106 research outputs found

    A System Dynamics Approach for Strategic Analysis of Project Portfolio Interdependencies

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    Understanding project portfolio interdependencies is essential in order to manage projects in complex and dynamic environments. Project environments across the globe are becoming increasingly complex, creating heightened challenges for project management (PM) and project portfolio management (PPM). Current research indicates that organisations globally fall short of understanding how project interdependencies affect portfolio outcomes. The literature on System Dynamics (SD) suggests that SD may be a suitable tool to encapsulate the âbigger pictureâ of PPM interdependencies. This research applies a client interactive approach using SD modelling techniques to represent interdependencies within a project portfolio. A case study was conducted with the Royal Australian Navy (RAN) to investigate SD as a potential tool for the management of project portfolio interdependencies The outcomes of the case study suggest that SD has the ability to challenge an organisationâs perceptions of their project portfolio interdependencies and to enhance strategic decisionmaking capabilities

    Characterization of the Role of Host and Dietary Factors in the Establishment of Bacteria in the Gastrointestinal Tract

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    Probiotic bacteria and synbiotics are used as therapeutic and prophylactic agents. The majority of probiotic and synbiotic applications contain bacterial strains that are allochthonous to the human gastrointestinal (GI) tract. Accordingly, many bacterial strains do not survive digestion, or are not capable of persisting and competing the resident gut microbiota, and are therefore washed out of the GI tract shortly after the treatment is discontinued. This might reduce the health effects of these treatments. Therefore, research is needed to address the ecological challenges that probiotic strains encounter in the GI tract in order to develop probiotic regimens. Determining which ecological factors are limiting the colonization of bacteria remains a challenge. To gain insight into the complex interplay between host and microbe, we chose Lactobacillus reuteri and its rodent host as a model to investigate which genes of L. reuteri contribute to tolerance towards host gastric acid secretion. We established the urease cluster as the predominant factor in mediating resistance to gastric acid, and a mutation of this cluster resulted in substantially decreased population levels of L. reuteri in mice. Secondly, we established a method to select for synergistic synbiotic combinations. Based on in vivo selection (IVS), autochthonous putative probiotic strains are enriched in the GI tract of subjects by the continued consumption of a prebiotic. We used IVS to select a strain of Bifidobacterium adolescentis that became enriched in a human feeding trail with galactooligosaccharides (GOS). Here we have shown that the synbiotic combination of Bifidobacterium adolescentis IVS-1 and GOS significantly enriched for the putative probiotic component in rats. IVS-1 became the most dominant operational taxonomic unit in the GI tract, outcompeting the resident Bifidobacterium species. Similarly, we tested this synbiotic in a human trial with obese adults. In this random, placebo-controlled parallel arm study, the synbiotic combination of IVS-1 and GOS led to establishment of IVS-1 in significantly higher numbers in the GI tract than a commercial synbiotic. Together, the studies presented in this dissertation allowed new insights into the colonization factors of a true GI symbiont, which could contribute to the development of improved probiotics, and provided novel insight into a rational selection of probiotics and synbiotics. Advisors: Robert W. Hutkins and Jens Walte

    Visualising project interdependencies for enhanced project portfolio decision-making

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    Project management (PM) and project portfolio management (PPM) communities face challenges in the management of complex and highly interdependent project portfolios, as these interdependencies must be understood and managed for best project and portfolio outcomes. The research reported in this paper provides benefits to the global PM and PPM community by introducing a new tool and by providing insights into the factors affecting an organisationâs ability to understand project interdependencies (PI). Visual project mapping (VPM), the creation of graphical displays of projects and their interdependencies as a network of nodes and arrows, is shown to provide benefits by supporting communication and strategic portfolio decision making. The research also highlights the importance of the environment and culture as well as processes and tools and indicates that they work together to improve an organisationâs understanding of project portfolio interdependencie

    Managing project interdependencies: exploring new approaches

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    The interdependencies between projects create complexities for the management of project portfolios within organisations. In times of uncertainty this challenge is even greater due to the difficulties in predicting the flow-on effects from changes to projects in the portfolio. Hence, in times of disruptive change a good understanding of project interdependencies is particularly important. This paper outlines two related studies that aim to improve the understanding and management of interdependencies within project portfolios. The paper first defines project portfolio management (PPM) and highlights its growing importance for optimising organisational outcomes, especially in dynamic environments. Project portfolio complexity and interdependencies between projects in a portfolio are then overviewed, highlighting the challenges that these interdependencies create for effective PPM, and introducing some of the methods used for understanding and managing these interdependencies including the dependency matrix and the related design structure matrix. Network analysis and mapping tools are then introduced and suggested as a novel method for improving understanding and managing project interdependencies. Finally, an example of the use of this type of method is presented and the current research projects are overviewed

    Synbiotics for Improved Human Health: Recent Developments, Challenges, and Opportunities

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    Research on combining pro- and prebiotics as synbiotics to enhance human and animal health has accelerated in the past 10 years, including many clinical trials that have assessed a diverse range of synbiotic formulations. In this review, we summarize these studies as well as the commercial applications of synbiotics that are available. In particular, we critically assess the claimed health benefits of synbiotic applications and the ecological and therapeutic factors to consider when designing synbiotics and discuss the implications of these concepts for future research in this field

    Probiotic \u3ci\u3eBifidobacterium\u3c/i\u3e strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics

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    Background: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. Results: IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P \u3c 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. Conclusion: This study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut

    Fluctuation spectra of large random dynamical systems reveal hidden structure in ecological networks

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    Understanding the relationship between complexity and stability in large dynamical systems - such as ecosystems - remains a key open question in complexity theory which has inspired a rich body of work developed over more than fifty years. The vast majority of this theory addresses asymptotic linear stability around equilibrium points, but the idea of ‘stability’ in fact has other uses in the empirical ecological literature. The important notion of ‘temporal stability’ describes the character of fluctuations in population dynamics, driven by intrinsic or extrinsic noise. Here we apply tools from random matrix theory to the problem of temporal stability, deriving analytical predictions for the fluctuation spectra of complex ecological networks. We show that different network structures leave distinct signatures in the spectrum of fluctuations, and demonstrate the application of our theory to the analysis ecological timeseries data of plankton abundances

    Effect of argon plasma pre-treatment of healing abutments on peri-implant microbiome and soft tissue integration: a proof-of-concept randomized study

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    Purpose: Biofilm-free implant surface is ultimate prerequisite for successful soft and bone tissue integration. Objective of the study was to estimate the effects of argon plasma healing abutment pre-treatment (PT) on peri-implant soft-tissue phenotype (PiSP), inflammation, plaque accumulation and the microbiome (PiM) between non-treated (NPT) and treated (PT) abutments following 3-months healing period. The hypothesis was that cell-conductive and antimicrobial properties of PT would yield optimal conditions for soft tissue integration. Material and Methods: Two months following second-phase surgery, microbiological and clinical parameters were assessed around thirty-six healing abutments with two types of microtopography, smooth surface (MACHINED) and ultrathin threaded microsurface (ROUGH). A two level randomization schema was used to achieve equal distribution and abutments were randomly divided into rough and machined groups, and then divided into PT and NPT groups. PiM was assessed using next-generation DNA sequencing. Results: PiM bacterial composition was highly diverse already two months post-implantation, consisting of key-stone pathogens, early and late colonizers, while the mycobiome was less diverse. PT was associated with lower plaque accumulation and inflammation without significant impact on PiSP, while in NPT clinical parameters were increased and associated with periopathogens. NPT mostly harbored late colonizers, while PT exerted higher abundance of early colonizers suggesting less advanced plaque formation. Interaction analysis in PT demonstrated S. mitis co-occurrence with pro-healthy Rothia dentocariosa and co-exclusion with Parvimonas micra, Porphyromonas endodontalis and Prevotella oris. PiSP parameters were generally similar between the groups, but significant association between PiM and keratinized mucosa width was observed in both groups, with remarkably more expressed diversity in NPT compared to PT. PT resulted in significantly lower BOP and PI around rough and machined abutments, respectively, without specific effect on PiM and PiSP. Conclusions: PT contributed to significantly the less advanced biofilm accumulation and inflammation without specific effects on PiSP

    \u3ci\u3eIn Vivo\u3c/i\u3e Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

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    One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract
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