Keynote Address

Few groups are likely to assemble today that would better know the shortcomings of international law than this group which I am privileged to address. You are aware of the confusions, of the incompleteness, of the lack of ordinary sanctions, and of all that might be said in criticism of international law. Yet here you are, assembled in Washington, at no little personal inconvenience, to reiterate your inveterate belief that international law is an existing and indestructible reality and offers the only hopeful foundation for an organized community of nations. There is no paradox in this. Those who best know the deficiencies of international law are those who also know the diversity and permanence of its accomplishments and its indispensability to a world that plans to live in peace. I am happy to join you in what amounts to a timely and resolute confession of faith

Climate Change and the Rule of Law: Adjudicating the Future in International Law

The article, which is based on a lecture delivered in London in September 2015, addresses the possibilities for adjudication of climate change issues before international courts and tribunals, finding them to be more favourable today than a few years ago. It argues for a role of international courts and tribunals in the determination of factual and scientific matters related to climate change, assessing the possible role of international courts of a more general jurisdiction, such as ITLOS and the ICJ

Genocide at 70: A reflection on its origins

On the anniversary of the Genocide Convention, it is useful that we look back at the history of the crime of genocide, its relationship with crimes against humanity and that we reflect on its relevance today.1 Over the last nine years, I have spent a significant amount of time grappling with these questions, whilst writing East West Street.2 The book is about the lives of individuals seeking to understand how their particular circumstances contributed to the roads they took and how the roads thus travelled changed the system of international law. Underneath this lurks a bigger question, a central question of identity: who are we? Are we individuals or members of a group? And how do we wish the law to protect us, as individuals or as members of a group

Of Refugees and Resignation

Building on topics explored in East West Street: on the Origins of Genocide and Crimes against Humanity, this article traces the development and publication of James McDonald’s Letter of Resignation of League of Nations High Commissioner for Refugees. Expanding on events outlined in his book, Sands describes how the letter was published in 1935 as a political statement in the wake of emerging news about Nazi atrocities against the Jews and other minority groups. Drawing analogies between these events and the contemporary refugee crisis, he raises questions about the current legal, political and moral frameworks associated with refugees, calling for an end of the ‘closing of the doors’ mentality

A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results. MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic. RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good. CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service

Is analysing the nitrogen use at the plant canopy level a matter of choosing the right optimization criterion?

Optimization theory in combination with canopy modeling is potentially a powerful tool for evaluating the adaptive significance of photosynthesis-related plant traits. Yet its successful application has been hampered by a lack of agreement on the appropriate optimization criterion. Here we review how models based on different types of optimization criteria have been used to analyze traits—particularly N reallocation and leaf area indices—that determine photosynthetic nitrogen-use efficiency at the canopy level. By far the most commonly used approach is static-plant simple optimization (SSO). Static-plant simple optimization makes two assumptions: (1) plant traits are considered to be optimal when they maximize whole-stand daily photosynthesis, ignoring competitive interactions between individuals; (2) it assumes static plants, ignoring canopy dynamics (production and loss of leaves, and the reallocation and uptake of nitrogen) and the respiration of nonphotosynthetic tissue. Recent studies have addressed either the former problem through the application of evolutionary game theory (EGT) or the latter by applying dynamic-plant simple optimization (DSO), and have made considerable progress in our understanding of plant photosynthetic traits. However, we argue that future model studies should focus on combining these two approaches. We also point out that field observations can fit predictions from two models based on very different optimization criteria. In order to enhance our understanding of the adaptive significance of photosynthesis-related plant traits, there is thus an urgent need for experiments that test underlying optimization criteria and competing hypotheses about underlying mechanisms of optimization

Proteasome Inhibitor Bortezomib Ameliorates Intestinal Injury in Mice

Background: Bortezomib is a proteasome inhibitor that has shown impressive efficacy in the treatment of multiple myeloma. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to acute colitis that can serve as an experimental animal model for human ulcerative colitis. Methodology/Principal Findings: Bortezomib treatment was shown to potently inhibit murine DSS-induced colitis. The attenuation of DSS-induced colitis was associated with decreased inflammatory cell infiltration in the colon. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4 + and CD8 + T cells in the colon and mesenteric lymph nodes. Bortezomib treatment significantly diminished interferon (IFN)-c expression in the colon and mesenteric lymph nodes. Furthermore, cytoplasmic IFN-c production by CD4 + and CD8 + T cells in mesenteric lymph nodes was substantially decreased by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting nuclear factor-kB activation during DSS-induced colitis. Conclusions/Significance: Bortezomib treatment is likely to induce T cell death, thereby suppressing DSS-induced colitis by reducing IFN-c production

Quality of Life as an outcome in Alzheimer's disease and other dementias- obstacles and goals

<p>Abstract</p> <p>Background</p> <p>The number of individuals at risk for dementia will probably increase in ageing societies as will the array of preventive and therapeutic options, both however within limited economic resources. For economic and medical purposes valid instruments are required to assess disease processes and the efficacy of therapeutic interventions for different forms and stages of illness. In principal, the impact of illness and success of an intervention can be assessed with biomedical variables, e.g. severity of symptoms or frequency of complications of a disease. However, this does not allow clear judgement on clinical relevance or comparison across different diseases.</p> <p>Discussion</p> <p>Outcome model variables such as quality of life (QoL) or health care resource utilization require the patient to appraise their own well-being or third parties to set preferences. In Alzheimer's disease and other dementias the evaluation process performed by the patient is subject to the disease process itself because over progress of the disease neuroanatomical structures are affected that mediate evaluation processes.</p> <p>Summary</p> <p>Published research and methodological considerations thus lead to the conclusion that current QoL-instruments, which have been useful in other contexts, are ill-suited and insufficiently validated to play a major role in dementia research, decision making and resource allocation. New models integrating biomedical and outcome variables need to be developed in order to meet the upcoming medical and economic challenges.</p