In vertebrate hearts, the ventricular trabecular myocardium develops as a sponge-like network of cardiomyocytes that is critical for contraction and conduction, ventricular septation, papillary ...muscle formation and wall thickening through the process of compaction
. Defective trabeculation leads to embryonic lethality
or non-compaction cardiomyopathy (NCC)
. There are divergent views on when and how trabeculation is initiated in different species. In zebrafish, trabecular cardiomyocytes extrude from compact myocardium
, whereas in chicks, chamber wall thickening occurs before overt trabeculation
. In mice, the onset of trabeculation has not been described, but is proposed to begin at embryonic day 9.0, when cardiomyocytes form radially oriented ribs
. Endocardium-myocardium communication is essential for trabeculation, and numerous signalling pathways have been identified, including Notch
and Neuregulin (NRG)
. Late disruption of the Notch pathway causes NCC
. Whereas it has been shown that mutations in the extracellular matrix (ECM) genes Has2 and Vcan prevent the formation of trabeculae in mice
and the matrix metalloprotease ADAMTS1 promotes trabecular termination
, the pathways involved in ECM dynamics and the molecular regulation of trabeculation during its early phases remain unexplored. Here we present a model of trabeculation in mice that integrates dynamic endocardial and myocardial cell behaviours and ECM remodelling, and reveal new epistatic relationships between the involved signalling pathways. NOTCH1 signalling promotes ECM degradation during the formation of endocardial projections that are critical for individualization of trabecular units, whereas NRG1 promotes myocardial ECM synthesis, which is necessary for trabecular rearrangement and growth. These systems interconnect through NRG1 control of Vegfa, but act antagonistically to establish trabecular architecture. These insights enabled the prediction of persistent ECM and cardiomyocyte growth in a mouse NCC model, providing new insights into the pathophysiology of congenital heart disease.
Summary Background Bronchiectasis is the outcome of a number of different airway insults. Very few studies have characterised the aetiology and utility of a dedicated screening proforma in adult ...patients attending a general bronchiectasis clinic. Methods A prospective observational study of 189 bronchiectasis patients attending two centres in the North East of England over a two-year period was performed. Results The aetiology of bronchiectasis was identified in 107/189(57%) patients. Idiopathic bronchiectasis (IB) represented the largest subgroup (43%). Post-infection bronchiectasis (PIB) constituted the largest proportion (24%) of known causes. Mean age (SD) at diagnosis was 54(20) years with a mean age at symptom onset of 37(24) years, accounting for a diagnostic delay of 17 years. Age of symptom onset was significantly younger in patients with PIB compared to IB ( p < 0.0001) and in Pseudomonas sputum positive patients ( p = 0.007). Screening for APBA and total immunoglobulin deficiency identified 9 (5%) patients who then had tailored treatment. Routine screening for other aetiologies was deemed unnecessary. Conclusion IB and PIB accounted for two thirds of cases of bronchiectasis in a general population. We recommend routine screening for ABPA and total immunoglobulin deficiency but not for other rarer aetiologies.
Many isotopes in nuclear materials exhibit strong peaks in neutron absorption cross sections in the epithermal energy range (1–1000eV). These peaks (often referred to as resonances) occur at energies ...specific to particular isotopes, providing a means of isotope identification and concentration measurements. The high penetration of epithermal neutrons through most materials is very useful for studies where samples consist of heavy-Z elements opaque to X-rays and sometimes to thermal neutrons as well. The characterization of nuclear fuel elements in their cladding can benefit from the development of high resolution neutron resonance absorption imaging (NRAI), enabled by recently developed spatially-resolved neutron time-of-flight detectors. In this technique the neutron transmission of the sample is measured as a function of spatial location and of neutron energy. In the region of the spectra that borders the resonance energy for a particular isotope, the reduction in transmission can be used to acquire an image revealing the 2-dimensional distribution of that isotope within the sample. Provided that the energy of each transmitted neutron is measured by the neutron detector used and the irradiated sample possesses neutron absorption resonances, then isotope-specific location maps can be acquired simultaneously for several isotopes. This can be done even in the case where samples are opaque or have very similar transmission for thermal neutrons and X-rays or where only low concentrations of particular isotopes are present (<0.1atom% in some cases). Ultimately, such radiographs of isotope location can be utilized to measure isotope concentration, and can even be combined to produce three-dimensional distributions using tomographic methods.
In this paper we present the proof-of-principle of NRAI and transmission Bragg edge imaging performed at Flight Path 5 (FP5) at the LANSCE pulsed, moderated neutron source of Los Alamos National Laboratory. A set of urania mockup fuel assemblies with intentionally introduced defects was investigated. The maps of elemental composition of pellets containing urania and tungsten were obtained simultaneously by resonance absorption imaging with spatial resolution better than ∼200μm, while the voids and cracks were revealed by the transmission images obtained with thermal and cold neutrons. Our proof-of-principle experiments demonstrate that simultaneous acquisition of resonance and Bragg edge spectra enables concurrent mapping of isotope distributions, imaging of cracks and voids as well as measurements of some crystallographic parameters of fuel assemblies and their cladding. A detailed study of energy-dependent neutron statistics achievable at FP5 with our present detection system is also presented for a wide range of neutron energies.
Leaching of nitrate (NO3-) from animal waste or fertilisers at
agricultural operations can result in NO3- contamination of
groundwater, lakes, and streams. Understanding the sources and fate of
...nitrate in groundwater systems in glacial sediments, which underlie many
agricultural operations, is critical for managing impacts of human food
production on the environment. Elevated NO3- concentrations in
groundwater can be naturally attenuated through mixing or denitrification.
Here we use isotopic enrichment of the stable isotope values of
NO3- to quantify the amount of denitrification in groundwater at
two confined feeding operations overlying glacial sediments in Alberta,
Canada. Uncertainty in δ15NNO3 and
δ18ONO3 values of the NO3- source and
denitrification enrichment factors are accounted for using a Monte Carlo
approach. When denitrification could be quantified, we used these values to
constrain a mixing model based on NO3- and Cl−
concentrations. Using this novel approach we were able to reconstruct the
initial NO3−N concentration and NO3-N/Cl- ratio at the
point of entry to the groundwater system. Manure filtrate had
total nitrogen (TN) of up to 1820 mg L−1, which was predominantly
organic N and NH3. Groundwater had up to 85 mg L−1 TN, which
was predominantly NO3-. The addition of NO3- to the
local groundwater system from temporary manure piles and pens equalled or
exceeded NO3- additions from earthen manure storages at these
sites. On-farm management of manure waste should therefore increasingly focus
on limiting manure piles in direct contact with the soil and encourage
storage in lined lagoons. Nitrate attenuation at both sites is attributed to
a spatially variable combination of mixing and denitrification, but is
dominated by denitrification. Where identified, denitrification reduced
agriculturally derived NO3- concentrations by at least half and,
in some wells, completely. Infiltration to groundwater systems in glacial
sediments where NO3- can be naturally attenuated is likely
preferable to off-farm export via runoff or drainage networks, especially if
local groundwater is not used for potable water supply.
Persistent surface water pools along non-perennial rivers represent an important water resource for plants, animals, and humans. While ecological studies of these features are not uncommon, these are ...rarely accompanied by a rigorous examination of the hydrological and hydrogeological characteristics that create or support persistent river pools. Here we present an overarching framework for understanding the hydrology of persistent pools. Perched surface water, alluvial water throughflow, and groundwater discharge are the key hydraulic mechanisms that control the persistence of pools along river channels. Groundwater discharge can be further categorized into that controlled by a geological contact or barrier and discharge controlled by topography. Emphasis is put on clearly defining throughflow of alluvial water and the different drivers of groundwater discharge. The suite of regional-scale and pool-scale diagnostic tools available for elucidating these hydraulic mechanisms are summarized and critiqued. Water fluxes to pools supported by throughflow alluvial and groundwater discharge can vary spatially and temporally, and quantitatively resolving pool water balance components is commonly non-trivial. This framework allows for the evaluation of the susceptibility of persistent pools along river channels to changes in climate or groundwater withdrawals. Finally, we demonstrate the application of this framework using a suite of the available tools to conduct a regional and pool-scale assessment of the hydrology of persistent river pools in the Hamersley Basin of north-western Australia.
Aims: The purpose of this study was to determine whether volatile organic compounds specific to Pseudomonas aeruginosa could be detected in clinical sputum specimens. Methods and Results: Patients ...were recruited from specialist bronchiectasis and cystic fibrosis clinics. The gold standard for diagnosing Ps. aeruginosa infection was a positive sputum culture. About 72 sputum headspace samples taken from patients at risk of or known to have prior Ps. aeruginosa infection were analysed by solid phase micro-extraction mass spectrometry. 2-nonanone was a marker in Ps. aeruginosa in sputum headspace gas with sensitivity of 72% and specificity of 88%. A combination of volatile compounds, a sputum library of 17 compounds with 2-nonanone, increased sensitivity in the detection of Ps. aeruginosa to 91% with specificity of 88%. Conclusions: In contrast to the 48-hour turnaround for classical microbiological culture, these results were available within 1-2 h. These data demonstrate the potential for rapid and accurate diagnosis of Ps. aeruginosa infection from sputum samples. Significance and impact of the study: 2-Nonanone is a compound requiring further study in the exhaled breath as it may improve diagnostic of Ps. aeruginosa infection when combined with other reported volatile markers.
Abstract
This study tested a psychosocial model of suicide risk in a sample of 156 Latino college students. Specifically, depression and loneliness were hypothesized to be important predictors of ...suicide risk (namely, hopelessness and suicidal behaviors) in Latino students. Results of conducting regression analyses indicated that, independent of age and gender, depression and loneliness were significant predictors of both indices of suicide risk examined in the present study. It is noteworthy that within the psychosocial predictor set of depression and loneliness, depression was consistently found to be nearly twice as strong a predictor than was loneliness. Moreover, we found evidence for a significant depression–loneliness interaction effect in predicting suicide risk. That is, the highest level of suicide risk was found among dysphoric Latino students who were also socially isolated. Our findings indicate that depression and loneliness are important factors to consider in understanding suicide risk among Latino college students.
Summary
Background
Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant ...and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012.
Objectives
To review and update the BSCA facial series.
Methods
We retrospectively reviewed the results from 12 UK and Ireland patch test centres’ facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified.
Results
Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres’ facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty‐five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%.
Conclusions
This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.
What is already known about this topic?
Facial dermatitis is one of the dominant presenting complaints of allergic contact dermatitis to cosmetics.
To ensure we are accurately diagnosing contact allergy, it is important that we patch test with relevant allergens.
Reviewing current literature and auditing patch test practice is a vital requirement to ensure we identify relevant and emerging allergens and highlight those that are outdated.
What does this study add?
Despite recommended patch test series, there is significant variation in practice among different patch test centres.
In response to this multicentre audit, the British Society for Cutaneous Allergy facial series has been updated and now contains 24 allergens: 15 allergens remain, 11 allergens have been dropped and nine new allergens have been added.
Linked Comment: Boonchai. Br J Dermatol 2021; 184:13.
Plain language summary available online
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