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Purpose: To investigate the association between the presence of type 1 choroidal neovascularization (CNV) and the localized progression of atrophy in age-related macular degeneration (AMD). Design: Analysis of patients’ data collected in the context of 2 noninterventional, prospective studies conducted at the Department of Ophthalmology, University of Bonn, Germany. Participants: A total of 98 eyes diagnosed with AMD of 59 patients (40 female, 19 male) with a mean (±standard deviation) age at baseline of 76.60±6.65 years and median (interquartile range) review period of 1.17 years (1.01–1.55) were included. Eyes were subdivided into 3 categories based on multimodal imaging and ocular history: retinal pigment epithelium (RPE) atrophy with treatment-naïve quiescent CNV (n=7), RPE atrophy with a history of exudative CNV (n=10), and RPE atrophy without evidence of coexisting CNV (n=81). Methods: Retinal pigment epithelium atrophy was delineated on the basis of serial fundus-autofluorescence and infrared-reflectance images. If CNV was detected by OCT angiography (OCTA), its location and dimension were spatially mapped to RPE atrophy. The localized progression of RPE atrophy in topographic relation to the CNV lesion was then analyzed using mixed-effects logistic regression. The spatial overlap (Dice coefficient) between predicted and observed RPE atrophy progression was evaluated to estimate the model accuracy. Main Outcome Measures: Odds ratio (OR) for localized RPE atrophy progression in areas overlying type 1 CNV. Results: The prediction model achieved a high overlap between predicted and observed RPE atrophy progression with a cross-validated Dice coefficient of 0.87 (95% confidence interval [CI], 0.85–0.89) reflecting a high accuracy. The odds for future RPE atrophy involvement were reduced by a factor of 0.21 (95% CI, 0.19–0.24) in the presence of treatment-naïve quiescent type 1 CNV and by a factor of 0.46 (95% CI, 0.41–0.51) in the presence of exudative type 1 CNV. Conclusions: The results indicate that there is markedly reduced RPE atrophy progression in areas co-localizing with quiescent and exudative type 1 CNV. This observation is compatible with a potential protective effect of type 1 CNV on the RPE and overlying neurosensory retina. These results may have relevant clinical implications for the management of CNV and lead to new therapeutic strategies to prevent atrophy progression.

Zusammenfassung Hintergrund Die vorliegende Studie verfolgt die Fragestellung, ob und inwieweit Patienten mit Asbestose langfristig von einer ambulanten medizinischen Rehabilitation (AMR) profitieren, die sich überwiegend aus bewegungs- und sporttherapeutischen Inhalten zusammensetzt und auf die Sicherung von Nachhaltigkeitseffekten ausgelegt ist. Methode 157 männliche Asbestosepatienten im Lebensalter von 65,2 ± 5,7 Jahren durchliefen 5-mal wöchentlich à 6 h über 3 Wochen Phase 1 (Aufbauphase) der AMR, bestehend aus standardisierten Inhalten der pneumologischen Rehabilitation. In der direkt folgenden Phase 2 (Stabilisierungsphase) absolvierten die Patienten 1-mal wöchentlich à 3 h über 12 Wochen weitere therapeutische Applikationen mit Schwerpunkt auf der Sport- und Bewegungstherapie und wurden anschließend in wohnortnahe Gesundheitssportgruppen überführt (Erhaltungsphase). Die Effekte der AMR wurden zu Beginn (T1), am Ende der Phase 1 (T2) und 2 (T3) sowie 6 (T4) und 20 Monate nach Phase 2 (T5) evaluiert. 61 Patienten (73,5 Jahre ± 5,6) konnten 6 weitere Jahre nach T5 (T6) ohne zwischenzeitliche Betreuung erneut untersucht werden. Ergebnisse 72,1 % der 61 Patienten (n = 44) absolvierten in T5 als auch in T6 8 Jahre nach T1 noch 2-mal wöchentlich Gesundheitssport und konnten sowohl ihre körperliche Leistungsfähigkeit (6-Minuten-Gehtest, Handkraft, PWC-Test) als auch die wahrgenommene Lebensqualität (SF-36, Baseline-/Transition-Dyspnoe-Index) altersentsprechend erhalten, während die Reha-Effekte der 17 Patienten, die nach T3 jegliche sportliche Aktivität abgebrochen hatten, signifikant (p Schlussfolgerungen Trotz einer irreversiblen restriktiven Lungenerkrankung kann eine gezielte Sport- und Bewegungstherapie eine Konditionierung im Sinne einer Aktivierung vorhandener Leistungsreserven sowie konsekutiv eine Vergrößerung der Lebensqualität und Belastbarkeit im Alltag bewirken. Diese positiven Effekte lassen sich durch ein regelmäßiges Training langfristig stabilisieren. Die Ergebnisse unterstreichen die Notwendigkeit der Einbindung von Nachsorgestrategien in das Rehabilitationskonzept unter besonderer Berücksichtigung der Selbstwirksamkeitserwartung.

As a complement to the HyGAL Stratospheric Observatory for Infrared Astronomy Legacy Program, we report the results of a ground-based absorption line survey of simple molecules in diffuse and translucent Galactic clouds. Using the Institut de Radioastronomie Millim\'etrique (IRAM) 30 m telescope, we surveyed molecular lines in the 2 mm and 3 mm wavelength ranges toward 15 millimeter continuum sources. These sources, which are all massive star-forming regions located mainly in the first and second quadrants of the Milky Way, form the subset of the HyGAL sample that can be observed by the IRAM 30 m telescope. We detected HCO$^+$ absorption lines toward 14 sightlines, toward which we identified 78 foreground cloud components, as well as lines from HCN, HNC, C$_2$H, and c-C$_3$H$_2$ toward most sightlines. In addition, CS and H$_2$S absorption lines are found toward at least half of the continuum sources. Static Meudon photodissociation region (PDR) isobaric models that consider ultraviolet-dominated chemistry were unable to reproduce the column densities of all seven molecular species by just a factor of a few, except for H$_2$S. The inclusion of other formation routes driven by turbulent dissipation could possibly explain the observed high column densities of these species in diffuse clouds. There is a tentative trend for H$_2$S and CS abundances relative to H$_2$ to be larger in diffuse clouds ($X$(H$_2$S) and $X$(CS) $\sim 10^{-8} - 10^{-7}$) than in translucent clouds ($X$(H$_2$S) and $X$(CS) $\sim 10^{-9} - 10^{-8}$) toward a small sample; however, a larger sample is required in order to confirm this trend. The derived H$_2$S column densities are higher than the values predicted from the isobaric PDR models, suggesting that chemical desorption of H$_2$S from sulfur-containing ice mantles may play a role in increasing the H$_2$S abundance., Comment: 41 pages, 25 figures, 10 tables, and 5 appendices. Accepted for publication in A&A

Spatially-resolved mapping of rod- and cone-function may facilitate monitoring of macular diseases and serve as a functional outcome parameter. However, mesopic and dark-adapted two-color fundus-controlled perimetry (FCP, also called “microperimetry”) constitute laborious examinations. We have devised a machine-learning-based approach to predict mesopic and dark-adapted (DA) retinal sensitivity in eyes with neovascular age-related macular degeneration (nAMD). Extensive psychophysical testing and volumetric multimodal retinal imaging data were acquired including mesopic, DA red and DA cyan FCP, spectral-domain optical coherence tomography and confocal scanning laser ophthalmoscopy infrared reflectance and fundus autofluorescence imaging. With patient-wise leave-one-out cross-validation, we have been able to achieve prediction accuracies of (mean absolute error, MAE [95% CI]) 3.94 dB [3.38, 4.5] for mesopic, 4.93 dB [4.59, 5.27] for DA cyan and 4.02 dB [3.63, 4.42] for DA red testing. Partial addition of patient-specific sensitivity data decreased the cross-validated MAE to 2.8 dB [2.51, 3.09], 3.71 dB [3.46, 3.96], and 2.85 dB [2.62, 3.08]. The most important predictive feature was outer nuclear layer thickness. This artificial intelligence-based analysis strategy, termed “inferred sensitivity”, herein, enables to estimate differential effects of retinal structural abnormalities on cone- and rod-function in nAMD, and may be used as quasi-functional surrogate endpoint in future clinical trials.

We present a full analysis of a broadband spectral line survey of Sagittarius B2 (Main), one of the most chemically rich regions in the Galaxy located within the giant molecular cloud complex Sgr B2 in the Central Molecular Zone. Our goal is to derive the molecular abundances and temperatures of the high-mass star-forming region Sgr B2(M) and thus its physical and astrochemical conditions. Sgr B2(M) was observed using the Heterodyne Instrument for the Far-Infrared (HIFI) on board the Herschel Space Observatory in a spectral line survey from 480 to 1907 GHz at a spectral resolution of 1.1 MHz, which provides one of the largest spectral coverages ever obtained toward this high-mass star-forming region in the submillimeter with high spectral resolution and includes frequencies > 1 THz unobservable from the ground. We model the molecular emission from the submillimeter to the far-IR using the XCLASS program. For each molecule, a quantitative description was determined taking all emission and absorption features of that species across the entire spectral range into account. Additionally, we derive velocity resolved ortho / para ratios for those molecules for which ortho and para resolved molecular parameters are available. Finally, the temperature and velocity distributions are analyzed and the derived abundances are compared with those obtained for Sgr B2(N) from a similar HIFI survey. A total of 92 isotopologues were identified, arising from 49 different molecules, ranging from free ions to complex organic compounds and originating from a variety of environments from the cold envelope to hot and dense gas within the cores. Sulfur dioxide, methanol, and water are the dominant contributors. For the ortho / para ratios we find deviations from the high temperature values between 13 and 27 %. In total 14 % of all lines remain unidentified., 67 pages, 102 figures, submitted to A&A

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019)

Aims. Current star formation research centers the characterization of the physical and chemical properties of massive stars, which are in the process of formation, at the spatial resolution of individual high-mass cores. Methods. We use sub-arcsecond resolution (~0.′′4) observations with the NOrthern Extended Millimeter Array at 1.37 mm to study the dust emission and molecular gas of 18 high-mass star-forming regions. With distances in the range of 0.7−5.5 kpc, this corresponds to spatial scales down to 300−2300 au that are resolved by our observations. We combined the derived physical and chemical properties of individual cores in these regions to estimate their ages. The temperature structures of these regions are determined by fitting the H2CO and CH3CN line emission. The density profiles are inferred from the 1.37 mm continuum visibilities. The column densities of 11 different species are determined by fitting the emission lines with XCLASS. Results. Within the 18 observed regions, we identified 22 individual cores with associated 1.37 mm continuum emission and with a radially decreasing temperature profile. We find an average temperature power-law index of q = 0.4 ± 0.1 and an average density power-law index of p = 2.0 ± 0.2 on scales that are on the order of several 1000 au. Comparing these results with values of p derived from the literature presumes that the density profiles remain unchanged from clump to core scales. The column densities relative to N(C18O) between pairs of dense gas tracers show tight correlations. We applied the physical-chemical model MUlti Stage ChemicaL codE to the derived column densities of each core and find a mean chemical age of ~60 000 yr and an age spread of 20 000−100 000 yr. With this paper, we release all data products of the CORE project. Conclusions. The CORE sample reveals well-constrained density and temperature power-law distributions. Furthermore, we characterized a large variety in molecular richness that can be explained by an age spread that is then confirmed by our physical-chemical modeling. The hot molecular cores show the greatest number of emission lines, but we also find evolved cores at an evolutionary stage in which most molecules are destroyed and, thus, the spectra appear line-poor once again.

The HyGAL SOFIA legacy program surveys six hydride molecules -- ArH+, OH+, H2O+, SH, OH, and CH -- and two atomic constituents -- C+ and O -- within the diffuse interstellar medium (ISM) by means of absorption-line spectroscopy toward 25 bright Galactic background continuum sources. This detailed spectroscopic study is designed to exploit the unique value of specific hydrides as tracers and probes of different phases of the ISM, as demonstrated by recent studies with the Herschel Space Observatory. The observations performed under the HyGAL program will allow us to address several questions related to the lifecycle of molecular material in the ISM and the physical processes that impact its phase transition, such as: (1) What is the distribution function of the H2 fraction in the ISM? (2) How does the ionization rate due to low-energy cosmic-rays vary within the Galaxy? (3) What is the nature of interstellar turbulence, and what mechanisms lead to its dissipation? This overview discusses the observing strategy, synergies with ancillary and archival observations, the data reduction and analysis schemes adopted; and presents the first results obtained toward three of the survey targets, W3(OH), W3IRS5 and NGC7538IRS1. Robust measurements of the column densities of these hydrides -- obtained through widespread observations of absorption lines-- help address the questions raised, and there is a timely synergy between these observations and the development of theoretical models, particularly pertaining to the formation of H2 within the turbulent ISM. The provision of enhanced HyGAL data products will therefore serve as a legacy for future ISM studies., 33 pages, 17 figures, 7 tables. Accepted for publication in the Astrophysical Journal

Purpose To longitudinally evaluate vision-related quality of life (VRQoL) in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and define its relation to visual function and structural biomarkers. Methods Patients with GA secondary to AMD were recruited in the context of the prospective, non-interventional, natural-history Directional Spread in Geographic-Atrophy study (NCT02051998). Fundus autofluorescence and infrared reflectance images were semi-automatically annotated for GA. Linear mixed-effects models were applied to investigate the association of putative determinants with the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) VRQoL. Results A total of 87 patients with a mean age ± SD of 77.07 ± 7.49 years were included in the analysis. At baseline, median (IQR) best-corrected visual acuity (BCVA) was 0.3 (0.51) for the better eye and 0.89 (0.76) for the worse eye; 46% of the patients showed binocular and 25.3% monocular non-central GA. The VRQoL composite score was impaired: 69.96 (24.03). Sixty-six patients with a median of 2 (2) follow-up visits after 1.08 (0.78) years were examined longitudinally. In the multivariable cross-sectional analysis, predictors of the VRQoL composite score were BCVA, GA size, and low-luminance visual acuity (LLVA) for the better eye and BCVA, foveal sparing status, and LLVA for the worse eye (cross-validated R2 = 0.32). In the longitudinal analysis, a similar prediction accuracy for VRQoL was determined (cross-validated R2 = 0.28). Prediction accuracy for VRQoL did not improve when follow-up time was added as an independent variable. Conclusions Vision-related quality of life is significantly impaired in patients with GA secondary to AMD. The cross-sectional and longitudinal association of VRQoL with visual functional and structural biomarkers supports the validity of the NEI VFQ-25 VRQoL.

Purpose To investigate the association between retinal microstructure and cone- and rod-function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using artificial-intelligence-(AI) algorithms. Design Prospective, observational case series Methods Forty-one eyes of 41 patients (75.8±8.4 years; 22 female) from a tertiary referral hospital were included (Directional-Spread-in-Geographic-Atrophy (DSGA) natural history study; NCT02051998). Mesopic, dark-adapted (DA) cyan and red sensitivity were assessed using fundus-controlled perimetry (“microperimetry”); retinal microstructure using spectral-domain optical-coherence-tomography (SD-OCT), fundus autofluorescence (FAF) and near-infrared-reflectance (IR) imaging. Layer-thicknesses and -intensities and FAF- and IR-intensities were extracted for each test-point. We evaluated the cross-validated mean absolute error (MAE) for random-forest-based predictions of retinal sensitivity with and without patient-specific training-data and the increase mean-squared error (%IncMSE) as measure of feature-importance. Results Retinal sensitivity was predicted with a MAE of 4.64 dB for mesopic, 4.89 dB for DA cyan and 4.40 dB for DA red testing in absence of patient-specific data. Partial addition of patient-specific sensitivity data to the training sets decreased the MAE to 2.89 dB, 2.86 dB and 2.77 dB. For all three types of testing, the outer nuclear layer-thickness constituted the most important predictive feature (35.0, 42.22 and 53.74 %IncMSE). Spatially-resolved mapping of “inferred sensitivity” revealed regions with differential degrees of mesopic and DA cyan sensitivity loss outside of the GA lesions. Conclusions “Inferred sensitivity” accurately reflected retinal function in patients with GA. Mapping of “inferred sensitivity” could facilitate monitoring of disease progression and serve as “quasi functional” surrogate outcome in clinical trials, especially in consideration of retinal regions beyond areas of GA.

The aim of this study was to evaluate the effects of an outpatient medical rehabilitation (OMR) mainly composed of exercise therapy and sports for patients with asbestosis and focused on keeping up sustainability effects. 157 male patients aged 65.2 ± 5.7 years suffering from asbestosis carried out over a period of three weeks 5 times weekly 6 h at a time phase 1 of the OMR consisting of evidence-based contents of the pulmonary rehabilitation. In the immediately following phase 2, the patients completed once a week for 3 hours over 12 weeks further therapeutic applications with the main focus on exercise therapy and sports and were subsequently transferred to health sports groups near to residence (phase 3). The effects of the OMR were evaluated at the beginning (T1), at the end of phase 1 (T2) and phase 2 (T3) as well as 6 (T4) and 20 months (T5) after T3. 61 patients (73.5 years ± 5.6) were re-examined 6 years after T5 (T6) without any interim care. 72.1 % of the 61 patients (n = 44) carried out health sports twice a week in T5 as well as in T6 eight years after T1 and were able to maintain their physical performance (6-minute walk test, hand force, PWC test) as well as the perceived quality of life (SF-36, baseline/transition dyspnea index) according to age, while the rehab effects of the 17 patients breaking off any sporting activities after T3 fell significantly (p .01) below the starting condition in T1. In spite of a restrictive pulmonary disease specific exercise therapy and sports are able to mobilize physical reserves of performance and induce an increasing quality of life as well as a higher resilience in activities of daily living. These positive effects could be stabilized in the long term by a regular training. The results underline the necessity of integrating aftercare strategies into the concept of rehabilitation with special consideration of perceived self-efficacy. Die vorliegende Studie verfolgt die Fragestellung, ob und inwieweit Patienten mit Asbestose langfristig von einer ambulanten medizinischen Rehabilitation (AMR) profitieren, die sich überwiegend aus bewegungs- und sporttherapeutischen Inhalten zusammensetzt und auf die Sicherung von Nachhaltigkeitseffekten ausgelegt ist. 157 männliche Asbestosepatienten im Lebensalter von 65,2 ± 5,7 Jahren durchliefen 5-mal wöchentlich à 6 h über 3 Wochen Phase 1 (Aufbauphase) der AMR, bestehend aus standardisierten Inhalten der pneumologischen Rehabilitation. In der direkt folgenden Phase 2 (Stabilisierungsphase) absolvierten die Patienten 1-mal wöchentlich à 3 h über 12 Wochen weitere therapeutische Applikationen mit Schwerpunkt auf der Sport- und Bewegungstherapie und wurden anschließend in wohnortnahe Gesundheitssportgruppen überführt (Erhaltungsphase). Die Effekte der AMR wurden zu Beginn (T1), am Ende der Phase 1 (T2) und 2 (T3) sowie 6 (T4) und 20 Monate nach Phase 2 (T5) evaluiert. 61 Patienten (73,5 Jahre ± 5,6) konnten 6 weitere Jahre nach T5 (T6) ohne zwischenzeitliche Betreuung erneut untersucht werden. 72,1 % der 61 Patienten (n = 44) absolvierten in T5 als auch in T6 8 Jahre nach T1 noch 2-mal wöchentlich Gesundheitssport und konnten sowohl ihre körperliche Leistungsfähigkeit (6-Minuten-Gehtest, Handkraft, PWC-Test) als auch die wahrgenommene Lebensqualität (SF-36, Baseline-/Transition-Dyspnoe-Index) altersentsprechend erhalten, während die Reha-Effekte der 17 Patienten, die nach T3 jegliche sportliche Aktivität abgebrochen hatten, signifikant (p ,01) unter den Status quo ante in T1 zurückfielen. Trotz einer irreversiblen restriktiven Lungenerkrankung kann eine gezielte Sport- und Bewegungstherapie eine Konditionierung im Sinne einer Aktivierung vorhandener Leistungsreserven sowie konsekutiv eine Vergrößerung der Lebensqualität und Belastbarkeit im Alltag bewirken. Diese positiven Effekte lassen sich durch ein regelmäßiges Training langfristig stabilisieren. Die Ergebnisse unterstreichen die Notwendigkeit der Einbindung von Nachsorgestrategien in das Rehabilitationskonzept unter besonderer Berücksichtigung der Selbstwirksamkeitserwartung.

International audience; A first performance test of the Coulomb excitation multipolarimetry (Coulex-multipolarimetry) method is presented. It is based on a $^{85}\hbox {Br}\,\pi p_{3/2}\rightarrow \pi p_{1/2}$ spin-flip experiment performed as part of the PreSPEC-AGATA campaign at the GSI Helmholtzzentrum für Schwerionenforschung (GSI). Via determination of background levels around the expected $^{85}\hbox {Br}$ excitations as well as measured $^{197}\hbox {Au}$ excitations, an upper limit for the M1 transition strength of the $1/2_1^-\rightarrow 3/2_\text {g.s.}^-$ transition in $^{85}\hbox {Br}$ and a lower beam time limit for upcoming experimental campaigns utilizing Coulex-multipolarimetry have been inferred. The impact of the use of AGATA in its anticipated $1\pi $ configuration on these estimates is deduced via Geant4 simulations.

Context. One of the goals of astrochemistry is to understand the degree of chemical complexity that can be reached in star-forming regions, along with the identification of precursors of the building blocks of life in the interstellar medium. To answer such questions, unbiased spectral surveys with large bandwidth and high spectral resolution are needed, in particular, to resolve line blending in chemically rich sources and identify each molecule (especially for complex organic molecules). These kinds of observations have already been successfully carried out, primarily towards the Galactic Center, a region that shows peculiar environmental conditions. Aims. We present an unbiased spectral survey of one of the most chemically rich hot molecular cores located outside the Galactic Center, in the high-mass star-forming region G31.41+0.31. The aim of this 3mm spectral survey is to identify and characterize the physical parameters of the gas emission in different molecular species, focusing on complex organic molecules. In this first paper, we present the survey and discuss the detection and relative abundances of the three isomers of C2H4O2: methyl formate, glycolaldehyde, and acetic acid. Methods. Observations were carried out with the ALMA interferometer, covering all of band 3 from 84 to 116 GHz (∼32 GHz bandwidth) with an angular resolution of 1.2″ × 1.2″ (∼ 4400 au × 4400 au) and a spectral resolution of ∼0.488 MHz (∼1.3-1.7 km s-1). The transitions of the three molecules have been analyzed with the software XCLASS to determine the physical parameters of the emitted gas. Results. All three isomers were detected with abundances of (2 ± 0.6) × 10-7, (4.3-8) × 10-8, and (5.0 ± 1.4) × 10-9 for methyl formate, acetic acid, and glycolaldehyde, respectively. Methyl formate and acetic acid abundances are the highest detected up to now, if compared to sources in the literature. The size of the emission varies among the three isomers with acetic acid showing the most compact emission while methyl formate exhibits the most extended emission. Different chemical pathways, involving both grain-surface chemistry and cold or hot gas-phase reactions, have been proposed for the formation of these molecules, but the small number of detections, especially of acetic acid and glycolaldehyde, have made it very difficult to confirm or discard the predictions of the models. The comparison with chemical models in literature suggests the necessity of grain-surface routes for the formation of methyl formate in G31, while for glycolaldehyde both scenarios could be feasible. The proposed grain-surface reaction for acetic acid is not capable of reproducing the observed abundance in this work, while the gas-phase scenario should be further tested, given the large uncertainties involved., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

Zur Verhutung und Verminderung der berufsbedingten Gonarthrose hat die Berufsgenossenschaft der Bauwirtschaft das Konzept des insgesamt 5 Phasen umfassenden Kniekollegs erarbeitet. In einer prospektiven Vergleichsstudie sollte untersucht werden, ob und inwieweit die auf Nachhaltigkeit ausgerichteten Phasen 1 und 2 des Kniekollegs zur sekundarpraventiven Behandlung berufsbedingter Gonarthrose in der Lage sind, positive Behandlungseffekte mittelfristig zu erhalten. Insgesamt durchliefen 329 mannliche Beschaftigte aus dem Baugewerbe mit Kniegelenkbeschwerden die dreiwochige Phase 1 des biopsychosozial ausgelegten Kniekollegs mit den Schwerpunkten Ergonomie und Muskelaufbautraining. In den nachfolgenden 12 Monaten (Phase 2) wurden die Teilnehmer mehrfach telefonisch kontaktiert, um sie zur Weiterfuhrung des Trainings zu motivieren. Wahrend 206 Beschaftigte das Training in ausgewahlten Fitnesszentren freiwillig und wohnortnah fortfuhrten (VG 1) und sich 45 Arbeitnehmer fur ein individuelles Heimprogramm entschieden (VG 2), beendeten 78 Teilnehmer jede sportliche Aktivitat (KG). Nach Phase 1 zeigten alle Gruppen signifikante Verbesserungen der untersuchten Parameter Maximalkraft der Oberschenkelmuskulatur, Gangsymmetrie, Kniegelenkbeschwerden und korperliche Leistungsfahigkeit. Wahrend sich die Parameter in VG 1 nach 12 Monaten weiter positiv entwickelten, remittierten die Messwerte in VG 2 mit Ausnahme der Muskelkraft moderat. In den Messvariablen der KG lies sich hingegen ein deutlicher Ruckgang beobachten. Im Rahmen der Nachsorge zeigt das Training im Fitnesszentrum mit begleitenden regelmasigen Telefonkontakten positive Effekte. Bei der Rekrutierung der Teilnehmer fur das Kniekolleg kommt der arbeitsmedizinischen Vorsorge eine Schlusselrolle zu.

We aim to characterize the physical and chemical properties of fragmented cores during the earliest evolutionary stages in the very young star-forming regions ISOSS J22478+6357 and ISOSS J23053+5953. NOEMA 1.3 mm data are used in combination with archival mid- and far-infrared observations to construct and fit the SEDs of individual fragmented cores. The radial density profiles are inferred from the 1.3 mm continuum visibility profiles and the radial temperature profiles are estimated from H2CO rotation temperature maps. Molecular column densities are derived with the line fitting tool XCLASS. The physical and chemical properties are combined by applying the physical-chemical model MUSCLE in order to constrain the chemical timescales of a few line-rich cores. The morphology and spatial correlations of the molecular emission are analyzed using the HOG method. The mid-infrared data show that both regions contain a cluster of young stellar objects. Bipolar molecular outflows are observed in the CO 2-1 transition toward the strong mm cores indicating protostellar activity. We find strong molecular emission of SO, SiO, H2CO, and CH3OH in locations which are not associated with the mm cores. These shocked knots can be either associated with the bipolar outflows or, in the case of ISOSS J23053+5953, with a colliding flow that creates a large shocked region between the mm cores. The mean chemical timescale of the cores is lower (20 000 yr) compared to that of the sources of the more evolved CORE sample (60 000 yr). With the HOG method, we find that the spatial emission of species tracing the extended emission and of shock-tracing molecules are well correlated within transitions of these groups., 34 pages, 17 figures, accepted for publication in A&A

Die erweiterte ambulante Physiotherapie (EAP) ist seit vielen Jahren als essenzielles Element der medizinischen Rehabilitation der gesetzlichen Unfallversicherung fest etabliert. Originar biomedizinisch ausgerichtet, verfolgt die EAP seit 2014 einen ganzheitlich ausgerichteten Ansatz und wurde zur Erreichung der beruflichen und sozialen Teilhabe um weitere Behandlungselemente, wie z. B. die Ergotherapie, die psychologische Betreuung oder die Patientenschulung, erganzt. Die praktische Umsetzung der resultierenden erhohten Anforderungen der EAP wird dargestellt mittels bewahrter Handlungsempfehlungen wie Berucksichtigung des beruflichen Tatigkeitsprofils, Einsatz von Assessments und Vereinbarung von Reha-Zielen und anhand zweier Fallbeispiele erlautert. Nach Statistiken der BG Ambulanz Bremen gelten durchschnittlich mehr als 90 % der Patienten bei Beendigung der EAP wieder als arbeitsfahig. Die zeitgemase biopsychosoziale Ausrichtung der EAP ist als positiv zu bewerten, jedoch auch verbunden mit einem deutlichen fachlichen und organisatorischen Mehraufwand.

IMPORTANCE: As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted. OBJECTIVE: To prospectively evaluate reading performance in geographic atrophy and to assess its association with established visual function assessments and structural biomarkers. DESIGN, SETTING, AND PARTICIPANTS: The noninterventional, prospective natural history Directional Spread in Geographic Atrophy study included patients with geographic atrophy secondary to AMD who were recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021. MAIN OUTCOMES AND MEASURES: Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semiautomatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of those variables with reading performance. RESULTS: A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4-82.1] years; 51 women [60%]; 34 men [40%]). Reading performance was impaired with a median (IQR) monocular reading acuity of 0.9 (0.4-1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (0-123) words per minute. In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield, classification of noncenter vs center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R(2) for reading acuity = 0.69). Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity, area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield, and in the inner-upper ETDRS subfield (R(2) for reading speed = 0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R(2) for reading acuity = 0.73; R(2) for reading speed = 0.70). Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ from reading performance in the better-seeing eye. CONCLUSIONS AND RELEVANCE: The association of reading acuity and speed with visual functional and structural biomarkers supports the validity of reading performance as a meaningful end point in clinical trials. These findings suggest that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

One-phonon states of vibrational nuclei with mixed proton–neutron symmetry have been observed throughout the nuclear chart besides the mass A ≈ 200 region. Very recently, it has been proposed that the 2 2 + state of 212Po is of isovector nature. This nucleus has two valence protons and two valence neutrons outside the doubly-magic 208Pb nucleus. The stable isotope 204Hg, featuring two valence-proton and valence-neutron holes, with respect to 208Pb, is the particle-hole mirror of 212Po. In order to compare the properties of low-lying isovector excitations in these particle-hole mirror nuclei, we have studied 204Hg by using the projectile Coulomb-excitation technique. The measured absolute B ( M 1 ; 2 2 + → 2 1 + ) strength of 0.20 ( 2 ) μ N 2 indicates that the 2 2 + level of 204Hg is at least the main fragment of the 2 1 , m s + state. For the first time in this mass region, both lowest-lying, one-quadrupole phonon excitations are established together with the complete set of their decay strengths. This allows for a microscopic description of their structures, achieved in the framework of the Quasi-particle Phonon Model.

We present a detailed observational and modeling study of the hot core VLA 3 in the high-mass star-forming region AFGL 2591, which is a target region of the NOrthern Extended Millimeter Array (NOEMA) large program CORE. Using NOEMA observations at 1.37 mm with an angular resolution of ~0."42 (1 400 au at 3.33 kpc), we derived the physical and chemical structure of the source. We modeled the observed molecular abundances with the chemical evolution code MUSCLE (MUlti Stage ChemicaL codE). Results. With the kinetic temperature tracers CH3CN and H2CO we observe a temperature distribution with a power-law index of q = 0.41+-0.08. Using the visibilities of the continuum emission we derive a density structure with a power-law index of p = 1.7+-0.1. The hot core spectra reveal high molecular abundances and a rich diversity in complex molecules. The majority of the molecules have an asymmetric spatial distribution around the forming protostar(s), which indicates a complex physical structure on scales < 1 400 au. Using MUSCLE, we are able to explain the observed molecular abundance of 10 out of 14 modeled species at an estimated hot core chemical age of ~21 100 years. In contrast to the observational analysis, our chemical modeling predicts a lower density power-law index of p < 1.4. Reasons for this discrepancy are discussed. Conclusions. Combining high spatial resolution observations with detailed chemical modeling allows us to derive a concise picture of the physical and chemical structure of the famous AFGL 2591 hot core. The next steps are to conduct a similar analysis for the whole CORE sample, and then use this analysis to constrain the chemical diversity in high-mass star formation to a much greater depth., 22 pages, 13 figures, accepted for publication in A&A

Purpose: To investigate residual sensitivity within geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Mesopic and dark-adapted (DA) cyan and red light sensitivity (Goldmann III) were investigated using fundus-controlled perimetry (microperimetry). Test points were placed within GA along an “iso-hull” with a distance of −0.645° to the atrophy boundary. The false-positive response rate was determined with suprathreshold stimuli to the optic disc (Heijl-Krakau method) and used to compute the expected sensitivity measurements for the assumption of absolute scotomata. The outermost visible retinal layer on spectral-domain optical coherence tomography at the location of each test point was determined. Results: Thirty eyes of 36 patients (75.55 ± 7.93 years; 19 female) from the prospective natural history study Directional Spread in Geographic Atrophy (NCT02051998), with a total of 1380 threshold determinations were analyzed. The measured sensitivities were significantly (P < 0.01) higher than the expected values for absolute scotomata (mean ± standard error of +6.92 ± 0.86 dB for mesopic, +2.57 ± 0.56 dB for DA cyan, and +4.93 ± 0.74 dB for DA red testing). For mesopic testing and DA red testing, the presence of a residual outer nuclear layer had a significant effect on this discrepancy (P < 0.001). There was no effect of fixation stability or any other reliability index on this discrepancy. Conclusions: Measured sensitivities within the inner junctional zone of GA may not be purely explained by patient-specific false-positive response rates or other reliability indices. The marked influence of the outer retinal configuration on measured sensitivity may be indicative of residual cone function within GA at the inner junctional zone.

The giant molecular cloud Sagittarius B2 (hereafter SgrB2) is the most massive region with ongoing high-mass star formation in the Galaxy. In the southern region of the 40-pc large envelope of SgrB2, we encounter the SgrB2(DS) region which hosts more than 60 high-mass protostellar cores distributed in an arc shape around an extended HII region. We use the Very Large Array in its CnB and D configurations, and in the frequency bands C (4--8 GHz) and X (8--12 GHz) to observe the whole SgrB2 complex. Continuum and radio recombination line maps are obtained. We detect radio continuum emission in SgrB2(DS) in a bubble-shaped structure. From 4 to 12 GHz, we derive a spectral index between -1.2 and -0.4, indicating the presence of non-thermal emission. We decompose the contribution from thermal and non-thermal emission, and find that the thermal component is clumpy and more concentrated, while the non-thermal component is more extended and diffuse. The radio recombination lines in the region are found to be not in local thermodynamic equilibrium (LTE) but stimulated by the non-thermal emission. The thermal free-free emission is likely tracing an HII region ionized by an O7 star, while the non-thermal emission can be generated by relativistic electrons created through first-order Fermi acceleration. We have developed a simple model of the SgrB2(DS) region and found that first-order Fermi acceleration can reproduce the observed flux density and spectral index., Accepted for publication in Astronomy & Astrophysics. 15 pages with 12 figures and 1 table, plus Appendices with extra figures. (Abstract modified)

Purpose: Based on exudative activity, choroidal neovascularization (CNV) in age-related macular degeneration (AMD) can be classified as “active” aCNV, pretherapied “silent” sCNV (i.e., a treatment-free interval >12 weeks), or treatment-naïve “quiescent” qCNV. We evaluated the qualitative and quantitative optical coherence tomography angiography (OCTA) features of these CNV subgroups. Methods: The presence of small-caliber vessels, peripheral arcades, and a ­perilesional OCTA signal attenuation as well as values for vessel length, density, and branching index were evaluated for each CNV network in a 6 × 6 mm OCTA scan pattern. Results: Fifty-one eyes of 51 patients with AMD (age 75.9 ± 7.5 years; 20 males [39.2%]) were included. The qCNV subgroup (n = 8) showed the highest prevalence of qualitative and quantitative values for OCTA activity criteria, reaching significance with regard to small-caliber vessels (p = 0.003), peripheral arcades (p = 0.039), vessel length (p = 0.020), and branching index (p < 0.001) when compared to the aCNV (n = 32) and sCNV (n = 11) subgroups. Qualitative criteria were inversely associated with the number of previous anti-VEGF injections (each p < 0.03), while quantitative metrics also suggested lower values. Conclusions: These findings suggest that OCTA may be supportive in the phenotypical differentiation of CNV lesions secondary to AMD, while the assessed structural changes appeared to be more indicative of previously administered anti-VEGF therapy than current exudative activity.

Estimation of the perioperative risk plays a decisive role in the surgical indications, particularly in view of the demographic change. For this reason, prehabilitation concepts for reducing perioperative risk nowadays play an increasingly important role.Presentation of the current recommendations for preoperative diagnostics in thoracic surgical interventions as well as existing prehabilitation concepts and their practical applicability.A selective review of the literature was carried out by searching the electronic databases PubMed, Cochrane Library and ISRCTN, including the guidelines of the American College of Chest Physicians (ACCP) and the European Society of Thoracic Surgery (ESTS).Preconditioning includes the conservative treatment of underlying diseases, smoking cessation and prehabilitation. Prehabilitation is an increasingly pressing concept in routine clinical practice, even though the evidence is limited due to the very heterogeneous study situation. Overall, however, there is a tendency for positive effects on the quality of life and postoperative complications as well as convalescence.In addition to preoperative diagnostics to assess the perioperative risk, effective preconditioning of patients is also necessary. For this an interdisciplinary approach including anesthesia, pneumology, psychotherapy and physiotherapy is necessary. In addition to the conservative medicinal optimization, prehabilitation concepts are gaining in importance and will certainly become established in routine clinical practice. From the surgical perspective, minimally invasive approaches and parenchyma-sparing resections also serve to reduce risks.

Excited states of $^{202}\mathrm{Hg}$ have been studied via the $^{12}\mathrm{C}(^{202}\mathrm{Hg},^{202}\mathrm{Hg}^{*})$ Coulomb excitation reaction at a beam energy of 890 MeV. The $\ensuremath{\gamma}$-ray transitions from the excited states of $^{202}\mathrm{Hg}$ were detected by the Gammasphere array. The intensities of the observed $\ensuremath{\gamma}$ rays determined the relative populations of the excited states which were used to extract the absolute $M1$ and $E2$ transition strength distributions for excited ${2}^{+}$ states of $^{202}\mathrm{Hg}$ up to 2 MeV. The measured absolute $B(M1;{2}_{7}^{+}\ensuremath{\rightarrow}{2}_{1}^{+})$ strength of $0.18(8){\ensuremath{\mu}}_{\mathrm{N}}^{2}$ indicates that the ${2}_{7}^{+}$ level of $^{202}\mathrm{Hg}$ is the main fragment of the proton-neutron mixed-symmetry ${2}_{1,\mathrm{ms}}^{+}$ state. Upper limits for the $F$-spin mixing matrix elements of ${}^{202,204}\mathrm{Hg}$ are determined as well.

In the massive star-forming region IRAS 21078+5211, a highly fragmented cluster (0.1~pc in size) of molecular cores is observed, located at the density peak of an elongated (1~pc in size) molecular cloud. A small (1~km/s per 0.1~pc) LSR velocity (Vlsr) gradient is detected across the axis of the molecular cloud. Assuming we are observing a mass flow from the harboring cloud to the cluster, we derive a mass infall rate of about 10^{-4}~M_{sun}~yr^{-1}. The most massive cores (labeled 1, 2, and 3) are found at the center of the cluster, and these are the only ones that present a signature of protostellar activity in terms of emission from high-excitation molecular lines or a molecular outflow. We reveal an extended (size about 0.1~pc), bipolar collimated molecular outflow emerging from core 1. We believe this is powered by a (previously discovered) compact (size, 25 pages, 16 figures

The high resolution vibrational spectrum of ethyl cyanide (C2H5CN) has been investigated in the far-IR using synchrotron-based Fourier transform spectroscopy. The assignment was performed using the Automated Spectral Assignment Procedure (ASAP) allowing accurate rotational energy levels of the four lowest fundamental vibrations of the species, namely the v 13 = 1 @ 205.934099(8) cm−1, v 21 = 1 @ 212.141101(8) cm−1, v 20 = 1 @ 372.635293(15) cm−1, and v 12 = 1 @ 532.699617(16) cm−1 states, to be determined. The analysis not only confirms the applicability of the ASAP in the treatment of (dense) high-resolution infrared spectra but also reveals some of its limitations. Complementary to the infrared study, the pure rotational spectrum of C2H5CN was also studied in selected frequency ranges from 75 to 255 GHz. New observations of a prototypical high-mass star-forming region, G327.3–0.6, performed with the Atacama Large Millimeter Array show that vibrational satellites of C2H5CN can be very intense, of order several tens of Kelvin in units of brightness temperature.

Specimens made from pre-alloyed Invar (Fe-36Ni) powder were fabricated by selective laser melting and stress-relief heat treated afterwards. A relative density of the fabricated parts of 99.6 % was determined by computed tomography. The microstructure and mechanical behavior under monotonic and particularly cyclic loading at ambient temperature were investigated. Results reveal a bimodal microstructure containing columnar and equiaxed grains with an average grain size of 75 μm and pronounced texture 〈001〉 || BD. The selective laser melted Invar is characterized by a homogeneous hardness distribution revealing no gradient with respect to the height of the fabricated parts. The mechanical response under monotonic tensile loading is characterized by a fairly ductile behavior. Total strain controlled low-cycle fatigue tests with varying strain amplitudes were performed. The cyclic deformation response is characterized by highly reproducible behavior in terms of stress amplitudes and number of cycles to failure. The corresponding half-life hysteresis loops reveal perfect Masing behavior. Post-mortem fractography revealed crack initiation in direct vicinity of the surfaces. The damage tolerance of Invar is found to be promoted by its high ductility. Finally, a low coefficient of thermal expansion, very similar to conventionally processed Invar, was shown by dilatometer tests in the temperature range of 0 °C–180 °C.

PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic atrophy (GA) secondary to age-related macular degeneration using patient-tailored perimetry grids for mesopic and dark-adapted two-color fundus-controlled perimetry. METHODS: Twenty-five eyes with GA of 25 patients (prospective, natural-history Directional Spread in Geographic Atrophy study [DSGA; NCT02051998]) and 40 eyes of 40 normal subjects were included. Patient-tailored perimetry grids were generated using annotated fundus autofluorescence data. Customized software positioned test-points along iso-hulls surrounding the GA boundary at distances of 0.43°, 0.86°, 1.29°, 2.15°, and 3.01°. The grids were used for duplicate mesopic and dark-adapted two-color (cyan and red) fundus-controlled perimetry. Age-adjusted reference-data were obtained through regression analysis of normative data followed by spatial interpolation. RESULTS: The mean sensitivity loss for mesopic testing decreased with the distance to GA (-10.3 dB [0.43°], -8.2 dB [0.86°], -7.1 dB [1.29°], -6.8 dB [2.15°], and -6.6 dB [3.01°]; P < 0.01). Dark-adapted cyan sensitivity loss exceeded dark-adapted red sensitivity loss for all iso-hulls (-14.8 vs. -11.7 dB, -13.5 vs. -10.1 dB, -12.8 vs. -9.1 dB, -11.6 vs. -8.2 dB, -10.7 vs. -8.0 dB; P < 0.01). CONCLUSION: Patient-tailored fundus-controlled perimetry grids allowed for testing of retinal function in the junctional zone of GA with high spatial resolution. A distinct decrease in mesopic sensitivity loss between 0.43° (125 µm) and 1.29° (375 µm) was observed that leveled off at more distant test-points. In proximity to the GA boundary, the results indicate that rod exceeded cone dysfunction.

Purpose: To investigate the choroidal blood flow in areas within and adjacent to retinal pigment epithelium (RPE) atrophy secondary to late-onset Stargardt disease (STGD1) and age-related macular degeneration (AMD). Methods: A total of 43 eyes (23 STGD1 and 20 AMD) of patients with RPE atrophy and 25 eyes of healthy controls without ocular pathology underwent multimodal imaging including optical coherence tomography angiography (OCT-A; PLEX Elite 9000 Swept-Source OCT). Using an exploratory approach, choriocapillaris and deeper choroid OCT-A slabs were evaluated in order to detect differences between STGD1 and AMD. The magnitude of absence-of-flow signal (AFS) was investigated in terms of area-fraction and size-frequency distribution. Results: Qualitative and quantitative analysis of areas of RPE atrophy revealed more pronounced rarefaction of the choriocapillaris flow signal in STGD1 as compared to AMD (AFS area fraction: 33.15% ± 6.86% vs. 31.68% ± 8.39%; P = 0.517), while outside RPE atrophy rarefaction was less pronounced in STGD1 (AFS area fraction: 17.41% ± 5.67% vs. 21.59% ± 6.90%; P < 0.001), to the level of nonsignificance compared to controls (13.27% ± 2.99%, P = 0.368). Given this discrepancy, the ratio of the AFS area fraction within/outside of RPE atrophy could be used to differentiate between STGD1 and AMD with 65.0% sensitivity and 92.3% specificity. Conclusions: Using OCT-A, comparison of choroidal flow signal within and outside the area of RPE atrophy revealed distinct differences between STGD1 and AMD, potentially implicating a differential role of the choroid in the pathogenesis of RPE atrophy in these two diseases.