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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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6. |
- Thoma, B, et al.
(author)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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In: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Journal article (peer-reviewed)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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7. |
- Bauer, M., et al.
(author)
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Association between polarity of first episode and solar insolation in bipolar I disorder
- 2022
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In: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 160
-
Journal article (peer-reviewed)abstract
- Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
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8. |
- Bauer, M., et al.
(author)
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Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder
- 2021
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In: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
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Journal article (peer-reviewed)abstract
- Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
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9. |
- Bauer, M., et al.
(author)
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Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder
- 2023
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In: International Journal of Bipolar Disorders. - 2194-7511. ; 11:1
-
Journal article (peer-reviewed)abstract
- BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P <= 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
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10. |
- Aoyama, T., et al.
(author)
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The anomalous magnetic moment of the muon in the Standard Model
- 2020
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In: Physics reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 887, s. 1-166
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Research review (peer-reviewed)abstract
- We review the present status of the Standard Model calculation of the anomalous magnetic moment of the muon. This is performed in a perturbative expansion in the fine-structure constant α and is broken down into pure QED, electroweak, and hadronic contributions. The pure QED contribution is by far the largest and has been evaluated up to and including O(α5) with negligible numerical uncertainty. The electroweak contribution is suppressed by (mμ/MW)2 and only shows up at the level of the seventh significant digit. It has been evaluated up to two loops and is known to better than one percent. Hadronic contributions are the most difficult to calculate and are responsible for almost all of the theoretical uncertainty. The leading hadronic contribution appears at O(α2) and is due to hadronic vacuum polarization, whereas at O(α3) the hadronic light-by-light scattering contribution appears. Given the low characteristic scale of this observable, these contributions have to be calculated with nonperturbative methods, in particular, dispersion relations and the lattice approach to QCD. The largest part of this review is dedicated to a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach. The final result reads aμSM = 116 591 810(43) x 10-11 and is smaller than the Brookhaven measurement by 3.7 σ. The experimental uncertainty will soon be reduced by up to a factor four by the new experiment currently running at Fermilab, and also by the future J-PARC experiment. This and the prospects to further reduce the theoretical uncertainty in the near future - which are also discussed here - make this quantity one of the most promising places to look for evidence of new physics.
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11. |
- Kasliwal, M. M., et al.
(author)
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Illuminating gravitational waves : A concordant picture of photons from a neutron star merger
- 2017
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6370, s. 1559-
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Journal article (peer-reviewed)abstract
- Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.
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12. |
- Bauer, M., et al.
(author)
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Solar insolation in springtime influences age of onset of bipolar I disorder
- 2017
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In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:6, s. 571-582
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Research review (peer-reviewed)abstract
- Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.
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13. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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14. |
- Chown, Ryan, et al.
(author)
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PDRs4All: IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
-
Journal article (peer-reviewed)abstract
- Context. Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 µm. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. These high-quality data allow for an unprecedentedly detailed view of AIBs. Aims. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR (i.e. the three H2 dissociation fronts), the atomic PDR, and the H II region. Methods. We used JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extracted five template spectra to represent the morphology and environment of the Orion Bar PDR. We investigated and characterised the AIBs in these template spectra. We describe the variations among them here. Results. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. The Orion Bar spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 µm with well-defined profiles. In addition, the spectra display a wealth of weaker features and sub-components. The widths of many AIBs show clear and systematic variations, being narrowest in the atomic PDR template, but showing a clear broadening in the H II region template while the broadest bands are found in the three dissociation front templates. In addition, the relative strengths of AIB (sub-)components vary among the template spectra as well. All AIB profiles are characteristic of class A sources as designated by Peeters (2022, A&A, 390, 1089), except for the 11.2 µm AIB profile deep in the molecular zone, which belongs to class B11.2. Furthermore, the observations show that the sub-components that contribute to the 5.75, 7.7, and 11.2 µm AIBs become much weaker in the PDR surface layers. We attribute this to the presence of small, more labile carriers in the deeper PDR layers that are photolysed away in the harsh radiation field near the surface. The 3.3/11.2 AIB intensity ratio decreases by about 40% between the dissociation fronts and the H II region, indicating a shift in the polycyclic aromatic hydrocarbon (PAH) size distribution to larger PAHs in the PDR surface layers, also likely due to the effects of photochemistry. The observed broadening of the bands in the molecular PDR is consistent with an enhanced importance of smaller PAHs since smaller PAHs attain a higher internal excitation energy at a fixed photon energy. Conclusions. Spectral-imaging observations of the Orion Bar using JWST yield key insights into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 µm AIB emission from class B11.2 in the molecular PDR to class A11.2 in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a “weeding out” of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called ‘grandPAHs’.
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16. |
- Habart, Emilie, et al.
(author)
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PDRs4All II. JWST’s NIR and MIR imaging view of the Orion Nebula
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
-
Journal article (peer-reviewed)abstract
- Context. The James Webb Space Telescope (JWST) has captured the most detailed and sharpest infrared (IR) images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). Aims. We investigate the fundamental interaction of far-ultraviolet (FUV) photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Methods. We utilized NIRCam and MIRI to obtain sub-arcsecond images over ∼150′′ and 42′′ in key gas phase lines (e.g., Pa α, Br α, [FeII] 1.64 µm, H2 1–0 S(1) 2.12 µm, 0–0 S(9) 4.69 µm), aromatic and aliphatic infrared bands (aromatic infrared bands at 3.3–3.4 µm, 7.7, and 11.3 µm), dust emission, and scattered light. Their emission are powerful tracers of the IF and DF, FUV radiation field and density distribution. Using NIRSpec observations the fractional contributions of lines, AIBs, and continuum emission to our NIRCam images were estimated. A very good agreement is found for the distribution and intensity of lines and AIBs between the NIRCam and NIRSpec observations. Results. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of ∼0.1–1′′ (∼0.0002–0.002 pc or ∼40–400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. The spatial distribution of the AIBs reveals that the PDR edge is steep and is followed by an extensive warm atomic layer up to the DF with multiple ridges. A complex, structured, and folded H0/H2 DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar as our observations show that a 3D “terraced” geometry is required to explain the JWST observations. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate. Conclusions. This study offers an unprecedented dataset to benchmark and transform PDR physico-chemical and dynamical models for the JWST era. A fundamental step forward in our understanding of the interaction of FUV photons with molecular clouds and the role of FUV irradiation along the star formation sequence is provided.
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17. |
- De Putte, Dries Van, et al.
(author)
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PDRs4All VIII. Mid-infrared emission line inventory of the Orion Bar
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Journal article (peer-reviewed)abstract
- Context . Mid-infrared emission features are important probes of the properties of ionized gas and hot or warm molecular gas, which are difficult to probe at other wavelengths. The Orion Bar photodissociation region (PDR) is a bright, nearby, and frequently studied target containing large amounts of gas under these conditions. Under the “PDRs4All” Early Release Science Program for JWST, a part of the Orion Bar was observed with MIRI integral field unit (IFU) spectroscopy, and these high-sensitivity IR spectroscopic images of very high angular resolution (0.2′′) provide a rich observational inventory of the mid-infrared (MIR) emission lines, while resolving the H II region, the ionization front, and multiple dissociation fronts. Aims . We list, identify, and measure the most prominent gas emission lines in the Orion Bar using the new MIRI IFU data. An initial analysis summarizes the physical conditions of the gas and demonstrates the potential of these new data and future IFU observations with JWST. Methods. The MIRI IFU mosaic spatially resolves the substructure of the PDR, its footprint cutting perpendicularly across the ionization front and three dissociation fronts. We performed an up-to-date data reduction, and extracted five spectra that represent the ionized, atomic, and molecular gas layers. We identified the observed lines through a comparison with theoretical line lists derived from atomic data and simulated PDR models. The identified species and transitions are summarized in the main table of this work, with measurements of the line intensities and central wavelengths. Results . We identified around 100 lines and report an additional 18 lines that remain unidentified. The majority consists of H I recombination lines arising from the ionized gas layer bordering the PDR. The H I line ratios are well matched by emissivity coefficients from H recombination theory, but deviate by up to 10% because of contamination by He I lines. We report the observed emission lines of various ionization stages of Ne, P, S, Cl, Ar, Fe, and Ni. We show how the Ne III/Ne II, S IV/S III, and Ar III/Ar II ratios trace the conditions in the ionized layer bordering the PDR, while Fe III/Fe II and Ni III/Ni II exhibit a different behavior, as there are significant contributions to Fe II and Ni II from the neutral PDR gas. We observe the pure-rotational H2 lines in the vibrational ground state from 0–0 S(1) to 0–0 S(8), and in the first vibrationally excited state from 1–1 S(5) to 1–1 S(9). We derive H2 excitation diagrams, and for the three observed dissociation fronts, the rotational excitation can be approximated with one thermal (∼700 K) component representative of an average gas temperature, and one nonthermal component (∼2700 K) probing the effect of UV pumping. We compare these results to an existing model of the Orion Bar PDR, and find that the predicted excitation matches the data qualitatively, while adjustments to the parameters of the PDR model are required to reproduce the intensity of the 0–0 S(6) to S(8) lines.
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18. |
- Peeters, Els, et al.
(author)
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PDRs4All: III. JWST's NIR spectroscopic view of the Orion Bar
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
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Journal article (peer-reviewed)abstract
- Context. JWST has taken the sharpest and most sensitive infrared (IR) spectral imaging observations ever of the Orion Bar photodis-sociation region (PDR), which is part of the nearest massive star-forming region the Orion Nebula, and often considered to be the 'prototypical'strongly illuminated PDR. Aims. We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the H II region to the atomic PDR -crossing the ionisation front (IF) -, and the subsequent transition to the molecular PDR -crossing the dissociation front (DF). Given the prevalence of PDRs in the interstellar medium and their dominant contribution to IR radiation, understanding the response of the PDR gas to far-ultraviolet (FUV) photons and the associated physical and chemical processes is fundamental to our understanding of star and planet formation and for the interpretation of any unresolved PDR as seen by JWST. Methods. We used high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science programme. We constructed a 3″ × 25″ spatio-spectral mosaic covering 0.97-5.27 μm at a spectral resolution R of ~2700 and an angular resolution of 0.075″-0.173″. To study the properties of key regions captured in this mosaic, we extracted five template spectra in apertures centred on the three H2 dissociation fronts, the atomic PDR, and the H II region. This wealth of detailed spatial-spectral information was analysed in terms of variations in the physical conditions-incident UV field, density, and temperature -of the PDR gas. Results. The NIRSpec data reveal a forest of lines including, but not limited to, He I, H I, and C I recombination lines; ionic lines (e.g. Fe III and Fe II); O I and N I fluorescence lines; aromatic infrared bands (AIBs, including aromatic CH, aliphatic CH, and their CD counterparts); pure rotational and ro-vibrational lines from H2; and ro-vibrational lines from HD, CO, and CH+, with most of them having been detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. In addition, we observed numerous smaller-scale structures whose typical size decreases with distance from θ1 Ori C and IR lines from C I, if solely arising from radiative recombination and cascade, reveal very high gas temperatures (a few 1000 K) consistent with the hot irradiated surface of small-scale dense clumps inside the PDR. The morphology of the Bar, in particular that of the H2 lines, reveals multiple prominent filaments that exhibit different characteristics. This leaves the impression of a 'terraced'transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. We attribute the different characteristics of the H2 filaments to their varying depth into the PDR and, in some cases, not reaching the C+/C/CO transition. These observations thus reveal what local conditions are required to drive the physical and chemical processes needed to explain the different characteristics of the DFs and the photochemical evolution of the AIB carriers. Conclusions. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star and planet formation as well as galaxy evolution.
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19. |
- O'Connor, C. M., et al.
(author)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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20. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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21. |
- Danilovich, Taissa, 1987, et al.
(author)
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Chemical tracers of a highly eccentric AGB–main-sequence star binary
- 2024
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In: Nature Astronomy. - 2397-3366.
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Journal article (peer-reviewed)abstract
- Binary interactions have been proposed to explain a variety of circumstellar structures seen around evolved stars, including asymptotic giant branch (AGB) stars and planetary nebulae. Studies resolving the circumstellar envelopes of AGB stars have revealed spirals, disks and bipolar outflows, with shaping attributed to interactions with a companion. Here we use a combined chemical and dynamical analysis to reveal a highly eccentric and long-period orbit for W Aquilae, a binary system containing an AGB star and a main-sequence companion. Our results are based on anisotropic SiN emission, the detections of irregular NS and SiC emission towards the S-type star, and density structures observed in the CO emission. These features are all interpreted as having formed during periastron interactions. Our astrochemistry-based method can yield stringent constraints on the orbital parameters of long-period binaries containing AGB stars, and will be applicable to other systems.
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22. |
- Jacquet, S., et al.
(author)
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Colonization of the Mediterranean basin by the vector biting midge species Culicoides imicola : an old story
- 2015
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In: Molecular Ecology. - : Wiley-Blackwell. - 0962-1083 .- 1365-294X. ; 24:22, s. 5707-5725
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Journal article (peer-reviewed)abstract
- Understanding the demographic history and genetic make-up of colonizing species is critical for inferring population sources and colonization routes. This is of main interest for designing accurate control measures in areas newly colonized by vector species of economically important pathogens. The biting midge Culicoides imicola is a major vector of orbiviruses to livestock. Historically, the distribution of this species was limited to the Afrotropical region. Entomological surveys first revealed the presence of C. imicola in the south of the Mediterranean basin by the 1970s. Following recurrent reports of massive bluetongue outbreaks since the 1990s, the presence of the species was confirmed in northern areas. In this study, we addressed the chronology and processes of C. imicola colonization in the Mediterranean basin. We characterized the genetic structure of its populations across Mediterranean and African regions using both mitochondrial and nuclear markers, and combined phylogeographical analyses with population genetics and approximate Bayesian computation. We found a west/east genetic differentiation between populations, occurring both within Africa and within the Mediterranean basin. We demonstrated that three of these groups had experienced demographic expansions in the Pleistocene, probably because of climate changes during this period. Finally, we showed that C. imicola could have colonized the Mediterranean basin in the Late Pleistocene or Early Holocene through a single event of introduction; however, we cannot exclude the hypothesis involving two routes of colonization. Thus, the recent bluetongue outbreaks are not linked to C. imicola colonization event, but rather to biological changes in the vector or the virus.
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23. |
- Wallström, Sofia, 1988, et al.
(author)
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ATOMIUM: Molecular inventory of 17 oxygen-rich evolved stars observed with ALMA
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 681
-
Journal article (peer-reviewed)abstract
- Context. The dusty winds of cool evolved stars are a major contributor of the newly synthesised material enriching the Galaxy and future generations of stars. However, the details of the physics and chemistry behind dust formation and wind launching have yet to be pinpointed. Recent spatially resolved observations show the importance of gaining a more comprehensive view of the circumstellar chemistry, but a comparative study of the intricate interplay between chemistry and physics is still difficult because observational details such as frequencies and angular resolutions are rarely comparable. Aims. Aiming to overcome these deficiencies, ATOMIUM is an ALMA Large Programme to study the physics and chemistry of the circumstellar envelopes of a diverse set of oxygen-rich evolved stars under homogeneous observing conditions at three angular resolutions between ∼0.02′1.4′. Here we summarize the molecular inventory of these sources, and the correlations between stellar parameters and molecular content. Methods. Seventeen oxygen-rich or S-Type asymptotic giant branch (AGB) and red supergiant (RSG) stars have been observed in several tunings with ALMA Band 6, targeting a range of molecules to probe the circumstellar envelope and especially the chemistry of dust formation close to the star. We systematically assigned the molecular carriers of the spectral lines and measured their spectroscopic parameters and the angular extent of the emission of each line from integrated intensity maps. Results. Across the ATOMIUM sample, we detect 291 transitions of 24 different molecules and their isotopologues. This includes several first detections in oxygen-rich AGB/RSG stars: PO v = 1, SO2 v1 = 1 and v2 = 2, and several high energy H2O transitions. We also find several first detections in S-Type AGB stars: vibrationally excited HCN v2 = 2,3 and SiS v = 4,5,6, as well as first detections of the molecules SiC, AlCl, and AlF in W Aql. Overall, we find strong correlations between the following molecular pairs: CS and SiS, CS and AlF, NaCl and KCl, AlO and SO, SO2 and SO, and SO2 and H2O; meaning both molecules tend to have more detected emission lines in the same sources. The measured isotopic ratios of Si and S are found to be consistent with previous measurements, except for an anomalously high 29Si/30Si ratio of 4 ± 1 in the RSG VX Sgr. Conclusions. This paper presents the overall molecular inventory and an initial analysis of the large ATOMIUM dataset, laying the groundwork for future work deriving molecular abundances and abundance profiles using radiative transfer modeling which will provide more rigorous tests for chemical models.
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24. |
- Danilovich, T., et al.
(author)
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ATOMIUM: halide molecules around the S-type AGB star W Aquilae
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
-
Journal article (peer-reviewed)abstract
- Context. S-type asymptotic giant branch (AGB) stars are thought to be intermediates in the evolution of oxygen- to carbon-rich AGB stars. The chemical compositions of their circumstellar envelopes are also intermediate but have not been studied in as much detail as their carbon- and oxygen-rich counterparts. W Aql is a nearby S-type star, with well-known circumstellar parameters, making it an ideal object for in-depth study of less common molecules. Aims. We aim to determine the abundances of AlCl and AlF from rotational lines, which have been observed for the first time towards an S-type AGB star. In combination with models based on PACS observations, we aim to update our chemical kinetics network based on these results. Methods. We analyse ALMA observations towards W Aql of AlCl in the ground and first two vibrationally excited states and AlF in the ground vibrational state. Using radiative transfer models, we determine the abundances and spatial abundance distributions of (AlCl)-Cl-35, (AlCl)-Cl-37, and AlF. We also model HCl and HF emission and compare these models to PACS spectra to constrain the abundances of these species. Results. AlCl is found in clumps very close to the star, with emission confined within 0 ''.1 of the star. AlF emission is more extended, with faint emission extending 0 ''.2 to 0 ''.6 from the continuum peak. We find peak abundances, relative to H-2, of 1.7 x 10(-7) for (AlCl)-Cl-35, 7 x 10(-8) for (AlCl)-Cl-37, and 1 x 10(-7) for AlF. From the PACS spectra, we find abundances of 9.7 x 10(-8) and <= 10(-8), relative to H-2, for HCl and HF, respectively. Conclusions. The AlF abundance exceeds the solar F abundance, indicating that fluorine synthesised in the AGB star has already been dredged up to the surface of the star and ejected into the circumstellar envelope. From our analysis of chemical reactions in the wind, we conclude that AlF may participate in the dust formation process, but we cannot fully explain the rapid depletion of AlCl seen in the wind.
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25. |
- Decin, L., et al.
(author)
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(Sub)stellar companions shape the winds of evolved stars
- 2020
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 369:6509, s. 1497-1500
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Journal article (peer-reviewed)abstract
- Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe.
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26. |
- Gottlieb, C. A., et al.
(author)
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ATOMIUM: ALMA tracing the origins of molecules in dust forming oxygen rich M-type stars: Motivation, sample, calibration, and initial results
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 660
-
Journal article (peer-reviewed)abstract
- This overview paper presents atomium, a Large Programme in Cycle 6 with the Atacama Large Millimeter/submillimeter Array (ALMA). The goal of atomium is to understand the dynamics and the gas phase and dust formation chemistry in the winds of evolved asymptotic giant branch (AGB) and red supergiant (RSG) stars. A more general aim is to identify chemical processes applicable to other astrophysical environments. Seventeen oxygen-rich AGB and RSG stars spanning a range in (circum)stellar parameters and evolutionary phases were observed in a homogeneous observing strategy allowing for an unambiguous comparison. Data were obtained between 213.83 and 269.71 GHz at high (0.025-0.050), medium (0.13-0.24), and low (~1) angular resolution. The sensitivity per ~1.3 km s-1 channel was 1.5-5 mJy beam-1, and the line-free channels were used to image the millimetre wave continuum. Our primary molecules for studying the gas dynamics and dust formation are CO, SiO, AlO, AlOH, TiO, TiO2, and HCN; secondary molecules include SO, SO2, SiS, CS, H2O, and NaCl. The scientific motivation, survey design, sample properties, data reduction, and an overview of the data products are described. In addition, we highlight one scientific result - the wind kinematics of the atomium sources. Our analysis suggests that the atomium sources often have a slow wind acceleration, and a fraction of the gas reaches a velocity which can be up to a factor of two times larger than previously reported terminal velocities assuming isotropic expansion. Moreover, the wind kinematic profiles establish that the radial velocity described by the momentum equation for a spherical wind structure cannot capture the complexity of the velocity field. In fifteen sources, some molecular transitions other than 12CO v = 0 J = 2 - 1 reach a higher outflow velocity, with a spatial emission zone that is often greater than 30 stellar radii, but much less than the extent of CO. We propose that a binary interaction with a (sub)stellar companion may (partly) explain the non-monotonic behaviour of the projected velocity field. The atomium data hence provide a crucial benchmark for the wind dynamics of evolved stars in single and binary star models.
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27. |
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28. |
- Smith, ER, et al.
(author)
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Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis
- 2023
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In: BMJ global health. - : BMJ. - 2059-7908. ; 8:1
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Journal article (peer-reviewed)abstract
- Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection—as compared with uninfected pregnant women—were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.
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29. |
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30. |
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31. |
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32. |
- Berne, Olivier, et al.
(author)
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PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
- 2022
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In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
-
Journal article (peer-reviewed)abstract
- Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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33. |
- Montargès, M., et al.
(author)
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The VLT/SPHERE view of the A TOMIUM cool evolved star sample: I. Overview: Sample characterization through polarization analysis
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
-
Journal article (peer-reviewed)abstract
- Context. Low- and intermediate-mass asymptotic giant stars and massive red supergiant stars are important contributors to the chemical enrichment of the Universe. They are among the most efficient dust factories of the Galaxy, harboring chemically rich circumstellar environments. Yet, the processes that lead to dust formation or the large-scale shaping of the mass loss still escape attempts at modeling. Aims. Through the ATOMIUM project, we aim to present a consistent view of a sample of 17 nearby cool evolved stars. Our goals are to unveil the dust-nucleation sites and morphologies of the circumstellar envelope of such stars and to probe ambient environments with various conditions. This will further enhance our understanding of the roles of stellar convection and pulsations, and that of companions in shaping the dusty circumstellar medium. Methods. Here we present and analyze VLT/SPHERE-ZIMPOL polarimetric maps obtained in the visible (645- 820 nm) of 14 out of the 17 ATOMIUM sources. They were obtained contemporaneously with the ALMA high spatial resolution data. To help interpret the polarized signal, we produced synthetic maps of light scattering by dust, through 3D radiative transfer simulations with the RADMC3D code. Results. The degree of linear polarization (DoLP) observed by ZIMPOL spreads across several optical filters. We infer that it primarily probes dust located just outside of the point spread function of the central source, and in or near the plane of the sky. The polarized signal is mainly produced by structures with a total optical depth close to unity in the line of sight, and it represents only a fraction of the total circumstellar dust. The maximum DoLP ranges from 0.03- 0.38 depending on the source, fractions that can be reproduced by our 3D pilot models for grains composed of olivine, melilite, corundum, enstatite, or forsterite. The spatial structure of the DoLP shows a diverse set of shapes, including clumps, arcs, and full envelopes. Only for three sources do we note a correlation between the ALMA CO ν = 0, J = 2-1 and SiO ν = 0, J = 5-4 lines, which trace the gas density, and the DoLP, which traces the dust. Conclusions. The clumpiness of the DoLP and the lack of a consistent correlation between the gas and the dust location show that, in the inner environment, dust formation occurs at very specific sites. This has potential consequences for the derived mass-loss rates and dust-to-gas ratio in the inner region of the circumstellar environment. Except for π1 Gru and perhaps GY Aql, we do not detect interactions between the circumstellar wind and the hypothesized companions that shape the wind at larger scales. This suggests that the orbits of any other companions are tilted out of the plane of the sky.
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34. |
- Battaglia, Manuela, et al.
(author)
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Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
- 2020
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:1, s. 5-12
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Journal article (peer-reviewed)abstract
- The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
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35. |
- Greer, M., et al.
(author)
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Lung transplantation after allogeneic stem cell transplantation: a pan-European experience
- 2018
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:2
-
Journal article (peer-reviewed)abstract
- Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001). Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.
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36. |
- van Houten, C. B., et al.
(author)
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Antibiotic misuse in respiratory tract infections in children and adultsa prospective, multicentre study (TAILORED Treatment)
- 2019
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In: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 38:3, s. 505-514
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Journal article (peer-reviewed)abstract
- Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3years and 64.5years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p<0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p<0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.
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37. |
- Velilla Prieto, Luis, 1981, et al.
(author)
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Circumstellar chemistry of Si-C bearing molecules in the C-rich AGB star IRC+10216
- 2018
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In: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 14, s. 535-537
-
Conference paper (peer-reviewed)abstract
- Silicon carbide together with amorphous carbon are the main components of dust grains in the atmospheres of C-rich AGB stars. Small gaseous Si-C bearing molecules (such as SiC, SiCSi, and SiC2) are efficiently formed close to the stellar photosphere. They likely condense onto dust seeds owing to their highly refractory nature at the lower temperatures (i.e., below about 2500 K) in the dust growth zone which extends a few stellar radii from the photosphere. Beyond this region, the abundances of Si-C bearing molecules are expected to decrease until they are eventually reformed in the outer shells of the circumstellar envelope, owing to the interaction between the gas and the interstellar UV radiation field. Our goal is to understand the time-dependent chemical evolution of Si-C bond carriers probed by molecular spectral line emission in the circumstellar envelope of IRC+10216 at millimeter wavelengths.
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38. |
- Baudry, A., et al.
(author)
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ATOMIUM: Probing the inner wind of evolved O-rich stars with new, highly excited H2O and OH lines
- 2023
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. Water (H2O) and the hydroxyl radical (OH) are major constituents of the envelope of O-rich late-type stars. Transitions involving energy levels that are rotationally or vibrationally highly excited (energies & GSIM;4000 K) have been observed in both H2O and OH. These and more recently discovered transitions can now be observed at a high sensitivity and angular resolution in the inner wind close to the stellar photosphere with the Atacama Large Millimeter/submillimeter Array (ALMA). Aims. Our goals are: (1) to identify and map the emission and absorption of H2O in several vibrational states, and of OH in Lambda-doubling transitions with similar excitation energies; and (2) to determine the physical conditions and kinematics in gas layers close to the extended atmosphere in a sample of asymptotic giant branch stars (AGBs) and red supergiants (RSGs). Methods. Spectra and maps of H2O and OH lines observed in a 27 GHz aggregated bandwidth and with an angular resolution of similar to 0."02-1."0 were obtained at two epochs with the main ALMA array. Additional observations with the Atacama Compact Array (ACA) were used to check for time variability of water transitions. Radiative transfer models of H2O were revisited to characterize masing conditions. Up-to-date chemical models were used for comparison with the observed OH/H2O abundance ratio. Results. Ten rotational transitions of H2O with excitation energies similar to 4000-9000 K were observed in vibrational states up to (& upsilon;(1),& upsilon;(2),& upsilon;(3)) = (0,1,1). All but one are new detections in space, and from these we have derived accurate rest frequencies. Hyperfine split Lambda-doubling transitions in & upsilon; = 0, J = 27/2 and 29/2 levels of the (2)& pi;(3/2) state, as well as J = 33/2 and 35/2 of the (2)& pi;(1/2) state of OH with excitation energies of similar to 4780-8900 K were also observed. Four of these transitions are new detections in space. Combining our measurements with earlier observations of OH, the & upsilon; = 0 and & upsilon; = 1 Lambda-doubling frequencies have been improved. Our H2O maps show compact emission toward the central star and extensions up to twelve stellar radii or more. The 268.149 GHz emission line of water in the & upsilon;(2) = 2 state is time variable, tends to be masing with dominant radiative pumping, and is widely excited in AGBs and RSGs. The widespread but weaker 262.898 GHz water line in the & upsilon;(2) = 1 state also shows signs of maser emission. The OH emission is weak and quasithermally excited. Emission and absorption features of H2O and OH reveal an infall of matter and complex kinematics influenced by binarity. From the OH and H2O column densities derived with nonmasing transitions in a few sources, we obtain OH/H2O abundance ratios of similar to(0.7-2.8) x 10(-2).
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39. |
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40. |
- Insel, Richard A, et al.
(author)
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Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association.
- 2015
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 38:10, s. 1964-1974
-
Journal article (peer-reviewed)abstract
- Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.
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41. |
- Le Pavec, J. M., et al.
(author)
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Lung transplantation for sarcoidosis: outcome and prognostic factors
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:2
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Journal article (peer-reviewed)abstract
- Study question In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation. Patients and methods We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres. Results Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications. Answer to the study question Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.
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42. |
- Mooley, K., et al.
(author)
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A mildly relativistic wide-angle outflow in the neutron-star merger event GW170817
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 554:7691, s. 207-210
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Journal article (peer-reviewed)abstract
- GW170817 was the first gravitational-wave detection of a binary neutron-star merger. It was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 40 megaparsecs. It has been proposed that the observed γ-ray, X-ray and radio emission is due to an ultra-relativistic jet being launched during the merger (and successfully breaking out of the surrounding material), directed away from our line of sight (off-axis). The presence of such a jet is predicted from models that posit neutron-star mergers as the drivers of short hard-γ-ray bursts. Here we report that the radio light curve of GW170817 has no direct signature of the afterglow of an off-axis jet. Although we cannot completely rule out the existence of a jet directed away from the line of sight, the observed γ-ray emission could not have originated from such a jet. Instead, the radio data require the existence of a mildly relativistic wide-angle outflow moving towards us. This outflow could be the high-velocity tail of the neutron-rich material that was ejected dynamically during the merger, or a cocoon of material that breaks out when a jet launched during the merger transfers its energy to the dynamical ejecta. Because the cocoon model explains the radio light curve of GW170817, as well as the γ-ray and X-ray emission (and possibly also the ultraviolet and optical emission), it is the model that is most consistent with the observational data. Cocoons may be a ubiquitous phenomenon produced in neutron-star mergers, giving rise to a hitherto unidentified population of radio, ultraviolet, X-ray and γ-ray transients in the local Universe.
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43. |
- Bauer, Michael, et al.
(author)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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In: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Journal article (peer-reviewed)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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46. |
- Gottlieb, S. L., et al.
(author)
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Gonococcal vaccines : Public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019
- 2020
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In: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 38:28, s. 4362-4373
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Journal article (peer-reviewed)abstract
- Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae, and new gonococcal vaccine candidates based on several approaches are currently in preclinical development. To further stimulate investment and accelerate development of gonococcal vaccines, greater understanding is needed regarding the overall value that gonococcal vaccines might have in addressing public health and societal goals in low-, middle-, and high-income country contexts and how future gonococcal vaccines might be accepted and used, if available. In January 2019, the World Health Organization (WHO) convened a multidisciplinary international group of experts to lay the groundwork for understanding the potential health, economic, and societal value of gonococcal vaccines and their likely acceptance and use, and for developing gonococcal vaccine preferred product characteristics (PPCs). WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper describes the main discussion points and conclusions from the January 2019 meeting of experts. Participants emphasized the need for vaccines to control N. gonorrhoeae infections with the ultimate goals of preventing adverse sexual and reproductive health outcomes (e.g., infertility) and reducing the impact of gonococcal AMR. Meeting participants also discussed important PPC considerations (e.g., vaccine indications, target populations, and potential immunization strategies) and highlighted crucial research and data needs for guiding the value assessment and PPCs for gonococcal vaccines and advancing gonococcal vaccine development.
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47. |
- Pavec, J. L., et al.
(author)
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Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study
- 2020
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In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 39:4
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Journal article (peer-reviewed)abstract
- PURPOSE: In the context of sarcoidosis, lung transplantation is often performed in patients with irreversible advanced lung disease unresponsive to medical therapy. The clinical phenotypes and posttransplant survival remain unclear, due primarily to the recurring nature of the disease and extrapulmonary involvement. The objective of this study in a large multicenter European cohort was to describe the clinical characteristics and outcomes of patients with pulmonary sarcoidosis treated by lung transplantation. METHODS: We retrospectively reviewed the data of 147 patients with pulmonary sarcoidosis who underwent lung or heart-lung transplantation between 1990 and 2019 at 15 European centers. Inclusion criteria were sarcoidosis meeting international diagnostic criteria and availability of data from pretransplantation right heart catheterization, lung function testing, and chest computed tomography (CT) staged using a standardized system. RESULTS: At transplantation, mean age was 50±8 years, 62% were male, and 20% had extrapulmonary manifestations. Mean values before transplantation were as follows: FVC (%pred), 46±17%; FEV1 (%pred), 38±19; FVC/FEV1 (%), 55±32; DLCO (%pred), 31±13; mPAP (mmHg), 36±13; PCWP (mmHg), 10±5; cardiac index (L/min/m²), 3.0±0.8; and pulmonary vascular resistance (dyn·s·cm-5), 480±340; furthermore, 60% of patients had severe pulmonary hypertension. Posttransplant survival rates after 1, 3, and 5 years were 85%, 69%, and 63%, respectively. During the median [range] follow-up of 43 [17-79] months, 38% of patients developed chronic lung allograft dysfunction. Factors significantly associated with outcomes were high emergency transplantation, era of transplantation, preoperative extrapulmonary sarcoidosis, and extent of fibrosis by CT. CONCLUSION: Posttransplant survival rates and freedom from chronic lung allograft dysfunction in patients with pulmonary sarcoidosis were similar to those in patients with other reasons for lung transplantation. Factors associated with worse outcomes were high emergency transplantation, earlier transplantation era, preoperative extrapulmonary sarcoidosis, and greater burden of fibrosis by CT. Copyright © 2020. Published by Elsevier Inc.
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48. |
- Pradere, P., et al.
(author)
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Lung transplantation for scleroderma lung disease: An international, multicenter, observational cohort study
- 2018
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In: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 37:7, s. 903-911
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Journal article (peer-reviewed)abstract
- BACKGROUND: Due to its multisystemic nature, scleroderma is considered a relative contraindication to lung transplantation at many centers. However, recent studies suggest similar post-transplant outcomes in patients with scleroderma compared to those with other causes of interstitial lung disease (ILD). Furthermore, it remains unknown whether scleroderma-associated pulmonary arterial hypertension (PAH) influences post-transplant outcomes. Our objective in this study was to assess the indications, survival, and prognostic factors of lung or heart lung transplantation for scleroderma lung disease. METHODS: We retrospectively reviewed the data of 90 patients with scleroderma who underwent lung or heart lung transplantation between 1993 and 2016 at 14 European centers. International criteria were used to diagnose scleroderma. Pulmonary hypertension (PH) was diagnosed during right heart catheterization based on international guidelines. RESULTS: Survival rates after 1, 3, and 5 years were 81%, 68%, and 61%, respectively. By univariate analysis, borderline-significant associations with poorer survival were found for female gender (hazard ratio 2.11; 95% confidence interval [CI] 0.99 to 4.50; p = 0.05) and PAH as the reason for transplantation (hazard ratio 1.90; 95% CI 0.96 to 3.92; p = 0.06). When both these factors were present in combination, the risk of death was 3-fold that in males without PAH. The clinical and histologic presentation resembled veno-occlusive disease in 75% of patients with PAH. CONCLUSIONS: Post-transplant survival rates and freedom from chronic lung allograft dysfunction in patients with scleroderma were similar to those in patients with other reasons for lung transplantation. Female sex and PAH in combination was associated with lower survival. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.
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49. |
- Rivière, A., et al.
(author)
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Lung transplantation for interstitial lung disease in idiopathic inflammatory myositis: A cohort study
- 2022
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 22:12, s. 2990-3001
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Journal article (peer-reviewed)abstract
- In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM-ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46–59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high-priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow-up (median, 33 [7–63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher-intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM-ILD was similar to that in international all-cause-transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all-cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease. © 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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