A beam-beam monitoring detector for the MPD experiment at NICA

The Multi-Purpose Detector (MPD) is to be installed at the Nuclotron Ion Collider fAcility (NICA) of the Joint Institute for Nuclear Research (JINR). Its main goal is to study the phase diagram of the strongly interacting matter produced in heavy-ion collisions. These studies, while providing insight into the physics of heavy-ion collisions, are relevant for improving our understanding of the evolution of the early Universe and the formation of neutron stars. In order to extend the MPD trigger capabilities, we propose to include a high granularity beam-beam monitoring detector (BE-BE) to provide a level-0 trigger signal with an expected time resolution of 30 ps. This new detector will improve the determination of the reaction plane by the MPD experiment, a key measurement for flow studies that provides physics insight into the early stages of the reaction. In this work, we use simulated Au+Au collisions at NICA energies to show the potential of such a detector to determine the event plane resolution, providing further redundancy to the detectors originally considered for this purpose namely, the Fast Forward Detector (FFD) and the Hadron Calorimeter (HCAL). We also show our results for the time resolution studies of two prototype cells carried out at the T10 beam line at the CERN PS complex.Comment: 16 pages, 12 figures. Updated to published version with added comments and correction

Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome

[EN] Objective: Uterine transplantation is now considered a feasible treatment for women with absolute uterine factor infertility and has been successfully performed for a woman with Asherman's syndrome (AS). The endometrium is a clinically and histologically distinct entity from the surrounding myometrium. Endometrial transplantation (ETx) may offer a less invasive option, with less immunogenic impact, to restore fertility in women with severe AS. The objective of this study was to assess the feasibility of ETx by evaluating surgical and reproductive outcomes following endometrial autotransplantation in a rabbit model. Study design: A longitudinal study assessing surgical, biochemical, radiological, reproductive and histological outcomes following endometrial autotransplantation in ten New Zealand white rabbits. Results: Ten procedures were performed, including 8 endometrial auto-transplants (ETx) and 2 endometrial resections (ER), to control against endometrial regeneration. Eight procedures were successful, whereas two rabbits from the ETx group died intra-operatively. Three rabbits were euthanised at 48, 72 and 96 h post-operatively to assess gross and histological appearances. Two rabbits, one from the ETx group and one from the ER group, died four weeks and eight weeks post-operatively. Three rabbits subsequently underwent two cycles of in-vitro fertilization. The first cycle resulted in an implantation rate of 57% in the un-operated uteri. In two rabbits who underwent ETx, an implantation rate of 28.6% was seen. In the second cycle, an implantation rate of 61.9 % (13 implantations) was observed in the control uteri. In the two ETx females, an implantation rate of 14.3 % was seen. No pregnancies were seen in either cycle in the animals who underwent ER. Despite successful implantations in both cycles in the ETx rabbits, no livebirths were achieved. Following death or euthanasia there was gross and microscopic evidence of viable endometrium following ETx, but not following ER. Conclusion: This study has revealed, for the first time, the feasibility of ETx with gross and microscopic evidence of viable endometrium, and the demonstration of clinical pregnancies. Whilst further studies are essential, and the achievement of successful livebirths fundamental, ETx may offer a potential fertility restoring opportunity for women with severe, treatment refractory cases of AS.The study was funded by registered charity Womb Transplant UK (1138559).Jones, BP.; Vali, S.; Saso, S.; Garcia-Dominguez, X.; Chan, M.; Thum, M.; Ghaem-Maghami, S.... (2020). Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology. 248:14-23. https://doi.org/10.1016/j.ejogrb.2020.03.011S1423248Asherman, J. G. (1950). TRAUMATIC INTRA-UTERINE ADHESIONS. BJOG: An International Journal of Obstetrics and Gynaecology, 57(6), 892-896. doi:10.1111/j.1471-0528.1950.tb06053.xHooker, A. B., de Leeuw, R., van de Ven, P. M., Bakkum, E. A., Thurkow, A. L., Vogel, N. E. A., … Huirne, J. A. F. (2017). Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. Fertility and Sterility, 107(5), 1223-1231.e3. doi:10.1016/j.fertnstert.2017.02.113Wallach, E. E., Schenker, J. G., & Margalioth, E. J. (1982). Intrauterine adhesions: an updated appraisal. Fertility and Sterility, 37(5), 593-610. doi:10.1016/s0015-0282(16)46268-0Westendorp, I. C., Ankum, W. M., Mol, B. W., & Vonk, J. (1998). Prevalence of Asherman’s syndrome after secondary removal of placental remnants or a repeat curettage for incomplete abortion. Human Reproduction, 13(12), 3347-3350. doi:10.1093/humrep/13.12.3347Wallach, E., & Czernobilsky, B. (1978). Endometritis and Infertility. Fertility and Sterility, 30(2), 119-130. doi:10.1016/s0015-0282(16)43448-5Baradwan, S., Baradwan, A., & Al-Jaroudi, D. (2018). The association between menstrual cycle pattern and hysteroscopic march classification with endometrial thickness among infertile women with Asherman syndrome. Medicine, 97(27), e11314. doi:10.1097/md.0000000000011314Hooker, A. B., Lemmers, M., Thurkow, A. L., Heymans, M. W., Opmeer, B. C., Brolmann, H. A. M., … Huirne, J. A. F. (2013). Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome. Human Reproduction Update, 20(2), 262-278. doi:10.1093/humupd/dmt045Yu, D., Wong, Y.-M., Cheong, Y., Xia, E., & Li, T.-C. (2008). Asherman syndrome—one century later. Fertility and Sterility, 89(4), 759-779. doi:10.1016/j.fertnstert.2008.02.096Yamamoto, N., Takeuchi, R., Izuchi, D., Yuge, N., Miyazaki, M., Yasunaga, M., … Inoue, Y. (2013). Hysteroscopic adhesiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes. Reproductive Medicine and Biology, 12(4), 159-166. doi:10.1007/s12522-013-0149-xThomson, A. J. M., Abbott, J. A., Kingston, A., Lenart, M., & Vancaillie, T. G. (2007). Fluoroscopically guided synechiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes. Fertility and Sterility, 87(2), 405-410. doi:10.1016/j.fertnstert.2006.06.035Deans, R., & Abbott, J. (2010). Review of Intrauterine Adhesions. Journal of Minimally Invasive Gynecology, 17(5), 555-569. doi:10.1016/j.jmig.2010.04.016Song, D., Liu, Y., Xiao, Y., Li, T.-C., Zhou, F., & Xia, E. (2014). A Matched Cohort Study Comparing the Outcome of Intrauterine Adhesiolysis for Asherman’s Syndrome After Uterine Artery Embolization or Surgical Trauma. Journal of Minimally Invasive Gynecology, 21(6), 1022-1028. doi:10.1016/j.jmig.2014.04.015Panchal, S., Patel, H., & Nagori, C. (2011). Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman′s syndrome. Journal of Human Reproductive Sciences, 4(1), 43. doi:10.4103/0974-1208.82360Singh, N., Mohanty, S., Seth, T., Shankar, M., Dharmendra, S., & Bhaskaran, S. (2014). Autologous stem cell transplantation in refractory Asherman′s syndrome: A novel cell based therapy. Journal of Human Reproductive Sciences, 7(2), 93. doi:10.4103/0974-1208.138864Tan, J., Li, P., Wang, Q., Li, Y., Li, X., Zhao, D., … Kong, L. (2016). Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome. Human Reproduction, 31(12), 2723-2729. doi:10.1093/humrep/dew235Santamaria, X., Cabanillas, S., Cervelló, I., Arbona, C., Raga, F., Ferro, J., … Simón, C. (2016). Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman’s syndrome and endometrial atrophy: a pilot cohort study. Human Reproduction, 31(5), 1087-1096. doi:10.1093/humrep/dew042Puntambekar, S., Telang, M., Kulkarni, P., Puntambekar, S., Jadhav, S., Panse, M., … Phadke, U. (2018). Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine Transplant: Our Experience of Two Patients. Journal of Minimally Invasive Gynecology, 25(4), 622-631. doi:10.1016/j.jmig.2018.01.009Saso, S., Haddad, J., Ellis, P., Lindsay, I., Sebire, N., McIndoe, A., … Smith, J. (2011). Placental site trophoblastic tumours and the concept of fertility preservation. BJOG: An International Journal of Obstetrics & Gynaecology, 119(3), 369-374. doi:10.1111/j.1471-0528.2011.03230.xViudes‐de‐Castro, M. P., Marco‐Jiménez, F., Más Pellicer, A., García‐Domínguez, X., Talaván, A. M., & Vicente, J. S. (2019). A single injection of corifollitropin alfa supplemented with human chorionic gonadotropin increases follicular recruitment and transferable embryos in the rabbit. Reproduction in Domestic Animals, 54(4), 696-701. doi:10.1111/rda.13411Garcia-Dominguez, X., Marco-Jimenez, F., Viudes-de-Castro, M. P., & Vicente, J. S. (2019). Minimally Invasive Embryo Transfer and Embryo Vitrification at the Optimal Embryo Stage in Rabbit Model. Journal of Visualized Experiments, (147). doi:10.3791/58055Esteves, P. J., Abrantes, J., Baldauf, H.-M., BenMohamed, L., Chen, Y., Christensen, N., … Mage, R. (2018). The wide utility of rabbits as models of human diseases. Experimental & Molecular Medicine, 50(5), 1-10. doi:10.1038/s12276-018-0094-1Graur, D., Duret, L., & Gouy, M. (1996). Phylogenetic position of the order Lagomorpha (rabbits, hares and allies). Nature, 379(6563), 333-335. doi:10.1038/379333a0Saso, S., Petts, G., David, A. L., Thum, M.-Y., Chatterjee, J., Vicente, J. S., … Smith, J. R. (2015). Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model. European Journal of Obstetrics & Gynecology and Reproductive Biology, 185, 164-169. doi:10.1016/j.ejogrb.2014.12.017Saso, S., Petts, G., Chatterjee, J., Thum, M.-Y., David, A. L., Corless, D., … Smith, J. R. (2014). Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: a long-term viability study. European Journal of Obstetrics & Gynecology and Reproductive Biology, 182, 185-193. doi:10.1016/j.ejogrb.2014.09.029Ozsoy, M., Gonul, Y., Bal, A., Ozkececi, Z. T., Celep, R. B., Adali, F., … Tosun, M. (2015). Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion. Annals of Surgical Treatment and Research, 88(2), 92. doi:10.4174/astr.2015.88.2.92Hare, A., & Olah, K. (2005). Pregnancy following endometrial ablation: a review article. Journal of Obstetrics and Gynaecology, 25(2), 108-114. doi:10.1080/01443610500040745Johannesson, L., Enskog, A., Molne, J., Diaz-Garcia, C., Hanafy, A., Dahm-Kahler, P., … Brannstrom, M. (2012). Preclinical report on allogeneic uterus transplantation in non-human primates. Human Reproduction, 28(1), 189-198. doi:10.1093/humrep/des381Brännström, M., Johannesson, L., Dahm-Kähler, P., Enskog, A., Mölne, J., Kvarnström, N., … Olausson, M. (2014). First clinical uterus transplantation trial: a six-month report. Fertility and Sterility, 101(5), 1228-1236. doi:10.1016/j.fertnstert.2014.02.02

Early lung cancer detection using spiral computed tomography and positron emission tomography

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions

Financial feasibility of end-user designed rainwater harvesting and greywater reuse systems for high water use households

© 2017, The Author(s). Water availability pressures, competing end-uses and sewers at capacity are all drivers for change in urban water management. Rainwater harvesting (RWH) and greywater reuse (GWR) systems constitute alternatives to reduce drinking water usage and in the case of RWH, reduce roof runoff entering sewers. Despite the increasing popularity of installations in commercial buildings, RWH and GWR technologies at a household scale have proved less popular, across a range of global contexts. For systems designed from the top-down, this is often due to the lack of a favourable cost-benefit (where subsidies are unavailable), though few studies have focused on performing full capital and operational financial assessments, particularly in high water consumption households. Using a bottom-up design approach, based on a questionnaire survey with 35 households in a residential complex in Bucaramanga, Colombia, this article considers the initial financial feasibility of three RWH and GWR system configurations proposed for high water using households (equivalent to >203L per capita per day). A full capital and operational financial assessment was performed at a more detailed level for the most viable design using historic rainfall data. For the selected configuration (‘Alt 2’), the estimated potable water saving was 44% (equivalent to 131m3/year) with a rate of return on investment of 6.5% and an estimated payback period of 23years. As an initial end-user-driven design exercise, these results are promising and constitute a starting point for facilitating such approaches to urban water management at the household scale

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery

To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery