Evaluating impact using time-series data

This is the final version. Available on open access from Elsevier via the DOI in this recordHumanity’s impact on the environment is increasing, as are strategies to conserve biodiversity, but a lack of understanding about how interventions affect ecological and conservation outcomes hampers decision-making. Time-series are often used to assess impacts, but ecologists tend to compare average values from before to after an impact; overlooking the potential for the intervention to elicit a change in trend. Without methods that allow for a range of responses, erroneous conclusions can be drawn. This is especially so for large, multi-time-series datasets which are increasingly available. Drawing on literature in other disciplines and pioneering work in ecology, we present a standardised framework to robustly assesses how interventions, like natural disasters or conservation policies, affect ecological time series.Royal Commission 1851Cambridge Trust Poynton ScholarshipCambridge Department of Zoology J.S. Gardiner StudentshipCambridge Philosophical SocietyAustralian Research Council (ARC)University of QueenslandEuropean Union Horizon 2020Villum FondenArcadiaLeverhulme Trus

Direct Observation of Localized Spin Antiferromagnetic Transition in PdCrO2 by Angle-Resolved Photoemission Spectroscopy

We report the first case of the successful measurements of a localized spin antiferromagnetic transition in delafossite-type PdCrO2 by angle-resolved photoemission spectroscopy (ARPES). This demonstrates how to circumvent the shortcomings of ARPES for investigation of magnetism involved with localized spins in limited size of two-dimensional crystals or multi-layer thin films that neutron scattering can hardly study due to lack of bulk compared to surface. Also, our observations give direct evidence for the spin ordering pattern of Cr3+ ions in PdCrO2 suggested by neutron diffraction and quantum oscillation measurements, and provide a strong constraint that has to be satisfied by a microscopic mechanism for the unconventional anomalous Hall effect recently reported in this system.X1118sciescopu

Role of NKp46+ natural killer cells in house dust mite-driven asthma

House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69+ NK cells in the bronchoalveolar lumen. However, genetically engineered Ncr1-DTA or Ncr1-DTR mice that constitutively or temporarily lack NK cells, still developed all key features of acute or chronic HDM-driven asthma, such as bronchial hyperreactivity, Th2 cytokine production, eosinophilia, mucus overproduction, and Th2-dependent immunoglobulin serum titers. The same results were obtained by administration of conventional NK1.1 or asialo-GM1 NK cell-depleting antibodies, antibody-mediated blocking of the NKG2D receptor, or genetic NKG2D deficiency. Thus, although NK cells accumulate in allergen-challenged lungs, our findings comprehensively demonstrate that these cells are not required for HDM-driven asthma in the mouse

Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status

The vascular endothelial growth factor (VEGF) signaling pathway appears to be the dominant pathway involved in tumor angiogenesis, providing a rationale for targeting the VEGF receptors (VEGFR-1, -2, and -3) in the treatment of cancers. In particular, VEGF signaling is thought to be important in renal cell carcinoma (RCC) because of the deregulation of the pathway through nearly uniform loss of the von Hippel Lindau protein. The tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib are approved by the US Food and Drug Administration for the treatment of advanced RCC; however, these multitargeted agents inhibit a wide range of kinase targets in addition to the VEGFRs, resulting in a range of adverse effects unrelated to efficient VEGF blockade. This article reviews recent advances in the development of the second-generation VEGFR TKIs, including the more selective VEGFR TKIs tivozanib and axitinib, and focuses on the potential benefits of novel inhibitors with improved potency and selectivity

Drawn out of the shadows: Surveying secretive forest species with camera trap distance sampling

With animal species disappearing at unprecedented rates, we need an efficient monitoring method providing reliable estimates of population density and abundance, critical for the assessment of population status and trend. We deployed 160 camera traps (CTs) systematically over 743 locations covering 17,127 km2 of evergreen lowland rainforest of Salonga National Park, block South, Democratic Republic of the Congo. We evaluated the applicability of CT distance sampling (CTDS) to species different in size and behaviour. To improve precision of estimates, we evaluated two methods estimating species' availability (‘A’) for detection by CTs. We recorded 16,700 video clips, revealing 43 different animal taxa. We estimated densities of 14 species differing in physical, behavioural and ecological traits, and extracted species-specific availability from available video footage using two methods (a) ‘ACa’ (Cappelle et al. [2019] Am. J. Primatol., 81, e22962) and (b) ‘ARo’ (Rowcliffe et al. [2014] Methods Ecol. Evol. 5, 1170). With sample sizes being large enough, we found minor differences between ACa and ARo in estimated densities. In contrast, low detectability and reactivity to the camera were main sources of bias. CTDS proved efficient for estimating density of homogenously rather than patchily distributed species. Synthesis and applications. Our application of camera trap distance sampling (CTDS) to a diverse vertebrate community demonstrates the enormous potential of this methodology for surveys of terrestrial wildlife, allowing rapid assessments of species' status and trends that can translate into effective conservation strategies. By providing the first estimates of understudied species such as the Congo peafowl, the giant ground pangolin and the cusimanses, CTDS may be used as a tool to revise these species' conservation status in the IUCN Red List of Threatened Species. Based on the constraints we encountered, we identify improvements to the current application, enhancing the general applicability of this method. © 2020 The Authors. Journal of Applied Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Societ

Developmental changes in the role of different metalinguistic awareness skills in Chinese reading acquisition from preschool to third grade

Copyright @ 2014 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.National Natural Science Foundation of China and Knowledge Innovation Program of the Chinese Academy of Sciences

Insights from two decades of the Student Conference on Conservation Science

Conservation science is a crisis-oriented discipline focused on reducing human impacts on nature. To explore how the field has changed over the past two decades, we analyzed 3245 applications for oral presentations submitted to the Student Conference on Conservation Science (SCCS) in Cambridge, UK. SCCS has been running every year since 2000, aims for global representation by providing bursaries to early-career conservationists from lower-income countries, and has never had a thematic focus, beyond conservation in the broadest sense. We found that the majority of projects submitted to SCCS were based on primary biological data collected from local scale field studies in the tropics, contrary to established literature which highlights gaps in tropical research. Our results showed a small increase over time in submissions framed around how nature benefits people as well as a small increase in submissions integrating social science. Our findings suggest that students and early-career conservationists could provide pathways to increase availability of data from the tropics and address well-known biases in the published literature towards wealthier countries. We hope this research will motivate efforts to support student projects, ensuring data and results are published and data made publicly available.The project was made possible through funding from: JG: EUs Horizon 2020 Marie Skłodowska-Curie program (No 676108) and VILLUM FONDEN (VKR023371), HA-P; National Council for Scientific and Technological Development (CNPq) (203407/2017-2), TA: The Australian Research Council Future Fellowship (FT180100354), The Grantham Foundation for the Protection of the Environment and The Kenneth Miller Trust, APC: the Natural Environment Research Council (NERC DTP [NE/L002507/1]), LC: Cambridge International Scholarship from the Cambridge Trust, FH: the Newton International Fellowship of the Royal Society, DM: the Australian Government, Endeavor Postgraduate Scholarhip, HM: Branco Weiss Fellowship Administered by the ETH Zürich and Drapers' Company Fellowship, Pembroke College BIS: the Natural Environment Research Council (NERC DTP[NE/L002507/1 and NE/S001395/1]) and the Royal Commission for the Exhibition of 1851 Research Fellowship, HW: Cambridge Trust Cambridge-Australia Poynton Scholarship and Cambridge Department of Zoology J. S. Gardiner Scholarship

Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers

Objective Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic exposure to axitinib and alter its safety profile. This study evaluated changes in axitinib plasma pharmacokinetic parameters and assessed safety and tolerability in healthy subjects, following axitinib co-administration with the potent CYP3A inhibitor ketoconazole. Methods In this randomized, single-blind, two-way crossover study, 32 healthy volunteers received placebo, followed by a single 5-mg oral dose of axitinib, administered either alone or on the fourth day of dosing with oral ketoconazole (400 mg/day for 7 days). Results Axitinib exposure was significantly increased in the presence of ketoconazole, with a geometric mean ratio for area under the plasma concentration–time curve from time zero to infinity of 2.06 (90% confidence interval [CI]: 1.84–2.30) and a geometric mean ratio for maximum plasma concentration (Cmax) of 1.50 (90% CI: 1.33–1.70). For axitinib alone or with ketoconazole, Cmax occurred 1.5 and 2.0 h after dosing, respectively. Adverse events were predominantly mild; the most commonly reported treatment-related adverse events were headache and nausea. Conclusions Axitinib plasma exposures and peak concentrations were increased following concurrent administration of axitinib and ketoconazole in healthy volunteers. Axitinib alone and in combination with ketoconazole was well tolerated. These findings provide an upper exposure for expected axitinib plasma concentrations in the presence of potent metabolic inhibition

The major barriers to evidence-informed conservation policy and possible solutions

Conservation policy decisions can suffer from a lack of evidence, hindering effective decision-making. In nature conservation, studies investigating why policy is often not evidence-informed have tended to focus on Western democracies, with relatively small samples. To understand global variation and challenges better, we established a global survey aimed at identifying top barriers and solutions to the use of conservation science in policy. This obtained the views of 758 people in policy, practice, and research positions from 68 countries across six languages. Here we show that, contrary to popular belief, there is agreement between groups about how to incorporate conservation science into policy, and there is thus room for optimism. Barriers related to the low priority of conservation were considered to be important, while mainstreaming conservation was proposed as a key solution. Therefore, priorities should focus on convincing the public of the importance of conservation as an issue, which will then influence policy-makers to adopt pro-environmental long-term policies.NERC (1653183) Grantham Foundation for the Protection of the Environment Kenneth Miller Trust (unknown) NERC (1653183) NERC (NE/L002507/1) European Commission (308454

Augmented visual feedback of movement performance to enhance walking recovery after stroke : study protocol for a pilot randomised controlled trial

Increasing evidence suggests that use of augmented visual feedback could be a useful approach to stroke rehabilitation. In current clinical practice, visual feedback of movement performance is often limited to the use of mirrors or video. However, neither approach is optimal since cognitive and self-image issues can distract or distress patients and their movement can be obscured by clothing or limited viewpoints. Three-dimensional motion capture has the potential to provide accurate kinematic data required for objective assessment and feedback in the clinical environment. However, such data are currently presented in numerical or graphical format, which is often impractical in a clinical setting. Our hypothesis is that presenting this kinematic data using bespoke visualisation software, which is tailored for gait rehabilitation after stroke, will provide a means whereby feedback of movement performance can be communicated in a more meaningful way to patients. This will result in increased patient understanding of their rehabilitation and will enable progress to be tracked in a more accessible way. The hypothesis will be assessed using an exploratory (phase II) randomised controlled trial. Stroke survivors eligible for this trial will be in the subacute stage of stroke and have impaired walking ability (Functional Ambulation Classification of 1 or more). Participants (n = 45) will be randomised into three groups to compare the use of the visualisation software during overground physical therapy gait training against an intensity-matched and attention-matched placebo group and a usual care control group. The primary outcome measure will be walking speed. Secondary measures will be Functional Ambulation Category, Timed Up and Go, Rivermead Visual Gait Assessment, Stroke Impact Scale-16 and spatiotemporal parameters associated with walking. Additional qualitative measures will be used to assess the participant's experience of the visual feedback provided in the study. Results from the trial will explore whether the early provision of visual feedback of biomechanical movement performance during gait rehabilitation demonstrates improved mobility outcomes after stroke and increased patient understanding of their rehabilitation