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bet Democratize Trade Policymaking to Better Protect Human Rights By feedproxy.google.com Published On :: Thu, 06 Jun 2019 12:11:18 +0000 12 June 2019 Dr Jennifer Ann Zerk Associate Fellow, International Law Programme There is growing interest in the use of human rights impact assessment to screen proposed trade agreements for human rights risks, and to ensure appropriate risk mitigation steps are taken. 2019-02-15-HumanRightsTradeAgreements-Smaller.jpg Tea pickers walk at dawn through the tea plantations of Munnar, Kerala, on 7 May 2017. Copyright: Pardeep Singh Gill/Getty Images With international trade discourse taking an increasingly transactional and sometimes belligerent tone, it would be easy to overlook the quiet revolution currently under way to bring new voices into trade policy development and monitoring. The traditional division of responsibilities between the executive and legislature – whereby treaties are negotiated and signed by the executive, and the legislature does what is necessary to implement them – may be undergoing some change.Growing awareness of the implications of trade and investment treaties for many aspects of day-to-day life – food standards, employment opportunities, environmental quality, availability of medicines and data protection, just to name a few – is fuelling demands by people and businesses for more of a say in the way these rules are formulated and developed.Various options for enhancing public and parliamentary scrutiny of trading proposals have recently been examined by two UK parliamentary select committees.[1] The reason for this interest is obviously Brexit, which has presented UK civil servants and parliamentarians with the unusual (some would say exciting) opportunity to design an approval and scrutiny process for trade agreements from scratch.Doubtless, EU authorization, liaison and approval procedures (which include a scrutinizing role for the European Parliament) will be influential,[2] as will the European Commission’s experience with stakeholder engagement on trade issues.[3] The recommendations of both UK select committees to include human rights impact assessment processes as part of pre-negotiation preparations[4] echo calls from UN agencies and NGOs for more rigorous and timely analysis of the human rights risks that may be posed by new trading relationships.[5] Again, EU practice with what it terms ‘sustainability impact assessment’ of future trade agreements provides a potential model to draw from.[6] However, process is no substitute for action. Human rights impact assessment is never an end in itself; rather, it is a means to a positive end, in this case a trade agreement which is aligned with the trading partners’ respective human rights obligations and aspirations. It bears remembering, though, that the idea of assessing trade proposals for future human rights risks is a relatively recent one. Do we have the tools and resources to make sure that this is a meaningful compliance and risk management exercise?Thus far there is little evidence that human rights impact assessment and stakeholder engagement exercises are having any real impact on the content of trade agreements.[7] This is the case even in the EU, where practice in these areas is the most advanced and systematic.[8]There are several possible reasons for this. First, the methodological challenges are enormous. Aside from the crystal-ball gazing needed to forecast the social, economic and environmental effects of a trade intervention well into the future, demonstrating causal links between a trade agreement and a predicted adverse impact is often highly problematic given the number of other economic and political factors that may be in play.[9]Secondly, there are many challenges around the need to engage with affected people and listen to their views.[10] The sheer number of possible impacts of a trade agreement on different individuals and communities, as well as the range of rights potentially engaged, makes this a difficult (some would say impossible) task. Some prioritization is always necessary.This makes for difficult decisions about who to engage with and how. Perceived bias or an apparent lack of even-handedness – favouring business compared to civil society, for instance – can sow mistrust about the true aims of such a process, undermining its future effectiveness as participants begin to question whether it is genuine or worthwhile.[11]The challenges are even more acute where impact assessment practitioners are tasked with investigating potential human rights impacts in other countries. Even if it is possible to get past the inevitable political sensitivities,[12] the sort of in-depth consultations required will be beyond the budget and time constraints of most assignments.[13]There are good reasons why trade policy should be subject to greater public and parliamentary scrutiny, and why there should be more opportunities for public participation in the formation of new trading regimes. By building more opportunities for stakeholder consultation at these stages, we can acquire perspectives on trade that are not available from other forms of assessment and analysis.However, policymakers should be wary of overstating the benefits of existing procedural models. Human rights impact assessment processes are still struggling to provide compelling analyses of the relationships between trade agreements and the enjoyment of human rights, let alone a roadmap for policymakers and trade negotiators as to what should be done.[14]And financial and practical barriers to participation in stakeholder engagement exercises mean that, at best, these will provide only a partial picture of stakeholder impacts and views.Experiences with human rights impact assessment of trade agreements so far demonstrate the need for realism about two things: first, the extent to which one can sensibly anticipate and analyse human rights-related risks and opportunities in the preparation stages for a new trading agreement; and, second, the extent to which problems identified in this way can be headed off with the right form of words in the treaty itself.Both recent UK select committee reports place considerable faith in the ability of pre-project transparency and scrutiny processes to flush out potential problems and prescribe solutions. Of course, there may be cases where frontloading the analysis in this way could be useful, for instance where the human rights implications are so clear that they can readily be addressed through upfront commitments by the parties concerned, whether by bespoke or standardized approaches.More often, though, for a trade agreement running many years into the future, human rights impacts and implications will take time to emerge, suggesting the need for robust monitoring and mitigation frameworks designed with longevity in mind. Ideally, pre-signing approval and assessment processes would lay the groundwork for future action by both trading partners, either jointly or separately (though preferably both).To this end, as well as developing ideas for more robust substantive provisions on human rights, policymakers should consider the institutional arrangements required – whether pursuant to the trade agreement or by complementary processes – to ensure that human rights-related risks identified during the planning stages are properly and proactively followed up, that emerging risks are tackled in a timely fashion, and that there are opportunities for meaningful stakeholder contributions to these processes.What needs to happenTrade policymakers can use human rights impact assessment to screen proposed trade treaties for human rights-related risks and to identify possible ways of mitigating those risks, whether through the terms of the agreement itself, domestic law reform or flanking measures.Building more opportunities for stakeholder consultations can enable perspectives on trade to be highlighted that are not available from other forms of assessment.Assessment is complicated, however, by methodological challenges and the difficulties of forecasting a trade agreement’s future impacts. Policymakers need to be realistic about the risks that can be anticipated, and the extent to which many of those identified can be addressed upfront in trade agreements’ terms.These inherent limitations may be overcome to some extent by better ongoing monitoring. Future trade agreements should include more robust human rights risk monitoring and mitigation frameworks, designed with longevity in mind.Notes[1] UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements, Seventeenth Report of Session 2017–19’, HC 1833 HL paper 310, 12 March 2019, https://publications.parliament.uk/pa/jt201719/jtselect/jtrights/1833/1833.pdf; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny, Sixth Report of Session 2017-2019’, HC 1043, 29 December 2018.[2] European Parliament and Directorate General for External Policies (2019), Parliamentary scrutiny of trade policies across the western world, study paper, March 2019, http://www.europarl.europa.eu/RegData/etudes/STUD/2019/603477/EXPO_STU(2019)603477_EN.pdf.[3] European Commission (2019), ‘Trade policy and you’, http://ec.europa.eu/trade/trade-policy-and-you/index_en.htm.[4] See UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements’, para 12; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny’, paras 124–34.[5] OHCHR (2003), Report of the High Commissioner for Human Rights on Human Rights, Trade and Investment, 2 July 2003, E/CN.4/Sub.2/2003/9, Annex, at para 63; UN Economic and Social Council (2017), ‘General Comment No 24 (2017) of the Committee on Economic, Social and Cultural Rights on State obligations under the International Covenant on Economic, Social and Cultural Rights in the context of business activities’, UN Doc. E/C.12/GC/24, 10 August 2017, para 13; and UN General Assembly (2011), ‘Guiding principles on human rights impact assessment of trade and investment agreements’, Report of the Special Rapporteur on the Right to Food, Olivier De Schutter, UN Doc. A/HRC/19/59/Add.5, 19 December 2011.[6] European Commission (2016), Handbook for Sustainability Impact Assessment (2nd ed.), Brussels: European Union, http://trade.ec.europa.eu/doclib/docs/2016/april/tradoc_154464.PDF.[7] Zerk, J. (2019), Human Rights Impact Assessment of Trade Agreements, Chatham House Research Paper, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/human-rights-impact-assessment-trade-agreements.[8] Ibid., pp. 11–13. For a detailed explanation of the EU’s approach to human rights impact assessment, see European Commission (2016), Handbook for Sustainability Impact Assessment.[9] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 14–21.[10] Ibid., pp. 21–22.[11] Ergon Associates (2011), Trade and Labour: Making effective use of trade sustainability impact assessments and monitoring mechanisms, Final Report to DG Employment, Social Affairs and Inclusion European Commission, September 2011; and Gammage, C. (2010), ‘A Sustainability Impact Assessment of the Economic Partnership Agreements: Challenging the Participatory Process’, Law and Development Review, 3(1): pp. 107–34. For a civil society view, see Trade Justice Movement (undated), ‘Trade Justice Movement submission to the International Trade Committee inquiry into UK Trade Policy Transparency and Scrutiny’, https://www.tjm.org.uk/resources/briefings/tjm-submission-to-the-international-trade-committee-inquiry-into-uk-trade-policy-transparency-and-scrutiny, esp. paras 23–32.[12] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 20–21.[13] Ibid., pp. 21–22.[14] Ibid.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
bet Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice By feedproxy.google.com Published On :: 2020-04-07 Taewook KangApr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882Research Full Article
bet Understanding Cybercrime for Better Policing: Regional and Global Challenges By feedproxy.google.com Published On :: Fri, 24 May 2019 15:25:01 +0000 Research Event 18 June 2019 - 9:00am to 5:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE In recent years, cybercrime has evolved from a niche technological concern into a prominent global issue with substantial preventative and remedial costs for businesses and governments alike. Despite heavy investment in sophisticated cybersecurity measures and the adoption of several legal, organizational and capacity-building measures, cybercrime remains a major threat which is evolving on a daily basis. Today’s cybercrime is more aggressive, more complex, more organized and – importantly – more unpredictable than ever before.The challenges posed by cybercrime are experienced acutely by countries undergoing digital transformations: as the level of connectivity rises, so too does the potential for online theft, fraud and abuse. Cybercrime is pervasive but governments can work to limit its impact by creating a resilient overall economy and robust institution, and appropriately equipping law enforcement and the justice system to navigate its novel challenges.To advance the discourse surrounding these issues, this workshop will assess the current cyber threat landscape and how it is evolving. It will identify the main obstacles encountered by law enforcement, the judiciary and prosecutors in their fight against cybercrime. It will also compare national, regional and global approaches that countries can use to effectively curb cybercrime and tackle its emerging challenges. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
bet Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb– relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction. Full Article
bet Comparison between 18F-FDG-PET- and CT-based criteria in non-small cell lung cancer (NSCLC) patients treated with Nivolumab By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Due to their peculiar mechanism of action, the evaluation of radiological response to immune checkpoint inhibitors (ICI) presents many challenges in solid tumors. We aimed to compare the evaluation of first response to Nivolumab by means of CT-based criteria with respect to fluorodeoxyglucose positron emission tomography (FDG-PET) response criteria in non-small-cell lung cancer (NSCLC) patients. Methods: 72 patients with advanced NSCLC were recruited in a mono-institutional ancillary trial within the expanded access program (EAP; NCT02475382) for Nivolumab. Patients underwent CT scan and FDG-PET at baseline and after 4 cycles (first evaluation). In case of progressive disease (PD), an additional evaluation was performed after two further cycles in order to confirm progression. We evaluated the response to treatment with CT scan by means of response evaluation criteria in solid tumors (RECIST) 1.1 and Immuno-related Response Criteria (IrRC) and with FDG-PET by means of PERCIST and immunotherapy-modified-PERCIST (imPERCIST) criteria. The concordance between CT- and PET-based criteria and the capability of each method to predict overall survival (OS) were evaluated. Results: 48/72 patients were evaluable for first response assessment with both PET- and CT-based criteria. We observed low concordance between CT- and PET-based criteria (Kappa value of 0.346 and 0.355 and Kappa value of 0.128 and 0.198 between PERCIST and imPERCIST versus RECIST and irRC respectively). Looking at OS, IrRC were more reliable to distinguish responders from non-responders. However thanks to the prognostic value of partial metabolic response assessed by both PERCIST and Immuno-PERCIST, PET-based response maintained prognostic significant in patients classified as progressive disease on the basis of irRC. Conclusion: Even though the present study did not support the routine use of FDG-PET in the general population of NSCLC patients treated with ICI, it suggests the added prognostic value of the metabolic response assessment, potentially improving the therapeutic decision-making. Full Article
bet Imaging P-glycoprotein Induction at the Blood-Brain Barrier of a Beta-Amyloidosis Mouse Model with 11C-Metoclopramide PET By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 P-glycoprotein (ABCB1) plays an important role at the blood-brain barrier (BBB) in promoting the clearance of neurotoxic beta-amyloid (Aß) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease (AD) patients. Treatment with drugs which induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aß deposits in the brain by enhancing the clearance of Aß peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer 11C-metoclopramide can measure ABCB1 induction at the BBB in a beta-amyloidosis mouse model (APP/PS1-21 mice) and in wild-type mice. Methods: Groups of wild-type and APP/PS1-21 mice aged 50 or 170 days underwent 11C-metoclopramide baseline PET scans or scans after intraperitoneal treatment with the rodent pregnane X receptor (PXR) activator 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN, 25 mg/kg) or its vehicle over 7 days. At the end of the PET scans, brains were harvested for immunohistochemical analysis of ABCB1 and Aß levels. In separate groups of mice, radiolabeled metabolites of 11C-metoclopramide were determined in plasma and brain at 15 min after radiotracer injection. As an outcome parameter of cerebral ABCB1 activity, the elimination slope of radioactivity washout from the brain (kE,brain) was calculated. Results: PCN treatment resulted in an increased clearance of radioactivity from the brain as reflected by significant increases in kE,brain (from +26% to +54% relative to baseline). Immunohistochemical analysis confirmed ABCB1 induction in the brains of PCN-treated APP/PS1-21 mice with a concomitant decrease in Aß levels. There was a significant positive correlation between kE,brain values and ABCB1 levels in the brain. In wild-type mice, a significant age-related decrease in kE,brain values was found. Metabolite analysis showed that the majority of radioactivity in the brain was composed of unmetabolized 11C-metoclopramide in all animal groups. Conclusion: 11C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in AD patients to non-invasively evaluate strategies to enhance the clearance properties of the BBB. Full Article
bet 11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of Beta-Cell-Mass in Patients with Type-1 Diabetes By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Full Article
bet Clinical Translation of a 68Ga-labeled Integrin {alpha}v{beta}6-targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer By jnm.snmjournals.org Published On :: 2020-02-21T14:46:23-08:00 The overexpression of integrin αvβ6 in pancreatic cancer makes it a promising target for noninvasive positron emission tomography (PET) imaging. However, currently, most integrin αvβ6-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a 68Ga-labeled integrin αvβ6-targeting cyclic peptide (68Ga-cycratide) for PET imaging of pancreatic cancer. Methods: 68Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (68Ga-linear-pep) in an integrin αvβ6-positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (two women and three men) underwent whole-body PET/CT imaging after injection of 68Ga-cycratide, and biodistribution and dosimetry calculations were determined. PET/CT imaging of two patients was performed to investigate the potential role of 68Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: 68Ga-cycratide exhibited significantly higher tumor uptake than did 68Ga-linear-pep in BxPC-3 tumor-bearing mice, owing—at least in part—to markedly improved in vivo stability. 68Ga-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that 68Ga-cycratide was comparable to 18F-fludeoxyglucose for diagnostic imaging and post-surgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin αvβ6-specific PET radiotracer with favorable pharmacokinetics and dosimetry profile. 68Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring. Full Article