Systematic Nonlinear Planning

This paper presents a simple, sound, complete, and systematic algorithm for domain independent STRIPS planning. Simplicity is achieved by starting with a ground procedure and then applying a general and independently verifiable, lifting transformation. Previous planners have been designed directly as lifted procedures. Our ground procedure is a ground version of Tate's NONLIN procedure. In Tate's procedure one is not required to determine whether a prerequisite of a step in an unfinished plan is guarnateed to hold in all linearizations. This allows Tate"s procedure to avoid the use of Chapman"s modal truth criterion. Systematicity is the property that the same plan, or partial plan, is never examined more than once. Systematicity is achieved through a simple modification of Tate's procedure.

Effectiveness and safety of cryotherapy after arthroscopic anterior cruciate ligament reconstruction. A systematic review of the literature

Cryotherapy is widely used in rehabilitation; however, its effectiveness after anterior cruciate ligament (ACL) reconstruction remains uncertain. To investigate the effectiveness and safety of cryotherapy following ACL reconstruction through a systematic review, randomized and quasi-randomized clinical trials were searched in the databases: MEDLINE, EMBASE, CENTRAL PEDro, SportDiscus, CINAHL, LILACS (June 2013). the primary outcomes measures were pain, edema and adverse events; the secondary outcomes were knee function, analgesic medication use, range of motion, blood loss, hospital stay, quality of life and patient satisfaction. the methodological quality of studies was evaluated using the Cochrane Collaboration risk-of-bias tool. Ten trials (a total of 573 patients) were included. Results of meta-analysis showed that the use of cold compression devices produced a significant reduction in pain scores 48 h after surgery (p < 0.00001), compared to no cryotherapy. the risk for adverse events did not differ between patients receiving cryotherapy versus no treatment (p = 1.00). the limited evidence currently available is insufficient to draw definitive conclusions on the effectiveness of cryotherapy for other outcomes. There is a need for well designed, good quality randomized trials to answer other questions related to this intervention and increase the precision of future systematic reviews. (C) 2014 Elsevier B.V. All rights reserved.

Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials

Background and purpose: Accelerated partial breast irradiation (APBI) is the strategy that allows adjuvant treatment delivery in a shorter period of time in smaller volumes. This study was undertaken to assess the effectiveness and outcomes of APBI in breast cancer compared with whole-breast irradiation (WBI). Material and methods: Systematic review and meta-analysis of randomized controlled trials of WBI versus APBI. Two authors independently selected and assessed the studies regarding eligibility criteria. Results: Eight studies were selected. A total of 8653 patients were randomly assigned for WBI versus APBI. Six studies reported local recurrence outcomes. Two studies were matched in 5 years and only one study for different time of follow-up. Meta-analysis of two trials assessing 1407 participants showed significant difference in the WBI versus APBI group regarding the 5-year local recurrence rate (HR = 4.54, 95% CI: 1.78-11.61, p = 0.002). Significant difference in favor of WBI for different follow-up times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed. Conclusions: APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

An inquiry-based learning (IBL) approach to molecular biology for biotechnology undergraduate students

Sin índice de impacto (2013)

Are the Current Ontologies used in Biology Good Ontologies?

Soldatova, L. N. and King R. D. (2005) Are the Current Ontologies used in Biology Good Ontologies? Nature Biotechnology 23:1095-1098

Systematic assessment of the training needs of health library staff

Urquhart, C., Spink, S., Thomas, R. & Durbin, J. (2005). Systematic assessment of the training needs of health library staff. Library and Information Research, 29(93), 35-42. Sponsorship: National Library for Health (NLH)

Synthetic biology: a utilitarian perspective

I examine the positive and negative features of synthetic biology (‘SynBio’) from a utilitarian ethical perspective. The potential beneficial outcomes from SynBio in the context of medicine are substantial; however it is not presently possible to predict precise outcomes due to the nascent state of the field. Potential negative outcomes from SynBio also exist, including iatrogenesis and bioterrorism; however it is not yet possible to quantify these risks. I argue that the application of a ‘precautionary’ approach to SynBio is ethically fraught, as is the notion that SynBio-associated knowledge ought to be restricted. I conclude that utilitarians ought to support a broadly laissez-faire stance in respect of SynBio.

Going retro: oxidative stress biomarkers in modern redox biology

The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process, and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting.

Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review

Paper published in PLoS Medicine in 2007.

Non-clinical outcomes of antiretroviral therapy for HIV/AIDS in developing countries: a systematic literature review

The impacts of antiretroviral therapy on quality of life, mental health, labor productivity, and economic wellbeing for people living with HIV/AIDS in developing countries are only beginning to be measured. We conducted a systematic literature review to analyze the effect of antiretroviral therapy (ART) on these non-clinical indicators in developing countries and assess the state of research on these topics. Both qualitative and quantitative studies were included, as were peer-reviewed articles, gray literature, and conference abstracts and presentations. Findings are reported from 12 full-length articles, 7 abstracts, and 1 presentation (representing 16 studies). Compared to HIV-positive patients not yet on treatment, patients on ART reported significant improvements in physical, emotional and mental health and daily function. Work performance improved and absenteeism decreased, with the most dramatic changes occurring in the first three months of treatment and then leveling off. Little research has been done on the impact of ART on household wellbeing, with modest changes in child and family wellbeing within households where adults are receiving ART reported so far. Studies from developing countries have not yet assessed non-clinical outcomes of therapy beyond the first year; therefore, longitudinal outcomes are still unknown. As ART roll out extends throughout high HIV prevalence, low-resource countries and is sustained over years and decades, both positive and adverse non-clinical outcomes need to be empirically measured and qualitatively explored in order to support patient adherence and maximize treatment benefits.

Systematic Review of Supported Housing Literature 1993 – 2008

Supported housing for individuals with severe mental illness strives to provide the services necessary to place and keep individuals in independent housing that is integrated into the community and in which the consumer has choice and control over his or her services and supports. Supported housing can be contrasted to an earlier model called the “linear residential approach” in which individuals are moved from the most restrictive settings (e.g., inpatient settings) through a series of more independent settings (e.g., group homes, supervised apartments) and then finally to independent housing. This approach has been criticized as punishing the client due to frequent moves, and as being less likely to result in independent housing. In the supported housing model (Anthony & Blanch, 1988) consumers have choice and control over their living environment, their treatment, and supports (e.g., case management, mental health and substance abuse services). Supports are flexible and faded in and out depending on needs. Results of this systematic review of supported housing suggest that there are several well-controlled studies of supported housing and several studies conducted with less rigorous designs. Overall, our synthesis suggests that supported housing can improve the living situation of individuals who are psychiatrically disabled, homeless and with substance abuse problems. Results show that supported housing can help people stay in apartments or homes up to about 80% of the time over an extended period. These results are contrary to concerns expressed by proponents of the linear residential model and housing models that espoused more restrictive environments. Results also show that housing subsidies or vouchers are helpful in getting and keeping individuals housed. Housing services appear to be cost effective and to reduce the costs of other social and clinical services. In order to be most effective, intensive case management services (rather than traditional case management) are needed and will generally lead to better housing outcomes. Having access to affordable housing and having a service system that is well-integrated is also important. Providing a person with supported housing reduces the likelihood that they will be re-hospitalized, although supported housing does not always lead to reduced psychiatric symptoms. Supported housing can improve clients’ quality of life and satisfaction with their living situation. Providing supported housing options that are of decent quality is important in order to keep people housed and satisfied with their housing. In addition, rapid entry into housing, with the provision of choices is critical. Program and clinical supports may be able to mitigate the social isolation that has sometimes been associated with supported housing.

Systematic Verification of Safety Properties of Arbitrary Network Protocol Compositions Using CHAIN

Formal correctness of complex multi-party network protocols can be difficult to verify. While models of specific fixed compositions of agents can be checked against design constraints, protocols which lend themselves to arbitrarily many compositions of agents-such as the chaining of proxies or the peering of routers-are more difficult to verify because they represent potentially infinite state spaces and may exhibit emergent behaviors which may not materialize under particular fixed compositions. We address this challenge by developing an algebraic approach that enables us to reduce arbitrary compositions of network agents into a behaviorally-equivalent (with respect to some correctness property) compact, canonical representation, which is amenable to mechanical verification. Our approach consists of an algebra and a set of property-preserving rewrite rules for the Canonical Homomorphic Abstraction of Infinite Network protocol compositions (CHAIN). Using CHAIN, an expression over our algebra (i.e., a set of configurations of network protocol agents) can be reduced to another behaviorally-equivalent expression (i.e., a smaller set of configurations). Repeated applications of such rewrite rules produces a canonical expression which can be checked mechanically. We demonstrate our approach by characterizing deadlock-prone configurations of HTTP agents, as well as establishing useful properties of an overlay protocol for scheduling MPEG frames, and of a protocol for Web intra-cache consistency.

Plasmid biology of natural Lactococcus lactis strains and molecular mechanisms of bacteriophage-host interaction

Lacticin 3147, enterocin AS-48, lacticin 481, variacin, and sakacin P are bacteriocins offering promising perspectives in terms of preservation and shelf-life extension of food products and should find commercial application in the near future. The studies detailing their characterization and bio-preservative applications are reviewed. Transcriptomic analyses showed a cell wall-targeted response of Lactococcus lactis IL1403 during the early stages of infection with the lytic bacteriophage c2, which is probably orchestrated by a number of membrane stress proteins and involves D-alanylation of membrane lipoteichoic acids, restoration of the physiological proton motive force disrupted following bacteriophage infection, and energy conservation. Sequencing of the eight plasmids of L. lactis subsp. cremoris DPC3758 from raw milk cheese revealed three anti-phage restriction/modification (R/M) systems, immunity/resistance to nisin, lacticin 481, cadmium and copper, and six conjugative/mobilization regions. A food-grade derivative strain with enhanced bacteriophage resistance was generated via stacking of R/M plasmids. Sequencing and functional analysis of the four plasmids of L. lactis subsp. lactis biovar. diacetylactis DPC3901 from raw milk cheese revealed genes novel to Lactococcus and typical of bacteria associated with plants, in addition to genes associated with plant-derived lactococcal strains. The functionality of a novel high-affinity regulated system for cobalt uptake was demonstrated. The bacteriophage resistant and bacteriocin-producing plasmid pMRC01 places a metabolic burden on lactococcal hosts resulting in lowered growth rates and increased cell permeability and autolysis. The magnitude of these effects is strain dependent but not related to bacteriocin production. Starters’ acidification capacity is not significantly affected. Transcriptomic analyses showed that pMRC01 abortive infection (Abi) system is probably subjected to a complex regulatory control by Rgg-like ORF51 and CopG-like ORF58 proteins. These regulators are suggested to modulate the activity of the putative Abi effectors ORF50 and ORF49 exhibiting topology and functional similarities to the Rex system aborting bacteriophage λ lytic growth.

Systematic delay-driven power optimisation and power-driven delay optimisation of combinational circuits

With the proliferation of mobile wireless communication and embedded systems, the energy efficiency becomes a major design constraint. The dissipated energy is often referred as the product of power dissipation and the input-output delay. Most of electronic design automation techniques focus on optimising only one of these parameters either power or delay. Industry standard design flows integrate systematic methods of optimising either area or timing while for power consumption optimisation one often employs heuristics which are characteristic to a specific design. In this work we answer three questions in our quest to provide a systematic approach to joint power and delay Optimisation. The first question of our research is: How to build a design flow which incorporates academic and industry standard design flows for power optimisation? To address this question, we use a reference design flow provided by Synopsys and integrate in this flow academic tools and methodologies. The proposed design flow is used as a platform for analysing some novel algorithms and methodologies for optimisation in the context of digital circuits. The second question we answer is: Is possible to apply a systematic approach for power optimisation in the context of combinational digital circuits? The starting point is a selection of a suitable data structure which can easily incorporate information about delay, power, area and which then allows optimisation algorithms to be applied. In particular we address the implications of a systematic power optimisation methodologies and the potential degradation of other (often conflicting) parameters such as area or the delay of implementation. Finally, the third question which this thesis attempts to answer is: Is there a systematic approach for multi-objective optimisation of delay and power? A delay-driven power and power-driven delay optimisation is proposed in order to have balanced delay and power values. This implies that each power optimisation step is not only constrained by the decrease in power but also the increase in delay. Similarly, each delay optimisation step is not only governed with the decrease in delay but also the increase in power. The goal is to obtain multi-objective optimisation of digital circuits where the two conflicting objectives are power and delay. The logic synthesis and optimisation methodology is based on AND-Inverter Graphs (AIGs) which represent the functionality of the circuit. The switching activities and arrival times of circuit nodes are annotated onto an AND-Inverter Graph under the zero and a non-zero-delay model. We introduce then several reordering rules which are applied on the AIG nodes to minimise switching power or longest path delay of the circuit at the pre-technology mapping level. The academic Electronic Design Automation (EDA) tool ABC is used for the manipulation of AND-Inverter Graphs. We have implemented various combinatorial optimisation algorithms often used in Electronic Design Automation such as Simulated Annealing and Uniform Cost Search Algorithm. Simulated Annealing (SMA) is a probabilistic meta heuristic for the global optimization problem of locating a good approximation to the global optimum of a given function in a large search space. We used SMA to probabilistically decide between moving from one optimised solution to another such that the dynamic power is optimised under given delay constraints and the delay is optimised under given power constraints. A good approximation to the global optimum solution of energy constraint is obtained. Uniform Cost Search (UCS) is a tree search algorithm used for traversing or searching a weighted tree, tree structure, or graph. We have used Uniform Cost Search Algorithm to search within the AIG network, a specific AIG node order for the reordering rules application. After the reordering rules application, the AIG network is mapped to an AIG netlist using specific library cells. Our approach combines network re-structuring, AIG nodes reordering, dynamic power and longest path delay estimation and optimisation and finally technology mapping to an AIG netlist. A set of MCNC Benchmark circuits and large combinational circuits up to 100,000 gates have been used to validate our methodology. Comparisons for power and delay optimisation are made with the best synthesis scripts used in ABC. Reduction of 23% in power and 15% in delay with minimal overhead is achieved, compared to the best known ABC results. Also, our approach is also implemented on a number of processors with combinational and sequential components and significant savings are achieved.

Investigations into selective metabolic aspects of bifidobacteria: carbohydrate metabolism, fatty acid biosynthesis and plasmid biology

The gastrointestinal tract (GIT) is a diverse ecosystem, and is colonised by a diverse array of bacteria, of which bifidobacteria are a significant component. Bifidobacteria are Gram-positive, saccharolytic, non-motile, non-sporulating, anaerobic, Y-shaped bacteria, which possess a high GC genome content. Certain bifidobacteria possess the ability to produce conjugated linoleic acid (CLA) from linoleic acid (LA) by a biochemical pathway that is hypothesised to be achieved via a linoleic isomerase. In Chapter two of this thesis it was found that the MCRA-specifying gene is not involved in CLA production in B. breve NCFB 2258, and that this gene specifies an oleate hydratase involved in the conversion of oleic acid into 10-hydroxystearic acid. Prebiotics are defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating growth and/or activity of one or a limited number of bacteria in the colon. Key to the development of such novel prebiotics is to understand which carbohydrates support growth of bifidobacteria and how such carbohydrates are metabolised. In Chapter 3 of this thesis we describe the identification and characterisation of two neighbouring gene clusters involved in the metabolism of raffinose-containing carbohydrates (plus related carbohydrate melibiose) and melezitose by Bifidobacterium breve UCC2003. The fourth chapter of this thesis describes the analysis of transcriptional regulation of the raf and mel clusters. In the final experimental chapter two putative rep genes, designated repA7017 and repB7017, are identified on the megaplasmid pBb7017 of B. breve JCM 7017, the first bifidobacterial megaplasmid to be reported. One of these, repA7017, was subjected to an in-depth characterisation. The work described in this thesis has resulted in an improved understanding of bifidobacterial fatty acid and carbohydrate metabolism, Furthermore, attempts were made to develop novel genetic tools.