706 research outputs found

    The Tevatron at the Frontier of Dark Matter Direct Detection

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    Direct detection of dark matter (DM) requires an interaction of dark matter particles with nucleons. The same interaction can lead to dark matter pair production at a hadron collider, and with the addition of initial state radiation this may lead to mono-jet signals. Mono-jet searches at the Tevatron can thus place limits on DM direct detection rates. We study these bounds both in the case where there is a contact interaction between DM and the standard model and where there is a mediator kinematically accessible at the Tevatron. We find that in many cases the Tevatron provides the current best limit, particularly for light dark matter, below 5 GeV, and for spin dependent interactions. Non-standard dark matter candidates are also constrained. The introduction of a light mediator significantly weakens the collider bound. A direct detection discovery that is in apparent conflict with mono-jet limits will thus point to a new light state coupling the standard model to the dark sector. Mono-jet searches with more luminosity and including the spectrum shape in the analysis can improve the constraints on DM-nucleon scattering cross section.Comment: 20 pages, 8 figures, final version in JHE

    Neuronal antibodies in pediatric epilepsy:Clinical features and long-term outcomes of a historical cohort not treated with immunotherapy

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    OBJECTIVE: In autoimmune encephalitis the etiologic role of neuronal cell-surface antibodies is clear; patients diagnosed and treated early have better outcomes. Neuronal antibodies have also been described in patients with pediatric epilepsy without encephalitis. The aim was to assess whether antibody presence had any effect on long-term outcomes in these patients.METHODS: Patients (n = 178) were recruited between 1988 and 1992 as part of the prospective Dutch Study of Epilepsy in Childhood; none received immunotherapy. Healthy age-matched bone-marrow donors served as controls (n = 112). All sera were tested for serum N-methyl-d-aspartate receptor (NMDAR), alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, leucine rich glioma inactivated 1, contactin associated protein like 2 (CASPR2), contactin-2, glutamic acid decarboxylase, and voltage gated potassium channel (VGKC)-complex antibodies by standard techniques. No cerebrospinal fluid (CSF) samples were available. Results were correlated with clinical data collected over 15 years.RESULTS: Seventeen patients (9.5%) were positive for VGKC complex (n = 3), NMDAR (n = 7), CASPR2 (n = 4), and contactin-2 (n = 3), compared to three (3/112; 2.6%) healthy controls (VGKC complex [n = 1], NMDAR [n = 2]; p = 0.03; Fisher's exact test). Titers were relatively low (≀1:100 for cell-surface antibodies), but 8 (47%) of the 17 positive samples bound to the surface of live hippocampal neurons consistent with a potential pathogenic antibody. Preexisting cognitive impairment was more frequent in antibody-positive patients (9/17 vs. 33/161; p = 0.01). Fourteen antibody-positive patients were treated with standard antiepileptic drugs (AEDs); three (17%) became intractable but this was not different from the 16 (10%) of 161 antibody-negative patients. In 96 patients with available follow-up samples at 6 and/or 12 months, 6 of 7 positive antibodies had disappeared and, conversely, antibodies had appeared for the first time in a further 7 patients.SIGNIFICANCE: Neuronal antibodies were found at low levels in 9.5% of patients with new-onset pediatric epilepsy but did not necessarily persist over time, and the development of antibodies de novo in later samples suggests they could be due to a secondary response to neuronal damage or inflammation. Moreover, as the response to standard AEDs and the long-term outcome did not differ from those of antibody-negative pediatric patients, these findings suggest that routine neuronal antibody testing is unlikely to be helpful in pediatric epilepsy. However, the higher incidence of preexisting cognitive problems in the antibody-positive group, the CASPR2 and contactin-2 antibodies in 7 of 17 patients, and the binding of 8 of 17 of serum samples to live hippocampal neurons suggest that neuronal antibodies, even if secondary, could contribute to the comorbidities of pediatric epilepsy.</p

    Bandwidth-controlled Mott transition in Îș−(BEDT−TTF)2Cu[N(CN)2]BrxCl1−x\kappa-(BEDT-TTF)_2 Cu [N(CN)_2] Br_x Cl_{1-x} I. Optical studies of localized charge excitations

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    Infrared reflection measurements of the half-filled two-dimensional organic conductors Îș\kappa-(BEDT-TTF)2_2Cu[N(CN)2_{2}]Brx_{x}Cl1−x_{1-x} were performed as a function of temperature (5K<T<3005 {\rm K}<T<300 K) and Br-substitution (x=0x=0%, 40%, 73%, 85%, and 90%) in order to study the metal-insulator transition. We can distinguish absorption processes due to itinerant and localized charge carriers. The broad mid-infrared absorption has two contributions: transitions between the two Hubbard bands and intradimer excitations from the charges localized on the (BEDT-TTF)2_2 dimer. Since the latter couple to intramolecular vibrations of BEDT-TTF, the analysis of both electronic and vibrational features provides a tool to disentangle these contributions and to follow their temperature and electronic-correlations dependence. Calculations based on the cluster model support our interpretation.Comment: 12 pages, 12 figure

    The Power of Environmental Observatories for Advancing Multidisciplinary Research, Outreach, and Decision Support: The Case of the Minnesota River Basin

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    Observatory‐scale data collection efforts allow unprecedented opportunities for integrative, multidisciplinary investigations in large, complex watersheds, which can affect management decisions and policy. Through the National Science Foundation‐funded REACH (REsilience under Accelerated CHange) project, in collaboration with the Intensively Managed Landscapes‐Critical Zone Observatory, we have collected a series of multidisciplinary data sets throughout the Minnesota River Basin in south‐central Minnesota, USA, a 43,400‐km2 tributary to the Upper Mississippi River. Postglacial incision within the Minnesota River valley created an erosional landscape highly responsive to hydrologic change, allowing for transdisciplinary research into the complex cascade of environmental changes that occur due to hydrology and land use alterations from intensive agricultural management and climate change. Data sets collected include water chemistry and biogeochemical data, geochemical fingerprinting of major sediment sources, high‐resolution monitoring of river bluff erosion, and repeat channel cross‐sectional and bathymetry data following major floods. The data collection efforts led to development of a series of integrative reduced complexity models that provide deeper insight into how water, sediment, and nutrients route and transform through a large channel network and respond to change. These models represent the culmination of efforts to integrate interdisciplinary data sets and science to gain new insights into watershed‐scale processes in order to advance management and decision making. The purpose of this paper is to present a synthesis of the data sets and models, disseminate them to the community for further research, and identify mechanisms used to expand the temporal and spatial extent of short‐term observatory‐scale data collection efforts

    2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

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    The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

    Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation

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    Objective-Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation. Approach and Results-Collagen-related peptide-induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (Smpd1(-/-)) when compared with platelets from wild-type mice (Smpd1(+/+)). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in Smpd1(-/-) platelets than in Smpd1(+/+) platelets. In contrast, platelet integrin alpha(IIb)beta(3) activation and aggregation, as well as activation-dependent Ca2+ flux, were not significantly different between Smpd1(-/-) and Smpd1(+/+) platelets. In vitro thrombus formation at shear rates of 1700 s(-1) and in vivo thrombus formation after FeCl3 injury were significantly blunted in Smpd1(-/-) mice while bleeding time was unaffected. Asm-deficient platelets showed significantly reduced activation-dependent ceramide formation, whereas exogenous ceramide rescued diminished platelet secretion and thrombus formation caused by Asm deficiency. Treatment of Smpd1(+/+) platelets with bacterial sphingomyelinase (0.01 U/mL) increased, whereas treatment with functional acid sphingomyelinase-inhibitors, amitriptyline or fluoxetine (5 mu mol/L), blunted activation-dependent platelet degranulation, phosphatidylserine exposure, and thrombus formation. Impaired degranulation and thrombus formation of Smpd1(-/-) platelets were again overcome by exogenous bacterial sphingomyelinase. Conclusions-Acid sphingomyelinase is a completely novel element in the regulation of platelet plasma membrane properties, secretion, and thrombus formation

    Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

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    Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

    Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

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    <p>Abstract</p> <p>Background</p> <p>Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.</p> <p>Methods/Design</p> <p>This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m<sup>2</sup>) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m<sup>2</sup>, oxaliplatin 100 mg/m<sup>2</sup>) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.</p> <p>Discussion</p> <p>The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.</p> <p>Trial registration</p> <p>clinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01314027">NCT01314027</a></p

    US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

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    This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference
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