Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy

OBJECTIVES: The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. METHODS: The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. RESULTS: The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. SIGNIFICANCE: Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology

Parameter dependence of magnetized CMB observables

Pre-decoupling magnetic fields affect the scalar modes of the geometry and produce observable effects which can be constrained also through the use of current (as opposed to forthcoming) data stemming from the Cosmic Microwave Background observations. The dependence of the temperature and polarization angular power spectra upon the parameters of an ambient magnetic field is encoded in the scaling properties of a set of basic integrals whose derivation is simplified in the limit of small angular scales. The magnetically-induced distortions patterns of the relevant observables can be computed analytically by employing scaling considerations which are corroborated by numerical results.Comment: 48 pages, 11 figures; corrected minor typos; discussions added; to appear in Physical Revie

Integron-mediated Multidrug Resistance in a Global Collection of Nontyphoidal Salmonella enterica Isolates

Horizontal gene transfer and clonal expansion contribute substantially to the dissemination of resistant strain

Peaks above the Harrison-Zel'dovich spectrum due to the Quark-Gluon to Hadron Transition

The quark-gluon to hadron transition affects the evolution of cosmological perturbations. If the phase transition is first order, the sound speed vanishes during the transition, and density perturbations fall freely. This distorts the primordial Harrison-Zel'dovich spectrum of density fluctuations below the Hubble scale at the transition. Peaks are produced, which grow at most linearly in wavenumber, both for the hadron-photon-lepton fluid and for cold dark matter. For cold dark matter which is kinetically decoupled well before the QCD transition clumps of masses below $10^{-10} M_\odot$ are produced.Comment: Extended version, including evolution of density perturbations for a bag model and for a lattice QCD fit (3 new figures). Spectrum for bag model (old figure) is available in astro-ph/9611186. 9 pages RevTeX, uses epsf.sty, 3 PS figure

Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific

The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination

Magnetized CMB observables: a dedicated numerical approach

Large-scale magnetic fields affect the scalar modes of the geometry whose ultimate effect is to determine the anisotropies of the Cosmic Microwave Background (CMB in what follows). For the first time, a consistent numerical approach to the magnetized CMB anisotropies is pursued with the aim of assessing the angular power spectra of temperature and polarization when the scalar modes of the geometry and a stochastic background of inhomogeneous magnetic fields are simultaneously present in the plasma. The effects related to the magnetized nature of the plasma are taken into account both at the level of the dynamical equations and at the level of the initial conditions of the Einstein-Boltzmann hierarchy. The temperature and polarization observables are exploited to infer the peculiar signatures of a pre-equality magnetic field. Using the extrapolated best fit to the three year WMAP data the increase and distortions of the first seven peaks in the TT autocorrelations are monitored for different values of the regularized magnetic field intensity and for the physical range of spectral indices. Similar analyses are also conducted for the first few anticorrelation (and corrrelation) peaks of the TE power spectra. Possible interesting degeneracies and stimulating perspectives are pointed out and explored.Comment: 44 pages, 25 included eps figure

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

On the Generation of Positivstellensatz Witnesses in Degenerate Cases

One can reduce the problem of proving that a polynomial is nonnegative, or more generally of proving that a system of polynomial inequalities has no solutions, to finding polynomials that are sums of squares of polynomials and satisfy some linear equality (Positivstellensatz). This produces a witness for the desired property, from which it is reasonably easy to obtain a formal proof of the property suitable for a proof assistant such as Coq. The problem of finding a witness reduces to a feasibility problem in semidefinite programming, for which there exist numerical solvers. Unfortunately, this problem is in general not strictly feasible, meaning the solution can be a convex set with empty interior, in which case the numerical optimization method fails. Previously published methods thus assumed strict feasibility; we propose a workaround for this difficulty. We implemented our method and illustrate its use with examples, including extractions of proofs to Coq.Comment: To appear in ITP 201

Association of Race and Ethnicity With COVID‐19 Outcomes in Rheumatic Disease: Data From the COVID‐19 Global Rheumatology Alliance Physician Registry

OBJECTIVE: Racial/ethnic minorities experience more severe outcomes of COVID-19 in the general United States (US) population. The aim of this study was to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease. METHODS: US patients with rheumatic disease and COVID-19 entered into the COVID-19 Global Rheumatology Alliance physician registry March 24 - August 26, 2020 were included. Race/ethnicity was defined as white, Black, Latinx, Asian and other/mixed race. Outcomes included hospitalization, requirement for ventilatory support, and death. Multivariable regression models were used to estimate odds ratios (OR) and 95% confidence intervals controlling for age, sex, smoking, rheumatic disease diagnosis, comorbidities, medications taken prior to infection, and rheumatic disease activity. RESULTS: A total of 1,324 patients were included, of whom 36% were hospitalized and 6% died; 26% of hospitalized patients required mechanical ventilation. In multivariable models, Black (OR=2.74, 95% CI 1.90, 3.95), Latinx (OR=1.71, 95% CI 1.18, 2.49), and Asian (OR=2.69, 95% CI 1.16, 6.24) patients had higher odds of being hospitalized compared to white patients. Latinx patients also had three-fold increased odds of requiring ventilatory support (OR=3.25, 95% CI 1.75, 6.05). No differences in mortality based on race/ethnicity were found, though power may have been limited to detect associations. CONCLUSION: Similar to findings in the general US population, racial/ethnic minorities with rheumatic disease and COVID-19 had increased odds of hospitalization and ventilatory support. These results illustrate significant health disparities related to COVID-19 in people with rheumatic diseases. The rheumatology community should proactively address the needs of patients currently experiencing inequitable health outcomes during the pandemic