Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study

BACKGROUND AND OBJECTIVES: To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing MS diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: CSF examination, brain and spinal cord MRI obtained ≤5 months from CIS onset, and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 CIS patients from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Score (EDSS) ≥ 3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), time (DIT) (including oligoclonal bands assessment) and DIS + DIT for predicting a second clinical attack (clinically definite [CD] MS) and EDSS ≥ 3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. RESULTS: At follow-up (median = 69.1 months), 406/785 CIS patients developed CDMS. At 36 months, the 2017 DIS + DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60) and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision = 3.2; 2010 revision = 13.0; CDMS = 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥ 3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. DISCUSSION: The 2017 McDonald criteria showed higher sensitivity, lower specificity and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria

Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD

PURPOSE: Evaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an “insufficient anatomic response” to prior anti-VEGF therapy with ranibizumab or bevacizumab. METHODS: The retrospective analysis included 96 eyes that had received at least three intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2 mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4 weeks after the third aflibercept injection. RESULTS: A significant reduction of mean CRT (−39 μm; p < 0.001) and maximum PED height (−46 μm; p < 0.001) as found 4 weeks after the third aflibercept injection. Eighty-two out of 96 eyes (85 %) had a PED just prior to switching to aflibercept. There was an improvement in BCVA of 1.9 letters 4 weeks after the last aflibercept injection; the vision gain, however, did not reach statistical significance (p = 0.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments. CONCLUSION: Retinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments

Two naphthalene degrading bacteria belonging to the genera Paenibacillus and Pseudomonas isolated from a highly polluted lagoon perform different sensitivities to the organic and heavy metal contaminants

Two bacterial strains were isolated in the presence of naphthalene as the sole carbon and energy source from sediments of the Orbetello Lagoon, Italy, which is highly contaminated with both organic compounds and metals. 16S rRNA gene sequence analysis of the two isolates assigned the strains to the genera Paenibacillus and Pseudomonas. The effect of different contaminants on the growth behaviors of the two strains was investigated. Pseudomonas sp. ORNaP2 showed a higher tolerance to benzene, toluene, and ethylbenzene than Paenibacillus sp. ORNaP1. In addition, the toxicity of heavy metals potentially present as co-pollutants in the investigated site was tested. Here, strain Paenibacillus sp. ORNaP1 showed a higher tolerance towards arsenic, cadmium, and lead, whereas it was far more sensitive towards mercury than strain Pseudomonas sp. ORNaP2. These differences between the Gram-negative Pseudomonas and the Gram-positive Paenibacillus strain can be explained by different general adaptive response systems present in the two bacteria

Stochastic backgrounds of relic gravitons: a theoretical appraisal

Stochastic backgrounds or relic gravitons, if ever detected, will constitute a prima facie evidence of physical processes taking place during the earliest stages of the evolution of the plasma. The essentials of the stochastic backgrounds of relic gravitons are hereby introduced and reviewed. The pivotal observables customarily employed to infer the properties of the relic gravitons are discussed both in the framework of the $\Lambda$CDM paradigm as well as in neighboring contexts. The complementarity between experiments measuring the polarization of the Cosmic Microwave Background (such as, for instance, WMAP, Capmap, Quad, Cbi, just to mention a few) and wide band interferometers (e.g. Virgo, Ligo, Geo, Tama) is emphasized. While the analysis of the microwave sky strongly constrains the low-frequency tail of the relic graviton spectrum, wide-band detectors are sensitive to much higher frequencies where the spectral energy density depends chiefly upon the (poorly known) rate of post-inflationary expansion.Comment: 94 pages, 32 figure

Varying constants, Gravitation and Cosmology

Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit