198 research outputs found

    Immune Recognition of the 60kD Heat Shock Protein: Implications for Subsequent Fertility

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    The 60kD heat shock protein (hsp60) is a highly conserved protein and a dominant antigen of most pathogenic bacteria. In some women, chronic or repeated upper genital tract infections with Chlamydia trachomatis, and possibly with other microorganisms, induces immune sensitization to epitopes of hsp60 that are present in both the microbial and human hsp60. Once a woman becomes sensitized to these conserved epitpes, any subsequent induction of human or bacterial hsp60 expression will reactivate hsp60-sensitized lymphocytes and initiate a pro-inflammatory immune response. Hsp60 is expressed during the early stages of pregnancy, by both the embryo and the maternal decidua. We examined, therefore, whether women who were sensitized to hsp60 experienced less successful pregnancy outcomes compared to women who were not sensitized to this antigen. In women undergoing in vitro fertilization (IVF), the presence of cervical IgA antibodies reactive with the C. trachomatis hsp60 correlated with implantation failure after embryo transfer. Further analysis revealed that an immunodominant epitope for these IgA antibodies was an hsp60 epitope shared between C. trachomatis and man. In subsequent studies of women not undergoing IVF, cervical IgA antibodies to the human hsp60 were identified in 13 of 91 reproductive age women. This antibody was most prevalent in those women with a history of primary infertility (p = 0.003). In addition, cervical anti-hsp60 IgA correlated with the detection of the pro-inflammatory cytokines interferon-γ (p = 0.001) and tumor necrosis factor-α (p = 0.02) in the cervix. Conversely, women with proven fertility had the highest prevalence of the anti-inflammatory cytokine, interleukin 10, in their cervices (p = 0.001). In an analysis of serum samples in a third study, women with a history of two or more consecutive first trimester spontaneous abortions had a higher prevalence (p = 0.01) of IgG antibodies to the human hsp60 (36.8%) than did age matched fertile women (11.1%) or women with primary infertility (11.8%). Immune sensitization to epitopes expressed by the human hsp60 may reduce the probability of a successful pregnancy outcome due to reactivation of hsp60-reactive lymphocytes, induction of a pro-inflammatory cytokine response and interference with early embryo development and/or implantation

    Role of a cardio‐renal multi‐disciplinary team meeting in managing cardiovascular risk in patients on kidney transplant waitlists

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    Background Waitlisted kidney transplant patients suffer from excess cardiovascular events. The benefits of regular cardiac investigations, potentially harmful and expensive, are unknown. We investigate the effectiveness of a cardio‐renal MDT in managing high cardiovascular risk waitlisted transplant patients to prevent events and enable transplantation. Methods Clinical outcomes in waitlisted transplant candidates managed by our cardio‐renal MDT protocol were compared against our standard protocol. Data compared include the transplantation, event, and death rates, cost of cardiac investigations and procedures, and graft, patient survival, and re‐hospitalization rates in transplanted patients. Results 207 patients were studied (81 standard, 126 cardio‐renal MDT). Over 2.7 years, the cardio‐renal MDT protocol transplanted more patients than the standard group (35% vs 21%; P = .02). The managing cost per patient per year was higher in the standard group (£692 vs £610). This was driven by more echocardiograms and more tests per patient in the standard group (P < .01). There was no difference in adverse events or death. There was no difference in re‐hospitalization, graft or patient survival rate in transplanted patients. Conclusions Our cardio‐renal MDT was effective in managing high‐risk kidney transplant candidates with greater rates of transplantation and low rates of events at a lower cost

    Planning a 'slum free' Trivandrum: housing upgrade and the rescaling of urban governance in India

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    This paper examines how India’s national urban development agenda is reshaping relationships between national, State and city-level governments. JNNURM, the flagship programme that heralded a new era of urban investment in India, contained a range of key governance aspirations: linking the analysis of urban poverty to city-level planning, developing holistic housing solutions for the urban poor, and above all empowering Urban Local Bodies to re-balance relationships between State and city-level governments in favour of the latter. Here, we trace JNNURM’s implementation in Kerala’s capital city, Trivandrum (Thiruvananthapuram), where the city’s decentralised urban governance structure and use of ‘pro-poor’ institutions to implement housing upgrade programmes could have made it an exemplar of success. In practice, Trivandrum’s ‘city visioning’ exercises and the housing projects it has undertaken have fallen short of JNNURM’s lofty goals. The contradictions between empowering cities and retaining centralised control embedded within this national programme, and the unintended city-level consequences of striving for JNNURM funding success, have reshaped urban governance in ways not envisaged within policy. As a result, JNNURM has been important in rescaling governance relationships through three interlinked dynamics of problem framing, technologies of governance and the scalar strategy of driving reform ‘from above’ that together have ensured the national state’s continued influence over the practices of urban governance in India

    Feature Selection by Multiobjective Optimization: Application to Spam Detection System by Neural Networks and Grasshopper Optimization Algorithm

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    Networks are strained by spam, which also overloads email servers and blocks mailboxes with unwanted messages and files. Setting the protective level for spam filtering might become even more crucial for email users when malicious steps are taken since they must deal with an increase in the number of valid communications being marked as spam. By finding patterns in email communications, spam detection systems (SDS) have been developed to keep track of spammers and filter email activity. SDS has also enhanced the tool for detecting spam by reducing the rate of false positives and increasing the accuracy of detection. The difficulty with spam classifiers is the abundance of features. The importance of feature selection (FS) comes from its role in directing the feature selection algorithm’s search for ways to improve the SDS’s classification performance and accuracy. As a means of enhancing the performance of the SDS, we use a wrapper technique in this study that is based on the multi-objective grasshopper optimization algorithm (MOGOA) for feature extraction and the recently revised EGOA algorithm for multilayer perceptron (MLP) training. The suggested system’s performance was verified using the SpamBase, SpamAssassin, and UK-2011 datasets. Our research showed that our novel approach outperformed a variety of established practices in the literature by as much as 97.5%, 98.3%, and 96.4% respectively.©2022 the Authors. Published by IEEE. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. For more information, see https://creativecommons.org/licenses/by-nc-nd/4.0/fi=vertaisarvioitu|en=peerReviewed

    Mosaic: A Satellite Constellation to Enable Groundbreaking Mars Climate System Science and Prepare for Human Exploration

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    The Martian climate system has been revealed to rival the complexity of Earth\u27s. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars\u27 diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars\u27 plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions

    Bridge to the future: Important lessons from 20 years of ecosystem observations made by the OzFlux network

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    In 2020, the Australian and New Zealand flux research and monitoring network, OzFlux, celebrated its 20th anniversary by reflecting on the lessons learned through two decades of ecosystem studies on global change biology. OzFlux is a network not only for ecosystem researchers, but also for those ‘next users’ of the knowledge, information and data that such networks provide. Here, we focus on eight lessons across topics of climate change and variability, disturbance and resilience, drought and heat stress and synergies with remote sensing and modelling. In distilling the key lessons learned, we also identify where further research is needed to fill knowledge gaps and improve the utility and relevance of the outputs from OzFlux. Extreme climate variability across Australia and New Zealand (droughts and flooding rains) provides a natural laboratory for a global understanding of ecosystems in this time of accelerating climate change. As evidence of worsening global fire risk emerges, the natural ability of these ecosystems to recover from disturbances, such as fire and cyclones, provides lessons on adaptation and resilience to disturbance. Drought and heatwaves are common occurrences across large parts of the region and can tip an ecosystem's carbon budget from a net CO2 sink to a net CO2 source. Despite such responses to stress, ecosystems at OzFlux sites show their resilience to climate variability by rapidly pivoting back to a strong carbon sink upon the return of favourable conditions. Located in under-represented areas, OzFlux data have the potential for reducing uncertainties in global remote sensing products, and these data provide several opportunities to develop new theories and improve our ecosystem models. The accumulated impacts of these lessons over the last 20 years highlights the value of long-term flux observations for natural and managed systems. A future vision for OzFlux includes ongoing and newly developed synergies with ecophysiologists, ecologists, geologists, remote sensors and modellers.</p
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