First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

Improved Tensor Current Limit from

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Angular Correlations in the ß Decay of

We present the first measurement of the α-ß-ν angular correlation in the Gamow-Teller ß^{+} decay of ^{8}B. This was accomplished using the Beta-decay Paul Trap, expanding on our previous work on the ß^{-} decay of ^{8}Li. The ^{8}B result is consistent with the V-A electroweak interaction of the standard model and, on its own, provides a limit on the exotic right-handed tensor current relative to the axial-vector current of |C_{T}/C_{A}|^{2}<0.013 at the 95.5% confidence level. This represents the first high-precision angular correlation measurements in mirror decays and was made possible through the use of an ion trap. By combining this ^{8}B result with our previous ^{8}Li results, we demonstrate a new pathway for increased precision in searches for exotic currents.

Direct Mass Measurements to Inform the Behavior of

Nuclear isomer effects are pivotal in understanding nuclear astrophysics, particularly in the rapid neutron-capture process where the population of metastable isomers can alter the radioactive decay paths of nuclei produced during astrophysical events. The ß-decaying isomer ^{128m}Sb was identified as potentially impactful since the ß-decay pathway along the A=128 isobar funnels into this state bypassing the ground state. We report the first direct mass measurements of the ^{128}Sb isomer and ground state using the Canadian Penning Trap mass spectrometer at Argonne National Laboratory. We find mass excesses of -84564.8(25) keV and -84608.8(21) keV, respectively, resulting in an excitation energy for the isomer of 43.9(33) keV. These results provide the first key nuclear data input for understanding the role of ^{128m}Sb in nucleosynthesis, and we show that it will influence the flow of the rapid neutron-capture process.

Improved Limit on Tensor Currents in the Weak Interaction from

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the ß-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a_{ßν}=-0.3325±0.0013_{stat}±0.0019_{syst} at 1σ for the case of coupling to right-handed neutrinos (C_{T}=-C_{T}^{'}), which is consistent with the standard model prediction.

Mirror-symmetry violation in bound nuclear ground states.

Conservation laws are deeply related to any symmetry present in a physical system1,2. Analogously to electrons in atoms exhibiting spin symmetries3, it is possible to consider neutrons and protons in the atomic nucleus as projections of a single fermion with an isobaric spin (isospin) of t = 1/2 (ref. 4). Every nuclear state is thus characterized by a total isobaric spin T and a projection Tz-two quantities that are largely conserved in nuclear reactions and decays5,6. A mirror symmetry emerges from this isobaric-spin formalism: nuclei with exchanged numbers of neutrons and protons, known as mirror nuclei, should have an identical set of states7, including their ground state, labelled by their total angular momentum J and parity π. Here we report evidence of mirror-symmetry violation in bound nuclear ground states within the mirror partners strontium-73 and bromine-73. We find that a J π = 5/2- spin assignment is needed to explain the proton-emission pattern observed from the T = 3/2 isobaric-analogue state in rubidium-73, which is identical to the ground state of strontium-73. Therefore the ground state of strontium-73 must differ from its J π = 1/2- mirror bromine-73. This observation offers insights into charge-symmetry-breaking forces acting in atomic nuclei.

Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro.

Brain penetrant microtubule stabilising agents (MSAs) are being increasingly validated as potential therapeutic strategies for neurodegenerative diseases and traumatic injuries of the nervous system. MSAs are historically used to treat malignancies to great effect. However, this treatment strategy can also cause adverse off-target impacts, such as the generation of debilitating neuropathy and axonal loss. Understanding of the effects that individual MSAs have on neurons of the central nervous system is still incomplete. Previous research has revealed that aberrant microtubule stabilisation can perturb many neuronal functions, such as neuronal polarity, neurite outgrowth, microtubule dependant transport and overall neuronal viability. In the current study, we evaluate the dose dependant impact of epothilone D, a brain penetrant MSA, on both immature and relatively mature mouse cortical neurons in vitro. We show that epothilone D reduces the viability, growth and complexity of immature cortical neurons in a dose dependant manner. Furthermore, in relatively mature cortical neurons, we demonstrate that while cellularly lethal doses of epothilone D cause cellular demise, low sub lethal doses can also affect mitochondrial transport over time. Our results reveal an underappreciated mitochondrial disruption over a wide range of epothilone D doses and reiterate the importance of understanding the dosage, timing and intended outcome of MSAs, with particular emphasis on brain penetrant MSAs being considered to target neurons in disease and trauma.

Preliminary outcome of Nellix-in-Nellix extensions in patients treated with failed endovascular aneurysm sealing.

BACKGROUND: The 1-year results of the use of the Nellix (Endologix Inc, Irvine, Calif) endovascular aneurysm sealing (EVAS) device were initially promising. However, midterm complications including migration and aneurysm growth occurred more frequently than expected, which provided an incentive to refine the instructions for use. Strategies for the management of complications arising after endovascular aneurysm repair are often not applicable for EVAS, given the unique configuration of the Nellix device, and new techniques are needed. This study analyzes the clinical outcomes of both elective and emergency deployment of a new Nellix device within a primarily placed device, for failure of EVAS, which we refer to as a Nellix-in-Nellix application (NINA). METHODS: This is a global, retrospective, observational cohort study focusing on the early outcome of NINA for failed EVAS, including data from 11 European institutions and 1 hospital in New Zealand. RESULTS: A total of 41 patients were identified who underwent a NINA procedure. Of these, 32 (78%) were placed electively and 9 (22%) were placed on an emergency basis. Seven patients were initially treated with chimney EVAS (n = 5 in the elective NINA group and n = 2 in the emergency NINA group). The average time between the primary EVAS procedure and NINA was 573 days (interquartile range, [IQR] 397-1078 days) and 478 days (IQR, 120-806) for the elective and emergency groups, respectively. The indication for elective NINA was endoleak with migration (50%), endoleak without migration (25%), migration without endoleak (16%), and other (9%). Chimney grafts were used in 21 of 32 patients in the elective group and 3 of 9 patients in the emergency group. Technical success was achieved in 94% of patients in the elective group and 100% of patients in the emergency group. At latest follow-up (median, 104 days; IQR, 49-328 days), there were three aneurysm-related deaths (9%), no ruptures, and five device-related reinterventions (16%) within the elective group. In the emergency group (median follow-up, 23 days; IQR, 7-61 days), there were four aneurysm-related deaths and three aneurysm-related reinterventions. CONCLUSIONS: In conclusion, a NINA can be used to treat late failures of EVAS with an acceptable technical success rate and can be used when more established treatment options are unfeasible or contraindicated. The durability of this technique needs to be further reviewed.

Red cell distribution width at hospital discharge and out-of hospital outcomes in critically ill non-cardiac vascular surgery patients.

OBJECTIVE: Red cell distribution width (RDW) is associated with mortality and bloodstream infection risk in the critically ill. In vascular surgery patients surviving critical care it is not known if RDW can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in RDW at hospital discharge in vascular surgery patients who received critical care would be associated with increased mortality following hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: We performed a two-center observational cohort study of critically ill non-cardiac vascular surgery patients surviving admission 18 years or older treated between November, 1997, and December 2012 in Boston, Massachusetts. EXPOSURES: RDW measured within 24 hours of hospital discharge and categorized a priori as ≤13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, >15.8%. MAIN OUTCOMES AND MEASURES: The primary outcome was all cause mortality in the 90 days following hospital discharge. RESULTS: The cohort included 4,715 patients (male 58%; white 83%; mean age 62.9 years). 90 and 365-day post discharge mortality was 7.5% and 14.4% respectively. In the cohort, 47.3% were discharged to a care facility and 14.8% of patients were readmitted within 30 days. After adjustment for age, gender, race, Deyo-Charlson comorbidity Index, patient type, acute organ failures, prior vascular surgery and vascular surgery category, patients with a discharge RDW 14.7-15.8% or >15.8% have an adjusted OR of 90-day post discharge mortality of 2.52 (95%CI, 1.29-4.90; P = 0.007) or 5.13 (95%CI, 2.70-9.75; P <0.001) relative to patients with a discharge RDW ≤13.3%. The adjusted odds of 30-day readmission in the RDW >15.8% group was 1.52 (95%CI, 1.12-2.07; P = 0.007) relative to patients with a discharge RDW ≤13.3%. Similar adjusted discharge RDW-outcome associations are present at 365 days following hospital discharge and for discharge to a care facility. CONCLUSIONS: In critically ill vascular surgery patients who survive hospitalization, an elevated RDW at hospital discharge is a strong predictor of subsequent mortality, hospital readmission and placement in a care facility. Patients with elevated RDW are at high risk for adverse out of hospital outcomes and may benefit from closer post discharge follow-up and higher intensity rehabilitation.

Precision Mass Measurements of Neutron-Rich Neodymium and Samarium Isotopes and Their Role in Understanding Rare-Earth Peak Formation.

The Canadian Penning Trap mass spectrometer at the Californium Rare Isotope Breeder Upgrade (CARIBU) facility was used to measure the masses of eight neutron-rich isotopes of Nd and Sm. These measurements are the first to push into the region of nuclear masses relevant to the formation of the rare-earth abundance peak at A∼165 by the rapid neutron-capture process. We compare our results with theoretical predictions obtained from "reverse engineering" the mass surface that best reproduces the observed solar abundances in this region through a Markov chain Monte Carlo technique. Our measured masses are consistent with the reverse-engineering predictions for a neutron star merger wind scenario.

Masses and ß-Decay Spectroscopy of Neutron-Rich Odd-Odd

The structure of deformed neutron-rich nuclei in the rare-earth region is of significant interest for both the astrophysics and nuclear structure fields. At present, a complete explanation for the observed peak in the elemental abundances at A∼160 eludes astrophysicists, and models depend on accurate quantities, such as masses, lifetimes, and branching ratios of deformed neutron-rich nuclei in this region. Unusual nuclear structure effects are also observed, such as the unexpectedly low energies of the first 2^{+} levels in some even-even nuclei at N=98. In order to address these issues, mass and ß-decay spectroscopy measurements of the ^{160}Eu_{97} and ^{162}Eu_{99} nuclei were performed at the Californium Rare Isotope Breeder Upgrade radioactive beam facility at Argonne National Laboratory. Evidence for a gap in the single-particle neutron energies at N=98 and for large deformation (ß_{2}∼0.3) is discussed in relation to the unusual phenomena observed at this neutron number.

Two-Year Outcomes of the Nellix EndoVascular Aneurysm Sealing System for Treatment of Abdominal Aortic Aneurysms.

PURPOSE: To analyze the 2-year outcomes of endovascular aneurysm sealing (EVAS) according to 2 versions of the instructions for use (IFU). METHODS: A retrospective study was conducted involving 355 consecutive patients treated with the first-generation EVAS device from April 2013 to December 31, 2015, at 3 high-volume centers. Out of 355 patients treated with EVAS, 264 were elective asymptomatic infrarenal EVAS procedures suitable for analysis. In this cohort, 168 (63.3%) patients were treated within the IFU 2013 criteria; of these 48 (18.2%) were in compliance with the revised IFU 2016 version. RESULTS: Overall technical success was 98.2% (165/168) in the IFU 2013 group and 97.9% (47/48) in the IFU 2016 subgroup (p=0.428). The 2-year freedom from reintervention estimates were 89.7% (IFU 2013) and 95.7% (IFU 2016), with significantly more reinterventions in the first 45 cases (p=0.005). The stenosis/occlusion estimates were 6.5% (IFU 2013) and 4.2% (IFU 2016; p=0.705). Nine (5.4%) endoleaks (8 type Ia and 1 type Ib) were observed within the IFU 2013 cohort; 3 (2.1%) were in the IFU 2016 subgroup (p=0.583). Migration ≥10 mm or ≥5 mm requiring intervention was reported in 12 (7.1%) patients in the IFU 2013 cohort but none within the IFU 2016 subgroup. Ten (6.0%) patients demonstrated aneurysm growth in the IFU 2013 cohort, of which 2 (4.2%) were in the IFU 2016 subgroup. Overall survival and freedom from aneurysm-related death estimates at 2 years were 90.9% and 97.6% in the IFU 2013 cohort (IFU 2016: 95.5% and 100.0%). The prevalence of complications seemed lower within IFU 2016 without significant differences. CONCLUSION: This study shows acceptable 2-year results of EVAS used within the IFU, without significant differences between the 2 IFU versions, though longer follow-up is indicated. The refined IFU significantly reduced the applicability of the technique.

Epothilone D accelerates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis.

AIMS: Degeneration of the distal neuromuscular circuitry is a hallmark pathology of Amyotrophic Lateral Sclerosis (ALS). The potential for microtubule dysfunction to be a critical pathophysiological mechanism in the destruction of this circuitry is increasingly being appreciated. Stabilization of microtubules to improve neuronal integrity and pathology has been shown to be a particularly favourable approach in other neurodegenerative diseases. We present evidence here that treatment with the microtubule-targeting compound Epothilone D (EpoD) both positively and negatively affects the spinal neuromuscular circuitry in the SOD1G93A mouse model of ALS. METHODS: SOD1G93A mice were treated every 5 days with 2 mg/kg EpoD. Evaluation of motor behaviour, neurological phenotype and survival was completed, with age-dependent histological characterization also conducted, using the thy1-YFP mouse. Motor neuron degeneration, axonal integrity, neuromuscular junction (NMJ) health and gliosis were also assessed. RESULTS: EpoD treatment prevented loss of the spinal motor neuron soma, and distal axon degeneration, early in the disease course. This, however, was not associated with protection of the NMJ synapse and did not improve motor phenotype or clinical progression. EpoD administration was also found to be neurotoxic at later disease stages. This was evidenced by accelerated motor neuron cell body loss, increasing gliosis, and was associated with detrimental outcomes to motor behaviour, clinical assessment and survival. CONCLUSIONS: The results suggest that EpoD accelerates disease progression in the SOD1G93A mouse model of ALS, and highlights that the pathophysiological involvement of microtubules in ALS is an evolving and underappreciated phenomenon.

Direct Evidence for Octupole Deformation in

Despite the more than 1 order of magnitude difference between the measured dipole moments in ^{144}Ba and ^{146}Ba, the octupole correlations in ^{146}Ba are found to be as strong as those in ^{144}Ba with a similarly large value of B(E3;3^{-}→0^{+}) determined as 48(+21-29) W.u. The new results not only establish unambiguously the presence of a region of octupole deformation centered on these neutron-rich Ba isotopes, but also manifest the dependence of the electric dipole moments on the occupancy of different neutron orbitals in nuclei with enhanced octupole strength, as revealed by fully microscopic calculations.

CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism?

There are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be multifactorial. However, selecting the most biologically plausible molecular targets that are relevant to the disorder is a critical first step to improve the probability of success. In this review, we outline previous methods for identifying and validating novel targets for CNS drug discovery, and, cognizant of previous failures, we discuss potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders.

Genomic analysis of gum disease and hypertrichosis in foxes.

Since the 1940s, a proliferative gingival disease called hereditary hyperplastic gingivitis (HHG) has been described in the farmed silver fox, Vulpes vulpes (Dyrendahl and Henricson 1960). HHG displays an autosomal recessive transmission and has a pleiotropic relationship with superior fur quality in terms of length and thickness of guard hairs. An analogous human disease, hereditary gingival fibromatosis (HGF), is characterized by a predominantly autosomal dominant transmission and a complex etiology, occurring either as an isolated condition or as a part of a syndrome. Similar to HHG, the symptom most commonly associated with syndromic HGF is hypertrichosis. Here we explore potential mechanisms involved in HHG by comparison to known genetic information about hypertrichosis co-occurring with HGF, using an Affymetrix canine genome microarray platform, quantitative PCR, and candidate gene sequencing. We conclude that the mitogen-activated protein kinase pathway is involved in HHG, however despite involvement of the mitogen-activated protein kinase kinase 6 gene in congenital hypertrichosis with gingival fibromatosis in humans, this gene did not contain any fixed mutations in exons or exon-intron boundaries in HHG-affected foxes, suggesting that it is not causative of HHG in the farmed silver fox population. Differential up-regulation of MAP2K6 gene in HHG-affected foxes does implicate this gene in the HHG phenotype.

Direct Evidence of Octupole Deformation in Neutron-Rich

The neutron-rich nucleus ^{144}Ba (t_{1/2}=11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV ^{144}Ba beam on a 1.0-mg/cm^{2} ^{208}Pb target. The measured value of the matrix element, ⟨3_{1}^{-}∥M(E3)∥0_{1}^{+}⟩=0.65(+17/-23) eb^{3/2}, corresponds to a reduced B(E3) transition probability of 48(+25/-34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.

Limit on Tensor Currents from

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear ß decay are dominated by a single measurement of the ß-ν[over ¯] correlation in ^{6}He ß decay dating back over a half century. In the present work, the ß-ν[over ¯]-α correlation in the ß decay of ^{8}Li and subsequent α-particle breakup of the ^{8}Be^{*} daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (C_{T}=-C_{T}^{'}) limits the tensor fraction to |C_{T}/C_{A}|^{2}<0.011 (95.5% C.L.). The measurement confirms the ^{6}He result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

First results from the CARIBU facility: mass measurements on the r-process path.

The Canadian Penning Trap mass spectrometer has made mass measurements of 33 neutron-rich nuclides provided by the new Californium Rare Isotope Breeder Upgrade facility at Argonne National Laboratory. The studied region includes the 132Sn double shell closure and ranges in Z from In to Cs, with Sn isotopes measured out to A=135, and the typical measurement precision is at the 100 ppb level or better. The region encompasses a possible major waiting point of the astrophysical r process, and the impact of the masses on the r process is shown through a series of simulations. These first-ever simulations with direct mass information on this waiting point show significant increases in waiting time at Sn and Sb in comparison with commonly used mass models, demonstrating the inadequacy of existing models for accurate r-process calculations.