Where Lies the Land?

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Scaling in Late Stage Spinodal Decomposition with Quenched Disorder

We study the late stages of spinodal decomposition in a Ginzburg-Landau mean field model with quenched disorder. Random spatial dependence in the coupling constants is introduced to model the quenched disorder. The effect of the disorder on the scaling of the structure factor and on the domain growth is investigated in both the zero temperature limit and at finite temperature. In particular, we find that at zero temperature the domain size, $R(t)$, scales with the amplitude, $A$, of the quenched disorder as $R(t) = A^{-\beta} f(t/A^{-\gamma})$ with $\beta \simeq 1.0$ and $\gamma \simeq 3.0$ in two dimensions. We show that $\beta/\gamma = \alpha$, where $\alpha$ is the Lifshitz-Slyosov exponent. At finite temperature, this simple scaling is not observed and we suggest that the scaling also depends on temperature and $A$. We discuss these results in the context of Monte Carlo and cell dynamical models for phase separation in systems with quenched disorder, and propose that in a Monte Carlo simulation the concentration of impurities, $c$, is related to $A$ by $A \sim c^{1/d}$.Comment: RevTex manuscript 5 pages and 5 figures (obtained upon request via email [email protected]

Experiences of care planning in England: interviews with patients with long term conditions.

BACKGROUND: The prevalence and impact of long term conditions continues to rise. Care planning for people with long term conditions has been a policy priority in England for chronic disease management. However, it is not clear how care planning is currently understood, translated and implemented in primary care. This study explores experience of care planning in patients with long term conditions in three areas in England. METHODS: We conducted semi-structured interviews with 23 predominantly elderly patients with multiple long term conditions. The interviews were designed to explore variations in and emergent experiences of care planning. Qualitative analysis of interview transcripts involved reflexively coding and re-coding data into categories and themes. RESULTS: No participants reported experiencing explicit care planning discussions or receiving written documentation setting out a negotiated care plan and they were unfamiliar with the term 'care planning'. However, most described some components of care planning which occurred over a number of contacts with health care professionals which we term "reactive" care planning. Here, key elements of care planning including goal setting and action planning were rare. Additionally, poor continuity and coordination of care, lack of time in consultations, and patient concerns about what was legitimate to discuss with the doctor were described. CONCLUSIONS: Amongst this population, elements of care planning were present in their accounts, but a structured, comprehensive process and consequent written record (as outlined in English Department of Health policy) was not evident. Further research needs to explore the advantages and disadvantages of different approaches to care planning for different patient groups.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B

BACKGROUND: Self-complementary adeno-associated virus (scAAV) vectors have become a desirable vector for therapeutic gene transfer due to their ability to produce greater levels of transgene than single-stranded AAV (ssAAV). However, recent reports have suggested that scAAV vectors are more immunogenic than ssAAV. In this study, we investigated the effects of a self-complementary genome during gene therapy with a therapeutic protein, human factor IX (hF.IX). METHODS: Hemophilia B mice were injected intramuscularly with ss or scAAV1 vectors expressing hF.IX. The outcome of gene transfer was assessed, including transgene expression as well as antibody and CD8(+) T cell responses to hF.IX. RESULTS: Self-complementary AAV1 vectors induced similar antibody responses (which eliminated systemic hF.IX expression) but stronger CD8(+) T cell responses to hF.IX relative to ssAAV1 in mice with F9 gene deletion. As a result, hF.IX-expressing muscle fibers were effectively eliminated in scAAV-treated mice. In contrast, mice with F9 nonsense mutation (late stop codon) lacked antibody or T cell responses, thus showing long-term expression regardless of the vector genome. CONCLUSIONS: The nature of the AAV genome can impact the CD8(+) T cell response to the therapeutic transgene product. In mice with endogenous hF.IX expression, however, this enhanced immunogenicity did not break tolerance to hF.IX, suggesting that the underlying mutation is a more important risk factor for transgene-specific immunity than the molecular form of the AAV genome

Urban Horticulture, from Local Initiatives to Global Success Stories

Urban horticulture describes economically viable horticultural production activities conducted in a city or suburb. It is a growing segment of horticulture in the United States as well as in developing countries, where the enormous growth of megalopolis is not backed by a simultaneous increase of farmland or agricultural productivity. Today, urban horticulture includes food sovereignty in underprivileged neighborhoods, increased availability of vegetables and fruits in big cities, healthy and diverse diets, improved food safety, low transportation costs, efficient resource use, and the mitigation of environmental impacts of horticultural production such as the emission of greenhouse gases. The workshop “Urban horticulture: From local initiatives to global success stories,” held at the 2018 American Society for Horticultural Science (ASHS) conference in Washington, DC, featured present and historical success stories of urban horticulture from Asia, Africa, Latin America, and the United States

Proposed revision of the higher tier testing requirements for EPPO Standard PP1/170: Test methods for evaluating the side-effects of plant protection products on honeybees

contribution to session I  Regulatory issues Background: Regulatory evaluations for the effects of pesticides on honeybees in the EU are based on the honeybee test guidelines and risk assessment scheme of the European Plant Protection Organisation (EPPO). While this is considered to be robust and effective, it is also recognised that a continuous process of review and appropriate development is necessary. A working group of the International Commission for Plant-Bee Relationships (ICPBR) had been set up to review the current guidance set out in the EPPO PP1/170 standard for higher tier testing i.e. semi-field (cage) test and full field studies. The aim of this group was to utilise the considerable experience obtained with honey bee testing. This paper presents the working group’s proposed revision to the EPPO standard PP1/170, taking into account feedback received from the 10th ICPBR Symposium in Bucharest.Results: The primary aim of the group has been to produce guidance that is sufficiently detailed yet suitably flexible so that it enables tests to be conducted and evaluated without being too prescriptive. In particular, it recognises that higher tier testing may arise as a result of various initial concerns e.g. adult toxicity, brood effects and systemic toxicity. The guidance is designed to provide the different emphasis that is required to meet the specific requirements of individual studies. Conclusion: The revision of higher tier testing for honeybees presented in this paper is proposed as an update to the current EPPO PP1/170 standard.Keywords: honey bees, test guidelines, higher tier, semi-field (cage) tests, field tests

Innate Immune Responses to AAV Vectors

Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is attractive as a potential treatment for a variety of genetic disorders. However, while AAV has been used successfully in many models, other experiments in clinical trials and in animal models have been hampered by undesired responses from the immune system. Recent studies of AAV immunology have focused on the elimination of transgene-expressing cells by the adaptive immune system, yet the innate immune system also has a critical role, both in the initial response to the vector and in prompting a deleterious adaptive immune response. Responses to AAV vectors are primarily mediated by the TLR9–MyD88 pathway, which induces the production of pro-inflammatory cytokines by activating the NF-κB pathways and inducing type I IFN production; self-complementary AAV vectors enhance these inflammatory processes. Additionally, the alternative NF-κB pathway influences transgene expression in cells transduced by AAV. This review highlights these recent discoveries regarding innate immune responses to AAV and discusses strategies to ablate these potentially detrimental signaling pathways

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66249/1/jphysiol.2004.072736.pd