Bioremediation of PAHs - Limitations and soultions

Introduction 1.1 Occurrence of polycyclic aromatic hydrocarbons (PAH) in the environment Worldwide industrial and agricultural developments have released a large number of natural and synthetic hazardous compounds into the environment due to careless waste disposal, illegal waste dumping and accidental spills. As a result, there are numerous sites in the world that require cleanup of soils and groundwater. Polycyclic aromatic hydrocarbons (PAHs) are one of the major groups of these contaminants (Da Silva et al., 2003). PAHs constitute a diverse class of organic compounds consisting of two or more aromatic rings with various structural configurations (Prabhu and Phale, 2003). Being a derivative of benzene, PAHs are thermodynamically stable. In addition, these chemicals tend to adhere to particle surfaces, such as soils, because of their low water solubility and strong hydrophobicity, and this results in greater persistence under natural conditions. This persistence coupled with their potential carcinogenicity makes PAHs problematic environmental contaminants (Cerniglia, 1992; Sutherland, 1992). PAHs are widely found in high concentrations at many industrial sites, particularly those associated with petroleum, gas production and wood preserving industries (Wilson and Jones, 1993). 1.2 Remediation technologies Conventional techniques used for the remediation of soil polluted with organic contaminants include excavation of the contaminated soil and disposal to a landfill or capping - containment - of the contaminated areas of a site. These methods have some drawbacks. The first method simply moves the contamination elsewhere and may create significant risks in the excavation, handling and transport of hazardous material. Additionally, it is very difficult and increasingly expensive to find new landfill sites for the final disposal of the material. The cap and containment method is only an interim solution since the contamination remains on site, requiring monitoring and maintenance of the isolation barriers long into the future, with all the associated costs and potential liability. A better approach than these traditional methods is to completely destroy the pollutants, if possible, or transform them into harmless substances. Some technologies that have been used are high-temperature incineration and various types of chemical decomposition (for example, base-catalyzed dechlorination, UV oxidation). However, these methods have significant disadvantages, principally their technological complexity, high cost , and the lack of public acceptance. Bioremediation, on the contrast, is a promising option for the complete removal and destruction of contaminants. 1.3 Bioremediation of PAH contaminated soil & groundwater Bioremediation is the use of living organisms, primarily microorganisms, to degrade or detoxify hazardous wastes into harmless substances such as carbon dioxide, water and cell biomass Most PAHs are biodegradable unter natural conditions (Da Silva et al., 2003; Meysami and Baheri, 2003) and bioremediation for cleanup of PAH wastes has been extensively studied at both laboratory and commercial levels- It has been implemented at a number of contaminated sites, including the cleanup of the Exxon Valdez oil spill in Prince William Sound, Alaska in 1989, the Mega Borg spill off the Texas coast in 1990 and the Burgan Oil Field, Kuwait in 1994 (Purwaningsih, 2002). Different strategies for PAH bioremediation, such as in situ , ex situ or on site bioremediation were developed in recent years. In situ bioremediation is a technique that is applied to soil and groundwater at the site without removing the contaminated soil or groundwater, based on the provision of optimum conditions for microbiological contaminant breakdown.. Ex situ bioremediation of PAHs, on the other hand, is a technique applied to soil and groundwater which has been removed from the site via excavation (soil) or pumping (water). Hazardous contaminants are converted in controlled bioreactors into harmless compounds in an efficient manner. 1.4 Bioavailability of PAH in the subsurface Frequently, PAH contamination in the environment is occurs as contaminants that are sorbed onto soilparticles rather than in phase (NAPL, non aqueous phase liquids). It is known that the biodegradation rate of most PAHs sorbed onto soil is far lower than rates measured in solution cultures of microorganisms with pure solid pollutants (Alexander and Scow, 1989; Hamaker, 1972). It is generally believed that only that fraction of PAHs dissolved in the solution can be metabolized by microorganisms in soil. The amount of contaminant that can be readily taken up and degraded by microorganisms is defined as bioavailability (Bosma et al., 1997; Maier, 2000). Two phenomena have been suggested to cause the low bioavailability of PAHs in soil (Danielsson, 2000). The first one is strong adsorption of the contaminants to the soil constituents which then leads to very slow release rates of contaminants to the aqueous phase. Sorption is often well correlated with soil organic matter content (Means, 1980) and significantly reduces biodegradation (Manilal and Alexander, 1991). The second phenomenon is slow mass transfer of pollutants, such as pore diffusion in the soil aggregates or diffusion in the organic matter in the soil. The complex set of these physical, chemical and biological processes is schematically illustrated in Figure 1. As shown in Figure 1, biodegradation processes are taking place in the soil solution while diffusion processes occur in the narrow pores in and between soil aggregates (Danielsson, 2000). Seemingly contradictory studies can be found in the literature that indicate the rate and final extent of metabolism may be either lower or higher for sorbed PAHs by soil than those for pure PAHs (Van Loosdrecht et al., 1990). These contrasting results demonstrate that the bioavailability of organic contaminants sorbed onto soil is far from being well understood. Besides bioavailability, there are several other factors influencing the rate and extent of biodegradation of PAHs in soil including microbial population characteristics, physical and chemical properties of PAHs and environmental factors (temperature, moisture, pH, degree of contamination). Figure 1: Schematic diagram showing possible rate-limiting processes during bioremediation of hydrophobic organic contaminants in a contaminated soil-water system (not to scale) (Danielsson, 2000). 1.5 Increasing the bioavailability of PAH in soil Attempts to improve the biodegradation of PAHs in soil by increasing their bioavailability include the use of surfactants , solvents or solubility enhancers.. However, introduction of synthetic surfactant may result in the addition of one more pollutant. (Wang and Brusseau, 1993).A study conducted by Mulder et al. showed that the introduction of hydropropyl-ß-cyclodextrin (HPCD), a well-known PAH solubility enhancer, significantly increased the solubilization of PAHs although it did not improve the biodegradation rate of PAHs (Mulder et al., 1998), indicating that further research is required in order to develop a feasible and efficient remediation method. Enhancing the extent of PAHs mass transfer from the soil phase to the liquid might prove an efficient and environmentally low-risk alternative way of addressing the problem of slow PAH biodegradation in soil.

Pet food: quality and quality improvement

Today’s pet food industry is growing rapidly, with pet owners demanding high-quality diets for their pets. The primary role of diet is to provide enough nutrients to meet metabolic requirements, while giving the consumer a feeling of well-being. Diet nutrient composition and digestibility are of crucial importance for health and well being of animals. A recent strategy to improve the quality of food is the use of “nutraceuticals” or “Functional foods”. At the moment, probiotics and prebiotics are among the most studied and frequently used functional food compounds in pet foods. The present thesis reported results from three different studies. The first study aimed to develop a simple laboratory method to predict pet foods digestibility. The developed method was based on the two-step multi-enzymatic incubation assay described by Vervaeke et al. (1989), with some modification in order to better represent the digestive physiology of dogs. A trial was then conducted to compare in vivo digestibility of pet-foods and in vitro digestibility using the newly developed method. Correlation coefficients showed a close correlation between digestibility data of total dry matter and crude protein obtained with in vivo and in vitro methods (0.9976 and 0.9957, respectively). Ether extract presented a lower correlation coefficient, although close to 1 (0.9098). Based on the present results, the new method could be considered as an alternative system of evaluation of dog foods digestibility, reducing the need for using experimental animals in digestibility trials. The second parte of the study aimed to isolate from dog faeces a Lactobacillus strain capable of exert a probiotic effect on dog intestinal microflora. A L. animalis strain was isolated from the faeces of 17 adult healthy dogs..The isolated strain was first studied in vitro when it was added to a canine faecal inoculum (at a final concentration of 6 Log CFU/mL) that was incubated in anaerobic serum bottles and syringes which simulated the large intestine of dogs. Samples of fermentation fluid were collected at 0, 4, 8, and 24 hours for analysis (ammonia, SCFA, pH, lactobacilli, enterococci, coliforms, clostridia). Consequently, the L. animalis strain was fed to nine dogs having lactobacilli counts lower than 4.5 Log CFU per g of faeces. The study indicated that the L animalis strain was able to survive gastrointestinal passage and transitorily colonize the dog intestine. Both in vitro and in vivo results showed that the L. animalis strain positively influenced composition and metabolism of the intestinal microflora of dogs. The third trail investigated in vitro the effects of several non-digestible oligosaccharides (NDO) on dog intestinal microflora composition and metabolism. Substrates were fermented using a canine faecal inoculum that was incubated in anaerobic serum bottles and syringes. Substrates were added at the final concentration of 1g/L (inulin, FOS, pectin, lactitol, gluconic acid) or 4g/L (chicory). Samples of fermentation fluid were collected at 0, 6, and 24 hours for analysis (ammonia, SCFA, pH, lactobacilli, enterococci, coliforms). Gas production was measured throughout the 24 h of the study. Among the tested NDO lactitol showed the best prebiotic properties. In fact, it reduced coliforms and increased lactobacilli counts, enhanced microbial fermentation and promoted the production of SCFA while decreasing BCFA. All the substrates that were investigated showed one or more positive effects on dog faecal microflora metabolism or composition. Further studies (in particular in vivo studies with dogs) will be needed to confirm the prebiotic properties of lactitol and evaluate its optimal level of inclusion in the diet.

Analisi delle preferenze per le diverse categorie di pomodoro trasformato nel food service

Il pomodoro è una delle colture principali del panorama agro-alimentare italiano e rappresenta un ingrediente base della tradizione culinaria nazionale. Il pomodoro lavorato dall’industria conserviera può essere trasformato in diverse tipologie merceologiche, che si differenziano in base alla tecniche di lavorazione impiegate ed alle caratteristiche del prodotto finito. la percentuale di spesa totale destinata all’acquisto di cibo fuori casa è in aumento a livello globale e l’interesse dell’industria alimentare nei confronti di questo canale di vendita è quindi crescente. Mentre sono numerose le indagine in letteratura che studiano i processi di acquisto dei consumatori finali, non ci sono evidenze di studi simili condotti sugli operatori del Food Service. Obiettivo principale della ricerca è quello di valutare le preferenze dei responsabili acquisti del settore Food Service per diverse tipologie di pomodoro trasformato, in relazione ad una gamma di attributi rilevanti del prodotto e di caratteristiche del cliente. La raccolta dei dati è avvenuta attraverso un esperimento di scelta ipotetico realizzato in Italia e alcuni mercati esteri. Dai risultati ottenuti dall’indagine emerge che i Pelati sono la categoria di pomodoro trasformato preferita dai responsabili degli acquisti del settore Food Service intervistati, con il 35% delle preferenze dichiarate nell'insieme dei contesti di scelta proposti, seguita dalla Polpa (25%), dalla Passata (20%) e dal Concentrato (15%). Dai risultati ottenuti dalla stima del modello econometrico Logit a parametri randomizzati è emerso che alcuni attributi qualitativi di fiducia (credence), spesso impiegati nelle strategie di differenziazione e posizionamento da parte dell’industria alimentare nel mercato Retail, possono rivestire un ruolo importante anche nell’influenzare le preferenze degli operatori del Food Service. Questo potrebbe quindi essere un interessante filone di ricerca da sviluppare nel futuro, possibilmente con l'impiego congiunto di metodologie di analisi basate su esperimenti di scelta ipotetici e non ipotetici.

Thermoelectric properties of TiNiSn and Zr 0.5 Hf 0.5 NiSn thin films and superlattices with reduced thermal conductivities

Durch steigende Energiekosten und erhöhte CO2 Emission ist die Forschung an thermoelektrischen (TE) Materialien in den Fokus gerückt. Die Eignung eines Materials für die Verwendung in einem TE Modul ist verknüpft mit der Gütezahl ZT und entspricht α2σTκ-1 (Seebeck Koeffizient α, Leitfähigkeit σ, Temperatur T und thermische Leitfähigkeit κ). Ohne den Leistungsfaktor α2σ zu verändern, soll ZT durch Senkung der thermischen Leitfähigkeit mittels Nanostrukturierung angehoben werden.rnBis heute sind die TE Eigenschaften von den makroskopischen halb-Heusler Materialen TiNiSn und Zr0.5Hf0.5NiSn ausgiebig erforscht worden. Mit Hilfe von dc Magnetron-Sputterdeposition wurden nun erstmals halbleitende TiNiSn und Zr0.5Hf0.5NiSn Schichten hergestellt. Auf MgO (100) Substraten sind stark texturierte polykristalline Schichten bei Substrattemperaturen von 450°C abgeschieden worden. Senkrecht zur Oberfläche haben sich Korngrößen von 55 nm feststellen lassen. Diese haben Halbwertsbreiten bei Rockingkurven von unter 1° aufgewiesen. Strukturanalysen sind mit Hilfe von Röntgenbeugungsexperimenten (XRD) durchgeführt worden. Durch Wachstumsraten von 1 nms 1 konnten in kürzester Zeit Filmdicken von mehr als einem µm hergestellt werden. TiNiSn zeigte den höchsten Leistungsfaktor von 0.4 mWK 2m 1 (550 K). Zusätzlich wurde bei Raumtemperatur mit Hilfe der differentiellen 3ω Methode eine thermische Leitfähigkeit von 2.8 Wm 1K 1 bestimmt. Es ist bekannt, dass die thermische Leitfähigkeit mit der Variation von Massen abnimmt. Weil zudem angenommen wird, dass sie durch Grenzflächenstreuung von Phononen ebenfalls reduziert wird, wurden Übergitter hergestellt. Dabei wurden TiNiSn und Zr0.5Hf0.5NiSn nacheinander abgeschieden. Die sehr hohe Kristallqualität der Übergitter mit ihren scharfen Grenzflächen konnte durch Satellitenpeaks und Transmissionsmikroskopie (STEM) nachgewiesen werden. Für ein Übergitter mit einer Periodizität von 21 nm (TiNiSn und Zr0.5Hf0.5NiSn jeweils 10.5 nm) ist bei einer Temperatur von 550 K ein Leistungsfaktor von 0.77 mWK 2m 1 nachgewiesen worden (α = 80 µVK 1; σ = 8.2 µΩm). Ein Übergitter mit der Periodizität von 8 nm hat senkrecht zu den Grenzflächen eine thermische Leitfähigkeit von 1 Wm 1K 1 aufgewiesen. Damit hat sich die Reduzierung der thermischen Leitfähigkeit durch die halb-Heusler Übergitter bestätigt. Durch die isoelektronischen Eigenschaften von Titan, Zirkonium und Hafnium wird angenommen, dass die elektrische Bandstruktur und damit der Leistungsfaktor senkrecht zu den Grenzflächen nur schwach beeinflusst wird.rn

Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5

(11)C-ABP-688 is a selective tracer for the mGluR5 receptor. Its kinetics is fast and thus favourable for an equilibrium approach to determine receptor-related parameters. The purpose of this study was to test the hypothesis that the pattern of the (11)C-ABP688 uptake using a bolus-plus-infusion (B/I) protocol at early time points corresponds to the perfusion and at a later time point to the total distribution volume. METHODS: A bolus and a B/I study (1 h each) was performed in five healthy male volunteers. With the B/I protocol, early and late scans were normalized to gray matter, cerebellum and white matter. The same normalization was done on the maps of the total distribution volume (Vt) and K(1) which were calculated in the study with bolus only injection and the Logan method (Vt) and a two-tissue compartment model (K(1)). RESULTS: There was an excellent correlation close to the identity line between the pattern of the late uptake in the B/I study and Vt of the bolus-only study for all three normalizations. The pattern of the early uptake in the B/I study correlated well with the K(1) maps, but only when normalized to gray matter and cerebellum, not to white matter. CONCLUSION: It is demonstrated that with a B/I protocol the (11)C-ABP688 distribution in late scans reflects the pattern of the total distribution volume and is therefore a measure for the density pattern of mGluR5. The early scans following injection are related to blood flow, although not in a fully quantitative manner. The advantage of the B/I protocol is that no arterial blood sampling is required, which is advantageous in clinical studies.

Interhemispheric coupling, the West Antarctic Ice Sheet and warm Antarctic interglacials

Ice core evidence indicates that even though atmospheric CO2 concentrations did not exceed ~300 ppm at any point during the last 800 000 years, East Antarctica was at least ~3–4 °C warmer than preindustrial (CO2~280 ppm) in each of the last four interglacials. During the previous three interglacials, this anomalous warming was short lived (~3000 years) and apparently occurred before the completion of Northern Hemisphere deglaciation. Hereafter, we refer to these periods as "Warmer than Present Transients" (WPTs). We present a series of experiments to investigate the impact of deglacial meltwater on the Atlantic Meridional Overturning Circulation (AMOC) and Antarctic temperature. It is well known that a slowed AMOC would increase southern sea surface temperature (SST) through the bipolar seesaw and observational data suggests that the AMOC remained weak throughout the terminations preceding WPTs, strengthening rapidly at a time which coincides closely with peak Antarctic temperature. We present two 800 kyr transient simulations using the Intermediate Complexity model GENIE-1 which demonstrate that meltwater forcing generates transient southern warming that is consistent with the timing of WPTs, but is not sufficient (in this single parameterisation) to reproduce the magnitude of observed warmth. In order to investigate model and boundary condition uncertainty, we present three ensembles of transient GENIE-1 simulations across Termination II (135 000 to 124 000 BP) and three snapshot HadCM3 simulations at 130 000 BP. Only with consideration of the possible feedback of West Antarctic Ice Sheet (WAIS) retreat does it become possible to simulate the magnitude of observed warming.

Moving along the mental number line: Interactions between whole-body motion and numerical cognition

Active head turns to the left and right have recently been shown to influence numerical cognition by shifting attention along the mental number line. In the present study, we found that passive whole-body motion influences numerical cognition. In a random-number generation task (Experiment 1), leftward and downward displacement of participants facilitated small number generation, whereas rightward and upward displacement facilitated the generation of large numbers. Influences of leftward and rightward motion were also found for the processing of auditorily presented numbers in a magnitude-judgment task (Experiment 2). Additionally, we investigated the reverse effect of the number-space association (Experiment 3). Participants were displaced leftward or rightward and asked to detect motion direction as fast as possible while small or large numbers were auditorily presented. When motion detection was difficult, leftward motion was detected faster when hearing small number and rightward motion when hearing large number. We provide new evidence that bottom-up vestibular activation is sufficient to interact with the higher-order spatial representation underlying numerical cognition. The results show that action planning or motor activity is not necessary to influence spatial attention. Moreover, our results suggest that self-motion perception and numerical cognition can mutually influence each other.

Hydrodynamic Characterization of Bile Salt Host-Guest Complexes by Pulsed Field Gradient NMR Spectroscopy

The work described herein is aimed at understanding primary and secondary aggregation of bile salt micelles and how micelles can perform chiral recognition of binapthyl analytes. Previous work with cholate and deoxycholate using micellar electrokinetic chromatography (MEKC) and nuclear magnetic resonance (NMR) has provided insightinto cholate and deoxycholate micelle formation, especially with respect to the critical micelle concentration (CMC). Chiral separations of the model analyte, 1,1â??-binaphthyl-2,2â??-diyl hydrogen phosphate (BNDHP), via cholate (C) and deoxycholate (DC) mediated MEKC separataions previously have shown the DC CMC to be 7-10 mM andthe cholate CMC at 14 mM at ph 12. A second model analyte,1,1â??-binaphthol (BN), was also previously investigated to probe micellar structure, but the MEKC data for this analyte implied a higher CMC, which may be interpreted as secondary aggregation. Thiswork extends the investigation of bile salts to include pulsed field gradient spin echo (PFGSE) NMR experiments being used to gain information about the size and degree of polydispersity of cholate and deoxycholate micelles. Concentrations of cholate below 10mM show a large variation in effective radius likely due to the existence of transient preliminary aggregates. The onset of the primary micelle shows a dramatic increase in effective radius of the micelle in cholate and deoxycholate. In the region of expectedsecondary aggregation a gradual increase of effective radius was observed with cholate; deoxycholate showed a persistent aggregate size in the secondary micelle region that is modulated by the presence of an analyte molecule. Effective radii of cholate anddeoxycholate (individually) were compared with and without R- and S-BNDHP in order to observe the effective radius difference of micelles with and without analyte present. The presence of S-BNDHP consistently resulted in a larger effective aggregate radius incholate and deoxycholate, confirming previous data of the S-BNDHP interacting more with the micelle than R-BNDHP. In total, various NMR techniques, like diffusion NMR can be used to gain a greater understanding of the bile salt micellization process and chiral resolution.

Practicability of nitrogen multiple-breath washout measurements in a pediatric cystic fibrosis outpatient setting

BACKGROUND: Although lung clearance index (LCI) is a sensitive indicator of mild cystic fibrosis (CF) lung disease, it is rarely measured due to lengthy protocols and the commercial unavailability of multiple-breath washout (MBW) setups and tracer gases. We used a newly validated, commercially available nitrogen (N(2) ) MBW setup to assess success rate, duration, and variability of LCI within a 20 min timeframe, during clinical routine. We also evaluated the relationship between LCI and other clinical markers of CF lung disease. METHODS: One hundred thirty six children (83 with CF) between 4 and 16 years were studied in a pediatric CF outpatient setting. One hundred eighteen out of 136 children were naïve to MBW. Within 20 min, each child was trained, N(2) MBW was performed, and LCI was analyzed. We assessed intra- and between-test reproducibility in a subgroup of children. RESULTS: At least one LCI was feasible in 123 (90%) children, with a mean (range) of 3.3 (1.2-6.4) min per test. Two or more measurements were feasible in 56 (41%) children. Comparing LCI in CF versus controls, LCI mean (SD) was 12.0 (3.9) versus 6.1 (0.9), and the intra- and inter-test coefficient of repeatability was 1.00 versus 0.81 and 0.96 versus 0.62, respectively. LCI was correlated with spirometry, blood gases, and Pseudomonas aeruginosa infection. CONCLUSIONS: Using available N(2) MBW equipment, LCI measurements are practical and fast in children. LCI is correlated with markers of CF lung disease. Longer timeframes would be required for triplicate N(2) MBW tests in inexperienced children. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Synthesis and two-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 in living cells

The synthesis of a photolabile derivative of inositol-1,4,5-trisphosphate (IP3) is described. This new caged second messenger (6-ortho-nitroveratryl)-IP3 (6-NV-IP3) has an extinction coefficient of 5000 M(-1) cm(-1) at 350 nm, and a quantum yield of photolysis of 0.12. Therefore, 6-NV-IP3 is photolyzed with UV light about three times more efficiently than the widely used P(4(5))-1-(2-nitrophenyl)ethyl-caged IP3 (NPE-IP3). 6-NV-IP3 has a two-photon cross-section of about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two-photon excitation in living cells at modest power levels. Using near-IR light (5 mW, 710 nm, 80 MHz, pulse-width 70 fs), we produced focal bursts of IP3 in HeLa cells, as revealed by laser-scanning confocal imaging of intracellular Ca2+ concentrations. Therefore, 6-NV-IP3 can be used for efficient, subcellular photorelease of IP3, not only in cultured cells but also, potentially, in vivo. It is in the latter situation that two-photon photolysis should reveal its true forte.

New aspects of airway mechanics in pre-term infants

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (f(ar,1)), is related to airway wall mechanics. The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37 weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340 g). Among the pre-term infants, there was good short-term repeatability of f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term infants (199 versus 257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue. Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.

Additive Hazards Models with Latent Treatment Effectiveness Lag Time

In many clinical trials to evaluate treatment efficacy, it is believed that there may exist latent treatment effectiveness lag times after which medical procedure or chemical compound would be in full effect. In this article, semiparametric regression models are proposed and studied to estimate the treatment effect accounting for such latent lag times. The new models take advantage of the invariance property of the additive hazards model in marginalizing over random effects, so parameters in the models are easy to be estimated and interpreted, while the flexibility without specifying baseline hazard function is kept. Monte Carlo simulation studies demonstrate the appropriateness of the proposed semiparametric estimation procedure. Data collected in the actual randomized clinical trial, which evaluates the effectiveness of biodegradable carmustine polymers for treatment of recurrent brain tumors, are analyzed.

On Time Series Analysis of Public Health and Biomedical Data

A time series is a sequence of observations made over time. Examples in public health include daily ozone concentrations, weekly admissions to an emergency department or annual expenditures on health care in the United States. Time series models are used to describe the dependence of the response at each time on predictor variables including covariates and possibly previous values in the series. Time series methods are necessary to account for the correlation among repeated responses over time. This paper gives an overview of time series ideas and methods used in public health research.

Comparison of climate field reconstruction techniques: Application to Europe

This paper presents a comparison of principal component (PC) regression and regularized expectation maximization (RegEM) to reconstruct European summer and winter surface air temperature over the past millennium. Reconstruction is performed within a surrogate climate using the National Center for Atmospheric Research (NCAR) Climate System Model (CSM) 1.4 and the climate model ECHO-G 4, assuming different white and red noise scenarios to define the distortion of pseudoproxy series. We show how sensitivity tests lead to valuable “a priori” information that provides a basis for improving real world proxy reconstructions. Our results emphasize the need to carefully test and evaluate reconstruction techniques with respect to the temporal resolution and the spatial scale they are applied to. Furthermore, we demonstrate that uncertainties inherent to the predictand and predictor data have to be more rigorously taken into account. The comparison of the two statistical techniques, in the specific experimental setting presented here, indicates that more skilful results are achieved with RegEM as low frequency variability is better preserved. We further detect seasonal differences in reconstruction skill for the continental scale, as e.g. the target temperature average is more adequately reconstructed for summer than for winter. For the specific predictor network given in this paper, both techniques underestimate the target temperature variations to an increasing extent as more noise is added to the signal, albeit RegEM less than with PC regression. We conclude that climate field reconstruction techniques can be improved and need to be further optimized in future applications.

Frailty and risk for heart failure in older adults: the health, aging, and body composition study

OBJECTIVE The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. BACKGROUND Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known. METHODS We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. RESULTS Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). CONCLUSIONS Frailty is independently associated with risk of HF in older adults.