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Abstract Systemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0–130.5] vs. HC 115.6 [97.8–158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361–0.381] vs. 0.381 [0.373–0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376–0.381] vs. 0.382 [0.377–0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.

This article explores the capacities of digital technologies to disrupt, redefine and multiply urban spaces, creating new ways of seeing and experiencing cities. Based on ethnographic research into the lives of men who desire men in Haikou, People’s Republic of China, and their uses of the location-aware dating app Blued, I show how the city is produced anew as a space imagined and engaged in relation to the perceptible presence of other men who desire men. In a sociopolitical context in which non-heterosexual lives are largely invisible in public spaces, the digitally mediated visibility of Blued users to one another invites a range of social practices through which urban spaces, as well as spatial categories of ‘the urban’ and ‘the rural,’ are reproduced at the intersections of sexuality, space and digital technologies. With its empirical focus on an ‘ordinary’ city in a non-Western context, this article challenges both the Eurocentricity of much digital geographies research and its tendency to focus on global cities.

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders' perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.

The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health, and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintain and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.

This paper summarizes recent efforts on Observing System Evaluation (OS-Eval) by the Ocean Data Assimilation and Prediction (ODAP) communities such as GODAE OceanView and CLIVAR-GSOP. It provides some examples of existing OS-Eval methodologies, and attempts to discuss the potential and limitation of the existing approaches. Observing System Experiment (OSE) studies illustrate the impacts of the severe decrease in the number of TAO buoys during 2012–2014 and TRITON buoys since 2013 on ODAP system performance. Multi-system evaluation of the impacts of assimilating satellite sea surface salinity data based on OSEs has been performed to demonstrate the need to continue and enhance satellite salinity missions. Impacts of underwater gliders have been assessed using Observing System Simulation Experiments (OSSEs) to provide guidance on the effective coordination of the western North Atlantic observing system elements. OSSEs are also being performed under H2020 AtlantOS project with the goal to enhance and optimize the Atlantic in-situ networks. Potential of future satellite missions of wide-swath altimetry and surface ocean currents monitoring is explored through OSSEs and evaluation of Degrees of Freedom for Signal (DFS). Forecast Sensitivity Observation Impacts (FSOI) are routinely evaluated for monitoring the ocean observation impacts in the US Navy's ODAP system. Perspectives on the extension of OS-Eval to coastal regions, the deep ocean, polar regions, coupled data assimilation, and biogeochemical applications are also presented. Based on the examples above, we identify the limitations of OS-Eval, indicating that the most significant limitation is reduction of robustness and reliability of the results due to their system-dependency. The difficulty of performing evaluation in near real time is also critical. A strategy to mitigate the limitation and to strengthen the impact of evaluations is discussed. In particular, we emphasize the importance of collaboration within the ODAP community for multi-system evaluation and of communication with ocean observational communities on the design of OS-Eval, required resources, and effective distribution of the results. Finally, we recommend further developing OS-Eval activities at international level with the support of the international ODAP (e.g., OceanPredict and CLIVAR-GSOP) and observational communities.

Are the data of an edition means to a particular and privileged presentation, or is the presentation a side effect? Because of the changing nature of computer systems, with constant progression in hardware and software, the encoded texts are the most important long-term outcome of the project—the representation of the knowledge— and presentation within a particular application is destined to become obsolete relatively quickly. However, it is most often the presentation output, rather than the source data, which is published and shared. We believe this is largely because there is currently no way of expressing, in the source encoding, aspects of presentation which are seen by editors as a crucial part of their work. Given a framework for encoding processing expectations for a variety of output formats, editors would be much more inclined to share the encoded files as their prime output, and intentions for presentation would be much more likely to survive repeated technology transitions as processing tools develop and change. We believe the collision between the individuality of research and the quest for common tools that aid in the creation of digital editions will be solved not by creating another piece of specialized publishing software but rather by creating a general framework for processing TEI documents and similar, modular solutions for other tasks in the publishing workflow. Such an abstraction layer admittedly still requires some fluency in computer technologies, but far less than for setting up a publication system from scratch in a general-purpose programming language.

During the Global Ocean Data Assimilation Experiment, seven international operational centers participated in a dedicated modeling system intercomparison exercise from February to April 2008. The objectives were: (1) to show GODAE global-ocean and basin-scale forecasting systems of different countries in routine interaction and continuous operation, (2) to assess the quality and perform scientific validation of the ocean analyses and the forecasting performance of each system, and (3) to learn from this exercise in order to increase interoperability and collaboration in real time. The validation methodology has steadily improved through several validation experiments and projects performed within the operational oceanography community. It relies on common approaches and standardization of outputs, with a set of diagnostics based on fully detailed metrics that characterize its strengths and weaknesses, but also provide error levels for ocean estimates. The ocean forecasting systems provide daily fields of mesoscale water mass distribution and ocean circulation, with an option for sea-ice variations. We present a subset of the intercomparisons performed over different areas, showing general ocean circulation in agreement with known patterns. We also present some accuracy assessments through comparison with observed data.

Ocean data assimilation has reached a sufficient level of maturity such that observations are routinely combined with model forecasts to produce a variety of ocean products. Approaches to ocean data assimilation vary widely both in terms of the sophistication of the method and the observations assimilated, and also in terms of specification of the forecast error covariances, model biases, observation errors, and quality-control procedures. In this paper, we describe some of the ocean data assimilation systems that have been developed within the Global Ocean Data Assimilation Experiment (GODAE) community. We discuss assimilation methods, observations assimilated, and techniques used to specify error covariances. In addition, we describe practical implementation aspects and present analysis performance results for some of the analysis systems. Finally, we describe plans for improving the assimilation systems in the post-GODAE time period beyond 2008.

Sea surface temperature (SST) measurements are vital to global weather prediction, climate change studies, fisheries management, and a wide range of other applications. Measurements are taken by several satellites carrying infrared and microwave radiometers, moored buoys, drifting buoys, and ships. Collecting all these measurements together and producing global maps of SST has been a difficult endeavor due in part to different data formats, data location and accessibility, and lack of measurement error estimates. The need for a uniform approach to SST measurements and estimation of measurement errors resulted in the formation of the international Global Ocean Data Assimilation Experiment (GODAE) High Resolution SST Pilot Project (GHRSST-PP). Projects were developed in Japan, Europe, and Australia. Simultaneously, in the United States, the Multi-sensor Improved SST (MISST) project was initiated. Five years later, the MISST project has produced satellite SST data from nine satellites in an identical format with ancillary information and estimates of measurement error. Use of these data in global SST analyses has been improved through research into modeling of the ocean surface skin layer and upper ocean diurnal heating. These data and research results have been used by several groups within MISST to produce high-resolution global maps of SSTs, which have been shown to improve tropical cyclone prediction. Additionally, the new SSTs are now used operationally for marine weather warnings and forecasts.

In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection.ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001).An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens.ClinicalTrials.gov NCT01366534.

This article examines the process of customization, digitization, up-conversion, and proofreading that took place as part of the Stationers' Register Online (SRO) project at the University of Oxford. This pilot SRO project received institutional funding to digitize the first four volumes of the book-entry Register of the Stationers' Company. This is an important source for book history in Britain as the Stationers' Register was the primary means through which ownership of texts was asserted, disputed, regulated, and monitored from 1577 until 1924. The article concentrates on the technical aspects of creating a byte-reduced TEI schema (tei_corset) which, because of the arrangement with the keying company, saved a significant amount of money. It looks at the creation of that schema, the up-conversion of the resulting XML, and the difficulties of proofreading such a large quantity of material.

Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection.The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant.The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection.ClinicalTrials.govNCT00870987.