Background
Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical ...data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty.
Aim
To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities.
Methods
A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants.
Results
Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence.
Conclusion
The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.
Cohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is less well understood. Using live-cell and ...super-resolved 3D microscopy, here we find that cohesin depletion in a human colon cancer derived cell line results in endomitosis and a single multilobulated nucleus with chromosome territories pervaded by interchromatin channels. Chromosome territories contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. These clusters form microscopically defined, active and inactive compartments, which likely correspond to A/B compartments, which are detected with ensemble Hi-C. Splicing speckles are observed nearby within the lining channel system. We further observe that the multilobulated nuclei, despite continuous absence of cohesin, pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity.
The prediction of a supersonic solar wind
was first confirmed by spacecraft near Earth
and later by spacecraft at heliocentric distances as small as 62 solar radii
. These missions showed that plasma ...accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy
. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams
. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii
, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age
.
Secondary organic aerosol (SOA) is a substantial component of total atmospheric organic particulate matter, but little is known about the composition of SOA formed through cloud processing. We ...conducted aqueous phase photo-oxidation experiments of methylglyoxal and hydroxyl radical to simulate cloud processing. In addition to predicted organic acid monomers, oligomer formation from methylglyoxal–hydroxyl radical reactions was detected by electrospray ionization mass spectrometry (ESI-MS). The chemical composition of the oligomers and the mechanism of their formation were investigated by ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and LCQ DUO ion trap mass spectrometry (ESI-MS-MS). Reaction products included 415 compounds detected in the mass range 245–800
Da and the elemental composition of all 415 compounds were determined by ultra-high resolution FT-ICR MS. The ratio of total organic molecular weight per organic carbon weight (OM:OC) of the oligomers (1.0–2.5) was lower than the OM:OC of the organic acid monomers (2.3–3.8) formed, suggesting that the oligomers are less hygroscopic than the organic acid monomers formed from methylglyoxal–hydroxyl radical reaction. The OM:OC of the oligomers (average=2.0) is consistent with that of aged atmospheric aerosols and atmospheric humic-like substances (HULIS). A mechanism is proposed in which the organic acid monomers formed through hydroxyl radical reactions oligomerize through esterification. The mechanism is supported by the existence of series of oligomers identified by elemental composition from FT-ICR MS and ion fragmentation patterns from ESI-MS-MS. Each oligomer series starts with an organic acid monomer formed from hydroxyl radical oxidation, and increases in molecular weight and total oxygen content through esterification with a hydroxy acid (C
3H
6O
3) resulting in multiple additions of 72.02113
Da (C
3H
4O
2) to the parent organic acid monomer. Methylglyoxal is a water-soluble product of both gas phase biogenic (i.e., isoprene) and anthropogenic (i.e., aromatics, alkenes) hydrocarbon oxidation. The varied and multiple sources of methylglyoxal increase the potential for these low volatility cloud processing products (e.g., oxalic acid and oligomers) to significantly contribute to SOA. Aqueous phase oligomer formation investigated here and aerosol phase oligomer formation appear to be more similar than previously realized, which may simplify the incorporation of oligomers into atmospheric SOA models.
Many aspects of the supposed hyperthermal Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, c. 182 Ma) are well understood but a lack of robust palaeotemperature data severely limits ...reconstruction of the processes that drove the T-OAE and associated environmental and biotic changes. New oxygen isotope data from calcite shells of the benthic fauna suggest that bottom water temperatures in the western Tethys were elevated by c. 3.5 °C through the entire T-OAE. Modelling supports the idea that widespread marine anoxia was induced by a greenhouse-driven weathering pulse, and is compatible with the OAE duration being extended by limitation of the global silicate weathering flux. In the western Tethys Ocean, the later part of the T-OAE is characterized by abundant occurrences of the brachiopod Soaresirhynchia, which exhibits characteristics of slow-growing, deep sea brachiopods. The unlikely success of Soaresirhynchia in a hyperthermal event is attributed here to low metabolic rate, which put it at an advantage over other species from shallow epicontinental environments with higher metabolic demand.
We aim to summarize the current state of knowledge regarding Galactic Faraday rotation in an all-sky map of the Galactic Faraday depth. For this we have assembled the most extensive catalog of ...Faraday rotation data of compact extragalactic polarized radio sources to date. In the map-making procedure we used a recently developed algorithm that reconstructs the map and the power spectrum of a statistically isotropic and homogeneous field while taking into account uncertainties in the noise statistics. This procedure is able to identify some rotation angles that are offset by an integer multiple of π. The resulting map can be seen as an improved version of earlier such maps and is made publicly available, along with a map of its uncertainty. For the angular power spectrum we find a power law behavior Cℓ ∝ ℓ-2.17 for a Faraday sky where an overall variance profile as a function of Galactic latitude has been removed, in agreement with earlier work. We show that this is in accordance with a 3D Fourier power spectrum P(k) ∝ k-2.17 of the underlying field neBr under simplifying geometrical and statistical assumptions.
Circadian and seasonal rhythms are seen in many species, modulate several aspects of human physiology, including brain functions such as mood and cognition, and influence many neurological and ...psychiatric illnesses. However, there are few data regarding the genome-scale molecular correlates underlying these rhythms, especially in the human brain. Here, we report widespread, site-specific and interrelated diurnal and seasonal rhythms of gene expression in the human brain, and show their relationship with parallel rhythms of epigenetic modification including histone acetylation, and DNA methylation. We also identify transcription factor-binding sites that may drive these effects. Further, we demonstrate that Alzheimer's disease pathology disrupts these rhythms. These data suggest that interrelated diurnal and seasonal epigenetic and transcriptional rhythms may be an important feature of human brain biology, and perhaps human biology more broadly, and that changes in such rhythms may be consequences of, or contributors to, diseases such as Alzheimer's disease.
Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting cell adhesion and repulsion, respectively. How the ...three proteins interact and function simultaneously is poorly understood. We show that Unc5D interacts with FLRT2 in cis, controlling cell adhesion in response to externally presented Lphn3. The ectodomains of the three proteins bind cooperatively. Crystal structures of the ternary complex formed by the extracellular domains reveal that Lphn3 dimerizes when bound to FLRT2:Unc5, resulting in a stoichiometry of 1:1:2 (FLRT2:Unc5D:Lphn3). This 1:1:2 complex further dimerizes to form a larger 'super-complex' (2:2:4), using a previously undescribed binding motif in the Unc5D TSP1 domain. Molecular dynamics simulations, point-directed mutagenesis and mass spectrometry demonstrate the stability and molecular properties of these complexes. Our data exemplify how receptors increase their functional repertoire by forming different context-dependent higher-order complexes.
While work-related fatigue has become an issue of concern among European employees, the relationship between fatigue, depression and work-related stressors is far from clear. The purposes of this ...study were (1) to determine the associations of fatigue with work-related stressors, severe medical disease, health behavior and depression in the working population and (2) to determine the unique impact of work-related stressors on fatigue.
We used cross-sectional data of N = 7,930 working participants enrolled in the Gutenberg Health Study (GHS) from 2007 to 2012 filled out the Personal Burnout Scale (PBS) of the Copenhagen Psychosocial Questionnaire (COPSOQ), the PHQ-9, and a list of work-related stressors.
A total of 27.5% reported increased fatigue, esp. women, younger persons with a lower social status and income, smokers, severely medically ill, previously and currently depressed participants. Fatigue was consistently associated with severe medical disease, health behavior and depression, which need to be taken into account as potential confounders when analyzing its relationship to work-related strains. Depression was consistently associated with work-related stressors. However, after statistically partialling out depression, fatigue was still significantly associated with work-related stress.
Fatigue as an indicator of allostatic load is consistently associated with work-related stressors such as work overload after controlling for depression. The brief Personal Burn-out Scale is suitable for assessing work-related fatigue in the general population.
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