Massless versus Kaluza-Klein Gravitons at the LHC

We show that the LHC will be able to differentiate between a four-dimensional model with quantum gravity at ~1 TeV where the (massless) graviton becomes strongly coupled to standard model particles at 1 TeV and brane world type models with a large extra-dimensional volume and massive Kaluza-Klein gravitons. We estimate that the 14 TeV LHC could put a limit of the order of ~5 TeV on the four dimensional Planck mass in a model independent way. Comment: 9 page

Massless versus Kaluza-Klein Gravitons at the LHC

We show that the LHC will be able to differentiate between a four-dimensional model with quantum gravity at ~1 TeV where the (massless) graviton becomes strongly coupled to standard model particles at 1 TeV and brane world type models with a large extra-dimensional volume and massive Kaluza-Klein gravitons. We estimate that the 14 TeV LHC could put a limit of the order of ~5 TeV on the four dimensional Planck mass in a model independent way.Comment: 9 page

Scaling MAP-Elites to Deep Neuroevolution

Quality-Diversity (QD) algorithms, and MAP-Elites (ME) in particular, have proven very useful for a broad range of applications including enabling real robots to recover quickly from joint damage, solving strongly deceptive maze tasks or evolving robot morphologies to discover new gaits. However, present implementations of MAP-Elites and other QD algorithms seem to be limited to low-dimensional controllers with far fewer parameters than modern deep neural network models. In this paper, we propose to leverage the efficiency of Evolution Strategies (ES) to scale MAP-Elites to high-dimensional controllers parameterized by large neural networks. We design and evaluate a new hybrid algorithm called MAP-Elites with Evolution Strategies (ME-ES) for post-damage recovery in a difficult high-dimensional control task where traditional ME fails. Additionally, we show that ME-ES performs efficient exploration, on par with state-of-the-art exploration algorithms in high-dimensional control tasks with strongly deceptive rewards.Comment: Accepted to GECCO 202

Dopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease

Objective: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD. Methods: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin‐containing retinal ganglion cells, in control and PD eyes from human donors. Results: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells were not reduced in number, but they showed cellular alterations compromising their adequate function: (1) a loss of mitochondria inside their lobular appendages, which may indicate an energetic failure; and (2) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal transmission from the rod pathway. Interpretation: The dopaminergic system impairment and the affection of the rod pathway through the AII cells may explain and be partially responsible for the reduced contrast sensitivity or electroretinographic response described in PD. Also, dopamine reduction and the loss of synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell loss previously described and to the disturbances in circadian rhythm and sleep reported in PD patients. These data support the idea that the retina reproduces brain neurodegeneration and is highly involved in PD pathology.This work was supported by the Michael J. Fox Foundation for Parkinson’s Research. I.O.-L. and X.S.-S. acknowledge financial support from the Ministry of Education, Spain (FPU 14/03166; FPU 16/04114). N.C. acknowledges financial support from the Ministry of Economy and Competitiveness, Spain (MINECO-FEDER-BFU2015-67139-R), Carlos III Institute of Health (RETICS-FEDER RD16/0008/0016), Retina Asturias Association, and Generalitat Valenciana-European Regional Development Fund (IDIFEDER/2017/064). The Brain and Body Donation Program has been supported by the NIH National Institute of Neurological Disorders and Stroke (U24 NS072026), the NIH National Institute on Aging (P30 AG19610), the Arizona Department of Health Services, the Arizona Biomedical Research Commission, and the Michael J. Fox Foundation for Parkinson’s Research

Global gravitational instability of FLRW backgrounds - interpreting the dark sectors

The standard model of cosmology is based on homogeneous-isotropic solutions of Einstein's equations. These solutions are known to be gravitationally unstable to local inhomogeneous perturbations, commonly described as evolving on a background given by the same solutions. In this picture, the FLRW backgrounds are taken to describe the average over inhomogeneous perturbations for all times. We study in the present article the (in)stability of FLRW dust backgrounds within a class of averaged inhomogeneous cosmologies. We examine the phase portraits of the latter, discuss their fixed points and orbital structure and provide detailed illustrations. We show that FLRW cosmologies are unstable in some relevant cases: averaged models are driven away from them through structure formation and accelerated expansion. We find support for the proposal that the dark components of the FLRW framework may be associated to these instability sectors. Our conclusion is that FLRW cosmologies have to be considered critically as for their role to serve as reliable models for the physical background.Comment: 15 pages, 13 figures, 1 table. Matches published version in CQ

QCD-based description of one-particle inclusive B decays

We discuss one-particle inclusive B decays in the limit of heavy b and c quarks. Using the large-N_C limit we factorize the non-leptonic matrix elements, and we employ a short distance expansion. Modeling the remaining nonperturbative matrix elements we obtain predictions for various decay channels and compare them with existing data.Comment: LaTeX, 22 pages, 6 figures (eps); analytical and numerical results unchanged, misrepresentation of experimental data in Fig. 5 corrected, final published versio

Long-term safety data from the cladribine tablets clinical development program in multiple sclerosis

Background: Long-term safety data are of particular interest for any newly approved treatment in multiple sclerosis such as cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg), which is approved in Europe and the USA. Here we provide the final report on the integrated analysis of the safety profile of cladribine tablets 3.5 mg/kg from the clinical development program, including final data from the PREMIERE registry. Methods: Safety data for cladribine tablets 3.5 mg/kg from three previously reported Phase III studies (CLARITY, CLARITY Extension and ORACLE-MS), as well as the prospective, observational PREMIERE registry (which ran from November 2009 to October 2018; consisting of patients who had participated in at least one of the Phase III trials) were combined to provide the Monotherapy Oral cohort. Serious adverse events (SAEs) and predefined SAEs of special interest were recorded. Observation-adjusted incidence rates per 100 patient-years (Adj-AE per 100 PY) were used to assess adverse events (AEs). Standardized incidence ratios for malignancies were calculated in relation to a matched GLOBOCAN reference population, and risk differences (cladribine tablets versus placebo) were estimated. Results: The Monotherapy Oral cohort comprised 923 patients who received cladribine tablets 3.5 mg/kg and 641 patients who received placebo. Overall, the reported number of SAEs was higher in the cladribine tablets 3.5 mg/kg group (133/923 [14.4%] patients with at least 1 SAE), versus the placebo group (68/641 [10.6%] patients with at least 1 SAE). Four patients in the cladribine tablets 3.5 mg/kg group had lymphopenia classified as a serious event (resulting in an Adj-AE of 0.10 per 100 PY) and 2 patients had serious herpes zoster (resulting in an Adj-AE of 0.05 per 100 PY). There were no cases in the corresponding placebo groups. There was no difference between the cladribine tablets 3.5 mg/kg group and placebo in the overall incidence of infections. However herpetic infection AEs occurred more frequently in the cladribine tablets 3.5 mg/kg group (driven primarily by herpes zoster, followed by oral herpes and herpes simplex). Overall, there was a numerical imbalance in malignancy incidence between cladribine tablets 3.5 mg/kg and placebo, with an Adj-AE of 0.26 and 0.12 per 100 PY, respectively; however the difference was not statistically significant. The rate of malignancies observed with cladribine tablets 3.5 mg/kg in the final integrated safety analysis was not different from the expected rate in the matched GLOBOCAN reference population (standardized incidence ratio, 0.88; 95% CI, 0.44-1.69). Conclusion: Additional patient-years of observation do not significantly alter the conclusions of earlier interim analyses, and no new major safety findings were identified in this consolidated analysis of safety data of cladribine tablets 3.5 mg/kg monotherapy in patients with relapsing-remitting multiple sclerosis

Urological Management at Discharge from Acute Spinal Cord Injury Rehabilitation: A Descriptive Analysis from a Population-based Prospective Cohort.

Background There is limited epidemiological evidence describing contemporary neuro-urological management of persons with acute spinal cord injury (SCI). Objective To describe neurogenic lower urinary tract dysfunction (NLUTD) management at discharge from SCI rehabilitation. Design setting and participants The population-based Swiss Spinal Cord Injury (SwiSCI) cohort study prospectively collected data from 602 adults undergoing specialized postacute SCI rehabilitation from 2013 to 2020. The management strategy was based on the European Association of Urology (EAU) Guidelines on Neuro-Urology. Outcome measurements and statistical analysis Data were collected at discharge using the International SCI Lower Urinary Tract Function Basic Data Set. Multivariable logistic regression adjusting for demographics, SCI characteristics, and center, with inverse probability weighting accounting for sampling bias, was used to produce prevalence estimates and identify predictors of lower urinary tract symptoms (LUTS) and NLUTD management outcomes. Results and limitations At discharge (median time after SCI: 5.0 mo [Q1-Q3: 3.0-7.2]), the prevalence of LUTS or managed NLUTD was 82% (95% confidence interval [CI]: 79-85%). SCI completeness was the main predictor of LUTS and managed NLUTD. The risk of urinary incontinence was elevated in females (odds ratio 1.98 [95% CI: 1.18-3.32]) and with complete lesions (odds ratio 4.71 [95% CI: 2.52-8.81]). Voiding dysfunction was most commonly managed with intermittent catheterization (prevalence 39% [95% CI: 35-42%]), followed by indwelling catheterization (prevalence 22% [95% CI: 18-25%]). The prevalence of antimuscarinic or mirabegron use was 29% (95% CI: 26-33%). Urodynamic and renal function data were not collected. Conclusions Our population-based description of urological management in Swiss SCI centers utilizing the EAU Guidelines on Neuro-Urology may be used as a reference for evaluation in other settings. Data further indicate a need for sex-specific neuro-urological management research. Patient summary At discharge from spinal cord injury (SCI) rehabilitation, a majority of patients have lower urinary tract problems, especially those with complete SCI. Women have a higher risk of urinary incontinence

Homeostatic competition drives tumor growth and metastasis nucleation

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa