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Edsel B Ing,1 Gabriela Lahaie Luna,2 Andrew Toren,3 Royce Ing,4 John J Chen,5 Nitika Arora,6 Nurhan Torun,7 Otana A Jakpor,8 J Alexander Fraser,9 Felix J Tyndel,10 Arun NE Sundaram,10 Xinyang Liu,11 Cindy TY Lam,1 Vivek Patel,12 Ezekiel Weis,13 David Jordan,14 Steven Gilberg,14 Christian Pagnoux,15 Martin ten Hove21Department of Ophthalmology and Vision Sciences, University of Toronto Medical School, Toronto, 2Department of Ophthalmology, Queen’s University, Kingston, ON, 3Department of Ophthalmology, University of Laval, Quebec, QC, 4Toronto Eyelid, Strabismus and Orbit Surgery Clinic, Toronto, ON, Canada; 5Mayo Clinic, Department of Ophthalmology and Neurology, 6Mayo Clinic, Department of Ophthalmology, Rochester, MN, 7Department of Surgery, Division of Ophthalmology, Harvard Medical School, Boston, MA, 8Harvard Medical School, Boston, MA, USA; 9Department of Clinical Neurological Sciences and Ophthalmology, Western University, London, 10Department of Medicine, University of Toronto Medical School, Toronto, ON, Canada; 11Department of Medicine, Fudan University Shanghai Medical College, Shanghai, People’s Republic of China; 12Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 13Departments of Ophthalmology, Universities of Alberta and Calgary, Edmonton and Calgary, AB, 14Department of Ophthalmology, University of Ottawa, Ottawa, ON, 15Vasculitis Clinic, Mount Sinai Hospital, Toronto, ON, CanadaPurpose: To develop and validate a diagnostic prediction model for patients with suspected giant cell arteritis (GCA).Methods: A retrospective review of records of consecutive adult patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at seven university centers. The pathologic diagnosis was considered the final diagnosis. The predictor variables were age, gender, new onset headache, clinical temporal artery abnormality, jaw claudication, ischemic vision loss (VL), diplopia, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet level. Multiple imputation was performed for missing data. Logistic regression was used to compare our models with the non-histologic American College of Rheumatology (ACR) GCA classification criteria. Internal validation was performed with 10-fold cross validation and bootstrap techniques. External validation was performed by geographic site.Results: There were 530 complete TABx records: 397 were negative and 133 positive for GCA. Age, jaw claudication, VL, platelets, and log CRP were statistically significant predictors of positive TABx, whereas ESR, gender, headache, and temporal artery abnormality were not. The parsimonious model had a cross-validated bootstrap area under the receiver operating characteristic curve (AUROC) of 0.810 (95% CI =0.766–0.854), geographic external validation AUROC’s in the range of 0.75–0.85, calibration pH–L of 0.812, sensitivity of 43.6%, and specificity of 95.2%, which outperformed the ACR criteria.Conclusion: Our prediction rule with calculator and nomogram aids in the triage of patients with suspected GCA and may decrease the need for TABx in select low-score at-risk subjects. However, misclassification remains a concern.Keywords: temporal artery biopsy, diagnosis, prediction rule, nomogram, giant cell arteritis, validation

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally. Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally). Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions. Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

Ultra-low-mass axions are a viable dark matter candidate and may form a coherently oscillating classical field. Nuclear spins in experiments on Earth might couple to this oscillating axion dark-matter field, when propagating on Earth's trajectory through our Galaxy. This spin coupling resembles an oscillating pseudo-magnetic field which modulates the spin precession of nuclear spins. Here we report on the null result of a demonstration experiment searching for a frequency modulation of the free spin-precession signal of \magHg in a 1 $\mu$T magnetic field. Our search covers the axion mass range $10^{-16}$ eV $\lesssim m_a \lesssim 10^{-13}$ eV and achieves a peak sensitivity to the axion-nucleon coupling of $g_{aNN} \approx 3.5 \times 10^{-6}$ GeV$^{-1}$.