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The ATLASGAL survey has characterised the properties of approximately 1000 embedded HII regions and found an empirical relationship between the clump mass and bolometric luminosity that covers 3-4 orders of magnitude. Comparing this relation with simulated clusters drawn from an initial mass function and using different star formation efficiencies we find that a single value is unable to fit the observed luminosity to mass ($L/M$) relation. We have used a Monte Carlo simulation to generate 200,000 clusters using the $L/M$-ratio as a constraint to investigate how the star formation efficiency changes as a function of clump mass. This has revealed that the star formation efficiency decreases with increasing clump mass with a value of 0.2 for clumps with masses of a few hundred solar masses and dropping to 0.08 for clumps with masses of a few thousand solar masses. We find good agreement between our results and star formation efficiencies determined from counts of embedded objects in nearby molecular clouds. Using the star formation efficiency relationship and the infrared excess time for embedded star formation of $2\pm1$, Myr we estimate the Galactic star formation rate to be approximately $0.9\pm0.45$ Msun yr$^{-1}$, which is in good agreement with previously reported values. This model has the advantage of providing a direct means of determining the star formation rate and avoids the difficulties encountered in converting infrared luminosities to stellar mass that affect previous galactic and extragalactic studies., Comment: 13 pages, 10 figures, accepted for publication in MNRAS

Transposable elements in eukaryotic organisms have historically been considered “selfish,” at best conferring indirect benefits to their host organisms. The Starships are a recently discovered feature in fungal genomes that are, in some cases, predicted to confer beneficial traits to their hosts and also have hallmarks of being transposable elements. Here, we provide experimental evidence that Starships are indeed autonomous transposons, using the model Paecilomyces variotii , and identify the HhpA “Captain” tyrosine recombinase as essential for their mobilization into genomic sites with a specific target site consensus sequence. Furthermore, we identify multiple recent horizontal gene transfers of Starships , implying that they jump between species. Fungal genomes have mechanisms to defend against mobile elements, which are frequently detrimental to the host. We discover that Starships are also vulnerable to repeat-induced point mutation defense, thereby having implications on the evolutionary stability of such elements.

Sleep-related breathing disorders are a common problem in infancy and childhood. The most common type of sleep-related breathing disorder in this age group is obstructive sleep apnea syndrome (OSAS), generally caused by factors affecting airway patency, such as tonsillar hypertrophy or obesity. However, in adults OSAS can also be caused by processes affecting the brainstem, such as central nervous system tumors. This report describes a 2-year-old girl who presented with symptoms of snoring, restless sleep, repeated night-time waking, and apneic events while asleep. She had no comorbidities, and examination revealed normal-sized tonsils. A sleep study demonstrated severe OSAS with an obstructive apnea/hypopnea index of 34. Her OSAS completely resolved on excision of the tumor. The case highlights the importance of neurological examination as part of evaluation of OSAS, especially in cases where tonsils are not enlarged and there are no other risk factors for OSAS. CITATION: Buller F, Kamal MA, Brown SK, et al. Obstructive sleep apnea syndrome as a rare presentation in a young girl with a central nervous system tumor. J Clin Sleep Med. 2022;18(4):1211–1214.

The COVID-19 pandemic has resulted in unprecedent changes to clinical practice, and as the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the United Kingdom was unknown, this was characterised via a national survey.An electronic survey was distributed to healthcare professionals involved in the exercise management of CF via established professional networks.In total, 31 CF centres participated. Findings included significant reductions in exercise testing and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue using virtual methods of engaging patients in future practice.These findings highlight adaptation to the COVID-19 pandemic and the need to develop sustainable and standardised telehealth services to manage patients moving forwards.

Fungal spore killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here, we overcome these experimental barriers by developing model systems in 2 evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast), similar to previous approaches taken to examine the

Transposable elements in eukaryotic organisms have historically been considered ‘selfish’, at best conferring indirect benefits to their host organisms. The Starships are a recently discovered feature in fungal genomes that are predicted to confer beneficial traits to their hosts and also have hallmarks of being transposable elements. Here, we provide experimental evidence that Starships are indeed autonomous transposons, using the model Paecilomyces variotii, and identify the HhpA ‘Captain’ tyrosine recombinase as essential for their mobilization into genomic sites with a specific target site consensus sequence. Furthermore, we identify multiple recent horizontal gene transfer of Starships, implying that they frequency jump between species. Fungal genomes have mechanisms to defend against mobile elements, which are frequently detrimental to the host. We discover that Starships are also vulnerable to repeat-induced point mutation defence, thereby having implications on the evolutionary stability of such elements.

Background The impact of lumacaftor/ivacaftor on exercise tolerance in people with cystic fibrosis (CF) has not been thoroughly studied. Methods We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants ≥ 12 years of age with CF homozygous for F508del-CFTR. The primary endpoint was relative change from baseline in maximum oxygen consumption (VO2max) during cardiopulmonary exercise testing (CPET) at Week 24. The key secondary endpoint was relative change from baseline in exercise duration during CPET at Week 24. Other secondary endpoints included changes in other indices of exercise tolerance and changes in CF assessments; safety and tolerability were assessed as an endpoint. Results Seventy participants were randomized to receive lumacaftor/ivacaftor (n = 34) or placebo (n = 36). The least-squares mean difference for lumacaftor/ivacaftor versus placebo in relative change in VO2max from baseline at Week 24 was −3.2% (95% CI: −9.2, 2.9; P=0.3021); the least-squares mean difference in relative change from baseline in exercise duration at Week 24 was −3.2% (95% CI: −8.0, 1.6). Safety results were consistent with the known lumacaftor/ivacaftor safety profile. Conclusions Definitive conclusions regarding the impact of lumacaftor/ivacaftor on exercise tolerance cannot be drawn from these results; however, multicenter studies using CPETs can be reliably performed with multiple time points and conventional methods, provided that calibration can be achieved. Future studies of exercise tolerance may benefit from lessons learned from this study. NCT02875366.

We present one of the very first extensive classifications of a large sample of molecular clouds based on their morphology. This is achieved using a recently published catalogue of 10663 clouds obtained from the first data release of the SEDIGISM survey. The clouds are classified into four different morphologies by visual inspection and using an automated algorithm -- J plots. The visual inspection also serves as a test for the J plots algorithm, as this is the first time it has been used on molecular gas. Generally, it has been found that the structure of molecular clouds is highly filamentary and our observations indeed verify that most of our molecular clouds are elongated structures. Based on our visual classification of the 10663 SEDIGISM clouds, 15% are ring-like, 57% are elongated, 15% are concentrated and 10% are clumpy clouds. The remaining clouds do not belong to any of these morphology classes and are termed unclassified. We compare the SEDIGISM molecular clouds with structures identified through other surveys, i.e. ATLASGAL elongated structures and the bubbles from Milky Way Project (MWP). We find that many of the ATLASGAL and MWP structures are velocity coherent. ATLASGAL elongated structures overlap with ~ 21% of the SEDIGISM elongated structures (elongated and clumpy clouds) and MWP bubbles overlap with ~ 25% of the SEDIGISM ring-like clouds. We also analyse the star-formation associated with different cloud morphologies using two different techniques. The first technique examines star formation efficiency (SFE) and the dense gas fraction (DGF), based on SEDIGISM clouds and ATLASGAL clumps data. The second technique uses the high-mass star formation (HMSF) threshold for molecular clouds. The results indicate that clouds with ring-like and clumpy morphologies show a higher degree of star formation., Comment: Accepted for publication in A&A. 40 pages (26 of Appendices), 55 figures, 13 tables. The updated SEDIGISM cloud catalogue, containing cloud morphology, will be available as part of the SEDIGISM database

ObjectiveThe impact on executive function performance of sleep-related disorders in asthmatic children has been scarcely studied in community settings. The aims of the present study were to assess the prevalence of sleep-related breathing disorders (SRBD) in children with intermittent or mild persistent asthma in primary care settings, and to examine the possible correlations with measures of executive function.MethodsWe performed a case–control study including 76 children with asthma (intermittent or mild persistent) and 85 healthy controls. The parents of both patients and controls completed the Paediatric Seep Questionnaire (PSQ) and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire.ResultsWe did not find any statistically significant differences regarding the scales of PSQ. Additionally, there were no statistical differences between asthmatic children and controls regarding the scales of the BRIEF questionnaire. In both asthmatic children and controls the score of the scale of obstructive sleep-related breathing disorder was significantly correlated with the T scores of the two composite scales (BRI and MI) and the Global Executive Composite.ConclusionIn children with intermittent or mild persistent asthma under the care of private general paediatricians there were no statistically significant differences regarding subjective SBD compared to the healthy controls. Also there were no statistical differences between asthmatic children and controls regarding behavioural correlates of executive function during everyday life.

ObjectivesRegular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training for pwCF in the UK was conducted over a decade ago. With the landscape of CF changing considerably during this time, this survey aimed to evaluate UK-based exercise testing and training practices for pwCF a decade on.DesignCross-sectional, online survey.ParticipantsA survey was distributed electronically to UK CF clinics and completed by the individual primarily responsible for exercise services. Descriptive statistics and qualitative analyses were undertaken.ResultsIn total, 31 CF centres participated, representing ~50% of UK specialist clinics. Of these, 94% reported using exercise testing, 48% of which primarily use cardiopulmonary exercise testing. Exercise testing mostly occurs at annual review (93%) and is most often conducted by physiotherapists (62%). A wide variation in protocols, exercise modalities, normative reference values and cut-offs for exercise-induced desaturation are currently used. All centres reportedly discuss exercise training with pwCF; 94% at every clinic appointment. However, only 52% of centres reportedly use exercise testing to inform individualised exercise training. Physiotherapists typically lead discussions around exercise training (74%).ConclusionsThese data demonstrate that the majority of respondent centres in the UK now offer some exercise testing and training advice for pwCF, representing a marked improvement over the past decade. However, continued efforts are now needed to standardise exercise practices, particularly regarding field testing practices and the translation of test results into personalised training programmes for pwCF.

Context. While over 1000 supernova remnants (SNRs) are estimated to exist in the Milky Way, only less than 400 have been found to date. In the context of this apparent deficiency, more than 150 SNR candidates were recently identified in the D-configuration Very Large Array (VLA-D) continuum images of the 4--8 GHz global view on star formation (GLOSTAR) survey, in the Galactic longitude range $-2^\circ, Comment: To be published in A&A. 21 pages, 15 figures

We present a study of the correlation between 22 GHz water maser emission and far-infrared/submillimeter (IR/sub-mm) sources. The generalized linear model (GLM) is used to predict H2O maser detection in a particular source with defined physical parameters. We checked the GLM predictions by observing a sample of selected sources with the Effelsberg 100 m telescope. In total, 359 sources were observed. H2O masers were detected in 124 sources, with 56 new detections. We found 22 sources with a significant flux variability. Using the GLM analysis, we estimate that 2392 ± 339 star formation regions (SFRs) in the Galaxy may harbor H2O masers detectable by single-dish observations at the noise level of ∼0.05 Jy. Analyzing the luminosity-to-mass ratio (L/M) of the ATLASGAL and Hi-GAL clumps associated with different maser species, we find that 22 GHz water masers have significantly lower values of L/M in comparison to 6.7 GHz class II methanol and 1665 MHz OH masers. This implies that 22 GHz water masers may appear prior to 6.7 GHz methanol and OH masers in the evolutionary sequence of SFRs. From the analysis of physical offsets between host clumps and maser interferometric positions, we found no significant difference between the H2O and class II methanol maser offsets against the host clump position. We conclude that the tight association between water masers and IR/sub-mm sources may provide insight into the pumping conditions of these masers and the evolutionary stages of their onset. © 2022. The Author(s). Published by the American Astronomical Society. Ministry of Education and Science of the Russian Federation, Minobrnauka: FEUZ-2020-0030; Russian Science Foundation, RSF: 18-12-00193, 20-72-00137 The work of D.A.L. on the generalized model analysis in Section , testing the GLM predictions from observations (Sections –, ), and the data analysis in Sections , , and , was supported by Russian Science Foundation grant 20-72-00137. The work of D.A.L. and A.M.S. on the maser velocity range analysis (Section ) and the source variability analysis from the archival data (Section ) was supported by Russian Science Foundation grant 18-12-00193. The work of D.A.L. on the correlation between maser species (Section ) was supported by the Ministry of Education and Science of Russia (the basic part of the State assignment, RK no. FEUZ-2020-0030). This work is based on observations with the 100 m radio telescope of the MPIfR (Max-Planck-Institut für Radioastronomie) at Effelsberg. We acknowledge the Effelsberg 100 m staff for their assistance with our observations. The ATLASGAL project is a collaboration between the Max-Planck-Gesellschaft, the European Southern Observatory (ESO), and the Universidad de Chile. It includes projects E-181.C-0885, E-078.F-9040(A), M-079.C-9501(A), and M-081.C-9501(A) plus Chilean data.

Here we explore the diversity of one morphologically distinguishable genus in the Mucoromycotina, Backusella, in south-eastern Australia. We isolated more than 200 strains from locations across the states of Victoria and Tasmania. Characterization of these strains using a combination of approaches including morphology, sucrose utilization and whole genome sequencing for 13 strains, revealed 10 new species. The genetic basis for interspecies variation in sucrose utilization was found to be the presence of a gene encoding an invertase enzyme. The genus Backusella is revised and a new key for species identification produced. Given that we have more than doubled the number of species in this genus, this work demonstrates that there may be considerable undiscovered species diversity in the early diverging fungal lineages.

A new species is described in the Mucorales family Syncephalastraceae: Syncephalastrum contaminatum, isolated as an in vitro culture from a laboratory contaminant. The species has variable copies of the internal transcribed spacer (ITS) regions, requiring cloning of these regions prior to Sanger sequencing before subsequent use in phylogenetic comparisons with other fungi. The genome of the strain was sequenced using short paired-reads to yield a draft genome of 28.6 Mb. Syncephalastrum contaminatum is distinguished by diverse DNA sequences at several loci from the other species of Syncephalastrum, including only 81% sequence identity with its ITS regions to that of S. racemosum. Its merosporangium produces four or more asexual spores and the genome sequencing information suggests that the species is heterothallic. The identification of this species highlights the limited knowledge about the early lineages of fungi both in Australia and globally.

Fungal spore-killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here we overcome these experimental barriers by developing model systems in two evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast). Using these systems, we show that the Podospora anserina spore killer protein Spok1 enacts killing through targeting DNA.Significance StatementNatural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi these loci are called spore-killers. Despite their importance in evolutionary processes and possible applications our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.

Class II methanol (CH$_{3}$OH) masers are amongst the clearest signposts of recent high-mass star formation (HMSF). A complete catalogue outlines the distribution of star formation in the Galaxy, the number of young star-forming cores, and the physical conditions of their environment. The Global View on Star Formation (GLOSTAR) survey, which is a blind survey in the radio regime of 4$-$8 GHz, maps the Galactic mid-plane in the radio continuum, 6.7 GHz methanol line, the 4.8 GHz formaldehyde line, and several radio recombination lines. We present the analysis of the observations of the 6.7 GHz CH$_{3}$OH maser transition using data from the D-configuration of the Very Large Array (VLA). We analyse the data covering Galactic longitudes from $-2^{\circ}< l, Accepted in A&A July 18, 2022

As part of the Global View on Star Formation (GLOSTAR) survey we have used the Karl G. Jansky Very Large Array (VLA) in its B-configuration to observe the part of the Galactic plane between longitudes of 28° and 36° and latitudes from −1° to +1° at the C-band (4–8 GHz). To reduce the contamination of extended sources that are not well recovered by our coverage of the (u, υ)-plane, we discarded short baselines that are sensitive to emission on angular scales >4″. The resulting radio continuum images have an angular resolution of 1.″0 and a sensitivity of ~60 µJy beam−1, making it the most sensitive radio survey covering a large area of the Galactic plane with this angular resolution. An automatic source extraction algorithm was used in combination with visual inspection to identify a total of 3325 radio sources. A total of 1457 radio sources are ≥7σ and comprise our highly reliable catalog; 72 of these are grouped as 22 fragmented sources, for example, multiple components of an extended and resolved source To explore the nature of the cataloged radio sources, we searched for counterparts at millimeter and infrared wavelengths. Our classification attempts resulted in 93 H II region candidates, 104 radio stars, and 64 planetary nebulae, while it is suggested that most of the remaining radio sources are extragalactic sources. We investigated the spectral indices (α, Sv ∝ vα) of radio sources classified as H II region candidates and found that many have negative values. This may imply that these radio sources represent young stellar objects that are members of the star clusters around the high-mass stars that excite the H II regions, but not these H II regions themselves. By comparing the peak flux densities from the GLOSTAR and CORNISH surveys, we have identified 49 variable radio sources, most of them with an unknown nature. Additionally, we provide a list of 1866 radio sources detected within 5 to 7σ levels.

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged ≥12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, while the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted forced expiratory volume in 1s (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, and stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: 117 patients (40% of target sample size) were randomized to an intervention (n=60) or control group (n=57). After 6 months, ΔFEV1 was significantly higher in the control group compared to the intervention group (2.70% predicted, 95% CI 0.13 to 5.26; p=0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01744561.

Robust antifungal screening is technically challenging particularly for filamentous fungi. We present a method for undertaking antifungal screening assays that builds upon existing broth dilution protocols and incorporates time resolved image-based assessment of fungal growth. We show that the method performs with different fungi, particularly those for which spores can be used as inoculum, and with different compound classes, can accurately assess susceptibility or otherwise in only few hours, performs well even without replication and can even account for differences in inherent growth properties of strains.

Robust antifungal screening is technically challenging particularly for filamentous fungi. We present a method for undertaking antifungal screening assays that builds upon existing broth dilution protocols and incorporates time resolved image-based assessment of fungal growth. We show that the method performs with different fungi, particularly those for which spores can be used as inoculum, and with different compound classes, can accurately assess susceptibility or otherwise in only few hours and can even account for differences in inherent growth properties of strains.

Rationale: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. Objectives: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (VO 2 peak) following rigorous adjustment for other predictors. Methods: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. Measurements and Main Results: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that VO 2 peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. Conclusions: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.

The COVID-19 pandemic has resulted in unprecedent change to clinical practice. As the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the UK was unknown, this was characterised via a national survey. In total, 31 CF centres participated. Principal findings included a significant reduction in exercise testing, and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue to use virtual methods of engaging patients in future practice. This does, however, highlight a need to develop sustainable and more standardised telehealth services further to manage patients moving forwards.