Search

We present the results of a spectral-line survey of the W51e1/e2 star-forming region at 68-88 GHz. 79 molecules and their isotopologues were detected, from simple diatomic or triatomic molecules, such as SO, SiO, and CCH, to complex organic compounds, such as CH$_3$OCH$_3$ or CH$_3$COCH$_3$. A number of lines that are absent from the Lovas list of molecular lines observed in space were detected, and most of these were identified. A significant number of the detected molecules are typical for hot cores. These include the neutral molecules HCOOCH$_3$, CH$_3$CH$_2$OH, CH$_3$COCH$_3$ etc, which are currently believed to exist in the gas phase only in hot cores and shock-heated gas. In addition, vibrationally excited C$_4$H and HC$_3$N lines with upper-level energies of several hundred Kelvins were found. Such lines can arise only in hot gas with temperatures on the order of 100 K or higher. Apart from neutral molecules, various molecular ions were also detected. Some of these (HC$^{18}$O$^+$, H$^{13}$CO$^+$, and HCS$^+$) usually exist in molecular clouds with high visual extinctions. Potential formation pathways of complex organic molecules (COMs) and of hydrocarbons, along with nitriles, are considered. These formation routes are first discussed in the context of laboratory experiments elucidating the synthesis of organic molecules in interstellar ices in cold molecular clouds, followed by sublimation into the gas phase in the hot core stage. Thereafter, we discuss the predominant formation of hydrocarbons and their nitriles in the gas phase through bimolecular neutral-neutral reactions., 22 pages, 8 figures, 5 tables, Accepted for publication in ApJ

Objective This study evaluated the impact of network latency on telestenting performance. Background The feasibility of long-distance robotic telestenting was recently demonstrated, yet the impact of network performance on telestenting remains unknown. Methods Ex vivo and in vivo telestenting models were constructed by connecting a robotic drive over a wired network to a robotic control system up to 103 miles away. During consecutive attempts to robotically wire a coronary artery, investigators randomly added signal latencies from 0 to 1,000 ms. Outcomes included wiring success, wiring time (time to advance wire to preselected target landmark), and perceived latency score (5 = imperceptible; 4 = noticeable but minor; 3 = noticeable; 2 = noticeable and major; 1 = unacceptable). Results Wiring success was achieved in 95 of 95 attempts in the ex vivo model and in 57 of 57 attempts in vivo. No significant difference in wiring time was observed across added latencies from 0 to 1,000 ms in the ex vivo (p = .64) or in vivo (p = .40) models. Compared to an added latency of 0 ms, perceived latency scores were not significantly different for added latencies of 150 and 250 ms (p = NS for both), but were significantly lower for latencies ≥400 ms (p Conclusions Added latencies up to 250 ms were not associated with perceived latency, but latencies ≥400 ms were perceptible. Based on these findings, future telestenting studies should utilize networks with latencies ≤250 ms if perceived latency is to be avoided.

CH2 transitions between 68 and 71 GHz were first detected toward the Orion-KL and W51 Main SFRs. Given their upper level energies of 225 K, they were thought to arise in dense, hot molecular cores near newly formed stars. However, this has not been confirmed by further observations of these lines and their origin has remained unclear. Generally, there is a scarcity of observational data for CH2 and, while it is an important compound in the astrochemical context, its actual occurrence in astronomical sources is poorly constrained. The present study, along with other recent observations of the Orion region we report, rule out the possibility of an association with gas that is both hot and dense. We find that the distribution of the CH2 emission closely follows that of the [CII] 158 um emission, while CH2 is undetected toward the hot core itself. The observations suggest, rather, that its extended emission arises from hot but dilute layers of PDRs and not from the denser parts of such regions as in the case of the Orion Bar. This hypothesis was corroborated by comparisons of the observed CH2 line profiles with those of CRRLs, well-known PDR tracers. In addition, we report the detection of the 70 GHz fine- and hfs lines of o-CH2 toward the W51E, W51M, W51N, W49N, W43, W75N, DR21, and S140 SFRs, and three of the fine- and hfs lines between 68-71 GHz toward W3 IRS5. Furthermore, using a non-LTE radiative transfer analysis, we can constrain the gas temperatures and H2 density to 163 K and 3.4e3 cm^-3, respectively. This analysis confirms our hypothesis that CH2 originates in warm and dilute PDR layers. Our analysis suggests that for the excitation conditions under the physical conditions that prevail in such regions, these lines are masering, with weak level inversion. The resulting amplification of the lines' spontaneous emission greatly aids in their detection., Accepted in A&A, 25 pages, 18 figures, 5 tables

OBJECTIVES This study was conducted to evaluate the association of geographic distance with robotic telestenting performance by comparing performance measures in transcontinental and regional pre-clinical models of telestenting. BACKGROUND Robotic telestenting, in which percutaneous coronary intervention (PCI) is performed on a remotely located patient, might improve PCI access, but has not been attempted over vast distances likely required to reach many underserved regions. METHODS Telestenting performance was compared in regional (Boston to New York [206 miles]) and transcontinental (Boston to San Francisco [3,085 miles]) ex vivo models of telestenting, wherein a physician in Boston attempted robotic PCI on endovascular simulators in New York and San Francisco, respectively. PCI was attempted over both wired and fifth generation (5G)-wireless networks. Outcome measures included procedural success, procedural time, and perceived latency. RESULTS Procedural success was achieved in 20 consecutive target lesions in the regional model and in 16 consecutive target lesions in the transcontinental model. The transcontinental model had a greater latency than the regional model over both wired (121.5 ± 2.4 ms vs. 67.8 ± 0.9 ms; p

Here we aim to characterise submillimetre water masers at 437, 439, 471, and 474 GHz towards a sample of evolved stars. We used the Atacama Pathfinder Experiment (APEX) to observe submillimetre water transitions and the CO (4-3) line towards 11 evolved stars. The sample included semi-regular and Mira variables, plus a red supergiant star. We performed radiative transfer modelling for the water masers. We also used the CO observations to determine mass loss rates for the stars. From the sample of 11 evolved stars, 7 display one or more of the masers at 437, 439, 471, and 474 GHz. We therefore find that these masers are common in evolved star circumstellar envelopes. The fact that the maser lines are detected near the stellar velocity indicates that they are likely to originate from the inner circumstellar envelopes of our targets. We tentatively link the presence of masers to the degree of variability of the target star, that is, masers are more likely to be present in Mira variables than in semi-regular variables. We suggest that this indicates the importance of strong shocks in creating the necessary conditions for the masers. Typically, the 437 GHz line is the strongest maser line observed among those studied here. We cannot reproduce the above finding in our radiative transfer models. In general, we find that maser emission is very sensitive to dust temperature in the lines studied here. To produce strong maser emission, the dust temperature must be significantly lower than the gas kinetic temperature. In addition to running grids of models in order to determine the optimum physical conditions for strong masers in these lines, we performed smooth wind modelling for which we cannot reproduce the observed line shapes. This also suggests that the masers must originate predominantly from the inner envelopes., Accepted for publication in A&A

Objectives The purpose of this study was to explore the feasibility and safety of robotic PCI performed using an off-siteremote-control system in an animal model. Background Access to primary percutaneous coronary intervention (PCI) remains a challenge in acute myocardial infarction management. The combination of telemedicine and robotic PCI allow the potential delivery of primary PCI to remote locations without the delay of transfer. Methods This single-center prospective pilot preclinical feasibility study compared robotic PCI with remote PCI on swine across three stages (adjacent room, different floor of the same building, two different buildings). Latency up to 1,000 ms was introduced into the operating environment to simulate decreased network quality (blinded to operator). The primary outcome measures were technical success and acute safety. The secondary outcome measures included lesion wiring time, procedural time and qualitative scoring of the PCI experience by the operator. Results Across 52 experiments in 15 animals, technical success was 100%. No procedural complications occurred during the study. No significant difference in lesion treatment time was detected between stages (p = .11) and between time per target vessel when latency up to 1,000 ms was introduced (p = .58). Injected delay >250 ms had the greatest impact on procedure perceived lag. Longer procedure time was associated with lower procedure impact score, regardless of injected latency. Conclusions Remote robotic PCI was feasible and safe in an animal model. Procedural duration was acceptable and unaffected by network latency. Future studies are needed to determine the safety and feasibility of remote PCI in humans.

Background: Evidence for pulmonary metastasectomy following colorectal cancer (CRC) is scarce. The aim of the study was to investigate long-term survival and identify prognostic factors to aid patient selection. Methods: We included all patients who underwent pulmonary resections for CRC metastases between January 1, 2004 and December 31, 2015 in a population-based cohort study. The primary outcome measure was all-cause mortality and was ascertained from Swedish national registers. The Kaplan-Meier estimator was used to calculate cumulative survival. We used Cox regression for estimation of hazard ratios (HR) and 95% confidence intervals (CI) for the association between patient characteristics and survival. Results: We included 184 patients. The number of procedures per year increased from 1 in 2004 to 34 in 2015. During a median follow-up time of 3.2 years, 36% (66/184) patients died. Overall survival at 5 years was 60% (95% CI: 50–68%) and was significantly lower compared to an age- and gender-matched Swedish population. Carcinoembryonic antigen (CEA) level was identified as a prognostic factor for mortality in the age and sex-adjusted analysis (HR, 2.46; 95% CI: 1.15–5.26, P=0.020). Conclusions: We found a steady increase in the number of pulmonary metastasectomies after CRC during the study period. We identified prethoracotomy CEA level as a prognostic factor for long-term survival, which was consistent with prior reports. The 5-year overall survival rate in our study was 60%, which was high in comparison with prior reports. Although our results indicated that current patient selection criteria were reasonable, definitive evidence of efficacy is pending.

Introduction: We review the current knowledge of CT screening for lung cancer and present an expert-based, joint protocol for the proper implementation of screening in the Nordic countries.Materials and methods: Experts representing all the Nordic countries performed literature review and concensus for a joint protocol for lung cancer screening.Results and discussion: Areas of concern and caution are presented and discussed. We suggest to perform CT screening pilot studies in the Nordic countries in order to gain experience and develop specific and safe protocols for the implementation of such a program.

The CorPath System is a robotic system for use in percutaneous coronary intervention (PCI). In a PCI procedure, balloon catheters are inflated at the coronary lesion to enlarge the narrowed vessel to restore blood flow. To visualize the devices inside the arteries, a fluoroscopy system is used, which exposes physicians to X-ray radiation during the procedure. The CorPath System allows the physician to navigate the devices deployed in PCI using robotic controls. Therefore, it significantly reduces physician exposure to radiation as well as musculoskeletal strain related to wearing heavy leaded aprons, as the physician can operate while seated at a radiation-shielded workstation. In addition, the robotic system allows higher precision than performing the procedure manually. In this chapter, the architecture of the CorPath GRX System, different functions of the robot, and the workflow of robotic-assisted PCI are presented. Moreover, kinematics of the arm used to position the robotic drive system is studied. Using the kinematics and workspace analysis, the arm is designed so that the robotic drive can reach to all the desired poses relative to the patient. Finally, a control model of the actuators used to manipulate the devices is developed and presented.

Specific inflammatory pathways are indicated to contribute to severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.This experimental study in human small bronchi aimed to provide insight into which of the type 2 and type 17 cytokines cause hyperresponsiveness of airway smooth muscle.Explanted small bronchi isolated from human lung tissue and human airway smooth muscle cells were treated for 2 and 1 day(s), respectively, with 100 ng/mL of IL-4, IL-5, IL-13, or IL-17A, and contractile responses, CaTreatment with IL-13 increased the potency of histamine, carbachol, and leukotriene DThe glucocorticoid-insensitive hyperrresponsiveness in isolated human airways induced by IL-13 and IL-4 provides further evidence that the IL-4Rα pathway should be targeted as a new strategy for the treatment of airway hyperresponsiveness in asthma.

// Ghazal Efazat 1, * , Metka Novak 1, * , Vitaliy O. Kaminskyy 2 , Luigi De Petris 1 , Lena Kanter 1 , Therese Juntti 1 , Per Bergman 3 , Boris Zhivotovsky 2 , Rolf Lewensohn 1 , Petra Haag 1 , Kristina Viktorsson 1 1 Karolinska Biomics Center, Department of Oncology-Pathology, Karolinska Institutet, SE-171 76 Stockholm, Sweden 2 Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden 3 Department of Molecular Medicine and Surgery (MMK), Thoracic Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden * These authors have contributed equally to this work Correspondence to: Kristina Viktorsson, email: Kristina.Viktorsson@ki.se Petra Haag, email: Petra.Haag@ki.se Keywords: Ephrin B3, EphA2, NSCLC, migration, invasion Received: September 17, 2015 Accepted: July 16, 2016 Published: August 11, 2016 ABSTRACT Ephrin receptors (Ephs) are reported to control metastatic signaling of non-small cell lung cancer (NSCLC) and other tumors. Here we show for the first time that blocking expression of the Eph ligand Ephrin B3 inhibits NSCLC cell migration and invasion. We demonstrate that Ephrin B3 directly binds the EphAs EphA2, EphA3, EphA4, and EphA5. EphA2 Ser897 was previously shown to drive migration propensity of tumor cells and our study reveals that EphA2 stays phosphorylated on Ser897 in the Ephrin B3/EphA2 complex in NSCLC cells of different histology. Moreover, we report that within such Ephrin B3/EphA2 complex both Akt Ser 129 and p38MAPK are found indicating a potential to drive migration/proliferation. We also found the EMT marker E-cadherin expression to be maintained or increased upon Ephrin B3 blockade in NSCLC cells. Expression of Ephrin B3 was furthermore analyzed in a cohort of NSCLC stage IA-IB cases (n=200) alongside EphA2 and Ephrin A1. We found that Ephrin B3 was concomitantly expressed with EphA2 and Ephrin A1 with higher Ephrin B3 levels found in non-squamous than in squamous tumors, whereas EphA2 was higher expressed in well-differentiated than in low-differentiated tumors. In the entire NSCLC cohort, Ephrin B3 expression was not linked to patient survival, whereas a high EphA2 expression was associated with improved survival (p=0.03). In conclusion, we show that blocking Ephrin B3 expression inhibits NSCLC proliferation-, migration- and invasion capacity which calls for further studies on interference with Ephrin B3 as a possible therapeutic avenue in this tumor malignancy.

Background: The aim of this nationwide observational cohort study was to investigate the early postoperative complications and long-term survival following video-assisted thoracoscopic surgery (VATS) lobectomy compared to open thoracotomy lobectomy for early stage non-small cell lung cancer (NSCLC). Methods: We used the Swedish national quality register for general thoracic surgery and included all patients who underwent lobectomy for NSCLC during 2012-2015. We compared postoperative complications and long-term survival in patients who underwent VATS lobectomy at our institution to patients who underwent open lobectomy at the other seven hospitals in Sweden. We used inverse probability of treatment weighting to limit differences in baseline characteristics between the groups and used standardized mean differences to assess balance after weighting. Results: We included 1,601 patients who underwent open (n=1,316) or VATS (n=285) lobectomy for NSCLC. The mean age was 67.7 years in both groups and comorbidities were well balanced, but the open thoracotomy group had a higher proportion of patients with more advanced cancer stage. After weighting, all baseline characteristics were well balanced. Most patients (84%) did not have postoperative complications; 83% vs . 86% in the open and VATS group, respectively (P=0.41). The 30- and 90-day mortality was 0.7% vs . 0.3% (P=0.38) and 1.7% vs . 0.3% (P=0.09) in the open thoracotomy and VATS group, respectively. There were significantly more transfusions (5.0% vs . 1.4%, P=0.008) and pneumonia (5.5% vs . 0.6%, P=0.002) in the in the open thoracotomy and VATS group, respectively. The overall survival at 1 and 5 years was 92% vs . 97% and 63% vs . 78% in the open thoracotomy and VATS group, respectively; HR (95% CI): 0.47 (0.33–0.68). Conclusions: We found less postoperative complications and better long-term survival following VATS lobectomy compared to open thoracotomy lobectomy for NSCLC. The implementation of a VATS lobectomy program did not compromise patient safety or the oncological efficacy.

This study aimed to describe overall survival following pulmonary metastasectomy for colorectal cancer (CRC) in Sweden, and to assess the discrimination of a recently proposed risk prediction model.Individual-level data of 756 patients who underwent resection of pulmonary metastases from CRC between 2009 and 2015 were obtained from ThoR, a Swedish national quality register for thoracic surgery. We classified patients into three risk categories according to the number of preoperative risk factors [age, disease-free interval (DFI), presence of extrathoracic lesions, number of pulmonary metastases] established in a prior study. We estimated the hazard ratios (HRs) and 95% confidence interval (CI) by Cox regression and the restricted mean survival time difference as group contrast measures.During a median follow-up time of 2.9 years, 35% (268/756) patients died. At 5 years, overall survival was 56% (95% CI: 51-60%). In a Cox regression model with risk category as the only independent variable, the HR for all-cause mortality was 1.94 (95% CI: 1.38-2.72, P0.001) and 4.35 (95% CI: 2.49-7.62, P0.001) in the moderate- (n=558) and high-risk categories (n=32), respectively, versus the low-risk category (n=166). At 5 years, the differences in restricted mean survival time were 6 months (P0.001) and 1.5 years (P0.001) in the moderate- and high-risk categories, respectively, versus the low-risk category.Five-year survival after surgery for pulmonary metastases from CRC in Sweden was similar or higher compared with contemporary reports. A prognostic model, initially developed in Japanese patients, had excellent discrimination in an external validation cohort of Swedish patients.

Context: We describe the new SEPIA (Swedish-ESO PI Instrument for APEX) receiver, which was designed and built by the Group for Advanced Receiver Development (GARD), at Onsala Space Observatory (OSO) in collaboration with ESO. It was installed and commissioned at the APEX telescope during 2015 with an ALMA Band 5 receiver channel and updated with a new frequency channel (ALMA Band 9) in February 2016. Aims: This manuscript aims to provide, for observers who use the SEPIA receiver, a reference in terms of the hardware description, optics and performance as well as the commissioning results. Methods: Out of three available receiver cartridge positions in SEPIA, the two current frequency channels, corresponding to ALMA Band 5, the RF band 158--211 GHz, and Band 9, the RF band 600--722 GHz, provide state-of-the-art dual polarization receivers. The Band 5 frequency channel uses 2SB SIS mixers with an average SSB noise temperature around 45K with IF (intermediate frequency) band 4--8 GHz for each sideband providing total 4x4 GHz IF band. The Band 9 frequency channel uses DSB SIS mixers with a noise temperature of 75--125K with IF band 4--12 GHz for each polarization. Results: Both current SEPIA receiver channels are available to all APEX observers., Accepted for publication in Astronomy & Astrophysics

Protoplasts of Brassica napus hypocotyls were transfected using electroporation. Parameters such as discharge potential, protoplast density and buffer constituents were tested to determine the most suitable conditions for gene transfer. To monitor the introduction of DNA into protoplasts a plasmid containing the β-glucuronidase (EC 3.2.1.31), and the neomycin phospotransferase (EC 2.7.1.95) genes was used. By using this construct, expression of a screenable marker gene for transient expression analysis as well as an antibiotic resistance marker gene for selection of stable transformants were obtained. Refined electroporation conditions resulted in a frequency of 0.1% transiently transformed protoplasts. Microcalluses were cultured under selective conditions in a bead-type culture system. Resistant callus, with an absolute transformation frequency of 4.9 × 10-5 and a relative transformation frequency of 0.3% could be achieved. X-ray irradiation of newly electroporated protoplasts did not enhance absolute transformation frequencies. From some of the resistant calluses, transgenic plants could be regenerated which were characterized by molecular analysis.

There is an on-going discussion regarding the recurrence rate after surgery for primary spontaneous pneumothorax by video assisted thoracic surgery (VATS) or by thoracotomy access. This study aimed to describe the recurrence rate, and to identify a possible learning curve, following surgery for primary spontaneous pneumothorax by VATS.All patients who underwent surgery for primary spontaneous pneumothorax by VATS at Karolinska University Hospital 2004-2013 were reviewed. Preoperative and operative characteristics were obtained from medical records. Patients were followed-up through telephone interviews or questionnaires and by review of medical records. The primary outcome of interest was time to recurrence of pneumothorax requiring intervention. Outcomes were compared between patients operated during 2004-June 2010 and July 2010-2013.219 patients who underwent 234 consecutive procedures were included. The mean follow-up times were 6.3 and 2.9 years in the early and late period, respectively. The postoperative recurrence rate in the early period was 16% (11%-25%), 18% (12%-27%), and 18% (12%-27%), at 1, 3 and 5 years, compared to 1.7% (0.4%-6.8%), 7.6% (3.7%-15%), and 9.8% (4.8%-19%) at 1, 3 and 5 years, in the late period (p = 0.016).We found that the recurrence rate after thoracoscopic surgery for primary spontaneous pneumothorax decreased significantly during the study period. Our results strongly suggest that thoracoscopic surgery for pneumothorax involve a substantial learning curve.

Taste-sensing type 2 receptors (TAS2Rs) have been implicated in extraoral functions. Airway smooth muscle expresses TAS2Rs and is strongly relaxed by TAS2R agonists. We hypothesised that TAS2R agonists might affect vascular smooth muscle as well. Moreover, the general pharmacological profile of TAS2R agonists, which are used to investigate the functions of TAS2R׳s, are undefined. The aim of this study was to pharmacologically characterise the effects of five prototype TAS2R agonists in vascular smooth muscle. Responses to the TAS2R agonists were investigated in guinea-pig aorta and taenia coli, mouse aorta (wild-type and caveolin-1(-/-) mice) and human pulmonary arteries. Chloroquine, denatonium, dextromethorphan, noscapine and quinine, agonists for TAS2R3, TAS2R4, TAS2R10 and TAS2R14, induced strong endothelium-independent relaxations (responses between 82-96% of maximal relaxations) in phenylephrine pre-contracted guinea-pig aorta that persisted in the presence of L-type Ca(2+) and KCa1.1-channel blockers. Experiments in guinea-pig taenia coli revealed that denatonium and quinine also inhibited relaxations to phenylephrine, indicating antagonism of α-adrenoceptors. Only chloroquine and noscapine mediated relaxations when the guinea pig aorta was pre-contracted by U-46619 or PGF2α. Relaxations to chloroquine and noscapine after U-46619 pre-contractions were however markedly impaired in aortae from caveolin-1(-/-) mice. Chloroquine and noscapine mediated relaxations of human pulmonary arteries that expressed also mRNA for TAS2R3, TAS2R4, TAS2R10 and TAS2R14, at levels similar to that of the α1A adrenoceptor. Notwithstanding whether TAS2Rs are involved or not, TAS2R agonists have profound effects on vascular smooth muscle. Chloroquine and noscapine are of special interest as their effects cannot be accounted for by conventional pathways. (Less)

We present 247-GHz molecular line observations of methanol (CH$_3$OH) toward sixteen massive star-forming regions, using the APEX telescope with an angular resolution of $25''$. The sample covers a range of evolutionary states, including warm molecular cores, hot molecular cores, and ultracompact HII regions. The hot cores, all of which include UC HII regions, show rich molecular line spectra, although the strength of different species and transitions varies from source to source. In contrast, the warm cores do not show significant molecular line emission. Multiple methanol transitions are detected toward nine of the hot cores; eight of these had enough transitions to use the rotation diagram method to estimate rotational temperatures and column densities. The temperatures lie in the range 104$-$168 K and column densities from $3\times10^{16}$ to $7\times10^{18}$ cm$^{-2}$. Using the average methanol line parameters, we estimate virial masses, which fall in the range from 145 to 720 M$_\odot$ and proved to be significantly higher than the measured gas masses. We discuss possible scenarios to explain the chemical differences between hot cores and warm molecular cores. One of the observed methanol lines, $4_{2}-5_{1}A^{+}$ at 247.228 GHz, is predicted to show class II maser emission, similar in intensity to previously reported $J_0-J_{-1}E$ masers at 157 GHz. We did not find any clear evidence for maser emission among the observed sources; however, a weak maser in this line may exist in G345.01+1.79., Accepted for publication in The Astronomical Journal

We have performed a study of the characteristics of the circumstellar environment of the binary object HD101584, that provides information on a likely evolutionary scenario. We have obtained and analysed ALMA observations, complemented with observations using APEX, of a large number of molecular lines. An analysis of the spectral energy distribution has also been performed. Emissions from 12 molecular species (not counting isotopologues) have been observed, and most of them mapped with angular resolutions in the range 0.1" to 0.6". Four circumstellar components are identified: i) a central compact source of size 0.15", ii) an expanding equatorial density enhancement (a flattened density distribution in the plane of the orbit) of size 3", iii) a bipolar high-velocity outflow (150 km/s), and iv) an hourglass structure. The outflow is directed almost along the line of sight. There is evidence of a second bipolar outflow. The mass of the circumstellar gas is 0.5[D/1 kpc]^2 Msun, about half of it lies in the equatorial density enhancement. The dust mass is 0.01[D/1 kpc]^2 Msun, and a substantial fraction of this is in the form of large-sized, up to 1 mm, grains. The estimated kinetic age of the outflow is 770[D/1 kpc] yr. The kinetic energy and the scalar momentum of the accelerated gas are estimated to be 7x10^(45)[D/1 kpc]^2 erg and 10^(39)[D/1 kpc]^2 g cm/s, respectively. We provide good evidence that the binary system HD101584 is in a post-common-envelope-evolution phase, that ended before a stellar merger. Isotope ratios combined with stellar mass estimates suggest that the primary star's evolution was terminated already on the first red giant branch (RGB). Most of the energy required to drive the outflowing gas was probably released when material fell towards the companion., Comment: Accepted for publication in A&A

In 2011, hydrogen peroxide (HOOH) was observed for the first time outside the solar system (Bergman et al., A&A, 2011, 531, L8). This detection appeared a posteriori quite natural, as HOOH is an intermediate product in the formation of water on the surface of dust grains. Following up on this detection, we present a search for HOOH in a diverse sample of sources in different environments, including low-mass protostars and regions with very high column densities, such as Infrared Dark Clouds (IRDCs). We do not detect the molecule in any other source than Oph A, and derive 3$��$ upper limits for the abundance of HOOH relative to H$_2$ lower than in Oph A for most sources. This result sheds a different light on our understanding of the detection of HOOH in Oph A, and shifts the puzzle to why this source seems to be special. Therefore we rediscuss the detection of HOOH in Oph A, as well as the implications of the low abundance of HOOH, and its similarity with the case of O$_2$. Our chemical models show that the production of HOOH is extremely sensitive to the temperature, and favored only in the range 20$-$30 K. The relatively high abundance of HOOH observed in Oph A suggests that the bulk of the material lies at a temperature in the range 20$-$30 K., 18 pages, 3 figures, invited refereed paper at the Faraday Discussion 168

The circumstellar environments of objects on the asymptotic giant branch and beyond are rich in molecular species. Nevertheless, methanol has never been detected in such an object, and is therefore often taken as a clear signpost for a young stellar object. However, we report the first detection of CH3OH in a post-AGB object, HD 101584, using ALMA. Its emission, together with emissions from CO, SiO, SO, CS, and H2CO, comes from two extreme velocity spots on either side of the object where a high-velocity outflow appears to interact with the surrounding medium. We have derived molecular abundances, and propose that the detected molecular species are the effect of a post-shock chemistry where circumstellar grains play a role. We further provide evidence that HD 101584 was a low-mass, M-type AGB star.

Background The aim was to analyze the association between baseline self-reported health-related quality of life and long-term survival after thoracic operations. Methods In a prospective population-based cohort study, we included patients scheduled for thoracic operations and obtained information about preoperative health-related quality of life using the validated quality-of-life instrument Short Form-36. Patients were categorized according to higher or lower physical and mental component scores, compared with an age- and sex-matched reference population. The primary outcome measure was all-cause mortality and was ascertained from Swedish national registers. We used Cox regression for estimation of hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between preoperative physical/mental quality of life and long-term survival while adjusting for differences in baseline characteristics, cancer stage, histopathologic process, and other factors. Results We included 249 patients between 2006 and 2008. During a median follow-up time of 8.0 years, 119 patients (48%) died. Having a physical component summary score less than reference was significantly associated with mortality (multivariable adjusted HR 2.02, 95% CI: 1.34 to 3.06, p = 0.001). A mental component summary score less than reference was not associated with mortality (adjusted HR 1.32, 95% CI: 0.84 to 3.06, p = 0.233). Conclusions In patients who underwent thoracic operations, a self-reported physical quality of life lower than reference value was associated with significantly worse survival independent of histopathologic process, cancer stage, extent of operations, and other patient-related factors. The preoperative mental component of quality of life was not associated with long-term survival.

The 7th TNM staging system for non-small cell lung cancer (NSCLC) developed by the International Association for the study of Lung Cancer (IASLC) has been applied in Sweden since the beginning of the year 2010. The aim of this retrospective study was to evaluate the prognostic role of the 7th TNM staging system in a surgical Swedish patient cohort with node-negative NSCLC.We collected data from stage I patients (pT1-2 pN0, 6th TNM system) who underwent surgery for NSCLC at Karolinska University Hospital from 1987 to 2002. Tumors were restaged according to the 7th TNM version. Cox multivariate survival analysis was implemented in order to determine the prognostic impact of pathological stage when classified according to either the 6th or the 7th TNM systems.The patient population consisted of 452 subjects. Tumor size was ≤ 3 cm in 51% of cases. The predominant histology was adenocarcinoma (53%) and lobectomy was the most common surgical procedure (82% of patients). The five-year survival rate in patients with stage IA vs. IB (6th TNM) was 62% vs. 51%, respectively (log-rank p = 0.036). Corresponding figures for the 7th TNM system were 70% in stage IA-T1a, 51% in stage IA-T1b, 54% in stage IB, 51% in stage IIA and 35% in stage IIB (log-rank p = 0.002). On multivariate analysis, adjusted by age, gender, histology, kind of surgery, grade of differentiation and smoking status, pathological stage was an independent prognostic factor if classified according to the 7th TNM version (p = 0.001), but not if scored according to the 6th TNM edition (p = 0.090).The 7th TNM classification system is a more accurate predictor of prognosis in stage I operated patients than the old classification. The new system should be implemented even on retrospective cohorts especially when investigating the prognostic implication of the expression of molecular biomarkers.

We present the results of VLA observations of a maser candidate in the low-mass star formation region L1157 in the 7(0)-6(1) A(+) transition at 44 GHz. The line is emitted by a compact, undoubtedly maser source associated with clump B0a, which is seen in maps of L1157 in thermal lines of methanol and other molecules. A much weaker compact source is associated with clump B1a, which is brighter than B0a in thermal methanol lines. The newly detected masers may form in thin layers of turbulent post-shock gas. In this case, the maser emission may be beamed, so that only an observer located in or near the planes of the layers can observe strong masers. On the other hand, the maser lines are double with a "red" asymmetry, indicating that the masers may form in collapsing clumps. A detailed analysis of collapsing-cloud maser models and their applicability to the masers in L1157 will be developed in subsequent papers.

Aims. In March 2008, the APEX facility instrument was installed on the telescope at the site of Lliano Chajnantor in northern Chile. The main objective of the paper is to introduce the new instrument to the radio astronomical community. It describes the hardware configuration and presents some initial results from the on-sky commissioning. Methods. The heterodyne instrument covers frequencies between 211 GHz and 1390 GHz divided into four bands. The first three bands are sideband-separating mixers operating in a single sideband mode and based on superconductor-insulator-superconductor (SIS) tunnel junctions. The fourth band is a hot-electron bolometer, waveguide balanced mixer. All bands are integrated in a closedcycle temperature-stabilized cryostat and are cooled to 4 K. Results. We present results from noise temperature, sideband separation ratios, beam, and stability measurements performed on the telescope as a part of the receiver technical commissioning. Examples of broad extragalactic lines are also included.

Context. Ring-like structures in the interstellar medium (ISM) are commonly associated with high-mass stars. Kinematic studies of large structures in giant molecular clouds (GMCs) toward these ring-like structures may help us to understand how massive stars form. Aims. The origin and properties of the ring-like structure G345.45+1.50 is investigated through observations of the 13CO(3-2) line. The aim of the observations is to determine the kinematics in the region and to compare physical characteristics estimated from gas emission with those previously determined using dust continuum emission. This area in the sky is well suited for studies like this because the ring is located 1°5 above the Galactic plane at 1.8 kpc from the Sun, thus molecular structures are rarely superposed on our line of sight, which minimizes confusion effects that might hinder identifying of individual molecular condensations. Methods. The 13CO(3-2) line was mapped toward the whole ring using the Atacama Pathfinder Experiment (APEX) telescope. The observations cover 17? × 20? in the sky with a spatial resolution of 0.2 pc and an rms of ~1 K at a spectral resolution of 0.1 km s-1. Results. The ring is found to be expanding with a velocity of 1.0 km s-1, containing a total mass of 6.9 × 103M?, which agrees well with that determined using 1.2 mm dust continuum emission. An expansion timescale of ~3 × 106 yr and a total energy of ~7 × 1046 erg are estimated. The origin of the ring might have been a supernova explosion, since a 35.5 cm source, J165920-400424, is located at the center of the ring without an infrared counterpart. The ring is fragmented, and 104 clumps were identified with diameters of between 0.3 and 1.6 pc, masses of between 2.3 and 7.5 × 102M?, and densities of between ~102 and ~ 104 cm-3. At least 18% of the clumps are forming stars, as is shown in infrared images. Assuming that the clumps can be modeled as Bonnor-Ebert spheres, 13 clumps are collapsing, and the rest of them are in hydrostatic equilibrium with an external pressure with a median value of 4 × 104 K cm-3. In the region, the molecular outflow IRAS 16562-3959 is identified, with a velocity range of 38.4 km s-1, total mass of 13 M?, and kinematic energy of 7 × 1045 erg. Finally, five filamentary structures were found at the edge of the ring with an average size of 3 pc, a width of 0.6 pc, a mass of 2 × 102M?, and a column density of 6 × 1021 cm-2.

There is no generally accepted evolutionary scheme for high mass star formation yet. A simple approach to address this problem is to cover several of the known stages during the formation of massive stars in the same cloud and then investigate their properties trying to construct an evolutionary sequence. Here we present such a project conducted with complementary APEX and ATCA observations. These observations show a compact and bright single hot core in the G327.3-0.6 region on a 0.03 pc scale with a mass of 500 M⊙ and 0.5–1.5 105 L⊙. Additionally a clumpy filament is seen in N2H+. Together with cm continuum observations, the data reveal like pearls on a string several stages of massive star formation, with likely the youngest stages hiding in the cold N2H+ cores analysed with a multilevel study of the APEX and ATCA observations.

Atherosclerosis of the thoracic aorta is an independent risk factor for stroke after cardiac surgery. No attention had so far been paid to its topography. The relationship between the topography of aortic atherosclerosis and stroke was studied in patients admitted for coronary surgery.The extent and location of atherosclerosis in the ascending aorta and arch was assessed intraoperatively with epiaortic ultrasound and transesophageal echocardiography in 611 consecutive patients. They were followed for 5.5 +/- 1.7 years (mean +/- SE), amounting to 3,358 patient-years.The incidence of early postoperative (30-day) stroke was 6.4% in patients with atherosclerosis of the ascending aorta and 1.5% in those without (p = 0.004). The five-year stroke-free survival rates (30 days after the operation) for patients without aortic disease, with less than 50%, and with greater than 50% of the ascending aorta affected, were 95.3 +/- 0.9%, 91.8 +/- 2.1%, and 65.0 +/- 14.6%, respectively (p0.0001).Atherosclerosis of the ascending aorta stands out as a predictor of late stroke. High risk is predominantly linked to atheromas in its distal part and lesser curvature.

Aims. Our aim is to better understand the complex chemistry of organic molecules in the interstellar medium, leading to the formation of pre-biotic molecules such as amino acids. Methods. We have performed a search for the pre-biotic molecules amino acetonitrile (H2 NC H2 CN) and vinyl acetylene (C2H3 CCH) towards four northern hot core sources using the Onsala 20 m telescope. Results. We have determined upper limits to the column density of amino acetonitrile (1–4 × 10 13 cm −2 ) and vinyl acetylene (2– 7 × 10 14 cm −2 ) in the observed sources. In addition, from the absence of other lines within the observed frequency band, we have further constrained the column density of oxiranecarbonitrile (c-C3H3 NO) and amino-ethanol (NH2 CH2 CH2 OH) in these sources.

The plant nucleoside diphosphate kinase (NDPK, EC 2.7.4.6) gene family consists of three groups whose gene products are found in different subcellular locations. In this study we discuss the evolutionary history, localization and expression of the NDPK genes, addressing the question of functional specialization of the different NDPKs. A phylogenetic analysis revealed that the three NDPK isoforms were present already in the last common ancestor of vascular plants and mosses. Our data also imply that the NDPK3 genes possess a higher degree of conservation than the NDPK1 and NDPK2 genes. The expression levels of the different NDPKs in Arabidopsis thaliana inflorescences, leaves and roots were evaluated using quantitative PCR as well as in silico methods. This analysis showed that NDPK1 is the most highly expressed NDPK gene in all the studied tissues. NDPK3a has the second highest NDPK expression, while NDPK3b is expressed to a very low extent. However, expression of NDPK3b is elevated in inflorescence tissue. In situ hybridization experiments performed on inflorescences showed NDPK3a expression in actively dividing cells. NDPK3b expression was observed during later stages of flower development, specifically in the tapetum, ovules and petals. Additionally, we show that an NDPK3 protein is able to direct the green fluorescent protein to both mitochondria and chloroplasts using transient expression in leaf protoplasts. The dual localisation of NDPK3 was confirmed by Western blot, which also demonstrated that the majority of the NDPK3 protein is found in the mitochondria.

In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer.We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level.NK cells in human lung tissue and matched peripheral blood from 132 subjects were analyzed by using 16-color flow cytometry and confocal microscopy.CD56Here, we characterize the major NK cell populations in the human lung. Our data suggest a model in which the majority of NK cells in the human lung dynamically move between blood and the lung rather than residing in the lung as bona fide tissue-resident CD69

Background Inhaled prostaglandin (PG) E 2 might inhibit asthmatic responses, but the mechanisms involved remain undefined. Objective We sought to characterize the direct and indirect effects of PGE 2 on human small airways with particular reference to the receptors mediating the responses. Methods Contraction and relaxation were studied in isolated human bronchi with an inner diameter of 1 mm or less. Results Low concentrations of PGE 2 (0.01-1 μmol/L) relaxed the bronchi precontracted by histamine. The bronchodilator response was inhibited by the E prostanoid (EP) subtype 4 receptor antagonist ONO-AE3-208 but unaffected by the EP 2 receptor antagonist PF-04418948. Higher concentrations of PGE 2 (10-100 μmol/L) contracted the small airways. However, the TP receptor agonists U-46,619, PGF 2α , and PGD 2 were more potent than PGE 2 . Moreover, the bronchoconstrictor responses to PGE 2 and all other tested prostanoids, including the EP 1 /EP 3 receptor agonist 17-phenyl trinor PGE 2 and the partial FP receptor agonist AL-8810, were uniformly abolished by the TP receptor antagonist SQ-29,548. In the presence of TP and EP 4 antagonists, PGE 2 inhibited the mast cell–mediated bronchoconstriction resulting from anti-IgE challenge. Measurement of the release of histamine and cysteinyl leukotrienes documented that this bronchoprotective action of PGE 2 was mediated by the EP 2 receptor, unrelated to bronchodilation, and increased with time of exposure. Conclusion The pharmacology of PGE 2 in isolated human small airways was different from its profile in animal models. This first demonstration of powerful EP 2 receptor–mediated inhibition of IgE-dependent contractions in human airways introduces a new selective target for the treatment of asthma. This EP 2 control of mast cell–mediated bronchoconstriction is presumably exaggerated in patients with aspirin-exacerbated respiratory disease.

This study aimed to investigate whether IL-13, a key mediator in the pathobiology of asthma and the induction of AHR, can directly alter human airway smooth muscle (HASM) function in isolated human small bronchi. Human small bronchi (diameter 2+ was visualised with Fluo-4 in HASM cells. IL-13 induced a 2.5-3.1 fold increase in the potency of contractions towards histamine (figure A) and carbachol in human small bronchi, whereas no effects on the maximal amplitude of these contractions were observed. Conversely, IL-13 reduced the efficacy and potency of salbutamol, whereas relaxations induced by formoterol and the TAS2R agonists chloroquine and noscapine remained unaltered. Intracellular Ca 2+ measurements in HASM cells revealed that IL-13 increased both the potency (figure B) and maximal amplitude of histamine-induced Ca 2+ mobilisation. Dexamethasone (100nM) did not prevent the IL-13-induced hyperreactivity in either human bronchi or HASM cells. This study demonstrates that IL-13 induces glucocorticoid-insensitive, functional remodelling of human airway smooth muscle that can contribute to the development and persistence of AHR.

International audience

One requirement in the biocides regulation (528/2012/EU) is that the efficacy of the biocidal product has to be demonstrated when applying for approval. It has to be shown that the product really h ...

This study investigated the previously uncertain relationship of embolic load captured during coronary artery bypass grafting and the extent of ascending aortic atherosclerosis as measured by wall thickness. Patients (n=113) underwent isolated arrested heart coronary artery bypass grafting. Ascending aortic wall thickness measures were obtained by epiaortic ultrasound. Aortic segmental values (distal, mid, proximal) were determined by the summation of measures (anterior lateral, posterior, medial) at each segment. An intraaortic filter (EMBOL-X) System, Edwards Lifesciences, Irvine, CA) was placed into the arterial cannula, distal to the aortic measurements, just before releasing the aortic cross-clamp. Particulate debris was found in 96% (109/113) of filters. Mean number of particles was 6.8+/-4.8 (range 0-23) and mean particle surface area was 5.5+/-7.0 mm(2) (range 0-51 mm(2)). Total aortic wall thickness, distal third, mid third, and proximal third thicknesses were 27.4+/-4.4 mm, 9.5+/-2.0 mm, 9.0+/-1.9 mm, and 8.8+/-1.4 mm, respectively. There was no significant correlation between the number of particles or surface area and any of the aortic wall thickness measures. These results suggest that during on-pump, arrested heart coronary artery bypass grafting, embolic load from the ascending aorta is independent of the extent of ascending aortic atherosclerosis in patients with low or moderate risk aortic pathology.

Aims. The new APEX telescope, located on Llano Chajnantor in Northern Chile, will have high resolution spectroscopic instruments covering the wavelength region from 0.20 to 1.30 mm (210-1500 GHz). Methods. In May 2005, the first facility receiver for the band 0.79-1.07 mm (279-381 GHz) was installed together with backends providing down to 60 kHz spectral resolution. This instrument that operates in double sideband mode uses superconducting tunnel junctions (SIS) as mixing elements operating at 4 K to achieve close to quantum-limited noise performances. The receiver is cooled by a closed-cycle cooling machine that allows continuous operation. The receiver design minimizes moving parts and is fully operated by remote to improve its reliability and the ease of use. Results. The double sideband (DSB) receiver temperatures are in the range 50-70 K, which typically results in a DSB system noise temperature of about 100 K in excellent weather conditions and between 100-200 K in good weather conditions.

The cosmic-ray ionization rate (zeta) of dense molecular clouds is a key parameter for their dynamics and chemistry. Variations of zeta are well established, but it is unclear if these are related to source column density or to Galactic location. Using the APEX telescope, we have mapped the 364 GHz line of H3O+ in the Sgr B2 region and observed the 307 GHz line at selected positions. With the IRAM 30-m telescope we have observed the 203 GHz line of H2O-18 at the same positions. Strong H3O+ emission is detected over a ~3x2 pc region, indicating H3O+ column densities of 10^15 - 10^16 cm^-2 in an 18" beam. The H3O+ abundance of ~3 x 10^-9 and H3O+/H2O ratio of ~1/50 in the Sgr B2 envelope are consistent with models with zeta ~4 x 10^-16 s^-1, 3x lower than derived from H3+ observations toward Sgr A, but 10x that of local dense clouds. The ionization rates of interstellar clouds thus seem to be to first order determined by the ambient cosmic-ray flux, while propagation effects cause a factor of ~3 decrease from diffuse to dense clouds.

Aims. The very high main beam efficiency (90%) of the telescope on the sub-millimetre wave satellite Odin, in combination with the small calibration errors in the absence of atmospheric attenuation, assures that observed line brightness temperatures are very accurately determined. Based on this, we attempt to determine the column density distribution of H-2, and the ortho-water abundance, in the Orion KL region. Methods. We have, for the first time, mapped the (CO)-C-12 J = 5-4 emission in a 7' x 7' region covering Orion KL, observed simultaneously with a (CO)-C-13 J = 5-4 map. Also presented are (CO)-O-18 J = 5-4 emission data at four different positions and a (CO)-O-17 J = 5-4 emission spectrum detected towards the Orion KL position. The Odin mapping was performed at 1' spacing ( beam full width at half maximum 126'' at 557 GHz). Results. The CO J = 5-4 narrow line emission from this region mainly arises in the warm, dense gas at the interface ( the photon-dominated region) between the M42 HII region and the Orion A molecular cloud, the Orion PDR. The (CO)-C-12 and (CO)-C-13 J = 5-4 emission maps have been used to determine the column density distribution of H-2 gas across the Orion KL region. The results have been verified by comparing to column densities obtained using the decidedly optically thin (CO)-O-18 emission as input to the RADEX radiative transfer code. We find H-2 column densities ranging from 5 x 10(21) cm(-2) at map edges to 7 x 10(22) cm(-2) at the molecular ridge. The mass of the gas in the mapped region is estimated to be 480 M-circle dot, of which 320 M-circle dot is situated towards the molecular ridge. We estimate that about half of this mass belongs to the warm Orion PDR interface layer. Finally, based on data from the positions where (CO)-O-18 J = 5-4 has been observed, we estimate the ortho-water abundance in the Orion PDR layer to be >= 8 x 10(-8), higher than previously estimated.

We present Odin observations of the AGB star W Hya in the ground-state transition of ortho-H2O, 1(10)-1(01), at 557GHz. The line is clearly of circumstellar origin. Radiative transfer modelling of the water lines observed by Odin and ISO results in a mass-loss rate of (2.5 +/- 0.5)E-7 Msol/yr, and a circumstellar H2O abundance of (2.0 +/- 1.0)E-3. The inferred mass-loss rate is consistent with that obtained from modelling the circumstellar CO radio line emission, and also with that obtained from the dust emission modelling combined with a dynamical model for the outflow. The very high water abundance, higher than the cosmic oxygen abundance, can be explained by invoking an injection of excess water from evaporating icy bodies in the system. The required extra mass of water is quite small, on the order of ~ 0.1 earth mass., Comment: 7 pages, 6 figures Accepted for publication in Astronomy and Astrophysics