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Natalie I Mazur, Deborah Higgins, Marta C Nunes, José A Melero, Annefleur C Langedijk, Nicole Horsley, Ursula J Buchholz, Peter J Openshaw, Jason S McLellan, Janet A Englund, Asuncion Mejias, Ruth A Karron, Eric Af Simões, Ivana Knezevic, Octavio Ramilo, Pedro A Piedra, Helen Y Chu, Ann R Falsey, Harish Nair, Leyla Kragten-Tabatabaie, Anne Greenough, Eugenio Baraldi, Nikolaos G Papadopoulos, Johan Vekemans, Fernando P Polack, Mair Powell, Ashish Satav, Edward E Walsh, Renato T Stein, Barney S Graham, Louis J Bont
The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development...
June 15, 2018: Lancet Infectious Diseases
Benjamin M Nowotny, Erwin Loh, Katherine Lorenz, Euan M Wallace
Learning from medical errors to prevent their recurrence is an important component of any healthcare system's quality and safety improvement functions. Traditionally, this been achieved principally from review of adverse clinical outcomes. The opportunity to learn systematically and in a system manner from patient complaints and litigation has been less well harnessed. Herein we describe the pathways and processes for both patient complaints and medicolegal claims in Victoria, and Australia more broadly, and assess the potential for these to be used for system improvement...
June 19, 2018: Australian Health Review: a Publication of the Australian Hospital Association
Cathleen E Willging, David H Sommerfeld, Elise Trott Jaramillo, Erik Lujan, Roxane Spruce Bly, Erin K Debenport, Steven P Verney, Ron Lujan
BACKGROUND: Public insurance reforms of the past two decades have failed to substantively address the healthcare needs of American Indians in general, let alone the particular needs of American Indian elders, ages 55 years and older. Historically, this population is more likely to be uninsured and to suffer from greater morbidities, poorer health outcomes and quality of life, and lower life expectancies compared to all other United States aging populations, representing a neglected group within the healthcare system...
June 18, 2018: BMC Health Services Research
P Rofouie, Z Wang, A D Rey
We present a model to investigate the formation of two-length scale surface patterns in biological and synthetic anisotropic soft matter materials through the high order interaction of anisotropic interfacial tension and capillarity at their free surfaces. The unique pattern-formation mechanism emerging from the presented model is based on the interaction between lower and higher order anchoring modes. Analytical and numerical solutions are used to shed light on why and how simple anisotropic anchoring generates two-lengthscale wrinkles whose amplitudes are given in terms of anchoring coefficients...
June 18, 2018: Soft Matter
Patrick A Mayes, Kenneth W Hance, Axel Hoos
Immune cell functions are regulated by co-inhibitory and co-stimulatory receptors. The first two generations of cancer immunotherapy agents consist primarily of antagonist antibodies that block negative immune checkpoints, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte protein 4 (CTLA4). Looking ahead, there is substantial promise in targeting co-stimulatory receptors with agonist antibodies, and a growing number of these agents are making their way through various stages of development...
June 15, 2018: Nature Reviews. Drug Discovery
Curtis H Kugel, Stephen M Douglass, Marie R Webster, Amanpreet Kaur, Qin Liu, Xiangfan Yin, Sarah A Weiss, Farbod Darvishian, Rami N Al-Rohil, Abibatou Ndoye, Reeti Behera, Gretchen M Alicea, Brett L Ecker, Mitchell Fane, Michael J Allegrezza, Nikolaos Svoronos, Vinit Kumar, Daniel Y Wang, Rajasekharan Somasundaram, Siwen Hu-Lieskovan, Alpaslan Ozgun, Meenhard Herlyn, Jose R Conejo-Garcia, Dmitry Gabrilovich, Erica L Stone, Theodore S Nowicki, Jeffrey Sosman, Rajat Rai, Matteo S Carlino, Georgina V Long, Richard Marais, Antoni Ribas, Zeynep Eroglu, Michael A Davies, Bastian Schilling, Dirk Schadendorf, Wei Xu, Ravi K Amaravadi, Alexander M Menzies, Jennifer L McQuade, Douglas B Johnson, Iman Osman, Ashani T Weeraratna
Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1. Experimental Design: We analyzed the relationship between age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumoral immune microenvironment in young versus aged mice and confirmed our findings in human melanoma biopsies. Results: Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy...
June 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Keita Matsuno, Masahiro Kajihara, Ryo Nakao, Naganori Nao, Akina Mori-Kajihara, Mieko Muramatsu, Yongjin Qiu, Shiho Torii, Manabu Igarashi, Nodoka Kasajima, Keita Mizuma, Kentaro Yoshii, Hirofumi Sawa, Chihiro Sugimoto, Ayato Takada, Hideki Ebihara
The recent emergence of novel tick-borne RNA viruses has complicated the epidemiological landscape of tick-borne infectious diseases, posing a significant challenge to public health systems that seek to counteract tick-borne diseases. The identification of two novel tick-borne phleboviruses (TBPVs), severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV), as causative agents of severe illness in humans has accelerated the investigation and discoveries of novel TBPVs. In the present study, we isolated a novel TBPV designated Mukawa virus (MKWV) from host-questing Ixodes persulcatus females captured in Japan...
June 27, 2018: MSphere
Nicolas Boissel, André Baruchel
Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents aged 15-20 years old, the use of full pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem cell transplantation...
June 12, 2018: Blood
Amanda Jager, Dorien A Maas, Kim Fricke, Rob B de Vries, Geert Poelmans, Jeffrey C Glennon
Aggressive behavior is often core or comorbid to psychiatric and neurodegenerative disorders. Transgenic animal models are commonly used to study the neurobiological mechanisms underlying aggressive phenotypes and have led to new insights into aggression. This systematic review critically evaluates the available literature on transgenic animal models tested for aggression with the resident-intruder test. By combining the available literature on this topic, we sought to highlight effective methods for laboratory aggression testing and provide recommendations for study design as well as aggression induction and measurement in rodents that are translational to humans, taking into consideration possible confounding factors...
August 2018: Neuroscience and Biobehavioral Reviews
Yong-Lei Wang, Xiaoyu Ma, Jing Xu, Zhi-Li Xiao, Alexey Snezhko, Ralu Divan, Leonidas E Ocola, John E Pearson, Boldizsar Janko, Wai-Kwong Kwok
Geometric frustration emerges when local interaction energies in an ordered lattice structure cannot be simultaneously minimized, resulting in a large number of degenerate states. The numerous degenerate configurations may lead to practical applications in microelectronics 1 , such as data storage, memory and logic 2 . However, it is difficult to achieve very high degeneracy, especially in a two-dimensional system3,4 . Here, we showcase in situ controllable geometric frustration with high degeneracy in a two-dimensional flux-quantum system...
June 11, 2018: Nature Nanotechnology
Nicole F Dear, Chifundo Kadangwe, Themba Mzilahowa, Andy Bauleni, Don P Mathanga, Chifundo Duster, Edward D Walker, Mark L Wilson
BACKGROUND: Malaria is increasing in some recently urbanized areas that historically were considered lower risk. Understanding what drives urban transmission is hampered by inconsistencies in how "urban" contexts are defined. A dichotomized "urban-rural" approach, based on political boundaries may misclassify environments or fail to capture local drivers of risk. Small-scale agriculture in urban or peri-urban settings has been shown to be a major risk determinant. METHODS: Household-level Anopheles abundance patterns in and around Malawi's commercial capital of Blantyre (~ 1...
June 8, 2018: Malaria Journal
Dmitriy Mitin, Alexander Kovacs, Thomas Schrefl, Arno Ehresmann, Dennis Holzinger, Manfred Albrecht
Magnetic stray fields generated by domain walls have attracted significant attention as they might be employed for precise positioning and active control of micro- and nano-sized magnetic objects in fluids or in the field of magnonics. The presented work intends to investigate the near-field response of magnetic stray field landscapes above generic types of charged domain walls as occurring in thin films with in-plane anisotropy and preferential formation of Néel type domain walls when disturbed by external magnetic fields...
June 8, 2018: Nanotechnology
Julien Papaïx, Loup Rimbaud, Jeremy J Burdon, Jiasui Zhan, Peter H Thrall
A multitude of resistance deployment strategies have been proposed to tackle the evolutionary potential of pathogens to overcome plant resistance. In particular, many landscape-based strategies rely on the deployment of resistant and susceptible cultivars in an agricultural landscape as a mosaic. However, the design of such strategies is not easy as strategies targeting epidemiological or evolutionary outcomes may not be the same. Using a stochastic spatially explicit model, we studied the impact of landscape organization (as defined by the proportion of fields cultivated with a resistant cultivar and their spatial aggregation) and key pathogen life-history traits on three measures of disease control...
June 2018: Evolutionary Applications
Iraj Daizadeh
BACKGROUND: FDA expedited program designations (EPDs) are intended to facilitate drug development for serious conditions with an unmet medical need. There are over 10 FDA-approved therapies for the rare disease pulmonary arterial hypertension (PAH). This work investigates the landscape of EPDs in the context of FDA-approved PAH therapies in order to inform on future drug development. METHODS: The publicly available FDA Action Package (AP) was manually culled for information related to EPDs for 10 FDA-approved treatments for PAH...
January 1, 2018: Therapeutic Innovation & Regulatory Science
Jaswanth K Yella, Suryanarayana Yaddanapudi, Yunguan Wang, Anil G Jegga
Efforts to maximize the indications potential and revenue from drugs that are already marketed are largely motivated by what Sir James Black, a Nobel Prize-winning pharmacologist advocated-"The most fruitful basis for the discovery of a new drug is to start with an old drug". However, rational design of drug mixtures poses formidable challenges because of the lack of or limited information about in vivo cell regulation, mechanisms of genetic pathway activation, and in vivo pathway interactions. Hence, most of the successfully repositioned drugs are the result of "serendipity", discovered during late phase clinical studies of unexpected but beneficial findings...
June 5, 2018: Pharmaceuticals
Jacqueline M Leung, Andrea L Graham, Sarah C L Knowles
The vertebrate gut teems with a large, diverse, and dynamic bacterial community that has pervasive effects on gut physiology, metabolism, and immunity. Under natural conditions, these microbes share their habitat with a similarly dynamic community of eukaryotes (helminths, protozoa, and fungi), many of which are well-known parasites. Both parasites and the prokaryotic microbiota can dramatically alter the physical and immune landscape of the gut, creating ample opportunities for them to interact. Such interactions may critically alter infection outcomes and affect overall host health and disease...
2018: Frontiers in Microbiology
Shinji Tanaka
Accumulated evidence suggests that multiple molecular and cellular interactions promote cancer evolution in vivo. Surgical oncology is of growing significance to a comprehensive understanding of the malignant diseases for therapeutic application. We have analyzed more than 1000 clinical samples from surgically resected tissue to identify molecular biomarkers and therapeutic targets for advanced malignancies. Cancer stemness and mitotic instability were then determined as the essential predictors of aggressive phenotype with poor prognosis...
March 2018: Annals of gastroenterological surgery
Megan C Engel, David M Smith, Markus A Jobst, Martin Sajfutdinow, Tim Liedl, Flavio Romano, Lorenzo Rovigatti, Ard A Louis, Jonathan P K Doye
The mechanical properties of DNA nanostructures are of widespread interest as applications that exploit their stability under constant or intermittent external forces become increasingly common. We explore the force response of DNA origami in comprehensive detail by combining AFM single molecule force spectroscopy experiments with simulations using oxDNA, a coarse-grained model of DNA at the nucleotide level, to study the unravelling of an iconic origami system: the Rothemund tile. We contrast the force-induced melting of the tile with simulations of an origami 10-helix bundle...
May 31, 2018: ACS Nano
J P Töpper, E Meineri, S L Olsen, K Rydgren, O Skarpaas, V Vandvik
In climate-change ecology, simplistic research approaches may yield unrealistically simplistic answers to often more complicated problems. In particular, the complexity of vegetation responses to global climate change begs a better understanding of the impacts of concomitant changes in several climatic drivers, how these impacts vary across different climatic contexts, and of the demographic processes underlying population changes. Using a replicated, factorial, whole-community transplant experiment, we investigate regional variation in demographic responses of plant populations to increased temperature and/or precipitation...
May 31, 2018: Global Change Biology
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