Benefit of irrigation water transfers in the National River Linking Project: a case study of the Ken-Betwa link

River basin managementRiver basin developmentDevelopment projectsWater transferIrrigation waterCrop productionCrop managementLivestock

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achievinghigh-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aimofthis study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-relatedadverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK.Methods We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durableresponse to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression.HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEsand survival. HRQoL data was compared with two norm-based datasets.Results Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity ofany grade occurred in 92%of patients and 43%had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients requiredsteroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyondsteroids.Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical rolefunctioning and general health compared with the normative population. There was a trend towards inferior scores in patientswith previous exposure to ipilimumab compared with those never exposed to ipilimumab.Conclusions Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicityand experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population’sunique survivorship needs.Peer reviewe

Global Analysis of the post-SNO Solar Neutrino Data for Standard and Non-Standard Oscillation Mechanisms

What can we learn from solar neutrino observations? Is there any solution to the solar neutrino anomaly which is favored by the present experimental panorama? After SNO results, is it possible to affirm that neutrinos have mass? In order to answer such questions we analyze the current available data from the solar neutrino experiments, including the recent SNO result, in view of many acceptable solutions to the solar neutrino problem based on different conversion mechanisms, for the first time, using the same statistical procedure. This allows us to do a direct comparison of the goodness of the fit among different solutions, from which we can discuss and conclude on the current status of each proposed dynamical mechanism. These solutions are based on different assumptions: (a) neutrino mass and mixing, (b) non-vanishing neutrino magnetic moment, (c) the existence of non-standard flavor-changing and non-universal neutrino interactions and (d) the tiny violation of the equivalence principle. We investigate the quality of the fit provided by each one of these solutions not only to the total rate measured by all the solar neutrino experiments but also to the recoil electron energy spectrum measured at different zenith angles by the Super-Kamiokande collaboration. We conclude that several non-standard neutrino flavor conversion mechanisms provide a very good fit to the experimental data which is comparable with (or even slightly better than) the most famous solution to the solar neutrino anomaly based on the neutrino oscillation induced by mass.Comment: Minor changes in the solar magnetic field profile used, and some refferences added. Final version to appear in PR

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

Theoretical study of lepton events in the atmospheric neutrino experiments at SuperK

Super-Kamiokande has reported the results for the lepton events in the atmospheric neutrino experiment. These results have been presented for a 22.5kT water fiducial mass on an exposure of 1489 days, and the events are divided into sub-GeV, multi-GeV and PC events. We present a study of nuclear medium effects in the sub-GeV energy region of atmospheric neutrino events for the quasielastic scattering, incoherent and coherent pion production processes, as they give the most dominant contribution to the lepton events in this energy region. We have used the atmospheric neutrino flux given by Honda et al. These calculations have been done in the local density approximation. We take into account the effect of Pauli blocking, Fermi motion, Coulomb effect, renormalization of weak transition strengths in the nuclear medium in the case of the quasielastic reactions. The inelastic reactions leading to production of leptons along with pions is calculated in a $\Delta$- dominance model by taking into account the renormalization of $\Delta$ properties in the nuclear medium and the final state interaction effects of the outgoing pions with the residual nucleus. We present the results for the lepton events obtained in our model with and without nuclear medium effects, and compare them with the Monte Carlo predictions used in the simulation and the experimentally observed events reported by the Super-Kamiokande collaboration.Comment: 23 pages, 13 figure

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Searches For High-Frequency Variations In The B-8 Solar Neutrino Flux At The Sudbury Neutrino Observatory

We have performed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory, motivated by the possibility that solar g-mode oscillations could affect the production or propagation of solar B-8 neutrinos. The first search looked for any significant peak in the frequency range 1-144 day(-1), with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the Solar and Heliospheric Observatory satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power across the entire frequency band. No statistically significant signal was detected in any of the three searches.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for InnovationDept. of Energy, USNational Energy Research Scientific Computing Center, USScience and Technologies Facilities Council, UKAstronom