Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study

The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1–45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (−1.1 µm, 95 % CI 1.4–0.7, p < 0.001) and mGCIPL (−1.1 µm, 95 % CI −1.4 to −0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (−0.03 µm, 95 % CI −0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury

The APOSTEL recommendations for reporting quantitative optical coherence tomography studies

OBJECTIVE: To develop consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results. METHODS: A panel of experienced OCT researchers (including 11 neurologists, 2 ophthalmologists, and 2 neuroscientists) discussed requirements for performing and reporting quantitative analyses of retinal morphology and developed a list of initial recommendations based on experience and previous studies. The list of recommendations was subsequently revised during several meetings of the coordinating group. RESULTS: We provide a 9-point checklist encompassing aspects deemed relevant when reporting quantitative OCT studies. The areas covered are study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition data analysis, recommended nomenclature, and statistical analysis. CONCLUSIONS: The Advised Protocol for OCT Study Terminology and Elements recommendations include core items to standardize and improve quality of reporting in quantitative OCT studies. The recommendations will make reporting of quantitative OCT studies more consistent and in line with existing standards for reporting research in other biomedical areas. The recommendations originated from expert consensus and thus represent Class IV evidence. They will need to be regularly adjusted according to new insights and practices

Low Scale Flavor Gauge Symmetries

We study the possibility of gauging the Standard Model flavor group. Anomaly cancellation leads to the addition of fermions whose mass is inversely proportional to the known fermion masses. In this case all flavor violating effects turn out to be controlled roughly by the Standard Model Yukawa, suppressing transitions for the light generations. Due to the inverted hierarchy the scale of new gauge flavor bosons could be as low as the electroweak scale without violating any existing bound but accessible at the Tevatron and the LHC. The mechanism of flavor protection potentially provides an alternative to Minimal Flavor Violation, with flavor violating effects suppressed by hierarchy of scales rather than couplings.Comment: 24 pages + appendices; v2) Refs. added and numerical examples improved. Results unchanged; v3) small typos in appendix B correcte

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

BACKGROUNG: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. OBJECTIVE: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. METHODS: In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. RESULTS: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm(3), p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm(3), p = .474). CONCLUSION: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials

The crucial role of particle surface reactivity in respirable quartz-induced reactive oxygen/nitrogen species formation and APE/Ref-1 induction in rat lung

Persistent inflammation and associated excessive oxidative stress have been crucially implicated in quartz-induced pulmonary diseases, including fibrosis and cancer. We have investigated the significance of the particle surface reactivity of respirable quartz dust in relation to the in vivo generation of reactive oxygen and nitrogen species (ROS/RNS) and the associated induction of oxidative stress responses in the lung. Therefore, rats were intratracheally instilled with 2 mg quartz (DQ12) or quartz whose surface was modified by either polyvinylpyridine-N-oxide (PVNO) or aluminium lactate (AL). Seven days after instillation, the bronchoalveolar lavage fluid (BALF) was analysed for markers of inflammation (total/differential cell counts), levels of pulmonary oxidants (H(2)O(2), nitrite), antioxidant status (trolox equivalent antioxidant capacity), as well as for markers of lung tissue damage, e.g. total protein, lactate dehydrogenase and alkaline phosphatase. Lung homogenates as well as sections were investigated regarding the induction of the oxidative DNA-lesion/oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) using HPLC/ECD analysis and immunohistochemistry, respectively. Homogenates and sections were also investigated for the expression of the bifunctional apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) by Western blotting and immunohistochemistry. Significantly increased levels of H(2)O(2 )and nitrite were observed in rats treated with non-coated quartz, when compared to rats that were treated with either saline or the surface-modified quartz preparations. In the BALF, there was a strong correlation between the number of macrophages and ROS, as well as total cells and RNS. Although enhanced oxidant generation in non-coated DQ12-treated rats was paralleled with an increased total antioxidant capacity in the BALF, these animals also showed significantly enhanced lung tissue damage. Remarkably however, elevated ROS levels were not associated with an increase in 8-OHdG, whereas the lung tissue expression of APE/Ref-1 protein was clearly up-regulated. The present data provide further in vivo evidence for the crucial role of particle surface properties in quartz dust-induced ROS/RNS generation by recruited inflammatory phagocytes. Our results also demonstrate that quartz dust can fail to show steady-state enhanced oxidative DNA damage in the respiratory tract, in conditions were it elicits a marked and persistent inflammation with associated generation of ROS/RNS, and indicate that this may relate to compensatory induction of APE/Ref-1 mediated base excision repair

Enhancing the reporting of implementation research

In the 10 years since the inception of Implementation Science, we have witnessed a continued rise in the number of submissions received, reflecting the continued global interest in methods to enhance the uptake of research findings into healthcare practice and policy. We receive over 750 submissions annually, and there is now a large gap between what is submitted and what gets published. In this editorial, we restate the journal scope and current boundaries. We also identify some specific reporting issues that if addressed will help enhance the scientific reporting quality and transparency of the manuscripts we receive. We hope that this editorial acts as a further guide to researchers seeking to publish their work in Implementation Science

Search for lepton-flavour-violating decays of Higgs-like bosons.

A search is presented for a Higgs-like boson with mass in the range 45 to 195 GeV/c2 decaying into a muon and a tau lepton. The dataset consists of proton-proton interactions at a centre-of-mass energy of 8 TeV , collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb-1 . The tau leptons are reconstructed in both leptonic and hadronic decay channels. An upper limit on the production cross-section multiplied by the branching fraction at 95% confidence level is set and ranges from 22 pb for a boson mass of 45 GeV/c2 to 4 pb for a mass of 195 GeV/c2

Yukawa-unified natural supersymmetry

Previous work on t-b-\tau Yukawa-unified supersymmetry, as expected from SUSY GUT theories based on the gauge group SO(10), tended to have exceedingly large electroweak fine-tuning (EWFT). Here, we examine supersymmetric models where we simultaneously require low EWFT ("natural SUSY") and a high degree of Yukawa coupling unification, along with a light Higgs scalar with m_h\sim125 GeV. As Yukawa unification requires large tan\beta\sim50, while EWFT requires rather light third generation squarks and low \mu\sim100-250 GeV, B-physics constraints from BR(B\to X_s\gamma) and BR(B_s\to \mu+\mu-) can be severe. We are able to find models with EWFT \Delta\lesssim 50-100 (better than 1-2% EWFT) and with Yukawa unification as low as R_yuk\sim1.3 (30% unification) if B-physics constraints are imposed. This may be improved to R_yuk\sim1.2 if additional small flavor violating terms conspire to improve accord with B-constraints. We present several Yukawa-unified natural SUSY (YUNS) benchmark points. LHC searches will be able to access gluinos in the lower 1-2 TeV portion of their predicted mass range although much of YUNS parameter space may lie beyond LHC14 reach. If heavy Higgs bosons can be accessed at a high rate, then the rare H, A\to \mu+\mu- decay might allow a determination of tan\beta\sim50 as predicted by YUNS models. Finally, the predicted light higgsinos should be accessible to a linear e+e- collider with \sqrt{s}\sim0.5 TeV.Comment: 18 pages, 7 figures, pdflatex; 3 references adde