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Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals’ unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference–determined cognitive statuses and subjective impairment. Results: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. Conclusions: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1–14)
This article reviews the major paradigm shifts that have occurred in the area of the application of clinical and experimental neuropsychology to epilepsy and epilepsy surgery since the founding of the International Neuropsychological Society. The five paradigm shifts discussed include: 1) The neurobiology of cognitive disorders in epilepsy – expanding the landscape of syndrome-specific neuropsychological impairment; 2) pathways to comorbidities: bidirectional relationships and their clinical implications; 3) discovering quality of life: The concept, its quantification and applicability; 4) outcomes of epilepsy surgery: challenging conventional wisdom; and 5) Iatrogenic effects of treatment: cognitive and behavioral effects of antiepilepsy drugs. For each area we characterize the status of knowledge, the key developments that have occurred, and how they have altered our understanding of the epilepsies and their management. We conclude with a brief overview of where we believe the field will be headed in the next decade which includes changes in assessment paradigms, moving from characterization of comorbidities to interventions; increasing development of new measures, terminology and classification; increasing interest in neurodegenerative proteins; transitioning from clinical seizure features to modifiable risk factors; and neurobehavioral phenotypes. Overall, enormous progress has been made over the lifespan of the INS with promise of ongoing improvements in understanding of the cognitive and behavioral complications of the epilepsies and their treatment. (JINS, 2017, 23, 791–805)
Radio-echo sounding (RES) techniques are used to examine spatial changes in bed reflectivity across relict ice streams inWest Antarctica. Measurements from adjacent interstream ridges are used to correct the measured power returned from the bed for attenuation and losses due to geometric spreading, scattering and absorption. RES measurements near boreholes drilled on Ice Stream C (ISC) indicate high coefficients of bed reflectivity (R > 0.1) in locations where the bed was thawed and boreholes connected to the basal water system, and low reflectivity coefficients (R < 0.02) at locations that were frozen and not connected. Intermediate values of bed reflectivity were measured at locations where the connection to the basal water system was weak. Measurements across four relict margins show that bed reflectivity usually jumps from low to high values several kilometers inside the outermost buried crevasses. We interpret this to be a transition from frozen to thawed basal conditions and discuss implications of these observations.
Objectives: The purpose of this study was to investigate the longitudinal trajectory of self- and informant-subjective cognitive complaints (SCC), and to determine if SCC predict longitudinal changes in objective measures (OM) of cognitive function. Methods: The study included healthy and cognitively normal late middle-aged adults enriched with a family history of AD who were evaluated at up to three visits over a 4-year period. At each visit (Visit 1–3), self- and informant-SCC and OM were evaluated. Linear mixed models were used to determine if the longitudinal rate of change of self- and informant-SCC were associated with demographic variables, depressive symptoms, family history (FH), and apolipoprotein epsilon 4 (APOE4) status. The same modeling approach was used to examine the effect of Visit 1 SCC on longitudinal cognitive change after controlling for the same variables. Results: At Visit 1, more self-SCC were associated with fewer years of education and more depressive symptoms. SCC were also associated with poorer performance on cognitive measures, such that more self-SCC at Visit 1 were associated with poorer performance on memory and executive functioning measures at Visit 1, while more informant-SCC were associated with faster rate of longitudinal decline on a measure of episodic learning and memory. FH and APOE4 status were not associated with SCC. Discussion: Self- and informant-SCC showed an association with OM, albeit over different time frames in our late middle-aged sample. Additional longitudinal follow-up will likely assist in further clarifying these relationships as our sample ages and more pronounced cognitive changes eventually emerge. (JINS, 2017, 23, 617–626)
Digital terrain models (DTM) are a very important tool for all sorts of glacier studies and serve as a basis for many applications. The latest development is the combination of DTM with digital image-processing techniques which enable a much better visualization of the DTM, and thus a better interpretation of glaciological phenomena.
These new technologies have been applied in an investigation of the Vaughan Lewis Icefall, Juneau Icefield, Alaska. A DTM has been produced by means of photogrammetrie measurements, and a glacier-flow velocity of up to 5.70 m d−1 in the steepest part has been derived. The possibilities for the interpretation of the glacier topography have been significantly improved by using digital image-processing algorithms for the visualization of the DTM.
We apply the immersed boundary (or IB) method to simulate deformation and detachment of a periodic array of wall-bounded biofilm colonies in response to a linear shear flow. The biofilm material is represented as a network of Hookean springs that are placed along the edges of a triangulation of the biofilm region. The interfacial shear stress, lift and drag forces acting on the biofilm colony are computed by using fluid stress jump method developed by Williams, Fauci and Gaver [Disc. Con-tin. Dyn. Sys. B 11(2):519–540, 2009], with a modified version of their exclusion filter. Our detachment criterion is based on the novel concept of an averaged equivalent continuum stress tensor defined at each IB point in the biofilm which is then used to determine a corresponding von Mises yield stress; wherever this yield stress exceeds a given critical threshold the connections to that node are severed, thereby signalling the onset of a detachment event. In order to capture the deformation and detachment behaviour of a biofilm colony at different stages of growth, we consider a family of four biofilm shapes with varying aspect ratio. For each aspect ratio, we varied the spacing between colonies to investigate role of spatial clustering in offering protection against detachment. Our numerical simulations focus on the behaviour of weak biofilms (with relatively low yield stress threshold) and investigate features of the fluid-structure interaction such as locations of maximum shear and increased drag. The most important conclusions of this work are: (a) reducing the spacing between colonies reduces drag by from 50 to 100% and alters the interfacial shear stress profile, suggesting that even weak biofilms may be able to grow into tall structures because of the protection they gain from spatial proximity with other colonies; (b) the commonly employed detachment strategy in biofilm models based only on interfacial shear stress can lead to incorrect or inaccurate results when applied to the study of shear induced detachment of weak biofilms. Our detachment strategy based on equivalent continuum stresses provides a unified and consistent IB framework that handles both sloughing and erosion modes of biofilm detachment, and is consistent with strategies employed in many other continuum based biofilm models.
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
El hallazgo de pipas en contextos fúnebres del litoral del Desierto de Atacama hace más de un siglo, ha sido la base para sugerir que los grupos de Pescadores, cazadores y recolectores marinos tuvieron como costumbre fumar durante el período Formativo (1500 a.C-1000 cal d.C). Lo que seguía siendo una incógnita es qué estaban fumando y de dónde provenían las sustancias consumidas. En la búsqueda de dar solución a este problema, presentamos el análisis de los residuos adheridos de cuatro pipas de piedra en forma de T invertida, recuperadas de un cementerio de la costa del Desierto de Atacama al norte de Chile, usando dos metodologías complementarias derivadas de la arqueobotánica y la química. Paralelamente, realizamos un análisis químico sobre cabello humano perteneciente a un individuo asociado a una de las pipas. Se logró identificar, al interior de éstas, la presencia de nicotina y otras sustancias, tales como microrrestos de Nicotiana y de otras especies, además de nicotina, en el cabello muestreado. Finalmente, discutimos estos resultados en función de la disponibilidad defuentes de estos recursos, estrategias de movilidad, relaciones de intercambio y el modo de vida de las poblaciones litorales.
Snuff trays are conspicuous objects that are found in archaeological contexts throughout Andean South America. At San Pedro de Atacama, in northern Chile, snuff trays that exhibit iconographic motifs similar to those found on Tiwanaku megalithic monuments have been assigned to the Tiwanaku style. In the present work, we propose a new definition for this style based on the occurrence of three morphological features: an overall trapezoidal shape, incurving sides, and sharp top corners. This group includes trays with iconography from the previously defined Tiwanaku style, as well as other trays without iconography. Principal component analysis shows that Tiwanaku-style trays with and without iconography make up a single group that is significantly different from plain, largely rectangular San Pedro-style trays. The relative proportion of Tiwanaku-style trays with and without iconography does not differ between cultural periods and archaeological sites. The results point to shape as an important trait for assigning trays to styles. Furthermore, the results show that during the Middle period four main types of snuff trays were in use: Tiwanaku trays with and without iconography and local San Pedro trays, also with and without iconography. We explore the possible social implications of this co-occurrence of styles.
The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed. (JINS, 2014, 20, 1–12)
If a photovoltaic (PV) technology is assessed today in a technical framework, then efficiency is the most commonly addressed parameter, followed by service lifetime. Cost, as the third parameter of the "magic triangle", is even less often reported. However, if a new technology is prepared to enter a market, other important parameters have to be considered, especially if non-standard PV applications are targeted.
Organic photovoltaic (OPV) is a well known but young PV technology of the so called third generation, which offers unique advantages for integrated products such as building integrated photovoltaics (BIPV). In this contribution we would like to highlight some of the advantages and challenges which are specific to the application of OPV in the field of building integration. Architectural design features of OPV include the ability to adapt semi-transparency, color and shape of the module. Moreover, glass-laminated OPV modules are deemed suitable for BIPV because of their ease of integration, good fire resistance, high energy harvest per nominal watt-peak and long lifetimes.
This paper gives a bird's-eye view of the various ingredients that make up a modern, model-checking-based approach to performability evaluation: Markov reward models, temporal logics and continuous stochastic logic, model-checking algorithms, bisimulation and the handling of non-determinism. A short historical account as well as a large case study complete this picture. In this way, we show convincingly that the smart combination of performability evaluation with stochastic model-checking techniques, developed over the last decade, provides a powerful and unified method of performability evaluation, thereby combining the advantages of earlier approaches.
Vitamin D and folate are associated with decreased colorectal cancer risk and their association with colorectal cancer prognosis is under investigation. We assessed the levels of plasma 25-hydroxyvitamin D3 (25(OH)D3), folate and vitamin B12 in an international pilot study in order to determine variability of these biomarkers based on geographical location. Plasma 25(OH)D3, folate and vitamin B12 concentrations were measured in 149 invasive, newly diagnosed colorectal cancer cases from Heidelberg (Germany), Seattle (WA, USA), and Tampa (FL, USA) and in ninety-one age- and sex-matched controls. Their associations with potential predictors were assessed using multivariate linear regression analyses. Plasma 25(OH)D3, folate and vitamin B12 concentrations differed by location. Other predictors were season for 25(OH)D3 and tumour stage (vitamin B12). Season-corrected average 25(OH)D3 concentrations were higher in Heidelberg (31·7 ng/ml; range 11·0–83·0 ng/ml) than in Seattle (23·3 ng/ml; range 4·0–80·0 ng/ml) and Tampa (21·1 ng/ml; range 4·6–51·6 ng/ml). In Heidelberg, a strong seasonal variation was observed. Folate (11·1 ng/ml) and vitamin B12 (395 pg/ml) concentrations in Heidelberg were lower than those in Seattle (25·3 ng/ml and 740 pg/ml, respectively) and Tampa (23·8 ng/ml and 522 pg/ml, respectively). Differences in plasma 25(OH)D3 and folate concentrations between Heidelberg and the US sites were observed, probably reflecting variation in outdoor activities and sun-avoidance behaviour during summer as well as in folic acid fortification and supplement use. Intra-site differences at each study location were greater than between-location variability, suggesting that individual health behaviours play a significant role. Nevertheless, the intra-site differences we observed may be due to chance because of the limited sample size. Our pilot study illustrates the value of an international cohort in studying colorectal cancer prognosis to discern geographical differences in a broad range of exposures.
MarcoPolo-R is a sample return mission to a primitive Near-Earth Asteroid (NEA) selected in February 2011 for the Assessment Study Phase at ESA in the framework of ESAfs Cosmic Vision 2 program. MarcoPolo-R is a European-led mission with a proposed NASA contribution. MarcoPolo-R takes advantage of three industrial studies completed as part of the previous Marco Polo mission (see ESA/SRE (2009)3). The aim of the new Assessment Study is to reduce the cost of the mission while maintaining its high science level, on the basis of advanced studies and technologies, as well as optimization of the mission. MarcoPolo-R will rendezvous with a unique kind of target, a primitive binary NEA, scientifically characterize it at multiple scales, and return a unique pristine sample to Earth unaltered by the atmospheric entry process or terrestrial weathering. The baseline target of MarcoPolo-R is the primitive binary NEA (175706) 1996 FG3, which offers a very efficient operational and technical mission profile. A binary target also provides enhanced science return: the choice of this target will allow new investigations to be performed more easily compared to a single object, and also enables investigations of the fascinating geology and geophysics of asteroids that are impossible to obtain from a single object. Precise measurements of the mutual orbit and rotation state of both components can be used to probe higher-level harmonics of the gravitational potential, and therefore the internal structure. A unique opportunity is offered to study the dynamical evolution driven by the YORP/Yarkovsky thermal effects. Possible migration of regolith on the primary from poles to equator allows the increasing maturity of asteroidal regolith with time to be expressed as a latitude-dependent trend, with the most-weathered material at the equator matching what is seen in the secondary. MarcoPolo-R will allow us to study the most primitive materials available to investigate early solar system formation processes. Moreover, MarcoPolo-R will provide a sample from a known target with known geological context. Direct investigation of both the regolith and fresh interior fragments is also impossible by any means other than sample return. The main goal of the MarcoPolo-R mission is to return unaltered NEA material for detailed analysis in ground-based laboratories. The limited sampling provided by meteorites does not offer the most primitive material available in near-Earth space. More primitive material, having experienced less alteration on the asteroid, will be more friable and would not survive atmospheric entry in any discernible amount. Only in the laboratory can instruments with the necessary precision and sensitivity be applied to individual components of the complex mixture of materials that forms an asteroid regolith, to determine their precise chemical and isotopic composition. Such measurements are vital for revealing the evidence of stellar, interstellar medium, pre-solar nebula and parent body processes that are retained in primitive asteroidal material, unaltered by atmospheric entry or terrestrial contamination. It is no surprise therefore that sample return missions are considered a priority by a number of the leading space agencies.