Unexplored Character Diversity in Onychophora (Velvet Worms): A Comparative Study of Three Peripatid Species

Low character variation among onychophoran species has been an obstacle for taxonomic and phylogenetic studies in the past, however we have identified a number of new and informative characters using morphological, molecular, and chromosomal techniques. Our analyses involved a detailed examination of Epiperipatus biolleyi from Costa Rica, Eoperipatus sp. from Thailand, and a new onychophoran species and genus from Costa Rica, Principapillatus hitoyensisgen. et sp. nov.. Scanning electron microscopy on embryos and specimens of varying age revealed novel morphological characters and character states, including the distribution of different receptor types along the antennae, the arrangement and form of papillae on the head, body and legs, the presence and shape of interpedal structures and fields of modified scales on the ventral body surface, the arrangement of lips around the mouth, the number, position and structure of crural tubercles and anal gland openings, and the presence and shape of embryonic foot projections. Karyotypic analyses revealed differences in the number and size of chromosomes among the species studied. The results of our phylogenetic analyses using mitochondrial COI and 12S rRNA gene sequences are in line with morphological and karyotype data. However, our data show a large number of unexplored, albeit informative, characters in the Peripatidae. We suggest that analysing these characters in additional species would help unravel species diversity and phylogeny in the Onychophora, and that inconsistencies among most diagnostic features used for the peripatid genera in the literature could be addressed by identifying a suite of characters common to all peripatids.This study was supported by a Ph.D. fellowship of the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq: 290029/2010-4) and by a SYNTHESYS grant (financed by the European Community Research Infrastructure Action - FP7 Integrating Activities Programme: http://www.synthesys.info/) to ISO. GM is a Research Group Leader supported by the Emmy Noether Programme of the German Research Foundation (DFG: Ma 4147/3-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Microstructure and Mechanical Behavior of Porous Ti-6Al-4V Processed by Spherical Powder Sintering

Reducing the stiffness of titanium is an important issue to improve the behavior of this material when working together with bone, which can be achieved by generating a porous structure. The aim of this research was to analyze the porosity and mechanical behavior of Ti-6Al-4V porous samples developed by spherical powder sintering. Four different microsphere sizes were sintered at temperatures ranging from 1300 to 1400 degrees C for 2, 4 and 8 h. An open, interconnected porosity was obtained, with mean pore sizes ranging from 54.6 to 140 mu m. The stiffness of the samples diminished by as much as 40% when compared to that of solid material and the mechanical properties were affected mainly by powder particles size. Bending strengths ranging from 48 to 320 MPa and compressive strengths from 51 to 255 MPa were obtained.The authors are grateful to the Spanish Ministry of Economy and Competitiveness for supporting this research by Project PIB2010BZ-00448. They also thank the Universitat Jaume I for funding the translation of this paper.Reig Cerdá, L.; Tojal Domenech, C.; Busquets Mataix, DJ.; Amigó Borrás, V. (2013). Microstructure and Mechanical Behavior of Porous Ti-6Al-4V Processed by Spherical Powder Sintering. Materials. 6(10):4868-4878. https://doi.org/10.3390/ma6104868S48684878610Özcan, M., & Hämmerle, C. (2012). Titanium as a Reconstruction and Implant Material in Dentistry: Advantages and Pitfalls. Materials, 5(9), 1528-1545. doi:10.3390/ma5091528Asaoka, K., & Kon, M. (2003). Sintered Porous Titanium and Titanium Alloys as Advanced Biomaterials. Materials Science Forum, 426-432, 3079-3084. doi:10.4028/www.scientific.net/msf.426-432.3079Niinomi, M. (2003). Recent research and development in titanium alloys for biomedical applications and healthcare goods. Science and Technology of Advanced Materials, 4(5), 445-454. doi:10.1016/j.stam.2003.09.002Reig, L., Amigó, V., Busquets, D. J., & Calero, J. A. (2012). Development of porous Ti6Al4V samples by microsphere sintering. Journal of Materials Processing Technology, 212(1), 3-7. doi:10.1016/j.jmatprotec.2011.06.026Sumitomo, N., Noritake, K., Hattori, T., Morikawa, K., Niwa, S., Sato, K., & Niinomi, M. (2008). Experiment study on fracture fixation with low rigidity titanium alloy. Journal of Materials Science: Materials in Medicine, 19(4), 1581-1586. doi:10.1007/s10856-008-3372-yNiinomi, M. (2008). Mechanical biocompatibilities of titanium alloys for biomedical applications. Journal of the Mechanical Behavior of Biomedical Materials, 1(1), 30-42. doi:10.1016/j.jmbbm.2007.07.001Zhou, Y.-L., & Niinomi, M. (2009). Ti–25Ta alloy with the best mechanical compatibility in Ti–Ta alloys for biomedical applications. Materials Science and Engineering: C, 29(3), 1061-1065. doi:10.1016/j.msec.2008.09.012Málek, J., Hnilica, F., Veselý, J., Smola, B., Bartáková, S., & Vaněk, J. (2012). Microstructure and mechanical properties of Ti-35Nb-6Ta alloy after thermomechanical treatment. Materials Characterization, 66, 75-82. doi:10.1016/j.matchar.2012.02.012Afonso, C. R. M., Aleixo, G. T., Ramirez, A. J., & Caram, R. (2007). Influence of cooling rate on microstructure of Ti–Nb alloy for orthopedic implants. Materials Science and Engineering: C, 27(4), 908-913. doi:10.1016/j.msec.2006.11.001Nugroho, A. W., Leadbeater, G., & Davies, I. J. (2010). Processing of a porous titanium alloy from elemental powders using a solid state isothermal foaming technique. Journal of Materials Science: Materials in Medicine, 21(12), 3103-3107. doi:10.1007/s10856-010-4162-xBarbas, A., Bonnet, A.-S., Lipinski, P., Pesci, R., & Dubois, G. (2012). Development and mechanical characterization of porous titanium bone substitutes. Journal of the Mechanical Behavior of Biomedical Materials, 9, 34-44. doi:10.1016/j.jmbbm.2012.01.008Wieding, J., Jonitz, A., & Bader, R. (2012). The Effect of Structural Design on Mechanical Properties and Cellular Response of Additive Manufactured Titanium Scaffolds. Materials, 5(8), 1336-1347. doi:10.3390/ma5081336Dezfuli, S. N., Sadrnezhaad, S. K., Shokrgozar, M. A., & Bonakdar, S. (2012). Fabrication of biocompatible titanium scaffolds using space holder technique. Journal of Materials Science: Materials in Medicine, 23(10), 2483-2488. doi:10.1007/s10856-012-4706-3Reig, L., Amigó, V., Busquets, D., & Calero, J. A. (2011). Stiffness variation of porous titanium developed using space holder method. Powder Metallurgy, 54(3), 389-392. doi:10.1179/003258910x12707304455068Amigó, V., Reig, L., Busquets, D. J., Ortiz, J. L., & Calero, J. A. (2011). Analysis of bending strength of porous titanium processed by space holder method. Powder Metallurgy, 54(1), 67-70. doi:10.1179/174329009x409697Amigó, V., Salvador, M. D., Romero, F., Solves, C., & Moreno, J. F. (2003). Microstructural evolution of Ti–6Al–4V during the sintering of microspheres of Ti for orthopedic implants. Journal of Materials Processing Technology, 141(1), 117-122. doi:10.1016/s0924-0136(03)00243-7Bansiddhi, A., Sargeant, T. D., Stupp, S. I., & Dunand, D. C. (2008). Porous NiTi for bone implants: A review. Acta Biomaterialia, 4(4), 773-782. doi:10.1016/j.actbio.2008.02.009RYAN, G., PANDIT, A., & APATSIDIS, D. (2006). Fabrication methods of porous metals for use in orthopaedic applications. Biomaterials, 27(13), 2651-2670. doi:10.1016/j.biomaterials.2005.12.002Kujala, S., Ryhänen, J., Danilov, A., & Tuukkanen, J. (2003). Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel–titanium bone graft substitute. Biomaterials, 24(25), 4691-4697. doi:10.1016/s0142-9612(03)00359-

Unsupervised domain adaptation in brain lesion segmentation with adversarial networks

Significant advances have been made towards building accu- rate automatic segmentation systems for a variety of biomedical applica- tions using machine learning. However, the performance of these systems often degrades when they are applied on new data that differ from the training data, for example, due to variations in imaging protocols. Man- ually annotating new data for each test domain is not a feasible solution. In this work we investigate unsupervised domain adaptation using ad- versarial neural networks to train a segmentation method which is more invariant to differences in the input data, and which does not require any annotations on the test domain. Specifically, we learn domain-invariant features by learning to counter an adversarial network, which attempts to classify the domain of the input data by observing the activations of the segmentation network. Furthermore, we propose a multi-connected domain discriminator for improved adversarial training. Our system is evaluated using two MR databases of subjects with traumatic brain in- juries, acquired using different scanners and imaging protocols. Using our unsupervised approach, we obtain segmentation accuracies which are close to the upper bound of supervised domain adaptation

CRI iAtlas: an interactive portal for immuno-oncology research.

The Cancer Research Institute (CRI) iAtlas is an interactive web platform for data exploration and discovery in the context of tumors and their interactions with the immune microenvironment. iAtlas allows researchers to study immune response characterizations and patterns for individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports computation and visualization of correlations and statistics among features related to the tumor microenvironment, cell composition, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, expression of key immunomodulators, and tumor infiltrating lymphocyte (TIL) spatial maps. iAtlas was launched to accompany the release of the TCGA PanCancer Atlas and has since been expanded to include new capabilities such as (1) user-defined loading of sample cohorts, (2) a tool for classifying expression data into immune subtypes, and (3) integration of TIL mapping from digital pathology images. We expect that the CRI iAtlas will accelerate discovery and improve patient outcomes by providing researchers access to standardized immunogenomics data to better understand the tumor immune microenvironment and its impact on patient responses to immunotherapy

Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8(+) T cells

Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8(+) T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4(+)CD25(+) regulatory T (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8(+) T cell reactivity to self-tissue and tumor. Surprisingly, enhanced antitumor efficacy and autoimmunity was caused by increased function rather than increased numbers of tumor-reactive T cells, as would be expected by homeostatic mechanisms. The γ (C) cytokines IL-7 and IL-15 were required for augmenting T cell functionality and antitumor activity. Removal of γ (C) cytokine–responsive endogenous cells using antibody or genetic means resulted in the enhanced antitumor responses similar to those seen after nonmyeloablative conditioning. These data indicate that lymphodepletion removes endogenous cellular elements that act as sinks for cytokines that are capable of augmenting the activity of self/tumor-reactive CD8(+) T cells. Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells

Observation and integrated Earth-system science: a roadmap for 2016–2025

This report is the response to a request by the Committee on Space Research of the International Council for Science to prepare a roadmap on observation and integrated Earth-system science for the coming ten years. Its focus is on the combined use of observations and modelling to address the functioning, predictability and projected evolution of interacting components of the Earth system on timescales out to a century or so. It discusses how observations support integrated Earth-system science and its applications, and identifies planned enhancements to the contributing observing systems and other requirements for observations and their processing. All types of observation are considered, but emphasis is placed on those made from space. The origins and development of the integrated view of the Earth system are outlined, noting the interactions between the main components that lead to requirements for integrated science and modelling, and for the observations that guide and support them. What constitutes an Earth-system model is discussed. Summaries are given of key cycles within the Earth system. The nature of Earth observation and the arrangements for international coordination essential for effective operation of global observing systems are introduced. Instances are given of present types of observation, what is already on the roadmap for 2016–2025 and some of the issues to be faced. Observations that are organised on a systematic basis and observations that are made for process understanding and model development, or other research or demonstration purposes, are covered. Specific accounts are given for many of the variables of the Earth system. The current status and prospects for Earth-system modelling are summarized. The evolution towards applying Earth-system models for environmental monitoring and prediction as well as for climate simulation and projection is outlined. General aspects of the improvement of models, whether through refining the representations of processes that are already incorporated or through adding new processes or components, are discussed. Some important elements of Earth-system models are considered more fully. Data assimilation is discussed not only because it uses observations and models to generate datasets for monitoring the Earth system and for initiating and evaluating predictions, in particular through reanalysis, but also because of the feedback it provides on the quality of both the observations and the models employed. Inverse methods for surface-flux or model-parameter estimation are also covered. Reviews are given of the way observations and the processed datasets based on them are used for evaluating models, and of the combined use of observations and models for monitoring and interpreting the behaviour of the Earth system and for predicting and projecting its future. A set of concluding discussions covers general developmental needs, requirements for continuity of space-based observing systems, further long-term requirements for observations and other data, technological advances and data challenges, and the importance of enhanced international co-operation

The CO2 record at the Amazon Tall Tower Observatory : A new opportunity to study processes on seasonal and inter-annual scales

High-quality atmospheric CO2 measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2. In this study, we present the first 6 years (2014-2019) of continuous, high-precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1 degrees S, 58.9 degrees W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal (Delta CO2obs) that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter-annual scales, we find differences in phase between Delta CO2obs and the local eddy covariance net ecosystem exchange (EC-NEE), which is interpreted as an indicator of a decoupling between local and non-local drivers of Delta CO2obs. In addition, we present how the 2015-2016 El Nino-induced drought was captured by our atmospheric record as a positive 2 sigma anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter-annual variability of Delta CO2obs together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non-optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data-driven non-optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.Peer reviewe

Reimbursement of innovative pharmaceuticals in English and Spanish hospitals-The example of isavuconazole.

Funder: Pfizer; Id: http://dx.doi.org/10.13039/100004319BACKGROUND: Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck-based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge-based healthcare systems. OBJECTIVES: The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain. PATIENTS/METHODS: Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied. RESULTS: This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay. CONCLUSIONS: Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs' cost-effectiveness and assessing its added value into reimbursement decisions is highly relevant

Sensitivity of the carbon cycle in the Arctic to climate change

The recent warming in the Arctic is affecting a broad spectrum of physical, ecological, and human/cultural systems that may be irreversible on century time scales and have the potential to cause rapid changes in the earth system. The response of the carbon cycle of the Arctic to changes in climate is a major issue of global concern, yet there has not been a comprehensive review of the status of the contemporary carbon cycle of the Arctic and its response to climate change. This review is designed to clarify key uncertainties an vulnerabilities in the response of the carbon cycle of the Arctic to ongoing climatic change. While it is clear that there are substantial stocks of carbon in the Arctic, there are also significant uncertainties associated with the magnitude of organic matter stocks contained in permafrost and the storage of methane hydrates beneath both subterranean and submerged permafrost of the Arctic. In the context of the global carbon cycle, this review demonstrates that the Arctic plays an important role in the global dynamics of both CO2 and CH4. Studies suggest that the Arctic has been a sink for atmospheric CO2 of between 0 and 0.8 Pg C/yr in recent decades, which is between 0% and 25% of the global net land/ocean flux during the 1990s. The Arctic is a substantial source of CH4 to the atmosphere (between 32 and 112 Tg CH4/yr), primarily because of the large area of wetlands throughout the region. Analyses to date indicate that the sensitivity of the carbon cycle of the Arctic during the remainder of the 21st century is highly uncertain. To improve the capability to assess the sensitivity of the carbon cycle of the Arctic to projected climate change, we recommend that (1) integrated regional studies be conducted to link observations of carbon dynamics to the processes that are likely to influence those dynamics, and (2) the understanding gained from these integrated studies be incorporated into both uncoupled and fully coupled carbon–climate modeling efforts

Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season