DynPeak : An algorithm for pulse detection and frequency analysis in hormonal time series

The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm.Comment: Nombre de pages : 35 ; Nombre de figures : 16 ; Nombre de tableaux :

Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics

Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p \u3c 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p \u3c 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p \u3c 0.05; 1.5-fold, repeated dose, p \u3c 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes

Shape of the concentration–response association between fine particulate matter pollution and human mortality in Beijing, China, and its implications for health impact assessment, The

Includes bibliographical references (pages 107009-12-107009-14).Publisher version: https://doi.org/10.1289/EHP4464.Background: Studies found approximately linear short-term associations between particulate matter (PM) and mortality in Western communities. However, in China, where the urban PM levels are typically considerably higher than in Western communities, some studies suggest nonlinearity in this association. Health impact assessments (HIA) of PM in China have generally not incorporated nonlinearity in the concentration–response (C-R) association, which could result in large discrepancies in estimates of excess deaths if the true association is nonlinear. Objectives: We investigated nonlinearity in the C-R associations between with PM with aerodynamic diameter ≤2.5μm (PM2.5) and mortality in Beijing, China, and the sensitivity of HIA to linearity assumptions. Methods: We modeled the C-R association between PM2.5 and cause-specific mortality in Beijing, China (2009–2012), using generalized linear models (GLM). PM2.5 was included through either linear, piecewise-linear, or spline functions to investigate evidence of nonlinearity. To determine the sensitivity of HIA to linearity assumptions, we estimated PM2.5-attributable deaths using both linear- and nonlinear-based C-R associations between PM2.5 and mortality. Results: We found some evidence that, for nonaccidental and circulatory mortality, the shape of the C-R association was relatively flat at lower concentrations of PM2.5, but then had a positive slope at higher concentrations, indicating nonlinearity. Conversely, the shape for respiratory mortality was positive and linear at lower concentrations of PM2.5, but then leveled off at the higher concentrations. Estimates of excess deaths attributable to short-term PM2.5 exposure were, in some cases, very sensitive to the linearity assumption in the association, but in other cases robust to this assumption. Conclusions: Our results demonstrate some evidence of nonlinearity in PM2.5–mortality associations and that an assumption of linearity in this association can influence HIAs, highlighting the importance of understanding potential nonlinearity in the PM2.5–mortality association at the high concentrations of PM2.5 in developing megacities like Beijing. https://doi.org/10.1289/EHP446

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms

Objectives: G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Methods: Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Nav1.8-expressing afferents. Results: GPCRs for gut hormones that were the most enriched in Nav1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Nav1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Nav1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Conclusion: Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Keywords: G protein-coupled receptors, Vagal afferent nerves, Gut-brain axis, Gut hormones, GLP1R, NTSR

Causal RLGC( Ƒ ) Models for Transmission Lines from Measured S-Parameters

Frequency-dependent causal RLGC(f) models are proposed for single-ended and coupled transmission lines. Dielectric loss, dielectric dispersion, and skin-effect loss are taken into account. The dielectric substrate is described by the two-term Debye frequency dependence, and the transmission line conductors are of finite conductivity. In this paper, three frequency-dependent RLGC models are studied. One is the known frequency-dependent analytical RLGC model ( RLGC-I), the second is the RLGC(f) model (RLGC-II) proposed in this paper, and the third (RLGC-III) is same as the RLGC -II, but with causality enforced by the Hilbert transform in frequency domain. The causalities of the three RLGC models are corroborated in the time domain by examining the propagation of a well-defined pulse through three different transmission lines: a single-ended stripline, a single-ended microstrip line, and an edge-coupled differential stripline pair. A clear time-domain start point is shown on each received pulse for the RLGC-II model and the RLGC-III model, where their corresponding start points overlap. This indicates that the proposed RLGC(f) model (RLGC-II) is causal. Good agreement of simulated and measured S-parameters has also been achieved in the frequency domain for the three transmission lines by using the proposed frequency-dependent RLGC (f) model

Heat-Related Mortality Projections for Cardiovascular and Respiratory Disease Under the Changing Climate in Beijing, China

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4 percent, 47.8 percent, and 69.0 percent in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6 percent, 73.8 percent and 134 percent in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP 8.5 scenario were found to reach a higher number and to increase more rapidly during the 21st century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks

A global product of fine-scale urban building height based on spaceborne lidar

Characterizing urban environments with broad coverages and high precision is more important than ever for achieving the UN's Sustainable Development Goals (SDGs) as half of the world's populations are living in cities. Urban building height as a fundamental 3D urban structural feature has far-reaching applications. However, so far, producing readily available datasets of recent urban building heights with fine spatial resolutions and global coverages remains a challenging task. Here, we provide an up-to-date global product of urban building heights based on a fine grid size of 150 m around 2020 by combining the spaceborne lidar instrument of GEDI and multi-sourced data including remotely sensed images (i.e., Landsat-8, Sentinel-2, and Sentinel-1) and topographic data. Our results revealed that the estimated method of building height samples based on the GEDI data was effective with 0.78 of Pearson's r and 3.67 m of RMSE in comparison to the reference data. The mapping product also demonstrated good performance as indicated by its strong correlation with the reference data (i.e., Pearson's r = 0.71, RMSE = 4.60 m). Compared with the currently existing products, our global urban building height map holds the ability to provide a higher spatial resolution (i.e., 150 m) with a great level of inherent details about the spatial heterogeneity and flexibility of updating using the GEDI samples as inputs. This work will boost future urban studies across many fields including climate, environmental, ecological, and social sciences

Exploring Spirituality in Teaching Within a Christian School Context Through Collaborative Action Research

This article reports on a collaborative action research project conducted in New Zealand, during 2012, exploring spirituality in teaching within a Christian school context. The experienced primary school teacher participant chose to take action around the issue of personal fear and insecurity which were believed to be hindering professional growth and relationships. Through self-directed inquiry, critical reflective journaling, Bible study, fellowship and prayer with trusted friends, the teacher experienced a renewed sense of peace and freedom in Christ. This personal transformation was believed to be influential on subsequent professional practice, assisting the teacher to become more relational, responsive and compassionate. The findings provide a rich description of the participant’s spirituality, the lived reality of a person’s spiritual life. This report will be of interest to teachers, teacher-leaders and teacher-educators who desire to explore Christian spirituality through practitioner-led inquiry

Effect of Health Literacy and Exercise Intervention on Medical Mistrust of Type 2 Diabetes Patients in the Community

BackgroundMedical distrust in patients has been related with poor compliance to medications and suboptimal clinical outcomes. Effective interventions may improve medical distrust in patients which is warranted specific studies.ObjectiveTo evaluate the effect of health literacy and exercise interventions on medical mistrust in patients with type 2 diabetes (T2DM) .MethodsThis study was based on a cluster randomized-controlled trial conducted during February 2015 to March 2016. A total of 800 T2DM patients were recruited from four community health service centers in Minhang and Changning Districts of Shanghai by using a multi-stage sampling method. All patients were randomly divided into the control group and 3 intervention groups in the community. Routine care was provided to all the patients, and on this basis, health literacy intervention, exercise intervention and health literacy + exercise intervention (comprehensive intervention) were performed to the three intervention groups based on partnership to improve diabetes education (PRIDE) toolkit, respectively. Information was collected using the Chinese versions of Health Literacy Management Scale (c-HeLMS) , the 5-item Diabetes Numeracy Test Scale (c-DNT-5) , and Medical Mistrust Index (c-MMI) at baseline, 3-, 6-, 12- (end of intervention) and 24-months follow-up (post-intervention) . The generalized estimating equation was used to evaluate the effect of the interventions at each time point.ResultsA total of 780 patients were recruited in this study. The c-MMI was a reliable and valid scale to measure medical mistrust in our subjects, with Cronbach's α of 0.826. The median score and interquartile range of c-MMI was 31 (7) at baseline while the rate of medical mistrust (scores≥30) was 65.9% (514/780) , both of which decreased at almost each follow-up survey in four groups. Compared with the control group, a lower risk of medical mistrust was observed at the 3-months〔OR (95%CI) =0.42 (0.23, 0.78) 〕 and 6-months of follow-up〔OR (95%CI) =0.46 (0.24, 0.88) 〕 for the health literacy group, at the 6-months〔OR (95%CI) =0.50 (0.25, 0.99) 〕, 12-months〔OR (95%CI) =0.43 (0.22, 0.86) 〕 and 24-months of follow-up〔OR (95%CI) =0.37 (0.19, 0.72) 〕 for the exercise group, and at the 6-months〔OR (95%CI) =0.30 (0.16, 0.56) 〕 for the comprehensive group.ConclusionBoth health literacy and exercise intervention may effectively decrease the scores of c-MMI and reduce the risk of medical mistrust in diabetes patients

Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy.

Dominant mutations in glycyl-tRNA synthetase (GlyRS) cause a subtype of Charcot-Marie-Tooth neuropathy (CMT2D). Although previous studies have shown that GlyRS mutants aberrantly interact with Nrp1, giving insight into the disease\u27s specific effects on motor neurons, these cannot explain length-dependent axonal degeneration. Here, we report that GlyRS mutants interact aberrantly with HDAC6 and stimulate its deacetylase activity on α-tubulin. A decrease in α-tubulin acetylation and deficits in axonal transport are observed in mice peripheral nerves prior to disease onset. An HDAC6 inhibitor used to restore α-tubulin acetylation rescues axonal transport deficits and improves motor functions of CMT2D mice. These results link the aberrant GlyRS-HDAC6 interaction to CMT2D pathology and suggest HDAC6 as an effective therapeutic target. Moreover, the HDAC6 interaction differs from Nrp1 interaction among GlyRS mutants and correlates with divergent clinical presentations, indicating the existence of multiple and different mechanisms in CMT2D. Nat Commun 2018 Mar 8; 9(1):1007