Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

We examined the association between bilingualism, executive function (EF), and brain volume in older monolinguals and bilinguals who spoke English, Spanish, or both, and were cognitively normal (CN) or diagnosed with Mild Cognitive Impairment (MCI) or dementia. Gray matter volume (GMV) was higher in language and EF brain regions among bilinguals, but no differences were found in memory regions. Neuropsychological performance did not vary across language groups over time; however, bilinguals exhibited reduced Stroop interference and lower scores on Digit Span Backwards and category fluency. Higher scores on Digit Span Backwards were associated with a younger age of English acquisition, and a greater degree of balanced bilingualism was associated with lower scores in category fluency. The initial age of cognitive decline did not differ between language groups. The influence of bilingualism appears to be reflected in increased GMV in language and EF regions, and to a lesser degree, in EF.

A laboratory intercomparison project was carried out on 20 annually resolved late-wood samples from the Danish oak record. The project included the following three laboratories: (1) the University of Arizona AMS Laboratory, University of Arizona, USA (AA); (2) HEKAL AMS Laboratory, MTA Atomki, Hungary (DeA); and (3) Aarhus AMS Centre (AARAMS), Aarhus University, Denmark (AAR). The large majority of individual data points (96%) lie within ±2σ of the weighted mean. Further assessment of the accuracy associated with the individual laboratories showed good agreement, indicating that consistent and reliable 14C measurements well in agreement with each other are produced at the three laboratories. However, the quoted analytical uncertainties appear to be underestimated when compared to the observed variance of differences from the geometric mean of the samples. This study provides a general quality check of the single-year tree-ring 14C measurements that are included in the new calibration curve.

The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.

From 2007 to 2010, the largest reported Q-fever epidemic occurred in the Netherlands with 4026 notified laboratory-confirmed cases. During the course of the epidemic, health-seeking behaviour changed and awareness among health professionals increased. Changes in laboratory workflows were implemented. The aim of this study was to analyse how these changes instigated adjustments of notification criteria and how these adjustments affected the monitoring and interpretation of the epidemic. We used the articles on laboratory procedures related to the epidemic and a description of the changes that were made to the notification criteria. We compared the output of a regional laboratory with notifications to the regional Public Health Service and the national register of infectious diseases. We compared the international notification criteria for acute Q-fever. Screening with ELISA IgM phase II and PCR was added to the diagnostic workflow. In the course of the epidemic, serology often revealed a positive IgG/IgM result although cases were not infected recently. With increasing background seroprevalence, the presence of IgM antibodies can only be suggestive for acute Q-fever and has to be confirmed either by seroconversion of IgG or a positive PCR result. Differences in sero-epidemiology make it unlikely that full harmonisation of notification criteria between countries is feasible.

We derive a mathematical model for the drawing of a two-dimensional thin sheet of viscous fluid in the direction of gravity. If the gravitational field is sufficiently strong, then a portion of the sheet experiences a compressive stress and is thus unstable to transverse buckling. We analyse the dependence of the instability and the subsequent evolution on the process parameters, and the mutual coupling between the weakly nonlinear buckling and the stress profile in the sheet. Over long time scales, the sheet centreline ultimately adopts a universal profile, with the bulk of the sheet under tension and a single large bulge caused by a small compressive region near the bottom, and we derive a canonical inner problem that describes this behaviour. The large-time analysis involves a logarithmic asymptotic expansion, and we devise a hybrid asymptotic–numerical scheme that effectively sums the logarithmic series.

Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7–9.0) for season 2011/2012, 36.7 (95% UI: 31.2–42.8) for 2012/2013, 9.1 (95% UI: 6.3–12.9) for 2013/2014, 41.1 (95% UI: 35.0–47.7) for 2014/2015, 39.4 (95% UI: 33.4–46.1) for 2015/2016 and 27.8 (95% UI: 22.7–33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation – with appropriately quantified uncertainty – of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.

Objectives: Maintaining two active languages may increase cognitive and brain reserve among bilingual individuals. We explored whether such a neuroprotective effect was manifested in the performance of memory tests for participants with amnestic mild cognitive impairment (aMCI). Methods: We compared 42 bilinguals to 25 monolinguals on verbal and nonverbal memory tests. We used: (a) the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive test that taps into proactive, retroactive, and recovery from proactive semantic interference (verbal memory), and (b) the Benson Figure delayed recall (nonverbal memory). A subsample had volumetric MRI scans. Results: The bilingual group significantly outperformed the monolingual group on two LASSI-L cued recall measures (Cued A2 and Cued B2). A measure of maximum learning (Cued A2) showed a correlation with the volume of the left hippocampus in the bilingual group only. Cued B2 recall (sensitive to recovery from proactive semantic interference) was correlated with the volume of the hippocampus and the entorhinal cortex of both cerebral hemispheres in the bilingual group, as well as with the left and right hippocampus in the monolingual group. The memory advantage in bilinguals on these measures was associated with higher inhibitory control as measured by the Stroop Color-Word test. Conclusions: Our results demonstrated a superior performance of aMCI bilinguals over aMCI monolinguals on selected verbal memory tasks. This advantage was not observed in nonverbal memory. Superior memory performance of bilinguals over monolinguals suggests that bilinguals develop a different and perhaps more efficient semantic association system that influences verbal recall. (JINS, 2019, 25, 15–28)

Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.

SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.

SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.

Introduction: EMS time factors such as total prehospital, activation, response, scene and transport intervals have been used as a measure of EMS system quality with the assumption that shorter EMS time factors save lives. The objective was to assess in adults and children accessing ground EMS (population), whether operational time factors (intervention and control) were associated with survival at hospital discharge (outcome). Methods: Medline, EMBASE, and CINAHL were searched up to January 2015 for articles reporting original data that associated EMS operational time factors and survival. Conference abstracts and non-English language articles were excluded. Two investigators independently assessed the candidate titles, abstracts, and full text with discrepant reviews resolved by consensus. Risk of bias was assessed using GRADE. Results: A total of 10,151 abstracts were screened for potential inclusion, 199 articles were reviewed in full-text, and 73 met inclusion criteria. Amongst included studies, 49 investigated response time, while 24 investigated other time factors. All articles were observational studies. Amongst the 14 (28.6%) studies where response time was the primary analysis, statistically significant associations between shorter response time and increased survival were found in 5 of 7 cardiac arrest, 1 of 5 general EMS population, and 0 of 2 trauma studies. Other time factors were reported in the primary analysis in 10 (41.7%) studies. One study reported shorter combined scene and transport intervals associated with increased survival in acute heart failure patients. Two studies in trauma patients had somewhat conflicting results with one study reporting shorter prehospital interval associated with increased survival whereas the other reported increased survival associated with longer scene and transport intervals. Study design, analysis, and methodological quality were of considerable variability, and thus, meta-analyses were not possible. Conclusion: There is a substantial body of literature describing the association between EMS time factors and survival, but evidence informing these relationships are heterogeneous and complex. Important details such as patient population, EMS system characteristics, and analytical approach must be taken into consideration to appropriately translate these findings to practice. These results will be important for EMS leaders wishing to create evidence-based time policies.

Violators of cooperation norms may be informally punished by their peers. How such norm enforcement is judged by others can be regarded as a meta-norm (i.e., a second-order norm). We examined whether meta-norms about peer punishment vary across cultures by having students in eight countries judge animations in which an agent who over-harvested a common resource was punished either by a single peer or by the entire peer group. Whether the punishment was retributive or restorative varied between two studies, and findings were largely consistent across these two types of punishment. Across all countries, punishment was judged as more appropriate when implemented by the entire peer group than by an individual. Differences between countries were revealed in judgments of punishers vs. non-punishers. Specifically, appraisals of punishers were relatively negative in three Western countries and Japan, and more neutral in Pakistan, UAE, Russia, and China, consistent with the influence of individualism, power distance, and/or indulgence. Our studies constitute a first step in mapping how meta-norms vary around the globe, demonstrating both cultural universals and cultural differences.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to use the baboon as a novel animal model for breath research and to identify and characterize baboon breath metabolites that reflect cardiometabolic function to inform us in the development of a noninvasive, cost-effective, and repeatable point-of-care diagnostic breath test. METHODS/STUDY POPULATION: Blood and urine was collected from control and IUGR at the approximate age of 3.5 years. Both groups were then placed on a high fat, high sugar, high salt diet for 7 weeks, after which blood, urine, and breath were collected. The breath samples were then subjected to comprehensive, 2-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Using ChromaTOF software, breath VOCs were identified with at least an 80% spectral match against the National Institute of Standards and Technology (NIST) chemical reference library. The raw data were then statistically analyzed using MetaboAnalyst. We then interrogated multiple online databases to characterize and identify the role of VOCs that were present in both control and IUGR groups. RESULTS/ANTICIPATED RESULTS: Preliminary analyses of the breath VOCs indicate differences in expression between sexes and in control Versus IUGR groups. These results indicate unique “breath signatures.” Further analysis of the breath VOCs reveals the presence of metabolites that are involved in β-oxidation and oxidative stress pathways. DISCUSSION/SIGNIFICANCE OF IMPACT: This breath study, a first of its kind, will develop the baboon as a superior animal model for breath biomarker research. Our observed unique “breath signatures” indicate changes in lipid metabolism and oxidative stress pathways, which we hypothesize are the early metabolic changes at the cellular level that are not yet reflected in clinical lab measures. Future directions include analyzing breath VOCs that did not meet 80% spectral match, validation using SPME technology and commercial standards, and initiating a human pilot study in clinically obese, at-risk children in collaboration with physicians at the Children’s Hospital of San Antonio to develop a noninvasive, cost-effective, rapid, and repeatable point-of-care diagnostic breath test.