Human visceral nociception: findings from translational studies in human tissue.

Peripheral sensitization of nociceptors during disease has long been recognized as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitization is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular, irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans and, in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons, the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurons combined with unbiased RNA-sequencing approaches have revealed fundamental differences in not only receptor/channel expression but also peripheral pain pathways.Non

Evaluation of Spontaneous Swallow Frequency in Healthy People and Those With, or at Risk of Developing, Dysphagia: A Review.

Dysphagia is a common and frequently undetected complication of many neurological disorders and of sarcopoenia in ageing persons. Spontaneous swallowing frequency (SSF) has been mooted as a possible tool to classify dysphagia risk. We conducted a review of the literature to describe SSF in both the healthy population and in disease-specific populations, in order to consider its utility as a screening tool to identify dysphagia. We searched Medline, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials databases. Metadata were extracted, collated and analysed to give quantitative insight. Three hundred and twelve articles were retrieved, with 19 meeting inclusion and quality criteria. Heterogeneity between studies was high (I2 = 99%). Mean SSF in healthy younger sub-groups was 0.98/min [CI: 0.67; 1.42]. In the Parkinson’s sub-group, mean SSF was 0.59/min [0.40; 0.87]. Mean SSF in healthy older, higher risk and dysphagic populations were similar (0.21/min [0.09; 0.52], 0.26/min [0.10; 0.72] and 0.30/min [0.16; 0.54], respectively). SSF is a novel, non-invasive clinical variable which warrants further exploration as to its potential to identify persons at risk of dysphagia. Larger, well-conducted studies are needed to develop objective, standardised methods for detecting SSF, and develop normative values in healthy populations

Estimating translational selection in Eukaryotic Genomes

Natural selection on codon usage is a pervasive force that acts on a large variety of prokaryotic and eukaryotic genomes. Despite this, obtaining reliable estimates of selection on codon usage has proved complicated, perhaps due to the fact that the selection coefficients involved are very small. In this work, a population genetics model is used to measure the strength of selected codon usage bias, S, in 10 eukaryotic genomes. It is shown that the strength of selection is closely linked to expression and that reliable estimates of selection coefficients can only be obtained for genes with very similar expression levels. We compare the strength of selected codon usage for orthologous genes across all 10 genomes classified according to expression categories. Fungi genomes present the largest S values (2.24–2.56), whereas multicellular invertebrate and plant genomes present more moderate values (0.61–1.91). The large mammalian genomes (human and mouse) show low S values (0.22–0.51) for the most highly expressed genes. This might not be evidence for selection in these organisms as the technique used here to estimate S does not properly account for nucleotide composition heterogeneity along such genomes. The relationship between estimated S values and empirical estimates of population size is presented here for the first time. It is shown, as theoretically expected, that population size has an important role in the operativity of translational selection

Resilience learning for water sector culture change

This is the author accepted manuscript. The final version is available from the European Water Association via the link in this recor

Clustered bottlenecks in mRNA translation and protein synthesis

We construct an algorithm that generates large, band-diagonal transition matrices for a totally asymmetric exclusion process (TASEP) with local hopping rate inhomogeneities. The matrices are diagonalized numerically to find steady-state currents of TASEPs with local variations in hopping rate. The results are then used to investigate clustering of slow codons along mRNA. Ribosome density profiles near neighboring clusters of slow codons interact, enhancing suppression of ribosome throughput when such bottlenecks are closely spaced. Increasing the slow codon cluster size, beyond $\approx 3-4$, does not significantly reduce ribosome current. Our results are verified by extensive Monte-Carlo simulations and provide a biologically-motivated explanation for the experimentally-observed clustering of low-usage codons

Detector-Agnostic Phase-Space Distributions

The representation of quantum states via phase-space functions constitutes an intuitive technique to characterize light. However, the reconstruction of such distributions is challenging as it demands specific types of detectors and detailed models thereof to account for their particular properties and imperfections. To overcome these obstacles, we derive and implement a measurement scheme that enables a reconstruction of phase-space distributions for arbitrary states whose functionality does not depend on the knowledge of the detectors, thus defining the notion of detector-agnostic phase-space distributions. Our theory presents a generalization of well-known phase-space quasiprobability distributions, such as the Wigner function. We implement our measurement protocol, using state-of-the-art transition-edge sensors without performing a detector characterization. Based on our approach, we reveal the characteristic features of heralded single- and two-photon states in phase space and certify their nonclassicality with high statistical significance

Pain Severity Correlates With Biopsy-Mediated Colonic Afferent Activation But Not Psychological Scores in Patients With IBS-D.

INTRODUCTION: Despite heterogeneity, an increased prevalence of psychological comorbidity and an altered pronociceptive gut microenvironment have repeatedly emerged as causative pathophysiology in patients with irritable bowel syndrome (IBS). Our aim was to study these phenomena by comparing gut-related symptoms, psychological scores, and biopsy samples generated from a detailed diarrhea-predominant IBS patient (IBS-D) cohort before their entry into a previously reported clinical trial. METHODS: Data were generated from 42 patients with IBS-D who completed a daily 2-week bowel symptom diary, the Hospital Anxiety and Depression score, and the Patient Health Questionnaire-12 Somatic Symptom score and underwent unprepared flexible sigmoidoscopy. Sigmoid mucosal biopsies were separately evaluated using immunohistochemistry and culture supernatants to determine cellularity, mediator levels, and ability to stimulate colonic afferent activity. RESULTS: Pain severity scores significantly correlated with the daily duration of pain (r = 0.67, P < 0.00001), urgency (r = 0.57, P < 0.0005), and bloating (r = 0.39, P < 0.05), but not with psychological symptom scores for anxiety, depression, or somatization. Furthermore, pain severity scores from individual patients with IBS-D were significantly correlated (r = 0.40, P < 0.008) with stimulation of colonic afferent activation mediated by their biopsy supernatant, but not with biopsy cell counts nor measured mediator levels. DISCUSSION: Peripheral pronociceptive changes in the bowel seem more important than psychological factors in determining pain severity within a tightly phenotyped cohort of patients with IBS-D. No individual mediator was identified as the cause of this pronociceptive change, suggesting that nerve targeting therapeutic approaches may be more successful than mediator-driven approaches for the treatment of pain in IBS-D

How organizational cognitive neuroscience can deepen understanding of managerial decision-making:a review of the recent literature and future directions

There is growing interest in exploring the potential links between human biology and management and organization studies, which is bringing greater attention to bear on the place of mental processes in explaining human behaviour and effectiveness. The authors define this new field as organizational cognitive neuroscience (OCN), which is in the exploratory phase of its emergence and diffusion. It is clear that there are methodological debates and issues associated with OCN research, and the aim of this paper is to illuminate these concerns, and provide a roadmap for rigorous and relevant future work in the area. To this end, the current reach of OCN is investigated by the systematic review methodology, revealing three clusters of activity, covering the fields of economics, marketing and organizational behaviour. Among these clusters, organizational behaviour seems to be an outlier, owing to its far greater variety of empirical work, which the authors argue is largely a result of the plurality of research methods that have taken root within this field. Nevertheless, all three clusters contribute to a greater understanding of the biological mechanisms that mediate choice and decision-making. The paper concludes that OCN research has already provided important insights regarding the boundaries surrounding human freedom to act in various domains and, in turn, self-determination to influence the workplace. However, there is much to be done, and emerging research of significant interest is highlighted