An Enchanted Tool? Humanitarian Assistance and the ILC Draft Articles on the Protection of Persons in the Event of Disasters

Despite previous attempts at codification of international law regarding international responses to natural and human-made disasters, there is currently no binding international legal framework to regulate the provision of humanitarian assistance outside armed conflicts. Nevertheless, since the International Law Commission (ILC) included the protection of persons in the event of disasters on its programme of work in 2006, it has provisionally adopted eleven draft articles that have the potential to create binding obligations on states and humanitarian actors in disaster settings. Draft articles adopted include the definition of ‘a disaster’, the relationship of the draft articles to the international humanitarian law of armed conflict, recognition of the inherent dignity of the human person, and the duty of international cooperation. However, the final form of the draft articles has not been agreed. The Codification Division of the UN Office of Legal Affairs has proposed a framework convention format, which has seen support in the ILC and the UN General Assembly Sixth Committee. The overall aim of this article is to provide an analysis of the potential forms of international regulation open to the ILC and states in the context of humanitarian responses to disasters. However to avoid enchanting the ILC draft articles with unwarranted power, any examination of form requires an understanding of the substantive subject matter of the planned international regulation. The article therefore provides an overview of the international legal regulation of humanitarian assistance following natural and human-made disasters, and the ILC’s work to date on the topic. It then examines two key issues that remain to be addressed by the ILC and representatives of states in the UN General Assembly Sixth Committee. Drawing on the UN Guiding Principles on Internal Displacement, the development and implications of binding and non-binding international texts are examined, followed by an analysis of the suggested framework convention approach identified by the Special Rapporteur as a potential outcome of the ILC work.

The role of immune-related myeloid cells in angiogenesis

Macrophage function is not restricted to the innate and adaptive immune responses, but also includes host defence, wound healing, angiogenesis and homeostatic processes. Within the spectrum of macrophage activation there are two extremes: M1 classically activated macrophages which have a pro-inflammatory phenotype, and M2 alternatively activated macrophages which are pro-angiogenic and anti-inflammatory. An important property of macrophages is their plasticity to switch from one phenotype to the other and they can be defined in their polarisation state at any point between the two extremes. In order to determine what stage of activation macrophages are in, it is essential to profile various phenotypic markers for their identification. This review describes the angiogenic role for myeloid cells: circulating monocytes, Tie-2 expressing monocytes (TEMs), myeloid-derived suppressor cells (MDSCs), tumour associated macrophages (TAMs), and neutrophils. Each cell type is discussed by phenotype, roles within angiogenesis and possible targets as a cell therapy. In addition, we also refer to our own research on myeloid angiogenic cells (MACs), outlining their ability to induce angiogenesis and their similarities to alternatively activated M2 macrophages. MACs significantly contribute to vascular repair through paracrine mechanisms as they lack the capacity to differentiate into endothelial cells. Since MACs also retain plasticity, phenotypic changes can occur according to disease states and the surrounding microenvironment. This pro-angiogenic potential of MACs could be harnessed as a novel cellular therapy for the treatment of ischaemic diseases, such as diabetic retinopathy, hind limb ischaemia and myocardial infarction; however, caution needs to be taken when MACs are delivered into an inflammatory milieu.

Dissolving Microneedle Delivery of Nanoparticle Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells

Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.

Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression

Macrophage migration inhibitory factor (MIF), which inhibits apoptosis and promotes angiogenesis, is expressed in cancers suppressing immune surveillance. Its biological role in human glioblastoma is, however, only poorly understood. We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III-IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in tumour cells. Stable knockdown of MIF by shRNA in glioma cells significantly increased tumour cell susceptibility towards NK cell-mediated cytotoxicity. Furthermore, supernatant from mock-transfected cells, but not from MIF knockdown cells, induced downregulation of the activating immune receptor NKG2D on NK and CD8+ T cells. We thus propose that human glioma cell-derived MIF contributes to the immune escape of malignant gliomas by counteracting NK and cytotoxic T-cell-mediated tumour immune surveillance. Considering its further cell-intrinsic and extrinsic tumour-promoting effects and the availability of small molecule inhibitors, MIF seems to be a promising candidate for future glioma therapy.

GDF-15 contributes to proliferation and immune escape of malignant gliomas

Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-beta family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiologic and pathologic conditions.

Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.

Minority Rights and Minority Protection in Europe

In order to gain access to the EU, nations must be seen to implement formal instruments that protect the rights of minorities. This book examines the ways in which these tools have worked in a number of post-communist states, and explores the interaction of domestic and international structures that determine the application of these policies.

Πολιτικες ασύλου της ΕΕ- A critical review of the European policies of asylum: The re-positioning of asylum seekers from refugees/victims in need of protection to criminals (illegal immigrants)

This publication traces how asylum seekers are repositioned in the existing European asylum legislation from asylum seekers as victims in need of protection, to criminals . It is argued that this is due to the European legislation concerning the area of freedom, security and justice. The latest asylum legislation seems to undermine the refugee status which -as it is widely known- is safeguarded by the 1951 Geneva Convention relating to the Status of Refugees and its relevant 1967 Protocol. Additionally, in this paper the role of social workers and other social scientists to protect the rights of asylum seekers and question the existing legislation is presented.

System level DSP synthesis using voltage overscaling, unequal error protection & adaptive quality tuning

In this paper, we propose a system level design approach considering voltage over-scaling (VOS) that achieves error resiliency using unequal error protection of different computation elements, while incurring minor quality degradation. Depending on user specifications and severity of process variations/channel noise, the degree of VOS in each block of the system is adaptively tuned to ensure minimum system power while providing "just-the-right" amount of quality and robustness. This is achieved, by taking into consideration system level interactions and ensuring that under any change of operating conditions only the "lesscrucial" computations, that contribute less to block/system output quality, are affected. The design methodology applied to a DCT/IDCT system shows large power benefits (up to 69%) at reasonable image quality while tolerating errors induced by varying operating conditions (VOS, process variations, channel noise). Interestingly, the proposed IDCT scheme conceals channel noise at scaled voltages. ©2009 IEEE.

Logic and Memory Design Based on Unequal Error Protection for Voltage-scalable, Robust and Adaptive DSP Systems

In this paper, we propose a system level design approach considering voltage over-scaling (VOS) that achieves error resiliency using unequal error protection of different computation elements, while incurring minor quality degradation. Depending on user specifications and severity of process variations/channel noise, the degree of VOS in each block of the system is adaptively tuned to ensure minimum system power while providing "just-the-right" amount of quality and robustness. This is achieved, by taking into consideration block level interactions and ensuring that under any change of operating conditions, only the "less-crucial" computations, that contribute less to block/system output quality, are affected. The proposed approach applies unequal error protection to various blocks of a system-logic and memory-and spans multiple layers of design hierarchy-algorithm, architecture and circuit. The design methodology when applied to a multimedia subsystem shows large power benefits ( up to 69% improvement in power consumption) at reasonable image quality while tolerating errors introduced due to VOS, process variations, and channel noise.

Epstein-Barr Virus Large Tegument Protein BPLF1 Contributes to Innate Immune Evasion through Interference with Toll-Like Receptor Signaling

Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR). TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpes)viruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV) is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs). The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts.

Protection of DNA against low-energy electrons by amino acids: A first-principles molecular dynamics study

Using first-principles molecular dynamics simulations, we have investigated the notion that amino acids can play a protective role when DNA is exposed to excess electrons produced by ionizing radiation. In this study we focus on the interaction of glycine with the DNA nucleobase thymine. We studied thymine-glycine dimers and a condensed phase model consisting of one thymine molecule solvated in amorphous glycine. Our results show that the amino acid acts as a protective agent for the nucleobase in two ways. If the excess electron is initially captured by the thymine, then a proton is transferred in a barrier-less way from a neighboring hydrogen-bonded glycine. This stabilizes the excess electron by reducing the net partial charge on the thymine. In the second mechanism the excess electron is captured by a glycine, which acts as a electron scavenger that prevents electron localization in DNA. Both these mechanisms introduce obstacles to further reactions of the excess electron within a DNA strand, e.g. by raising the free energy barrier associated with strand breaks.

Resilience and Burnout in Child protection social work: Individual and organisational themes from a systematic literature review

Child protection social work is acknowledged as a very stressful occupation, with high turnover and poor retention of staff being a major concern. This paper highlights themes that emerged from findings of sixty-five articles that were included as part of a systematic literature review. The review focused on the evaluation of research findings, which considered individual and organisational factors associated with resilience or burnout in child protection social work staff. The results identified a range of individual and organisational themes for staff in child protection social work. Nine themes were identified in total. These are categorised under ‘Individual’ and ‘Organisational’ themes. Themes categorised as individual included personal history of maltreatment, training and preparation for child welfare, coping, secondary traumatic stress, compassion fatigue and compassion satisfaction. Those classified as organisational included workload, social support and supervision, organisational culture and climate, organisational and professional commitment, and job satisfaction or dissatisfaction. The range of factors is discussed with recommendations and areas for future research are highlighted.

Pitfalls in Protection: How Theory Can Enrich Our Understanding of Regulatory Compliance Problems in Planning Practice

This paper responds to demands for greater academic investigation into environmental protection, specifically the practical and structural problems which underpin regulatory compliance in the planning system. It critiques traditional theories of regulation and answers calls for the development of a thematic lens to facilitate the scrutiny of not only operational practice, but also the broader institutional regime. An empirical investigation builds upon the construct of really responsive regulation to study planning control and it becomes apparent that not only are there significant procedural planning difficulties facing regulatory compliance, but also that a much wider raft of issues must be considered if the complex equation is to be solved. The findings demonstrate how theory can be applied to enrich our rudimentary understanding of deep-seated problems and foster insights into areas of structural importance which are relevant to both planning and the wider regulatory arena.

Reducing Child Protection Error in Social Work: Towards an Holistic-Rational Perspective

Social work in the United Kingdom remains embroiled in concerns about child protection error. The serious injury or death of vulnerable children continues to evince much consternation in the public and private spheres. Governmental responses to these concerns invariably draw on technocratic solutions involving more procedures, case management systems, information technology and bureaucratic regulation. Such solutions flow from an implicit use of instrumental rationality based on a ‘means-end’ logic. While bringing an important perspective to the problem of child protection error, instrumental rationality has been overused limiting discretion and other modes of rational inquiry. This paper argues that the social work profession should apply an enlarged form of rationality comprising not only the instrumental-rational mode but also the critical-rational, affective-rational and communicative-rational forms. It is suggested that this combined, conceptual arsenal of rational inquiry leads to a gestalt which has been termed the holistic-rational perspective. It is also argued that embracing a more rounded perspective such as this might offer greater opportunities for reducing child protection error.