Search

Context. Recent observations found close-in planets with significant atmospheres of hydrogen and helium in great abundance. These are the so-called super-Earths and mini-Neptunes. Their atmospheric composition suggests that they formed early during the gas-rich phase of the circumstellar disk and were able to avoid becoming hot Jupiters. As a possible explanation, recent studies explored the recycling hypothesis and showed that atmosphere-disk recycling is able to fully compensate for radiative cooling and thereby halt Kelvin-Helmholtz contraction to prevent runaway gas accretion. Aims. To understand the parameters that determine the efficiency of atmospheric recycling, we extend our earlier studies by exploring the effects of the core mass, the effect of circumstellar gas on sub-Keplerian orbits (headwind), and the optical depth of the surrounding gas on the recycling timescale. Additionally, we analyze their effects on the size and mass of the forming atmosphere. Methods. We used three-dimensional (3D) radiation-hydrodynamic simulations to model a local shearing box centered on the planet. Our planet is located at a separation of ap= 0.1 au from its solar-type host star, and we scanned the core mass range from 1 to 10 MEarth. In order to measure and track the recycling of the atmosphere, we employed tracer particles as well as tracer fluids after thermodynamic equilibrium was reached. Results. For the explored parameter space, all simulations eventually reach an equilibrium where heating due to hydrodynamic recycling fully compensates radiative cooling. In this equilibrium, the atmosphere-to-core mass ratio stays well below 10%, preventing the atmosphere from becoming self-gravitating and entering runaway gas accretion. Higher core masses cause the atmosphere to become turbulent, which further enhances recycling. Compared to the core mass, the effect of the headwind on the recycling timescale is negligible. The opacity has no significant effect on the recycling timescale, which demonstrates that the Kelvin-Helmholtz contraction timescale and the atmosphere-disk recycling timescale are independent of each other. Conclusions. Even for our highest core mass of 10 MEarth, atmosphere-disk recycling is efficient enough to fully compensate for radiative cooling and prevent the atmosphere from becoming self-gravitating. Hence, in-situ formation of hot Jupiters is very unlikely, and migration of gas giants is a key process required to explain their existence. Our findings imply that atmosphere-disk recycling is the most natural explanation for the prevalence of close-in super-Earths and mini-Neptunes. [ABSTRACT FROM AUTHOR]

Context. There is growing evidence that massive stars grow by disk accretion in a similar way to their low-mass counterparts. Early in evolution, these disks can achieve masses that are comparable to the current stellar mass, and therefore the forming disks are highly susceptible to gravitational fragmentation. Aims. We investigate the formation and early evolution of an accretion disk around a forming massive protostar, focussing on its fragmentation physics. To this end, we follow the collapse of a molecular cloud of gas and dust, the formation of a massive protostar, the formation of its circumstellar disk, and the formation and evolution of the disk fragments. Methods. We used a grid-based, self-gravity radiation hydrodynamics code including a sub-grid module for stellar evolution and dust evolution. We purposely do not use a sub-grid module for fragmentation such as sink particles to allow for all paths of fragment formation and destruction, but instead we keep the spatial grid resolution high enough to properly resolve the physical length scales of the problem, namely the pressure scale height and Jeans length of the disk. Simulations are performed on a grid in spherical coordinates with a logarithmic spacing of the grid cells in the radial direction and a cosine distribution of the grid cells in the polar direction, focusing the spatial resolution on the disk midplane. As a consequence, roughly 25% of the total number of grid cells, corresponding to ~26 million grid cells, are used to model the disk physics. These constitute the highest resolution simulations performed up to now on disk fragmentation around a forming massive star with the physics considered here. For a better understanding of the effects of spatial resolution and to compare our high-resolution results with previous lower resolution studies in the literature, we perform the same simulation at five different resolutions, each run differing in resolution from its predecessor by a factor of two. Results. The cloud collapses and a massive (proto)star is formed in its center surrounded by a fragmenting Keplerian-like accretion disk with spiral arms. The fragments have masses of ~1 M⊙, and their continuous interactions with the disk, spiral arms, and other fragments result in eccentric orbits. Fragments form hydrostatic cores surrounded by secondary disks with spiral arms that also produce new fragments. We identified several mechanisms of fragment formation, interaction, and destruction. Central temperatures of the fragments can reach the hydrogen dissociation limit, form second Larson cores, and evolve into companion stars. Based on this, we study the multiplicity predicted by the simulations and find approximately six companions at different distances from the primary: from possible spectroscopic multiples, to companions at distances between 1000 and 2000 au. [ABSTRACT FROM AUTHOR]

Context. Massive stars live short but intense lives. While less numerous than low-mass stars, they enormously impact their surroundings by several feedback mechanisms. They form in opaque and far-away regions of the galaxy, such that one of these feedback mechanisms also becomes a record of their evolution: their bright large-scale jets and outflows. Aims. In a comprehensive convergence study, we investigate the computational conditions necessary to resolve (pseudo-) disk formation and jet-launching processes, and analyze possible caveats. We explore the magneto-hydrodynamic (MHD) processes of the collapse of massive prestellar cores in detail, including an analysis of the forces involved and their temporal evolution for up to two free-fall times. Methods. We conduct MHD simulations using the state-of-the-art code PLUTO, combining nonideal MHD, self-gravity, and very high resolutions as they have never been achieved before. Our setup includes a 100 M⊙ cloud core that collapses under its own self-gravity to self-consistently form a dense disk structure and launch tightly collimated magneto-centrifugal jets and wide-angle tower flows. Results. We show a comprehensive evolutionary picture of the collapse of a massive prestellar core with a detailed analysis of the physical processes involved and our high-resolution simulations can resolve a magneto-centrifugal jet and a magnetic pressure-driven outflow, separately. The nature of the outflows depends critically on spatial resolution. Only high-resolution simulations are able to differentiate a magneto-centrifugally launched, highly collimated jet from a slow wide-angle magnetic-pressure-driven tower flow. Of these two outflow components, the tower flow dominates angular-momentum transport. The mass outflow rate is dominated by the entrained material from the interaction of the jet with the stellar environment and only part of the ejected medium is directly launched from the accretion disk. A tower flow can only develop to its full extent when much of the original envelope has already dispersed. Taking into account both the mass launched from the surface of the disk and the entrained material from the envelope, we find an ejection-to-accretion efficiency of 10%. Nonideal MHD is required to form centrifugally supported accretion disks and the disk size is strongly dependent on spatial resolution. A converged result for disk and both outflow components requires a spatial resolution of Δx ≤ 0.17 au at 1 au and sink-cell sizes ≤3.1 au. Conclusions. Massive stars not only possess slow wide-angle tower flows, but also produce magneto-centrifugal jets, just as their low-mass counterparts. The actual difference between low-mass and high-mass star formation lies in the "embeddedness" of the high-mass star which implies that the jet and tower flow interact with the infalling large-scale stellar environment, potentially resulting in entrainment. [ABSTRACT FROM AUTHOR]

The surroundings of massive protostars constitute an accretion disc which has numerically been shown to be subject to fragmentation and responsible for luminous accretion-driven outbursts. Moreover, it is suspected to produce close binary companions which will later strongly influence the star's future evolution in the Hertzsprung-Russel diagram. We present three-dimensional gravitation-radiation-hydrodynamic numerical simulations of 100M⊙ prestellar cores. We find that accretion discs of young massive stars violently fragment without preventing the (highly variable) accretion of gaseous clumps on to the protostars. While acquiring the characteristics of a nascent low-mass companion, some disc fragments migrate on to the central massive protostar with dynamical properties showing that its final Keplerian orbit is close enough to constitute a close massive protobinary system, having a young highand a low-mass components. We conclude on the viability of the disc fragmentation channel for the formation of such short-period binaries, and that both processes - close massive binary formation and accretion bursts - may happen at the same time. FU-Orionis-type bursts, such as observed in the young high-mass star S255IR-NIRS3, may not only indicate ongoing disc fragmentation, but also be considered as a tracer for the formation of close massive binaries - progenitors of the subsequent massive spectroscopic binaries - once the high-mass component of the system will enter the main-sequence phase of its evolution. Finally, we investigate the Atacama Large (sub-)Millimeter Array observability of the disc fragments. [ABSTRACT FROM AUTHOR]

Context. In a molecular cloud dust opacity typically dominates over gas opacity, yet in the vicinities of forming stars dust is depleted, and gas is the sole provider of opacity. In the optically thin circumstellar environments the radiation temperature cannot be assumed to be equal to the gas temperature, hence the two-temperature Planck means are necessary to calculate the radiative equilibrium. Aims. By using the two-temperature mean opacity one does obtain the proper equilibrium gas temperature in a circumstellar environment, which is in a chemical equilibrium. A careful consideration of a radiative transfer problem reveals that the equilibrium temperature solution can be degenerate in an optically thin gaseous environment. Methods. We compute mean gas opacities based on the publicly available code DFSYNTHE by Kurucz and Castelli. We performed the calculations assuming local thermodynamic equilibrium and an ideal gas equation of state. The values were derived by direct integration of the high-resolution opacity spectrum. Results. We produced two sets of gas opacity tables: Rosseland means and two-temperature Planck means. For three metallicities [Me/H] = 0.0, ±0.3 we covered the parameter range 3.48 ≤ log Trad [K] ≤ 4.48 in radiation temperature, 2.8 ≤ log Tgas [K] ≤ 6.0 in gas temperature, and −10 ≤ log P [dyn cm−2] ≤ 6 in gas pressure. We show that in the optically thin circumstellar environment for a given stellar radiation field and local gas density there are several equilibrium gas temperatures possible. Conclusions. We conclude that, in general, equilibrium gas temperature cannot be determined without treating the temperature evolution. [ABSTRACT FROM AUTHOR]

Studies of the evolution of massive protostars and the evolution of their host molecular cloud cores are commonly treated as separate problems. However, interdependencies between the two can be significant. Here, we study the simultaneous evolution of massive protostars and their host molecular cores using a multi-dimensional radiation hydrodynamics code that incorporates the effects of the thermal pressure and radiative acceleration feedback of the centrally forming protostar. The evolution of the massive protostar is computed simultaneously using the stellar evolution code STELLAR, modified to include the effects of variable accretion. The interdependencies are studied in three different collapse scenarios. For comparison, stellar evolutionary tracks at constant accretion rates and the evolution of the host cores using pre-computed stellar evolutionary tracks are computed. The resulting interdependencies of the protostellar evolution and the evolution of the environment are extremely diverse and depend on the order of events, in particular the time of circumstellar accretion disk formation with respect to the onset of the bloating phase of the star. Feedback mechanisms affect the instantaneous accretion rate and the protostar's radius, temperature, and luminosity on timescales t ⩽ 5 kyr, corresponding to the accretion timescale and Kelvin-Helmholtz contraction timescale, respectively. Nevertheless, it is possible to approximate the overall protostellar evolution in many cases by pre-computed stellar evolutionary tracks assuming appropriate constant average accretion rates. [ABSTRACT FROM AUTHOR]

There is a strong need to better predict the survival of patients with newly diagnosed multiple myeloma (MM). As gene expression profiles (GEPs) reflect the biology of MM in individual patients, we built a prognostic signature based on GEPs. GEPs obtained from newly diagnosed MM patients included in the HOVON65/GMMG-HD4 trial (n=290) were used as training data. Using this set, a prognostic signature of 92 genes (EMC-92-gene signature) was generated by supervised principal component analysis combined with simulated annealing. Performance of the EMC-92-gene signature was confirmed in independent validation sets of newly diagnosed (total therapy (TT)2, n=351; TT3, n=142; MRC-IX, n=247) and relapsed patients (APEX, n=264). In all the sets, patients defined as high-risk by the EMC-92-gene signature show a clearly reduced overall survival (OS) with a hazard ratio (HR) of 3.40 (95% confidence interval (CI): 2.19-5.29) for the TT2 study, 5.23 (95% CI: 2.46-11.13) for the TT3 study, 2.38 (95% CI: 1.65-3.43) for the MRC-IX study and 3.01 (95% CI: 2.06-4.39) for the APEX study (P<0.0001 in all studies). In multivariate analyses this signature was proven to be independent of the currently used prognostic factors. The EMC-92-gene signature is better or comparable to previously published signatures. This signature contributes to risk assessment in clinical trials and could provide a tool for treatment choices in high-risk MM patients. [ABSTRACT FROM AUTHOR]

Context. When massive stars exert a radiation pressure onto their environment that is higher than their gravitational attraction (super- Eddington condition), they launch a radiation-pressure-driven outflow, which creates cleared cavities. These cavities should prevent any further accretion onto the star from the direction of the bubble, although it has been claimed that a radiative Rayleigh-Taylor instability should lead to the collapse of the outflow cavity and foster the growth of massive stars. Aims. We investigate the stability of idealized radiation-pressure-dominated cavities, focusing on its dependence on the radiation transport approach used in numerical simulations for the stellar radiation feedback. Methods. We compare two different methods for stellar radiation feedback: gray flux-limited diffusion (FLD) and ray-tracing (RT). Both methods are implemented in our self-gravity radiation hydrodynamics simulations for various initial density structures of the collapsing clouds, eventually forming massive stars. We also derive simple analytical models to support our findings. Results. Both methods lead to the launch of a radiation-pressure-dominated outflow cavity. However, only the FLD cases lead to prominent instability in the cavity shell. The RT cases do not show such instability; once the outflow has started, it precedes continuously. The FLD cases display extended epochs of marginal Eddington equilibrium in the cavity shell, making them prone to the radiative Rayleigh-Taylor instability. In the RT cases, the radiation pressure exceeds gravity by 1-2 orders of magnitude. The radiative Rayleigh-Taylor instability is then consequently suppressed. It is a fundamental property of the gray FLD method to neglect the stellar radiation temperature at the location of absorption and thus to underestimate the opacity at the location of the cavity shell. Conclusions. Treating the stellar irradiation in the gray FLD approximation underestimates the radiative forces acting on the cavity shell. This can lead artificially to situations that are affected by the radiative Rayleigh-Taylor instability. The proper treatment of direct stellar irradiation by massive stars is crucial for the stability of radiation-pressure-dominated cavities [ABSTRACT FROM AUTHOR]

The Akaike information criterion for model selection presupposes that the parameter space is not subject to order restrictions or inequality constraints. Anraku (1999) proposed a modified version of this criterion, called the order-restricted information criterion, for model selection in the one-way analysis of variance model when the population means are monotonic. We propose a generalization of this to the case when the population means may be restricted by a mixture of linear equality and inequality constraints. If the model has no inequality constraints, then the generalized order-restricted information criterion coincides with the Akaike information criterion. Thus, the former extends the applicability of the latter to model selection in multi-way analysis of variance models when some models may have inequality constraints while others may not. Simulation shows that the information criterion proposed in this paper performs well in selecting the correct model. [ABSTRACT FROM PUBLISHER]

Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis and relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS) were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk (NHR) patients with IKZF1 deletions exhibited a ∼12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone NHR-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses mutations in familial platelet disorder (FPD) with enhanced risk for acute myeloid leukemia (AML).

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals. PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging. INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise. MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of 'poor outcome' (death, institutionalization, or severe clinical decline), and costs. RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval = -3.1-8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, 'poor outcome' (41.4% vs 35.4%, P=.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group. CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesions. [ABSTRACT FROM AUTHOR]

Gross cytogenetic anomalies are traditionally being used as diagnostic, prognostic and therapeutic markers in the clinical management of cancer, including childhood acute lymphoblastic leukemia (ALL). Recently, it has become increasingly clear that genetic lesions driving tumorigenesis frequently occur at the submicroscopic level and, consequently, escape standard cytogenetic observations. Therefore, we profiled the genomes of 40 childhood ALLs at high resolution. We detected multiple de novo genetic lesions, including gross aneuploidies and segmental gains and losses, some of which were subtle and affected single genes. Many of these lesions involved recurrent (partially) overlapping deletions and duplications, containing various established leukemia-associated genes, such as ETV6, RUNX1 and MLL. Importantly, the most frequently affected genes were those controlling G1/S cell cycle progression (e.g. CDKN2A, CDKN1B and RB1), followed by genes associated with B-cell development. The latter group includes microdeletions of the B-lineage transcription factors PAX5, EBF, E2-2 and IKZF1 (Ikaros), as well as genes with other established roles in B-cell development, that is RAG1 and RAG2, FYN, PBEF1 or CBP/PAG. The fact that we frequently encountered multiple lesions affecting genes involved in cell cycle regulation and B-cell differentiation strongly suggests that both these processes need to be targeted independently and simultaneously to trigger ALL development.Leukemia (2007) 21, 1258–1266. doi:10.1038/sj.leu.2404691; published online 19 April 2007 [ABSTRACT FROM AUTHOR]

Toxicological effects of the widely used flame retardant, tetrabromobisphenol A (TBBPA) were assessed in a partial life-cycle test with zebrafish (Danio rerio). Exposure of adult fish during 30 days to water-borne TBBPA in nominal concentrations ranging from 0 (control) to 1.5 μM was followed by exposure of the offspring in early life stages up to 47 days posthatching (dph) to the same concentrations. Adults exposed to 3 and 6 μM showed severe disorientation and lethargy shortly after beginning of exposure and were euthanized. Because semistatic exposure resulted in fluctuating water concentrations, pooled fish samples were chemically analyzed for internal dose assessment. Egg production was decreased in fish exposed to TBBPA concentrations of 0.047 μM and higher, and a critical effect level of 7.2 μg/g lipid with a lower 5% confidence limit of 3.9 μg/g lipid for 50% decreased egg production was calculated. Histology of adult ovaries indicated a relative increase of premature oocytes in two surviving females exposed to 1.5 μM. Hatching of TBBPA-exposed larvae was decreased except in animals exposed to 0.375 μM. In the highest exposure concentration, early posthatching mortality was high (81%) in larvae and the surviving juveniles showed a significant predominance of the female phenotype. Exposure of eggs from control parents up to 6 μM TBBPA resulted in increasing malformation and pericardial fluid accumulation from 1.5 μM; at higher concentrations, all embryos failed to hatch. The presented results indicate decreased reproductive success in zebrafish at environmentally relevant TBBPA concentrations. [ABSTRACT FROM AUTHOR]

PURPOSE. To analyze the degree to which standardized nursing language was used by baccalaureate nursing students completing Outcome-Present State-Test (OPT) model worksheets in a clinical practicum. METHODS. A scoring instrument was developed and 100 worksheets were retrospectively analyzed. FINDINGS. NANDA nursing diagnoses were correctly stated in 92% of the OPT models. Nursing Outcomes Classification (NOC) outcomes were explicitly stated in 22%, and implied in 72%. Interventions matched appropriate Nursing Interventions Classification (NIC) activities in 61%. CONCLUSIONS. NANDA, NIC, and NOC (NNN) language was used inconsistently by students in this sample. IMPLICATIONS FOR PRACTICE. If NNN language is to advance nursing knowledge, its promotion, representation in curriculum development, and active use is necessary. Educational research is needed on the facilitators and barriers to NNN language use. [ABSTRACT FROM AUTHOR]

This research was conducted to test the efficacy of audiotapes as a method of recording reflections of senior baccalaureate nursing students in a clinical preceptorship.The over-all aim of the research was to promote cognitive and metacognitive thinking processes with self-regulated learning strategies for problem solving in clinical situations.Verbal protocol technique revealed a consistent use of self-regulated learning strategies with a focus on environmental structuring for metacognitive activities. Common themes of thought were found in both clinical experiences and the use of critical thinking skills. [ABSTRACT FROM AUTHOR]

A correction to the article "A gene expression signature for high-risk multiple myeloma" that was published in the previous issue of the journal is presented.

Context. The fragmentation of high-mass star-forming regions depends on a variety of physical parameters, including density, the magnetic field, and turbulent gas properties. Aims. We evaluate the importance of the density and magnetic field structures in relation to the fragmentation properties during high-mass star formation. Methods. Observing the large parsec-scale Stokes I millimeter dust continuum emission with the IRAM 30 m telescope and the intermediate-scale (<0.1 pc) polarized submillimeter dust emission with the Submillimeter Array toward a sample of 20 high-mass star-forming regions allows us to quantify the dependence of the fragmentation behavior of these regions on the density and magnetic field structures. Results. Based on the IRAM 30 m data, we infer density distributions n ∝ r−p of the regions with typical power-law slopes p around ~1.5. There is no obvious correlation between the power-law slopes of the density structures on larger clump scales (~1 pc) and the number of fragments on smaller core scales (<0.1 pc). Comparing the large-scale single-dish density profiles to those derived earlier from interferometric observations at smaller spatial scales, we find that the smaller-scale power-law slopes are steeper, typically around ~2.0. The flattening toward larger scales is consistent with the star-forming regions being embedded in larger cloud structures that do not decrease in density away from a particular core. The magnetic fields of several regions appear to be aligned with filamentary structures that lead toward the densest central cores. Furthermore, we find different polarization structures; some regions exhibit central polarization holes, whereas other regions show polarized emission also toward the central peak positions. Nevertheless, the polarized intensities are inversely related to the Stokes I intensities, following roughly a power-law slope of ∝ SI−0.62. We estimate magnetic field strengths between ~0.2 and ~4.5 mG, and we find no clear correlation between magnetic field strength and the fragmentation level of the regions. A comparison of the turbulent to magnetic energies shows that they are of roughly equal importance in this sample. The mass-to-flux ratios range between ~2 and ~7, consistent with collapsing star-forming regions. Conclusions. Finding no clear correlations between the present-day large-scale density structure, the magnetic field strength, and the smaller-scale fragmentation properties of the regions, indicates that the fragmentation of high-mass star-forming regions may not be affected strongly by the initial density profiles and magnetic field properties. However, considering the limited evolutionary range and spatial scales of the presented CORE analysis, future research directions should include density structure analysis of younger regions that better resemble the initial conditions, as well as connecting the observed intermediate-scale magnetic field structure with the larger-scale magnetic fields of the parental molecular clouds. [ABSTRACT FROM AUTHOR]

Context. The fragmentation mode of high-mass molecular clumps and the accretion processes that form the most massive stars (M ≳ 8 M⊙) are still not well understood. A growing number of case studies have found massive young stellar objects (MYSOs) to harbour disk-like structures, painting a picture that the formation of high-mass stars may proceed through disk accretion, similar to that of lower-mass stars. However, the properties of such structures have yet to be uniformly and systematically characterised. Aims. The aim of this work is to uniformly study the kinematic properties of a large sample of MYSOs and characterise the stability of possible circumstellar disks against gravitational fragmentation. Methods. We have undertaken a large observational programme (CORE) making use of interferometric observations from the Northern Extended Millimetre Array (NOEMA) for a sample of 20 luminous (L > 104L⊙) protostellar objects in the 1.37 mm wavelength regime in both continuum and spectral line emission, reaching 0.4″ resolution (800 au at 2 kpc). Results. We present the gas kinematics of the full sample and detect dense gas emission surrounding 15 regions within the CORE sample. Using the dense gas tracer CH3CN, we find velocity gradients across 13 cores perpendicular to the directions of bipolar molecular outflows, making them excellent disk candidates. The extent of the CH3CN emission tracing the disk candidates varies from 1800 to 8500 au. Analysing the free-fall to rotational timescales, we find that the sources are rotationally supported. The rotation profiles of some disk candidates are well described by differential rotation while for others the profiles are poorly resolved. Fitting the velocity profiles with a Keplerian model, we find protostellar masses in the range of ~ 10–25 M⊙. Modelling the level population of CH3CN (12K–11K) K = 0–6 lines, we present temperature maps and find median temperature in the range 70–210 K with a diversity in distributions. Radial profiles of the specific angular momentum (j) for the best disk candidates span a range of 1–2 orders of magnitude, on average ~10−3 km s−1 pc, and they follow j ∝ r1.7, which is consistent with a poorly resolved rotating and infalling envelope-disk model. Studying the Toomre stability of the disk candidates, we find almost all (11 out of 13) disk candidates to be prone to fragmentation due to gravitational instabilities at the scales probed by our observations, as a result of their high disk to stellar mass ratio. In particular, disks with masses greater than ~ 10–20% of the mass of their host (proto)stars are Toomre unstable, and more luminous YSOs tend to have disks that are more massive compared to their host star and hence more prone to fragmentation. Conclusions. In this work, we show that most disk structures around high-mass YSOs are prone to disk fragmentation early in their formation due to their high disk to stellar mass ratio. This impacts the accretion evolution of high-mass protostars which will have significant implications for the formation of the most massive stars. [ABSTRACT FROM AUTHOR]

The star-forming ability of a molecular cloud depends on the fraction of gas it can cycle into the dense-phase. Consequently, one of the crucial questions in reconciling star formation in clouds is to understand the factors that control this process. While it is widely accepted that the variation in ambient conditions can alter significantly the ability of a cloud to spawn stars, the observed variation in the star-formation rate in nearby clouds that experience similar ambient conditions, presents an interesting question. In this work, we attempted to reconcile this variation within the paradigm of colliding flows. To this end we develop self-gravitating, hydrodynamic realizations of identical flows, but allowed to collide off-centre. Typical observational diagnostics such as the gas-velocity dispersion, the fraction of dense-gas, the column density distribution (N-PDF), the distribution of gas mass as a function of K-band extinction and the strength of compressional/solenoidal modes in the post-collision cloud were deduced for different choices of the impact parameter of collision. We find that a strongly sheared cloud is terribly inefficient in cycling gas into the dense phase and that such a cloud can possibly reconcile the sluggish nature of star formation reported for some clouds. Within the paradigm of cloud formation via colliding flows this is possible in case of flows colliding with a relatively large impact parameter. We conclude that compressional modes - though probably essential - are insufficient to ensure a relatively higher star-formation efficiency in a cloud. [ABSTRACT FROM AUTHOR]

Context. Most massive stars are located in multiple stellar systems. The modeling of disk fragmentation, a mechanism that may plausibly lead to stellar multiplicity, relies on parallel 3D simulation codes whose agreement remains to be evaluated. Aims. Cartesian adaptive-mesh refinement (AMR) and spherical codes have frequently been used in the past decade to study massive star formation. We aim to study how the details of collapse and disk fragmentation depend on these codes. Methods. Using the Cartesian AMR code RAMSES within its self-gravity radiation-hydrodynamical framework, we compared disk fragmentation in a centrally condensed protostellar system to the findings of earlier studies performed on a grid in spherical coordinates using PLUTO. Results. To perform the code comparison, two RAMSES runs were considered, effectively giving qualitatively distinct pictures. On the one hand, when allowing for unlimited sink particle creation with no initial sink, Toomre instability and subsequent gas fragmentation leads to a multiple stellar system whose multiplicity is affected by the grid when triggering fragmentation and via numerically assisted mergers. On the other hand, using a unique, central, fixed-sink particle, a centrally-condensed system forms that is similar to that reported by PLUTO. Hence, the RAMSES-PLUTO comparison was performed with the latter and an agreement between the two codes is found as to the first rotationally supported disk formation, the presence of an accretion shock onto it, and the first fragmentation phase. Gaseous fragments form. The properties of the fragments (i.e., number, mass, and temperature) are dictated by local thermodynamics and are in agreement between the two codes given that the system has entered a highly nonlinear phase. Over the simulations, the stellar accretion rate is made of accretion bursts and continuous accretion on the same order of magnitude. As a minor difference between both codes, the dynamics of the fragments causes the disk structure to be sub-Keplerian in RAMSES, whereas it is found to be Keplerian, thus reaching quiescence, in PLUTO. We attribute this discrepancy to the central star being twice less massive in RAMSES because of the different stellar accretion subgrid models in use - rather than the potential grid effects. Conclusions. In a centrally condensed system, the agreement between RAMSES and PLUTO regarding many of the collapse properties and fragmentation process is good. In contrast, fragmentation occurring in the innermost region and given specific numerical choices (use of sink particles, grid, etc.) have a crucial impact when similar but smooth initial conditions are employed. These aspects prove more crucial than the choice of code, with regard to the system being multiple or centrally condensed. [ABSTRACT FROM AUTHOR]

Accretion-driven luminosity outbursts are a vivid manifestation of variable mass accretion on to protostars. They are known as the so-called FU Orionis phenomenon in the context of low-mass protostars. More recently, this process has been found in models of primordial star formation. Using numerical radiation hydrodynamics simulations, we stress that present- day forming massive stars also experience variable accretion and show that this process is accompanied by luminous outbursts induced by the episodic accretion of gaseous clumps falling from the circumstellar disc on to the protostar. Consequently, the process of accretion-induced luminous flares is also conceivable in the high-mass regime of star formation and we propose to regard this phenomenon as a general mechanism that can affect protostars regardless of their mass and/or the chemical properties of the parent environment in which they form. In addition to the commonness of accretion-driven outbursts in the star formation machinery, we conjecture that luminous flares from regions hosting forming high-mass stars may be an observational implication of the fragmentation of their accretion discs. [ABSTRACT FROM AUTHOR]

Massive stars that have been ejected from their parent cluster and supersonically sailing away through the interstellar medium (ISM) are classified as exiled. They generate circumstellar bow-shock nebulae that can be observed. We present two-dimensional, axisymmetric hydro-dynamical simulations of a representative sample of stellar wind bow shocks from Galactic OB stars in an ambient medium of densities ranging from nISM = 0.01 up to 10.0 cm-3. Independently of their location in the Galaxy, we confirm that the infrared is the most appropriated waveband to search for bow shocks from massive stars. Their spectral energy distribution is the convenient tool to analyse them since their emission does not depend on the temporary effects which could affect unstable, thin-shelled bow shocks. Our numerical models of Galactic bow shocks generated by high-mass (≈40 Mʘ) runaway stars yield H a fluxes which could be observed by facilities such as the SuperCOSMOS H-Alpha Survey. The brightest bow-shock nebulae are produced in the denser regions of the ISM. We predict that bow shocks in the field observed at H α by means of Rayleigh-sensitive facilities are formed around stars of initial mass larger than about 20 Mʘ. Our models of bow shocks from OB stars have the emission maximum in the wavelength range 3 ≤ λ ≤ 50 µm which can be up to several orders of magnitude brighter than the runaway stars themselves, particularly for stars of initial mass larger than 20 Mʘ. [ABSTRACT FROM AUTHOR]

Mice respond to a cage change (CC) with altered activity, disrupted sleep and increased anxiety. A bi-weekly cage change is, therefore, preferred over a shorter CC interval and is currently the prevailing routine for Individually ventilated cages (IVCs). However, the build-up of ammonia (NH3) during this period is a potential threat to the animal health and the literature holds conflicting reports leaving this issue unresolved. We have therefor examined longitudinally in-cage activity, animal health and the build-up of ammonia across the cage floor with female and male C57BL/6 mice housed four per IVC changed every other week. We used a multicentre design with a standardised husbandry enabling us to tease-out features that replicated across sites from those that were site-specific. CC induce a marked increase in activity, especially during daytime (~50%) when the animals rest. A reduction in density from four to two mice did not alter this response. This burst was followed by a gradual decrease till the next cage change. Female but not male mice preferred to have the latrine in the front of the cage. Male mice allocate more of the activity to the latrine free part of the cage floor already the day after a CC. A behaviour that progressed through the CC cycle but was not impacted by the type of bedding used. Reducing housing density to two mice abolished this behaviour. Female mice used the entire cage floor the first week while during the second week activity in the latrine area decreased. Measurement of NH3 ppm across the cage floor revealed x3 higher values for the latrine area compared with the opposite area. NH3 ppm increases from 0–1 ppm to reach ≤25 ppm in the latrine free area and 50–100 ppm in the latrine area at the end of a cycle. As expected in-cage bacterial load covaried with in-cage NH3 ppm. Histopathological analysis revealed no changes to the upper airways covarying with recorded NH3 ppm or bacterial load. We conclude that housing of four (or equivalent biomass) C57BL/6J mice for 10 weeks under the described conditions does not cause any overt discomfort to the animals. [ABSTRACT FROM AUTHOR]

Background Modulation of the host immune response by helminths has been reported to be essential for parasite survival and also to benefit the host by suppressing inflammatory diseases such as allergies. We have previously shown that excretory-secretory products of Trichinella spiralis muscle larvae have immunomodulatory properties and induce in vitro the expansion of CD4+CD25+FOXP3+ Treg cells in a TGF-β-dependent manner. Objective We aimed at determining the effect of the acute (intestinal) and the chronic (muscle) phase of T. spiralis infection on experimental allergic airway inflammation ( EAAI) to Ovalbumin (OVA) and the involvement of Treg cells. Methods The chronic phase was established before OVA-sensitization/challenge and the acute phase at two-time points, before and after OVA-sensitization. Mice were infected with 400 T. spiralis larvae and after euthanasia different pathological features of EAAI were measured. Adoptive transfer of CD4+ T cells from Trichinella infected mice to OVA sensitized/challenged recipients was also performed. Results We found that the chronic as well as the acute phase of Trichinella infection suppress EAAI as indicated by reduction in airway inflammation, OVA-specific IgE levels in sera, Th2-cytokine production and eosinophils in bronchoalveolar lavage. This protective effect was found to be stronger during the chronic phase and to be associated with increased numbers of splenic CD4+CD25+FOXP3+ Treg cells with suppressive activity. Adoptive transfer of splenic CD4+ T cells from chronically infected mice with elevated numbers of Treg cells resulted in partial protection against EAAI. Conclusions and Clinical Relevance These results demonstrate that the protective effect of T. spiralis on EAAI increases as infection progresses from the acute to the chronic phase. Here, Treg cells may play an essential role in the suppression of EAAI. Elucidating the mechanisms and molecular helminth structures responsible for this regulatory process is relevant to develop alternative tools for preventing or treating allergic asthma. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the role of microRNAs in the pathogenesis of multiple myeloma (MM).

The pH value of the abomasal contents in adult cattle is normally constant and has a value of 2. Abomasal contents with pH values of 5.5 and higher could give rise to bacterial fermentation with subsequent gas production. The accumulation of gas is thought to form a key event in the pathogenesis of abomasal displacement. The aim of the present study was to determine the pH values of abomasal contents of dairy cows in the first 3 weeks after calving. The pH of the abomasal contents was, over several days, higher than the pH value of the abomasal juice in mid-lactation cows. The highest pH values were measured on day 14 after calving, thereafter the pH declined. Possible explanations for the rise in the pH value of the abomasal contents are discussed. [ABSTRACT FROM AUTHOR]

In looking towards the 21st century, the faculty at the Presbyterian Hospital School of Nursing, along with the Presbyterian Health Services Corporation and Queen's College, adopted a 1-2-1 programme. The process of developing a new nursing curriculum is presented as the task force proceeded from the philosophy and goals to conceptual framework and curriculum objectives. After discussions with nurse administrators and educators, extensive literature reviews and brainstorming sessions, concepts and subconcepts were chosen to form a philosophy. The metaparadigm of nursing and other related concepts were then organized into a conceptual framework. Ongoing communication and feedback from the faculty ensured group ownership of all documents. The eclectic organizational scheme was a good fit for a large faculty with differing beliefs and values about a nursing curriculum. The process of developing a future orientated nursing curriculum has been exciting, challenging and rewarding. The faculty is committed to the new philosophy, goals and conceptual framework and believe that the 1-2-1 programme will educate future practitioners who are prepared to meet the challenges and changes in health care for the 21st century. [ABSTRACT FROM AUTHOR]

We have studied the dust density, temperature, and velocity distributions of the archetypal massive young stellar object (MYSO) AFGL 2591. Given its high luminosity (⁠|$L=2\times 10^5\, \mbox{L$_{\odot}$}$|⁠) and distance (d  = 3.3 kpc), AFGL 2591 has one of the highest |$\sqrt{L}/d$| ratio, giving better resolved dust emission than any other MYSO. As such, this paper provides a template on how to use resolved multiwavelength data and radiative transfer to obtain a well-constrained 2D axisymmetric analytic rotating infall model. We show for the first time that the resolved dust continuum emission from Herschel 70-  μ m observations is extended along the outflow direction, whose origin is explained in part from warm dust in the outflow cavity walls. However, the model can only explain the kinematic features from CH3CN observations with unrealistically low stellar masses (<15 M⊙), indicating that additional physical processes may be playing a role in slowing down the envelope rotation. As part of our three-step continuum and line fitting, we have identified model parameters that can be further constrained by specific observations. High-resolution mm visibilities were fitted to obtain the disc mass (6 M⊙) and radius (2200 au). A combination of SED and near-infrared observations were used to estimate the luminosity and envelope mass together with the outflow cavity inclination and opening angles. [ABSTRACT FROM AUTHOR]

Aims. In order to understand the observed molecular diversity in high-mass star-forming regions, we have to determine the underlying physical and chemical structure of those regions at high angular resolution and over a range of evolutionary stages. Methods. We present a detailed observational and modeling study of the hot core VLA 3 in the high-mass star-forming region AFGL 2591, which is a target region of the NOrthern Extended Millimeter Array (NOEMA) large program CORE. Using NOEMA observations at 1.37 mm with an angular resolution of ~0″. 42 (1400 au at 3.33 kpc), we derived the physical and chemical structure of the source. We modeled the observed molecular abundances with the chemical evolution code MUSCLE (MUlti Stage ChemicaL codE). Results. With the kinetic temperature tracers CH3CN and H2CO we observe a temperature distribution with a power-law index of q = 0.41 ± 0.08. Using the visibilities of the continuum emission we derive a density structure with a power-law index of p = 1.7 ± 0.1. The hot core spectra reveal high molecular abundances and a rich diversity in complex molecules. The majority of the molecules have an asymmetric spatial distribution around the forming protostar(s), which indicates a complex physical structure on scales <1400 au. Using MUSCLE, we are able to explain the observed molecular abundance of 10 out of 14 modeled species at an estimated hot core chemical age of ~21 100 yr. In contrast to the observational analysis, our chemical modeling predicts a lower density power-law index of p < 1.4. Reasons for this discrepancy are discussed. Conclusions. Combining high spatial resolution observations with detailed chemical modeling allows us to derive a concise picture of the physical and chemical structure of the famous AFGL 2591 hot core. The next steps are to conduct a similar analysis for the whole CORE sample, and then use this analysis to constrain the chemical diversity in high-mass star formation to a much greater depth. [ABSTRACT FROM AUTHOR]

Context. The formation process of high-mass stars (>8 M⊙) is poorly constrained, particularly the effects of clump fragmentation creating multiple systems and the mechanism of mass accretion onto the cores. Aims. We study the fragmentation of dense gas clumps, and trace the circumstellar rotation and outflows by analyzing observations of the high-mass (~500 M⊙) star-forming region IRAS 23033+5951. Methods. Using the Northern Extended Millimeter Array (NOEMA) in three configurations and the IRAM 30 m single-dish telescope at 220 GHz, we probe the gas and dust emission at an angular resolution of ~0.45′′, corresponding to 1900 au. Results. In the millimeter (mm) continuum emission, we identify a protostellar cluster with at least four mm-sources, where three of them show a significantly higher peak intensity well above a signal-to-noise ratio of 100. Hierarchical fragmentation from large to small spatial scales is discussed. Two fragments are embedded in rotating structures and drive molecular outflows, traced by 13CO (2–1) emission. The velocity profiles across two of the cores are similar to Keplerian but are missing the highest-velocity components close to the center of rotation, which is a common phenomena from observations like these, and other rotation scenarios are not excluded entirely. Position–velocity diagrams suggest protostellar masses of ~6 and 19 M⊙. Rotational temperatures from fitting CH3CN (12K− 11K) spectra are used for estimating the gas temperature and thereby also the disk stability against gravitational fragmentation, utilizing Toomre's Q parameter. Assuming that the candidate disk is in Keplerian rotation about the central stellar object and considering different disk inclination angles, we identify only one candidate disk as being unstable against gravitational instability caused by axisymmetric perturbations. Conclusions. The dominant sources cover different evolutionary stages within the same maternal gas clump. The appearance of rotation and outflows of the cores are similar to those found in low-mass star-forming regions. [ABSTRACT FROM AUTHOR]

We present the highest angular resolution (∼20 × 15 mas–44 × 33 au) Atacama Large Millimeter/sub-millimeter Array (ALMA) observations that are currently possible of the proto-O-star G17.64+0.16 in Band 6. The Cycle 5 observations with baselines out to 16 km probe scales < 50 au and reveal the rotating disc around G17.64+0.16, a massive forming O-type star. The disc has a ring-like enhancement in the dust emission that is especially visible as arc structures to the north and south. The Keplerian kinematics are most prominently seen in the vibrationally excited water line, H2O 55, 0−64, 3 ν2 = 1 (Eu = 3461.9 K). The mass of the central source found by modelling the Keplerian rotation is consistent with 45 ± 10 M⊙. The H30α (231.9 GHz) radio-recombination line and the SiO (5-4) molecular line were detected at up to the ∼10σ level. The estimated disc mass is 0.6 − 2.6 M⊙ under the optically thin assumption. Analysis of the Toomre Q parameter in the optically thin regime indicates that the disc stability is highly dependent on temperature. The disc currently appears stable for temperatures > 150 K; this does not preclude that the substructures formed earlier through disc fragmentation. [ABSTRACT FROM AUTHOR]

Context. This study is part of the CORE project, an IRAM/NOEMA large program consisting of observations of the millimeter continuum and molecular line emission towards 20 selected high-mass star-forming regions. The goal of the program is to search for circumstellar accretion disks, study the fragmentation process of molecular clumps, and investigate the chemical composition of the gas in these regions. Aims. We focus on IRAS 23385+6053, which is believed to be the least-evolved source of the CORE sample. This object is characterized by a compact molecular clump that is IR-dark shortward of 24 μm and is surrounded by a stellar cluster detected in the near-IR. Our aim is to study the structure and velocity field of the clump. Methods. Observations were performed at ~1.4 mm and employed three configurations of NOEMA and additional single-dish maps, merged with the interferometric data to recover the extended emission. Our correlator setup covered a number of lines from well-known hot core tracers and a few outflow tracers. The angular (~0′′.45–0′′.9) and spectral (0.5 km s−1) resolutions were sufficient to resolve the clump in IRAS 23385+6053 and investigate the existence of large-scale motions due to rotation, infall, or expansion. Results. We find that the clump splits into six distinct cores when observed at sub-arcsecond resolution. These are identified through their 1.4 mm continuum and molecular line emission. We produce maps of the velocity, line width, and rotational temperature from the methanol and methyl cyanide lines, which allow us to investigate the cores and reveal a velocity and temperature gradient in the most massive core. We also find evidence of a bipolar outflow, possibly powered by a low-mass star. Conclusions. We present the tentative detection of a circumstellar self-gravitating disk lying in the most massive core and powering a large-scale outflow previously known in the literature. In our scenario, the star powering the flow is responsible for most of the luminosity of IRAS 23385+6053 (~3000 L⊙). The other cores, albeit with masses below the corresponding virial masses, appear to be accreting material from their molecular surroundings and are possibly collapsing or on the verge of collapse. We conclude that we are observing a sample of star-forming cores that is bound to turn into a cluster of massive stars. [ABSTRACT FROM AUTHOR]

Context. The hierarchical process of star formation has so far mostly been studied on scales from thousands of au to parsecs, but the smaller sub-1000 au scales of high-mass star formation are still largely unexplored in the submillimeter regime. Aims. We aim to resolve the dust and gas emission at the highest spatial resolution to study the physical properties of the densest structures during high-mass star formation. Methods. We observed the high-mass hot core region G351.77-0.54 with the Atacama Large Millimeter Array with baselines extending out to more than 16 km. This allowed us to dissect the region at sub-50 au spatial scales. Results. At a spatial resolution of 18/40 au (depending on the distance), we identify twelve sub-structures within the inner few thousand au of the region. The brightness temperatures are high, reaching values greater 1000 K, signposting high optical depth toward the peak positions. Core separations vary between sub-100 au to several 100 and 1000 au. The core separations and approximate masses are largely consistent with thermal Jeans fragmentation of a dense gas core. Due to the high continuum optical depth, most spectral lines are seen in absorption. However, a few exceptional emission lines are found that most likely stem from transitions with excitation conditions above 1000 K. Toward the main continuum source, these emission lines exhibit a velocity gradient across scales of 100–200 au aligned with the molecular outflow and perpendicular to the previously inferred disk orientation. While we cannot exclude that these observational features stem from an inner hot accretion disk, the alignment with the outflow rather suggests that it stems from the inner jet and outflow region. The highest-velocity features are found toward the peak position, and no Hubble-like velocity structure can be identified. Therefore, these data are consistent with steady-state turbulent entrainment of the hot molecular gas via Kelvin–Helmholtz instabilities at the interface between the jet and the outflow. Conclusions. Resolving this high-mass star-forming region at sub-50 au scales indicates that the hierarchical fragmentation process in the framework of thermal Jeans fragmentation can continue down to the smallest accessible spatial scales. Velocity gradients on these small scales have to be treated cautiously and do not necessarily stem from disks, but may be better explained with outflow emission. Studying these small scales is very powerful, but covering all spatial scales and deriving a global picture from large to small scales are the next steps to investigate. [ABSTRACT FROM AUTHOR]

Context. High-mass stars form in clusters, but neither the early fragmentation processes nor the detailed physical processes leading to the most massive stars are well understood. Aims. We aim to understand the fragmentation, as well as the disk formation, outflow generation, and chemical processes during high-mass star formation on spatial scales of individual cores. Methods. Using the IRAM Northern Extended Millimeter Array (NOEMA) in combination with the 30 m telescope, we have observed in the IRAM large program CORE the 1.37 mm continuum and spectral line emission at high angular resolution (~0.4″) for a sample of 20 well-known high-mass star-forming regions with distances below 5.5 kpc and luminosities larger than 104L⊙. Results. We present the overall survey scope, the selected sample, the observational setup, and the main goals of CORE. Scientifically, we concentrated on the mm continuum emission on scales on the order of 1000 AU. We detect strong mm continuum emission from all regions, mostly due to the emission from cold dust. The fragmentation properties of the sample are diverse. We see extremes where some regions are dominated by a single high-mass core whereas others fragment into as many as 20 cores. A minimum-spanning-tree analysis finds fragmentation at scales on the order of the thermal Jeans length or smaller suggesting that turbulent fragmentation is less important than thermal gravitational fragmentation. The diversity of highly fragmented vs. singular regions can be explained by varying initial density structures and/or different initial magnetic field strengths. Conclusions. A large sample of high-mass star-forming regions at high spatial resolution allows us to study the fragmentation properties of young cluster-forming regions. The smallest observed separations between cores are found around the angular resolution limit which indicates that further fragmentation likely takes place on even smaller spatial scales. The CORE project with its numerous spectral line detections will address a diverse set of important physical and chemical questions in the field of high-mass star formation. [ABSTRACT FROM AUTHOR]

Context. Circumstellar discs around massive stars could mediate the accretion onto the star from the infalling envelope, and could minimize the effects of radiation pressure. Despite such a crucial role, only a few convincing candidates have been provided for discs around deeply embedded O-type (proto)stars. Aims. In order to establish whether disc-mediated accretion is the formation mechanism for the most massive stars, we have searched for circumstellar, rotating discs around a limited sample of six luminous (>105 L⊙) young stellar objects. These objects were selected on the basis of their IR and radio properties in order to maximize the likelihood of association with disc+jet systems. Methods. We used ALMA with ~0".2 resolution to observe a large number of molecular lines typical of hot molecular cores. In this paper we limit our analysis to two disc tracers (methyl cyanide, CH3CN, and its isotopologue, 13CH3CN), and an outflow tracer (silicon monoxide, SiO). Results. We reveal many cores, although their number depends dramatically on the target. We focus on the cores that present prominent molecular line emission. In six of these a velocity gradient is seen across the core, three of which show evidence of Keplerian-like rotation. The SiO data reveal clear but poorly collimated bipolar outflow signatures towards two objects only. This can be explained if real jets are rare (perhaps short-lived) in very massive objects and/or if stellar multiplicity significantly affects the outflow structure. For all cores with velocity gradients, the velocity field is analysed through position-velocity plots to establish whether the gas is undergoing rotation with 3rot ∝ R-α, as expected for Keplerian-like discs. Conclusions. Our results suggest that in three objects we are observing rotation in circumstellar discs, with three more tentative cases, and one core where no evidence for rotation is found. In all cases but one, we find that the gas mass is less than the mass of any embedded O-type star, consistent with the (putative) discs undergoing Keplerian-like rotation. With the caveat of low number statistics, we conclude that the disc detection rate could be sensitive to the evolutionary stage of the young stellar object. In young, deeply embedded sources, the evidence for discs could be weak because of confusion with the surrounding envelope, while in the most evolved sources the molecular component of the disc could have already been dispersed. Only in those objects that are at an intermediate stage of the evolution would the molecular disc be sufficiently prominent and relatively less embedded to be detectable by mm/submm observations. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a cumulative term applied to a clinically and genetically heterogeneous group of neoplasms that occur in the bowel. Based on twin studies, up to 45 % of the CRC cases may involve a heritable component. Yet, only in 5-10 % of these cases high-penetrant germline mutations are found (e.g. mutations in APC and DNA mismatch repair genes) that result in a familial aggregation and/or an early onset of the disease. Genome-wide association studies have revealed that another ~5 % of the CRC cases may be explained by a cumulative effect of low-penetrant risk factors. Recent attempts to identify novel genetic factors using whole exome and whole genome sequencing has proven to be difficult since the remaining, yet to be discovered, high penetrant CRC predisposing genes appear to be rare. In addition, most of the moderately penetrant candidate genes identified so far have not been confirmed in independent cohorts. Based on literature examples, we here discuss how careful patient and cohort selection, candidate gene and variant selection, and corroborative evidence may be employed to facilitate the discovery of novel CRC predisposing genes. Conclusions: The picture emerges that the genetic predisposition to CRC is heterogeneous, involving complex interplays between common and rare (inter)genic variants with different penetrances. It is anticipated, however, that the use of large clinically well-defined patient and control datasets, together with improved functional and technical possibilities, will yield enough power to unravel this complex interplay and to generate accurate individualized estimates for the risk to develop CRC. [ABSTRACT FROM AUTHOR]

STARBENCH is a project focused on benchmarking and validating different star formation and stellar feedback codes. In this first STARBENCH paper we perform a comparison study of the D-type expansion of an HII region. The aim of this work is to understand the differences observed between the 12 participating numerical codes against the various analytical expressions examining the D-type phase of HII region expansion. To do this, we propose two well-defined tests which are tackled by 1D and 3D grid- and smoothed particle hydrodynamics-based codes. The first test examines the 'early phase' D-type scenario during which the mechanical pressure driving the expansion is significantly larger than the thermal pressure of the neutral medium. The second test examines the 'late phase' D-type scenario during which the system relaxes to pressure equilibrium with the external medium. Although they are mutually in excellent agreement, all 12 participating codes follow a modified expansion law that deviates significantly from the classical Spitzer solution in both scenarios. We present a semi-empirical formula combining the two different solutions appropriate to both early and late phases that agrees with high-resolution simulations to ≲ 2 per cent. This formula provides a much better benchmark solution for code validation than the Spitzer solution. The present comparison has validated the participating codes and through this project we provide a data set for calibrating the treatment of ionizing radiation hydrodynamics codes. [ABSTRACT FROM AUTHOR]

Aims. We study the fragmentation and collapse properties of the dense gas during the onset of high-mass star formation. Methods. We observed the massive (~800 M⊙) starless gas clump IRDC18310-4 with the Plateau de Bure Interferometer (PdBI) at subarcsecond resolution in the 1.07 mm continuum and N2H+(3-2) line emission. Results. Zooming from a single-dish low-resolution map to previous 3 mm PdBI data, and now the new 1.07 mm continuum observations, the substructures hierarchically fragment on the increasingly smaller spatial scales. While the fragment separations may still be roughly consistent with pure thermal Jeans fragmentation, the derived core masses are almost two orders of magnitude larger than the typical Jeans mass at the given densities and temperatures. However, the data can be reconciled with models using non-homogeneous initial density structures, turbulence, and/or magnetic fields. While most subcores remain (far-)infrared dark even at 70 µm, we identify weak 70 µm emission toward one core with a comparably low luminosity of ~16 L⊙, supporting the notion of the general youth of the region. The spectral line data always exhibit multiple spectral components toward each core with comparably small line widths for the individual components (in the 0.3 to 1.0 km s-1 regime). Based on single-dish C18O(2-1) data we estimate a low virial-to-gas-mass ratio ≤0.25. We propose that the likely origin of these spectral properties may be the global collapse of the original gas clump that results in multiple spectral components along each line of sight. Even within this dynamic picture the individual collapsing gas cores appear to have very low levels of internal turbulence. [ABSTRACT FROM AUTHOR]

Background: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development.Methods: To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53(lox/lox)/FAK(+/+)/WapCre, p53(lox/lox)/FAK(flox/+)/WapCre and p53(lox/lox)/FAK(flox/-)/WapCre mice, and mice with WapCre-mediated conditional expression of p53(R270H), the mouse equivalent of human p53(R273H) hot spot mutation, together with conditional deletion of FAK, P53(R270H/+)/FAK(lox/+)/WapCre and p53(R270H/+)/FAK(flox/-)/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours.Results: Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53(R270H)-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures.Conclusions: Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion kinase deletion reduced proliferative capacity of p53 null and p53(R270H) mammary epithelial cells but did not lead to increased apoptosis in vivo. Our data identify FAK as an important regulator in mammary epithelial cell proliferation in p53-mediated and p53(R270H)-induced mammary tumour development. [ABSTRACT FROM AUTHOR]

Background:Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development.Methods:To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53lox/lox/FAK+/+/WapCre, p53lox/lox/FAKflox/+/WapCre and p53lox/lox/FAKflox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53R270H, the mouse equivalent of human p53R273H hot spot mutation, together with conditional deletion of FAK, P53R270H/+/FAKlox/+/WapCre and p53R270H/+/FAKflox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours.Results:Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures.Conclusions:Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion kinase deletion reduced proliferative capacity of p53 null and p53R270H mammary epithelial cells but did not lead to increased apoptosis in vivo. Our data identify FAK as an important regulator in mammary epithelial cell proliferation in p53-mediated and p53R270H-induced mammary tumour development. [ABSTRACT FROM AUTHOR]

We present a new publicly available tool (DustPol) aimed to model the polarised thermal dust emission. The module DustPol, which is publicly available, is part of the ARTIST (Adaptable Radiative Transfer Innovations for Submillimetre Telescopes) package, which also offers tools for modelling the polarisation of line emission together with a model library and a Python-based user interface. DustPol can easily manage analytical as well as pre-gridded models to generate synthetic maps of the Stokes I, Q, and U parameters. These maps are stored in FITS format which is straightforwardly read by the data reduction software used, e.g., by the Atacama Large Millimeter Array (ALMA). This turns DustPol into a powerful engine for the prediction of the expected polarisation features of a source observed with ALMA or the Planck satellite as well as for the interpretation of existing submillimetre observations obtained with other telescopes. DustPol allows the parameterisation of the maximum degree of polarisation and we find that, in a prestellar core, if there is depolarisation, this effect should happen at densities of 106 cm-3 or larger. We compare a model generated by DustPol with the observational polarisation data of the low-mass Class 0 object NGC 1333 IRAS 4A, finding that the total and the polarised emission are consistent. [ABSTRACT FROM AUTHOR]

Response to therapy as determined by minimal residual disease (MRD) is currently used for stratification in treatment protocols for pediatric acute lymphoblastic leukemia (ALL). However, the large MRD-based medium risk group (MRD-M; 50-60% of the patients) harbors many relapses. We analyzed MRD in 131 uniformly treated precursor-B-ALL patients and evaluated whether combined MRD and IKZF1 (Ikaros zinc finger-1) alteration status can improve risk stratification. We confirmed the strong prognostic significance of MRD classification, which was independent of IKZF1 alterations. Notably, 8 of the 11 relapsed cases in the large MRD-M group (n=81; 62%) harbored an IKZF1 alteration. Integration of both MRD and IKZF1 status resulted in a favorable outcome group (n=104; 5 relapses) and a poor outcome group (n=27; 19 relapses), and showed a stronger prognostic value than each of the established risk factors alone (hazard ratio (95%CI): 24.98 (8.29-75.31)). Importantly, whereas MRD and IKZF1 status alone identified only 46 and 54% of the relapses, respectively, their integrated use allowed prediction of 79% of all the relapses with 93% specificity. Because of the unprecedented sensitivity in upfront relapse prediction, the combined parameters have high potential for future risk stratification, particularly for patients originally classified as non-high risk, such as the large group of MRD-M patients. [ABSTRACT FROM AUTHOR]

The article presents a study on Ten-Eleven-Translocation 2 (TET2) mutation on children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It mentions that DNA sequence analysis was performed before using DNA primers on TET2 gene on 104 childhoods AML with permission from Dutch Childhood Oncology Group. It states that DNA during remission did not express TET2 mutation. The study shows that TET2 mutations in childhood AML presents lower rate compared to adult AML.

Although cancer is mostly regarded as an acquired disease, familial predisposition plays a significant role in many cancer types. Thus far, several high penetrant cancer predisposing genes have been identified. As yet, however, these genes explain only a fraction of the familial and/or hereditary cases of cancer. This has led to the exploration of the human genome for novel cancer predisposing genes. The identification of such genes will not only increase our understanding of cancer predisposition and development, but will also have direct implications for genetic counseling and personalized management of the patients and their family members. Here we provide an inventory of currently known molecular mechanisms related to familial colorectal cancer development and an outline of copy number analysis-based strategies to identify new predisposing genes. Finally, we discuss a novel copy number-associated epigenetic mechanism underlying the predisposition to colorectal cancer. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with male predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1–5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently non-amplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.Leukemia (2009) 23, 125–133; doi:10.1038/leu.2008.278; published online 16 October 2008 [ABSTRACT FROM AUTHOR]