University libraries as active agents for change. The BitViews Project : how University librarians can turn all journals green and clear the path to open science

There can be no open science without Open Access (OA). This paper is a call to arms to individual University librarians to make a decisive move towards open access. The short-term objective of OA is defined as the immediate, cost-free, online access to the content of all peer reviewed scientific, medical, and scholarly articles. This amounts to unrestricted access to the author’s approved manuscripts (AAMs) deposited in institutional and other repositories. Even in the current academic publishing ecosystem, largely directed and managed by a few oligopolistic commercial publishers, 80% of peer reviewed articles can be deposited as AAMs, but only a small minority of researchers choose to do so. The reason for this failure is that currently there are no individual incentives for researchers to promote their AAMs, as the main currency of academic recognition and esteem (the citation count) resides with published articles. The author has described elsewhere how an open-source blockchain application (BitViews) can collect, validate, and disseminate at minimal cost online usage data of all AAMs available on institutional repositories. The resulting public ledger of usage data can be used to arrange discipline-specific non-citation research impact measures thereby providing the incentive for more authors to deposit their AAMs in a virtuous circle. The green OA thus achieved allows researchers in the global South to enter scholarly communication not only as consumers but also as producers of peer-reviewed knowledge. BitViews Project allows individual university libraries to be catalysts for change. The paper explains how a novel application of game theory (conditional crowdfunding) will empower individual libraries to spread the relatively miniscule costs of setting up BitViews using a two-stage mechanism that minimises free-riding and offers a no-risk opportunity to libraries to deploy their institutional repositories not just as stores of information, but as active tools to achieve open access.Publisher PD

Reversible effect of magnetic fields on human lymphocyte activation patterns: different sensitivity of naive and memory lymphocyte subsets.

The aim of this study was to investigate the influence of 50 Hz magnetic or static magnetic fields of 0.5 mT on subsets of human CD4+ T cells in terms of cytokine release/content, cell proliferation and intracellular free calcium concentration. CD4+ T cells can be divided into different subsets on the basis of surface marker expression, such as CD45, and T cells can be divided into naive (CD45RA+) and memory (CD45RA2) cells. In this study, the effects of magnetic fields after 24 and 48 h of cell culture were analyzed. We found that the CD4+CD45RA2 T subset were more sensitive after 2 h of exposure. Decreases in the release/content of IFN-c, in cell proliferation and in intracellular free calcium concentrations were observed in exposed CD4+CD45RA2 T cells compared to CD4+CD45RA+ T cells. The results suggest that exposure to the magnetic fields induces a delay in the response to stimulants and that modifications are rapidly reversible, at least after a short exposure

A two-phase problem with Robin conditions on the free boundary

We study for the first time a two-phase free boundary problem in which the solution satisfies a Robin boundary condition. We consider the case in which the solution is continuous across the free boundary and we prove an existence and a regularity result for minimizers of the associated variational problem. Finally, in the appendix, we give an example of a class of Steiner symmetric minimizers

Renal Toxicities in Cancer Patients Receiving Immune-Checkpoint Inhibitors: A Meta-Analysis

Aim: We performed a meta-analysis of the available clinical trials of immune-checkpoint inhibitors to assess risk differences and relative risks of renal toxicity. Methods: 17 randomized phase III studies were selected, including 10,252 patients. Results: The administration of immune-checkpoint inhibitors resulted in an overall low-grade, high-grade and all-grade renal toxicity Risk Difference of: 0.746% (95% CI 0.629% to 1.15%, p < 0.001—random), 0.61% (95% CI, 0.292–0.929%, p < 0.001—fixed) and 1.2% (95% CI, 0.601–1.85%—random), respectively. The pooled Relative Risk of low-grade, high-grade and all-grade renal toxicity was: 2.185 (95% CI 1.515–3.152—fixed), 2.610 (95% CI, 1.409–4.833, p = 0.002—fixed) and 2.473 (95% CI, 1.782–3.431, p < 0.001—fixed), respectively. An increased risk of renal toxicity was evident in some subgroups more than others. Conclusion: Immune-checkpoint inhibitors are associated with an increased risk of renal toxicity

Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities

In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) subsets in patients with active TB disease, in terms of frequency, phenotype, functional features, and gene expression signature. Full-blood counts from Healthy Donors (H.D.), Latent TB infected, active TB, and cured TB patients were performed. Frequency, phenotype, burst activity, and suppressor T cell activity of the two different subsets were assessed by flow cytometry while NETosis and phagocytosis were evaluated by confocal microscopy. Expression analysis was performed by using the semi-quantitative RT-PCR array technology. Elevated numbers of total neutrophils and a high neutrophil/lymphocyte ratio distinguished patients with active TB from all the other groups. PBMCs of patients with active TB disease contained elevated percentages of LDNs compared with those of H.D., with an increased expression of CD66b, CD33, CD15, and CD16 compared to NDNs. Transcriptomic analysis of LDNs and NDNs purified from the peripheral blood of TB patients identified 12 genes differentially expressed: CCL5, CCR5, CD4, IL10, LYZ, and STAT4 were upregulated, while CXCL8, IFNAR1, NFKB1A, STAT1, TICAM1, and TNF were downregulated in LDNs, as compared to NDNs. Differently than NDNs, LDNs failed to phagocyte live Mycobacterium tuberculosis (M. tuberculosis) bacilli, to make oxidative burst and NETosis, but caused significant suppression of antigen-specific and polyclonal T cell proliferation which was partially mediated by IL-10. These insights add a little dowel of knowledge in understanding the pathogenesis of human TB

Study of a high spatial resolution 10B-based thermal neutron detector for application in neutron reflectometry: the Multi-Blade prototype

Although for large area detectors it is crucial to find an alternative to detect thermal neutrons because of the 3He shortage, this is not the case for small area detectors. Neutron scattering science is still growing its instruments' power and the neutron flux a detector must tolerate is increasing. For small area detectors the main effort is to expand the detectors' performances. At Institut Laue-Langevin (ILL) we developed the Multi-Blade detector which wants to increase the spatial resolution of 3He-based detectors for high flux applications. We developed a high spatial resolution prototype suitable for neutron reflectometry instruments. It exploits solid 10B-films employed in a proportional gas chamber. Two prototypes have been constructed at ILL and the results obtained on our monochromatic test beam line are presented here

Multidisciplinarity in Transition Pathways for Patients With Kidney Disease: The Current State of Play

In the field of medical care, successful transition from pediatric-centered to adult-oriented healthcare can provide a sense of continuity in the development of youth, and prepare them to accept responsibility for and manage their own chronic kidney condition in complete autonomy. The so-called transition process requires the presence of some basic aspects: a multidisciplinary team, which acts as a bridge between child and adult services; a comprehensive clinical, cognitive, psychological, and social change for the young people; the involvement of family and caregivers. Within the framework of transition and chronicity during the developmental age, we selected international papers explaining models which agreed on some important steps in the transition process, although many differences can be observed between different countries. In fact, in Europe, the situation appears to be heterogeneous as regards certain aspects: the written transition plan, the educational programmes, the timing of transfer to adult services, the presence of a transition coordinator, a dedicated off-site transition clinic. We then analyzed some studies focusing on patients with renal diseases, including the first to contain a standardized protocol for transition which was launched recently in the USA, and which seems to have already achieved important positive, although limited, results. In Italy, the issue of transition is still in its infancy, however important efforts in the management of chronic kidney disease have already been initiated in some regions, including Emila Romagna, which gives us hope for the future of many young people

The fundamental problem blocking open access and how to overcome it : the BitViews project

In our view the fundamental obstacle to open access (OA) is the lack of any incentive-based mechanism that unbundles authors’ accepted manuscripts (AMs) from articles (VoRs). The former can be seen as the public good that ought to be openly accessible, whereas the latter is owned by publishers and rightly paywall-restricted. We propose one such mechanism to overcome this obstacle: BitViews. BitViews is a blockchain-based application that aims to revolutionize the OA publishing ecosystem. Currently, the main academic currency of value is the citation. There have been attempts in the past to create a second currency whose measure is the online usage of research materials (e.g., PIRUS). However, these have failed due to two problems. Firstly, it has been impossible to find a single agency willing to co-ordinate and fund the validation and collation of global online usage data. Secondly, online usage metrics have lacked transparency in how they filter non-human online activity. BitViews is a novel solution which uses blockchain technology to bypass both problems: online AM usage will be recorded on a public, distributed ledger, obviating the need for a central responsible agency, and the rules governing activity-filtering will be part of the open-source BitViews blockchain application, creating complete transparency. Once online AM usage has measurable value, researchers will be incentivized to promote and disseminate AMs. This will fundamentally re-orient the academic publishing ecosystem. A key feature of BitViews is that its success (or failure) is wholly and exclusively in the hands of the worldwide community of university and research libraries, as we suggest that it ought to be financed by conditional crowdfunding, whereby the actual financial commitment of each contributing library depends on the total amount raised. If the financing target is not reached, then all contributions are returned in full and if the target is over-fulfilled, then the surplus is returned pro rata.Publisher PDFPeer reviewe

Immune response to tick-borne hemoparasites: Host adaptive immune response mechanisms as potential targets for therapies and vaccines

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T-and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens