The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the inferior frontal gyrus and ...subthalamic nucleus is hypothesized to mediate movement inhibition, but there is limited evidence for this in humans. We recorded high spatial and temporal resolution field potentials from both the inferior frontal gyrus and subthalamic nucleus in 21 subjects. Cortical potentials evoked by subthalamic stimulation revealed short latency events indicative of monosynaptic connectivity between the inferior frontal gyrus and ventral subthalamic nucleus. During a stop signal task, stopping-related potentials in the cortex preceded stopping-related activity in the subthalamic nucleus, and synchronization between these task-evoked potentials predicted the stop signal reaction time. Thus, we show that a prefrontal-subthalamic hyperdirect pathway is present in humans and mediates rapid stopping. These findings may inform therapies to treat disorders featuring perturbed movement inhibition.
•Demonstration of a monosynaptic, prefrontal hyperdirect pathway in humans•Fastest fibers between the inferior frontal gyrus and ventral subthalamic nucleus•Stopping elicits co-activation of the origin and target of this pathway•Degree of co-activation predicts stopping speed
Chen et al. identify a fast, non-stop pathway between the prefrontal cortex and subthalamic nucleus in humans using multisite invasive brain recordings. This pathway is critically involved in the stopping of ongoing actions. Modulation of this pathway may be a means of treating disorders of inhibitory control, such as impulsivity.
The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases
, including steroid-resistant acute graft versus host disease (SR-aGvHD)
. ...However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes
. Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation
. Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 10
cells per kg body weight, to a maximum of 1 × 10
cells per infusion (cohort A), or 2 × 10
cells per kg body weight, to a maximum dose of 2 × 10
cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.
We present the results of a deep, wide-area variability survey in the Southern hemisphere, the first of its kind. As part of the Catalina Sky Surveys, the Siding Spring Survey (SSS) has covered ...14,800 deg2 in the declination range of ... To mine the enormous SSS data set efficiently, we have developed two algorithms: automatic period selection (APS) and automatic Fourier decomposition (AFD), which aim to sharpen the period estimation and produce robust light-curve models. Armed with the APS and AFD outputs, we classify 10,540 ab-type RR Lyrae (RRab) stars (~90 per cent of which are new) across the southern sky. As well as the positional information we supply photometric metallicities, and unreddened distances. For the RRab stars in the halo, a study of the photometric metallicity distribution reveals a nearly Gaussian shape with a mean metallicity of Fe/H = -1.4 dex and a dispersion of 0.3 dex. A spatial study of the RRab metallicities shows no significant radial gradient in the first ~7 kpc from the Galaxy centre. However, further out, a small negative gradient is clearly present. This is complemented by a very obvious correlation of the mean RR Lyrae metallicity with distance above the Galactic plane, z. We have also carried out an initial sub-structure search using the discovered RRab, and present the properties of the candidates with significance greater than 2... Most prominent among these is a southern extension of the Sagittarius dwarf galaxy's stream system, reaching down to declinations ... (ProQuest: ... denotes formulae/symbols omitted.)
Extent health humanities readings of Gabriel García Márquez’s
Love in the Time of Cholera
have focused on the doctor-patient relationship, the physician-scientist as a model for aspiring ...practitioners, and how individuals relate to the novel’s health themes of death, disease, and disability. However, such medicine-focused readings neglect the population-level public health concerns of the novel as they relate to contagion, community, and quarantine. This paper contributes to the growing field of public health humanities by using a close reading method to explore how the competing endemic and epidemic public health issues shape the plot and metaphors of the novel.
We report on the results from the first six months of the Catalina Real-Time Transient Survey (CRTS). In order to search for optical transients (OTs) with timescales of minutes to years, the CRTS ...analyses data from the Catalina Sky Survey which repeatedly covers 26,000 of square degrees on the sky. The CRTS provides a public stream of transients that are bright enough to be followed up using small telescopes. Since the beginning of the survey, all CRTS transients have been made available to astronomers around the world in real time using HTML tables,RSS feeds, and VOEvents. As part of our public outreach program, the detections are now also available in Keyhole Markup Language through Google Sky. The initial discoveries include over 350 unique OTs rising more than 2 mag from past measurements. Sixty two of these are classified as supernovae (SNe), based on light curves, prior deep imaging and spectroscopic data. Seventy seven are due to cataclysmic variables (CVs; only 13 previously known), while an additional 100 transients were too infrequently sampled to distinguish between faint CVs and SNe. The remaining OTs include active galactic nucleus, blazars, high-proper-motions stars, highly variable stars (such as UV Ceti stars), and transients of an unknown nature. Our results suggest that there is a large population of SNe missed by many current SN surveys because of selection biases. These objects appear to be associated with faint host galaxies. We also discuss the unexpected discovery of white dwarf binary systems through dramatic eclipses.
Abstract
Here, we present the results from our analysis of 6 yr of optical photometry taken by the Siding Spring Survey (SSS). This completes a search for periodic variable stars within the 30 000 ...deg2 of the sky covered by the Catalina Surveys. The current analysis covers 81 million sources with declinations between −20° and −75° with median magnitudes in the range 11 < V < 19.5. We find approximately 34 000 new periodic variable stars in addition to the ∼9000 RR Lyrae that we previously discovered in SSS data. This brings the total number of periodic variables identified in Catalina data to ∼110 000. The new SSS periodic variable stars mainly consist of eclipsing binaries, RR Lyrae, LPVs, RS CVn stars, δ Scutis, and Anomalous Cepheids. By cross-matching these variable stars with those from prior surveys, we find that ∼90 per cent of the sources are new discoveries and recover ∼95 per cent of the known periodic variables in the survey region. For the known sources, we find excellent agreement between our catalogue and prior values of luminosity, period, and amplitude. However, we find many variable stars that had previously been misclassified. Examining the distribution of RR Lyrae, we find a population associated with the Large Magellanic Cloud (LMC) that extends more than 20° from its centre confirming recent evidence for the existence of a very extended stellar halo in the LMC. By combining SSS photometry with Dark Energy Survey data, we identify additional LMC halo RR Lyrae, thus confirming the significance of the population.
•A modified transient hot-wire needle probe is investigated as a technique for measuring thermophysical properties of a variety of liquids.•Seven liquids are selected for study, whose thermal ...conductivities, corrosive potential, and electrical conductivities vary substantially.•Temperature-dependent correlations are developed for all measurements with uncertainty being quantified.
Many power generation processes feature some type of working fluid that plays a critical role in the transfer of heat throughout the system. To optimize thermal efficiencies, an accurate characterization of the temperature-dependent thermal conductivity of the fluid is needed. This study develops a time-domain Modified Transient Hot-wire Needle Probe to overcome phenomena that have impaired traditional measurement techniques when the fluid is both corrosive and at an elevated temperature. First, the physical design of the instrument is presented to demonstrate features that limit interference from corrosion, electrical conduction, and convective and radiative heat transfer. Next, a governing equation for 1D (radial) heat conduction is fully developed using the thermal quadrupoles technique. A finite-element study is performed for validation. A sensitivity analysis is done to assess the time-dependent influence of critical parameters in the governing equation for several samples. Finally, thermal conductivity measurements are presented for seven different liquid substances by fitting the thermal model to experimental data across a range of temperatures. Reference correlations are included for comparison. The sample thermal conductivity and ambient temperature of the experimental conditions range from 0.125–16.5WmK and 10–400∘C, respectively. The total uncertainty, comprised of both the experimental design and fitting process, of all measurements is quantified.
Abstract Introduction Deep brain stimulation (DBS) is an established therapy for movement disorders, and is under active investigation for other neurologic and psychiatric indications. While many ...studies describe outcomes and complications related to stimulation therapies, the majority of these are from large academic centers, and results may differ from those in general neurosurgical practice. Methods Using data from both the Centers for Medicare and Medicaid Services (CMS) and the National Surgical Quality Improvement Program (NSQIP), we identified all DBS procedures related to primary placement, revision, or removal of intracranial electrodes. Cases of cortical stimulation and stimulation for epilepsy were excluded. Results Over 28,000 cases of DBS electrode placement, revision, and removal were identified during the years 2004–2013. In the Medicare dataset, 15.2% and of these procedures were for intracranial electrode revision or removal, compared to 34.0% in the NSQIP dataset. In NSQIP, significant predictors of revision and removal were decreased age (odds ratio (OR) of 0.96; 95% CI: 0.94, 0.98) and higher ASA classification (OR 2.41; 95% CI: 1.22, 4.75). Up to 48.5% of revisions may have been due to improper targeting or lack of therapeutic effect. Conclusion Data from the multiple North American databases suggest that intracranial neurostimulation therapies have a rate of revision and removal higher than previously reported, between 15.2 and 34.0%. While there are many limitations to registry-based studies, there is a clear need to better track and understand the true prevalence and nature of such failures as they occur in the wider surgical community.
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