Deep learning enabled multi-organ segmentation of mouse embryos.

The International Mouse Phenotyping Consortium (IMPC) has generated a large repository of three-dimensional (3D) imaging data from mouse embryos, providing a rich resource for investigating phenotype/genotype interactions. While the data is freely available, the computing resources and human effort required to segment these images for analysis of individual structures can create a significant hurdle for research. In this paper, we present an open source, deep learning-enabled tool, Mouse Embryo Multi-Organ Segmentation (MEMOS), that estimates a segmentation of 50 anatomical structures with a support for manually reviewing, editing, and analyzing the estimated segmentation in a single application. MEMOS is implemented as an extension on the 3D Slicer platform and is designed to be accessible to researchers without coding experience. We validate the performance of MEMOS-generated segmentations through comparison to state-of-the-art atlas-based segmentation and quantification of previously reported anatomical abnormalities in a Cbx4 knockout strain. This article has an associated First Person interview with the first author of the paper.

Characteristics Associated With Disparities Among Older Adults in Coronavirus Disease 2019 Outcomes in an Academic Health Care System.

BACKGROUND: An improved understanding of the coronavirus disease 2019 (COVID-19) pandemic is needed to identify predictors of outcomes among older adults with COVID-19. OBJECTIVE: The objective of this study was to examine patient and health system factors predictive of in-hospital mortality, intensive care unit (ICU) admission, and readmission among patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of patients aged 18 years and older with COVID-19 discharged from 5 New York hospitals within the Mount Sinai Health System (March 1, 2020-June 30, 2020). MEASURES: Patient-level characteristics (age, sex, race/ethnicity, comorbidities/serious illness, transfer from skilled nursing facility, severe acute respiratory syndrome coronavirus 2 viral load, Sequential Organ Failure Assessment score, treatments); hospital characteristics. OUTCOMES: All-cause in-hospital mortality; ICU admission; 30-day readmission. RESULTS: Among 7556 subjects, mean age 61.1 (62.0) years; 1556 (20.6%) died, 949 (12.6%) had an ICU admission, and 227 (9.1%) had a 30-day readmission. Increased age [aged 55-64: odds ratio (OR), 3.28; 95% confidence interval (CI), 2.41-4.46; aged 65-74: OR, 4.67; 95% CI, 3.43-6.35; aged 75-84: OR, 10.73; 95% CI, 7.77-14.81; aged 85 y and older: OR, 20.57; 95% CI, 14.46-29.25] and comorbidities (OR, 1.11; 95% CI, 1.16, 2.13) were independent risk factors for in-hospital mortality. Yet older adults (aged 55-64 y: OR, 0.56; 95% CI, 0.40-0.77; aged 65-74: OR, 0.46; 95% CI, 0.33-0.65; aged 75-84: OR, 0.27; 95% CI, 0.18-0.40; aged above 85 y: OR, 0.21; 95% CI, 0.13-0.34) and those with Medicaid (OR, 0.74; 95% CI, 0.56-0.99) were less likely to be admitted to the ICU. Race/ethnicity, crowding, population density, and health system census were not associated with study outcomes. CONCLUSIONS: Increased age was the single greatest independent risk factor for mortality. Comorbidities and serious illness were independently associated with mortality. Understanding these risk factors can guide medical decision-making for older adults with COVID-19. Older adults and those admitted from a skilled nursing facility were half as likely to be admitted to the ICU. This finding requires further investigation to understand how age and treatment preferences factored into resource allocation.

Biodegradation and fate of ethyl tert-butyl ether (ETBE) in soil and groundwater: A review.

This review summarises the current state of knowledge on the biodegradation and fate of the gasoline ether oxygenate ethyl tert-butyl ether (ETBE) in soil and groundwater. Microorganisms have been identified in soil and groundwater with the ability to degrade ETBE aerobically as a carbon and energy source, or via cometabolism using alkanes as growth substrates. Aerobic biodegradation of ETBE initially occurs via hydroxylation of the ethoxy carbon by a monooxygenase enzyme, with subsequent formation of intermediates which include acetaldehyde, tert-butyl acetate (TBAc), tert-butyl alcohol (TBA), 2-hydroxy-2-methyl-1-propanol (MHP) and 2-hydroxyisobutyric acid (2-HIBA). Slow cell growth and low biomass yields on ETBE are believed to result from the ether structure and slow degradation kinetics, with potential limitations on ETBE metabolism. Genes known to facilitate transformation of ETBE include ethB (within the ethRABCD cluster), encoding a cytochrome P450 monooxygenase, and alkB-encoding alkane hydroxylases. Other genes have been identified in microorganisms but their activity and specificity towards ETBE remains poorly characterised. Microorganisms and pathways supporting anaerobic biodegradation of ETBE have not been identified, although this potential has been demonstrated in limited field and laboratory studies. The presence of co-contaminants (other ether oxygenates, hydrocarbons and organic compounds) in soil and groundwater may limit aerobic biodegradation of ETBE by preferential metabolism and consumption of available dissolved oxygen or enhance ETBE biodegradation through cometabolism. Both ETBE-degrading microorganisms and alkane-oxidising bacteria have been characterised, with potential for use in bioaugmentation and biostimulation of ETBE degradation in groundwater.

Influence of contaminant exposure on the development of aerobic ETBE biodegradation potential in microbial communities from a gasoline-impacted aquifer.

Aerobic biodegradation of ethyl tert butyl ether (ETBE) in a gasoline-impacted aquifer was investigated in laboratory microcosms containing groundwater and aquifer material from ETBE-impacted and non-impacted locations amended with either ETBE, or ETBE plus methyl tert butyl ether (MTBE). As sole substrate, ETBE was biodegraded (maximum rate of 0.54 day-1) without a lag in ETBE-impacted microcosms but with a lag of up to 66 days in non-impacted microcosms (maximum rate of 0.38 day-1). As co-substrate, ETBE was biodegraded preferentially (maximum rate of 0.25 and 0.99 day-1 in non-impacted and impacted microcosms, respectively) before MTBE (maximum rate of 0.24 and 0.36 day-1 in non-impacted and impacted microcosms, respectively). Further addition of ETBE and MTBE reduced lags and increased biodegradation rates. ethB gene copy numbers increased significantly (>100 fold) after exposure to ETBE, while overall cell numbers remained constant, suggesting that ethB-containing microorganisms come to dominate the microbial communities. Deep sequencing of 16S rRNA genes identified members of the Comamonadaceae family that increased in relative abundance upon exposure to ETBE. This study demonstrates the potential for ETBE biodegradation within the unsaturated and saturated zone, and that ETBE biodegrading capability is rapidly developed and maintained within the aquifer microbial community over extended timescales.

Acceptability of intravenous propofol sedation for adolescent dental care.

PURPOSE: Propofol is an intravenous anaesthetic agent commonly utilised in general anaesthesia, however in sub-anaesthetic concentrations can be utilised to provide sedation through automated dosing of target-controlled infusion (TCI). TCI has been shown to provide accurate and stable predicted plasma and effect-site concentrations of propofol. A four-part mixed-method prospective study was undertaken to evaluate the safety and patient acceptability of intravenous propofol sedation in adolescent patients requiring dental care. There is a paucity in the literature on patient-reported outcomes and patient safety in the management of adolescent patients for dental treatment. METHODS: Demographics were recorded including age, gender, ASA Classification and Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) completed pre-operatively. Behaviour ratings of the Frankl and Houpt scales were recorded followed by post-operative questionnaire and telephone consultation. Consultation was completed following the procedure to determine patient satisfaction, memory of the procedure and any reported side effects of treatment. Qualitative thematic analysis was utilised. RESULTS: 55 patients were recruited for the study, of which 49 (mean age 14.67 years) completed the sedation study and were treated safely with no post-operative complications. The mean lowest oxygen saturation was 98.12% SpO2 (SD 2.6). Thematic analysis demonstrated positive patient-reported outcomes to IV sedation. CONCLUSION: Propofol TCI sedation is an effective treatment modality for the management of dentally anxious adolescents as a safe alternative to general anaesthesia, allowing the opportunity for increased provision of treatment per visit on those patients with a high dental need. Further randomised controlled trials comparing propofol TCI to other pharmacological managements are required.

Influence of artificial drainage system design on the nitrogen attenuation potential of gley soils: Evidence from hydrochemical and isotope studies under field-scale conditions.

In North Atlantic Europe intensive dairy farms have a low nitrogen (N) use efficiency, with high N surpluses often negatively affecting water quality. Low feed input systems on heavy textured soils often need artificial drainage to utilise low cost grassland and remain profitable. Heavy textured soils have high but variable N attenuation potential, due to soil heterogeneity. Furthermore, drainage system design can influence the potential for N attenuation and subsequent N loadings in waters receiving drainage from such soils. The present study utilises end of pipe, open ditch and shallow groundwater sampling points across five sites in SW Ireland to compare and rank sites based on N surplus, water quality and "net denitrification", and to develop a conceptual framework for the improved management of heavy textured dairy sites to inform water quality N sustainability. This includes both drainage design and "net denitrification" criterion, as developed within this study.N surplus ranged from 211 to 292 kg N/ha (mean of 252 kg N/sourha) with a common source of organic N across all locations. The predicted soil organic matter (SOM) N release potential from top-subsoil layers was high, ranging from 115 to >146 kg N/ha. Stable isotopes analyses showed spatial variation in the extent of specific N-biotransformation processes, according to drainage location and design. Across all sites, nitrate (NO3-N) was converted to ammonium (NH4+-N), which migrated offsite through open ditch and shallow groundwater pathways. Using the ensemble data the potential for soil N attenuation could be discriminated by 3 distinct groups reflecting the relative dominance of in situ N-biotransformation processes deduced from water composition: Group 1 (2 farms, ranked with high sustainability, NH4+ < 0.23 mg N/l, δ15N-NO3- > 5‰ and δ18O-NO3- > 10‰), low NH4+-N concentration coupled with a high denitrification potential; Group 2 (1 farm with moderate sustainability, NH4+ < 0.23 mg N/l, δ15N-NO3- < 8‰ and δ18O-NO3- < 8‰), low NH4+-N concentration with a high nitrification potential and a small component of complete denitrification; Group 3 (2 farms, ranked with low sustainability, NH4+ > 0.23 mg N/l, 14‰ > Î´15N-NO3- > 5‰ and 25‰ > Î´18O-NO3- > -2‰), high NH4+-N concentration due to low denitrification. The installation of a shallow drainage system (e.g. mole or gravel moles at 0.4 m depth) reduced the "net denitrification" ranking of a site, leading to water quality issues. From this detailed work an N sustainability tool for any site, which presents the relationship between drainage class, drainage design (if present), completeness of denitrification, rate of denitrification and NH4-N attenuation was developed. This tool allows a comparison or ranking of sites in terms of their N sustainability. The tool can also be used pre-land drainage and presents the consequences of future artificial land drainage on water quality and gaseous emissions at a given site.

Defining Multiple Characteristic Raman Bands of α-Amino Acids as Biomarkers for Planetary Missions Using a Statistical Method.

Biomarker molecules, such as amino acids, are key to discovering whether life exists elsewhere in the Solar System. Raman spectroscopy, a technique capable of detecting biomarkers, will be on board future planetary missions including the ExoMars rover. Generally, the position of the strongest band in the spectra of amino acids is reported as the identifying band. However, for an unknown sample, it is desirable to define multiple characteristic bands for molecules to avoid any ambiguous identification. To date, there has been no definition of multiple characteristic bands for amino acids of interest to astrobiology. This study examined L-alanine, L-aspartic acid, L-cysteine, L-glutamine and glycine and defined several Raman bands per molecule for reference as characteristic identifiers. Per amino acid, 240 spectra were recorded and compared using established statistical tests including ANOVA. The number of characteristic bands defined were 10, 12, 12, 14 and 19 for L-alanine (strongest intensity band: 832 cm(-1)), L-aspartic acid (938 cm(-1)), L-cysteine (679 cm(-1)), L-glutamine (1090 cm(-1)) and glycine (875 cm(-1)), respectively. The intensity of bands differed by up to six times when several points on the crystal sample were rotated through 360 °; to reduce this effect when defining characteristic bands for other molecules, we find that spectra should be recorded at a statistically significant number of points per sample to remove the effect of sample rotation. It is crucial that sets of characteristic Raman bands are defined for biomarkers that are targets for future planetary missions to ensure a positive identification can be made.

A new tool for quantifying and characterizing asymmetry in bilaterally paired structures.

This paper introduces a new tool to quantify and characterize asymmetry in bilaterally paired structures. This method uses deformable registration to produce a dense vector field describing the point correspondences between two images of bilaterally paired structures. The deformation vector field properties are clustered to detect and describe regions of relevant asymmetry. Three methods are provided to analyze the asymmetries: the global asymmetry score uses cluster features to quantify overall asymmetry, the local asymmetry score quantifies asymmetry in user-defined regions of interest, and the asymmetry similarity measure quantifies pairwise similarity of individual asymmetry. The scores and image distances generated by this tool are shown to correlate highly with asymmetry ratings assigned by an expert.

Bovine tuberculosis trends in the UK and the Republic of Ireland, 1995-2010.

Selected demographic features and trends in bovine tuberculosis (BTB) from 1995 to 2010 are described for the countries of the UK and the Republic of Ireland, using standardised definitions and measures. All countries experienced a reduction in the number of cattle and herds and in the proportion of dairy herds, while average herd size increased. In general, the trends indicate a stable situation of very low BTB prevalence in Scotland and, over most of the period, a rising prevalence in England and Wales. The prevalence in the Republic of Ireland declined while Northern Ireland experienced both a rise and fall. Differences in demography, BTB programme structure and test results were noted, particularly between the island of Ireland and Great Britain. Further investigation of these differences may provide valuable insights into risk factors for BTB and optimisation of existing BTB programmes.

A landmark-free framework for the detection and description of shape differences in embryos.

This paper introduces a new method to quantify and characterize shape changes during early facial development without the use of landmarks. Landmarks are traditionally used in morphometric analysis, but very few can be identified reliably across all stages of embryonic development. This method uses deformable registration to produce a dense vector field describing the point correspondences between two images. Low and mid-level features are extracted from the deformable vector field to find regions of organized differences that are biologically relevant. These methods are shown to detect regions of difference when evaluated on chick embryo images warped with small magnitude deformations in regions critical to midfacial development.

Outbreak of tuberculosis caused by Mycobacterium bovis in golden Guernsey goats in Great Britain.

An outbreak of caprine tuberculosis caused by Mycobacterium bovis was disclosed in June 2008, affecting goats of the golden Guernsey breed kept on 10 separate smallholdings in south-west Wales and the west of England. Following the initial diagnosis at postmortem examination, 30 goats that reacted positively to the single intradermal comparative cervical tuberculin (SICCT) test, together with five in-contact animals, were euthanased and subjected to postmortem examination and mycobacterial culture. Spoligotyping and variable number tandem repeat analysis of isolates showed that they were all of the same genotype, endemic to south-west Wales. Retrospective movement tracings identified a goat herd in south-west Wales, by then completely dispersed, as the probable common source of infection. There was a perfect correlation between the SICCT test and culture results in all slaughtered goats. Grossly visible tubercular lesions were observed at postmortem examination in all but one reactor.

Intraoperative local anaesthesia for paediatric postoperative oral surgery pain--a randomized controlled trial.

The aim of this study was to improve the pain experience for children following oral surgery under general anaesthesia. To this end, the efficacy and safety of intraoperative local anaesthetic (2% lidocaine with 1:200,000 epinephrine) for postoperative pain control was investigated. In a randomized controlled trial, 142 patients aged 12 years or less, who were scheduled for dental extractions under general anaesthesia, received local anaesthesia or saline intraoral injection after induction of anaesthesia. There was statistically no significant difference between groups for pain scores recorded preoperatively, on waking, at 30 min, at 24h, or for distress scores recorded preoperatively, on waking and at 30 min. 'Severe' pain scores were recorded for 13% of treatment and 12% of control patients and 'very severe' for 13% of treatment and 10% of control patients on waking. These rates were similar at 30 min but reduced at 24h. Lip/cheek biting injuries occurred in one control and three treatment patients. Intraoperative local anaesthesia has been found to be effective for pain control following a range of other surgical procedures, but we did not find it to be effective in reducing postoperative pain or distress in children after oral surgery. Reasons may include unfamiliarity with altered orofacial sensation.

A comparison of deep vs. awake removal of the laryngeal mask airway in paediatric dental daycase surgery. A randomised controlled trial.

Dental anaesthesia provides a potential conflict between anaesthetist and surgeon because of the shared airway. The laryngeal mask airway (LMA) has helped to improve airway control for these procedures, but there is little evidence for best practice on the timing of their removal after airway surgery in the paediatric population. We compared 'awake' and 'deep' removal of the LMA in 196 patients aged from 2 to 15 years in a randomised, controlled study. We found that average peripheral oxygen saturation (SpO2) was lower in the deep group and this was statistically significant (96.2% vs. 94.9%, p = 0.04). It was also found that the deep group had a higher incidence of patients with SpO2 < 95% (p = 0.003) and of patients who coughed (p = 0.003). We conclude that the LMA should be taken out awake in these patients.

Isolation and phylogenetic characterization of acidophilic microorganisms indigenous to acidic drainage waters at an abandoned Norwegian copper mine.

The biodiversity of culturable acidophilic microbes in three acidic (pH 2.7-3.7), metal-rich waters at an abandoned subarctic copper mine in central Norway was assessed. Acidophilic bacteria were isolated by plating on selective solid media, and dominant isolates were identified from their physiological characteristics and 16S rRNA gene sequences. The dominant iron-oxidizing acidophile in all three waters was an Acidithiobacillus ferrooxidans-like eubacterium, which shared 98% 16S rDNA identity with the type strain. A strain of Leptospirillum ferrooxidans was obtained from one of the waters after enrichment in pyrite medium, but this iron oxidizer was below detectable levels in the acidic waters themselves. In two sites, there were up to six distinct heterotrophic acidophiles, present at 10(3) ml(-1). These included Acidiphilium-like isolates (one closely related to Acidiphilium rubrum, a second to Acidiphilium cryptum and a third apparently novel isolate), an Acidocella-like isolate (96% 16S rDNA identity to Acidocella facilis) and a bacterium that shared 94.5% 16S rDNA identity to Acidisphaera rubrifaciens. The other numerically significant heterotrophic isolate was not apparently related to any known acidophile, with the closest match (96% 16S rDNA sequence identity) to an acetogen, Frateuria aurantia. The results indicated that the biodiversity of acidophilic bacteria, especially heterotrophs, in acidic mine waters may be much greater than previously recognized.

Infection of Arabidopsis thaliana leaves with Albugo candida (white blister rust) causes a reprogramming of host metabolism.

Abstract Albugo candida (Pers.) (O.) Kunze is a biotrophic pathogen which infects the crucifer Arabidopsis thaliana (L.) Heynh forming discrete areas of infection. Eight days after inoculation of leaves, white blisters became visible on the under surface of the leaf although no symptoms were apparent on the upper surface. By day 14, the region of leaf invaded by fungal mycelium had become chlorotic. Recently it has been hypothesized that an accumulation of soluble carbohydrates, following an increase in invertase activity, may trigger sugar signal transduction pathways leading to the repression of photosynthetic gene expression and to the induction of defence proteins. This hypothesis was investigated by quantifying localized changes in carbohydrate and photosynthetic metabolism and the expression of genes encoding photosynthetic and defence proteins. Quantitative imaging of chlorophyll fluorescence revealed that the rate of photosynthesis declined progressively in the invaded regions of the leaf. However, in uninfected regions of the infected leaf the rate of photosynthesis was similar to that measured in the control leaf until late on during the infection cycle when it declined. Images of nonphotochemical fluorescence quenching (NPQ) suggested that the capacity of the Calvin cycle had been reduced in infected regions and that there was a complex metabolic heterogeneity within the infected leaf. A. candida also caused localized changes in the carbohydrate metabolism of the leaf; soluble carbohydrates accumulated in the infected region whereas the amount of starch declined. The reverse was seen in uninfected regions of the infected leaf; carbohydrates did not accumulate until late on during infection and the amount of starch increased as the infection progressed. There was an increase in the activity of invertases which was confined to regions of the leaf invaded by the fungal mycelium. The increase in apoplastic invertase activity was of host origin, as mRNA levels of the ATbetaFRUCT1 gene (measured by semiquantitative RT-PCR) increased 40-fold in the infected region. The increase in soluble invertase activity resulted from the appearance of a new isoform in the invaded region of the leaf. Current evidence suggests that this was of fungal origin. Northern blot analysis of cab and rbcS showed that photosynthetic gene expression was repressed in the infected leaf from 6 days after inoculation (DAI) when compared to control leaves. In contrast, there was no detectable induction of defence proteins in the infected leaf. These data are discussed in the context of the sugar-sensing hypothesis presented above.

Countertransference in the treatment of patients with eating disorders.

THE term countertransference has undergone considerable change in meaning in recent decades. Freud (1910/1957) defined countertransference as the emotional reaction of the analyst to a patient's transference. It was seen as the unresolved needs and conflicts of the therapist, often unconscious, which interfered with his/her understanding of the patient. Recently, Abend (1989) chronicled the shift in the definition of the term and noted Kernberg's (1965) more totalistic" description of countertransference. In Kernberg's view, the therapist's reactions have more to do with the patient's often intense transference and with the therapist's capacity to withstand the subsequent stress and anxiety, than with any particular problem from the patient's past. Abend (1989) concluded that most clinicians refer to countertransference in this revised way and used the term quite broadly to denote "all those reactions of the analyst to the patient that may help or hinder treatment" (Slakter 1987, p. 3).

Purification and characterisation of soluble invertases from leaves of Arabidopsis thaliana.

Multiple isoforms of beta-fructofuranosidase (invertase, EC 3.2.1.26) were identified in mature green leaves of the cruciferous plant Arabidopsis thaliana (L.) Heynh. There were four major and one minor isoforms of soluble acid invertase and an additional activity which could be released from the cell wall by buffers of high ionic strength. This study reports the separation and characterisation of three soluble isoforms following ammonium sulphate and polyethylene glycol 6000 precipitations, Concanavalin A, MonoQ ion exchange, Superose 12 size-exclusion chromatography and chromatofocusing. These isoforms, designated INV1, INV2 and INV3, had isoelectric points of 4.75, 4.70 and 4.65 and a Km for sucrose of 5, 12 and 5 mM, respectively. Each had a pH optimum of 5.5, exhibited optimal activity at 45 degrees C and used sucrose as the preferred substrate. All fractions containing these isoforms contained a 52-kDa polypeptide which was specifically detected by immunoblotting with an antibody raised against deglycosylated wheat invertase. The N-terminal amino-acid sequence of this polypeptide was homologous to acid invertases isolated from other plant species. The possible origin of isoforms of soluble acid invertase is discussed.