Localized Darier disease: three cases of Type 1 segmental mosaicism.

Darier disease (DD) is an autosomal dominant acantholytic dermatosis with an estimated prevalence of 1 in 30 000-100 000. A localized form of DD was first described by Kreibich in 1906 and is thought to account for 10% of all cases. A number of clinical variants have been reported including: unilateral, linear, segmental or zosteriform DD. We present a case series of three patients with localized DD.

A neglected source of household air pollution: a preliminary, mixed methods study of purposely produced household smoke in Wollo, Ethiopia.

BACKGROUND: Ill health associated with household air pollution (HAP) is increasingly recognized as a public health problem in sub-Saharan Africa. To date, attempts to reduce HAP have focussed on smoke from cooking fires and have ignored traditional cultural practices which generate purposely produced smoke (PPS). This study aimed to investigate PPS prevalence, reasons for use and safety perceptions. METHODS: The study was conducted in Wollo, Ethiopia, and used a mixed methods approach of quantitative surveys (analysed descriptively) and qualitative interviews with householders and healthcare workers (analysed thematically). RESULTS: PPS use was reported by 99% of survey respondents and it was considered a fundamental part of life. Although reasons for use included housekeeping, culture/religion and well-being, coffee ceremony was most commonly cited (44% of respondents). Both householders and healthcare workers appeared to assume PPS is safe, except for people with certain underlying conditions. Healthcare workers felt the lack of evidence of harm from PPS meant there was no justification for intervention. CONCLUSION: This study, the first in-depth study of PPS, has shown its use to be widespread, with many perceived benefits and thus a very important part of local culture in this sample Ethiopian community. Consequently, any public health interventions aimed at reducing HAP in this setting need to consider PPS.

How Well Do We Know the Neutron-Matter Equation of State at the Densities Inside Neutron Stars? A Bayesian Approach with Correlated Uncertainties.

We introduce a new framework for quantifying correlated uncertainties of the infinite-matter equation of state derived from chiral effective field theory (χEFT). Bayesian machine learning via Gaussian processes with physics-based hyperparameters allows us to efficiently quantify and propagate theoretical uncertainties of the equation of state, such as χEFT truncation errors, to derived quantities. We apply this framework to state-of-the-art many-body perturbation theory calculations with nucleon-nucleon and three-nucleon interactions up to fourth order in the χEFT expansion. This produces the first statistically robust uncertainty estimates for key quantities of neutron stars. We give results up to twice nuclear saturation density for the energy per particle, pressure, and speed of sound of neutron matter, as well as for the nuclear symmetry energy and its derivative. At nuclear saturation density, the predicted symmetry energy and its slope are consistent with experimental constraints.

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.

Short-term safety and effectiveness of sugammadex for surgical patients with end-stage renal disease: a two-centre retrospective study.

Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.

Modeling Epidemics in Seed Systems and Landscapes To Guide Management Strategies: The Case of Sweet Potato in Northern Uganda.

Seed systems are critical for deployment of improved varieties but also can serve as major conduits for the spread of seedborne pathogens. As in many other epidemic systems, epidemic risk in seed systems often depends on the structure of networks of trade, social interactions, and landscape connectivity. In a case study, we evaluated the structure of an informal sweet potato seed system in the Gulu region of northern Uganda for its vulnerability to the spread of emerging epidemics and its utility for disseminating improved varieties. Seed transaction data were collected by surveying vine sellers weekly during the 2014 growing season. We combined data from these observed seed transactions with estimated dispersal risk based on village-to-village proximity to create a multilayer network or "supranetwork." Both the inverse power law function and negative exponential function, common models for dispersal kernels, were evaluated in a sensitivity analysis/uncertainty quantification across a range of parameters chosen to represent spread based on proximity in the landscape. In a set of simulation experiments, we modeled the introduction of a novel pathogen and evaluated the influence of spread parameters on the selection of villages for surveillance and management. We found that the starting position in the network was critical for epidemic progress and final epidemic outcomes, largely driven by node out-degree. The efficacy of node centrality measures was evaluated for utility in identifying villages in the network to manage and limit disease spread. Node degree often performed as well as other, more complicated centrality measures for the networks where village-to-village spread was modeled by the inverse power law, whereas betweenness centrality was often more effective for negative exponential dispersal. This analysis framework can be applied to provide recommendations for a wide variety of seed systems.[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Bacterial Community Shift and Coexisting/Coexcluding Patterns Revealed by Network Analysis in a Uranium-Contaminated Site after Bioreduction Followed by Reoxidation.

A site in Oak Ridge, TN, USA, has sediments that contain >3% iron oxides and is contaminated with uranium (U). The U(VI) was bioreduced to U(IV) and immobilized in situ through intermittent injections of ethanol. It then was allowed to reoxidize via the invasion of low-pH (3.6 to 4.0), high-nitrate (up to 200 mM) groundwater back into the reduced zone for 1,383 days. To examine the biogeochemical response, high-throughput sequencing and network analysis were applied to characterize bacterial population shifts, as well as cooccurrence and coexclusion patterns among microbial communities. A paired t test indicated no significant changes of α-diversity for the bioactive wells. However, both nonmetric multidimensional scaling and analysis of similarity confirmed a significant distinction in the overall composition of the bacterial communities between the bioreduced and the reoxidized sediments. The top 20 major genera accounted for >70% of the cumulative contribution to the dissimilarity in the bacterial communities before and after the groundwater invasion. Castellaniella had the largest dissimilarity contribution (17.7%). For the bioactive wells, the abundance of the U(VI)-reducing genera Geothrix, Desulfovibrio, Ferribacterium, and Geobacter decreased significantly, whereas the denitrifying Acidovorax abundance increased significantly after groundwater invasion. Additionally, seven genera, i.e., Castellaniella, Ignavibacterium, Simplicispira, Rhizomicrobium, Acidobacteria Gp1, Acidobacteria Gp14, and Acidobacteria Gp23, were significant indicators of bioactive wells in the reoxidation stage. Canonical correspondence analysis indicated that nitrate, manganese, and pH affected mostly the U(VI)-reducing genera and indicator genera. Cooccurrence patterns among microbial taxa suggested the presence of taxa sharing similar ecological niches or mutualism/commensalism/synergism interactions.IMPORTANCE High-throughput sequencing technology in combination with a network analysis approach were used to investigate the stabilization of uranium and the corresponding dynamics of bacterial communities under field conditions with regard to the heterogeneity and complexity of the subsurface over the long term. The study also examined diversity and microbial community composition shift, the common genera, and indicator genera before and after long-term contaminated-groundwater invasion and the relationship between the target functional community structure and environmental factors. Additionally, deciphering cooccurrence and coexclusion patterns among microbial taxa and environmental parameters could help predict potential biotic interactions (cooperation/competition), shared physiologies, or habitat affinities, thus, improving our understanding of ecological niches occupied by certain specific species. These findings offer new insights into compositions of and associations among bacterial communities and serve as a foundation for future bioreduction implementation and monitoring efforts applied to uranium-contaminated sites.

Diagnostic virology and patient care: from vaguely interesting to vitally important.

The existence of pathogenic viruses was inferred by experiments at the turn of the twentieth century. Key developments in detection of viruses, including electron microscopy and monolayer cell culture, were made in the middle of that century. However, in terms of patient care, the results from the virology laboratory often arrived the patient was 'better or dead'. The advent of molecular techniques, particularly polymerase chain reaction and more recently whole genome sequencing made timely and accurate diagnosis of viral infections feasible. A range of approaches have been taken to identify and characterise new viruses. Vaccines against viruses have made it possible to eliminate two pathogenic mammalian viruses altogether, with several others close to eradication. The role of biomedical scientists working in diagnostic virology is more relevant to patient care than ever.

Non-diffractive computational ghost imaging.

Computational ghost imaging (CGI) enables an image to be recorded using a single-pixel detector. The image can be reconstructed from correlations between the scene and a series of known projected intensity patterns. In this work we investigate the performance of CGI using pseudo non-diffracting (ND) speckle patterns. We demonstrate an extended depth-of-field that is ∼ 2-3 times greater than that achievable with conventional speckle, when only computing each intensity pattern to a single depth. In addition, the average speckle grain size of ND speckle is reduced by a factor of ∼ 1.5 relative to conventional speckle, which enhances the lateral Rayleigh-limit resolving power of our reconstructed images. However, the point-spread function (PSF) of our imaging system takes the form of a Bessel beam, which manifests itself as long-range correlations between speckle grains in the projected patterns. We discuss the trade-off between enhancement of the depth-of-field and the lateral resolution when using ND speckle, at the expense of a reduction in image contrast. Our work demonstrates that the tailoring of lateral and axial correlations in projected intensity patterns permits PSF engineering in CGI.

The effects of heavy load carriage on physiological responses to graded exercise.

PURPOSE: Many emergency response occupations require heavy load carriage with backpacks. The purpose of this experiment was to study the effects of heavy load carriage on physiological responses and performance during graded exercise. METHODS: Fifty males (age: 28 ± 6 years, height: 182.8 ± 6.2 cm, mass: 85.4 ± 12.1 kg) provided written informed consent before completing two randomly ordered graded exercise tests to measure ventilatory threshold and peak oxygen consumption (˙VO2peak). During the loaded test, each subject carried a correctly sized and fitted 80 L backpack weighing 25 kg. Mass, volume and load distribution were consistent between all packs. Modified Balke treadmill tests were completed by walking at 1.5 m s(−1) with stage increases of 2% grade until exhaustion. RESULTS: Analysis revealed a small but significant decrease in ˙VO2 at ventilatory threshold (3.9%) and peak exercise (2.5%) under load. Power output at ventilatory threshold and ˙VO2peak were significantly decreased by 23.6 and 11.1%, respectively, and test duration was reduced by 29.8% in the loaded condition. CONCLUSIONS: While heavy load carriage had relatively small effects on physiological responses at ventilator threshold and peak exercise, the reductions in power output and test duration were more substantial. Despite the absolute mass of the pack and the large range of subject size, the only change in performance associated with body size was test duration. These results have implications for evaluation of fitness for duty in occupations where heavy load carriage is required.

'Lissajous-like' trajectories in optical tweezers.

When a microscopic particle moves through a low Reynolds number fluid, it creates a flow-field which exerts hydrodynamic forces on surrounding particles. In this work we study the 'Lissajous-like' trajectories of an optically trapped 'probe' microsphere as it is subjected to time-varying oscillatory hydrodynamic flow-fields created by a nearby moving particle (the 'actuator'). We show a breaking of time-reversal symmetry in the motion of the probe when the driving motion of the actuator is itself time-reversal symmetric. This symmetry breaking results in a fluid-pumping effect, which arises due to the action of both a time-dependent hydrodynamic flow and a position-dependent optical restoring force, which together determine the trajectory of the probe particle. We study this situation experimentally, and show that the form of the trajectories observed is in good agreement with Stokesian dynamics simulations. Our results are related to the techniques of active micro-rheology and flow measurement, and also highlight how the mere presence of an optical trap can perturb the environment it is in place to measure.

Power counting of contact-range currents in effective field theory.

We analyze the power counting of two-body currents in nuclear effective field theories (EFTs). We find that the existence of nonperturbative physics at low energies, which is manifest in the existence of the deuteron and the ^{1}S_{0} NN virtual bound state, combined with the appearance of singular potentials in versions of nuclear EFT that incorporate chiral symmetry, modifies the renormalization-group flow of the couplings associated with contact operators that involve nucleon-nucleon pairs and external fields. The order of these couplings is thereby enhanced with respect to the naive-dimensional-analysis estimate. Consequently, short-range currents enter at a lower order in the chiral EFT than has been appreciated up until now, and their impact on low-energy observables is concomitantly larger. We illustrate the changes in the power counting with a few low-energy processes involving external probes and few-nucleon systems, including electron-deuteron elastic scattering and radiative neutron capture by protons.

Trophic behaviour of juvenile reef fishes inhabiting interlinked mangrove-seagrass habitats in offshore mangrove islets.

Stable isotope (δ(13)C and δ(15)N) and gut content analyses were used to investigate size-related feeding habits of four reef fishes (the beaugregory Stegastes leucostictus, the french grunt Haemulon flavolineatum, the schoolmaster snapper Lutjanus apodus and the yellowtail snapper Ocyurus chrysurus) inhabiting an offshore (non-estuarine) mangrove islet off Belize, Central America. Comparisons of isotopic niche space and Schoener diet similarity index suggested a low to moderate degree of niche overlap between fish size groups. The δ(13)C gradient between mangrove and seagrass prey as well as results of Bayesian mixing models revealed that sampled fishes relied mostly on seagrass prey items. Only small and large juveniles of the carnivorous species L. apodus derived a part of their diet from mangroves by targeting mangrove-associated Grapsidae crabs and fish prey, respectively. Isotopic niche shifts were particularly obvious for carnivorous fishes that ingested larger prey items (Xanthidae crabs and fishes) during their ontogeny. The utilization of mangrove food resources is less than expected and depends on the ecology and life history of the fish species considered. This research highlights that mangrove-derived carbon contributed relatively little to the diets of four fish taxa from an offshore mangrove islet.

MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases.

BACKGROUND: Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear. METHODS: We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38). RESULTS: There were significant (P<0.05) differences in tumour grade between the TAM and EC groups, with more favourable morphology in the latter. K-RAS mutations, predominantly G>A, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P<0.05) fewer mutations and methylations in TAM cases. CONCLUSIONS: Although the difference in coincidence did not reach significance with the current sample size, the findings suggest that epigenetic processes may play a role in the way tamoxifen induces endometrial cancer.

Dynamic stereo microscopy for studying particle sedimentation.

We demonstrate a new method for measuring the sedimentation of a single colloidal bead by using a combination of optical tweezers and a stereo microscope based on a spatial light modulator. We use optical tweezers to raise a micron-sized silica bead to a fixed height and then release it to observe its 3D motion while it sediments under gravity. This experimental procedure provides two independent measurements of bead diameter and a measure of Faxén's correction, where the motion changes due to presence of the boundary.

Four-directional stereo-microscopy for 3D particle tracking with real-time error evaluation.

High-speed video stereo-microscopy relies on illumination from two distinct angles to create two views of a sample from different directions. The 3D trajectory of a microscopic object can then be reconstructed using parallax to combine 2D measurements of its position in each image. In this work, we evaluate the accuracy of 3D particle tracking using this technique, by extending the number of views from two to four directions. This allows us to record two independent sets of measurements of the 3D coordinates of tracked objects, and comparison of these enables measurement and minimisation of the tracking error in all dimensions. We demonstrate the method by tracking the motion of an optically trapped microsphere of 5 µm in diameter, and find an accuracy of 2-5 nm laterally, and 5-10 nm axially, representing a relative error of less than 2.5% of its range of motion in each dimension.

Size at birth, morning cortisol and cardiometabolic risk markers in healthy Indian children.

OBJECTIVE: Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis may link reduced foetal growth with higher adult chronic disease risk. South Asians have a high prevalence of low birth weight and a thin-fat phenotype, which is associated with subsequent type 2 diabetes and the metabolic syndrome. Altered HPA activity could be one of the pathological processes underlying this link. METHODS: Plasma morning cortisol and corticosteroid-binding globulin (CBG) concentrations were determined in 528 children aged 9·5 years from a prospective birth cohort in India. They had detailed anthropometry at birth, and current measurements of anthropometry, plasma glucose, insulin and lipid concentrations and blood pressure. Insulin resistance (Homeostasis Model Assessment) and insulin secretion (the 30-min insulin increment) were also assessed. RESULTS: None of the birth measurements were associated with cortisol concentrations, but both birth weight (P = 0·03) and length (P = 0·004) were inversely associated with CBG concentrations. Cortisol concentrations were inversely associated with current body mass index (P = 0·02), and positively associated with glucose (fasting: P < 0·001; 30-min: P = 0·002) concentrations, and systolic blood pressure (P = 0·005), but not insulin resistance or the insulin increment. CONCLUSION: Higher morning cortisol is associated with higher cardiometabolic risk markers in Indian children. Although cortisol concentrations did not appear to be related to birth size, small size at birth was associated with higher CBG levels, and may be one of the processes by which foetal undernutrition affects adult health. The findings suggest a need for dynamic testing of HPA axis activity (such as measuring stress responses).

Measurement of Compton scattering from the deuteron and an improved extraction of the neutron electromagnetic polarizabilities.

The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data-and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here, we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world data set. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using chiral effective field theory with dynamical Δ(1232) degrees of freedom shows the data are consistent with and within the world data set. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities, and combining them with a recent result for the proton, we obtain the neutron polarizabilities as αn=[11.55±1.25(stat)±0.2(BSR)±0.8(th)]×10(-4) fm(3) and ßn=[3.65∓1.25(stat)±0.2(BSR)∓0.8(th)]×10(-4) fm(3), with χ(2)=45.2 for 44 degrees of freedom.

Dietary total antioxidant capacity is related to glucose tolerance in older people: the Hertfordshire Cohort Study.

BACKGROUND AND AIMS: Dietary antioxidants may play a protective role in the aetiology of type 2 diabetes. However, observational studies that examine the relationship between the antioxidant capacity of the diet and glucose metabolism are limited, particularly in older people. We aimed to examine the relationships between dietary total antioxidant capacity (TAC) and markers of glucose metabolism among 1441 men and 1253 women aged 59-73 years who participated in the Hertfordshire Cohort Study, UK. METHODS AND RESULTS: Diet was assessed by food frequency questionnaire. Dietary TAC was estimated using published databases of TAC measured by four different assays: oxygen radical absorbance capacity (ORAC), ferric-reducing ability of plasma (FRAP), total radical-trapping antioxidant parameter (TRAP) and trolox equivalent antioxidant capacity (TEAC). Fasting and 120-min plasma glucose and insulin concentrations were measured during a standard 75-g oral glucose tolerance test. In men, dietary TAC estimated by all four assays was inversely associated with fasting insulin concentration and homoeostasis model assessment of insulin resistance (HOMA-IR); with the exception of ORAC, dietary TAC was also inversely related to 120-min glucose concentration. There were no associations with fasting glucose or 120-min insulin concentrations. In women, with the exception of the association between ORAC and 120-min insulin concentration, dietary TAC estimated by all assays showed consistent inverse associations with fasting and 120-min glucose and insulin concentrations and HOMA-IR. These associations were more marked among women with BMI ≥ 30 kg/m(2). CONCLUSION: These findings suggest dietary TAC may have important protective effects on glucose tolerance, especially in older obese women.