Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral pain systems

<p>Abstract</p> <p>Background</p> <p>The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding.</p> <p>Results</p> <p>Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable.</p> <p>Conclusion</p> <p>This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.</p

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic M&#xfc;llerian mimicry, thought &#x2013; but rarely demonstrated &#x2013; to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between M&#xfc;llerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Antibiotic knowledge, attitudes, and practices: new insights from cross-sectional rural health behaviour surveys in low- and middle-income South-East Asia

Introduction: Low- and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices, and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains underrepresented in AMR research. Objective: To (1) describe antibiotic-related knowledge, attitudes, and practices of the general population in two LMICs and to (2) assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers. Design: Observational study: cross-sectional rural health behaviour survey, representative on the population level. Setting: General rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018. Participants: 2141 adult members (≥18 years) of the general rural population, representing 712,000 villagers. Outcome measures: Antibiotic-related knowledge, attitudes, and practices across sites and healthcare access channels. Findings: Villagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p<0.001) and drug resistance (Chiang Rai: 74.8%; Salavan: 62.5%; p<0.001), but the usage of technical concepts for antibiotics was dwarfed by local expressions like “anti-inflammatory medicine” in Chiang Rai (87.6%; 95% confidence interval [CI]: 84.9–90.0) and “ampi” in Salavan (75.6%; 95% CI: 71.4–79.4). Multivariate linear regression suggested that attitudes against over-the-counter antibiotics were linked to 0.12 additional antibiotic use episodes from public healthcare providers in Chiang Rai (95% CI: 0.01 – 0.23) and 0.53 in Salavan (95% CI: 0.16 – 0.90). Conclusions: Locally specific conceptions and counter-intuitive practices around antimicrobials can complicate AMR communication efforts and entail unforeseen consequences. Overcoming “knowledge deficits” alone will therefore be insufficient for global AMR behaviour change. We call for an expansion of behavioural AMR strategies towards “AMR-sensitive interventions” that address context-specific upstream drivers of antimicrobial use (e.g. unemployment insurance) and complement education and awareness campaigns

Characteristics of predictor sets found using differential prioritization

<p>Abstract</p> <p>Background</p> <p>Feature selection plays an undeniably important role in classification problems involving high dimensional datasets such as microarray datasets. For filter-based feature selection, two well-known criteria used in forming predictor sets are relevance and redundancy. However, there is a third criterion which is at least as important as the other two in affecting the efficacy of the resulting predictor sets. This criterion is the degree of differential prioritization (DDP), which varies the emphases on relevance and redundancy depending on the value of the DDP. Previous empirical works on publicly available microarray datasets have confirmed the effectiveness of the DDP in molecular classification. We now propose to establish the fundamental strengths and merits of the DDP-based feature selection technique. This is to be done through a simulation study which involves vigorous analyses of the characteristics of predictor sets found using different values of the DDP from toy datasets designed to mimic real-life microarray datasets.</p> <p>Results</p> <p>A simulation study employing analytical measures such as the distance between classes before and after transformation using principal component analysis is implemented on toy datasets. From these analyses, the necessity of adjusting the differential prioritization based on the dataset of interest is established. This conclusion is supported by comparisons against both simplistic rank-based selection and state-of-the-art equal-priorities scoring methods, which demonstrates the superiority of the DDP-based feature selection technique. Reapplying similar analyses to real-life multiclass microarray datasets provides further confirmation of our findings and of the significance of the DDP for practical applications.</p> <p>Conclusion</p> <p>The findings have been achieved based on analytical evaluations, not empirical evaluation involving classifiers, thus providing further basis for the usefulness of the DDP and validating the need for unequal priorities on relevance and redundancy during feature selection for microarray datasets, especially highly multiclass datasets.</p

Unemployment and Portfolio Choice: Does Persistence Matter?

We use a life cycle model of consumption and portfolio choice to study the effects of social security on the investment decisions of households for the European case. Our model is mainly based on the one developed by Cocco, Gomes, and Maenhout (2005). We extend it by unemployment risk using Markov chains to model the transition between different employment states. In contrast to most models in the life cycle literature, our model allows for three different states, namely employment, short-term as well as long-term unemployment. This allows us to examine the effects of persistence in the unemployment process on portfolio choice. Our main findings are, first, that in case of short-term unemployment only, social security systems as those established in the EU are able to offset the negative impact of unemployment risk on the portfolio-share invested in risky assets. Second, the simulation results reveal that when allowing for long-term unemployment the equity-share is suppressed, especially for young investors. We show that this negative effect of unemployment is mainly driven by its persistence

Digit Ratio Predicts Sense of Direction in Women

The relative length of the second-to-fourth digits (2D:4D) has been linked with prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values in males than females, and appears to correlate with diverse measures of behavior. However, the relationship between digit ratio and cognition, and spatial cognition in particular, has produced mixed results. In the present study, we hypothesized that spatial tasks separating cue conditions that either favored female or male strategies would examine this structure-function correlation with greater precision. Previous work suggests that males are better in the use of directional cues than females. In the present study, participants learned a target location in a virtual landscape environment, in conditions that contained either all directional (i.e., distant or compass bearing) cues, or all positional (i.e., local, small objects) cues. After a short delay, participants navigated back to the target location from a novel starting location. Males had higher accuracy in initial search direction than females in environments with all directional cues. Lower digit ratio was correlated with higher accuracy of initial search direction in females in environments with all directional cues. Mental rotation scores did not correlate with digit ratio in either males or females. These results demonstrate for the first time that a sex difference in the use of directional cues, i.e., the sense of direction, is associated with more male-like digit ratio.National Science Foundation (U.S.) (NSF ECCS-1028319)National Science Foundation (U.S.) (NSF Graduate Student Fellowship)Mary Elisabeth Rennie Endowment for Epilepsy Researc

A Practical Platform for Blood Biomarker Study by Using Global Gene Expression Profiling of Peripheral Whole Blood

Background: Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study. Methods and Findings: We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal. Conclusion: We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study

Epidemiological risk factors for adult dengue in Singapore: an 8-year nested test negative case control study

10.1186/s12879-016-1662-4BMC Infectious Diseases16132