Untersuchung zur Bestimmung quantitativer Parameter der Lungenventilation mittels CT und MRT

Die zuverlässige Berechnung von quantitativen Parametern der Lungenventilation ist für ein Verständnis des Verhaltens der Lunge und insbesondere für die Diagnostik von Lungenerkrankungen von großer Bedeutung. Nur durch quantitative Parameter sind verlässliche und reproduzierbare diagnostische Aussagen über den Gesundheitszustand der Lunge möglich. Im Rahmen dieser Arbeit wurden neue quantitative Verfahren zur Erfassung der Lungenventilation basierend auf der dynamischen Computer- (CT) und Magnetresonanztomographie (MRT) entwickelt. Im ersten Teil dieser Arbeit wurde die Frage untersucht, ob das Aufblähen der Lunge in gesunden Schweinelungen und Lungen mit Akutem Lungenversagen (ARDS) durch einzelne, diskrete Zeitkonstanten beschrieben werden kann, oder ob kontinuierliche Verteilungen von Zeitkonstanten die Realität besser beschreiben. Hierzu wurden Serien dynamischer CT-Aufnahmen während definierter Beatmungsmanöver (Drucksprünge) aufgenommen und anschließend aus den Messdaten mittels inverser Laplace-Transformation die zugehörigen Verteilungen der Zeitkonstanten berechnet. Um die Qualität der Ergebnisse zu analysieren, wurde der Algorithmus im Rahmen von Simulationsrechnungen systematisch untersucht und anschließend in-vivo an gesunden und ARDS-Schweinelungen eingesetzt. Während in den gesunden Lungen mono- und biexponentielle Verteilungen bestimmt wurden, waren in den ARDS-Lungen Verteilungen um zwei dominante Zeitkonstanten notwendig, um die gemessenen Daten auf der Basis des verwendeten Modells verlässlich zu beschreiben. Es wurden sowohl diskrete als auch kontinuierliche Verteilungen gefunden. Die CT liefert Informationen über das solide Lungengewebe, während die MRT von hyperpolarisiertem 3He in der Lage ist, direkt das eingeatmete Gas abzubilden. Im zweiten Teil der Arbeit wurde zeitlich hochaufgelöst das Einströmen eines 3He-Bolus in die Lunge erfasst. Über eine Entfaltungsanalyse wurde anschließend das Einströmverhalten unter Idealbedingungen (unendlich kurzer 3He-Bolus), also die Gewebeantwortfunktion, berechnet und so eine Messtechnik-unabhängige Erfassung des Einströmens von 3He in die Lunge ermöglicht. Zentrale Fragestellung war hier, wie schnell das Gas in die Lunge einströmt. Im Rahmen von Simulationsrechnungen wurde das Verhalten eines Entfaltungsalgorithmus (basierend auf B-Spline Repräsentationen) systematisch analysiert. Zusätzlich wurde ein iteratives Entfaltungsverfahren eingesetzt. Aus zeitlich hochaufgelösten Messungen (7ms) an einer gesunden und einer ARDS-Schweinelunge konnte erstmals nachgewiesen werden, dass das Einströmen in-vivo in weniger als 0,1s geschieht. Die Ergebnisse zeigen Zeitkonstanten im Bereich von 4ms–50ms, wobei zwischen der gesunden Lungen und der ARDS-Lunge deutliche Unterschiede beobachtet wurden. Zusammenfassend ermöglichen daher die in dieser Arbeit vorgestellten Algorithmen eine objektivere Bestimmung quantitativer Parameter der Lungenventilation. Dies ist für die eindeutige Beschreibung ventilatorischer Vorgänge in der Lunge und somit für die Lungendiagnostik unerlässlich. Damit stehen quantitative Methoden für die Lungenfunktionsdiagnostik zur Verfügung, deren diagnostische Relevanz im Rahmen wissenschaftlicher und klinischer Studien untersucht werden kann.

Entschlüsselung des Carotinoid-Metabolismus im marinen Schwamm Suberites domuncula

Die Enzyme des Carotinoidstoffwechsels spalten Provitamin A-Carotinoide in wichtige Retinoide (z.B. Vitamin A, Retinsäure), die Organismen während der Entwicklung und in visuellen Systemen benötigen. Die vorliegende Arbeit präsentiert erstmalig eine Carotinoxygenase (BCO) aus Schwämmen (S. domuncula), die einzigartig im Tierreich ist und nur einen orthologen Vertreter in Pflanzen (Crocus sativus) wieder findet. Das Enzym ist eine 7,8(7’,8’)-Carotinoxygenase, die C40-Carotinoide zu einem C10-Apocarotinoid und 8’-Apocarotinal spaltet. Mittels HPLC wurden sowohl die Primärspaltprodukte von β-Carotin, Lykopin und Zeaxanthin als auch das für alle identische innere Kettenstück (Crocetin) bei Doppelspaltung nachgewiesen. Der Nachweis der BCO-Transkripte (unter anderem in-situ) belegt eine Beteiligung des Enzyms während Entwicklungsprozessen und offenbart sowohl eine streng räumlich-zeitliche als auch eine über Rückkopplungsprozesse gesteuerte Regulierung des Enzyms. Ein weiteres hier identifiziertes Gen ähnelt einer bakteriellen Apocarotinoidoxygenase (ACO), welche das 8’-Apocarotinal der BCO erneut spaltet und so Retinal generiert. Letzteres dient als Chromophor zahlreicher visueller Systeme und kann über Enzyme des Retinoidstoffwechsels entweder gespeichert, oder in das wichtige Morphogen Retinsäure umgesetzt werden. Hier werden zwei potentielle Enzyme vorgestellt, die an dieser Interkonversion Retinal/Retinol (Speicher) beteiligt sein könnten als auch eines, das evtl. Retinal zu Retinsäure umsetzt. Die hier vorgestellten Ergebnisse unterstützen die Hypothese, dass Retinsäure kein autapomorphes Morphogen der Chordaten darstellt.

Analisi climatica ad alta risoluzione delle precipitazioni sul nord Italia (1961-2005)

L’obiettivo di questo lavoro di tesi è di ottenere un’analisi climatica giornaliera ad alta risoluzione della precipitazione sul territorio del nord Italia realizzata con tecniche di controllo statistico, di analisi e di strumenti di descrizione dei risultati presentati nella recente letteratura. A tal fine, sono stati utilizzati i dati dell’Archivio ARCIS. In seguito alle fasi di controllo qualità, omogeneità e sincronicità i dati sono stati utilizzati per realizzare un’analisi giornaliera su grigliato regolare a 10 km di risoluzione utile alla rappresentazione della variabilità spazio-temporale della precipitazione sul Nord Italia per il periodo 1961-2005. I risultati di tale analisi mettono in evidenza dei valori medi di precipitazione annuale abbastanza intensi sulla parte centrale dell’arco Alpino, con massimi (oltre 2000 mm) sull’estremità orientale e sull’Appennino Ligure. Valori minimi (500 – 600 mm) sono osservati lungo le aree prospicienti il fiume Po, in Val d’Aosta ed in Alto Adige. La corrispondente analisi del trend temporale indica la presenza di lievi cali statisticamente significativi solo in aree limitate del territorio. In coerenza con questi risultati, la variazione nel tempo della precipitazione annuale mediata su tutto il territorio mette in evidenza un’intensa variabilità decennale, ma solo una lieve flessione lineare sull’intero periodo. Il numero annuo di giorni piovosi ed il 90° percentile della precipitazione giornaliera presentano invece trend lineari un po’ più pronunciati. In particolare, sul periodo considerato si nota un calo del numero di giorni piovosi su gran parte del territorio e solo su alcune aree del territorio un aumento dell’intensità del 90° percentile, sia a scala annuale che stagionale. Nell’ultima parte di questo lavoro è stato realizzato uno studio della relazione fra la forzante climatica e l’evoluzione della morfologia dell’Appennino Emiliano-Romagnolo. I risultati mostrano che a parità di quota, di pendenza e di litologia, la franosità è influenzata dalle precipitazioni.

Gait analysis using a single wearable inertial measurement unit

Procedures for quantitative walking analysis include the assessment of body segment movements within defined gait cycles. Recently, methods to track human body motion using inertial measurement units have been suggested. It is not known if these techniques can be readily transferred to clinical measurement situations. This work investigates the aspects necessary for one inertial measurement unit mounted on the lower back to track orientation, and determine spatio-temporal features of gait outside the confines of a conventional gait laboratory. Apparent limitations of different inertial sensors can be overcome by fusing data using methods such as a Kalman filter. The benefits of optimizing such a filter for the type of motion are unknown. 3D accelerations and 3D angular velocities were collected for 18 healthy subjects while treadmill walking. Optimization of Kalman filter parameters improved pitch and roll angle estimates when compared to angles derived using stereophotogrammetry. A Weighted Fourier Linear Combiner method for estimating 3D orientation angles by constructing an analytical representation of angular velocities and allowing drift free integration is also presented. When tested this method provided accurate estimates of 3D orientation when compared to stereophotogrammetry. Methods to determine spatio-temporal features from lower trunk accelerations generally require knowledge of sensor alignment. A method was developed to estimate the instants of initial and final ground contact from accelerations measured by a waist mounted inertial device without rigorous alignment. A continuous wavelet transform method was used to filter and differentiate the signal and derive estimates of initial and final contact times. The technique was tested with data recorded for both healthy and pathologic (hemiplegia and Parkinson’s disease) subjects and validated using an instrumented mat. The results show that a single inertial measurement unit can assist whole body gait assessment however further investigation is required to understand altered gait timing in some pathological subjects.

Neural network activity in the neonatal acute slice, slice culture and cell culture

Information processing and storage in the brain may be presented by the oscillations and cell assemblies. Here we address the question of how individual neurons associate together to assemble neural networks and present spontaneous electrical activity. Therefore, we dissected the neonatal brain at three different levels: acute 1-mm thick brain slice, cultured organotypic 350-µm thick brain slice and dissociated neuronal cultures. The spatio-temporal properties of neural activity were investigated by using a 60-channel Micro-electrode arrays (MEA), and the cell assemblies were studied by using a template-matching method. We find local on-propagating as well as large- scale propagating spontaneous oscillatory activity in acute slices, spontaneous network activity characterized by synchronized burst discharges in organotypic cultured slices, and autonomous bursting behaviour in dissociated neuronal cultures. Furthermore, repetitive spike patterns emerge after one week of dissociated neuronal culture and dramatically increase their numbers as well as their complexity and occurrence in the second week. Our data indicate that neurons can self-organize themselves, assembly to a neural network, present spontaneous oscillations, and emerge spatio-temporal activation patterns. The spontaneous oscillations and repetitive spike patterns may serve fundamental functions for information processing and storage in the brain.

Hox genes and the regulation of programmed cell death in the embryonic central nervous system of Drosophila melanogaster

This study deals with the function and regulation of programmed cell death, or apoptosis, in the development of the embryonic central nervous system of Drosophila melanogaster. The first part provides a description of apoptosis-deficient embryos, which showed that preventing apoptosis does not cause gross morphological defects in the CNS, as it appears well organized despite the presence of too many cells. An analysis of the incidence and pattern of apoptosis over the course of development discloses a partly very orderly pattern suggesting tight spatio-temporal control, but also reveals random apoptotic cells, which suggests a certain amount of plasticity in the embryo. This analysis also allowed precise identification of some of the dying neural cells in the embryo, and establishment of single cell models for studying regulation of segment-specific apoptosis in the embryonic CNS. In the second part of the work, further investigations into mechanisms controlling segment-specific apoptosis revealed the involvement of two Hox genes, Antennapedia (Antp) and Ultrabithorax (Ubx), in this process. Hox genes control the formation of segment-specific structures in their domains of expression, but also regulate organ and tissue morphogenesis. The study presented here shows that Antp and Ubx play antagonistic roles in motoneuron survival in the embryo. Ubx expression in the CNS is strongly upregulated at a late point in development, when most cells have begun to differentiate. This upregulation shortly precedes Ubx-dependent, segment-specific apoptosis of two differentiated motoneurons. It could further be demonstrated that Antp is required for proper development of the NB7-3 lineage and for survival of the NB7-3 motoneuron in the anterior thoracic segments. In segments where Antp and Ubx expression overlaps, Ubx counteracts the anti-apoptotic function of Antp, resulting in cell death. Thus, these two Hox genes play opposing roles in the survival of differentiated neurons in the late developing nervous system. They thereby contribute to establishment of correct connections between outward-projecting neurons and their targets, which is crucial for the assembly of functional neural circuits, as these have to fulfill region-specific locomotion and sensory requirements along the antero-posterior body axis.

Temperature Variation Aware Energy Optimization in Heterogeneous MPSoCs

Thermal effects are rapidly gaining importance in nanometer heterogeneous integrated systems. Increased power density, coupled with spatio-temporal variability of chip workload, cause lateral and vertical temperature non-uniformities (variations) in the chip structure. The assumption of an uniform temperature for a large circuit leads to inaccurate determination of key design parameters. To improve design quality, we need precise estimation of temperature at detailed spatial resolution which is very computationally intensive. Consequently, thermal analysis of the designs needs to be done at multiple levels of granularity. To further investigate the flow of chip/package thermal analysis we exploit the Intel Single Chip Cloud Computer (SCC) and propose a methodology for calibration of SCC on-die temperature sensors. We also develop an infrastructure for online monitoring of SCC temperature sensor readings and SCC power consumption. Having the thermal simulation tool in hand, we propose MiMAPT, an approach for analyzing delay, power and temperature in digital integrated circuits. MiMAPT integrates seamlessly into industrial Front-end and Back-end chip design flows. It accounts for temperature non-uniformities and self-heating while performing analysis. Furthermore, we extend the temperature variation aware analysis of designs to 3D MPSoCs with Wide-I/O DRAM. We improve the DRAM refresh power by considering the lateral and vertical temperature variations in the 3D structure and adapting the per-DRAM-bank refresh period accordingly. We develop an advanced virtual platform which models the performance, power, and thermal behavior of a 3D-integrated MPSoC with Wide-I/O DRAMs in detail. Moving towards real-world multi-core heterogeneous SoC designs, a reconfigurable heterogeneous platform (ZYNQ) is exploited to further study the performance and energy efficiency of various CPU-accelerator data sharing methods in heterogeneous hardware architectures. A complete hardware accelerator featuring clusters of OpenRISC CPUs, with dynamic address remapping capability is built and verified on a real hardware.

Charakteristika und zeitliche Merkmale des Blickrichtungsnacheffekts

In der vorliegenden Arbeit werden verschiedene, insbesondere zeitliche Aspekte des Blickrichtungsnacheffekts (gaze aftereffect) untersucht. Dieser Effekt besagt, dass nach längerer Betrachtung von Bildern, die Personen mit abgewandtem Blick zeigen, die Wahrnehmung von Blickrichtungen in Richtung des adaptierten Blickes verschoben ist. Betrachter halten dann zugewandte Blicke fälschlicherweise für in die Gegenrichtung verschoben, und Blicke in die Adaptationsblickrichtung fälschlicherweise für geradeaus, d.h. sie fühlen sich angeschaut, obwohl sie es nicht werden. In dieser Dissertation wird der Blickrichtungsnacheffekt mit vier psychophysischen Experimenten untersucht, in denen die Probanden einfache kategoriale Urteile über die Blickrichtung der Testbilder abzugeben hatten.rnrnDas erste Experiment untersucht die Induktion des Blickrichtungsnacheffekts. Es wird gezeigt, dass keine separate Adaptationsphase für die Induktion des Nacheffekts notwendig ist. Auch die alleinige, relativ kurze Darbietung des zur Adaptation verwendeten Reizes (TopUp-Display) vor der Präsentation eines Testbildes führt im Laufe wiederholter experimenteller Darbietungen zu einer Verschiebung der allgemeinen Blickrichtungs-Tuningkurve, sowie zu ihrer Verbreiterung. In einem zweiten Experiment wird nachgewiesen, dass die Ausprägung des Blickrichtungsnacheffekts von der jeweiligen Darbietungszeit des Adaptationsreizes abhängt. Zwar ist der Nacheffekt umso stärker, je länger das TopUp-Display gezeigt wird. Aber auch bei sehr kurzen Darbietungszeiten von einer Sekunde kommt der Effekt bereits zustande, hier zeigt sich eine lokal begrenztere Wirkung. Die Auswertung des zeitlichen Verlaufs ergibt, dass sich der Effekt rasch vollständig aufbaut und bereits innerhalb der ersten Darbietungen entsteht. Das dritte Experiment zeigt, dass dem Nacheffekt sowohl kurzfristige Einwirkungen der direkt vor dem Testbild erfolgten Reizung zugrunde liegen, als auch langfristige Memory-Effekte, die über die im Laufe des Experiments gegebenen Wiederholungen akkumuliert werden. Bei Blickwinkeln von 5° halten sich kurzfristige und langfristige Einwirkungen in etwa die Waage. Bei Blickwinkeln von 10° aber sind nur knapp 20% kurzfristig, und etwa 80% langfristige Einwirkungen für den Effekt verantwortlich. In einem vierten Experiment wird die zeitliche Rückbildung des Effekts untersucht und gezeigt, dass sich der Blickrichtungsnacheffekt im Kontrast zu seiner schnellen Entstehung langsam, nämlich innerhalb mehrerer Minuten zurückbildet.rnrnDie Diskussion der Ergebnisse kommt zu dem Schluss, dass die hier gefundene zeitliche Dynamik des Blickrichtungsnacheffekts Adaptationsprozesse auf höheren Schichten der visuellen Informationsverarbeitung als die zugrunde liegenden Mechanismen nahe legt.

Megistobenthic faunal diversity of the Antalya Gulf: Crustacea

The spatio-temporal distribution of megistobenthic crustacean assemblages from the Antalya Gulf, located in the Levantine Sea is described. In order to provide a comprehensive overview of the spatio-temporal patterns of the crustacean community, 3 transect including depth of 10, 25, 75, 125 and 200 m, were studied between 2014 and 2015 to investigate their association with a set of environmental parameters in representative months of each season (spring, summer, autumn and winter). For its economic importance in Levantine waters, a focus analysis of deep-water rose shrimp Parapenaeus longirostris (Lucas, 1846) was done, to investigate the length frequency composition of the population of the Antalya Gulf. A total of 58 crustacean species were encountered in the study area, of these species identified, 18 species were recognized as alien species in the Mediterranean Sea. Throughout the year the most frequent species of the study were the hermit crab Pagurus prideaux (Leach, 1815) and Parapenaeus longirostris (Lucas, 1846) followed by the Indo-Pacific swimming crab Charybdis longicollis (Leene, 1938) and by the invasive shrimp Marsupenaeus japonicus (Spence Bate, 1888). Few species contributing to a high amount to the total biomass were found throughout the year. These species were Charybdis longicollis and Parapenaeus longirostris. Stations of the study area showed similar values of diversity indices of benthic crustacean community among the three transect. The highest values of faunistic indices were detected in autumn and winter (October and February), and also varied along the depth gradient, with the highest values found between 25 and 75 meters. The multivariate analyses conducted on the abundance data point out major differences between depths and between seasons. Therefore, according to cluster analysis and ordination over abundance and biomass, three main crustacean assemblages were detected: the first corresponding to shallow bottoms (10, 25 meters), the second corresponding to intermediate waters (75 meters) and the last to deeper waters (125, 200 meters). Depth was the main factor governing the distribution of megistobenthic crustacean in the area. Besides the depth, the structure of the sediment is the most important factor in determining the crustacean assemblage. Therefore, all factors governing the crustacean distribution were found to be related to the bottom depth. The population of Parapenaeus longirostris in the Antalya Gulf showed significant differences in depth. It was found that females dominated the population of the study area (65.11%), and were significantly larger than males for each cohort identified. The size-weight relationships revealed a slight negative allometry in growth, a bit more pronounced in females than in males.

Rapid adaptation of visual search in simulated hemianopia

Patients with homonymous hemianopia have altered visual search patterns, but it is unclear how rapidly this develops and whether it reflects a strategic adaptation to altered perception or plastic changes to tissue damage. To study the temporal dynamics of adaptation alone, we used a gaze-contingent display to simulate left or right hemianopia in 10 healthy individuals as they performed 25 visual search trials. Visual search was slower and less accurate in hemianopic than in full-field viewing. With full-field viewing, there were improvements in search speed, fixation density, and number of fixations over the first 9 trials, then stable performance. With hemianopic viewing, there was a rapid shift of fixation into the blind field over the first 5-7 trials, followed by continuing gradual improvements in completion time, number of fixations, and fixation density over all 25 trials. We conclude that in the first minutes after onset of hemianopia, there is a biphasic pattern of adaptation to altered perception: an early rapid qualitative change that shifts visual search into the blind side, followed by more gradual gains in the efficiency of using this new strategy, a pattern that has parallels in other studies of motor learning.

Emotions, Arousal, and Frontal Alpha Rhythm Asymmetry During Beethoven's 5th Symphony

Music is capable of inducing emotional arousal. While previous studies used brief musical excerpts to induce one specific emotion, the current study aimed to identify the physiological correlates of continuous changes in subjective emotional states while listening to a complete music piece. A total of 19 participants listened to the first movement of Ludwig van Beethoven's 5th symphony (duration: ~7.4 min), during which a continuous 76-channel EEG was recorded. In a second session, the subjects evaluated their emotional arousal during the listening. A fast fourier transform was performed and covariance maps of spectral power were computed in association with the subjective arousal ratings. Subjective arousal ratings had good inter-individual correlations. Covariance maps showed a right-frontal suppression of lower alpha-band activity during high arousal. The results indicate that music is a powerful arousal-modulating stimulus. The temporal dynamics of the piece are well suited for sequential analysis, and could be necessary in helping unfold the full emotional power of music.

Debris-flow activity in abandoned channels of the Manival torrent reconstructed with LiDAR and tree-ring data

Hydrogeomorphic processes are a major threat in many parts of the Alps, where they periodically damage infrastructure, disrupt transportation corridors or even cause loss of life. Nonetheless, past torrential activity and the analysis of areas affected during particular events remain often imprecise. It was therefore the purpose of this study to reconstruct spatio-temporal patterns of past debris-flow activity in abandoned channels on the forested cone of the Manival torrent (Massif de la Chartreuse, French Prealps). A Light Detecting and Ranging (LiDAR) generated Digital Elevation Model (DEM) was used to identify five abandoned channels and related depositional forms (lobes, lateral levees) in the proximal alluvial fan of the torrent. A total of 156 Scots pine trees (Pinus sylvestris L.) with clear signs of debris flow events was analyzed and growth disturbances (GD) assessed, such as callus tissue, the onset of compression wood or abrupt growth suppression. In total, 375 GD were identified in the tree-ring samples, pointing to 13 debris-flow events for the period 1931–2008. While debris flows appear to be very common at Manival, they have only rarely propagated outside the main channel over the past 80 years. Furthermore, analysis of the spatial distribution of disturbed trees contributed to the identification of four patterns of debris-flow routing and led to the determination of three preferential breakout locations. Finally, the results of this study demonstrate that the temporal distribution of debris flows did not exhibit significant variations since the beginning of the 20th century.

Interleukin-6 is an efficacious marker of axonal transport disruption during experimental glaucoma and stimulates neuritogenesis in cultured retinal ganglion cells

It is increasingly recognised that chronically activated glia contribute to the pathology of various neurodegenerative diseases, including glaucoma. One means by which this can occur is through the release of neurotoxic, proinflammatory factors. In the current study, we therefore investigated the spatio-temporal patterns of expression of three such cytokines, IL-1β, TNFα and IL-6, in a validated rat model of experimental glaucoma. First, only weak evidence was found for increased expression of IL-1β and TNFα following induction of ocular hypertension. Second, and much more striking, was that robust evidence was uncovered showing IL-6 to be synthesised by injured retinal ganglion cells following elevation of intraocular pressure and transported in an orthograde fashion along the nerve, accumulating at sites of axonal disruption in the optic nerve head. Verification that IL-6 represents a novel marker of disrupted axonal transport in this model was obtained by performing double labelling immunofluorescence with recognised markers of fast axonal transport. The stimulus for IL-6 synthesis and axonal transport during experimental glaucoma arose from axonal injury rather than ocular hypertension, as the response was identical after optic nerve crush and bilateral occlusion of the carotid arteries, each of which is independent of elevated intraocular pressure. Moreover, the response of IL-6 was not a generalised feature of the gp130 family of cytokines, as it was not mimicked by another family member, ciliary neurotrophic factor. Finally, further study suggested that IL-6 may be an early part of the endogenous regenerative response as the cytokine colocalised with growth-associated membrane phosphoprotein-43 in some putative regenerating axons, and potently stimulated neuritogenesis in retinal ganglion cells in culture, an effect that was additive to that of ciliary neurotrophic factor. These data comprise clear evidence that IL-6 is actively involved in the attempt of injured retinal ganglion cells to regenerate their axons.

Limitations of Remotely-sensed Aerosol as a Spatial Proxy for Fine Particulate Matter

Recent research highlights the promise of remotely-sensed aerosol optical depth (AOD) as a proxy for ground-level PM2.5. Particular interest lies in the information on spatial heterogeneity potentially provided by AOD, with important application to estimating and monitoring pollution exposure for public health purposes. Given the temporal and spatio-temporal correlations reported between AOD and PM2.5 , it is tempting to interpret the spatial patterns in AOD as reflecting patterns in PM2.5 . Here we find only limited spatial associations of AOD from three satellite retrievals with PM2.5 over the eastern U.S. at the daily and yearly levels in 2004. We then use statistical modeling to show that the patterns in monthly average AOD poorly reflect patterns in PM2.5 because of systematic, spatially-correlated error in AOD as a proxy for PM2.5 . Furthermore, when we include AOD as a predictor of monthly PM2.5 in a statistical prediction model, AOD provides little additional information to improve predictions of PM2.5 when included in a model that already accounts for land use, emission sources, meteorology and regional variability. These results suggest caution in using spatial variation in AOD to stand in for spatial variation in ground-level PM2.5 in epidemiological analyses and indicate that when PM2.5 monitoring is available, careful statistical modeling outperforms the use of AOD.

TRENDS IN PARTICULATE MATTER AND MORTALITY: AN APPROACH TO THE ASSESSMENT OF UNMEASURED CONFOUNDING

We propose a method for diagnosing confounding bias under a model which links a spatially and temporally varying exposure and health outcome. We decompose the association into orthogonal components, corresponding to distinct spatial and temporal scales of variation. If the model fully controls for confounding, the exposure effect estimates should be equal at the different temporal and spatial scales. We show that the overall exposure effect estimate is a weighted average of the scale-specific exposure effect estimates. We use this approach to estimate the association between monthly averages of fine particles (PM2.5) over the preceding 12 months and monthly mortality rates in 113 U.S. counties from 2000-2002. We decompose the association between PM2.5 and mortality into two components: 1) the association between “national trends” in PM2.5 and mortality; and 2) the association between “local trends,” defined as county-specificdeviations from national trends. This second component provides evidence as to whether counties having steeper declines in PM2.5 also have steeper declines in mortality relative to their national trends. We find that the exposure effect estimates are different at these two spatio-temporalscales, which raises concerns about confounding bias. We believe that the association between trends in PM2.5 and mortality at the national scale is more likely to be confounded than is the association between trends in PM2.5 and mortality at the local scale. If the association at the national scale is set aside, there is little evidence of an association between 12-month exposure to PM2.5 and mortality.