Developing a video expert panel as a reference standard to evaluate respiratory rate counting in paediatric pneumonia diagnosis: protocol for a cross-sectional study

INTRODUCTION: Manual counting of respiratory rate (RR) in children is challenging for health workers and can result in misdiagnosis of pneumonia. Some novel RR counting devices automate the counting of RR and classification of fast breathing. The absence of an appropriate reference standard to evaluate the performance of these devices is a challenge. If good quality videos could be captured, with RR interpretation from these videos systematically conducted by an expert panel, it could act as a reference standard. This study is designed to develop a video expert panel (VEP) as a reference standard to evaluate RR counting for identifying pneumonia in children. METHODS AND ANALYSIS: Using a cross-sectional design, we will enrol children aged 0–59 months presenting with suspected pneumonia at different levels of health facilities in Dhaka and Sylhet, Bangladesh. We will videorecord a physician/health worker counting RR manually and also using an automated RR counter (Children’s Automated Respiration Monitor) from each child. We will establish a standard operating procedure for capturing quality videos, make a set of reference videos, and train and standardise the VEP members using the reference videos. After that, we will assess the performance of the VEP as a reference standard to evaluate RR counting. We will calculate the mean difference and proportions of agreement within±2 breaths per minute and create Bland-Altman plots with limits of agreement between VEP members. ETHICS AND DISSEMINATION: The study protocol was approved by the National Research Ethics Committee of Bangladesh Medical Research Council, Bangladesh (registration number: 39315022021) and Edinburgh Medical School Research Ethics Committee (EMREC), Edinburgh, UK (REC Reference: 21-EMREC-040). Dissemination of the study findings will be through conference presentations and publications in peer-reviewed scientific journals

Down Syndrome: Let's Work Together to End the Stereotypes

Each year, we observe the 21st day of March as our World Down Syndrome Day. The goal is to raise public awareness of Down syndrome (DS) and encourage all member states, relevant organizations of the UN system, all member states, other international organizations, non-governmental organizations, and the private sector to join this effort. The epidemiology of DS is complex. The incidence of DS is estimated to be somewhere between 1 in 1,000 and 1 in 1,200 live births worldwide, but there may well be some temporal, racial/ethnic, and geographical variability in the prevalence of DS. Most infants with DS have an extra copy of chromosome 21, which occurs due to the failure of chromosome 21 to separate during gametogenesis. However, a minority with the same phenotype may have a Robertsonian translocation, an isochromosome, or a ring chromosome. Increasing information suggests that many of the most frequently seen phenotypic features may be rooted in sequential variability in only one band, the 21q22. The characteristic facial appearance, cardiac anomalies such as the endocardial cushion defect, neurodevelopmental delay, and many dermatoglyphic changes could result from a small region including the genes for superoxide dismutase in the region 21q22.1, the amyloid precursor protein mapping in 21q11.2-21.05, and six probes for single-copy sequences: D21S46 in 21q11.2-21.05, D21S47 and SF57 in 21q22.1-22.3, and D21S39, D21S42, and D21S43 in 21q22.3. Speaking from this medical perspective, we need to understand the pathophysiology of DS to meet their healthcare needs. If we could do so, we could make a small change in this world

Effects of neuroactive steroids on the recombinant GABAA receptor in Xenopus oocyte

Introduction: Neuroactive steroids represent a class of both synthetic and naturally occurring steroids that have an effect on neural function. In addition to classical genomic mechanism by the hormones progesterone, deoxycorticosterone and testosterone 3α-OH metabolites of these hormones enhance GABAA receptor through rapid non-genomic mechanism. The site(s) of action of these neuroactive steroids namely 3α-OH-5α-pregnan-20 one, (3α,5α)-3,21-deoxycorticosterone(3α5α-THDOC) and 5α androstane-3α,17β-diol on GABAA receptor are distinct from that of benzodiazepines and barbiturate binding sites. The modulation site(s) has a well-defined structure activity relationship with a 3α-hydroxy and a 20-ketone configuration in the pregnane molecule required for agonistic action. Pregnenolone sulfate is a noncompetitive GABAA receptor antagonist and inhibit GABA activated Cl- current in an activation dependant manner. 3β-hydroxy A-ring reduced pregnane steroids are also GABAA receptor antagonist and inhibit GABAA receptor function and its potentiation induced by their 3α-diesteromers in a noncompetitive manner. Aim: The aim was to investigate if the effect of GABA, pentobarbital antagonism by bicuculline and if the effect of GABA-agonist and antagonist neuroactive steroids including pregnenolone sulfate is dependant on the α-subunits of GABAA receptor. Furthermore, the studies aimed at investigating the binding site of pregnenolone sulfate and if its effect is dependent on γ-subunit. In addition, the inhibitory effect of pregnenolone sulfate and 3β-hydroxy steroids has been characterized. We also wanted to investigate if the neuroactive steroids effect vary between the human and rat recombinant α1β2γ2L receptors and between the long (L) and short (S) variants of γ2-subunit. Method: Experiments were performed by the two electrodes voltage-clamp technique using oocytes of Xenopus laevis expressed with recombinant GABAA receptors containing α1, α4 or α5, β2, γ2L and γ2S-subunits. Results: There was no difference between the α1, α4 and α5-containing subunits regarding GABA and pentobarbital inhibition by bicuculline. GABA-activated current in the binary αβ was potent than that of ternary αβγ receptor. Unlike Zn2+ effect, inhibition by pregnenolone sulfate on the GABAA receptor is not dependant on the γ-subunit. It is likely that the 2’ residue closest to the N-terminus of the protein at M2 helix on both α1 and β2 subunit are critical to the inhibitory actions of PS and the function of Cl- channels. Point mutation at M2 helix of the β2-subunit (b2A252S) can dramatically reduce the inhibitory effect of PS on the GABAA receptors without affecting the inhibitory properties of 3β-hydroxysteroids. Agonist and antagonist steroids also varied in their efficacy between the human and rat α1β2γ2L receptor. Neuroactive steroids also showed difference between human γ2L and γ2S-containing receptor. Conclusions: GABA and pentobarbital antagonism by bicuculline is not dependant on α-subunit. Pregnenolone sulfate binding site is different from that of Zn2+. 3β-hydroxysteroids and pregnenolone sulfate inhibit GABAA receptor through different mechanisms. Neuroactive steroids also differ between species and between the long and short variant of γ- subunit

Dark-to-bright Transition of Coronal Holes and Spectropolarimetric Imaging of Type III Solar Radio Bursts Using the MWA.

Low-frequency (80-240 MHz) radio observations of coronal holes (CHs) and type III solar radio bursts are presented using the Murchison Widefield Array (MWA). The first chapter presents a short overview of the solar corona, quiet Sun, active regions, solar flares, and CHs. The second chapter describes dark-to-bright transitions of CHs as a function of frequency. This transition is attributed to refraction of radio waves into the low density CH regions. A qualitative model is developed based on this idea and the relative optical depths. The third chapter addresses the circular polarization of type III bursts. Higher polarization fractions are found when the burst source is near disk center and lower polarization fractions are obtained near the limb. Total intensity (Stokes I), circularly polarized intensity (Stokes V), and polarization fraction (|V|/I) profiles and images of type III bursts are studied as a function of position at times near burst maximum. At burst onset, we find higher polarization fractions for the burst source, which is interpreted in terms of a larger contribution from fundamental plasma emission. At burst maximum the polarization fraction is lower, corresponding to a mixture of fundamental and harmonic emission. During the decay phase, the emission is dominated again by the fundamental component, which decays with lesser polarization fraction due to scattering. The decay time is measured, finding larger values and frequency dependences than previous observations. The fourth chapter discusses burst source sizes, flux densities, and brightness temperatures in both Stokes I and V images. The source area, fluxes and brightness temperatures increase as frequency decreases. The interpretation is that the observed changes in source size are mostly due to divergence of open magnetic field lines. The last chapter summarizes the results and suggests future work

Electrical properties of boron delta-layers in silicon

726-731<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">Electrical properties or MBE grown boron δ- layer in Si have been investigated in the temperature range 10-300 K and a comparative study with their uniform doping counterpart has been presented. Various boron doping levels from 1012-1014 <span style="font-size:14.0pt;line-height:115%;font-family: " times="" new="" roman";mso-fareast-font-family:hiddenhorzocr;color:black;mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">cm-2 in the δ- layer show that, with the fall of temperature from 300 to 50 K. Hall mobility first increases followed by a rapid decrease, and at temperature ≤50 K, it becomes almost constant. Higher doping level in the sample grossly lowers the value of Hall mobility but its variations with temperature are almost similar to each other. Existence of the dominant carrier scattering mechanism has also been reported. In all the samples, freeze-out of carriers have been clearly noticed below 100K. Existence of a Mott metal-non-metal transition in the sample has been observed at low temperature region when the doping <span style="font-size:14.0pt;line-height:115%;font-family: " times="" new="" roman";mso-fareast-font-family:hiddenhorzocr;color:black;mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">concentration exceeds a critical high value of 6×10-13 cm-2, and this has been found consistently with the other observations like zero activation energy and negative TCR. The value of minimal metallic conductance for the samples has also been reported.</span

Electrophysiological characterization of voltage-dependent calcium-currents and TRPV4-currents in human pulmonary fibroblasts

We have presented indirect evidence of a key role for voltage-dependent Ca2+-currents in TGFβ-induced synthetic function in human pulmonary fibroblast (HPF) as well as in bleomycin-induced pulmonary fibrosis in mice. Others, however, have provided indirect evidence for TRPV4 channels in both of those effects. Unfortunately, definitive electrophysiological descriptions of both currents in HPFs have been entirely lacking. In this study, we provide the first direct electrophysiological and pharmacological evidence of the currents in HPFs at rest and during overnight stimulation with TGFβ. These currents include a Ca2+-dependent K+-current, a TRPV4-current, a chloride current, and an L-type voltage-dependent Ca2+-current. Evidence for the TRPV4-current include activation of a large conductance change by two putatively TRPV4-selective agonists (4α-phorbol-12,13-didecanoate; GSK1016790A), with a reversal potential near 0 mV, partial sensitivity to two different TRPV4-selective blockers (RN1734; HC067047), and partial reduction following removal of external Na+. Substantial reduction of the evoked current was seen following the co-application of RN1734, DIDS and niflumic acid, suggesting that a chloride current is also involved. The voltage-dependent Ca2+-current is found to be 'L-type' in nature, as indicated by the voltage- and time-dependence of its activation, deactivation and inactivation properties, and by its pharmacology (sensitivity to replacement with barium; inhibition by nifedipine, verapamil or mibefradil). We also found that overnight treatment with TGFβ evoked a periodic current (inward at negative holding potentials, with reversal potential near 0 mV) which is sufficient to trigger the voltage-dependent Ca2+-currents and thereby account for the rhythmic Ca2+-oscillations which we have described previously in these cells.status: publishe

<span style="font-size: 22.5pt;mso-bidi-font-size:15.5pt;font-family:"Times New Roman","serif"; mso-bidi-font-weight:bold">Anomalous resistive transition and frequency dependent dielectric constant of <span style="font-size:21.5pt; mso-bidi-font-size:14.5pt;font-family:"Arial","sans-serif";mso-bidi-font-weight: bold;mso-bidi-font-style:italic">Zn_1-_{<span style="font-size:23.0pt;mso-bidi-font-size:16.0pt;font-family:"Times New Roman","serif"; mso-bidi-font-weight:bold;mso-bidi-font-style:italic">x</span>}<span style="font-size:23.0pt;mso-bidi-font-size:16.0pt;font-family:"Times New Roman","serif"; mso-bidi-font-weight:bold;mso-bidi-font-style:italic">M_xO <span style="font-size:22.5pt;mso-bidi-font-size:15.5pt;font-family:"Times New Roman","serif"; mso-bidi-font-weight:bold">[M=Li (Mg, Ba)] system </span></span></span></span>

211-216<span style="font-size: 15.0pt;mso-bidi-font-size:8.0pt;font-family:" times="" new="" roman","serif""="">The II-VI materials of Zn1-xMxO have been synthesized by solid-state reaction method and their structural, electrical and dielectric properties studied. The lattice parameters of these materials are found to be consistent with the reported values. The dielectric constant measured at different five frequencies agrees well with the published values and found to be maximum for doping concentration <span style="font-size:15.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman","serif""="">x= 0.2, at all frequencies. A de resistive anomaly was found for all samples at a certain temperature called transition temperature (Td-s) from dielectric to semiconducting state, which depends on the concentration and nature of the dopant atoms in ZnO. </span

Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility

Guinea pig mesenteric lymphatic vessels exhibit rhythmic constrictions induced by action potential (AP)-like spikes and initiated by entrainment of spontaneous transient depolarizations (STDs). To characterize STDs and the signaling mechanisms responsible for their occurrence, we used intracellular microelectrodes, Ca²⁺ imaging, and pharmacological agents. In our investigation of the role of intracellular Ca²⁺ released from Ca²⁺ stores, we observed that intracellular Ca²⁺ transients accompanied some STDs, although there were many exceptions where Ca²⁺ transients occurred without accompanying STDs. STD frequency and amplitude were markedly affected by activators/inhibitors of inositol 1,4,5-trisphosphate receptors (IP₃Rs) but not by treatments known to alter Ca²⁺ release via ryanodine receptors. A role for Ca²⁺-activated Cl⁻ (ClCa) channels was indicated, as STDs were dependent on the Cl⁻ but not Na⁺ concentration of the superfusing solution and were inhibited by the ClCa channel blockers niflumic acid (NFA), anthracene 9-carboxylic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid but not by the volume-regulated Cl⁻ blocker DIDS. Increases in STD frequency and amplitude induced by agonist stimulation were also inhibited by NFA. Nifedipine, the hyperpolarization-activated inward current blocker ZD-7288, and the nonselective cation/store-operated channel blockers SKF-96365, Gd³⁺, and Ni²⁺ had no or marginal effects on STD activity. However, nifedipine, 2-aminoethoxydiphenyl borate, NFA, SKF-96365, Gd³⁺, and Ni²⁺ altered the occurrence of spontaneous APs. Our findings support a role for Ca²⁺ release through IP₃Rs and a resultant opening of ClCa channels in STD generation and confirm the importance of these events in the initiation of lymphatic spontaneous APs and subsequent contractions. The abolition of spontaneous APs by blockers of other excitatory ion channels suggests a contribution of these conductances to lymphatic pacemaking