Diagnostic and Therapeutic Challenges

This case is submitted by Drs. Salvador Pastor-Idoate, Manchester Royal Eye Hospital, and Manchester Vision Regeneration (MVR) Lab at NIHR/Wellcome Trust, Manchester CRF, United Kingdom; Heinrich Heimann, Royal Liverpool and Broadgreen University Hospitals NHS Trust; Pearse A. Keane, Moorfields Eye Hospital, London, United Kingdom, and Konstantinos Balaskas; Manchester Royal Eye Hospital, Manchester, United Kingdom; commented by Dr. Brandon J. Lujan, Portland, Oregon

Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis.

PURPOSE:Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. METHODS:A patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. RESULTS:Despite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely within the lesion, the subject got 48% correct, compared to 78% correct when the stimulus was outside the lesion. TSLO microperimetry revealed reduced, but detectible, sensitivity thresholds within the lesion. CONCLUSIONS AND IMPORTANCE:Fundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images

Predictions from non trivial Quark-Lepton complementarity

The complementarity between the quark and lepton mixing matrices is shown to provide robust predictions. We obtain these predictions by first showing that the matrix V_M, product of the quark (CKM) and lepton (PMNS) mixing matrices, may have a zero (1,3) entry which is favored by experimental data. We obtain that any theoretical model with a vanishing (1,3) entry of V_M that is in agreement with quark data, solar, and atmospheric mixing angle leads to $\theta_{13}^{PMNS}=(9{^{+1}_{-2}})^\circ$. This value is consistent with the present 90% CL experimental upper limit. We also investigate the prediction on the lepton phases. We show that the actual evidence, under the only assumption that the correlation matrix V_M product of CKM and PMNS has a zero in the entry (1,3), gives us a prediction for the three CP-violating invariants J, S_1, and S_2. A better determination of the lepton mixing angles will give stronger prediction for the CP-violating invariants in the lepton sector. These will be tested in the next generation experiments. Finally we compute the effect of non diagonal neutrino mass in "l_i -> l_j gamma" in SUSY theories with non trivial Quark-Lepton complementarity and a flavor symmetry. The Quark-Lepton complementarity and the flavor symmetry strongly constrain the theory and we obtain a clear prediction for the contribution to "mu -> e gamma" and the "tau" decays "tau -> e gamma" and "tau -> mu gamma". If the Dirac neutrino Yukawa couplings are degenerate but the low energy neutrino masses are not degenerate, then the lepton decays are related among them by the V_M entries. On the other hand, if the Dirac neutrino Yukawa couplings are hierarchical or the low energy neutrino masses are degenerate, then the prediction for the lepton decays comes from the CKM hierarchy.Comment: 15 pages, 5 figures, ws-ijmpa class included, Proceedings of the CTP Symposium on Sypersymmetry at LH

Explicit SO(10) Supersymmetric Grand Unified Model for the Higgs and Yukawa Sectors

A complete set of fermion and Higgs superfields is introduced with well-defined SO(10) properties and U(1) x Z_2 x Z_2 family charges from which the Higgs and Yukawa superpotentials are constructed. The structures derived for the four Dirac fermion and right-handed Majorana neutrino mass matrices coincide with those previously obtained from an effective operator approach. Ten mass matrix input parameters accurately yield the twenty masses and mixings of the quarks and leptons with the bimaximal atmospheric and solar neutrino vacuum solutions favored in this simplest version.Comment: Published version appearing in PRL in which small modifications to original submission and a paragraph concerning proton decay appea

Development of learning objectives for neurology in a veterinary curriculum: Part II: Postgraduates

Background: Specialization in veterinary medicine in Europe is organized through the Colleges of the European Board of Veterinary Specialization. To inform updating of the curriculum for residents of the European College of Veterinary Neurology (ECVN) job analysis was used. Defining job competencies of diploma holders in veterinary neurology can be used as references for curriculum design of resident training. With the support of the diplomates of the ECVN and the members of the European Society of Veterinary Neurology (ESVN) a mixed-method research, including a qualitative search of objectives and quantitative ranking with 149 Likert scale questions and 48 free text questions in 9 categories in a survey was conducted. In addition, opinions of different groups were subjected to statistical analysis and the result compared. Results: A return rate of 62% (n = 213/341) was achieved. Of the competencies identified by the Delphi process, 75% objectives were expected to attain expert level; 24% attain advanced level; 1% entry level. In addition, the exercise described the 11 highly ranked competencies, the 3 most frequently seen diseases of the central and peripheral nervous systems and the most frequently used immunosuppressive, antiepileptic and chemotherapeutic drugs. Conclusion: The outcomes of this “Delphi job analysis” provide a powerful tool to align the curriculum for ECVN resident training and can be adapted to the required job competencies, based on expectations. The expectation is that for majority of these competencies diplomates should attain an expert level. Besides knowledge and clinical skills, residents and diplomates are expected to demonstrate high standards in teaching and communication. The results of this study will help to create a European curriculum for postgraduate education in veterinary neurology

Feature selection for chemical sensor arrays using mutual information

We address the problem of feature selection for classifying a diverse set of chemicals using an array of metal oxide sensors. Our aim is to evaluate a filter approach to feature selection with reference to previous work, which used a wrapper approach on the same data set, and established best features and upper bounds on classification performance. We selected feature sets that exhibit the maximal mutual information with the identity of the chemicals. The selected features closely match those found to perform well in the previous study using a wrapper approach to conduct an exhaustive search of all permitted feature combinations. By comparing the classification performance of support vector machines (using features selected by mutual information) with the performance observed in the previous study, we found that while our approach does not always give the maximum possible classification performance, it always selects features that achieve classification performance approaching the optimum obtained by exhaustive search. We performed further classification using the selected feature set with some common classifiers and found that, for the selected features, Bayesian Networks gave the best performance. Finally, we compared the observed classification performances with the performance of classifiers using randomly selected features. We found that the selected features consistently outperformed randomly selected features for all tested classifiers. The mutual information filter approach is therefore a computationally efficient method for selecting near optimal features for chemical sensor arrays