REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology ...relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease (‘secondary RBD’) is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with ‘idiopathic’ RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.
Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major ...pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed.
The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic ‘tumor’ measurements were also assessed.
We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation—dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death—cholesterol clefts; and (iii) tissue repair—neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P<0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop ‘Immune-Related Pathologic Response Criteria’ (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT median per-case %RVT variability 5% (0%–29%) versus 10% (0%–58%), P=0.007 and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P=0.002).
irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.
The Juno spacecraft acquired direct observations of the jovian magnetosphere and auroral emissions from a vantage point above the poles. Juno’s capture orbit spanned the jovian magnetosphere from bow ...shock to the planet, providing magnetic field, charged particle, and wave phenomena context for Juno’s passage over the poles and traverse of Jupiter’s hazardous inner radiation belts. Juno’s energetic particle and plasma detectors measured electrons precipitating in the polar regions, exciting intense aurorae, observed simultaneously by the ultraviolet and infrared imaging spectrographs. Juno transited beneath the most intense parts of the radiation belts, passed about 4000 kilometers above the cloud tops at closest approach, well inside the jovian rings, and recorded the electrical signatures of high-velocity impacts with small particles as it traversed the equator.
ABSTRACT
Understanding the properties of transient gravitational waves (GWs) and their sources is of broad interest in physics and astronomy. Bayesian inference is the standard framework for ...astrophysical measurement in transient GW astronomy. Usually, stochastic sampling algorithms are used to estimate posterior probability distributions over the parameter spaces of models describing experimental data. The most physically accurate models typically come with a large computational overhead which can render data analsis extremely time consuming, or possibly even prohibitive. In some cases highly specialized optimizations can mitigate these issues, though they can be difficult to implement, as well as to generalize to arbitrary models of the data. Here, we investigate an accurate, flexible, and scalable method for astrophysical inference: parallelized nested sampling. The reduction in the wall-time of inference scales almost linearly with the number of parallel processes running on a high-performance computing cluster. By utilizing a pool of several hundreds or thousands of CPUs in a high-performance cluster, the large wall times of many astrophysical inferences can be alleviated while simultaneously ensuring that any GW signal model can be used ‘out of the box’, i.e. without additional optimization or approximation. Our method will be useful to both the LIGO-Virgo-KAGRA collaborations and the wider scientific community performing astrophysical analyses on GWs. An implementation is available in the open source gravitational-wave inference library pBilby (parallel bilby).
In this paper, we describe the first data release of the Visible and Infrared Survey Telescope for Astronomy (VISTA) Deep Extragalactic Observations (VIDEO) survey. VIDEO is a ∼12 deg2 survey in the ...near-infrared Z, Y, J, H and K
s bands, specifically designed to enable the evolution of galaxies and large structures to be traced as a function of both epoch and environment from the present day out to z = 4, and active galactic nuclei (AGNs) and the most massive galaxies up to and into the epoch of reionization. With its depth and area, VIDEO will be able to fully explore the period in the Universe where AGN and starburst activity were at their peak and the first galaxy clusters were beginning to virialize. VIDEO therefore offers a unique data set with which to investigate the interplay between AGN, starbursts and environment, and the role of feedback at a time when it was potentially most crucial.
We provide data over the VIDEO-XMM3 tile, which also covers the Canada-France-Hawaii Telescope Legacy Survey Deep-1 field (CFHTLS-D1). The released VIDEO data reach a 5σ AB-magnitude depth of Z = 25.7, Y = 24.5, J = 24.4, H = 24.1 and K
s = 23.8 in 2 arcsec diameter apertures (the full depth of Y = 24.6 will be reached within the full integration time in future releases). The data are compared to previous surveys over this field and we find good astrometric agreement with the Two Micron All Sky Survey, and source counts in agreement with the recently released UltraVISTA survey data. The addition of the VIDEO data to the CFHTLS-D1 optical data increases the accuracy of photometric redshifts and significantly reduces the fraction of catastrophic outliers over the redshift range 0 < z < 1 from 5.8 to 3.1 per cent in the absence of an i-band luminosity prior. However, we expect that the main improvement in photometric redshifts will come in the redshift range 1 < z < 4 due to the sensitivity to the Balmer and 4000 Å breaks provided by the near-infrared VISTA filters. All images and catalogues presented in this paper are publicly available through ESO's phase 3 archive and the VISTA Science Archive.
To determine if synucleinopathy pathology is related to REM sleep behavior disorder (RBD) plus dementia or parkinsonism.
The clinical and neuropathologic findings were analyzed on all autopsied cases ...evaluated at Mayo Clinic Rochester from January 1990 to April 2002 who were diagnosed with RBD and a neurodegenerative disorder. Ubiquitin and/or alpha-synuclein immunocytochemistry was used in all cases. The clinical and neuropathologic diagnoses were based on published criteria.
Fifteen cases were identified (14 men). All had clear histories of dream enactment behavior, and 10 had RBD confirmed by polysomnography. RBD preceded dementia or parkinsonism in 10 (66.7%) patients by a median of 10 (range 2 to 29) years. The clinical diagnoses included dementia with Lewy bodies (DLB) (n = 6); multiple-system atrophy (MSA) (n = 2); combined DLB, AD, and vascular dementia (n = 1); dementia (n = 1); dementia with parkinsonism (n = 1); PD (n = 1); PD with dementia (n = 1); dementia/parkinsonism/motor neuron disease (n = 1); and AD/Binswanger's disease (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD) in 12 (neocortical in 11 and limbic in 1) and MSA in 3. Three also had argyrophilic grain pathology. In the LBD cases, concomitant AD pathology was present in six (one also with Binswanger's pathology, and one also with multiple subcortical infarcts).
In the setting of degenerative dementia or parkinsonism, RBD often reflects an underlying synucleinopathy.
Background
Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD‐PM) aims to improve data ...on stillbirth to enable prevention.
Objectives
To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD‐PM.
Search strategy
We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016.
Selection criteria
Reports of stillbirth causes in unselective cohorts.
Data collection and analysis
Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD‐PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC).
Main results
Eighty‐five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD‐PM. All stillbirth causes mapped to ICD‐PM. In a subset from HIC, mapping obscured major causes.
Conclusions
There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well‐resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings.
Funding
HR, SH, SHL, and AW were supported by an NHMRC‐CRE grant (APP1116640). VF was funded by an NHMRC‐CDF (APP1123611).
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Urgent need to improve data on causes of stillbirths across all settings to meet global targets.
Plain Language Summary
Background and methods
Nearly three million babies are stillborn every year. These deaths have deep and long‐lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high‐, middle‐, and low‐income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths.
Findings
We found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low‐, middle‐, and high‐income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low‐income countries, stillbirths were often attributed to Infection and Complications during labour and birth. In middle‐ and high‐income countries, stillbirths were often reported as Placental complications.
Limitations
We may have missed some reports as searches were carried out in English only. The available reports were of poor quality.
Implications
Many countries, particularly those where the majority of stillbirths occur, do not report any information about these deaths. Where there are reports, the quality is often poor. It is important to improve the investigation and reporting of stillbirth using a standardised system so that policy makers and healthcare workers can develop effective stillbirth prevention programs. All stillbirths should be investigated and reported in line with the World Health Organization standards.
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Urgent need to improve data on causes of stillbirths across all settings to meet global targets.
The European Space Agency's three Swarm satellites were launched on 22 November 2013 into nearly polar, circular orbits, eventually reaching altitudes of 460 km (Swarm A and C) and 510 km (Swarm B). ...Swarm's multiyear mission is to make precision, multipoint measurements of low‐frequency magnetic and electric fields in Earth's ionosphere for the purpose of characterizing magnetic fields generated both inside and external to the Earth, along with the electric fields and other plasma parameters associated with electric current systems in the ionosphere and magnetosphere. Electric fields perpendicular to the magnetic field
B→ are determined through ion drift velocity
v→i and magnetic field measurements via the relation
E→⊥=−v→i×B→. Ion drift is derived from two‐dimensional images of low‐energy ion distribution functions provided by two Thermal Ion Imager (TII) sensors viewing in the horizontal and vertical planes;
v→i is corrected for spacecraft potential as determined by two Langmuir probes (LPs) which also measure plasma density ne and electron temperature Te. The TII sensors use a microchannel‐plate‐intensified phosphor screen imaged by a charge‐coupled device to generate high‐resolution distribution images (66 × 40 pixels) at a rate of 16 s−1. Images are partially processed on board and further on the ground to generate calibrated data products at a rate of 2 s−1; these include
v→i,
E→⊥, and ion temperature Ti in addition to electron temperature Te and plasma density ne from the LPs.
Key Points
Swarm TII sensors provide ion velocity and temperature from core ion distribution function images
CCD‐based imaging detectors in the TIIs support event rates that are much higher than possible with charge amplifier‐based systems
Swarm LPs use a harmonic‐mode technique to obtain electron density, temperature, and spacecraft potential at high rates
Growth in terrestrial gross primary production (GPP)-the amount of carbon dioxide that is 'fixed' into organic material through the photosynthesis of land plants-may provide a negative feedback for ...climate change. It remains uncertain, however, to what extent biogeochemical processes can suppress global GPP growth. As a consequence, modelling estimates of terrestrial carbon storage, and of feedbacks between the carbon cycle and climate, remain poorly constrained. Here we present a global, measurement-based estimate of GPP growth during the twentieth century that is based on long-term atmospheric carbonyl sulfide (COS) records, derived from ice-core, firn and ambient air samples. We interpret these records using a model that simulates changes in COS concentration according to changes in its sources and sinks-including a large sink that is related to GPP. We find that the observation-based COS record is most consistent with simulations of climate and the carbon cycle that assume large GPP growth during the twentieth century (31% ± 5% growth; mean ± 95% confidence interval). Although this COS analysis does not directly constrain models of future GPP growth, it does provide a global-scale benchmark for historical carbon-cycle simulations.
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