VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG

<p>Abstract</p> <p>Background</p> <p>This work tests the hypothesis that increased levels of vascular endothelial growth factor (VEGF) observed during bladder inflammation modulates nerve plasticity.</p> <p>Methods</p> <p>Chronic inflammation was induced by intravesical instillations of Bacillus Calmette-Guérin (BCG) into the urinary bladder and the density of nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) or pan-neuronal marker PGP9.5 was used to quantify alterations in peripheral nerve plasticity. Some mice were treated with B20, a VEGF neutralizing antibody to reduce the participation of VEGF. Additional mice were treated systemically with antibodies engineered to specifically block the binding of VEGF to NRP1 (anti-NRP1^B) and NRP2 (NRP2^B), or the binding of semaphorins to NRP1 (anti-NRP1 ^A) to diminish activity of axon guidance molecules such as neuropilins (NRPs) and semaphorins (SEMAs). To confirm that VEGF is capable of inducing inflammation and neuronal plasticity, another group of mice was instilled with recombinant VEGF₁₆₅or VEGF₁₂₁into the urinary bladder.</p> <p>Results</p> <p>The major finding of this work was that chronic BCG instillation resulted in inflammation and an overwhelming increase in both PGP9.5 and TRPV1 immunoreactivity, primarily in the sub-urothelium of the urinary bladder. Treatment of mice with anti-VEGF neutralizing antibody (B20) abolished the effect of BCG on inflammation and nerve density.</p> <p>NRP1^Aand NRP1^Bantibodies, known to reduce BCG-induced inflammation, failed to block BCG-induced increase in nerve fibers. However, the NRP2^Bantibody dramatically potentiated the effects of BCG in increasing PGP9.5-, TRPV1-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivity (IR). Finally, instillation of VEGF₁₂₁or VEGF₁₆₅into the mouse bladder recapitulated the effects of BCG and resulted in a significant inflammation and increase in nerve density.</p> <p>Conclusions</p> <p>For the first time, evidence is being presented supporting that chronic BCG instillation into the mouse bladder promotes a significant increase in peripheral nerve density that was mimicked by VEGF instillation. Effects of BCG were abolished by pre-treatment with neutralizing VEGF antibody. The present results implicate the VEGF pathway as a key modulator of inflammation and nerve plasticity, introduces a new animal model for investigation of VEGF-induced nerve plasticity, and suggests putative mechanisms underlying this phenomenon.</p

Cake Cutting Algorithms for Piecewise Constant and Piecewise Uniform Valuations

Cake cutting is one of the most fundamental settings in fair division and mechanism design without money. In this paper, we consider different levels of three fundamental goals in cake cutting: fairness, Pareto optimality, and strategyproofness. In particular, we present robust versions of envy-freeness and proportionality that are not only stronger than their standard counter-parts but also have less information requirements. We then focus on cake cutting with piecewise constant valuations and present three desirable algorithms: CCEA (Controlled Cake Eating Algorithm), MEA (Market Equilibrium Algorithm) and CSD (Constrained Serial Dictatorship). CCEA is polynomial-time, robust envy-free, and non-wasteful. It relies on parametric network flows and recent generalizations of the probabilistic serial algorithm. For the subdomain of piecewise uniform valuations, we show that it is also group-strategyproof. Then, we show that there exists an algorithm (MEA) that is polynomial-time, envy-free, proportional, and Pareto optimal. MEA is based on computing a market-based equilibrium via a convex program and relies on the results of Reijnierse and Potters [24] and Devanur et al. [15]. Moreover, we show that MEA and CCEA are equivalent to mechanism 1 of Chen et. al. [12] for piecewise uniform valuations. We then present an algorithm CSD and a way to implement it via randomization that satisfies strategyproofness in expectation, robust proportionality, and unanimity for piecewise constant valuations. For the case of two agents, it is robust envy-free, robust proportional, strategyproof, and polynomial-time. Many of our results extend to more general settings in cake cutting that allow for variable claims and initial endowments. We also show a few impossibility results to complement our algorithms.Comment: 39 page

Sequential Deliberation for Social Choice

In large scale collective decision making, social choice is a normative study of how one ought to design a protocol for reaching consensus. However, in instances where the underlying decision space is too large or complex for ordinal voting, standard voting methods of social choice may be impractical. How then can we design a mechanism - preferably decentralized, simple, scalable, and not requiring any special knowledge of the decision space - to reach consensus? We propose sequential deliberation as a natural solution to this problem. In this iterative method, successive pairs of agents bargain over the decision space using the previous decision as a disagreement alternative. We describe the general method and analyze the quality of its outcome when the space of preferences define a median graph. We show that sequential deliberation finds a 1.208- approximation to the optimal social cost on such graphs, coming very close to this value with only a small constant number of agents sampled from the population. We also show lower bounds on simpler classes of mechanisms to justify our design choices. We further show that sequential deliberation is ex-post Pareto efficient and has truthful reporting as an equilibrium of the induced extensive form game. We finally show that for general metric spaces, the second moment of of the distribution of social cost of the outcomes produced by sequential deliberation is also bounded

Measurement invariance of the kidney disease and quality of life instrument (KDQOL-SF) across Veterans and non-Veterans

<p>Abstract</p> <p>Background</p> <p>Studies have demonstrated that perceived health-related quality of life (HRQOL) of patients receiving hemodialysis is significantly impaired. Since HRQOL outcome data are often used to compare groups to determine health care effectiveness it is imperative that measures of HRQOL are valid. However, valid HRQOL comparisons between groups can only be made if instrument invariance is demonstrated. The Kidney Disease Quality of Life-Short Form (KDQOL-SF) is a widely used HRQOL measure for patients with chronic kidney disease (CKD) however, it has not been validated in the Veteran population. Therefore, the purpose of this study was to examine the measurement invariance of the KDQOL-SF across Veterans and non-Veterans with CKD.</p> <p>Methods</p> <p>Data for this study were from two large prospective observational studies of patients receiving hemodialysis: 1) Veteran End-Stage Renal Disease Study (VETERAN) (N = 314) and 2) Dialysis Outcomes and Practice Patterns Study (DOPPS) (N = 3,300). Health-related quality of life was measured with the KDQOL-SF, which consists of the SF-36 and the Kidney Disease Component Summary (KDCS). Single-group confirmatory factor analysis was used to evaluate the goodness-of-fit of the hypothesized measurement model for responses to the subscales of the KDCS and SF-36 instruments when analyzed together; and given acceptable goodness-of-fit in each group, multigroup CFA was used to compare the structure of this factor model in the two samples. Pattern of factor loadings (configural invariance), the magnitude of factor loadings (metric invariance), and the magnitude of item intercepts (scalar invariance) were assessed as well as the degree to which factors have the same variances, covariances, and means across groups (structural invariance).</p> <p>Results</p> <p>CFA demonstrated that the hypothesized two-factor model (KDCS and SF-36) fit the data of both the Veteran and DOPPS samples well, supporting configural invariance. Multigroup CFA results concerning metric and scalar invariance suggested partial strict invariance for the SF-36, but only weak invariance for the KDCS. Structural invariance was not supported.</p> <p>Conclusions</p> <p>Results suggest that Veterans may interpret the KDQOL-SF differently than non-Veterans. Further evaluation of measurement invariance of the KDQOL-SF between Veterans and non-Veterans is needed using large, randomly selected samples before comparisons between these two groups using the KDQOL-SF can be done reliably.</p

Summary of the LHC Controls and Operations Forum held at CERN on 1-2 December 1999

The LHC Controls-Operations Forum in December attempted to identify the challenges of running the LHC and the implications for controls and equipment. An outline of the forum, its objectives, summaries of the various sessions, conclusions and some recommendations are presented. It is anticipated that this information will act as input into current and future development

TRADISI DAN KELEMBAGAAN MASYARAKAT DALAM PENGELOLAAN SUMBERDAYA PESISIR DAN LAUT DI KOTA TIDORE KEPULAUAN PROVINSI MALUKU UTARA

Increasing of global awareness related to environmental management, ecosystems, and fisheries resources is a trigger in the reactualization of community traditions and institutions. People of Tidore Islands City, known as indigenous people with their coastal and marine institutional traditions in North Maluku Province, have a local order handed down in the utilization of the coastal and marine resources. This study aimed to analyze the existence of traditions and institutions and their effects on managing coastal and marine resources in the City of Tidore Islands. The research was conducted on June-August 2019 in the city of Tidore Islands. This research encompass 4 Subdistrict and 2 villages namely, Tomalou, Mareku, Soasio and Dowora Subdistrict as well as Mare Gam and Maitara village,. The research applied a qualitative method, which involves in-depth interview techniques, observation, and documentation. Data were analysed using a qualitative descriptive analysis. The results of the study showed that there are five local wisdoms that are maintained by the people of Tidore Islands City nowadays. These local wisdom is a legacy from the ancestors in the management of coastal and marine resources, namely Karo Kahiya (Calling the Dolphins), Fola Sow (Lit. House of Medicine), Jere (Sacred), Cofa (Fish breeding) and Saihu (Leader/Fishing Master). The approach to management of coastal and marine resources with procedures or traditions and institutions contributed a significant impact (very effective) on local communities in relation to the sustainable use of coastal and marine resources. as well as the preservation of local traditions and customary institutions. ABSTRAK Meningkatnya kesadaran global terkait pengelolaan lingkungan, ekosistem dan pemanfaatan sumberdaya perikanan menjadi pemicu dalam reaktualisasi tradisi dan kelembagaan masyarakat. Masyarakat Kota Tidore Kepulauan yang dikenal sebagai masyarakat adat dengan tradisi kelembagaan pesisir dan lautnya di Provinsi Maluku Utara, merupakan masyarakat yang memiliki tatanan lokal yang turun temurun dalam pemanfaatan sumberdaya pesisir dan laut dimaksud. Penelitian ini bertujuan untuk menganlisis eksistensi tradisi dan kelembagaan serta pengaruhnya terhadap pengelolaan sumberdaya pesisir dan laut di Kota Tidore Kepulauan. Penelitian ini dilaksanakan pada Juni- Agustus 2019, di Kota Tidore Kepulauan meliputi 2 desa dan 4 kelurahan yakni, Desa Mare Gam, Desa Maitara, Kelurahan Tomalou dan Kelurahan Mareku, Kelurahan Soasio dan kelurahan Dowora. Penelitian ini merupakan penelitian kualitatif, yang melibatkan teknik-teknik wawancara mendalam, observasi, dan dokumentasi. Analisis data dilakukan secara deskriptif kualitatif. Hasil Penelitian menunjukkan sampai saat ini masih terdapat lima kearifan lokal yang tetap terjaga oleh masyarakat Kota Tidore Kepulauan yang merupakan warisan dari para leluhur dalam pengelolaan sumbedaya pesisir dan laut, yakni Karo Kahiya (Memanggil Lumba Lumba), Fola Sow (Rumah Obat), Jere (Keramat), Cofa (Penangkaran Ikan) dan Saihu (Pemimpin/Nakoda dalam Operasi Penangkapan Ikan). Pendekatan pengelolaan sumberdaya pesisir dan lautan dengan tradisi dan kelembagaan telah memberikan dampak yang sangat signifikan (sangat efektif) bagi masyarakat setempat dalam pemanfaatan sumberdaya pesisir dan lautan yang berkelanjutan maupun pelestarian tradisi dan kelembagaan adat istiadat setempat. Kata Kunci: Tradisi, kelembagaan, pengelolaan, sumberdaya, Tidor

Participatory collective farming as a leverage point for fostering human-nature connectedness

Human-nature connectedness is key to foster environmental and socio-cultural sustainability in agricultural landscapes since it promotes the establishment of belonging, stewardship, and connections to nature. Cooperation, collective action, and the role of women at sustainable agroecological practices could be leverage points in which small interventions may hold great potential for system transformation. We analyse the different types of human-nature connectedness mediated by the Agrolab participatory collective farming initiative running in Madrid (Spain). Our results described and quantified a participatory collective farming initiative using the leverage point perspective, and identified factors explaining nature relatedness of participants (i.e. social importance of agricultural landscapes, linkages with farming activities, time spent outdoors, gender and a negative relationship with the rural residence). We found that women showed a stronger and broader worldview on the philosophical arguments about their connection with nature, while men identified themselves and nature through more cognitive responses. Our results give indication of participatory collecting farming as a leverage point to foster human-nature connectedness. Finally, we discussed how participatory collective farming activities are suitable for introducing nature into people’s daily lives and may help to identify pathways towards a stronger human-nature connectedness.This study received funding from: (1) Environmental and social services provided by agroecological farming systems (FP20-SERVIAGROECO), (2) from the European Union's Horizon 2020 research and innovation programme under grant agreement N◦ 81819, by the project entitled: Co-design of novel contract models for innovative agri-environmental-climate measures and for valorisation of environmental public goods, and from (3) the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line of action encouraging youth research doctors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (SI1/PJI/2019-00444), through SAVIA-Sowing Alternatives for Agroecological Innovation project

The LHC Sector Test

The proposal to inject beam into a sector of the partially completed LHC is presented. The test will provide an important milestone, force preparation of a number of key systems, and allow a number of critical measurements with beam. The motivation for the test is discussed, along with the proposed beam studies, the radiation issues and the potential impact on ongoing installation. The demands on the various accelerator systems implicated are presented along with the scheduling of the preparatory steps, the test itself and the recovery phase