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The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

Abstract Objective Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that predominantly affects children and young people. The pathophysiology and molecular mechanisms of CNO remain poorly understood, and diagnostic criteria and biomarkers are lacking. As a result, treatment is empiric and follows personal experience, case series and expert consensus plans. Methods A survey was designed to gain insight on clinician and patient experiences of diagnosing and treating CNO and to collate opinions on research priorities. A version containing 24 questions was circulated among international expert clinicians and clinical academics (27 contacted, 21 responses). An equivalent questionnaire containing 20 questions was shared to explore the experience and priorities of CNO patients and family members (93 responses). Results Responses were used to select topics for four moderated roundtable discussions at the “International Conference on CNO and autoinflammatory bone disease” (Liverpool, United Kingdom, May 25-26th, 2022). The group identified deciphering the pathophysiology of CNO to be the highest priority, followed by clinical trials, necessary outcome measures and classification criteria. Surprisingly, mental wellbeing scored behind these items. Conclusions Agreement exists among clinicians, academics, patients and families that deciphering the pathophysiology of CNO is of highest priority to inform clinical trials that will allow for the approval of medications for the treatment of CNO by regulatory agencies.

Abstract Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Fragile X syndrome (FXS), the leading heritable cause of intellectual disability, has a co-occurrence rate of autism spectrum disorder (ASD) estimated at ~60%. The onset and rates of motor development in FXS are slower relative to neurotypical development, and even more so in the context of co-occurring FXS + ASD. Extant evidence suggests these differences are likely to affect communication, yet this developmental process or how it varies in the context of co-occurring ASD remains unknown in FXS. We aimed to delineate developmental associations between early motor abilities and their rate of development from 9 to 60 months of age on communication outcomes in 51 children with FXS, 28 of whom had co-occurring ASD. We also aimed to identify variation in these developmental associations in the context of co-occurring ASD. Results captured within-syndrome variability in these developmental associations as a function of co-occurring ASD. Fine motor proved to be a robust predictor of receptive communication regardless of co-occurring ASD, but we identified differences between FXS with and without ASD in the association between aspects of motor development and expressive outcomes. Findings provide evidence for differential developmental processes in the context of co-occurring ASD with implications for timely developmental intervention.

Purpose: The "Fragile X Messenger Ribonucleoprotein-1 (FMR1)" premutation (FXpm) is a genetic variant that is common in the general population and is associated with health symptoms and disease in adulthood. However, poor understanding of the clinical phenotype during childhood has hindered the development of clinical practice guidelines for screening and intervention. Given that social communication difficulties have been widely documented in adults with the FXpm and are linked with reduced psychosocial functioning, the present study aimed to characterize the communication profile of the FXpm during early childhood. Method: Eighteen children with the FXpm who were identified through cascade testing (89%) or screening at birth (11%) were compared to 21 matched typically developing children, aged 2-4 years. Participants completed standardized assessments of language (Mullen Scales of Early Learning) and adaptive communication (Vineland Adaptive Behavior Scales--II). Social communication was rated from seminaturalistic interaction samples using the Brief Observation of Social Communication Change. Results: Children with the FXpm showed delayed social communication development, with the magnitude of group differences highlighting social communication as a feature that distinguishes children with the FXpm from their peers (p = 0.046, [partial eta-squared] = 0.12). The groups did not differ on the standardized language and adaptive communication measures (ps > 0.297, [partial eta-squared]s < 0.03). Conclusions: Early screening and treatment of social communication delays may be key to optimizing outcomes for children with the FXpm. Further research is needed to replicate findings in a larger sample, delineate the trajectory and consequences of social communication difficulties across the life span in the FXpm, and determine the potential epidemiological significance of "FMR1" as a mediator of developmental communication differences within the general population.

There exists a significant limitation in the variety of organisms for which microarrays have been developed because of a lack of genomic sequence data. A near-term solution to this limitation is to use microarrays designed for one species to analyze RNA samples from closely related species. The assumption is that conservation of gene sequences between species will be sufficient to generate a reasonable amount of goodquality data. While there have been relatively few published reports describing the use of microarrays for cross-species hybridizations, this technique is potentially a powerful tool for understanding genomics in model organisms such as nonhuman primates. Here we describe the analysis and comparison of hybridization characteristics and data variability from a set of crossspecies (rhesus macaque) and same-species (human) hybridization experiments using human high-density Affymetrix oligonucleotide arrays. The data reveal that a large fraction of probe sets are effective at transcript detection in the cross-species hybridization, validating the application of cross-species hybridizations for nonhuman primate genomics research.