STUDIES ON CONSTANT PARAMAGNETISM: PART I.

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STUDIES ON CONSTANT PARAMAGNETISM : PART II: Diamagnetic compounds containing a transition element.

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Participatory development of decision support systems: which features of the process lead to improved uptake and better outcomes?

Decision support systems (DSSs) are important in decision-making environments with conflicting interests. Many DSSs developed have not been used in practice. Experts argue that these tools do not respond to real user needs and that the inclusion of stakeholders in the development process is the solution. However, it is not clear which features of participatory development of DSSs result in improved uptake and better outcomes. A review of papers, reporting on case studies where DSSs and other decision tools (information systems, software and scenario tools) were developed with elements of participation, was carried out. The cases were analysed according to a framework created as part of this research; it includes criteria to evaluate the development process and the outcomes. Relevant aspects to consider in the participatory development processes include establishing clear objectives, timing and location of the process; keeping discussions on track; favouring participation and interaction of individuals and groups; and challenging creative thinking of the tool and future scenarios. The case studies that address these issues show better outcomes; however, there is a large degree of uncertainty concerning them because developers have typically neither asked participants about their perceptions of the processes and resultant tools nor have they monitored the use and legacy of the tools over the long term.The authors would like to thank COST Action FP0804-Forest Management Decision Support Systems (FORSYS) for financing a three month Short-Term Scientific Mission (STSM) in Forest Research (Roslin, UK) in 2012, making possible this research; Spanish Ministry of Economy and Competitiveness for supporting the project Multicriteria Techniques and Participatory Decision-Making for Sustainable Management (Ref. ECO2011-27369) where the leading author is involved; and the Regional Ministry of Education, Culture and Sports (Valencia, Spain) for financing a research fellowship (Ref. ACIF/2010/248).Valls Donderis, P.; Ray, D.; Peace, A.; Stewart, A.; Lawrence, A.; Galiana, F. (2013). Participatory development of decision support systems: which features of the process lead to improved uptake and better outcomes?. Scandinavian Journal of Forest Research. 29(1):71-83. https://doi.org/10.1080/02827581.2013.837950S7183291Arnstein, S. R. (1969). A Ladder Of Citizen Participation. Journal of the American Institute of Planners, 35(4), 216-224. doi:10.1080/01944366908977225Atwell, R. C., Schulte, L. A., & Westphal, L. M. (2011). Tweak, Adapt, or Transform: Policy Scenarios in Response to Emerging Bioenergy Markets in the U.S. Corn Belt. Ecology and Society, 16(1). doi:10.5751/es-03854-160110Barac, A., Kellner, K., & De Klerk, N. (2004). Land User Participation in Developing a Computerised Decision Support System for Combating Desertification. Environmental Monitoring and Assessment, 99(1-3), 223-231. doi:10.1007/s10661-004-4022-6Bennet, A., & Bennet, D. (2008). The Decision-Making Process in a Complex Situation. Handbook on Decision Support Systems 1, 3-20. doi:10.1007/978-3-540-48713-5_1Blackstock, K. L., Kelly, G. J., & Horsey, B. L. (2007). Developing and applying a framework to evaluate participatory research for sustainability. Ecological Economics, 60(4), 726-742. doi:10.1016/j.ecolecon.2006.05.014Breuer, N. E., Cabrera, V. E., Ingram, K. T., Broad, K., & Hildebrand, P. E. (2007). AgClimate: a case study in participatory decision support system development. Climatic Change, 87(3-4), 385-403. doi:10.1007/s10584-007-9323-7Bunch, M. J., & Dudycha, D. J. (2004). Linking conceptual and simulation models of the Cooum River: collaborative development of a GIS-based DSS for environmental management. Computers, Environment and Urban Systems, 28(3), 247-264. doi:10.1016/s0198-9715(03)00021-8Byrne, E., & Sahay, S. (2007). Participatory design for social development: A South African case study on community-based health information systems. Information Technology for Development, 13(1), 71-94. doi:10.1002/itdj.20052Cain, J. ., Jinapala, K., Makin, I. ., Somaratna, P. ., Ariyaratna, B. ., & Perera, L. . (2003). Participatory decision support for agricultural management. A case study from Sri Lanka. Agricultural Systems, 76(2), 457-482. doi:10.1016/s0308-521x(02)00006-9Chakraborty, A. (2011). Enhancing the role of participatory scenario planning processes: Lessons from Reality Check exercises. Futures, 43(4), 387-399. doi:10.1016/j.futures.2011.01.004Cinderby, S., Bruin, A. de, Mbilinyi, B., Kongo, V., & Barron, J. (2011). Participatory geographic information systems for agricultural water management scenario development: A Tanzanian case study. Physics and Chemistry of the Earth, Parts A/B/C, 36(14-15), 1093-1102. doi:10.1016/j.pce.2011.07.039Drew, C. H., Nyerges, T. L., & Leschine, T. M. (2004). Promoting Transparency of Long‐Term Environmental Decisions: The Hanford Decision Mapping System Pilot Project. Risk Analysis, 24(6), 1641-1664. doi:10.1111/j.0272-4332.2004.00556.xDriedger, S. M., Kothari, A., Morrison, J., Sawada, M., Crighton, E. J., & Graham, I. D. (2007). Using participatory design to develop (public) health decision support systems through GIS. International Journal of Health Geographics, 6(1), 53. doi:10.1186/1476-072x-6-53Evers, M. (2008). An analysis of the requirements for DSS on integrated river basin management. Management of Environmental Quality: An International Journal, 19(1), 37-53. doi:10.1108/14777830810840354Iivari, N. (2011). Participatory design in OSS development: interpretive case studies in company and community OSS development contexts. Behaviour & Information Technology, 30(3), 309-323. doi:10.1080/0144929x.2010.503351Innes, J. E., & Booher, D. E. (1999). Consensus Building and Complex Adaptive Systems. Journal of the American Planning Association, 65(4), 412-423. doi:10.1080/01944369908976071Jakku, E., & Thorburn, P. J. (2010). A conceptual framework for guiding the participatory development of agricultural decision support systems. Agricultural Systems, 103(9), 675-682. doi:10.1016/j.agsy.2010.08.007Jessel, B., & Jacobs, J. (2005). Land use scenario development and stakeholder involvement as tools for watershed management within the Havel River Basin. Limnologica, 35(3), 220-233. doi:10.1016/j.limno.2005.06.006Kautz, K. (2011). Investigating the design process: participatory design in agile software development. Information Technology & People, 24(3), 217-235. doi:10.1108/09593841111158356Kowalski, K., Stagl, S., Madlener, R., & Omann, I. (2009). Sustainable energy futures: Methodological challenges in combining scenarios and participatory multi-criteria analysis. European Journal of Operational Research, 197(3), 1063-1074. doi:10.1016/j.ejor.2007.12.049Lawrence, A. (2006). ‘No Personal Motive?’ Volunteers, Biodiversity, and the False Dichotomies of Participation. Ethics, Place & Environment, 9(3), 279-298. doi:10.1080/13668790600893319Mao, J., & Song, W. (2008). Empirical study of distinct features and challenges of joint development of information systems: The case of ABC bank. Tsinghua Science and Technology, 13(3), 414-419. doi:10.1016/s1007-0214(08)70066-xMenzel, S., Nordström, E.-M., Buchecker, M., Marques, A., Saarikoski, H., & Kangas, A. (2012). Decision support systems in forest management: requirements from a participatory planning perspective. European Journal of Forest Research, 131(5), 1367-1379. doi:10.1007/s10342-012-0604-yMoote, M. A., Mcclaran, M. P., & Chickering, D. K. (1997). RESEARCH: Theory in Practice: Applying Participatory Democracy Theory to Public Land Planning. Environmental Management, 21(6), 877-889. doi:10.1007/s002679900074Peleg, M., Shachak, A., Wang, D., & Karnieli, E. (2009). Using multi-perspective methodologies to study users’ interactions with the prototype front end of a guideline-based decision support system for diabetic foot care. International Journal of Medical Informatics, 78(7), 482-493. doi:10.1016/j.ijmedinf.2009.02.008Pretty, J. N. (1995). Participatory learning for sustainable agriculture. World Development, 23(8), 1247-1263. doi:10.1016/0305-750x(95)00046-fReed MS. 2008. Stakeholder participation for environmental management: a literature review. Sustainability Research Institute, School of Earth and Environment, University of Leeds.Reed, M. S., & Dougill, A. J. (2010). Linking degradation assessment to sustainable land management: A decision support system for Kalahari pastoralists. Journal of Arid Environments, 74(1), 149-155. doi:10.1016/j.jaridenv.2009.06.016Rowe, G., & Frewer, L. J. (2000). Public Participation Methods: A Framework for Evaluation. Science, Technology, & Human Values, 25(1), 3-29. doi:10.1177/016224390002500101Schielen, R. M. J., & Gijsbers, P. J. A. (2003). DSS-large rivers: developing a DSS under changing societal requirements. Physics and Chemistry of the Earth, Parts A/B/C, 28(14-15), 635-645. doi:10.1016/s1474-7065(03)00109-8Sheppard, S. R. J., & Meitner, M. (2005). Using multi-criteria analysis and visualisation for sustainable forest management planning with stakeholder groups. Forest Ecology and Management, 207(1-2), 171-187. doi:10.1016/j.foreco.2004.10.032Thursky, K. A., & Mahemoff, M. (2007). User-centered design techniques for a computerised antibiotic decision support system in an intensive care unit. International Journal of Medical Informatics, 76(10), 760-768. doi:10.1016/j.ijmedinf.2006.07.011Webler, S. T., Thomas. (1999). Voices from the Forest: What Participants Expect of a Public Participation Process. Society & Natural Resources, 12(5), 437-453. doi:10.1080/089419299279524Van Meensel, J., Lauwers, L., Kempen, I., Dessein, J., & Van Huylenbroeck, G. (2012). Effect of a participatory approach on the successful development of agricultural decision support systems: The case of Pigs2win. Decision Support Systems, 54(1), 164-172. doi:10.1016/j.dss.2012.05.002Von Geibler, J., Kristof, K., & Bienge, K. (2010). Sustainability assessment of entire forest value chains: Integrating stakeholder perspectives and indicators in decision support tools. Ecological Modelling, 221(18), 2206-2214. doi:10.1016/j.ecolmodel.2010.03.02

Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

We describe two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalized nuclei, myofibrillar disarray, and “corona” fibres. Both affected siblings were found to be compound heterozygous for c.3425G>A (p.Arg1142Gln) and c.1123T>C (p.Cys375Arg) mutations in SCN4A on exome sequencing, and the parents were confirmed carriers of one of the mutations. Electrophysiological characterization of the mutations revealed the Cys375Arg confers full and Arg1142Gln mild partial loss-of-function. Loss of function of the Nav1.4 channel leads to a decrement of the action potential and subsequent reduction of muscle contraction. The unusual muscle biopsy features suggest a more complex pathomechanism, and broaden the phenotype associated with SCN4A mutations

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Real-Time Dynamic Imaging of Virus Distribution In Vivo

The distribution of viruses and gene therapy vectors is difficult to assess in a living organism. For instance, trafficking in murine models can usually only be assessed after sacrificing the animal for tissue sectioning or extraction. These assays are laborious requiring whole animal sectioning to ascertain tissue localization. They also obviate the ability to perform longitudinal or kinetic studies in one animal. To track viruses after systemic infection, we have labeled adenoviruses with a near-infrared (NIR) fluorophore and imaged these after intravenous injection in mice. Imaging was able to track and quantitate virus particles entering the jugular vein simultaneous with injection, appearing in the heart within 500 milliseconds, distributing in the bloodstream and throughout the animal within 7 seconds, and that the bulk of virus distribution was essentially complete within 3 minutes. These data provide the first in vivo real-time tracking of the rapid initial events of systemic virus infection

Analysis of Large Phenotypic Variability of EEC and SHFM4 Syndromes Caused by K193E Mutation of the TP63 Gene

EEC (ectrodactyly, ectodermal dysplasia, clefting; OMIM 604292) is an autosomal dominant developmental disorder resulting mainly from pathogenic mutations of the DNA-binding domain (DBD) of the TP63 gene. In this study, we showed that K193E mutation in nine affected individuals of a four-generation kindred with a large degree of phenotypic variability causes four different syndromes or TP63-related disorders: EEC, Ectrodactyly-ectodermal dysplasia (EE), isolated ectodermal dysplasia, and isolated Split Hand/Foot Malformation type 4 (SHFM4). Genotype-phenotype and DBD structural modeling analysis showed that the K193-located loop L2-A is associated with R280 through hydrogen bonding interactions, while R280 mutations also often cause large phenotypic variability of EEC and SHFM4. Thus, we speculate that K193 and several other DBD mutation-associated syndromes may share similar pathogenic mechanisms, particularly in the case of the same mutation with different phenotypes. Our study and others also suggest that the phenotypic variability of EEC is attributed, at least partially, to genetic and/or epigenetic modifiers

Virulence related sequences: insights provided by comparative genomics of Streptococcus uberis of differing virulence

Background: Streptococcus uberis, a Gram-positive, catalase-negative member of the family Streptococcaceae is an important environmental pathogen responsible for a significant proportion of subclinical and clinical bovine intramammary infections. Currently, the genome of only a single reference strain (0140J) has been described. Here we present a comparative analysis of complete draft genome sequences of an additional twelve S. uberis strains. Results: Pan and core genome analysis revealed the core genome common to all strains to be 1,550 genes in 1,509 orthologous clusters, complemented by 115-246 accessory genes present in one or more S. uberis strains but absent in the reference strain 0140J. Most of the previously predicted virulent genes were present in the core genome of all 13 strains but gene gain/loss was observed between the isolates in CDS associated with clustered regularly interspaced short palindromic repeats (CRISPRs), prophage and bacteriocin production. Experimental challenge experiments confirmed strain EF20 as non-virulent; only able to infect in a transient manner that did not result in clinical mastitis. Comparison of the genome sequence of EF20 with the validated virulent strain 0140J identified genes associated with virulence, however these did not relate clearly with clinical/non-clinical status of infection. Conclusion: The gain/loss of mobile genetic elements such as CRISPRs and prophage are a potential driving force for evolutionary change. This first “whole-genome” comparison of strains isolated from clinical vs non-clinical intramammary infections including the type virulent vs non-virulent strains did not identify simple gene gain/loss rules that readily explain, or be confidently associated with, differences in virulence. This suggests that a more complex dynamic determines infection potential and clinical outcome not simply gene content

Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas

1–5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineated in a series of 1051 cancer patients receiving a first course of chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996 (CLB-1996 cohort), and then validated in a series of patients treated in the same department in 1997 (CLB-1997), in a prospective cohort of patients with aggressive non-Hodgkin's lymphoma (NHL) (CLB-NHL), and in a prospective cohort of patients with metastatic breast cancer (MBC series) receiving first-line chemotherapy. In the CLB-1996 series, 43 patients (4.1%) experienced early. In univariate analysis, age > 60, PS > 1, lymphocyte (ly) count ≤ 700 μl−1 immediately prior to chemotherapy (d1), d1-platelet count ≤ 150 Gl−1, and the type of chemotherapy were significantly correlated to the risk of early death (P ≤ 0.01). Using logistic regression, PS > 1 (hazard ratio 3.9 (95% Cl 2.0–7.5)) and d1-ly count ≤ 700 μl−1 (3.1 (95% Cl 1.6–5.8)) were identified as independent risk factors for ED. The calculated probability of ED was 20% (95% Cl 10–31) in patients with both risk factors, 6% (95% Cl 4–9) for patients with only 1 risk factor, and 1.7% (95% Cl 0.9–3) for patients with none of these 2 risk factors. In the CLB-97, CLB-NHL and MBC validation series, the observed incidences of early death in patients with both risk factors were 19%, 25% and 40% respectively and did not differ significantly from those calculated in the model. In conclusion, poor performance status and lymphopenia identify a subgroup of patients at high risk for early death after chemotherapy. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

BACKGROUND: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. METHODS: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. RESULTS: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems