Ab initio calculation of the neutron-proton mass difference

The existence and stability of atoms rely on the fact that neutrons are more massive than protons. The measured mass difference is only 0.14\% of the average of the two masses. A slightly smaller or larger value would have led to a dramatically different universe. Here, we show that this difference results from the competition between electromagnetic and mass isospin breaking effects. We performed lattice quantum-chromodynamics and quantum-electrodynamics computations with four nondegenerate Wilson fermion flavors and computed the neutron-proton mass-splitting with an accuracy of $300$ kilo-electron volts, which is greater than $0$ by $5$ standard deviations. We also determine the splittings in the $\Sigma$, $\Xi$, $D$ and $\Xi_{cc}$ isospin multiplets, exceeding in some cases the precision of experimental measurements.Comment: 57 pages, 15 figures, 6 tables, revised versio

Optimal solution characterization for infinite positive semi-definite programming

We give a set-theoretic description of the set of optimal solutions to a general positive semi-definite quadratic programming problem over an affine set. We also show that the solution space is again an affine set, thus offering the opportunity to find an optimal solution by solving a corresponding operator equation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31452/1/0000373.pd

Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women

Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer

Convergence of selections with applications in optimization

We consider the problem of finding an easily implemented tie-breaking rule for a convergent set-valued algorithm, i.e., a sequence of compact, non-empty subsets of a metric space converging in the Hausdorff metric. Our tie-breaking rule is determined by nearest-point selections defined by "uniqueness" points in the space, i.e., points having a unique best approximation in the limit set of the convergent algorithm. Convergence of the algorithm is shown to be equivalent to convergence of all such nearest-point selections. Under reasonable additional hypotheses, all points in the metric space have the uniqueness property. Consequently, all points yield convergent nearest-point selections, i.e., tie-breaking rules, for a convergent algorithm.We then show how to apply these results to approximate solutions for the following types of problems: infinite systems of inequalities, semi-infinite mathematical programming, non-convex optimization, and infinite horizon optimization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29485/1/0000571.pd

Dravet syndrome as epileptic encephalopathy: Evidence from long-term course and neuropathology

Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy

An all-solid-state laser source at 671 nm for cold atom experiments with lithium

We present an all solid-state narrow line-width laser source emitting $670\,\mathrm{mW}$ output power at $671\,\mathrm{nm}$ delivered in a diffraction-limited beam. The \linebreak source is based on a fre-quency-doubled diode-end-linebreak pumped ring laser operating on the ${^4F}_{3/2} \rightarrow {^4I}_{13/2}$ transition in Nd:YVO$_4$. By using periodically-poled po-tassium titanyl phosphate (ppKTP) in an external build-up cavity, doubling efficiencies of up to 86% are obtained. Tunability of the source over $100\,\rm GHz$ is accomplished. We demonstrate the suitability of this robust frequency-stabilized light source for laser cooling of lithium atoms. Finally a simplified design based on intra-cavity doubling is described and first results are presented

PRIMA1 mutation: A new cause of nocturnal frontal lobe epilepsy

Objective Nocturnal frontal lobe epilepsy (NFLE) can be sporadic or autosomal dominant; some families have nicotinic acetylcholine receptor subunit mutations. We report a novel autosomal recessive phenotype in a single family and identify the causative gene. Methods Whole exome sequencing data was used to map the family, thereby narrowing exome search space, and then to identify the mutation. Results Linkage analysis using exome sequence data from two affected and two unaffected subjects showed homozygous linkage peaks on chromosomes 7, 8, 13, and 14 with maximum LOD scores between 1.5 and 1.93. Exome variant filtering under these peaks revealed that the affected siblings were homozygous for a novel splice site mutation (c.93+2T>C) in the PRIMA1 gene on chromosome 14. No additional PRIMA1 mutations were found in 300 other NFLE cases. The c.93+2T>C mutation was shown to lead to skipping of the first coding exon of the PRIMA1 mRNA using a minigene system. Interpretation PRIMA1 is a transmembrane protein that anchors acetylcholinesterase (AChE), an enzyme hydrolyzing acetycholine, to membrane rafts of neurons. PRiMA knockout mice have reduction of AChE and accumulation of acetylcholine at the synapse; our minigene analysis suggests that the c.93+2T>C mutation leads to knockout of PRIMA1. Mutations with gain of function effects in acetylcholine receptor subunits cause autosomal dominant NFLE. Thus, enhanced cholinergic responses are the likely cause of the severe NFLE and intellectual disability segregating in this family, representing the first recessive case to be reported and the first PRIMA1 mutation implicated in disease

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy

First published: 16 February 2022Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.Arlene M. D’Silva, Sandra Holland, Didu Kariyawasam, Karen Herbert, Peter Barclay, Anita Cairns, Suzanna C. MacLennan, Monique M. Ryan, Hugo Sampaio, Nicholas Smith, Ian R. Woodcock, Eppie M. Yiu, Ian E. Alexander and Michelle A. Farra

Physics of Solar Prominences: I - Spectral Diagnostics and Non-LTE Modelling

This review paper outlines background information and covers recent advances made via the analysis of spectra and images of prominence plasma and the increased sophistication of non-LTE (ie when there is a departure from Local Thermodynamic Equilibrium) radiative transfer models. We first describe the spectral inversion techniques that have been used to infer the plasma parameters important for the general properties of the prominence plasma in both its cool core and the hotter prominence-corona transition region. We also review studies devoted to the observation of bulk motions of the prominence plasma and to the determination of prominence mass. However, a simple inversion of spectroscopic data usually fails when the lines become optically thick at certain wavelengths. Therefore, complex non-LTE models become necessary. We thus present the basics of non-LTE radiative transfer theory and the associated multi-level radiative transfer problems. The main results of one- and two-dimensional models of the prominences and their fine-structures are presented. We then discuss the energy balance in various prominence models. Finally, we outline the outstanding observational and theoretical questions, and the directions for future progress in our understanding of solar prominences.Comment: 96 pages, 37 figures, Space Science Reviews. Some figures may have a better resolution in the published version. New version reflects minor changes brought after proof editin

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm