Remotely triggered scaffolds for controlled release of pharmaceuticals

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold

Estimating and modeling the dynamics of the intensity of infection with Schistosoma japonicum in villagers of Leyte, Philippines. Part II: Intensity-specific transmission of S. japonicum. The schistosomiasis transmission and ecology project

A dynamic model of Schistosoma japonicum transmission is presented that incorporates effects of infection intensity, age, and sex. We use four infection intensity classes to investigate the impact of ecologic changes and public health interventions on the burden of infection within communities. Age- and sex-specific infection data from three disease-endemic villages in the Philippines are used to estimate the parameters of the model. The model gives good qualitative agreement with observed fecal egg counts adjusted for the accuracy of the Kato-Katz examination. Our results suggest that differences in infection burden between villages are caused by differences in both the infection process and the recovery process in humans. We describe the potential impact of mass treatment of all humans on the numbers with high infection. Furthermore, we show that a sudden reduction in snail population size would affect high prevalence and low prevalence communities in different ways. Copyright © 2005 by The American Society of Tropical Medicine and Hygiene.published_or_final_versio

Assessing the Impact of Misclassification Error on an Epidemiological Association between Two Helminthic Infections

Hookworm, roundworm, and whipworm are collectively known as soil-transmitted helminths. These worms are prevalent in most of the developing countries along with another parasitic infection called schistosomiasis. The tests commonly used to detect infection with these worms are less than 100% accurate. This leads to misclassification of infection status since these tests cannot always correctly indentify infection. We conducted an epidemiological study where such a test, the Kato-Katz technique, was used. In our study we tried to show how misclassification error can influence the association between soil-transmitted helminth infection and schistosomiasis in humans. We used a statistical technique to calculate epidemiological measures of association after correcting for the inaccuracy of the test. Our results show that there is a major difference between epidemiological measures of association before and after the correction of the inaccuracy of the test. After correction of the inaccuracy of the test, soil-transmitted helminth infection was found to be associated with increased risk of acquiring schistosomiasis. This has major public health implications since effective control of one worm can lead to reduction in the occurrence of another and help to reduce the overall burden of worm infection in affected regions

Redefining disease emergence to improve prioritization and macro-ecological analyses

AbstractMicrobial infections are as old as the hosts they sicken, but interest in the emergence of pathogens and the diseases they cause has been accelerating rapidly. The term ‘emerging infectious disease’ was coined in the mid-1900s to describe changes in disease dynamics in the modern era. Both the term and the phenomena it is meant to characterize have evolved and diversified over time, leading to inconsistencies and confusion. Here, we review the evolution of the term ‘emerging infectious disease’ (EID) in the literature as applied to human hosts. We examine the pathways (e.g., speciation or strain differentiation in the causative agent vs. rapid geographic expansion of an existing pathogen) by which diseases emerge. We propose a new framework for disease and pathogen emergence to improve prioritization. And we illustrate how the operational definition of an EID affects conclusions concerning the pathways by which diseases emerge and the ecological and socioeconomic drivers that elicit emergence. As EIDs appear to be increasing globally, and resources for science level off or decline, the research community is pushed to prioritize its focus on the most threatening diseases, riskiest potential pathogens, and the places they occur. The working definition of emerging infectious diseases and pathogens plays a crucial role in prioritization, but we argue that the current definitions may be impeding these efforts. We propose a new framework for classifying pathogens and diseases as “emerging” that distinguishes EIDs from emerging pathogens and novel potential pathogens. We suggest prioritization of: 1) EIDs for adaptation and mitigation, 2) emerging pathogens for preventive measures, and 3) novel potential pathogens for intensive surveillance

Discordance in investigator-reported and adjudicated sudden death in TIOSPIR

Accurate and consistent determination of cause of death is challenging in chronic obstructive pulmonary disease (COPD) patients. TIOSPIR (N=17 135) compared the safety and efficacy of tiotropium Respimat 5/2.5 µg with HandiHaler 18 µg in COPD patients. All-cause mortality was a primary end-point. A mortality adjudication committee (MAC) assessed all deaths. We aimed to investigate causes of discordance in investigator-reported and MAC-adjudicated causes of death and their impact on results, especially cardiac and sudden death. The MAC provided independent, blinded assessment of investigator-reported deaths (n=1302) and assigned underlying cause of death. Discordance between causes of death was assessed descriptively (shift tables). There was agreement between investigator-reported and MAC-adjudicated deaths in 69.4% of cases at the system organ class level. Differences were mainly observed for cardiac deaths (16.4% investigator, 5.1% MAC) and deaths assigned to general disorders including sudden death (17.4% investigator, 24.6% MAC). Reasons for discrepancies included investigator attribution to the immediate (e.g. myocardial infarction (MI)) over the underlying cause of death (e.g. COPD) and insufficient information for a definitive cause. Cause-specific mortality varies in COPD, depending on the method of assignment. Sudden death, witnessed and unwitnessed, is common in COPD and often attributed to MI without supporting evidence

Ground vs. excited state interaction in ruthenium-thienyl dyads:implications for through bond interactions in multicomponent systems

The vibrational and photophysical properties of mononuclear ruthenium(II) and ruthenium(III) polypyridyl complexes based on the ligands 2-(5'-(pyridin-2"-yl)-1'H-1',2',4'-triaz-3'-yl)-thiophene, 2-(5'-(pyrazin-2"-yl)-1'H-1',2',4'-triaz-3'-yl)-thiophene, are reported. The effect of the introduction of the non-innocent thiophene group on the properties of the triazole based ruthenium(II) complex is examined. The pH sensitive 1,2,4-triazole group, although influenced by the electron withdrawing nature of the thiophene group, does not facilitate excited state interaction of the thiophene and Ru(II) centre. Deuteriation and DFT calculations are employed to enable a deeper understanding of the interaction between the two redox-active centres and rationalise the difference between the extent of ground and excited state interaction in this simple dyad. The results obtained provide considerable evidence in support of earlier studies examining differences in ground and excited state interaction in multinuclear thiophene-bridged systems, in particular with respect to HOMO- and LUMO- mediated superexchange interaction processes.

Elucidating excited state electronic structure and intercomponent interactions in multicomponent and supramolecular systems

Rational design of supramolecular systems for application in photonic devices requires a clear understanding of both the mechanism of energy and electron transfer processes and how these processes can be manipulated. Central to achieving these goals is a detailed picture of their electronic structure and of the interaction between the constituent components. We review several approaches that have been taken towards gaining such understanding, with particular focus on the physical techniques employed. In the discussion, case studies are introduced to illustrate the key issues under consideration

Management options for the South Australian rock lobster fishery (Jasus edwardsii) fishery: a case study of co-operative assessment and policy design by fishers and biologists

A modelling workshop process was used to bring biologists and commercial fishers together to develop a spatial model for population dynamics and harvest regulation of the South Australian rock lobster (Jasus edwardsii) fishery. The resulting model provided a credible reconstruction of how the space, time, and size structures of the stock have changed over the history of the fishery, and offers a rich variety of regulatory policy options for exploration of how the stock might have behaved (and might behave in the future) if managed differently. Initial use of the model has been to test options for reducing risk of recruitment overfishing by increasing spawning stock and egg production. A number of regulations ranging from increased size limits to large spatial refuges could accomplish this risk reduction aim. One option is to simply reduce the fishing season length dramatically. The model predicts that short-term yield loss under this strategy would eventually be regained through increased survival and higher catch rates of larger lobsters, and offers the economic advantage of greatly reduced fishing costs. This policy hypothesis can be tested in the field by a management experiment allowing fishers to see for themselves whether an area with a short season does indeed result in catch rates high enough to compensate for fishing time loss