The spread and uptake of diabetes prevention programs around the world : a case study from Finland and Australia

Type 2 diabetes is a major public health issue in most countries around the world. Efficacy trials have demonstrated that lifestyle modification programs can significantly reduce the risk of type 2 diabetes. Two key challenges are: [1] to develop programs that are more feasible for “real world” implementation and [2] to extend the global reach of such programs, particularly to resource-poor countries where the burden of diabetes is substantial. This paper describes the development, implementation, and evaluation of such “real world” programs in Finland and Australia, the exchange between the two countries, and the wider uptake of such programs. Drawing on the lessons from these linked case studies, we discuss the implications for improving the “spread” of diabetes prevention programs by more effective uptake of lifestyle change programs and related strategies for more resource-poor countries and settings.

Arsenic behaviour from groundwater and soil to crops:impacts on agriculture and food safety

High levels of As in groundwater commonly found in Bangladesh and other parts of Asia not only pose a risk via drinking water consumption but also a risk in agricultural sustainability and food safety. This review attempts to provide an overview of current knowledge and gaps related to the assessment and management of these risks, including the behaviour of As in the soil-plant system, uptake, phytotoxicity, As speciation in foods, dietary habits, and human health risks. Special emphasis has been given to the situation in Bangladesh, where groundwater via shallow tube wells is the most important source of irrigation water in the dry season. Within the soil-plant system, there is a distinct difference in behaviour of As under flooded conditions, where arsenite (AsIII) predominates, and under nonflooded conditions, where arsenate (AsV) predominates. The former is regarded as most toxic to humans and plants. Limited data indicate that As-contaminated irrigation water can result in a slow buildup of As in the topsoil. In some cases the buildup is reflected by the As levels in crops, in others not. It is not yet possible to predict As uptake and toxicity in plants based on soil parameters. It is unknown under what conditions and in what time frame As is building up in the soil. Representative phytotoxicity data necessary to evaluate current and future soil concentrations are not yet available. Although there are no indications that crop production is currently inhibited by As, long-term risks are clearly present. Therefore, with concurrent assessments of the risks, management options to further prevent As accumulation in the topsoil should already have been explored. With regard to human health, data on As speciation in foods in combination with food consumption data are needed to assess dietary exposure, and these data should include spatial and seasonal variability. It is important to control confounding factors in assessing the risks. In a country where malnutrition is prevalent, levels of inorganic As in foods should be balanced against the nutritional value of the foods. Regarding agriculture, As is only one of the many factors that may pose a risk to the sustainability of crop production. Other risk factors such as nutrient depletion and loss of organic matter also must be taken into account to set priorities in terms of research, management, and overall strategy.

Glykopolymere für biomedizinsche Anwendungen : Synthese von mannosylierten N-(2-Hydroxyprpyl)methacrylamid Polymersystemen für die Adressierung von Zellen des Immunsystems

Das Ziel dieser Arbeit lag darin mannosylierte Polymersysteme hauptsächlich auf der Basis von N-(Hydroxy)propylmethacrylat zu synthetisieren, um gezielt Zellen des Immunsystems zu adressieren. Dazu wurden zunächst verschiedene Reaktivesterpolymere auf der Basis von Pentafluorophenylmethacrylat (PFPMA) unter Verwendung der RAFT-Polymerisation mit enger Molekulargewichtsverteilung und unterschiedlichen Anteilen an LMA (Laurylmethacrylat) hergestellt.rnUm eine genaue Aussage über den Aufbau eines statistischen PFPMA-LMA Copolymers treffen zu können, wurde die Copolymerisation von PFPMA und LMA mittels Echtzeit 1H-NMR Kinetikmessungen untersucht. Dies ermöglichte es, die Copolymerisationsparameter zu berechnen und genaue Aussagen über den Aufbau eines statistischen PFPMA-LMA Copolymers zu treffen. Die so erhaltenen Reaktivesterpolymere wurden dann in einer polymeranalogen Reaktion unter Erhalt des Polymerisationsgrades in die gewünschten HPMA-Polymere umgewandelt. Um die quantitative Umsetzung ohne auftretende Nebenreaktionen zu untersuchen, wurden verschiedene Reaktionsbedingungen gewählt und unterschiedliche Analysemethoden verwendet. Damit konnte gezeigt werden, dass es möglich ist, über den Reaktivesteransatz qualitativ hochwertige amphiphile Polymersysteme herzustellen, die auf anderen Wegen schwer zu synthetisieren und charakterisieren sind. Ein weiterer Vorteil dieser Syntheseroute ist, dass gleichzeitig sowohl Marker für die Visualisierung der Polymere in vitro und in vivo, als auch Targetliganden für die Adressierung bestimmter Zellen eingeführt werden können. Dafür wurde hauptsächlich Mannose als einfache Zuckerstruktur angebunden, da bekannt ist, dass mannosylierte Polymersysteme von Zellen des Imunsystems aufgenommen werden. Zusätzlich konnten die mannosylierten Polymere mit hydrophobem Wirkstoff beladen werden, wobei die Stabilität von beladenen Mizellen anhand der Einlagerung eines hydrophoben radioaktiven Komplexes genauer untersucht werden konnte.rnAnschließende in vitro Experimente der mannosylierten Polymermizellen an dendritischen Zellen zeigten wie erwartet eine mannosespezifische und verstärkte Aufnahme. Für eine mögliche Untersuchung dieser Systeme in vivo mittels PET konnte gezeigt werden, dass es möglich ist HPMA Polymere radioaktiv zu markieren, wobei auch erste Markierungsversuche mit einem langlebigen Radionuklid für Langzeitbiodistributionsstudien durchgeführt werden konnte.rn

Suppression of the high affinity phosphate uptake system:A mechanism of arsenate tolerance in Holcus lanatus L.

In Holcus lanatus L. phosphate and arsenate are taken up by the same transport system. Short-term uptake kinetics of the high affinity arsenate transport system were determined in excised roots of arsenate-tolerant and non-tolerant genotypes. In tolerant plants the V_max of ion uptake in plants grown in phosphate-free media was decreased compared to non-tolerant plants, and the affinity of the uptake system was lower than in the non-tolerant plants. Both the reduction in V_max and the increase in K_m led to reduced arsenate influx into tolerant roots. When the two genotypes were grown in nutrient solution containing high levels of phosphate, there was little change in the uptake kinetics in tolerant plants. In non-tolerant plants, however, there was a marked decrease in the V_max to the level of the tolerant plants but with little change in the K_m. This suggests that the low rate of arsenate uptake over a wide range of differing root phosphate status is due to loss of induction of the synthesis of the arsenate (phosphate) carrier. © 1992 Oxford University Press.

Differential uptake, partitioning and transfer of Cd and Zn in the soil-pea plant-aphid system

The biomagnification of trace metals during transfer from contaminated soil to higher trophic levels may potentially result in the exposure of predatory arthropods to toxic concentrations of these elements. This study examined the transfer of Cd and Zn in a soil−plant−arthropod system grown in series of field plots that had received two annual applications of municipal biosolids with elevated levels of Cd and Zn. Results showed that biosolids amendment significantly increased the concentration of Cd in the soil and the shoots of pea plants and the concentration of Zn in the soil, pea roots, shoots, and pods. In addition, the ratio of Cd to Zn concentration showed that Zn was preferentially transferred compared to Cd through all parts of the system. As a consequence, Zn was biomagnified by the system whereas Cd was biominimized. Cd and Zn are considered to exhibit similar behaviors in biological systems. However, the Cd/Zn ratios demonstrated that in this system, Cd is much less labile in the root−shoot−pod and shoot−aphid pathways than Zn.

The uptake of an early warning system in an Australian emergency department : a pilot study

Objectives: To evaluate the uptake of an emergency department early warning system (ED EWS) for recognition of, and response to, clinical deterioration.

Design, setting and participants: A descriptive exploratory study conducted in an urban district hospital in Melbourne, Australia. Systematic sampling was used to identify every 10th patient for whom the ED EWS was activated from May 2009 to May 2011.

Main outcome measures: Patient characteristics, ED system data and ED EWS activation characteristics.

Results: ED EWS activation occurred in 1.5% of ED patients; 204 patients were included in this pilot study. The median age was 65.1 years (interquartile range [IQR], 47.8-77.5 years), 89.2% of patients were classified as triage category 2 or 3, and 82.4% of patients were seen by medical staff before ED EWS activation. Hypotension (27.7%) and tachycardia (23.7%) were the most common reasons for ED EWS activation. Median duration of clinical instability was 39 minutes (IQR, 5- 129 minutes). Nurses made 93.1% of ED EWS activations. Median time between documenting physiological abnormalities and ED EWS activation was 5 minutes (IQR, 0- 20). Most patients (57.8%) required hospital admission: 4.4% of patients required intensive care unit admission.

Conclusions: The ED EWS resulted in at least two formal reports of clinical deterioration in ED patients per day, indicating reasonable uptake by clinicians. A greater understanding of clinical deterioration in ED patients is warranted to inform an evidence-based approach to recognition of, and response to, clinical deterioration in ED patients.

Molecular and cellular characterisation of the zinc uptake (Znu) system of Nostoc punctiforme

Metal homoeostasis in cyanobacteria is based on uptake and export systems that are controlled by their own regulators. This study characterises the zinc uptake (Znu) system in Nostoc punctiforme. The system was found to comprise of three subunits in an ACB operon: a Zn2+-binding protein (ZnuA18), a transmembrane domain (ZnuB) and an ATPase (ZnuC). These proteins are encoded within the znu operon regulated by a zinc uptake transcription repressor (Zur). Interestingly, a second Zn2+-binding protein (ZnuA08) was also identified at a distal genomic location. Interactions between components of the ZnuACB system were investigated using knockouts of the individual genes. The znuA08-, znuA18-, znuB- and znuC- mutants displayed overall reduced znuACB transcript levels, suggesting that all system components are required for normal expression of znu genes. Zinc uptake assays in the Zn2+-binding protein mutant strains showed that the disruption of znuA18 had a greater negative effect on zinc uptake than disruption of znuA08. Complementation studies in Escherichia coli indicated that both znuA08 and znuA18 were able to restore zinc uptake in a znuA- mutant, with znuA18 permitting the highest zinc uptake rate. The N. punctiforme zur was also able to complement the E. coli zur- mutant.

The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation.

The yeast Saccharomyces cerevisiae has two separate systems for zinc uptake. One system has high affinity for substrate and is induced in zinc-deficient cells. The second system has lower affinity and is not highly regulated by zinc status. The ZRT1 gene encodes the transporter for the high-affinity system, called Zrt1p. The predicted amino acid sequence of Zrt1p is similar to that of Irt1p, a probable Fe(II) transporter from Arabidopsis thaliana. Like Irt1p, Zrt1p contains eight potential transmembrane domains and a possible metal-binding domain. Consistent with the proposed role of ZRT1 in zinc uptake, overexpressing this gene increased high-affinity uptake activity, whereas disrupting it eliminated that activity and resulted in poor growth of the mutant in zinc-limited media. Furthermore, ZRT1 mRNA levels and uptake activity were closely correlated, as was zinc-limited induction of a ZRT1-lacZ fusion. These results suggest that ZRT1 is regulated at the transcriptional level by the intracellular concentration of zinc. ZRT1 is an additional member of a growing family of metal transport proteins.

Water uptake of aerosols with a focus on seeded aerosols and instrumentation techniques

This thesis focuses on the volatile and hygroscopic properties of mixed aerosol species. In particular, the influence organic species of varying solubility have upon seed aerosols. Aerosol studies were conducted at the Paul Scherrer Institut Laboratory for Atmospheric Chemistry (PSI-LAC, Villigen, Switzerland) and at the Queensland University of Technology International Laboratory for Air Quality and Health (QUT-ILAQH, Brisbane, Australia). The primary measurement tool employed in this program was the Volatilisation and Hygroscopicity Tandem Differential Mobility Analyser (VHTDMA - Johnson et al. 2004). This system was initially developed at QUT within the ILAQH and was completely re-developed as part of this project (see Section 1.4 for a description of this process). The new VHTDMA was deployed to the PSI-LAC where an analysis of the volatile and hygroscopic properties of ammonium sulphate seeds coated with organic species formed from the photo-oxidation of á-pinene was conducted. This investigation was driven by a desire to understand the influence of atmospherically prevalent organics upon water uptake by material with cloud forming capabilities. Of particular note from this campaign were observed influences of partially soluble organic coatings upon inorganic ammonium sulphate seeds above and below their deliquescence relative humidity (DRH). Above the DRH of the seed increasing the volume fraction of the organic component was shown to reduce the water uptake of the mixed particle. Below the DRH the organic was shown to activate the water uptake of the seed. This was the first time this effect had been observed for á-pinene derived SOA. In contrast with the simulated aerosols generated at the PSI-LAC a case study of the volatile and hygroscopic properties of diesel emissions was undertaken. During this stage of the project ternary nucleation was shown, for the first time, to be one of the processes involved in formation of diesel particulate matter. Furthermore, these particles were shown to be coated with a volatile hydrophobic material which prevented the water uptake of the highly hygroscopic material below. This result was a first and indicated that previous studies into the hygroscopicity of diesel emission had erroneously reported the particles to be hydrophobic. Both of these results contradict the previously upheld Zdanovksii-Stokes-Robinson (ZSR) additive rule for water uptake by mixed species. This is an important contribution as it adds to the weight of evidence that limits the validity of this rule.