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In the first paper of this series, we examined existing methods of optical meteor trajectory estimation and developed a novel method which simultaneously uses both the geometry and the dynamics of meteors to constrain their trajectories. We also developed a simulator which uses an ablation model to generate realistic synthetic meteor trajectories which we use to test meteor trajectory solvers. In this second paper, we perform simulation validation to estimate radiant and velocity accuracy, which may be achieved by various meteor observation systems as applied to several meteor showers. For low-resolution all-sky systems, where the meteor deceleration is generally not measurable, the multi-parameter fit method assuming a constant velocity better reproduces the radiant and speed of synthetic meteors. For moderate field of view systems, our novel method performs the best at all convergence angles, while multi-parameter fit methods generally produce larger speed errors. For high-resolution, narrow field of view systems, we find our new method of trajectory estimation reproduces radiant and speed more accurately than all other methods tested. The ablation properties of meteoroids are commonly found to be the limiting factor in velocity accuracy. We show that the true radiant dispersion of meteor showers can be reliably measured with moderate field of view (or more precise) systems provided appropriate methods of meteor trajectory estimation are employed. Finally, we compare estimated and real angular radiant uncertainty and show that for the solvers tested the real radiant error is on average underestimated by a factor of two. [ABSTRACT FROM AUTHOR]

Many existing optical meteor trajectory estimation methods use the approximation that the velocity of the meteor at the beginning of its luminous phase is equivalent to its velocity before atmospheric entry. Meteoroid kinetic energy loss prior to the luminous phase cannot be measured, but for some masses and entry geometries neglecting this loss may lead to non-negligible deceleration prior to thermal ablation. Using a numerical meteoroid ablation model, we simulate the kinematics of meteoroids beginning at 180 km with initial velocities ranging from 11 km s−1 to 71 km s−1, and compare model velocities at the moment of detection to measurements. We validate the simulations by comparing the simulated luminous beginning heights with observed beginning heights of different populations of meteors detected with different optical systems. We find that most low-velocity meteoroids have a significant velocity difference of 100 m s−1 to 750 m s−1 (depending on meteoroid type, mass, and observation system). This systematic underestimate of meteoroid speeds also results in systematically lower semimajor axes for meteoroid orbits. [ABSTRACT FROM AUTHOR]

Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes. [ABSTRACT FROM AUTHOR]

Dormant comets in the near-Earth object (NEO) population are thought to be involved in the terrestrial accretion of water and organic materials. Identification of dormant comets is difficult as they are observationally indistinguishable from their asteroidal counterparts, however, they may have produced dust during their final active stages which potentially are detectable today as weak meteor showers at the Earth. Here we present the result of a reconnaissance survey looking for dormant comets using 13 567 542 meteor orbits measured by the Canadian Meteor Orbit Radar (CMOR). We simulate the dynamical evolution of the hypothetical meteoroid streams originated from 407 near-Earth asteroids in cometary orbits that resemble orbital characteristics of Jupiter-family comets (JFCs). Out of the 44 hypothetical showers that are predicted to be detectable by CMOR, we identify five positive detections that are statistically unlikely to be chance associations, including three previously known associations. This translates to a lower limit to the dormant comet fraction of 2.0 ± 1.7 per cent in the NEO population and a dormancy rate of ∼10−5 yr−1 per comet. The low dormancy rate confirms disruption and dynamical removal as the dominant end state for near-Earth JFCs. We also predict the existence of a significant number of meteoroid streams whose parents have already been disrupted or dynamically removed. [ABSTRACT FROM AUTHOR]

Motivation: The three dimensional tertiary structure of a protein at near atomic level resolution provides insight alluding to its function and evolution. As protein structure decides its functionality, similarity in structure usually implies similarity in function. As such, structure alignment techniques are often useful in the classifications of protein function. Given the rapidly growing rate of new, experimentally determined structures being made available from repositories such as the Protein Data Bank, fast and accurate computational structure comparison tools are required. This paper presents SPalignNS, a non-sequential protein structure alignment tool using a novel asymmetrical greedy search technique. Results: The performance of SPalignNS was evaluated against existing sequential and nonsequential structure alignment methods by performing trials with commonly used datasets. These benchmark datasets used to gauge alignment accuracy include (i) 9538 pairwise alignments implied by the HOMSTRAD database of homologous proteins; (ii) a subset of 64 difficult alignments from set (i) that have low structure similarity; (iii) 199 pairwise alignments of proteins with similar structure but different topology; and (iv) a subset of 20 pairwise alignments from the RIPC set. SPalignNS is shown to achieve greater alignment accuracy (lower or comparable root-mean squared distance with increased structure overlap coverage) for all datasets, and the highest agreement with reference alignments from the challenging dataset (iv) above, when compared with both sequentially constrained alignments and other non-sequential alignments. [ABSTRACT FROM AUTHOR]

A growing number of supernovae (SNe) are now known to exhibit evidence for significant interaction with a dense, pre-existing, circumstellar medium (CSM). SNe Ibn comprise one such class that can be characterized by both rapidly evolving light curves and persistent narrow He  i lines. The origin of such a dense CSM in these systems remains a pressing question, specifically concerning the progenitor system and mass-loss mechanism. In this paper, we present multiwavelength data of the Type Ibn SN 2020nxt, including HST /STIS ultraviolet spectra. We fit the data with recently updated CMFGEN models designed to handle configurations for SNe Ibn. The UV coverage yields strong constraints on the energetics and, when combined with the CMFGEN models, offer new insight on potential progenitor systems. We find the most successful model is a ≲4 M⊙ helium star that lost its |$\sim 1\, {\rm M}_\odot$| He-rich envelope in the years preceding core collapse. We also consider viable alternatives, such as a He white dwarf merger. Ultimately, we conclude at least some SNe Ibn do not arise from single, massive (>30 M⊙) Wolf–Rayet-like stars. [ABSTRACT FROM AUTHOR]

Meteor showers and their outbursts are the dominant source of meteoroid impact risk to spacecraft on short time-scales. Meteor shower prediction models depend on historical observations to produce accurate forecasts. However, the current lack of quality and persistent world-wide monitoring at optical meteoroid sizes has left some recent major outbursts poorly observed. A novel method of computing meteor shower flux is developed and applied to Global Meteor Network data. The method is verified against previously published observations of the Perseids and the Geminids. The complete mathematical and algorithmic details of computing meteor shower fluxes from video observations are described. As an example application of our approach, the flux measurements of the 2021 Perseid outburst, the 2020–2022 Quadrantids, and 2020–2021 Geminids are presented. The flux of the 2021 Perseids reached similar levels to the 1991–1994 and 2016 outbursts (ZHR ∼ 280). The flux of the Quadrantids shows high year-to-year variability in the core of the stream while the longer lasting background activity is less variable, consistent with an age difference between the two components. The Geminids show a double peak in flux near the time of peak. [ABSTRACT FROM AUTHOR]

This article examines the role of stigma in social and institutional responses to infectious disease emergencies, to better understand and minimize these dynamics in the event of a pandemic of virulent influenza. In addition to their impact on human suffering, fear and stigma can seriously delay detection and treatment efforts, cooperation with contact tracing and isolation measures, and the effective distribution of resources for the prevention and control of infectious diseases. These dynamics are illustrated by the Indian plague epidemic of 1994, which occurred in a region where H5N1 influenza has been detected recently. Public fear and stigma also played a significant role in the social and institutional responses to the 1918 influenza pandemic. These historical models provide important lessons for pandemic preparedness and global health policy. [ABSTRACT FROM AUTHOR]

Well-known examples of high-amplitude, large-scale fluctuations of small-mammal populations include vole cycles in the boreal zone of Eurasia, lemming cycles in the high-arctic tundra of Eurasia and North America, snowshoe hare cycles in the boreal zone of North America, and outbreaks of house mice in southeastern Australia. We synthesize the recent knowledge of three key aspects of these animals' population cycles: (1) periodicity, amplitude, and asphaltite synchrony; (2) reproduction and survival; and (3) underlying mechanisms. Survival rather than reproductive rate appears to drive rates of population increase during these fluctuations. Food limitation may stop increases of cyclic vole; lemming, and hare populations, whereas the decline from peak numbers is caused by predation mortality. In house mice, without coevolved predators, outbreaks may he driven by rainfall, food supply, and disease. [ABSTRACT FROM AUTHOR]

Physical properties of ten millimetre-sized meteoroids from the Southern Delta Aquariids (SDA) shower are derived using optical observations from the Canadian Automated Meteor Observatory between 2020 and 2023. The meteors are found to ablate in two distinct erosion stages, the second stage showing a single, bright leading fragment. Our modelling interprets these observations as evidence for equal masses of compact grains embedded in a porous, low density matrix. The average bulk density of SDA meteors is found to be 1420 ± 100   |$\rm {kg \ m^{-3}}$|⁠ , with the compact component having a density of 2310 ± 160 |$\rm {kg \ m^{-3}}$| and the porous component a density of 700 ± 110   |$\rm {kg \ m^{-3}}$|⁠. The high bulk density of SDA meteors is comparable to densities found for the Quadrantid and Geminid showers, both of which also have low perihelion distances. This suggests that thermal desorption may play a significant role in the processing of meteoroids. [ABSTRACT FROM AUTHOR]

Database(2019)Vol.2019:articleIDbaz085; doi:10.1093/database/baz085 This manuscript has been updated in order to amended incorrect affiliation indices for several authors. (pagenumbernotforcitationpurposes) Database,2020,1-1 doi: 10.1093/database/baz138 Erratum Erratum Large expert-curated database for benchmarking document similarity detection in biomedical literature search Peter Brown 1,RELISH Consortium 3 and Yaoqi Zhou 1,2, * 1 School of Information and Communication Technology, Griffith University, Gold Coast, QLD 4222, Australia, 2 InstituteforGlycomics,GriffithUniversity,GoldCoast,QLD4222,Australiaand 3 See collaboratorssection *Correspondingauthor:Tel.:+61755528228;Fax:+61755529040;Email:yaoqi.zhou@griffith.edu.au Citationdetails:Brown,P.,RELISHConsortium,Zhou,Y.Largeexpert-curateddatabaseforbenchmarkingdocument similaritydetectioninbiomedicalliteraturesearch. [Extracted from the article]

We present photometric and spectroscopic observations and analysis of SN 2021bxu (ATLAS21dov), a low-luminosity, fast-evolving Type IIb supernova (SN). SN 2021bxu is unique, showing a large initial decline in brightness followed by a short plateau phase. With |$M_r = -15.93 \pm 0.16\, \mathrm{mag}$| during the plateau, it is at the lower end of the luminosity distribution of stripped-envelope supernovae (SE-SNe) and shows a distinct ∼10 d plateau not caused by H- or He-recombination. SN 2021bxu shows line velocities which are at least |$\sim 1500\, \mathrm{km\, s^{-1}}$| slower than typical SE-SNe. It is photometrically and spectroscopically similar to Type IIb SNe during the photospheric phases of evolution, with similarities to Ca-rich IIb SNe. We find that the bolometric light curve is best described by a composite model of shock interaction between the ejecta and an envelope of extended material, combined with a typical SN IIb powered by the radioactive decay of 56Ni. The best-fitting parameters for SN 2021bxu include a 56Ni mass of |$M_{\mathrm{Ni}} = 0.029^{+0.004}_{-0.005}\, \mathrm{{\rm M}_{\odot }}$|⁠ , an ejecta mass of |$M_{\mathrm{ej}} = 0.61^{+0.06}_{-0.05}\, \mathrm{{\rm M}_{\odot }}$|⁠ , and an ejecta kinetic energy of |$K_{\mathrm{ej}} = 8.8^{+1.1}_{-1.0} \times 10^{49}\, \mathrm{erg}$|⁠. From the fits to the properties of the extended material of Ca-rich IIb SNe we find a trend of decreasing envelope radius with increasing envelope mass. SN 2021bxu has M Ni on the low end compared to SE-SNe and Ca-rich SNe in the literature, demonstrating that SN 2021bxu-like events are rare explosions in extreme areas of parameter space. The progenitor of SN 2021bxu is likely a low-mass He star with an extended envelope. [ABSTRACT FROM AUTHOR]

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RE levant LI terature S earc H consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. [ABSTRACT FROM AUTHOR]

It has recently been shown by Egal et al. that some types of existing meteor in-atmosphere trajectory estimation methods may be less accurate than others, particularly when applied to high-precision optical measurements. The comparative performance of trajectory solution methods has previously only been examined for a small number of cases. Besides the radiant, orbital accuracy depends on the estimation of pre-atmosphere velocities, which have both random and systematic biases. Thus, it is critical to understand the uncertainty in velocity measurement inherent to each trajectory estimation method. In this first of a series of two papers, we introduce a novel meteor trajectory estimation method that uses the observed dynamics of meteors across stations as a global optimization function and that does not require either a theoretical or an empirical flight model to solve for velocity. We also develop a 3D observational meteor trajectory simulator that uses a meteor ablation model to replicate the dynamics of meteoroid flight, as a means to validate different trajectory solvers. We both test this new method and compare it to other methods, using synthetic meteors from three major showers spanning a wide range of velocities and geometries (Draconids, Geminids, and Perseids). We determine which meteor trajectory solving algorithm performs better for all-sky, moderate field-of-view, and high-precision narrow-field optical meteor detection systems. The results are presented in the second paper in this series. Finally, we give detailed equations for estimating meteor trajectories and analytically computing meteoroid orbits, and provide the python code of the methodology as open-source software. [ABSTRACT FROM AUTHOR]

In June 2019 the Earth will approach within 5° mean anomaly of the centre of the Taurid resonant swarm, its closest post-perihelion encounter with Earth since 1975. This will be the best viewing geometry to detect and place limits on the number of NEOs proposed to reside at the swarm centre until the early 2030s. We present an analysis of the optimal times and pointing locations to image NEOs associated with the swarm. [ABSTRACT FROM AUTHOR]

The article discusses the study which aims to examine information loss associated with the use of categorical density scales. It states that the categorization of the percent mammographic density (PMD) measures into categorical density scales resulted to significant information loss. It also states that risk models of breast cancer using categorical mammographic density scales perform more poorly than the continuous PMD measures.

Aims Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate and alter the function of a variety of proteins in vitro ; however, its function in the heart is poorly understood. The present study investigates the role of SETD7 in myocardial ischaemic injury. Methods and results Experiments were performed in neonatal rat ventricular myocytes (NRVMs), SETD7 knockout mice (SETD7−/−) undergoing myocardial ischaemia/reperfusion (I/R) injury, left ventricular (LV) myocardial samples from patients with ischaemic cardiomyopathy (ICM), and peripheral blood mononuclear cells (PBMCs) from patients with ST-elevation MI (STEMI). We show that SETD7 is activated upon energy deprivation in cultured NRVMs and methylates the Hippo pathway effector YAP, leading to its cytosolic retention and impaired transcription of antioxidant genes manganese superoxide dismutase (MnSOD) and catalase (CAT). Such impairment of antioxidant defence was associated with mitochondrial reactive oxygen species (mtROS), organelle swelling, and apoptosis. Selective pharmacological inhibition of SETD7 by (R) -PFI-2 restored YAP nuclear localization, thus preventing mtROS, mitochondrial damage, and apoptosis in NRVMs. In mice, genetic deletion of SETD7 attenuated myocardial I/R injury, mtROS, and LV dysfunction by restoring YAP-dependent transcription of MnSOD and CAT. Moreover, in cardiomyocytes isolated from I/R mice and ICM patients, (R) -PFI-2 prevented mtROS accumulation, while improving Ca2+-activated tension. Finally, SETD7 was up-regulated in PBMCs from STEMI patients and negatively correlated with MnSOD and CAT. Conclusion We show a methylation-dependent checkpoint regulating oxidative stress during myocardial ischaemia. SETD7 inhibition may represent a valid therapeutic strategy in this setting. [ABSTRACT FROM AUTHOR]

Early-time radiative signals from Type Ia supernovae (SNe Ia) can provide important constraints on the explosion mechanism and the progenitor system. We present observations and analysis of SN 2019np, a nearby SN Ia discovered within 1–2 days after the explosion. Follow-up observations were conducted in optical, ultraviolet, and near-infrared bands, covering the phases from ∼−16.7 d to ∼+ 367.8 d relative to its B -band peak luminosity. The photometric and spectral evolutions of SN 2019np resemble the average behaviour of normal SNe Ia. The absolute B -band peak magnitude and the post-peak decline rate are M max(B) = −19.52 ± 0.47 mag and Δ m 15(B) = 1.04 ± 0.04 mag, respectively. No Hydrogen line has been detected in the nebular-phase spectra of SN 2019np. Assuming that the 56Ni powering the light curve is centrally located, we find that the bolometric light curve of SN 2019np shows a flux excess up to 5.0 per cent in the early phase compared to the radiative diffusion model. Such an extra radiation perhaps suggests the presence of an additional energy source beyond the radioactive decay of central nickel. Comparing the observed colour evolution with that predicted by different models, such as interactions of SN ejecta with circumstellar matter (CSM)/companion star, a double-detonation explosion from a sub-Chandrasekhar mass white dwarf (WD) and surface 56Ni mixing, we propose that the nickel mixing is more favoured for SN 2019np. [ABSTRACT FROM AUTHOR]

Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance-related pathological circuit interactions. [ABSTRACT FROM AUTHOR]

Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson's disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson's disease, and that together these different states predict motor impairment with high fidelity. Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz. Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients' hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone. We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems. [ABSTRACT FROM AUTHOR]

The Global Meteor Network (GMN) utilizes highly sensitive low-cost CMOS video cameras which run open-source meteor detection software on Raspberry Pi computers. Currently, over 450 GMN cameras in 30 countries are deployed. The main goal of the network is to provide long-term characterization of the radiants, flux, and size distribution of annual meteor showers and outbursts in the optical meteor mass range. The rapid 24-h publication cycle the orbital data will enhance the public situational awareness of the near-Earth meteoroid environment. The GMN also aims to increase the number of instrumentally observed meteorite falls and the transparency of data reduction methods. A novel astrometry calibration method is presented which allows decoupling of the camera pointing from the distortion, and is used for frequent pointing calibrations through the night. Using wide-field cameras (88° × 48°) with a limiting stellar magnitude of +6.0 ± 0.5 at 25 frames per second, over 220 000 precise meteoroid orbits were collected since 2018 December until 2021 June. The median radiant precision of all computed trajectories is 0.47°, 0.32° for |$\sim 20{{\ \rm per\ cent}}$| of meteors which were observed from 4 + stations, a precision sufficient to measure physical dispersions of meteor showers. All non-daytime annual established meteor showers were observed during that time, including five outbursts. An analysis of a meteorite-dropping fireball is presented which showed visible wake, fragmentation details, and several discernible fragments. It had spatial trajectory fit errors of only ∼40 m, which translated into the estimated radiant and velocity errors of 3 arcmin and tens of meters per second. [ABSTRACT FROM AUTHOR]

Tracking wood formation in semiarid regions during the seasonal march of precipitation extremes has two important applications. It can provide (i) insight into the adaptive capacities of trees to drought and (ii) a basis for a richer interpretation of tree-ring data, assisting in a deeper understanding of past and current climate. In the southwestern USA, the anatomical signature of seasonally bimodal precipitation is the 'false ring'—a band of latewood-like cells in the earlywood. These occur when a particularly deep drought during the early growing season ends abruptly with timely, mid-growing season monsoonal rains. Such conditions presented in southern Arizona in 2014, enabling us to explore false-ring formation in ponderosa pine (Pinus ponderosa Lawson and C. Lawson) and Douglas-fir (Pseudotsuga menziesii Mirb. Franco) in mixed-conifer forest at 2573 m above sea level. We ask: what were the cell-by-cell timings and durations in the phases of wood cell development in 2014? How do these seasonal patterns relate to strongly fluctuating environmental conditions during the growing season? We took weekly microcores from March through November from six ponderosa pine and seven Douglas-fir trees at a well-instrumented flux tower site. Thin sections were prepared, and we counted cells in cambial, expansion, cell wall thickening and mature phases. For ponderosa pine trees forming a false ring, the first impact of intensifying seasonal drought was seen in the enlarging phase and then, almost a month later, in cambial activity. In this species, recovery from drought was associated with recovery first in cambial activity, followed by cell enlargement. This timing raised the possibility that cell division may be affected by atmospheric moisture increases before soil recharge. In both species, the last false-ring cells matured during the summer rainy season. Bimodal cambial activity coincident with moisture availability was observed in both species, whether or not they formed a false ring. This deeper knowledge of the precise timing of both developmental and environmental events should help define mechanistic connections among these factors in creating bimodal growth patterns. [ABSTRACT FROM AUTHOR]

We present optical and ultraviolet photometry, as well as optical spectra, for the type II supernova (SN) 2015bf. Our observations cover the phases from ∼2 to ∼200 d after explosion. The first spectrum is characterized by a blue continuum with a blackbody temperature of ∼24 000 K and flash-ionized emission lines. After about 1 week, the spectra of SN 2015bf evolve like those of a regular SN II. From the luminosity of the narrow emission component of H α, we deduce that the mass-loss rate is larger than |${\sim}3.7\times 10^{-3}\, {\rm M_\odot \, yr^{-1}}$|⁠. The disappearance of the flash features in the first week after explosion indicates that the circumstellar material is confined within ∼6 × 1014 cm. Thus, we suggest that the progenitor of SN 2015bf experienced violent mass loss shortly before the supernova explosion. The multiband light curves show that SN 2015bf has a high peak luminosity with an absolute visual magnitude MV  = −18.11 ± 0.08 mag and a fast post-peak decline with a V -band decay of 1.22 ± 0.09 mag within ∼50 d after maximum light. Moreover, the R -band tail luminosity of SN 2015bf is fainter than that of SNe II with similar peak by 1–2 mag, suggesting a small amount of 56Ni (⁠|${\sim}0.009\, {\rm M_\odot }$|⁠) synthesized during the explosion. Such a low nickel mass indicates that the progenitor of SN 2015bf could be a super-asymptotic-giant-branch star that collapsed owing to electron capture. [ABSTRACT FROM AUTHOR]

Pain is a frequent and poorly treated symptom of Parkinson's disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson's disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with pain processing in Parkinson's disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception and processing in Parkinson's disease. To explore this, we discuss data from human neurophysiological and psychophysical investigations. We review studies demonstrating the clinical efficacy of deep brain stimulation of the subthalamic nucleus for pain relief in Parkinson's disease. Finally, we present some of the key insights from investigations in animal models, healthy humans and Parkinson's disease patients into the aberrant neurobiology of pain processing and consider their implications for the pain-relieving effects of subthalamic nucleus neuromodulation. The evidence from clinical and experimental studies supports the hypothesis that altered central processing is critical for pain generation in Parkinson's disease and that the subthalamic nucleus is a key structure in pain perception and modulation. Future preclinical and clinical research should consider the subthalamic nucleus as an entry point to modulate different types of pain, not only in Parkinson's disease but also in other neurological conditions associated with abnormal pain processing. [ABSTRACT FROM AUTHOR]

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography with the spatial resolution of MRI tractography to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing deep brain stimulation of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: (i) a beta band network to supplementary motor area, where activity in this region was found to drive activity in the NBM; (ii) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus; and (iii) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function, respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype. [ABSTRACT FROM AUTHOR]

We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from ∼5 d before maximum light [ t max(B) on |$58707.8$| MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 × 1042 erg s−1 and indicates that only 0.031 M⊙ of 56Ni was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of |$M_\rm {V} = -16.4$| mag. The estimated date of explosion is t 0 = |$58698.2$| MJD and implies a short rise time of t rise = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code tardis. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax. [ABSTRACT FROM AUTHOR]

A search for metre-sized and larger exo-atmosphere Perseid meteoroids via their surface reflected sunlight has been made with the 1.2-m Elginfield Telescope. A total survey time of 9.66 h was accumulated during the nights of 2002 August 10, 11 and 12. To a limiting apparent magnitude of +17, we made no distinct detection of any large exo-atmosphere Perseid meteoroids. Our telescopic survey results constrain the upper limit to the spatial number density of metre-sized and larger Perseid meteoroids to be less than per 109 km3. We have also analysed a data set of possible in-atmosphere Perseid fireball events detected by space-based optical and infrared sensors. Operating at a detection threshold of magnitude −17, the space-based sensors have detected eight possible Perseid fireballs in the 15-d window, centred on the time of shower maximum, over the cumulative time interval from 1978 August to 2000 August. The space-based sensor data yield a spatial number density of per 109 km3 for metre-sized and larger Perseid meteoroids. [ABSTRACT FROM AUTHOR]

The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson's disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-frequency interactions with gamma oscillations in a cortico-subcortical network of interconnected regions and normalizes the balance between beta and gamma oscillations. To this end we acquired resting state high-density (256 channels) EEG from 31 patients with Parkinson's disease who underwent deep brain stimulation to compare spectral power and power-to-power cross-frequency coupling using a beamformer algorithm for coherent sources. To show that modulations exclusively relate to stimulation frequencies that alleviate motor symptoms, two clinically ineffective frequencies were tested as control conditions. We observed a robust reduction of beta and increase of gamma power, attested in the regions of a cortical (motor cortex, supplementary motor area, premotor cortex) and subcortical network (subthalamic nucleus and cerebellum). Additionally, we found a clear cross-frequency coupling of narrowband gamma frequencies to the stimulation frequency in all of these nodes, which negatively correlated with motor impairment. No such dynamics were revealed within the control posterior parietal cortex region. Furthermore, deep brain stimulation at clinically ineffective frequencies did not alter the source power spectra or cross-frequency coupling in any region. These findings demonstrate that clinically effective deep brain stimulation of the subthalamic nucleus differentially modifies different oscillatory activities in a widespread network of cortical and subcortical regions. Particularly the cross-frequency interactions between finely tuned gamma oscillations and the stimulation frequency may suggest an entrainment mechanism that could promote dynamic neural processing underlying motor symptom alleviation. [ABSTRACT FROM AUTHOR]

The Type Ia supernovae (SNe Ia) 2011by, hosted in NGC 3972, and 2011fe, hosted in M101, are optical 'twins,' having almost identical optical light-curve shapes, colours, and near-maximum-brightness spectra. However, SN 2011fe had significantly more ultraviolet (UV; 1600 < λ < 2500 Å) flux than SN 2011by before and at peak luminosity. Several theoretical models predict that SNe Ia with higher progenitor metallicity should (1) have additional UV opacity and thus lower UV flux; (2) have an essentially unchanged optical spectral-energy distribution; (3) have a similar optical light-curve shape; and (4) because of the excess neutrons, produce more stable Fe-group elements at the expense of radioactive 56Ni and thus have a lower peak luminosity. Following these predictions, Foley and Kirshner suggested that the difference in UV flux between SNe 2011by and 2011fe was the result of their progenitors having significantly different metallicities. They also measured a large, but insignificant, difference between the peak absolute magnitudes of the SNe (Δ M V, peak = 0.60 ± 0.36 mag), with SN 2011fe being more luminous. We present a new Cepheid-based distance to NGC 3972, substantially improving the precision of the distance measurement for SN 2011by. With these new data, we determine that the SNe have significantly different peak luminosities (Δ M V, peak = 0.335 ± 0.069 mag). Consequently, SN 2011fe produced 38 per cent more 56Ni than SN 2011by, consistent with predictions for progenitor metallicity differences for these SNe, although alternative models may also explain this difference. We discuss how progenitor metallicity differences can contribute to the intrinsic scatter for light-curve-shape-corrected SN luminosities, the use of 'twin' SNe for measuring distances, and implications for using SNe Ia for constraining cosmological parameters. [ABSTRACT FROM AUTHOR]

Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson's disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson's disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications. [ABSTRACT FROM AUTHOR]

The bright transient AT2018cow has been unlike any other known type of transient. Its high brightness, rapid rise and decay, and initially nearly featureless spectrum are unprecedented and difficult to explain using models for similar burst sources. We present evidence for faint γ-ray emission continuing for at least 8 d, and featureless spectra in the ultraviolet bands – both unusual for eruptive sources. The X-ray variability of the source has a burst-like character. The UV-optical spectrum does not show any CNO line but is well described by a blackbody. We demonstrate that a model invoking the tidal disruption of a |$0.1\!-\!0.4\, \mathrm{M}_\odot$| helium white dwarf (WD) by a |$10^5\!-\!10^6\, \mathrm{M}_\odot$| black hole located in the outskirts of galaxy Z 137-068 could provide an explanation for most of the characteristics shown in the multiwavelength observations. A blackbody-like emission is emitted from an opaque photosphere, formed by the debris of the WD disruption. Broad features showing up in the optical/infrared spectra in the early stage are probably velocity broadened lines produced in a transient high-velocity outward moving cocoon. The asymmetric optical/infrared lines that appeared at a later stage are emission from an atmospheric layer when it detached from thermal equilibrium with the photosphere, which undergoes more rapid cooling. The photosphere shrinks when its temperature drops, and the subsequent infall of the atmosphere produced asymmetric line profiles. Additionally, a non-thermal jet might be present, emitting X-rays in the 10–150 keV band. [ABSTRACT FROM AUTHOR]

There is increasing evidence that the medial prefrontal cortex participates in conflict and feedback monitoring while the subthalamic nucleus adjusts actions. Yet how these two structures coordinate their activity during cognitive control remains poorly understood. We recorded from the human prefrontal cortex and the subthalamic nucleus simultaneously while participants (n = 22) performed a novel task involving high conflict trials, complete response inhibition trials, and trial-to-trial behavioural adaptations to conflict and errors. Overall, we found that within-trial adaptions to both conflict and complete response inhibition involved changes in the theta band while across-trial behavioural adaptations to both conflict and errors involved changes in the beta band (P < 0.05). Yet the role each region's theta and beta oscillations played during the task differed significantly between the two sites. Trials that involved either within-trial conflict or complete response inhibition were associated with increased theta phase synchrony between the medial prefrontal cortex and the subthalamic nucleus (P < 0.05). Despite increased synchrony, however, increases in prefrontal theta power were associated with response inhibition, while increases in subthalamic theta power were associated with response execution (P < 0.05). In the beta band, post-response increases in prefrontal beta power were suppressed when the completed trial contained either conflict or an erroneous response (P < 0.05). Subthalamic beta power, on the other hand, was only modified during the subsequent trial that followed a conflict or error trial. Notably, these adaptation trials exhibited slower response times (P < 0.05), suggesting that both brain regions contribute to across-trial adaptations but do so at different stages of the adaptation process. Taken together, our data shed light on the mechanisms underlying within-trial and across-trial cognitive control and how disruption of this network can negatively impact cognition. More broadly, however, our data also demonstrate that the specific role of a brain region, rather than the frequency being utilized, governs the behavioural correlates of oscillatory activity. [ABSTRACT FROM AUTHOR]

Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation. [ABSTRACT FROM AUTHOR]

The bulk density of a meteoroid affects its dynamics in space, its ablation in the atmosphere, and the damage it does to spacecraft and lunar or planetary surfaces. Meteoroid bulk densities are also notoriously difficult to measure, and we are typically forced to assume a density or attempt to measure it via a proxy. In this paper, we construct a density distribution for sporadic meteoroids based on existing density measurements. We considered two possible proxies for density: the KB parameter introduced by Ceplecha and Tisserand parameter, TJ. Although KB is frequently cited as a proxy for meteoroid material properties, we find that it is poorly correlated with ablation-model-derived densities.We therefore followthe example of Kikwaya et al. in associating density with the Tisserand parameter. We fit two density distributions to meteoroids originating from Halley-type comets (TJ < 2) and those originating from all other parent bodies (TJ > 2); the resulting two-population density distribution is the most detailed sporadic meteoroid density distribution justified by the available data. Finally, we discuss the implications for meteoroid environment models and spacecraft risk assessments. We find that correcting for density increases the fraction of meteoroid-induced spacecraft damage produced by the helion/\antihelion source. [ABSTRACT FROM AUTHOR]

We present the results of an extensive observational campaign on the nearby Type Ibn SN 2015G, including data from radio through ultravioletwavelengths. SN2015Gwas asymmetric, showing late-time nebular lines redshifted by ~1000 km s-1. It shared many features with the prototypical SN Ibn 2006jc, including extremely strong He I emission lines and a late-time blue pseudo-continuum. The young SN 2015G showed narrow P-Cygni profiles of He I, but never in its evolution did it showany signature of hydrogen - arguing for a dense, ionized and hydrogenfree circumstellar medium moving outward with a velocity of ~1000 km s-1 and created by relatively recent mass-loss from the progenitor star. Ultraviolet through infrared observations show that the fading SN 2015G (which was probably discovered some 20 d post-peak) had a spectral energy distribution that was well described by a simple, single-component blackbody. Archival HST images provide upper limits on the luminosity of SN 2015G's progenitor, while non-detections of any luminous radio afterglow and optical non-detections of outbursts over the past two decades provide constraints upon its mass-loss history. [ABSTRACT FROM AUTHOR]

Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and interhemispheric synchronization. This may compromise information coding capacity and thereby motor processing. Dopaminergic activity limits this uncontrolled beta synchronization by terminating long duration beta bursts, with positive consequences on network state and motor symptoms. [ABSTRACT FROM AUTHOR]

See Vidailhet et al. (doi:10.1093/brain/awx140) for a scientific commentary on this article. Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the tremor stability index, which can discriminate Parkinson’s disease tremor and essential tremor with high diagnostic accuracy. The tremor stability index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson’s disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 55 tremulous Parkinson’s disease and essential tremor recordings. Clinical diagnosis was used as gold standard. One hundred seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression and by receiver operating characteristic analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the receiver operating characteristic curve, and by cross-validation. Tremor stability index with a cut-off of 1.05 gave good classification performance for Parkinson’s disease tremor and essential tremor, in both test and validation datasets. Tremor stability index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. Receiver operating characteristic analysis showed an area under the curve of 0.916 (95% confidence interval 0.797–1.000) for the test dataset and a value of 0.855 (95% confidence interval 0.754–0.957) for the validation dataset. Classification accuracy proved independent of recording device and posture. The tremor stability index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and non-invasive tremor recordings, and is independent of operator or postural context in its interpretation. [ABSTRACT FROM AUTHOR]

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered. [ABSTRACT FROM AUTHOR]

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. [ABSTRACT FROM AUTHOR]

Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost. [ABSTRACT FROM AUTHOR]

Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. [ABSTRACT FROM AUTHOR]

Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6-20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL. [ABSTRACT FROM AUTHOR]

We present observations of SN Hunt 248, a new supernova (SN) impostor in NGC 5806, which began a multistage outburst in 2014 May. The '2014a' discovery brightening exhibited an absolute magnitude of M ≈ - 12 and the spectral characteristics of a cool, dense outflow, including P Cygni lines of FeII, HI, and NaI, and line blanketing from metals. The source rapidly climbed and peaked at M ≈ 15 mag after two additional weeks. During this bright '2014b' phase the spectrum became dominated by Balmer emission and a stronger blue continuum, similar to the SN impostor SN 1997bs. Archival images from the Hubble Space Telescope between 1997 and 2005 reveal a luminous (4 x 105 L⊙) variable precursor star. Its location on the Hertzsprung-Russell diagram is consistent with a massive (Minit ≈ 30 M⊙) cool hypergiant having an extremely dense wind and an Eddington ratio (Γ) just below unity. At the onset of the 2014a brightening, however, the object was super-Eddington (Γ = 4-12). The subsequent boost in luminosity during the 2014b phase probably resulted from circumstellar interaction. SN Hunt 248 provides the first case of a cool hypergiant undergoing a giant eruption reminiscent of outbursts from luminous blue variable stars (LBVs). This lends support to the hypothesis that some cool hypergiants, such as ρ Cas, could be LBVs masquerading under a pseudo-photosphere created by their extremely dense winds. Moreover, SN Hunt 248 demonstrates that eruptions stemming from such stars can rival in peak luminosity the giant outbursts of much more massive systems like η Car. [ABSTRACT FROM AUTHOR]