70 research outputs found
Abusive Romantic Relationships among Adolescent and Young Adult Mothers
The associations between intimate partner violence (IPV) and mental health among adolescents and young adults were compared in the current study. The connections among marriage status, Latino heritage and abusive experiences were also analyzed. 672 women including 282 adolescents between the ages of 14 and 19 and 390 young adults aged 20 or 21 participated in the study. Significant correlations were discovered between anxiety and depression symptoms among adolescents while anxiety and IPV, anxiety and depression, depression and IPV were all significantly correlated among young adults. In addition, IPV and marriage status as well as marriage status and Latina heritage were significantly correlated among young adults. No significant findings came from linear or logistic regressions conducted with the adolescent data but, among young adults, linear regressions with IPV as the dependent variable led to significant relationships between IPV and marital status. In addition, logistic regressions indicated significant links in the young adult data between IPV and depression and anxiety symptoms. IPV during adolescence may be a different phenomenon than adult IPV or mental health symptoms may be latent variables that are reported later in life. Prevention programs for adolescents as well as young adults are encouraged.
Postpartum Transitions in Adolescent Mothers\u27 Romantic and Maternal Relationships
Minority adolescent mothers (N = 375) were interviewed during the prepartum (or early postpartum) period and approximately 1 year later (N = 186) regarding their maternal and romantic relationships, depressive symptomatology, and negative life events. Over time, adolescents reported that male partners provided more support than did mothers and that partners\u27 support was equally important to mothers\u27 support. Further, while support from mothers decreased over time, strain increased. Results highlight the importance of considering relationship stability, At Time 2, partner support was negatively associated with depression only among adolescents who retained the same partner (17%). In addition, adolescents who sustained a romantic relationship disruption (38%) reported more negative life events than did those who had not. Implications for research, intervention, and policy are discussed
Relative sea-level rise around East Antarctica during Oligocene glaciation
During the middle and late Eocene (∼48-34 Myr ago), the Earth's climate cooled and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarcticainduced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rosedespite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line
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Report on the sixth blind test of organic crystal structure prediction methods.
The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.The organisers and participants are very grateful to the crystallographers who supplied the candidate structures: Dr. Peter Horton (XXII), Dr. Brian Samas (XXIII), Prof. Bruce Foxman (XXIV), and Prof. Kraig Wheeler (XXV and XXVI). We are also grateful to Dr. Emma Sharp and colleagues at Johnson Matthey (Pharmorphix) for the polymorph screening of XXVI, as well as numerous colleagues at the CCDC for assistance in organising the blind test. Submission 2: We acknowledge Dr. Oliver Korb for numerous useful discussions. Submission 3: The Day group acknowledge the use of the IRIDIS High Performance Computing Facility, and associated support services at the University of Southampton, in the completion of this work. We acknowledge funding from the EPSRC (grants EP/J01110X/1 and EP/K018132/1) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC through grant agreements n. 307358 (ERC-stG- 2012-ANGLE) and n. 321156 (ERC-AG-PE5-ROBOT). Submission 4: I am grateful to Mikhail Kuzminskii for calculations of molecular structures on Gaussian 98 program in the Institute of Organic Chemistry RAS. The Russian Foundation for Basic Research is acknowledged for financial support (14-03-01091). Submission 5: Toine Schreurs provided computer facilities and assistance. I am grateful to Matthew Habgood at AWE company for providing a travel grant. Submission 6: We would like to acknowledge support of this work by GlaxoSmithKline, Merck, and Vertex. Submission 7: The research was financially supported by the VIDI Research Program 700.10.427, which is financed by The Netherlands Organisation for Scientific Research (NWO), and the European Research Council (ERC-2010-StG, grant agreement n. 259510-KISMOL). We acknowledge the support of the Foundation for Fundamental Research on Matter (FOM). Supercomputer facilities were provided by the National Computing Facilities Foundation (NCF). Submission 8: Computer resources were provided by the Center for High Performance Computing at the University of Utah and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1053575. MBF and GIP acknowledge the support from the University of Buenos Aires and the Argentinian Research Council. Submission 9: We thank Dr. Bouke van Eijck for his valuable advice on our predicted structure of XXV. We thank the promotion office for TUT programs on advanced simulation engineering (ADSIM), the leading program for training brain information architects (BRAIN), and the information and media center (IMC) at Toyohashi University of Technology for the use of the TUT supercomputer systems and application software. We also thank the ACCMS at Kyoto University for the use of their supercomputer. In addition, we wish to thank financial supports from Conflex Corp. and Ministry of Education, Culture, Sports, Science and Technology. Submission 12: We thank Leslie Leiserowitz from the Weizmann Institute of Science and Geoffrey Hutchinson from the University of Pittsburgh for helpful discussions. We thank Adam Scovel at the Argonne Leadership Computing Facility (ALCF) for technical support. Work at Tulane University was funded by the Louisiana Board of Regents Award # LEQSF(2014-17)-RD-A-10 “Toward Crystal Engineering from First Principles”, by the NSF award # EPS-1003897 “The Louisiana Alliance for Simulation-Guided Materials Applications (LA-SiGMA)”, and by the Tulane Committee on Research Summer Fellowship. Work at the Technical University of Munich was supported by the Solar Technologies Go Hybrid initiative of the State of Bavaria, Germany. Computer time was provided by the Argonne Leadership Computing Facility (ALCF), which is supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-06CH11357. Submission 13: This work would not have been possible without funding from Khalifa University’s College of Engineering. I would like to acknowledge Prof. Robert Bennell and Prof. Bayan Sharif for supporting me in acquiring the resources needed to carry out this research. Dr. Louise Price is thanked for her guidance on the use of DMACRYS and NEIGHCRYS during the course of this research. She is also thanked for useful discussions and numerous e-mail exchanges concerning the blind test. Prof. Sarah Price is acknowledged for her support and guidance over many years and for providing access to DMACRYS and NEIGHCRYS. Submission 15: The work was supported by the United Kingdom’s Engineering and Physical Sciences Research Council (EPSRC) (EP/J003840/1, EP/J014958/1) and was made possible through access to computational resources and support from the High Performance Computing Cluster at Imperial College London. We are grateful to Professor Sarah L. Price for supplying the DMACRYS code for use within CrystalOptimizer, and to her and her research group for support with DMACRYS and feedback on CrystalPredictor and CrystalOptimizer. Submission 16: R. J. N. acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. [EP/J017639/1]. R. J. N. and C. J. P. acknowledge use of the Archer facilities of the U.K.’s national high-performance computing service (for which access was obtained via the UKCP consortium [EP/K014560/1]). C. J. P. also acknowledges a Leadership Fellowship Grant [EP/K013688/1]. B. M. acknowledges Robinson College, Cambridge, and the Cambridge Philosophical Society for a Henslow Research Fellowship. Submission 17: The work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. The work at the University of Silesia was supported by the Polish National Science Centre Grant No. DEC-2012/05/B/ST4/00086. Submission 18: We would like to thank Constantinos Pantelides, Claire Adjiman and Isaac Sugden of Imperial College for their support of our use of CrystalPredictor and CrystalOptimizer in this and Submission 19. The CSP work of the group is supported by EPSRC, though grant ESPRC EP/K039229/1, and Eli Lilly. The PhD students support: RKH by a joint UCL Max-Planck Society Magdeburg Impact studentship, REW by a UCL Impact studentship; LI by the Cambridge Crystallographic Data Centre and the M3S Centre for Doctoral Training (EPSRC EP/G036675/1). Submission 19: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 20: The work at New York University was supported, in part, by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1-0387 (MET and LV) and, in part, by the Materials Research Science and Engineering Center (MRSEC) program of the National Science Foundation under Award Number DMR-1420073 (MET and ES). The work at the University of Delaware was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. Submission 21: We thank the National Science Foundation (DMR-1231586), the Government of Russian Federation (Grant No. 14.A12.31.0003), the Foreign Talents Introduction and Academic Exchange Program (No. B08040) and the Russian Science Foundation, project no. 14-43-00052, base organization Photochemistry Center of the Russian Academy of Sciences. Calculations were performed on the Rurik supercomputer at Moscow Institute of Physics and Technology. Submission 22: The computational results presented have been achieved in part using the Vienna Scientific Cluster (VSC). Submission 24: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 25: J.H. and A.T. acknowledge the support from the Deutsche Forschungsgemeinschaft under the program DFG-SPP 1807. H-Y.K., R.A.D., and R.C. acknowledge support from the Department of Energy (DOE) under Grant Nos. DE-SC0008626. This research used resources of the Argonne Leadership Computing Facility at Argonne National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-06CH11357. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DEAC02-05CH11231. Additional computational resources were provided by the Terascale Infrastructure for Groundbreaking Research in Science and Engineering (TIGRESS) High Performance Computing Center and Visualization Laboratory at Princeton University.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1107/S2052520616007447
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases
Inflammatory biomarkers in Alzheimer's disease plasma
Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio
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Observation of electroweak production of two jets in association with an isolated photon and missing transverse momentum, and search for a Higgs boson decaying into invisible particles at 13 TeV with the ATLAS detector
This paper presents the measurement of the electroweak production of two jets
in association with a pair with the boson decaying into two
neutrinos. It also presents the search for invisible or partially invisible
decays of a Higgs boson with a mass of 125 GeV produced through vector-boson
fusion with a photon in the final state. These results use data from LHC
proton-proton collisions at = 13 TeV collected with the ATLAS
detector corresponding to an integrated luminosity of 139 fb. The event
signature, shared by all benchmark processes considered for measurements and
searches, is characterized by a significant amount of unbalanced transverse
momentum and a photon in the final state, in addition to a pair of forward
jets. For electroweak production of in association with two jets, the
background-only hypothesis is rejected with an observed (expected) significance
of 5.2 (5.1) standard deviations. The measured fiducial cross-section for this
process is 1.310.29 fb. Observed (expected) upper limit of 0.37 (0.34) at
95% confidence level is set on the branching ratio of a 125 GeV Higgs boson to
invisible particles, assuming the Standard Model production cross-section. The
signature is also interpreted in the context of decays of a Higgs boson to a
photon and a dark photon. An observed (expected) 95% CL upper limit on the
branching ratio for this decay is set at 0.018 (0.017), assuming the 125 GeV
Standard Model Higgs boson production cross-section
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The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2
The design and performance of the inner detector trigger for the high level
trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-18
data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector
recorded 35.6 fb, 46.9 fb, and 60.6 fb respectively of
proton-proton collision data at a centre-of-mass energy of 13 TeV. In order to
deal with the very high interaction multiplicities per bunch crossing expected
with the 13 TeV collisions the inner detector trigger was redesigned during the
long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of
these developments is provided and the performance of the tracking in the
trigger for the muon, electron, tau and -jet signatures is discussed. The
high performance of the inner detector trigger with these extreme interaction
multiplicities demonstrates how the inner detector tracking continues to lie at
the heart of the trigger performance and is essential in enabling the ATLAS
physics programme
The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2
The design and performance of the inner detector trigger for the high level
trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-18
data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector
recorded 35.6 fb, 46.9 fb, and 60.6 fb respectively of
proton-proton collision data at a centre-of-mass energy of 13 TeV. In order to
deal with the very high interaction multiplicities per bunch crossing expected
with the 13 TeV collisions the inner detector trigger was redesigned during the
long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of
these developments is provided and the performance of the tracking in the
trigger for the muon, electron, tau and -jet signatures is discussed. The
high performance of the inner detector trigger with these extreme interaction
multiplicities demonstrates how the inner detector tracking continues to lie at
the heart of the trigger performance and is essential in enabling the ATLAS
physics programme
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