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A bstract Observables in quantum gravity are famously defined asymptotically, at the boundary of AdS or Minkowski spaces. However, by gauge fixing a coordinate system or suitably dressing the field operators, an approximate, “quasi-local” approach is also possible, that can give account of the measurements performed by a set of observers living inside the spacetime. In particular, one can attach spatial coordinates to the worldlines of these observers and use their proper times as a time coordinate. Here we highlight that any such local formulation has to face the relativity of the event , in that changing frame (= set of observers) implies a reshuffling of the point-events and the way they are identified. As a consequence, coordinate transformations between different frames become probabilistic in quantum gravity. We give a concrete realization of this mechanism in Jackiw-Teitelboim gravity, where a point in the bulk can be defined operationally with geodesics anchored to the boundary. We describe different ways to do so, each corresponding to a different frame , and compute the variances of the transformations relating some of these frames. In particular, we compute the variance of the location of the black hole horizon, which appears smeared in most frames. We then suggest how to calculate this effect in Einstein gravity, assuming knowledge of the wavefunction of the metric. The idea is to expand the latter on a basis of semiclassical states. Each element of this basis enjoys standard/deterministic coordinate transformations and the result is thus obtained by superposition. As a divertissement , we sabotage Lorentz boosts by adding to Minkoswki space a quantum superposition of gravitational waves and compute the probabilistic coordinate transformation to a boosted frame at linear order. Finally, we attempt to translate the relativity of the event into the language of dressed operators.

A bstract It was recently argued that certain relativistic theories at finite density can exhibit an unconventional spectrum of Goldstone excitations, with gapped Goldstones whose gap is exactly calculable in terms of the symmetry algebra. We confirm this result as well as previous ones concerning gapless Goldstones for non-relativistic systems via a coset construction of the low-energy effective field theory. Moreover, our analysis unveils additional gapped Goldstones, naturally as light as the others, but this time with a model-dependent gap. Their exact number cannot be inferred solely from the symmetry breaking pattern either, but rather depends on the details of the symmetry breaking mechanism — a statement that we explicitly verify with a number of examples. Along the way we provide what we believe to be a particularly transparent interpretation of the so-called inverse-Higgs constraints for spontaneously broken spacetime symmetries.

A bstract We classify condensed matter systems in terms of the spacetime symmetries they spontaneously break. In particular, we characterize condensed matter itself as any state in a Poincaré-invariant theory that spontaneously breaks Lorentz boosts while preserving at large distances some form of spatial translations, time-translations, and possibly spatial rotations. Surprisingly, the simplest, most minimal system achieving this symmetry breaking pattern — the framid — does not seem to be realized in Nature. Instead, Nature usually adopts a more cumbersome strategy: that of introducing internal translational symmetries — and possibly rotational ones — and of spontaneously breaking them along with their space-time counterparts, while preserving unbroken diagonal subgroups. This symmetry breaking pattern describes the infrared dynamics of ordinary solids, fluids, superfluids, and — if they exist — supersolids. A third, “extra-ordinary”, possibility involves replacing these internal symmetries with other symmetries that do not commute with the Poincaré group, for instance the galileon symmetry, supersymmetry or gauge symmetries. Among these options, we pick the systems based on the galileon symmetry, the “ galileids ”, for a more detailed study. Despite some similarity, all different patterns produce truly distinct physical systems with different observable properties. For instance, the low-energy 2 → 2 scattering amplitudes for the Goldstone excitations in the cases of framids, solids and galileids scale respectively as E 2 , E 4 , and E 6 . Similarly the energy momentum tensor in the ground state is “trivial” for framids ( ρ + p = 0), normal for solids ( ρ + p > 0) and even inhomogenous for galileids.

A bstract For relativistic quantum field theories, we consider Lorentz breaking, spatially homogeneous field configurations or states that evolve in time along a symmetry direction. We dub this situation “spontaneous symmetry probing” (SSP). We mainly focus on internal symmetries, i.e. on symmetries that commute with the Poincaré group. We prove that the fluctuations around SSP states have a Lagrangian that is explicitly time independent, and we provide the field space parameterization that makes this manifest. We show that there is always a gapless Goldstone excitation that perturbs the system in the direction of motion in field space. Perhaps more interestingly, we show that if such a direction is part of a non-Abelian group of symmetries, the Goldstone bosons associated with spontaneously broken generators that do not commute with the SSP one acquire a gap , proportional to the SSP state’s “speed”. We outline possible applications of this formalism to inflationary cosmology.

Spacetime measurements and gravitational experiments are made by using objects, matter fields or particles and their mutual relationships. As a consequence, any operationally meaningful assertion about spacetime is in fact an assertion about the degrees of freedom of the matter (i.e. non gravitational) fields; those, say for definiteness, of the Standard Model of particle physics. As for any quantum theory, the dynamics of the matter fields can be described in terms of a unitary evolution of a state vector in a Hilbert space. By writing the Hilbert space as a generic tensor product of “subsystems” we analyse the evolution of a state vector on an information theoretical basis and attempt to recover the usual spacetime relations from the information exchanges between these subsystems. We consider generic interacting second quantized models with a finite number of fermionic degrees of freedom and characterize on physical grounds the tensor product structure associated with the class of “localized systems” and therefore with “position”. We find that in the case of free theories no spacetime relation is operationally definable. On the contrary, by applying the same procedure to the simple interacting model of a one-dimensional Heisenberg spin chain we recover the tensor product structure usually associated with “position”. Finally, we discuss the possible role of gravity in this framework.

The minimal requirement for cosmography—a non-dynamical description of the universe—is a prescription for calculating null geodesics, and time-like geodesics as a function of their proper time. In this paper, we consider the most general linear connection compatible with homogeneity and isotropy, but not necessarily with a metric. A light-cone structure is assigned by choosing a set of geodesics representing light rays. This defines a “scale factor” and a local notion of distance, as that travelled by light in a given proper time interval. We find that the velocities and relativistic energies of free-falling bodies decrease in time as a consequence of cosmic expansion, but at a rate that can be different than that dictated by the usual metric framework. By extrapolating this behavior to photons’ redshift, we find that the latter is in principle independent of the “scale factor”. Interestingly, redshift–distance relations and other standard geometric observables are modified in this extended framework, in a way that could be experimentally tested. An extremely tight constraint on the model, however, is represented by the blackbody-ness of the cosmic microwave background. Finally, as a check, we also consider the effects of a non-metric connection in a different set-up, namely, that of a static, spherically symmetric spacetime.

Background In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results A total of 1029 patients with a median age of 45 years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs ( p  < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% ( p  < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%;   p  = 0.341) and seizure response (39.7% vs. 26.9%; p  = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p  = 0.017). Conclusion The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Background The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug’s profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. Objective The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. Methods The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age (‘older’) vs those aged <65 years (‘younger’). Results There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100–175] mg in the older group and 100 [100–200] mg in the younger group ( p = 0.036); it was 150 [100–200] mg in both groups either at 6 months ( p = 0.095) or 12 months ( p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% ( p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively ( p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam ( p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients ( p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups. Conclusions Adjunctive brivaracetam was efficacious, had good tolerability, and no new or unexpected safety signals emerged when used to treat older patients with uncontrolled focal seizures in clinical practice. Adjunctive brivaracetam can be a suitable therapeutic option in this special population.

ObjectivesTo provide new insights into neurological manifestations of COVID-19. We describe a patient with mild COVID-19 associated with diplopia from right sixth cranial nerve palsy and early diffuse leukoencephalopathy, successfully treated with intravenous methylprednisolone.MethodsThe patient was evaluated for diplopia that occurred 1 day after the onset of fever, myalgia, and headache. A complete neurological workup, including neurological examination, cerebrospinal fluid (CSF) analysis with viral polymerase chain reaction (PCR), serum autoimmune encephalitis, and anti-nerve antibodies and brain magnetic resonance imaging (MRI), was performed.ResultsClinical examination revealed incomplete right sixth cranial nerve palsy. Brain MRI showed diffuse confluent fluid-attenuated inversion recovery (FLAIR) hyperintense white matter abnormalities, while CSF analysis showed mild hyperproteinorrachia (61 mg/dL) without pleocytosis. The patients were treated with high-dose intravenous methylprednisolone with rapid improvement of neurological symptoms and resolution of CSF and MRI abnormalities.DiscussionOur report shows that COVID-19 may predominantly present with neurological symptoms; furthermore, it argues the notion of leukoencephalopathy as a typical feature of a severe case of the disease. Mechanisms underpinning neurological symptoms in COVID-19 still need to be elucidated; nonetheless, early recognition and prompt management may ensure their improvement or even complete recovery and are therefore recommended.

I investigate spacetime singularities from the point of view of the wavefunction of the universe. In order to extend the classical notion of geodesic incompleteness one has to include the proper time of an observer as a degree of freedom in the Wheeler DeWitt equation. This leads to a Schrödinger equation along the observer worldline. Near the singularity, as in the classical BLK treatment, I ignore spatial gradients and effectively describe the spacetime around the worldline in the mini-superspace approximation. Then the problem proves identical to a spherically symmetric scattering of a quantum particle off a central potential and singularity avoidance is tantamount to unitary evolution for this system. Standard types of matter (dust, radiation) correspond to regular potentials and thus lead to a bounce. The most singular component, spatial anisotropy, is associated to a conserved charge and yields a negative inverse-square potential -- like standard angular momentum, but with opposite sign. This potential is critical, in that the unitarity of the evolution depends on the actual numerical factor in front of it, i.e., on the anisotropy charge.