Radiotherapy for Intubated Patients with Malignant Airway Obstruction: Futile or Facilitating Extubation?

IntroductionThe optimal approach to patients with malignant airway obstruction who require intubation and mechanical ventilation but are ineligible for bronchoscopic interventions is uncertain. Radiotherapy (RT) may be delivered but requires substantial resources in this patient population. In the absence of evidence, it is unknown whether RT facilitates extubation or delays an appropriate transition to end-of-life care.MethodsWe performed a 10-year retrospective review of intensive care unit (ICU) patients treated with RT while on mechanical ventilation for malignant airway obstruction. Primary study endpoints were overall survival (OS) and extubation success (ES), defined as 48 hours or more without reintubation or death. Secondary endpoints included rates of discharge from the ICU and to home. Logistic regression and Cox regression analyses were performed to identify factors associated with OS and ES.ResultsTwenty-six patients were eligible for analysis. Seven patients (27%) were extubated; extubations occurred between days 4 and 22 after RT initiation. All patients were discharged from the ICU and most (n = 6) were also discharged home. An association between higher radiation doses and ES was observed (odds ratio per 5 Gy increase: 0.63; p = 0.080). Median OS was only 0.36 months (range, 0–113 months), and 6-month OS was 11%. On Cox regression analysis, increased radiation dose was predictive of improved OS (hazard ratio per 5 Gy increase: 0.74; p = 0.016).ConclusionsA significant minority of patients receiving RT were successfully extubated. Higher radiation doses were predictive of improved OS and showed a trend for increased ES. Survival beyond 6 months was uncommon, however, the majority of patients with ES were able to be discharged home

Environmentally relevant exposure to an antidepressant alters courtship behaviours in a songbird

Pharmaceuticals in the environment are a recently identified global threat to wildlife, including birds. Like other human pharmaceuticals, the antidepressant fluoxetine (Prozac) enters the environment via sewage and has been detected at wastewater treatment plants. Birds foraging on invertebrates at these sites can be exposed to pharmaceuticals, although the implications of exposure are poorly understood. We conducted experiments to test whether chronic exposure to a maximally environmentally relevant concentration of fluoxetine (2.7 μg day-1) altered courtship behaviour and female reproductive physiology in wild-caught starlings (Sturnus vulgaris), a species commonly found foraging on invertebrates at wastewater treatment plants. When paired with a female over two days, males sang less and were more aggressive towards fluoxetine-treated females than controls. Fluoxetine-treated females were initially aggressive towards males, becoming significantly less aggressive by the second day. In contrast, control females expressed intermediate levels of aggression throughout. We found no effect of female treatment on female courtship behaviour. Female body condition, circulating testosterone and circulating oestradiol were unaffected by treatment and did not account for male preference. Our findings suggest that exposure to an antidepressant reduced female attractiveness, adding to growing evidence that environmental concentrations of pharmaceuticals can alter important traits related to individual fitness and population dynamics

Detecting fluoxetine and norfluoxetine in wild bird tissues and feathers

The contamination of the environment with human pharmaceuticals is widespread and demand for such products is mounting globally. Wild vertebrates may be at particular risk from any effects from pharmaceuticals, because of the evolutionary conservation of drug targets. However, exposure of wildlife to pharmaceuticals is poorly characterised, partly due to challenges associated with detecting rapidly metabolised compounds. As part of a wider study on the behavioural effects of fluoxetine (Prozac) on Eurasian starlings (Sturnus vulgaris), we investigated which avian samples are best suited for detecting exposure to fluoxetine in free-living birds. We analysed plasma, various tissues and tail feathers (grown both in the wild and in captivity during the dosing period) from fluoxetine-treated birds (dosed daily with 0.035 mg kg-1 bodyweight for 28 weeks), and liver tissue and tail feathers from sham-dosed birds. We detected fluoxetine in only two of twelve plasma samples from dosed birds. In dosed birds, median concentrations of free fluoxetine/norfluoxetine in tissues (two hour post-final dose) were: 111.2/67.6 ng g-1 in liver, 29.6/5.7 ng g-1 in kidney, 14.2/4.0 ng g-1 in lung, 15.1/1.6 ng g-1 in brain. We estimated that fluoxetine would remain detectable in liver and kidney approximately 4.5 times longer (90 h) than in brain (20h). In dosed birds, fluoxetine was detected in feathers regrown during the dosing period (median concentration = 11.4 ng g-1) at concentrations significantly higher than in regrown feathers from control birds. Fluoxetine residues were detected in wild-grown feathers (grown before the birds were brought into captivity) at concentrations up to 27.0 ng g-1, providing some evidence of likely exposure in the wild. Our results show liver and kidney can be used for detecting fluoxetine in avian carcasses and provide a first indication that feathers may be useful for assessing exposure to fluoxetine, and possibly other pharmaceuticals

Hearing Feelings: Affective Categorization of Music and Speech in Alexithymia, an ERP Study

Background: Alexithymia, a condition characterized by deficits in interpreting and regulating feelings, is a risk factor for a variety of psychiatric conditions. Little is known about how alexithymia influences the processing of emotions in music and speech. Appreciation of such emotional qualities in auditory material is fundamental to human experience and has profound consequences for functioning in daily life. We investigated the neural signature of such emotional processing in alexithymia by means of event-related potentials. Methodology: Affective music and speech prosody were presented as targets following affectively congruent or incongruent visual word primes in two conditions. In two further conditions, affective music and speech prosody served as primes and visually presented words with affective connotations were presented as targets. Thirty-two participants (16 male) judged the affective valence of the targets. We tested the influence of alexithymia on cross-modal affective priming and on N400 amplitudes, indicative of individual sensitivity to an affective mismatch between words, prosody, and music. Our results indicate that the affective priming effect for prosody targets tended to be reduced with increasing scores on alexithymia, while no behavioral differences were observed for music and word targets. At the electrophysiological level, alexithymia was associated with significantly smaller N400 amplitudes in response to affectively incongruent music and speech targets, but not to incongruent word targets. Conclusions: Our results suggest a reduced sensitivity for the emotional qualities of speech and music in alexithymia during affective categorization. This deficit becomes evident primarily in situations in which a verbalization of emotional information is required

ICDP workshop on the Lake Tanganyika Scientific Drilling Project: a late Miocene–present record of climate, rifting, and ecosystem evolution from the world's oldest tropical lake

The Neogene and Quaternary are characterized by enormous changes in global climate and environments, including global cooling and the establishment of northern high-latitude glaciers. These changes reshaped global ecosystems, including the emergence of tropical dry forests and savannahs that are found in Africa today, which in turn may have influenced the evolution of humans and their ancestors. However, despite decades of research we lack long, continuous, well-resolved records of tropical climate, ecosystem changes, and surface processes necessary to understand their interactions and influences on evolutionary processes. Lake Tanganyika, Africa, contains the most continuous, long continental climate record from the mid-Miocene (∼10 Ma) to the present anywhere in the tropics and has long been recognized as a top-priority site for scientific drilling. The lake is surrounded by the Miombo woodlands, part of the largest dry tropical biome on Earth. Lake Tanganyika also harbors incredibly diverse endemic biota and an entirely unexplored deep microbial biosphere, and it provides textbook examples of rift segmentation, fault behavior, and associated surface processes. To evaluate the interdisciplinary scientific opportunities that an ICDP drilling program at Lake Tanganyika could offer, more than 70 scientists representing 12 countries and a variety of scientific disciplines met in Dar es Salaam, Tanzania, in June 2019. The team developed key research objectives in basin evolution, source-to-sink sedimentology, organismal evolution, geomicrobiology, paleoclimatology, paleolimnology, terrestrial paleoecology, paleoanthropology, and geochronology to be addressed through scientific drilling on Lake Tanganyika. They also identified drilling targets and strategies, logistical challenges, and education and capacity building programs to be carried out through the project. Participants concluded that a drilling program at Lake Tanganyika would produce the first continuous Miocene–present record from the tropics, transforming our understanding of global environmental change, the environmental context of human origins in Africa, and providing a detailed window into the dynamics, tempo and mode of biological diversification and adaptive radiations.© Author(s) 2020. This open access article is distributed under the Creative Commons Attribution 4.0 License

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)