section. Prevention of unnecessary primary C-sections and promoting safe trial of labor should be priorities in addressing C-section over-use and reducing inequalities. Unnecessary primary C-sections and ubiquitous repeat C-sections drive overall C-section rates and C-section inequalities.

The circuit architecture of cortical multisensory processing: Distinct functions jointly operating within a common anatomical network.

Our perceptual systems continuously process sensory inputs from different modalities and organize these streams of information such that our subjective representation of the outside world is a unified experience. By doing so, they also enable further cognitive processing and behavioral action. While cortical multisensory processing has been extensively investigated in terms of psychophysics and mesoscale neural correlates, an in depth understanding of the underlying circuit-level mechanisms is lacking. Previous studies on circuit-level mechanisms of multisensory processing have predominantly focused on cue integration, i.e. the mechanism by which sensory features from different modalities are combined to yield more reliable stimulus estimates than those obtained by using single sensory modalities. In this review, we expand the framework on the circuit-level mechanisms of cortical multisensory processing by highlighting that multisensory processing is a family of functions - rather than a single operation - which involves not only the integration but also the segregation of modalities. In addition, multisensory processing not only depends on stimulus features, but also on cognitive resources, such as attention and memory, as well as behavioral context, to determine the behavioral outcome. We focus on rodent models as a powerful instrument to study the circuit-level bases of multisensory processes, because they enable combining cell-type-specific recording and interventional techniques with complex behavioral paradigms. We conclude that distinct multisensory processes share overlapping anatomical substrates, are implemented by diverse neuronal micro-circuitries that operate in parallel, and are flexibly recruited based on factors such as stimulus features and behavioral constraints.

Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice during track running and flanking sleep periods. Locomotor activity, basic firing and spatial coding properties of CA1 cells in knockout mice were not different from wild-type mice. During active behavior, however, knockout animals showed a significantly shifted balance in LFP power, with a relative loss in high-frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover, during track-running, knockout mice showed a decrease in phase locking of spiking activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been associated with memory consolidation and replay, showed only minor differences in dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1 effects on memory formation are not only manifested at the level of molecular pathways regulating synaptic plasticity, but also at the systems level. The disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss of spike-field phase locking may affect memory encoding during initial storage and memory consolidation stages.

Hyperpolarization-activated cyclic nucleotide-gated 1 independent grid cell-phase precession in mice.

Cell assemblies code information in both the temporal and spatial domain. One tractable example of temporal coding is the phenomenon of phase precession. In medial entorhinal cortex, theta-phase precession is observed in spatially specific grid cells, with grid spike-times shifting to earlier phases of the extracellular theta rhythm as the animal passes through the grid field. Although the exact mechanisms underlying spatial-temporal coding remain unknown, computational work points to single-cell oscillatory activity as a biophysical mechanism capable of producing phase precession. Support for this idea comes from observed correlations between single-cell resonance and entorhinal neurons characterized by phase precession. Here, we take advantage of the absence of single-cell theta-frequency resonance in hyperpolarization-activated cyclic nucleotide-gated (HCN) 1 knockout (KO) mice to examine the relationship between intrinsic rhythmicity and phase precession. We find phase precession is highly comparable between forebrain-restricted HCN1 KO and wild-type mice. Grid fields in HCN1 KO mice display more experience-dependent asymmetry however, consistent with reports of enhanced long-term potentiation in the absence of HCN1 and raising the possibility that the loss of HCN1 improves temporal coding via the rate-phase transformation. Combined, our results clarify the role of HCN1 channels in temporal coding and constrain the number of possible mechanisms generating phase precession. © 2013 Wiley Periodicals, Inc.

Collapse behavior and forces of multistack nanolines.

Two types of multistack nanolines (MNLs), Si-substrate (Si)/siliconoxynitride (SiON)/amorphous Si (a-Si)/ SiO(2) and Si/ SiO(2) /polycrystalline Si (poly-Si)/ SiO(2) were used to measure the collapse force and to investigate their collapse behavior by an atomic force microscope (AFM). The Si/SiON/a-Si/ SiO(2) MNL showed a larger length of fragment in the collapse patterns at a smaller collapse force. The Si/ SiO(2) /poly-Si/ SiO(2) MNL, however, demonstrated a smaller length of fragment at a higher applied collapse force. The collapse forces increased by the square of the linewidth in both Si/SiON/a-Si/ SiO(2) and Si/SiO(2) /poly-Si/ SiO(2) MNLs. Once an AFM tip touches an Si/SiON/a-Si/ SiO(2) line, which is a softer MNL, it was delaminated first at the Si/SiON interface. One end of the delaminated line was first broken and then the other end was bent until it was broken. A harder MNL, Si/ SiO(2) /poly-Si/ SiO(2), however, was broken at two ends simultaneously after the delamination occurred at the Si/ SiO(2) /poly-Si interface. The different collapse behaviors were attributed to the magnitude of adhesion forces at the stack material interfaces and the mechanical strength of MNLs.

Sensitivity and specificity of single IgA and IgG antibody concentrations for early diagnosis of pertussis in adults: an evaluation for outbreak management in public health practice.

BACKGROUND: An accurate, practical laboratory test is needed to confirm clinical diagnosis of pertussis in adults during the first 3 symptomatic weeks, when treatment is effective and transmission can be interrupted. METHODS: The sensitivity and specificity of single IgA and IgG levels were assessed in a cohort study of a pertussis epidemic in 99 adults in a closed community. Sensitivities were assessed in the sera of 46 laboratory confirmed clinical pertussis cases during the first 3 weeks. Specificities were calculated in sera of 35 asymptomatic controls without clinical symptoms or laboratory confirmed infections from the same community (internal controls). We compared these specificities with the specificities of single IgA and IgG levels in 4275 external controls from a cross-section of the general Dutch population aged 21-79 years who had not coughed for more than 2 weeks in the past year, and without pertussis diagnoses. The study was done in the Netherlands when whole-cell pertussis vaccine was used in the national vaccination programme. RESULTS: Levels of 24 U/ml for IgA and 27 U/ml for IgG gave sensitivities of 100% and 75%, respectively, in the first 2 weeks, 100% in the third week, and 97% after the fourth week. The levels were reached within 2 days after onset of increase, and remained above these levels for roughly 7.2 and 5.1 months, respectively. Specificity was 82% for IgA and 89% for IgG in the internal controls and 90% in the external controls, respectively. CONCLUSION: We suggest levels of 24 U/ml for IgA level and 27 U/ml (= 27 International Units (IU)/ml) for IgG as sensitive, specific, and practical for laboratory confirmation of clinical pertussis in adults in the first 3 weeks of outbreak management.

A pertussis outbreak associated with social isolation among elderly nuns in a convent.

The pertussis incidence during an outbreak in a convent in The Netherlands in 1992 was higher among 75 retired (unvaccinated) nuns (60%) than among 24 staff members (8%) and was higher among 9 nuns with only a convent career (100%) than among 66 nuns who had a career outside of the convent (55%). The pertussis incidence increased with duration of social isolation but not with age.

Recombinant P-selectin glycoprotein ligand-immunoglobulin, a P-selectin antagonist, as an adjunct to thrombolysis in acute myocardial infarction. The P-Selectin Antagonist Limiting Myonecrosis (PSALM) trial.

BACKGROUND: Inflammatory responses induced by reperfusion of previously ischemic myocardial tissue may lead to further damage of the microvascular structures. A group of cell adhesion molecules, named selectins, initiate those inflammatory changes at the endothelial wall surface. Recombinant P-selectin glycoprotein ligand-immunoglobulin (rPSGL-Ig), a P-selectin antagonist, was shown to have beneficial effects in several animal models of acute myocardial ischemia. We performed a mechanistic study with positron emission tomography to test the potential benefits of rPSGL-Ig in patients with ST-segment elevation acute myocardial infarction. METHODS: Patients with ST-elevation acute myocardial infarction presenting within the first 6 hours of onset of chest pain were enrolled. All patients received alteplase. Patients were randomly assigned in a 1:1:1 ratio to 3 treatment groups: placebo; 75 mg rPSGL-Ig; 150 mg rPSGL-Ig, given intravenously. Coronary angiography was performed 90 minutes after the start of thrombolytic therapy for TIMI flow grading. Myocardial blood flow (MBF) was measured with 13NH3 at rest and after adenosine administration on day 5. Myocardial blood flow at rest was measured again at day 30, followed by measurement of 18FDG uptake. In addition, a multigated acquisition, gated equilibrium blood pool study was performed at day 30. Continuous 12-lead electrocardiogram recording was performed during the first 24 hours. RESULTS: The trial was prematurely stopped by the sponsor for lack of efficacy in an accompanying larger trial after enrolling 88 patients in the current study. Median MBF in the infarct-related territory (expressed as percentage of the normalized blood flow) at day 5 was similar in the 3 treatment groups (9.1% in the placebo group vs 3.8% in the 75-mg dose and 4.3% in the 150-mg rPSGL-Ig treatment group; P = not significant). No significant differences in MBF reserve, myocardial metabolism, ST-segment resolution, left ventricular ejection fraction, or TIMI flow grade were found among the 3 groups. CONCLUSIONS: In this prematurely stopped mechanistic study, there was no evidence of a benefit of rPSGL-Ig given as an adjunct to thrombolysis on epicardial vessel patency, myocardial tissue reperfusion, or recovery of function.

Risk of introduction of poliovirus into a Dutch Cape Verdian community during an outbreak of poliovirus in Cape Verde, 2000.

OBJECTIVE: To assess the risk of introduction of polio virus in a Cape Verdian community of Rotterdam, during the polio epidemic in Cape Verde in 2000. METHODS: All 225 insufficiently vaccinated 0-14-year-old Cape Verdian children (n=4188) and a random sample of 285 out of all 15-30-year-old Cape Verdians (n=5074) in Rotterdam were surveyed to assess travel behaviour and vaccination coverage. Faecal specimens were collected and sewage samples taken in neighbourhoods with a sizable Cape Verdian population for testing of polio virus. RESULTS: During the polio epidemic in Cape Verde, 10% of insufficiently vaccinated children aged 0-14 years and 17% of adults aged 15-30 years living in Rotterdam reported travelling to Cape Verde. 94.6% of Cape Verdians in Rotterdam aged 0-14 years were sufficiently vaccinated against polio, but 9 of 91 insufficiently vaccinated children had travelled to Cape Verde during the epidemic. Of those aged 15-30 years, 10% were not vaccinated against polio. In the faeces of 80 insufficiently vaccinated individuals aged 0-14 years and in 74 adults aged 15-30 years, no poliovirus was detected. Samples of sewage from six sites were negative for poliovirus. CONCLUSION: No evidence of poliovirus infection was found in the Cape Verde population in Rotterdam despite extensive travel to the Cape Verde during the outbreak.

Defining the transmurality of a chronic myocardial infarction by ultrasonic strain-rate imaging: implications for identifying intramural viability: an experimental study.

BACKGROUND: In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. METHODS AND RESULTS: After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SR(SYS)) and systolic strains (epsilon(SYS)) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SR(SYS) (dobutamine: bs, 4.8+/-0.4 s(-1); 20 microg x kg(-1) x min(-1), 9.9+/-0.7 s(-1); P<0.0001) and an initial increase of epsilon(SYS) at low dose (bs, 58+/-5%; at 5 microg x kg(-1) x min(-1), 78+/-6%; P<0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SR(SYS) and epsilon(SYS) were significantly lower than prestent values (SR(SYS), 2.9+/-0.5 s(-1) and epsilon(SYS), 32+/-6%, P<0.05 versus prestent). During dobutamine infusion, SR(SYS) increased slightly at 5 microg x kg(-1) x min(-1) (4.7+/-0.6 s(-1), P<0.05) but fell during higher infusion rates, whereas epsilon(SYS) showed no change. For nontransmural infarctions, transmural scar extension correlated closely with epsilon(SYS) at bs (r=0.88). For transmural infarctions, SR(SYS) at bs was significantly reduced and epsilon(SYS) was almost not measurable (SR(SYS), 1.8+/-0.3 s(-1); epsilon(SYS), 3+/-4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. CONCLUSIONS: Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.