The properties of exotic nuclei on the verge of existence play a fundamental part in our understanding of nuclear interactions. Exceedingly neutron-rich nuclei become sensitive to new aspects of ...nuclear forces. Calcium, with its doubly magic isotopes (40)Ca and (48)Ca, is an ideal test for nuclear shell evolution, from the valley of stability to the limits of existence. With a closed proton shell, the calcium isotopes mark the frontier for calculations with three-nucleon forces from chiral effective field theory. Whereas predictions for the masses of (51)Ca and (52)Ca have been validated by direct measurements, it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Here we report the mass determination of the exotic calcium isotopes (53)Ca and (54)Ca, using the multi-reflection time-of-flight mass spectrometer of ISOLTRAP at CERN. The measured masses unambiguously establish a prominent shell closure at neutron number N = 32, in excellent agreement with our theoretical calculations. These results increase our understanding of neutron-rich matter and pin down the subtle components of nuclear forces that are at the forefront of theoretical developments constrained by quantum chromodynamics.
Abstract Background The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United ...States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) Objectives This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. Methods Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry. Results The 54,782 TAVR patients demonstrated decreases in expected risk of 30-day operative mortality (STS PROM) 7% to 6% and TAVR PROM (TVT PROM) 4% to 3% (both p<.0001) from 2012 to 2015. Observed in-hospital mortality decreased from 5.7% to 2.9% and one-year mortality decreased from 25.8% to 21.6. However, 30-day post procedure pacemaker insertion increased from 8.8% in 2013 to 12.0% in 2015. The 2,556 patients who underwent TMC in 2015 were similar to 2013-14 patients with hospital mortality of 2% with mitral regurgitation reduced to gradient ≤ 2 in 87% of patients (p<.0001). The 349 patients who underwent MViV and MViR procedures were high risk with, an STS PROM for MVR of 11%. The observed hospital mortality was 7.2% and 30-day post procedure was 8.5%. Summary The TVT Registry is an innovative registry that that monitors quality, patient safety and trends for these rapidly evolving new technologies. Condensed Abstract The STS/ACC TVT Registry captures all Food and Drug Administration (FDA) approved transcatheter valve devices preformed in the United States and is mandated as a condition for reimbursement by the Centers for Medicare Services. TAVR patients’ expected risks of mortality and actual in-hospital mortality decreased. Transcatheter mitral clip procedures had a low mortality with reduced in mitral regurgitation to grade ≤ 2 in 87%. Mitral valve in valve or valve in ring patients were high risk for mortality, but actual hospital mortality was lower. The TVT Registry is an innovative registry that monitors quality, safety and trends of these evolving technologies
Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in ...a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities.
Single‐layer graphene stabilization: An efficient methodology to make stable aqueous solutions of single‐layer graphene has been demonstrated by exploiting charge‐transfer interactions with a ...coronene tetracarboxylate acceptor molecule (see figure). Microscopic studies reveal exfoliation of few‐layer graphene and selective stabilization of single‐layer graphene in large quantities.
N-methyl-D-aspartate glutamate receptor (NMDA-R) antagonists produce schizophrenia-like positive and negative symptoms in healthy human subjects. Preclinical research suggests that NMDA-R antagonists ...interfere with the function of gamma-aminobutyric acid (GABA) neurons and alter the brain oscillations. These changes have been hypothesized to contribute to psychosis. In this investigation, we evaluated the hypothesis that the NMDA-R antagonist ketamine produces alterations in cortical functional connectivity during rest that are related to symptoms. We administered ketamine to a primary sample of 22 subjects and to an additional, partially overlapping, sample of 12 subjects. Symptoms before and after the experimental session were rated with the Positive and Negative Syndrome Scale (PANSS). In the primary sample, functional connectivity was measured via functional magnetic resonance imaging almost immediately after infusion began. In the additional sample, this assessment was repeated after 45 min of continuous ketamine infusion. Global, enhanced functional connectivity was observed at both timepoints, and this hyperconnectivity was related to symptoms in a region-specific manner. This study supports the hypothesis that pathological increases in resting brain functional connectivity contribute to the emergence of positive and negative symptoms associated with schizophrenia.
A higher rate than expected of Central Line Associated Bloodstream Infections (CLABSI) and other device-related infections was occurring in a 31 bed Medical/Surgical Intensive Care Unit (ICU) within ...a 350-bed hospital. Staff had limited awareness of hospital associated infections (HAI) as they occurred on their unit. To drive change to reduce ICU HAIs and improve hand hygiene, a formal team was needed to create unit-based content experts to bring information to the bedside through mentoring and educating their peers.
Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are ...greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 × '20 Initiative."
AbstractObjectiveTo develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).DesignCohort ...study with logistic regression analysis to combine predictors and treatment modality.SettingSubarachnoid Haemorrhage International Trialists’ (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.ParticipantsResearchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Main outcome measurePredicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.ResultsClinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a “neuroimaging model,” with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.ConclusionThe prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.
ABSTRACT
Pulsar timing array collaborations have recently reported evidence for a noise process with a common spectrum among the millisecond pulsars in the arrays. The spectral properties of this ...common-noise process are consistent with expectations for an isotropic gravitational-wave background (GWB) from inspiralling supermassive black hole binaries. However, recent simulation analyses based on Parkes Pulsar Timing Array data indicate that such a detection may arise spuriously. In this paper, we use simulated pulsar timing array data sets to further test the robustness of the inference methods for spectral and spatial correlations from a GWB. Expanding on our previous results, we find strong support (Bayes factors exceeding 105) for the presence of a common-spectrum noise process in data sets where no common process is present, under a wide range of timing noise prescriptions per pulsar. We show that these results are highly sensitive to the choice of Bayesian priors on timing noise parameters, with priors that more closely match the injected distributions of timing noise parameters resulting in diminished support for a common-spectrum noise process. These results emphasize shortcomings in current methods for inferring the presence of a common-spectrum process, and imply that the detection of a common process is not a reliable precursor to detection of the GWB. Future searches for the nanohertz GWB should remain focused on detecting spatial correlations, and make use of more tailored specifications for a common-spectrum noise process.
Abstract Although migrations are essential for soil microorganisms to exploit scarce and heterogeneously distributed resources, bacterial mobility in soil remains poorly studied due to experimental ...limitations. In this study, time-lapse images collected using live microscopy techniques captured collective and coordinated groups of B. subtilis cells exhibiting “crowd movement”. Groups of B. subtilis cells moved through transparent soil (nafion polymer with particle size resembling sand) toward plant roots and re-arranged dynamically around root tips in the form of elongating and retracting “flocks” resembling collective behaviour usually associated with higher organisms (e.g., bird flocks or fish schools). Genetic analysis reveals B. subtilis flocks are likely driven by the diffusion of extracellular signalling molecules (e.g., chemotaxis, quorum sensing) and may be impacted by the physical obstacles and hydrodynamics encountered in the soil like environment. Our findings advance understanding of bacterial migration through soil matrices and expand known behaviours for coordinated bacterial movement.
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